Delhi Journal of Ophthalmology

Delhi Journal of Ophthalmology Editor

Rohit Saxena

Managing Editor

Editorial Board

Editorial Committee Parijat Chandra Tushar Agarwal Shibal Bhartiya Munish Dhawan Harinder Sethi Raghav Gupta Ashish Kakkar Rachana Meel Digvijay Singh

Jitendra Jithani M.Vanathi Prakash Chand Agarwal Swati Phuljhele Reena Sharma Varun Gogia Sashwat Ray Saptorshi Majumdar Shraddha Puranik

Rajesh Sinha

Rajvardhan Azad Atul Kumar Ashok K Grover Mahipal S Sachdev Lalit Verma Sharad Lakhotia P V Chaddha Dinesh Talwar K P S Malik Tanuj Dada

Vimla Menon Pradeep Sharma V P Gupta S. Bharti Ashok Garg P K Pandey Ramanjit Sihota Divender Sood Rishi Mohan Namrata Sharma

Rasik B Vajpayee Rajinder Khanna Harbans Lal Amit Khosla B Ghosh Kirti Singh B P Guliani S P Garg Arun Baweja Sanjay Mishra Tarun Sharma

General Information Delhi Journal of Ophthalmology (DJO), once called Visiscan, is a quarterly journal brought out by the Delhi Ophthalmological Society. The journal aims at providing a platform to its readers for free exchange of ideas and information in accordance with the rules laid out for such publication. The DJO aims to become an easily readable referenced journal which will provide the specialists with up to date data and the residents with articles providing expert opinions supported with references.

Contribution Methodology Author/Authors must have made significant contribution in carrying out the work and it should be original. It should be accompanied by a letter of transmittal.The article can be sent by email to the Editor or a hard copy posted. Articles receive will be sent to reviewers whose comment will be emailed to the author(s) within 4-6 weeks. The identity of the authors and the reviewers will not be revealed to each other by the editorial team. Detailed instructions to the contributors and for advertisement are included at the end of the journal.

Editorial Process

The DJO has Dr Rohit Saxena as its Editor who is assisted by a team of renowned ophthalmologists and an illustrous editorial board. The reviewers,who are leaders in their respective fields, form the back bone of the journal by setting standards for the published work.

Disclaimer The journal does not take any responsibility for the articles published in the journal unless it is explicitly stated so. The views expressed in the articles and editorials are of the authors and do not in any way reflect the policy of the Delhi Journal of Ophthalmology. The journal does not endorse or guarantee the quality or efficacy of any product or service mentioned or advertised in the journal issues. Advertisements carried in this journal are expected to conform to internationally accepted medical, ethical and business standards.

Editorial Office

Dr Rohit Saxena, Room No. 479, Dr R.P. Centre for Ophthalmic Sciences, AIIMS, New Delhi-110029 Ph +91-011-26593182, Email : [email protected]

Published by

Dr Rohit Saxena, Editor DJO, on behalf of Delhi Ophthalmological Society, Delhi

Editorial Assistant Varun Kumar

Vol. 21, No. 3, January-March, 2011

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Delhi Journal of Ophthalmology

Contents Editorial 3.

Where the mind is without fear Dr. Rohit Saxena

Major Review 4. 9. 15. 19. 23.

Endophthalmitis Shivani Pahuja, Ritesh Narula

The Operation Theatre : Basic Architecture Sapna, Saptorshi Majumdar, Pradeep Venkatesh

Upshoot And Downshoot In Duane’s Retraction Syndrome Suma Ganesh

Marcus Gunn Jaw-Winking Phenomenon : A Review Dewang Angmo, Mandeep S. Bajaj, Neelam Pushker, Supriyo Ghose

Review of doses of important drugs in ophthalmology Yogesh Bhadange, Bhavin Shah , Brijesh Takkar, Rajesh Sinha

Preferred Practice Pattern 28.

Systematic Approach to a Case of Disc Pallor Digvijay Singh, Rohit Saxena, Pradeep Sharma, Vimla Menon

Case Reports 33. 38.

Bilateral Mooren’s Ulcer with perforation and Iris prolapse Uday Gajiwala, Jyotsom Ganatra, Rajesh Patel, Parin Shah, Rohan Chariwala

Acute Onset Myopia and Angle Closure Glaucoma after Topiramate Administration Nidhi Verma, Ashok Kumar

Instrument Scan 40.

Understanding your Direct Ophthalmoscope



Digvijay Singh, Rohit Saxena, Pradeep Sharma, Vimla Menon

Original Article 45. 48.



Study of Colour Blindness in Tibetan Population Navjot Kaur, Avinash Kumar, Gurinder Kaur, Jasjeet Kaur Dhillon, K.D.Singh

Manual Sutureless Small Incision Technique for Exchange of dislocated Posterior Chamber IOL Lakshminarayana Pasumala

Instructions to Authors

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Vol. 21, No. 3, January-March, 2011

Delhi Journal of Ophthalmology

Editorial Where the mind is without fear

The relevance of Rabindranath Tagore’s poem for today’s ophthalmologist.

WHERE the mind is without fear and the head is held high (in OPD’s, rounds, OT’s) Where knowledge is free (conferences, symposiums, internet) Where the world has not been broken up into fragments By narrow domestic walls (zones, institutions vs individual, govt. v/s pvt.) Where words come out from the depth of truth (in free paper sessions, articles) Where tireless striving stretches its arms towards perfection (in our work) Where the clear stream of reason has not lost its way (Duke Elder, Kanski…) Into the dreary desert sand of dead habit (routine of OPD-rounds-OT) Where the mind is led forward by thee (God who gave us the opportunity to give sight) Into ever-widening thought and action (think and reach beyond routine clinical work) Into that heaven of freedom, my Father, let my country (us ophthalmologist) awake.

Dear friends, The relevance of the above poem is timeless and for everyone whichever occupation we may be pursuing. It is just a reminder that we must get out of our routine and think towards becoming better and more accomplished in our work and our duty of serving the patients for which we are here. Let us resolve to give our best towards the care of our patients…. The result of course is always out of our hands. This is the penultimate issue of the Delhi Journal of Ophthalmology with yours truly as the Editor and I must accept that despite the challenges of bringing out the journal regularly with a content that is somewhat accurate, interesting and scientifically sound, my period as editor has been most enjoyable and fulfilling.

Dr. Rohit Saxena

The Delhi journal of Ophthalmology is now indexed at Index Copernicus. The editorial board is involved in the task of getting the journal indexed in other sites as well as improving the quality of articles and their presentation. This is only possible with the support of each and every DOS member. In addition to the present heads, the DJO also publishes original research including thesis work of residents. We also welcome to article comments and advise on how to improve the DJO. Any DOS member who has not received the previous four issues please contact DOS Secretariat [email protected], [email protected] or Editor, DJO editordjo@gmail. com. Some copies have come back due to incorrect addresses, so members are requested to please provide correct addresses and contact details to DOS Secretariat.

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Major Review

Endophthalmitis Shivani Pahuja1, Ritesh Narula2 1 Guru Nanak Eye Centre, 2 Shroff Charity Eye Hospital. Endophthalmitis is an inflammation of the internal layers of the eye resulting from intraocular colonization of infectious agents and manifesting with an exudation into vitreous cavity. Though the word endophthalmitis means any inflammation of the internal ocular spaces but in clinical practice it is usually taken to mean inflammation secondary to intraocular infection. Endophthalmitis can be divided into two main types based on the mode of infection as: Exogenous and Endogenous (ie, metastatic). Exogenous endophthalmitis results from direct inoculation as a complication of ocular surgery, foreign bodies, blunt or penetrating ocular trauma. Endogenous endophthalmitis [1] results from the hematogenous spread of organisms from a distant source of infection (eg, endocarditis). Endogenous endophthalmitis is quite rare. Various studies have reported incidence varying from 2% to 15%. In endogenous endophthalmitis, blood-borne organisms permeate the bloodocular barrier either by direct invasion (septic emboli) or by changes in vascular endothelium caused by substrates released during infection. Destruction of intraocular tissues may be due to direct invasion by the organism and/or from inflammatory mediators of the immune response. Due to increase in the spread of AIDS, more frequent use of immunosuppressive agents, and the use of more invasive procedures, the patients at risk of endogenous endophthalmitis are increasing . Most cases of exogenous endophthalmitis (49% to 76% as reported by various studies) occur after intraocular surgery. When surgery is implicated in the cause, endophthalmitis usually begins within 1 week after surgery. Post cataract endophthalmitis [2] is the most common form, with approximately 0.1-0.3% of operations having this complication. This is largely due to large number of cataract surgeries being done. But the exact incidence varies in different set ups and may be very low at certain places. The overall incidence of endophthalmitis has decreased over the past several decades largely due to improved surgical technique and patient preparation. Modern estimates indicate that the incidence of infectious endophthalmitis ranges from 0.13% to 0.7%. Endophthalmitis following penetrating keratoplasty [3] may occur early or late, the incidence of which is reported upto 2%. The infection could be due to contamination of donor

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material, infectious keratitis or as a complication of suture removal. These patients are also at risk of infections due to prolonged corticosteroid use following surgery. Endophthalmitis as a complication of vitreoretinal surgery is relatively uncommon. Scleral buckle infection usually appears between the second and seventh day of surgery, and, presents as severe lid oedema with conjunctival chemosis associated with severe ocular pain and headache. Intraocular inflammation may develop associated with media haziness, subretinal exudation and localised exudative retinal detachment. In delayed subacute cases fistula and granuloma form, resulting in exposure of the buckle. Diabetes and prolonged duration of surgery have been identified as specific risk factors in this setting. Incidence of endophthalmitis following pars plana vitrectomy has been reported as low as 0.051%. The risk factors are different for isolated and cluster endophthalmitis. Patient factors play a predominant role in isolated postoperative endophthalmitis. Patients own bacterial flora may gain entry at the time of surgery and thus increasing the development of postoperative endophthalmitis. It is very important to rule out diseases like chronic blepharitis, conjunctivitis, canaliculitis and keratoconjuntivitis sicca, chronic dacryocystitis before planning ocular surgery for the patient. The other important intraoperative risk factors for isolated postoperative endophthalmitis are inadequate eyelid or conjunctival disinfection, prolonged surgery, vitreous loss, prolene haptics of IOLs. The above factors can be taken care of by the use of pre-operative topical antibiotics for 24 hours, facial scrub, povidone iodine into the conjunctival sac, adhesive plastic drapes to separate eyelashes, surgeon gloves, subconjunctival antibiotics at the end of the surgery. The role of antibiotics in the irrigating solutions is still questionable. One drop of 5% povidone iodine [4] has proved to be beneficial in protecting against endophthalmitis. External factors are the major risk factors in the causation of cluster postoperative endophthalmitis. There have been various reports from all over the world describing bacterial as well as fungal postoperative cluster endophthalmitis. Defects in sterlisation of instruments, contamination of tap water, multiple dose fluids and drugs have been held responsible

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Endophthalmitis

for bacterial cluster postoperative endophthalmitis. Fungal cluster postoperative endophthalmitis has been reported after contaminated irrigating solutions, IOLs, viscoelastics, improper ventilation system, poor OT hygiene and even after hospital construction activity. To prevent the occurrence of these cluster infections, we have to remain on guard for any breach in infection control measures and use standardized irrigating solutions and drugs. Infectious postoperative endophthalmitis needs to be carefully differentiated from non infectious vitreous inflammation following surgery. This form of sterile endophthalmitis is also known as the toxic anterior segment syndrome (TASS).There are multiple potential causes of TASS including toxic effects from intraocular fluids, medications, lenses, instruments, endotoxins, and sterilization techniques. The differentiation from infectious endophthalmitis is vital , as the treatments and positive outcomes are different. Often, the presenting signs and symptoms of infectious endophthalmitis occur within the first 48 to 72 hours after surgery. If endophthalmitis is caused by fungal or less virulent organisms, the onset of symptoms can occur as late as weeks to months after surgery. TASS usually presents sooner than infectious endophthalmitis (12 to 24 hours after surgery) and differs from infectious endophthalmitis in presentation. Patients often have decreased visual acuity, corneal edema, a nonreactive, dilated pupil, and a moderate to severe anterior chamber reaction with cells, flare, hypopyon, and especially fibrin. Pain is mild to moderate if present. Patients with TASS can have marked corneal edema and even permanent, irreversible corneal decompensation. The corneal edema is characteristically “limbus to limbus.” Inflammation secondary to TASS will respond readily to topical steroid treatment as apposed to patients of endophthalmitis who will show worsening.

Clinical Features of Endophthalmitis The typical clinical characteristics are increasing pain and redness associated with decreasing visual acuity or sometimes profound loss of vision. Hypopyon is usually present but may be absent. lid oedema and raised intraocular pressure may be present. Occasionally the signs and symptoms may be subtle and misleading in the early stages until the course becomes more fulminant and Intraocular inflammation greater than expected in the postsurgical period should always be viewed with suspicion. Blurring of vision is the most common symptom and was reported by 94% of patients in the EVS study. Pain was characteristically absent in 25% cases in the EVS study group. Other clinical signs which may be present are lid edema, conjunctival hyperemia, chemosis, circumcorneal congestion, ring abscess, suture abscess, wound dehiscence, fibrinous AC reaction, posterior synchiae, vitreous cells, vitreous exudates, retinal exudates and periphelbitis. Vol. 21, No. 3, January-March, 2011

Delhi Journal of Ophthalmology

Post surgical endophthalmitis can be again divided into 2 categories – Early onset post operative endophthalmitis and late onset post operative endophthalmitis depending on the time after the surgery at which the patient presents. Majority of patients of post cataract endophthalmitis usually present in the first post op week. Severe acute postoperative endophthalmitis usually presents within 1-4 days after surgery. Patients usually present with decreased visual acuity and pain. Ciliary injection is usually present. corneal oedema ,anterior chamber reaction and vitreous inflammation are important clinical features indicating acute endophthalmitis. Afferent pupillary defect may be present. The organisms implicated are Staphylococcus aureus, Streptococcus and gramnegative organisms such as Serratia marcescens, Proteus and Pseudomonas. Chronic or late endophthalmitis usually presents after about 6 weeks of cataract surgery. It usually presents with minimal pain, hypopyon, granular keratic precipitates and mild vitritis. Staph. Epidermidis[5], candida and Propionobacterium acnes are usually responsible for chronic endophthalmitis. The most important clinical feature of P acnes endophthalmitis [6] is the presence of a white intracapsular plaque composed of sequestered micro-organisms in the capsular bag. It is a low grade chronic smouldering type of endophthalmitis. Because of its atypical presentation it is often difficult to diagnose and may be confused with posterior capular opacification. Other important type of endophthalmitis which deserve special mention include Post traumatic endophthalmitis [7]. It occurs in 4-13% of all penetrating ocular injuries. Incidence of endophthalmitis with perforating injuries in rural settings is higher when compared with non rural settings. Delay in the repair of a penetrating globe injury is correlated with increased risk of developing endophthalmitis. Incidence of endophthalmitis with retained intraocular foreign bodies is 7-31%. Common agents are Staph epidermidis, Bacillus species, streptococcus species, Staph. aureus, various fungi and P. acnes[8]. Endophthalmitis associated with filtering blebs is also sometimes seen in patients. Bacteria enter the eye through intact or leaking conjunctival filtering blebs. Streptococcus, Pneumococcus and Haemophilus influenzae are some of the organisms.

HOW TO EXAMINE A CASE OF ENDOPHTHALMITIS ? The examination of the suspected patient should include a detailed history, visual acuity assessment, examination of ocular adnexa (any sign of lid swelling), anterior chamber evaluation (using a slit lamp) and examination of the vitreous. Associated signs like leaking filtering blebs, wound leak etc.

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should be noted if any. Fundus view may be obscured because of anterior chamber reaction or due to vitreous exudates. The clarity of ocular media could be assessed by indirect ophthalmoscopy.

Management The prognosis in postoperative endophthalmitis depends on the virulence of the microorganisms and early intervention. For early recognition of postoperative infection, frequent postoperative follow up at 24 hours, 72 hour and 7 days is necessary. Every follow up examination comprises of recording visual acuity, slit lamp biomicroscopic examination and looking for media clarity. After the clinical diagnosis of endophthalmitis is made, the further management depends on the presenting visual acuity and the microbiological spectrum.. Data from the Endophthalmitis Vitrectomy Study indicate that initial management for patients who meet EVS entry criteria should include 3 port pars plana vitrectomy if patients present with vision worse than hand motions, but that an initial vitreous tap/biopsy with intravitreal antibiotics should generally be sufficient if presenting vision is hand motions or better. Systemic antibiotics were not found of benefit in this study.

Limitations of Endophthalmitis Vitrectomy Study •

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It only includes cases of post operative endophthalmitis 70% of which were due to Staph. Epidermidis. The results cannot be extrapolated to other forms of endophthalmitis such as bleb related, traumatic and endogenous which are more likely to be caused by organisms of greater virulence. Amikacin and Ceftazidime were the only systemic antibiotics evaluated in the EVS. Although patients in the EVS derived no demonstrable benefit from these systemic antibiotics, the study made no recommendations regarding treatment with additional antimicrobial agents (eg, systemic fluoroquinolones) or systemic antimicrobial agents for other types of endophthalmitis (eg, chronic, bleb-associated, traumatic, fungal, and endogenous forms) Potential study subjects with significant opacification of the anterior chamber or without light perception were excluded from the EVS. Because these eyes with more severe infection or involving more virulent organisms were excluded from the EVS, the effect might have shifted the EVS outcomes to more favorable results.

Endophthalmitis

an immediate vitreal tap and instillation of intravitreal antibiotics. Vitreous sample is immediately subjected to gram stain[11], KOH and calcoflour smear. The sample is also innoculated on blood agar, chocolate agar, liquid agar and Sabauraud’s dextrose agar. A eubacterial PCR and fungal PCR should be done if the facilities are available. A combination of Intravitreal antibiotics[12] which is commonly used include Vancomycin (1 mg/0.1ml) and Ceftazidime (2.25mg/0.1ml) because 94% of the culture positive cases are caused by gram positive organisms which are 100% sensitive to Vancomycin and 6% of culture positive cases are by gram negative group of organisms which are 90% sensitive to Ceftazidime. EVS did not recommend systemic antibiotics for cases of acute bacterial postoperative endophthalmitis. However, the drug used in EVS were the once with poorer intravitreal penetration. The current generation of fluoroquinolones which have a high intravitreal penetration and achieve required MICs for most organisms should be used as an adjunct. The indications for pars plana vitrectomy are • Poor visual acuity at presentation • deterioration or no improvement despite intravitreal antibiotics • delayed onset endophthalmitis • fungal endophthalmitis. The precautions while performing pars plana vitrectomy in endophthalmitis are • use of 6mm infusion cannula • clearing AC hypopyon and exudative membrane • collection of undiluted vitreous sample from midvitreous cavity • aim to clear only core vitreous • IOL explantation in cases of gross infection Treatment approaches for P acnes endophthalmitis [14] include • Intra-vitreal vancomycin 1mg / 0.1 ml which has to be given into the capsular bag • May have to be combined with vitrectomy, total capsulectomy and IOL explantation.

Fungal Endophthalmitis • •

Though EVS did provide general guidelines for treatment of endophthalmitis, clinicians should individualise treatrment for each patient based on the clinical course, signs and symptoms. Once a clinical diagnosis of acute bacterial endophthalmitis made, it is to be considered as a medical emergency requiring

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Endogenous fungal endophthalmitis is frequently an ocular manifestation of a systemic disease. Endogenous infections usually occur in patients risk factors like immunosuppression, intravenous drug abuse, bacterial sepsis, prolonged hyperalimentation, systemic antibiotics, corticosteroid therapy, recent abdominal surgery, malignancy, alcoholism, diabetes mellitus, trauma, and hemodialysis. Vol. 21, No. 3, January-March, 2011

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Endophthalmitis

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Candida albicans is by far the most common pathogen isolated in endogenous fungal endophthalmitis. Other pathogens include Aspergillus, Coccidioides, Cryptococcus, Blastomyces, and Sporothrix species. The diagnosis of endogenous fungal endophthalmitis should be considered in patients who present with vitritis accompanied by a chorioretinal focus in the clinical setting of a recent or current debilitating illness. Clinical suspicion plays an important role in identifying patients who may have fungal endophthalmitis Exogenous infections usually are secondary to trauma or surgery. A variety of fungi, including Paecilomyces, Acremonium, and Sporothrix species, have been associated with endophthalmitis following intraocular surgery or trauma The prognosis of fungal endophthalmitis depends on the virulence of the organism, the extent of intraocular involvement, and the timing and mode of interventions. Blood cultures, urine cultures, sputum cultures, and cerebrospinal fluid (CSF) cultures should be obtained in patients suspected of endogenous endophthalmitis. In addition, direct examination of fungi with Giemsa, Gomori-methenamine-silver (GMS), and periodic-acid Schiff (PAS) stains should be obtained. Culture of the fungus confirms the diagnosis. Fungal cultures can be positive in 44-70% of patients diagnosed clinically. Vitrectomy samples are more sensitive for fungal cultures than vitreous needle biopsies. The culture must be kept at the laboratory for at least 4-6 weeks to ensure that slow-growing or fastidious fungal organisms are not missed. A useful, recently introduced diagnostic tool for fungal endophthalmitis is the polymerase chain reaction (PCR) [15]. The main advantages of PCR over conventional fungal cultures are the higher sensitivity and the rapid results obtained with PCR. It helps to make an early differentiation between bacterial endophthalmitis and fungal endophthalmitis Systemic amphotericin has been the treatment of choice because of its broad-spectrum coverage; however, the penetration of the vitreous cavity is poor. Doses of 5- to 10-mg intravitreal amphotericin [16] have been used. A new systemic treatment is voriconazole [17], when administered orally or intravenously, it has good intravitreal concentrations. Intravitreal administration of voriconazole [18] seems safe without evidence of retinal toxicity with concentrations up to 25 mg/mL. The advent of pars plana vitrectomy has improved the treatment results of fungal endophthalmitis. The advantages of pars plana vitrectomy are that it provides material for culture, removes viable organisms and inflammatory end products from the infected vitreous,

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and provides intravitreal access to antifungal agents (eg, amphotericin B). Vitrectomy and intravitreal amphotericin B[19] should be considered in those cases of endogenous fungal endophthalmitis where the disease is progressing despite initial therapy with an appropriate systemic antifungal agent. Voriconazole may be a particularly attractive agent to consider for infections with fluconazole-resistant, voriconazole-susceptible strains. Choroidal neovascularization at the site of chorioretinal scars, epiretinal membranes, tractional retinal detachment are some of the complications of fungal endophthalmitis.

References 1. Albert DM, ed; Jakobiec FA. Endogenous endophthalmitis. In: Principles and Practice of Ophthalmology. Vol 5. W B Saunders Co; 1994:3120-3125. 2. Albert DM, Jakobiec FA. Postoperative endophthalmitis. In: Principles and Practice of Ophthalmology. W B Saunders Co; 2000:2441-2462. 3. Guss RB, Koenig S, De La Pena W, et al. Endophthalmitis after penetrating keratoplasty. Am J Ophthalmol 95:651-658,1983. 4. Speaker MJ, Menikoff JA. Prophylaxis of endophthalmitis with topical providone-iodine. Ophthalmology 98:1769-1775, 1991 5. Jett BD, Shepard B, Gilmore MS. Detection of Staphylococcus epidermidis and Staphylococcus aureus in vitreous by polymerase chain reaction. Invest Ophthalmol Vis Sci 36:s788, 1995. 6. Lai YJ, Chen KH, Lin YC, Hsu WM, Lee SM. Propionibacterium acnes DNA from an explanted intraocular lens detected by polymerase chain reaction in a case of chronic pseudophakic endophthalmitis. J Cataract Refract Surg 2006 ;32(3) : 522-525 7. Alfaro DV, Roth D, Liggett PE. Posttraumatic endophthalmitis. Causative organisms, treatment, and prevention. Retina. 1994;14(3):206-11. 8. EI-Asrar AM, Al-Obeidan SA, Yeboah EA. Late onset posttraumatic Propionibacterium acnes endophthalmitis. Eur J Ophthalmol. 2004 ; 14(5) : 442-444. 9. Johnson MW, Doft BH, Kelsey SF, Barza M, Wilson LA, Barr CC, Wisniewski SR: The Endophthalmitis Vitrectomy Study: Relationship between clinical presentation and microbiologic spectrum. Ophthalmology 104: 261-272, 1997 10. Endophthalmitis Vitrectomy Study Group: The Endophthalmitis Vitrectomy Study: Microbiologic factors and visual outcome. Am J Ophthalmol 22: 830-846, 1996. 11. Hahn Tw, Osterhout GJ, O’Brien TP, et al. Utility of a rapid fluorescent Gram stain for recognition of live bacteria in ocular infection. Invest Ophthalmol Vis Sci 36:s797, 1995. 12. Doft BH, Bazara M. Ceftazidime or amikacin:Choice of intravitreal antimicrobials in the treatment of postoperative endophthalmitis. Arch Ophthalmol 112:17-18, 1994.

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13. A.R. Watts1, J.I. Prydal1, K. Tambe1 and D.R. Jenkins. Linezolid, a New Antibiotic for the Treatment of Post-operative Endophthalmitis. Invest Ophthalmol Vis Sci 2003;44: 1451. 14. Aldave AJ, Stein JD, Deramo VA, Shah GK, Fischer DH, Maguire JI. Treatment strategies for postoperative Propionibacterium acnes endophthalmitis. Ophthalmology 1999 ; 106(12) : 23952401. 15. Anand A, Madhavan H, Neelam V, Lily T. Use of polymerase chain reaction in the diagnosis of fungal endophthalmitis. Ophthalmology. Feb 2001;108(2):326-30 16. Blumenkranz MS, Stevens DA. Therapy of endogenous fungal endophthalmitis: miconazole or amphotericin B for coccidioidal and candidal infection. Arch Ophthalmol. Jul 1980;98(7):121620. 17. Breit SM, Hariprasad SM, Mieler WF et al. Management of endogenous fungal endophthalmitis with voriconazole and caspofungin. Am J Ophthalmol. Jan 2005;139(1):135-40. 18. Gao H, Pennesi ME, Shah K, Qiao X, Hariprasad SM, Mieler WF, et al. Intravitreal voriconazole: an electroretinographic and histopathologic study. Arch Ophthalmol. Nov 2004;122(11):1687-92. 19. Martinez-Vazquez C, Fernandez-Ulloa J, Bordón J, Sopena B, de la Fuente J, Ocampo A, et al. Candida albicans endophthalmitis in brown heroin addicts: response to early vitrectomy preceded and followed by antifungal therapy. Clin Infect Dis. Nov 1998;27(5):1130-3.

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Vol. 21, No. 3, January-March, 2011

Delhi Journal of Ophthalmology

Major Review

The Operation Theatre : Basic Architecture Sapna, Saptorshi Majumdar, Pradeep Venkatesh Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi

Introduction Cleanliness of the hospital environment is the best starting point to achieve the highest patient safety mandate. There is a need to decrease the bio-burden present in the environment in an operating room. A systematic method of cleaning will decrease the possibility of the transmission of pathogens. Florence Nightingale, “The Lady with the Lamp,” and Joseph Lister (1827–1912), a professor at London’s King College Hospital were one of the first persons to realize the importance of sterilization. Joseph Lister successfully introduced carbolic acid (phenol) to sterilize surgical instruments and to clean wounds. During the 1990s, the US Department of Labor, Occupational Safety and Health Administration (OSHA) passed a regulation known as the Blood Borne Pathogen Standard. The standard required institutions to implement policies and procedures for the identification of potential exposure to blood borne pathogens. The Association of peri Operative Registered Nurses (AORN) developed “Recommended Practices for Environmental Cleaning in the Surgical Practice Setting,” which was approved by AORN’s board of directors and became effective from January 1, 2003.

Asepsis in Operation Theatre

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Stores room Nursing staff room Anaesthetist room Recovery room

C. Aseptic Zone - Scrub area - Preparation room - Operation theatre - Area used for instrument packing and sterilization. D. Disposal Zone Area where used equipments are cleaned and bio-hazardous waste is disposed. Marble or polished stone flooring is the preferred type with glazed tile walls. No false ceiling is permissible. The OT needs to be well ventilated such that it prevents any deposition of dust particles. Air circulation with a laminar air flow system through High efficiency particulate air filter (HEPA) (0.3µm) serves the best purpose. As per US Public Health services minimum requirements for OT air are 25 changes per hour, positive pressure compared with corridors, temperature between 18 & 24º C and humidity of 50 to 55%.[1]

Aseptic technique is a set of specific practices and procedures performed under carefully controlled conditions with the goal of minimizing contamination by pathogens.

Cleaning and Disinfection of OT

The Operation Theatre: Basic architecture

Cleaning

The design and location of OT complex is one of the most important components of OT asepsis. OT complex is located away from the inpatient area, often in a blind wing or on the top or bottom floor. It is a scientifically planned barrier system, such that it keeps the flow of traffic from clean areas to dirty ones and never vice versa. It consists of 4 zones: A. Outer zone Areas for receiving patients relatives, toilets, administrative function. B. Restricted Zone - Changing room - Patient transfer area

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Cleaning, disinfection and sterilization are the cornerstones in ensuring operation theatre asepsis.

General Cleaning: General cleaning involves scrubbing with detergents and rinsing with water. This is the first step, albeit very important, before any disinfection measure can be undertaken. Spot cleaning of walls and ceiling should be undertaken as needed everyday. Open shelves need to be cleaned daily with a detergent while closed cabinets may be cleaned once weekly. The floor should ideally be sprayed and wet vacuum pick up used after each surgical procedure and at the end of the days’ schedule. All horizontal surfaces in the OT (e.g. furniture, surgical lights, and equipment) should be damp-dusted with an Environmental Protection Agency (EPA) registered disinfectant like lysol brand deordorizing disinfectant cleaner

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and clorox disinfecting spray III at the end of each case and cleaned thoroughly at the end of the day. The lights and other portable equipment should additionally be steam cleaned weekly. Similarly, anesthesia equipment needs to be cleaned and processed according to AORN’s recommended practices. The sink area should be cleaned several times daily and kept as dry as possible The outside of autoclaves should be cleaned daily while the inside surface is cleaned weekly. Soiled linen should never be left on the floor or transported on a trolley used for other purposes. Liquid waste material such as the contents of suction bottles should never be disposed off in a scrub sink or utility sink but only into a container meant for the purpose. Cleaning before subsequent surgery For each subsequent surgical case, a safe environment needs to be re- established. Preparation of the OT should involve visual inspection and spot cleaning of visible contamination. Walls, doors, surgical lights and ceilings should be spot cleaned in the event of being soiled with blood, tissue or body fluids. Visibly soiled areas on the floor should be cleaned using a new or freshly laundered mop head and an EPA- registered hospital-grade germicidal agent. The OT bed should be moved to check for such items as sponges and instruments that may have fallen into open spaces. Data does not support cleaning the entire floor after each case. Terminal Cleaning Because a clean surgical environment assists in the reduction of microorganisms, each surgical procedure room and scrub/ utility area should be terminally cleaned at the end of the day’s schedule. An EPA-registered agent lysol brand deordorizing disinfectant cleaner and clorox disinfecting spray III and mechanical friction needs to be used to clean all surfaces, including the surgical lights, all furniture, scrub and utility areas, scrub sinks etc. Disinfection of the OT There are three levels of disinfection: High, intermediate, and low. High- level disinfection kills all organisms, except high levels of bacterial spores and prions, and is effected with a chemical germicide cleared for marketing as a sterilant by the Food and Drug Administration like glutraldehyde based and orthopthaldehyde based agents (available in India) . Intermediate- level disinfection kills mycobacteria, most viruses, and bacteria with a chemical germicide registered as a tuberculocide by the Environmental Protection Agency (EPA). Low- level disinfection kills some viruses and bacteria with a chemical germicide registered as a hospital disinfectant by the EPA.

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The Operation Theatre : Basic Architecture

Chemical Disinfection a)Formaldehyde fumigation Commonly used to sterilize the OT. Requirement (For an area of 1000 cubic feet) - 500 ml of 40% formaldehyde in one liter of water - Stove or hot plate for heating formalin - 300 ml of 10% Ammonia Procedure Close all doors & windows air tight and switch off fans and A.C. Heat formalin solution till boiling dry Leave the OT unentered over night Enter the OT next day morning with 300ml of ammonia Keep the ammonia solution for 2-3 hrs to neutralize formalin vapours Open the OT to start surgery Advised fumigation at weekly intervals Mode of Action Formaldehyde inactivates microorganisms by alkylating the aminoacid and sulfhydryl groups of proteins and ring nitrogen atoms of purine bases. Disadvantages OSHA indicated that Formaldehyde should be handled in the workplace as potential carcinogen and set an employee exposure standard for Formaldehyde that limits an 8-hour time- weighted average exposure concentration of 0.75ppm. b) Commercially available disinfectant Baccilocid rasant A newer and effective compound in environmental decontamination with very good cost/benefit ratio, good material compatibility, excellent cleaning properties and virtually no residues. It has the advantage of being a Formaldehyde-free disinfectant cleaner with low use concentration. Active ingredients: Glutaral 100 mg/g, benzyl-C12-18alkyldimethylammonium chlorides 60 mg/ g, didecyldimethylammonium chloride 60 mg/g. Advantages - Provides complete asepsis within 30 to 60 minutes. - Cleaning with detergent or carbolic acid not required. - Formalin fumigation not required. - Shutdown of O.T. for 24 hrs not required. c) Aldekol A new method of fumigation has been evolved using ‘Aldekol’, a mixture containing 6% formaldehyde, 6% glutaraldehyde Vol. 21, No. 3, January-March, 2011

The Operation Theatre : Basic Architecture

and 5% benzalkonium120 chloride

Disinection by radiation Ultraviolet radiation - Daily U.V. Irradiation for 12 -16 hrs - To be switched off 2 hrs before

Processing of Equipment, Instruments and Other Reusable Items Steps involved are 1. Decontamination of Equipment, Instruments, and Other Reusable Items Immediately after use, all surgical instruments, reusable gloves, and other items that have been in contact with blood or other body fluids should be placed in a plastic bucket containing a solution of 0.5% chlorine for 10 minutes.[2] After 10 minutes, the items should be removed from the chlorine solution and rinsed with water or cleaned immediately 2. Cleaning of Equipment, Instruments, and Other Reusable Items The instruments and other items should be scrubbed vigorously with a brush (a tooth brush is a good option) in lukewarm water with detergent to remove all blood, tissue, and other residue. Cleaning instruments with ultrasonic cleaner is used for cleaning of micro surgical instruments and instruments with hinged areas and serrated edges, endoscopes or other lumened devices such as phaco or irrigation & aspiration hand pieces. 3. Sterilization and high level disinfection of equipments Sterilization is complete destruction of all microorganisms, both the vegetative forms and their spores. It is the terminus of the continuum where risk of contamination is, effectively, reduced to the lowest practical point. Although sterilization is the safest and the most effective method for the final processing of instruments, often sterilization equipment is either not available or not suitable. In these cases, High Level Disinfection is the only acceptable alternative.[3] The threat of infection by spores or prions does not exist in all circumstances so sterilization of all items used on or by patients is unnecessary. The system used to determine whether items should be cleaned, disinfected, or sterilized was given in 1968 by Earl Spaulding According to the Spaulding system, the level of processing required is based on the nature of the item and the manner in which it is to be used.[4] 1). Items that enter sterile tissue or the vascular system are categorized as critical and should be sterile when used. Examples of critical items include most of the surgical Vol. 21, No. 3, January-March, 2011

Delhi Journal of Ophthalmology

instruments, catheters, needles, implants, etc 2) Items that come in contact with non intact skin or mucous membranes are considered semi critical and should receive a minimum of high-level disinfection immediately before use. This includes the anesthesia equipment, respiratory therapy equipment etc. 3) Items that come in contact only with intact skin are categorized as noncritical items and should receive intermediate-level disinfection, low-level disinfection, or cleaning. This is explained as intact skin acts as an effective barrier to most organisms. (1) Examples of noncritical items include the tourniquets and blood pressure cuffs, linens, etc.

Methods of High Level Disinfection of equipments Physical methods • HLD by Boiling: Boling destroys all vegetative forms of bacteria, viruses (including HBV, HCV and HIV), yeasts and fungi, but does not kill all endospores reliably. 20 minutes of immersion time is needed, after the water has started boiling. Once the instruments are dry, if any pooled water remains in the bottom of the container, remove the dry items and place them in another high-level disinfected container that is dry and can be tightly covered. If stored in an ordinary covered container, the objects can be used for up to 24 hours only. • HLD by Steaming (moist heat) Essentially all vegetative forms of bacteria are killed by moist heat at temperatures of 60– 75 0C within 10 minutes [5] Hepatitis B virus, which is one of the most difficult viruses to kill, is inactivated in 10 minutes when heated to 80 0C. In contrast, although many types of spores are killed when boiled at 99.5 0C for 15 to 20 minutes, Clostridium tetani spores are quite heat-resistant and can even survive boiling for up to 90 minutes.The highest temperature that boiling water or lowpressure steam will reach is 100 0C (212 0F) at sea level. Because the boiling point of water is 1.1 0C lower for each 1,000 feet in altitude, it is best to boil or steam items to be high-level disinfected for a minimum of 20 minutes • High level disinfection only by chemical method Although a number of disinfectants are commercially available in most countries, four disinfectants— chlorine, glutaraldehyde, formaldehyde and peroxide— are routinely used as high-level disinfectants. These chemicals can achieve high-level disinfection if the items being disinfected are thoroughly cleaned before immersion.[6,7] A highlevel disinfectant should be selected for use based on the characteristics of the items to be disinfected, the physical area and the skills of personnel available to do the procedure.[8,9]

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A brief review of each of the above agents is provided here: Chlorine solutions are fast acting, very effective against HBV, HCV and HIV/ AIDS, inexpensive and readily available (CDC 1987; WHO 1989).[10,11,12] Formaldehyde (8%), which is inexpensive and readily available, is an effective high-level disinfectant (HLD) but, the vapours are very irritating and it is classified as a potential carcinogen. Do not dilute with chlorinated water as a dangerous gas (bischloromethyl-ether) can be produced. Glutaraldehydes are less irritating than formaldehyde, but staff and clients still need to be protected from the fumes when mixing and using these solutions Hydrogen Peroxide (H2O2), which must be diluted to a 6% solution, often is available locally and is less expensive than other chemical disinfectants. The 3% H2O2 solutions used as antiseptics, however, should not be used as a disinfectant. The major disadvantage of peroxide is that it is highly corrosive and should not be used to disinfect copper, aluminum, zinc or brass. Alcohols and Iodophors Although alcohols and iodophors are inexpensive and readily available, they are no longer classified as high-level disinfectants. Alcohols do not kill some viruses and are not sporicidal. Pseudomonas species have been shown to multiply in iodophors. [13]

Sterilization of equipment Steam Sterilization (Autoclaving) Steam sterilization (frequently referred to as autoclaving) depends on the use of steam above 100 0C. Temperatures ranging from 121-134 0C at pressures of 15-30 psi are generally recommended. Steam readily penetrates all wrapped materials with the destruction of all viruses and bacteria, including the most resistant spores. [14,15] It acts by denaturing the major cell constituents. Minimum holding times for the sterilization of medical equipment are 15 minutes at 121 0C, 10 minutes at 1260C, and 3 minutes at 1340C. Flash Sterilization It is a method of emergency sterilization. The equipments to be decontaminated are kept at 132º C at 30 lbs of pressure for 3 minutes. Chemical Sterilization (Liquids)

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The Operation Theatre : Basic Architecture

The use of chemical solutions as a sterilization technique for surgical equipment is frequently employed, but it should be stressed that most solutions only disinfect and do not guarantee sterility. When the necessity for maintaining sterility is a critical factor, as in the implantation of prosthetic devices, indwelling catheters or vascular access ports, disinfection in chemical solutions is not recommended. [16] Glutaraldehyde( 2%) It is suitable for instruments that cannot be autoclaved like sharp cutting instruments, plastic & rubber items, and endoscopes. It is effective against vegetative pathogens in 15 minutes and resistant pathogenic spores in 3 hrs. It is not recommended for lumen containing instruments such as irrigating cannulae as the residual glutaraldehyde, even after rinsing, causes corneal edema, endothelial cell damage and uveitis. The recommended time period for effective sterilization is 8- 10 hours. Articles can then be stored in a covered sterile container for up to 7 days.

Chemical Sterilization (Gas) Ethylene Oxide (E. T. O.) E. T. O. kills micro organisms by alkylating their DNA. Widely used for re -sterilizing ‘packaged heat sensitive devices’ like sharp knives and blades. It is non-corrosive and safe for most plastic and polyethylene materials. Thus, it is the preferred method for sterilizing heat labile tubings, vitrectomy cutters, cryoprobes, light pipes, laser probes, diathermy leads, cannulated instruments like endoscopes etc. However, it is not applicable to liquids or to articles in impervious packaging material. A typical ETO sterilization cycle includes 1. Packing of the articles to be sterilized. 2. Arranging and loading the sterilizer. 3. Air removal with a vacuum pump. 4. Heating to the required temperature (45 0C– 55 0C). 5. Steam humidification maintained at a relative humidity of 60 %. 6. Exposure to the ETO at 5 psi for 12 hours or at 10 psi for 6 hours. 7. Gas removal by 70 psi vacuum. 8. Air flush by filtered air repeated 4 times to re -establish atmospheric pressure. 9. Aeration to elute residual ETO - Articles should be well aerated prior to use to minimize the potential for tissue toxicity. Ethylene oxide gas is a potential carcinogen and mutagen and represents a potential occupational health hazard for personnel operating the sterilizers.

Sterilization by radiation

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Delhi Journal of Ophthalmology

The Operation Theatre : Basic Architecture

Gamma irradiation This is a method for cold sterilization with high penetrating power which is lethal to DNA.

India) impregnated with spores of Bacillus stereothermophillus are used. For ETO sterilizer, the biological indicator is a Bacillus subtilis spore.

Sterilization methods of choice for articles during ocular surgery 1. Linen (Gowns, Caps, Masks, Drapes)- Autoclaving. 2. Glassware (Syringes) - Dry heat sterilization, or use disposables from reputed firms. 3. Metal instruments- Autoclaving. 4. Plastic instruments/ Components- Ethylene oxide sterilization, formalin chamber. 5. Sharp edges instruments (e.g. Vannas scissors, keratome) ETO/ Hot air oven/ Chemical disinfection. 6. Sutures (including monofilament nylon) - Can be autoclaved. 7. Diathermy, Cautery electrodes- Autoclaving. 8. Endoilluminators/ probes- Ethylene oxide sterilization. 9. Silicone oil/ buckles/ sponges- Autoclaving.

Principles of sterile technique in OT

Monitoring

•

Surveillance of Operation theatre: Microbiological monitoring Swabs are collected from various locations in the OT and cultured as described. The areas swabbed include 1. Operation table at the head end 2. Over head lamp 3. Four Walls 4. Floor below the head end of the table 5. Instrument trolley 6. AC duct 7. Microscope handles. The swabs obtained are cultured for aerobic (Chocolate agar) and anaerobic (Robertson’s Cooked Meat Medium) growth. [13]

Evaluation of Quality of air in OT Settle plate method: One plate of blood agar and Sabouraud’s dextrose agar (SDA) is placed in the center of the OT (Close to operation table) and the lid is kept open for 30 min. Blood agar is then incubated at 37° C for 48 hrs,& SDA at 27° C for 7 days. Colony counts of bacteria and fungi are reported.[5] Slit sampler method (from given volume): Very Effective, highly sensitive. Fixed volume of air is sucked and bacterial counts are made.Bacterial colony count of more than 10 per plate and fungal colony of more than one per plate are considered unacceptable.

Testing efficacy of autoclaves Biological indicators (BI) containing bacterial spores are used for monitoring the efficacy of sterilizers. Commercially available spore strips (Hi- Media, Mumbai and by Cole Palmer, Vol. 21, No. 3, January-March, 2011

• • • • • • • • •

• • • •

•

All items in a sterile field must be sterile. Sterile packages or fields are opened or created as close as possible to time of actual use. Moist areas are not considered sterile. Contaminated items must be removed immediately from the sterile field. Only areas that can be seen by the clinician are considered sterile, i.e., the back of the clinician is not sterile. Gowns are considered sterile only in the front, from chest to waist and from the hands to slightly above the elbow. Tables are considered sterile only at or above the level of the table. Nonsterile items should not cross above a sterile field. There should be no talking, laughing, coughing, or sneezing across a sterile field. Personnel with colds should avoid working while ill or apply a double mask. Edges of sterile areas or fields (generally the outer inch) are not considered sterile. When in doubt about sterility, discard the potentially contaminated item and begin again. A safe space or margin of safety is maintained between sterile and nonsterile objects and areas. When pouring fluids, only the lip and inner cap of the pouring container is considered sterile. The pouring container should not touch the receiving container, and splashing should be avoided. Tears in barriers are considered breaks in sterility.

Legal responsibility In each hospital, an interdisciplinary team should meet periodically to discuss the process of cleaning the operating rooms. Role of Microbiology Departments lies in identifying the pathogens, monitoring of antibiotic therapy and proper education on specimen collection and transportation. They should also be updated with information on common antibiogram patterns, and communicate the same to the clinical staff. They maintain data on hospital infection and surveillance of the Hospital environment. The team must consider changes needed in the cleaning protocol in response to rising infection rates with increased multidrug-resistant bacteria or newly emerging pathogens. Importance of Staff Education cannot be over emphasized. They need to be well trained in a scientific manner with specific duties and responsibilities allotted to each. Written policies and protocols lay the groundwork for all personnel to have the same understanding of the outcome expected.

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References 1. Sehulster LM. Chinn RYW, Arduino MJ, Carpenter J, Donlan R, Ashford D, et al Guidelines for environmental refection control in health care facilities. Recommendations from CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC) November 2003. 2. McIntosh N et al. 1994. Practical Methods for High-Level Disinfection of Surgical Gloves. Paper presented at American Public Health Association Annual Meeting. Session no. 2285, Washington, D.C., 31 October–4 November. 3. Rutala WA. Disinfection and sterilization of patient care items In: Herwaldt LA, Decker MD. A Practical Handbook for Hospital Epidemiologists. Thorofare, NJ BLACK Inc; 1998:271-280. 4. Spaulding EH. 1939. Studies on chemical sterilization of surgical instruments. Surg Gyne Obstet 69: 738–744. 5. Salle AJ. 1973. Fundamental Principles of Bacteriology, 7th ed. McGraw- Hill Book Company: New York. 6. Spaulding EH Role of chemical disinfection in the prevention of nosocomial infections In: Brachman PS, Eickhoff TC, eds Proceedings for the International Conference on Nosocomial Infections, 1970 Chicago, IL: American Hospital Association: 1971:247-254. 7. Spaulding EH. Chemical disinfection and antisepsis in the hospital J Heap Res 1972;9:5-31. 8. Rutala WA. Selection and use of disinfectants in health care. In: Mayhall CG Hospital Epidemiology and Infection Control 1st ed Baltimore, MD: Williams & Wilkins; 1996:913-936.

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Tietjen LG, W Cronin and N McIntosh. 1992. High-level disinfection, in Infection Prevention Guidelines for Family Planning Programs. Essential Medical Information Systems, Inc.: Durant, OK, pp 74–84. 10. Centers for Disease Control (CDC). 1987. Recommendations for prevention of HIV transmission in health care settings. MMWR 36(Suppl 2): 1S–18S 11. Rutala WA et al. 1998. Stability and bactericidal activity of chlorine solutions. Infect Control Hosp Epidemiol 19(5): 323– 327. 12. Rutala WA. 1996. APIC guidelines for selection and use of disinfectants. Am J Infect Control, 24(4): 313–342. 13. Favero MS. 1985. Sterilization, disinfection, and antisepsis in the hospital, in Manual of Clinical Microbiology, 4th ed. Lennette EH et al (eds). American Society for Microbiology: Washington, DC, pp 129–137. 14. Perkins JJ. 1983. Principles and Methods of Sterilization in Health Sciences, 2nd ed. Charles C. Thomas Publisher Ltd.: Springfield, IL. 15. Russell AD, WB Hugo and GA Ayliffe. 1982. Principles and Practice of Disinfection, Preservation and Sterilization. Blackwell Scientific Publications: Oxford, England. 16. Spaulding EH. Chemical disinfection of medical and surgical instruments In: Lawrence CA, Block SS. eds. Disinfection, Sterilization, and Preservation Philadelphia, PA: Lea & Febiger; 1968.

Vol. 21, No. 3, January-March, 2011

Delhi Journal of Ophthalmology

Major Review

Upshoot And Downshoot In Duane’s Retraction Syndrome: Mechanism And Treatment Suma Ganesh Department of Pediatric Ophthalmology and Strabismus, Dr Shroffs Charity Eye Hospital, New Delhi

Definition Duane syndrome (DS) is a rare, congenital eye movement disorder most commonly characterized by the inability of the eye to turn out. The syndrome was first described by Jakob Stilling (1887) and Siegmund Türk (1896), and subsequently named for Alexander Duane who discussed the disorder in more detail in 1905[1].

Clinical Features DS is a miswiring of the eye muscles that causes some eye muscles to contract when they should not and other eye muscles not to contract when they should. People with DS have abduction deficiency, narrowing of the palpebral fissure with retraction of globe on attempted adduction, and upshoot or downshoot, which can be the most prominent feature[2].

Upshoot and Downshoot: Mechanism The upshoots and downshoots are seen in 25% to 39% of patients with Duane’s retraction syndrome[3]. Upshoots and downshoots are classified into two types: mechanical and innervational[4]. In the mechanical type upshoot and downshoot in DS is due to tight lateral rectus attached to the crest of the globe, which causes the muscle to slip off the globe when the eye is adducting. This upshoot may look cosmetically very disfiguring even in patients with orthtropic Duane’s syndrome. Removal of the muscle from the crest of the globe can be achieved either by a very large recession of the lateral rectus muscle or by Y splitting the lateral rectus muscle. (figure 1a and b). In the innervational type, there is gradually increasing upshot or downshoot of the eye in the horizontal position as it moves into adduction. This is due to co-innervation of the vertical rectus muscle with the lateral rectus muscle. The innervational type can be improved with recession of the appropriate vertical rectus muscle[4].

Management Indications for surgery Not all patients of Duane’s Retraction Syndrome require surgery. Indications for surgery include a significant deviation in primary position, abnormal head posture, retraction and Vol. 21, No. 3, January-March, 2011

narrowing of palpebral fissure, and significant upshoot or downshoot[5].Successful surgery results in a straighter head position, a lessening of enophthalmos and upshoot and downshoot, and better alignment in primary position. Surgical Options Various surgical techniques have been employed for the treatment of upshoot and downshoot. Eisenbaum and Parks [6] reported performing posterior fixation suture (Faden operation) on vertical and horizontal muscles to treat upshoot and downshoot in patients with Duane retraction syndrome. Stabilization of the lateral rectus muscle, however, did produce satisfactory results with elimination of the upshoot. Recession of both horizontal recti Recession of both horizontal rectus muscles has been shown to decrease the elevation and depression of the adducted eye and improvement in retraction of the globe[7,8]. The amount of recession of both horizontal rectus muscles, if balanced, will not adversely effect alignment or motility[7,8]. However, it is necessary to consider the primary position deviation when deciding on the amount of surgical intervention. The medial rectus muscle should be recessed relatively more than the lateral rectus muscle in cases of esotropia in primary position whereas in exotropia the recession of lateral rectus may be proportionately increased. The following case illustrates improvement with this procedure.

Case 1 A 16-year-old female presented with squinting and an enophthalmic appearance of left eye. Unaided visual acuity was 6/6 in both eyes. She had normal head posture .Orthoptic examination showed she had exotropia of 12 prism diopters with limitation of movement in adduction of left eye and severe upshoot on adduction. Surgery Large recession of the medial (10-mm) & Lateral rectus (12mm) was performed in the ipsilateral eye. Postoperatively a left hypertropia 2 prism diopters and residual exotropia of 8 prism diopters was recorded. The enophthalmic appearance of the eye improved and there was no upshoot during adduction.

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Upshoot And Downshoot In Duane’s Retraction Syndrome: Mechanism And Treatment

Upgaze

Primary

syndrome. The patients showed a marked decrease in upshoot and downshoot, without vertical deviation, after surgery. Das et al reported marked amelioration of upshoot and downshoot with Y-splitting of the lateral rectus muscle at the insertion in a patient with type-I Duane retraction syndrome with cosmetically unacceptable upshoot in adduction. The following two cases are examples to show an improvement in upshots and down shoot after Y split surgery.

Downgaze

Figure 1A : Severe upshoot and downshoot on adduction

Upgaze

Primary

Downgaze

Figure 1B : Postop pictures showing improvement after Y split

Y – split of lateral rectus The splitting of the ends of the lateral rectus muscle into a Y-configuration (figure 2a & b) is a unique idea first advocated by Jampolsky[9]. The bifurcation of the muscle decreases the upward or downward rotation of the globe because the halves are positioned to stabilize the muscle’s position on the eye. Subsequently, Rogers and Bremer[10] performed Y-splitting of the lateral rectus muscle along with medial rectus muscle recession in five patients with Duane retraction

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Figure 2 : The bifurcation and recession of the lateral rectus (top) for upshoot and downshoot acts by removing the muscle from the crest of the globe, with the two recessed muscle arms spread apart. Each muscle arms are vertically transposed such that the two arms are spread apart a total of 20 mm and each arm recessed 5-10 mm as appropriate for each case. This ameliorates both the globe retraction and the upshoot and or downshoot. This figure is adapted from: Jampolsky A. Duane Syndrome in Rosenbaum A L. Santiago A P. Clinical Strabismus Management: Principles and Techniques 1999. W B Saunders Company: 335-336.

Case 2 A 12-year-old girl presented with complaints of squinting Vol. 21, No. 3, January-March, 2011

Upshoot And Downshoot In Duane’s Retraction Syndrome: Mechanism And Treatment

since childhood. Unaided visual acuity was 6/6 OU. She did not have abnormal head posture and there was no squint in the primary position. However, Version tests revealed that there was limitation of abduction of the left eye and there was severe upshoot and down shoot on adduction.

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Delhi Journal of Ophthalmology

Case 3 A 25- year- old male came to SCEH with complaints of abnormal head posture since childhood. Unaided visual acuity was 6/6 in both eyes. He had face turn to the right side. He had left exotropia of 20 prism diopters when his head was straight. Version testing showed a limitation of abduction of his left eye and retraction of the globe and narrowing of the palpebral fissure on adduction was noted. A significant upshoot and downshoot was noted in elevation and depression in the adducted position. Fusion and stereopsis was present with abnormal head posture and he had stereopsis of 400 arcs second on the Titmus test.

Downshoot Figure 4A : Improvement in head posture after surgery Figure 3 A: Preop photos

Surgery She underwent 5 mm MR recession combined with 7 mm lateral rectus recession combined with lateral rectus Y split. After surgery her upshoot and downshoot were corrected and she looked much better cosmetically. Figure 3a & b

Figure 4B : Marked upshoot in dextroversion pre operatively

Figure 3 B: Improvement in Upshoot & Downshoot

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Figure 4C : Improvement in upshoot post operatively

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Upshoot And Downshoot In Duane’s Retraction Syndrome: Mechanism And Treatment

Preop The patient underwent lateral rectus recession of 8 mm combined with a Y splitting of the lateral rectus 20 mm apart. Post- operatively his head posture had completely resolved but he had some residual upshoot which was not cosmetically disturbing to patient. Figure 4 a, b & c References 1 Duane A. Congenital deficiency of abduction associated with impairment of adduction, retraction movement, contraction of the palpebral fissure and oblique movements of the eye. Arch Ophthalmol. 1905;34:133–159. 2. Das JC, Chaudhuri Z, Bhomaj S, Sharma P. Lateral rectus split in the management of Duane’s retraction syndrome. Ophthalmic Surgery and Lasers 2000;31:499-501 3. Mohan K, Saroha V, Sharma A. Factors predicting upshoots an downshoots in duane retraction syndrome. J Pediatric Ophthalmol Strabismus 4. Kraft SP. Surgical approach for Duane syndrome. J Pediatric Ophthalmol strabismus1988;25 : 119- 130 5. Gobin MH. Surgical management of Duane’s syndrome. Br J Ophthalmol. 1974;58:301–306.

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6.

Eisenbaum AM, Parks MM. A study of various surgical approaches for the leash effect in Duane’s syndrome. Presented at the joint session of the American Association for Pediatric Ophthalmology and Strabismus and the American Academy of Ophthalmology, Chicago, IL, November 5, 1989 7. von Noorden GK. Recession of both horizontal recti muscles in Duane’s retraction syndrome with elevation and depression of the adducted eye. Am J Ophthalmol. 1992;114:311–313. 8. Sprunger DT. Recession of both horizontal rectus muscles in Duane’s syndrome with globe retraction in primary position. J Pediatr Ophthalmol Strabismus. 1997;1:31–33. 9. Jampolsky A. Discussion of Eisenbaum AM, Parks MM. A study of various surgical approach to the leash effect in Duane’s syndrome. Presented at the joint session of the American Association for pediatric ophthalmology and strabismus and the American Academy of Ophthalmology, Chicago, IL, November 5, 1980 10. Rogers GL, Bremmer DL. Surgical treatment of the upshoot and downshoot in Duane’s retraction syndrome. Ophthalmology. 1984;91:1380–1382 11. Feretis D. Papastratigakis B, Tsanparlakis J. Planning surgery in Duane’s retraction syndrome. Ophthalmologica. 1981;183:148– 153.

Vol. 21, No. 3, January-March, 2011

Delhi Journal of Ophthalmology

Major Review

Marcus Gunn Jaw-Winking Phenomenon : A Review Dewang Angmo, Mandeep S. Bajaj, Neelam Pushker, Supriyo Ghose Dr. Rajendra Prasad Centre for Ophthalmic Sciences, AIIMS, New Delhi Marcus Gunn jaw-winking phenomenon is the most common form of congenital synkinetic neurogenic ptosis. In this synkinetic phenomenon, the unilaterally ptotic eyelid elevates with jaw movements. The movement that most commonly causes elevation of the ptotic eyelid is lateral mandibular movement to the contralateral side. This phenomenon is usually first noticed by the mother when she is feeding or nursing the baby. This article presents a review of Marcus Gunn jaw-winking phenomenon including clinical features, pathophysiology and treatment modalities.

In 1883 Robert Marcus Gunn described a 15yr girl with a peculiar type of congenital ptosis that included an associated winking motion of affected eyelid on the movement of jaw1. This synkinetic jaw-winking phenomenon now bears its name.

Figure2: Patient with Marcus Gunn Jaw-Winking phenomenon. (A) 22 yrs female with unilateral upper eyelid ptosis as part of Marcus Gunn phenomenon. (B) Left upper eyelid raises with the jaw movement to opposite side.

Figure 1: Patient with Marcus Gunn Jaw-Winking phenomenon. (A) 5year old child with unilateral upper eyelid ptosis as part of Marcus Gunn phenomenon. (B) Elevation of concomitant upper eyelid with mouth opening

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The Marcus Gunn phenomenon is known variously as jawwinking (a misnomer as eyelid rises rather than falls) and more descriptively, as pterygoid-levator synkinesis2. The Marcus Gunn phenomenon has been associated with congenital blepharoptosis with an incidence of 4-6% [2,3,4]. Acquired

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forms have been described after eye surgery, trauma, post Bells palsy and pontine tumors[2]. Spontaneous remission of the acquired form may be expected, whereas the congenital form persists (no improvement with age)[12]. Patients with Marcus Gunn jaw-winking phenomenon have a variable degree of blepharoptosis in the resting and primary position. Although Marcus Gunn jaw-winking syndrome is usually unilateral[12-13] it can present bilaterally in rare cases.

2) Functional Interference 1. Irritation of normally dormant connection 2. Disinhibition of pre-existing phylogenetically more primitive mechanisms (Ascher): This is thought to explain why individuals who are not affected will often open their mouth while attempting to widely open their eyes to place eye drops 3. Spread of impulses by irradiation

The characteristic feature of the phenomenon is that the raising; and not winking of the affected eyelid is synchronous with and proportionate to the opening of the mouth. The wink reflex consists of a momentary upper eyelid retraction or elevation to an equal or higher level than the normal fellow eyelid upon stimulation of the ipsilateral pterygoid muscle 12-13.

3) Atavistic Reversion 1. In fish a strong associated movement of jaw opening and eye opening i.e., deep muscle contracting and superficial muscle relaxing. Thus a weak levator may only elevate the lid when its antagonist, the orbicularis (superficial muscle) is reflexly relaxed by jaw opening (external pterygoid-deep muscle contraction ) 2. EMG study suggested dysfunction in the midbrain and brainstem

This response is followed by a rapid return to a lower position. The amplitude of the wink tends to be worse in downgaze. This rapid, abnormal motion of the eyelid can be the most disturbing aspect of the jaw-winking syndrome.

MARCUS GUNN JAW-WINKING PHENOMENON The wink phenomenon i.e., retraction of the ptotic lid occurs in conjunction with stimulation of pterygoid muscle, which is elicited by opening the mouth, thrusting the jaw to the contra lateral side, jaw protrusion, chewing, smiling or sucking. This wink phenomenon is often discovered early, as the infant is bottle-feeding or breastfeeding[14]. Jaw-winking ptosis is almost always sporadic, but familial cases with an irregular autosomal dominant inheritance pattern have been reported[15].

Pathophysiology A complete explanation has not yet been advanced to elucidate the rationale of jaw-winking phenomenon. Various theories have been hypothesized [15,16]. 1) Aberrant connection This hypothesis is favored by most authors, though they differ in opinion as to the location of the aberration 1. Cortical or sub cortical connections 2. Internuclear connections or faulty distribution in the posterior longitudinal bundle 3. Infranuclear connection exists between motor branches of the trigeminal nerve (CN V3) innervating the external pterygoid and the fibers of superior division of the oculomotor nerve (CN III) that innervates the levator muscle of the upper lid 4. Peripherally - some CN V fibers may reach the levator via the auriculo- temporal nerve

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Marcus Gunn Jaw-Winking Phenomenon : A Review

Measurement of Mgjwp The amount of jaw-winking is the excursion of the upper eyelid with synkinetic mouth movement. It is measured with a millimeter ruler. Jaw-winking is assessed as [2,10] : Mild < 2mm ; Moderate 2-5mm; Severe ≥ 6mm

Frequency Approximately 50% of blepharoptosis cases are congenital. Incidence of Marcus Gunn jaw-winking syndrome among this population is approximately 4-5% [12,13].

Associations 1. Ocular 1. Strabismus (50%-60%)[9] 1. Superior Rectus Palsy-25% 2. Double Elevator Palsy-25% 2. Anisometropia (5%-25%)[9] Incidence of anisometropia among patients with Marcus Gunn jaw-winking syndrome is reported to be 5-25%. 3. Amblyopia (30-60%)[9] Almost always secondary to strabismus or anisometropia, and only rarely, is due to occlusion by a ptotic eyelid. 2. Systemic Systemic anomalies in association with Marcus Gunn phenomenon are rare. 1. Cleft lip/ Cleft palate 2. CHARGE Syndrome reported in association with bilateral cases. 3. Renal calculi (Awan 1976) Schultz and Burian (1960) reported a case of MGP associated with several systemic malformations. These included Vol. 21, No. 3, January-March, 2011

Marcus Gunn Jaw-Winking Phenomenon : A Review

ectrodactly, bilateral pes cavus with ankle varus, spina bifida occulta, bilateral undescended testis and supernumerary incisors.

Race No known racial predilection exists.

Sex Early reports showed jaw-winking ptosis to be more prevalent in females than in males; however, larger case series have shown an equal prevalence among males and females4, 9.

Age Marcus Gunn jaw-winking syndrome is usually evident at birth. The winking phenomenon is often first noted by the parents when the infant is feeding.

Treatment 1. Medical Care If amblyopia is encountered, treat aggressively with occlusion therapy and/or correction of anisometropia prior to any consideration of ptosis surgery. 2. Surgical Care As with any patient who requires eyelid surgery, first address associated strabismus. 1. Superior rectus palsy Superior rectus palsy can be corrected by resecting the superior rectus muscle but only in the absence of inferior rectus restriction. Since the superior rectus is loosely bound to the overlying levator, the upper eyelid will be pulled inferiorly during resection, exacerbating any ptosis already present. This can be addressed during the subsequent ptosis repair. 2. Double elevator palsy Double elevator palsy manifests as a deficit in the elevation of the globe in all fields of gaze. It may be the result of superior rectus and inferior oblique palsy and/or inferior rectus restriction. Inferior rectus restriction may be suggested by the following 1. Positive forced duction in elevation 2. Normal force generations in up gaze indicating an absence of superior rectus or inferior oblique palsy 3. Poor or absent Bells phenomenon on the affected side Inferior rectus restriction is treated by recession of the inferior rectus muscle. A combined superior rectus and inferior oblique (double elevator) palsy requires a transposition procedure to displace the medial and lateral recti muscles superiorly (Knapp’s Vol. 21, No. 3, January-March, 2011

Delhi Journal of Ophthalmology

procedure). 3.Consider eyelid surgery only when the parents (or the patient) and the surgeon agree about whether the most cosmetically objectionable condition is the ptosis or the jawwinking or whether it is a combination of both. 4. Many techniques are described for the correction of jawwinking ptosis, reflecting the ongoing controversy regarding the surgical management of this condition. 5. If the jaw-winking is cosmetically insignificant, it can be ignored in the treatment of the ptosis. If the ptosis is mild, the patient may elect not to proceed with surgery. If correction is desired, perform a Muller muscle and conjunctival resection (MMCR), a Fasanella-Servat procedure or a standard external levator resection[14,18]. If the ptosis is moderate to severe, a levator resection may be indicated. Beard advocated performing more resection than normal to avoid undercorrection[13]. In severe ptosis, a super maximum (>30 mm) levator resection or frontalis suspension is necessary [19]. 6. Although the amount of ptosis and synkinetic eyelid movement is variable, those patients with more severe ptosis tend to have the worse aberrant upper eyelid movement. 7. The jaw-wink is considered cosmetically significant if it is 2 mm or more [2]. 8. Any attempt to repair the ptosis without addressing the jawwinking would result in an exaggeration of the aberrant eyelid movement to a level well above the superior corneal limbus, which would be unacceptable to the patient. 9. Several techniques have been suggested to obliterate levator function, which effectively dampens the aberrant eyelid movement. Bullock advocated complete excision of the levator aponeurosis and muscle all the way to the orbital apex [18]. Dillman and Anderson argued that removal of a portion of the levator muscle above the Whitnall’s ligament (i.e., myectomy) is adequate to obliterate its function without extensive dissection and damage to eyelid structures [8,19]. Bowyer and Sullivan describe the removal of a portion of levator muscle above the Whitnall ligament through a posterior conjunctival approach[16]. Dryden et al proposed suturing the transected levator aponeurosis to the arcus marginalis of the superior orbital rim[20]. This technique not only effectively deactivates the muscle but also allows the procedure to be reversed, if necessary. 10. Beard and others have advocated bilateral excision of the levator muscle and bilateral frontalis suspension[12]. While this approach almost completely eliminates the wink and arguably results in better symmetry, it is often difficult to persuade the parents and the patient to perform surgery on and effectively damage the normal contralateral levator muscle. 11. Satisfactory and predictable results also can be obtained

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after only unilateral levator excision on the affected side, combined with bilateral frontalis suspension (Callahan) [24]. This leaves the normal functioning levator muscle to elevate the nonptotic eyelid in primary position but produces a lag in downgaze for improved symmetry. 12. Kersten et al advocate unilateral levator muscle excision and frontalis sling only on the affected side[21]. If the postoperative result is judged to be unsatisfactory, the parents or the patient can opt for further surgery to the contralateral side. Any amblyopia and strabismus should first be addressed, as there may be insufficient drive to lift the disinserted eyelid. 13. Islam et al described a technique of dissecting a frontalis flap hinged superiorly through a suprabrow incision that is then brought down into an eyelid crease incision[22]. The frontalis flap is used to suspend the ptotic eyelid after extirpation of the levator muscle. 14. Lemagne and Neuhaus described techniques that involve transection of the involved levator followed by transposition of the distal segment to the brow, which effectively suspends the eyelid to the frontalis muscle[7,23]. Their techniques maintain normal eyelid contour, as the levator aponeurotic attachments are left undisturbed. References 1. Gunn RM. Congenital ptosis with peculiar associated movements of the affected lid. Trans Ophthal Soc UK. 1883; 3:283-7. 2. Demirci H, Frueh BR, NelsonCC: Marcus Gunn Jaw-Winking Synkinesis: Clinical Features and Management: Ophthalmology ,Feb2010. 3. Park DH, Choi WS, Yoon SH. Treatment of jaw winking syndrome. Ann Plast Surg 2008; 60(4): 404-9. 4. Khwarg SF, Tarbet KJ, Dortzbach RK, Lucarelli MJ. Management of moderate to severe Marcus Gunn jaw-winking ptosis. Ophthalmology 1999; 106(6): 1191-6. 5. Barthowski SB, Zapata J, Wyszynska. Management of MG ptosis in 19 patients. J Craniomaxillofac Surg 1999; 27(1): 259. 6. Morax S, Mimoun G. Surgical treatment of MG syndrome. Ophthalmologie 1989; 3(2): 160-3. 7. Neuhaus RW. Eyelid suspension with transposed LPS muscle. Am J Ophthalmol 1985; 100(2): 308-11. 8. Dillman DB, Anderson RL. Levator myomectomy in synkinetic ptosis. Arch Ophthalmol 1984; 102(3): 422-3. 9. Pratt SG, Beyer ,CK Johnson CC. The Marcus Gunn phenomenon : A retrospective review of 71 cases. Ophthalmology 1984;90:2730.

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Marcus Gunn Jaw-Winking Phenomenon : A Review 10. Doucet TW; Crawford JS. The quantification, natural course and surgical results in 57eyes with Marcus Gunn (Jaw-Winking) Syndrome. Am J Ophthal 1981; 92: 702-707. 11. Mauriello JA, Wagner RS, Caputo AR et al. Treatment of congenital ptosis by maximum levator resection. Ophthalmol; 1986:93; 466-9. 12. Doucet TW; Crawford JS. The quantification, natural course and surgical results in 57eyes with Marcus Gunn (Jaw-Winking) Syndrome. Am J Ophthal 1981; 92: 702-707. 13. Beard C. Ptosis, 3rd ed. St. Louis, CV Mosby; 1981: Pg 76143,150-74,184 207. 14. Pratt SG, Beyer CK, Johnson CC. The Marcus Gunn phenomenon. A review of 71 cases. Ophthalmology. 1984;91(1):27-30 15. Duke Elder S: Normal and abnormal development; congenital deformities. In: System of Ophthalmology. Vol 3, pt 2. St. Louis: CV Mosby; 1963:900-5. 16. Bowyer JD, Sullivan TJ. Management of Marcus Gunn jaw winking synkinesis. Ophthal Plast Reconstr Surg. 2004; 20(2):92-8. 17. Putterman AM. Jaw-winking blepharoptosis treated by the Fasanella-Servat procedure. Am J Ophthalmol. 1973; 75(6):1016-22. 18. Bullock JD. Marcus-Gunn jaw-winking ptosis: classification and surgical management. J Pediatr Ophthalmol Strabismus. 1980;17(6):3759 19. Epstein GA, Putterman AM. Super-maximum levator resection for severe unilateral congenital ptosis. Ophthalmic Surg. 1984; 15(12):971-9. 20. Dryden RM, Fleming JC, Quickert MH. Levator transposition and frontalis sling procedure in severe unilateral ptosis and the paradoxically innervated levator. Arch Ophthalmol. 1982; 100(3):462-4. 21. Kersten RC, Bernardini FP, Khouri L, et al. Unilateral frontalis sling for the surgical correction of unilateral poor-function ptosis. Ophthal Plast Reconstr Surg. 2005; 21(6):412-6; discussion 416-7. 22. Islam ZU, Rehman HU, Khan MD. Frontalis muscle flap advancement for jaw-winking ptosis. Ophthal Plast Reconstr Surg. 2002; 18(5):365-9. 23. Lemagne JM. Transposition of the levator muscle and its reinnervation. Eye. 1988; 2 (Pt 2):189-92. 24. Callahan A. Correction of unilateral blepharoptosis with bilateral eyelid suspension. Am J Ophthal 1972; Vol-74; Pg 321-326.

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Delhi Journal of Ophthalmology

Major Review

Review of Doses of Important Drugs in Ophthalmology Yogesh Bhadange, Bhavin Shah , Brijesh Takkar, Rajesh Sinha Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India.

Introduction Dispensing medications in the correct concentration and dosage plays a vital role in the outcome of most ocular pathologies. This article mainly describes about the preparation and doses of commonly used ocular medication in its most simplified form.

B. Antifungal Agents

1. Topical Drugs A. Fortified Antibiotics Cefazolin or ceftazidime (50mg/ml) • Add 9.2ml of artificial tears to a vial of cefazolin, 1gm (powder for injection). • Dissolve and take 5 ml of this solution and add it to 5 ml of artificial tears. • Refrigerate. Shake well before use. Tobramycin or gentamycin (14 mg/ml) • Withdraw 2 ml of tobramycin or gentamycin injectable vial (40mg/ml) • Add 2 ml to a tobramycin or gentamycin ophthalmic solution (5 ml) to give 14 mg/ml solution. Vancomycin (15mg/ml; 25mg/ml; 50mg/ml) • Add 33ml of 0.9% NaCl or artificial tears to 500 mg vial to get 15mg/ml solution. • Add 20ml of 0.9% NaCl or artificial tears to 500 mg vial to get 25mg/ml solution • Add 10ml of 0.9% NaCl or artificial tears to 500 mg vial to get 50mg/ml solution

C. Antiviral Agents

Amikacin (40mg/ml) • Direct use of commercially available solution. Trimethoprim - Sulfamethoxazole(16mg/ml - 80mg/ml) • Direct use of commercially available solution

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Review of Doses of Important Drugs in Ophthalmology

D. Immunosuppresive Agents

E. Autologous Serum Allow 5 ml of patient’s blood sample to clot in a test tube for 30 minutes. Centrifuge the serum that separates at 1500 – 2000 rpm for 10 - 15 minutes. Dilute 1 ml of supernatant with 4 ml of normal saline to get final concentration of 20%. F. Contents Of Pharmacy Prepared Artificial Tears: • Hydroxyl Propyl Methyl Cellulose0.3%; • glycerine0.4%; • sodium chloride0.4%; • thiomersal 0.005% (preservative).

Solution from each combination above withdrawn in separate syringes and mounted on a diplojet injector. When the common plunger is depressed, the fibrin sealer solution and the thrombin solution are combined in the nosecone, in equal volumes, to form the resulting fibrin sealant that is directly applied to the designated tissues. 4+5 (Thrombin component; rapid release) – used in vascular and neurosurgeries.

2. Subconjuntival A. Antibiotics

G. Hyperosmotic Agents Dilute 5 gram / 6 gram of commercially available sodium chloride in upto 100 ml of distilled water to give 5% / 6% hypersol respectively. H. Glue Tisseel VH Fibrin sealant (Baxter AG, Vienna, Austria) 1. Large Blue Bottle: • Clottable protein - 75 to 115mg • Fibrinogen - 70 to 110mg • Plasma fibronectin - 2 to 9 mg • Factor XIII - 10 to 50 IU • Plasminogen - 40 to 120 mg (microgram) 2. Small Blue Bottle: Aprotinin solution, bovine 3000 KIU / ml 3. White Bottle: Thrombin 4 (bovine), freeze dried reconstituted contains 4IU/ml 4. Large Black Bottle: Thrombin 500 (bovine), freeze dried reconstituted contains 500 IU/ml 5. Small Black Bottle: Calcium chloride solution, 40mmol/L 1+2 (Fibrin component) Bottles 1, 2, 3 and 5 are warmed for 30 minutes in Fibrotherm device. Add 1 + 2 (Fibrin Sealer Solution); Resultant is warmed and stirred. Add 3+5 (Calcium - Thrombin component; slow release) – used in Ophthalmology.

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Subconjunctival drugs injected post cataract surgery: • Gentamycin – 0.4 ml (20 -40 mg/ml) • Dexamethasone – 0.4 ml (4 mg/ml) • Xylocaine – 0.2 ml (20 mg/ml) B. ANTI-VEGF (Bevacizumab) Bleb Rescue: 1.25 mg / 0.05 ml subconjuctivally close to bleb. Corneal Vascularisation: 2.5 mg / 0.1 ml subconjuctivally close to the limbus in the quadrant of vascularisation. C. Immunosuppressive Agents: Mitomycin C: applied subconjunctivally using specialised sponges such as Meroseal in conc. of 0.02% and 0.04%. Diluting 2mg of Mitomycin C in 10 ml / 5 ml of Distilled water gives 0.02% and 0.04% respectively. 5 – Fluorouracil: injected subconjunctivally in a conc. of 50 mg/ml to prevent or treat a failing bleb. D. Cycloplegic – Mydriatics: Atropine sulphate (0.6 mg/ml vial)-0.2 ml subconjunctival dose.

3.Intrastromal A. Antifungal Agents:

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Review of Doses of Important Drugs in Ophthalmology

Voriconazole 50microgram/0.1ml Amphotericin B 5-7.5microgram/0.1ml B. Antibiotics: Ciprofloxacin - 0.3mg/0.1ml. C. Antiproliferative Agents Mitomycin C – for reducing the risk of postoperative corneal haze after surface or stromal ablation; applied at a concentration of 0.2mg/ml (0.02%) for 12 to 120 seconds. Mitomycin C is also used intraoperatively in pterygium excision in concentration of 0.2mg/ml (0.02%) to 0.4mg/ ml(0.04%) for 5 min over the exposed stroma and the sclera.

Acetate A cortisone, synthetic analogue of cortisol acetate with no glucocorticoid activity; acts by suppression of extracellular proteases elaborated by activated endothelial cells and also decreases VEGF level. Dose-15mg posterior juxta scleral depot injection every 6 months for treatment of wet ARMD.

5. Intravitreal Drugs A. Antibiotics Vancomycin (1mg\0.1ml) – available commercially as 500 mg powder.

4. Intracameral Agents A. Antibiotics Prophylactic as well as Therapeutic uses. Bolus dose or maintenance dose in the irrigating fluid. Bolus dose of commonly used antibiotics

Ceftazidime (2.25mg\0.1ml) – available commercially as 500mg powder injection

Amikacin (400microgram\0.1ml) – commercially available as 100mg in 2ml or 50 mg/ml. Antibiotics used in irrigating fluids

Gentamycin (200microgram\0.1ml) : commercially available as 80mg in 2ml or 40mg in 1ml B. Mydriatics Adrenaline tartarate (0.1% w/v; 1:1000) is diluted ten times ie.0 .1 ml of adrenaline diluted in 0.9ml of BSS ;used as bolus dose. For maintaining mydriasis 0.8cc adrenaline tartarate (0.1% w/v 1:1000) is diluted in 350 ml of BSS. C. Miotics: Pilocarpine 0.1 ml of the drug (25mg/ml) is diluted in 0.1ml ringer lactate; used as bolus dose. 0.8ml of pilocarpine (0.5% of ophthalmic preparation) is added to 350 cc of BSS; used as maintenance dose. Posterior Subtenon Injection 20mg / 0.5ml of triamcinolone acetonide either with benzyl alcohol preservative (kenacort\ tricot) or as preservative free preparation (retilone\ aurocot) is injected using the Smith and Novak’s technique with 26 Gauge needle or the cannula technique. Posterior Juxta Scleral Depot Injection of Anacortave Vol. 21, No. 3, January-March, 2011

Dexamethasone (400microgram\0.1ml): Each 2ml vial contains 8mg

B. Antifungal Amphotericin B (5 microgram\0.1ml) – available commercially as 50mg powder

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Voriconazole – available commercially as 200mg powder or 50-100micrgram\0.1ml

Fluconazole Intravitreal: 25 microgram/0.1 ml

C. Antiviral Drugs Acyclovir Intravitreal dose: 10 to 40 micrograms/0.1ml Gancyclovir used mainly in acyclovir resistant cases; Induction dose -2 mg/0.1ml; 0.1 ml injected 2 times per week for 3 wks; Maintenance dose- 2mg/0.1 ml once a week Gancicovir implant (Vitrasert) Provides local sustained conc. of the drug with decrease risk of systemic SE without repeated injections. Therapeutic levels up to 8 months.4.5 mg drug in 2.5 mm pellet completely coated by drug permeable poly vinyl alcohol and incompletely coated with impermeable ethyl vinyl acetate. Releases drug at rate of 1 micro gm/hr. Mean intravitreal concentration achieved is 4.1 microgm/ ml. Valgancyclovir Prodrug; Dose - 0.2 to 0.4 mg/0.1ml twice weekly till disease regresses. Foscarnet Virustatic; Used in cases of resistance to gancyclovir; 1.2 mg in 0.05 ml injected intravitreally. Induction Dose Two injections once per week for 3 weeks. Maintenance dose one injection per week. Cidofovir 20mg / 0.1ml every 6 weekly. Oral probencid 2gm before injection and 1 gm after post injection Fomiversen 330 μg intravitreal every 2 weekly for 2 doses for induction. Maintenance dose: 330 μg intravitreally / month; 4th line drug treatment of CMV retinitis

Dexamethsone intravitreal implant - Porsudex (Ozurdex) Dexamethasone 350 mcg or700 mcg biodegradable implant (small pellets); lasts for 37 days; can be injected as an office procedure. Fluocinolone acetonide intravitreal implant– (Retisert) 0.59 mg non-biodegradable implant injected through a pars plana incision; designed to release fluocinolone acetonide at initial rate of 0.6 µg/day; decreasing over the first month to a steady state between 0.3-0.4 µg/day over approximately 30 months. The implant consists of a tablet encased in a silicone elastomer cup containing a release orifice and a polyvinyl alcohol membrane positioned between the tablet and the orifice. The silicone elastomer cup assembly is attached to a polyvinyl alcohol suture tab with silicone adhesive. Each RETISERT is approximately 3 mm x 2 mm x 5 mm.Each implant is stored in a clear polycarbonate case within a foil pouch within a peelable overwrap. Each packaged implant is provided in a carton which includes the package insert. E. ANTIVEGF Pegatinib sodium (Macugen) Chemically synthesized single strand of nucleic acid, complementary to RNA (APTAMER).Molecular weight of 50 kilo daltons. Selective vegf 165 inhibitor. Dose 0.3 mg/0.09ml intravitreally every 4- 6 wk.T 1/2-in vitreous is 83 to 94 hrs Bevacizumab (Avastin) Nonselective recombitant humanized chimeric anti VEGF antibody.Produced in chinese hamster ovary. Molecular weight of 150 kilo daltons thus cannot cross retinal ILM and RPE into subretinal space. Dose 1.25mg/0.05ml intravitreally; T ½: 20 days. Each bevacizumab vial is available in 4ml and 16ml vial in conc. of 25mg/ml

D. Steroids

Ranibizumab(Lucentis) Recombinant monoclonal fragment nonselective antibody .Molecular weight 48 kilo daltons. Nonselective VEGF antibody. Dose 0.3-0.5mg/0.05ml.each lucentis carton contain 0.2ml.T1/2 10 days.

Triamcinolone acetate 1 mg / 4 mg intravitreal injection; available most commonly as a suspension of triamcinolone crystals containing preservative benzyl alcohol 0.99% (Kenacort 40 mg/ml and Tricort 40 mg/ ml,) and also as preservative free preparation (Triesence, Retilone, Aurocot – 40 mg/ml)

siRNA (bevaciranib) Small interfering RNA cause elective degeneration of mRNA transcript containing a sequence homologous to the siRNA (VEGF) thereby blocking the synthesis of VEGF. Dose: 70/150/300 microgram in 0.05 ml (under trial).

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Review of Doses of Important Drugs in Ophthalmology

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Delhi Journal of Ophthalmology

Review of Doses of Important Drugs in Ophthalmology

VEGF trap Contains Ig domain of VEGF Receptors 1 and 2; High affinity binding and neutralisation of receptors. Dose: 0.05 to 4 mg intravitreally single injection at intervals of 6 wks. (under trial)

F. Cyclosporine Impairs T - Cell mediated immunity; used as steroid sparing agent

G. Intraocular Gases

References 1. G Geerling, S MacLennan, D Hartwig. Autologous serum eye drops for ocular surface disorders. Br J Ophthalmology. 2004; issue 88: page 1467–1474. 2. Anita Panda, Sandeep Kumar, Abhiyan Kumar, Raseena Bansal, Shibal Bharti. Fibrin glue in ophthalmology. Current ophthalmology. 2009; vol 57; issue 5: page 371-379. 3. Duch,Susana, Buchacra, Oscar, Milla, Elena, Andreu, David,Tellez, Jesús. Intracameral Bevacizumab (Avastin) for Neovascular Glaucoma. Journal of Glaucoma. February 2009 ;vol 18 ; issue 2 : page 140-143

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Indications • Uveitis • Behcet’s disease • Scleritis • Orbital inflammatory disease • Non-responding posterior uveitis • Graft rejection Dose 2mg intravitreal implant

4.

5.

Saravia M, Zapata G, Ferraiolo P, Racca L, Berra A .AntiVEGF monoclonal antibody-induced regression of corneal neovascularization and inflammation in a rabbit model of herpetic stromal keratitis. October 2009 ;vol 247:page 1409-16. Safety and efficacy of intravitreal triamcinolone for cystoid macular oedema in uveitis. Young S,LarkinG., Branley M,Lightman S.Clinical & Experimental Ophthalmology. February 2001; vol 29; issue 1: page 2–6.

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Preferred Practice Pattern

Systematic Approach to a Case of Disc Pallor Digvijay Singh, Rohit Saxena, Pradeep Sharma, Vimla Menon Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India Disc pallor is often the sequel of various optic nerve disorders and signifies partial or total optic atrophy. It may be present with symptoms or signs ranging from subtle visual dysfunction to total blindness or may even be an incidental finding during routine ophthalmological checkup. Discovering the cause of such a case can baffle neurologists and ophthalmologists alike. We describe a systematic clinically oriented approach to a case of disc pallor to help arrive at a diagnosis.

Introduction

Clinical Approach

An ophthalmologist is frequently faced with optic disc pallor on fundoscopy and may be perplexed regarding how to approach the case and identify the etiology behind this clinical presentation. In this paper, we describe an approach to disc pallor and clues to discover its etiology.

The clinical approach to a case of disc pallor is akin to solving a jigsaw puzzle. With every piece put in its place, the picture becomes clearer. The systematic process of arriving at a diagnosis should begin with clues from the demographic profile of the patient, followed by a directed clinical history. This should precede an ocular and systemic examination guided by the history. Investigations including neuro-imaging would finally establish the etiology[2,3,4]. The protocol and clinical interpretations are discussed in the appropriate headings below.

Disc pallor is the manifestation of partial or total optic atrophy and is a consequence of loss of nerve fibers. Optic atrophy has classically been described into primary and secondary types. Primary optic atrophy is secondary to a lesion affecting the visual pathway from the optic nerve head to the lateral geniculate body. The disc in such cases is flat and pale with clearly demarcated margins. Disc edema precedes secondary optic atrophy which presents with a dirty white to grey looking disc with poorly delineated margins. The etiology of unexplained disc pallor can be revealed by appropriate investigations in a large majority of cases. This was demonstrated in a multicentre study where of all cases of optic atrophy only 8% remained unexplained. Further directed investigations including neuro-imaging led to am etiological diagnosis in another 20% of these cases. The authors had recommended use of neuro-imaging in all cases of unexplained optic atrophy[1]. The need for a definitive diagnosis in any case of disc pallor stems from the fact that optic nerve diseases behave in a very varied manner while carry different treatments and outcomes. Some disorders such as optic neuritis are self limiting but may be recurrent whereas others like toxic neuropathies are partially reversible. Hereditary optic atrophies may be progressive and with rare exception, do not show improvement. An Ischemic optic neuropathy such as arteritic AION can rapidly involve the fellow eye if not treated on time. Damage to nerve in toxic optic neuropathy can be halted by removing the offending agent.

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Demographic profile The age, gender and race of a patient is often the first clue to the diagnosis, but has to be interpreted with caution. Age The age is probably the most important of the demographic parameters while short listing possible etiologies of disc pallor. A brief list of various disorders and the presenting age is below but one has to understand that there are no watertight compartments and significant overlap of diagnosis exists between each age group. Glaucoma can present with disc pallor at any age and has been deliberately omitted from the list and further discussion. The table depicts the causes for disc pallor categorized by age group of presentation. Gender This guides us in favoring one diagnosis over another but one has to be aware that there is no clear segregation of optic nerve afflictions on gender. Male: LHON, Traumatic neuropathy, some tapeto-retinal degenerations, toxic neuropathy( lead,arsenic heavy metal occupational exposure, methyl alcohol), Nutritional deficiency(chronic alcoholism).Female: multiple sclerosis, meningioma, autoimmune/collagen vascular diseases, Sheehan syndrome, ecclampsia,

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Systematic Approch to a Case of Disc Pallor

Race The type of optic neuropathy and severity may demonstrate a ethnic variation. For example, blacks were found to have lower incidence of ischemic optic neuropathy than whites and had lower incidence of severe visual loss secondary to idiopathic intracranial hypertension than whites.5 Caucasians are more likely to be afflicted with multiple sclerosis and optic neuritis than Asians or Hispanics. Overall optic atrophy is more prevalent in African-Americans (0.3%) than whites (0.05%).

Clinical History

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Chief complaints Blurring or decrease of vision, pain on eyeball movement, inability to see part of visual field Clinical picture and interpretation • Onset Acute onset (over hours to days) is seen in optic neuritis, ischemic optic neuropathies and traumatic optic neuropathy. Sub-acute onset (over few days) is seen in non demyelinating inflammatory neuropathy and compressive neuropathy. Insidious onset is characteristic of toxic and nutritional deficiency neuropathy as well as hereditary neuropathies. • Course If the symptoms had self resolved without any intervention or recurrent episodes of decrease of vision are present, a previous demyelinating pathology should be suspected. On the other hand a residual poor vision after an episode or progressive deterioration or protracted course should point towards any of the other pathologies. • Laterality Unilateral disease is found in typical optic neuritis, ischemic neuropathy (Non-arteritic), traumatic neuropathy and compressive lesions. Bilateral presentation (though may be asymmetrical) is observed Vol. 21, No. 3, January-March, 2011

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in toxic/nutritional deficient neuropathy, hereditary neuropathy, atypical optic neuritis and arteritic anterior ischemic optic neuropathy. Ocular history such as red eye episodes, painful eye movements(retrobulbar optic neuritis), diplopia and proptosis Systemic history such as fever, jaw claudication, palpitations, breathlessness and symptoms suggestive of systemic illness like diabetes, hypertension, hyperthyroidism, recent viral infection, tuberculosis etcetera. History of CNS disease in form of headache, meningitis, seizures, projectile vomiting, Transient ischemic attacks, motor weakness, paraesthesia and other sensory symptoms etcetera. History of trauma Occupational and social history with special emphasis on alcohol/drug intake, smoking, diet and unsafe sexual practices. Family history is important to diagnose hereditary neuropathy. History of previous medications guides us regarding the possibility of toxic neuropathy.

Ocular Examination A complete and thorough ophthalmic examination is mandatory. The neuro-ophthalmology specific ocular examination includes• Visual acuity Typically disc pallor secondary to optic neuritis, LHON, Nutritional deficiency optic neuropathy, NAAION and inflammatory neuropathies presents with a visual acuity of around 20/200. Hereditary optic neuropathies (AD/AR), AAION, post papilledema and traumatic optic neuropathies on the other hand present

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with a poor visual acuity and even absence of light perception. Toxic optic neuropathies have a variable and unpredictable visual acuity. Visual fields Confrontation visual fields can give a quick assessment of any large scotomas or hemi field or altitudinal defects. A carefully done confrontation field test and a tangent screen test with a red target provide a fairly accurate result. Color desaturation test The patient may be shown a red capped bottle and asked to compare the red color separately with both eyes. The eye with disc pallor would give a washed out red or pink appearance in contrast to the bright red color seen by the fellow eye. Pupils A relative afferent papillary defect is characteristically found in cases of disc pallor though it is absent in bilateral symmetrically affected cases. RAPD can be quantitatively assessed using neutral density filters for comparison of any future worsening of neuropathy. Macula/Posterior pole One needs to look for presence of exudates in the form of a star or fan or sequel thereof. Occasionally an optic disc pit may be associated with central serous choroidoretinopathy or a choroidal neovascular membrane. Disc[6] Size This may be measured by various techniques using a direct ophthalmoscope (use 50 cone of Welch Allen ophthalmoscope), indirect ophthalmoscope or on slit lamp biomicroscopy (When using a 90D lens multiply the height of the slit measured in mm by 1.3 when it is focused and just equal to the disc to get disc size in mm). The importance of disc size comes when a case of optic disc hypoplasia is confused with a disc pallor post neuropathy. Shape : The disc normally appears round or oval. Any variation from this should alert towards a congenital anomaly or traumatic avulsion. Color : The disc is normally salmon pink in color though the actual color varies from race to race. A disc is described as pale if it loses the pink hue to turn towards a whitish yellow color or a lemon tint. It is described as hyperemic if it becomes reddish pink (a sign of increased vascularity). There are methods described in literature to objectively or subjectively assess and document the color of the disc. These involve recording ophthalmoscopic appearances and digital stereoscopic disc images followed by analyzing them. One should establish their own protocol and document progression of disc pallor during follow up visits. A word of precaution which merits mention is that the 90D lens may make the disc look falsely healthier(less pale) due to its the yellow tint. Cup : Disc Ratio: This shows great variability and can range from no visible cupping to 0.6 and beyond in

Systematic Approch to a Case of Disc Pallor the normal subjects. A deep excavated cup is of more significance compared to a large shallow cup. The size of a cup can also be measured similar to that described for the disc above. Both direct and indirect ophthalmoscopy underestimates the cupping in comparison to slit lamp biomicroscopy.  Neuroretinal rim : This is a congregation of nerve fibers from the retina converging upon the disc to form the optic nerve. A pale disc secondary to a neuro-ophthalmic disease often has a uniform thin neuroretinal rim but there is no focal notching or loss in contrast to glaucoma.  Disc Margins : These should be well defined. In disc edema they are usually blurred in the INST sequence. Often one may notice a pallid disc edema in circulatory compromise of the disc. LHON may present with pseudoedema.  Disc Vascularity : Kestenbaum count is the number of capillaries observed on the disc. The normal number is 10 while optic atrophy will have a count of less than 6.  Peripapilla : Presence of peripapillary atrophy (alpha zone and beta zone) needs to be documented.  Retinal nerve fibre layer : The presence of any RNFL defects should be noted. This is best examined with a red free green filter. The appearance of the disc can give a clue about the possible etiology[7]. Some diagnostic categories and the corresponding disc appearance are as follows: Ischemic Optic Neuropathy 1. Retinal arterial attenuation and sheathing 2. Pallid disc edema 3. Superior or inferior disc pallor 4. Disc hemorrhages 5. Fellow eye may show small disc with absent cup( disc at risk) Optic Neuritis 1. Typical : Normal disc or mild temporal pallor (Unilateral) 2. Atypical: Pallid disc edema or diffuse or bilateral disc pallor with arterial attenuation and disc hemorrhages.

Figure 1: Bowtie optic atrophy

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Systematic Approch to a Case of Disc Pallor

Figure 2: Post papilledemic optic atrophy

Figure 3: Primary optic atrophy

Figure 4: Hemi atrophy post AION

Infectious/Infiltrative neuropathy 1. Usually following an episode of unilateral or bilateral disc edema with macular star 2. Disc pallor is typically subtle and diffuse Toxic/Nutritional Optic Neuropathy 1. Temporal Disc pallor 2. Usually symmetric bilateral but may show significant asymmetry in early stages. Vol. 21, No. 3, January-March, 2011

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Hereditary optic neuropathy (AD/Non Leber’s) 1. Disc pallor is usually subtle, mostly temporal and occasionally diffuse 2. Non-glaucomatous cupping with peripapillary atrophy and/or arterial attenuation is noted. Lebers Hereditary optic neuropathy 1. Sequential bilateral presentation 2. Temporal disc pallor with RNFL defects in papillomacular bundle 3. Non-glaucomatous cupping with arterial attenuation 4. Fellow eye may show disc at risk picture and during acute vision loss stage may demonstrate pseudoedema with disc hemorrhages and peripaillary telangectasias. Optic Chiasm/Tract lesion 1. Bilateral involvement 2. Bow tie atrophy of contralateral disc (Superior and inferior sparing) Compressive neuropathy 1. Unilateral or bilateral disc edema and/or disc pallor 2. Painless progressive disc pallor on follow up 3. Optico-ciliary shunts/disc collaterals Radiation neuropathy 1. Rapidly developing disc pallor (4 wks) 2. Usually disc edema not noted at any stage 3. Associated with radiation retinopathy (diabetic retinopathy like findings) Traumatic neuropathy 1. Anterior lesions show early ophthalmoscopic findings such as in optic nerve avulsion and disc edema with early onset disc pallor(3-4 weeks) 2. Posterior lesions show late onset disc pallor with no other fundus change Papilledema 1. A dirty grey-white optic pallor with ill defined disc details and margins are the typical signs of a secondary optic atrophy following long standing pailledema. 2. The disc may show an excavated appearance. Systemic Examination A detailed systemic examination forms an important part of any neuro-ophthalmology workup. The key factors looked for are: 1. General demeanor to look for nutritional deficiency or chronic illness 2. Pulse to look for any cardiovascular signs. 3. Blood pressure, specifically for ischemic optic neuropathy 4. Conjunctival pallor for anemia which may provide evidence of nutritional deficiency 5. Icterus to rule out systemic illness causing jaundice and neuropathy such as hepatitis, syphilis, viral infections,leptospira, malignancy etc. Also to suspect toxic neuropathy.

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6. Lymphadenopathy, seen in diseases such as tuberculosis, Collagen vascular diseases, syphilis, viral infections, malignancy etc. 7. Specific systems including cardiovascular, respiratory, gastrointestinal, skin and musculoskeletal to rule out ischemic heart disease, arrhythmias, major vessel obstructions, tuberculosis, sarcoidosis, malignancy, collagen vascular diseases, viral exanthems, syphilis etc. 8. Central and peripheral nervous system examination to look for any associated neurological diseases including but not limited to meningitis, encephalitis, multiple sclerosis, neuromyelitis optica, Friedriech ataxia and malignancy. On the basis of the history, ocular and systemic examination, one should create a list of differential diagnosis and proceed towards investigations. Ocular Investigations The ocular investigations should be done at baseline and appropriate follow up visits. The follow up protocol can be tailored by each institution on the basis of patient load and human resource availability. We recommend these investigations on first visit and at 1 month follow up to establish a baseline. Then, they may be repeated once at 3 months and 6 monthly thereon. The investigations that should be done in a case of disc pallor include 1. Color vision (Ishihara or HRR plates). Note both the number and type of unread plates. 2. Contrast sensitivity: Pelli Robinson or FACT 3. Visual fields: Both Goldmann/Humphrey visual fields. 4. Color and red free fundus photograph centered on the disc. 5. Flourescein fundus angiogram needs to be undertaken only if specific indication. 6. Optical coherence tomography of the optic disc to document nerve head and retinal nerve fiber status. 7. Electrophysiology: Visual evoked reponse (Preferably pattern, if possible or else flash), Electroretinogram and Electrooculogram to look for any associated retinal dysfunction. Systemic Investigations The systemic investigative lineup for a case of disc pallor may be divided into first line investigations and second line or specific testing. First line tests 1. Hemogram with peripheral smear, Complete blood count with differential count 2. Liver function test 3. ESR 4. Mantoux test 5. Chest X-ray 6. MRI of Head and Orbit with thin cuts and fat suppression

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Systematic Approch to a Case of Disc Pallor 7. VDRL (syphilis serology) 8. Lumbar puncture Specific tests based on suspected cause 1. Sarcoidosis: Serum ACE, serum Calcium levels, Gallium scan 2. Collagen Vascular disease: Immunology workup; ANCA, Anti-dsDNA, RF, Complement levels 3. Tuberculosis: Sputum smear AFB, Quantiferon Gold assay, Lymph node FNAC/biopsy 4. Nutritional deficiency neuropathy: Serum B12 and Folate levels 5. Toxic neuropathy: Heavy metal screening 6. Post infectious optic neuritis: TORCH titers 7. Hereditary neuropathy : LHON mutation testing (preferably full mitochondrial sequencing or at least the common primary mutations) 8. Paraneoplastic syndrome: Antibody profile such as CRMP5 for small cell CA of lung 9. Thyroid eye disease: Serum T3, T4 and TSH levels. 10. Devic’s disease: MRI spine, Anti NMO antibody titer. 11. AAION: Temporal artery biopsy, CRP levels Conclusion A systematic approach to a case of disc pallor will result in a definite diagnosis in majority of the cases without undue loss of time or resources. Nonetheless, there are still cases which remain unexplained and for them, the ophthalmologist, on his part can keep a close follow up initially to ensure a non progressive condition. While visual prognosis remains guarded for patients with disc pallor at present, the future holds promise with the advent of stem cell therapy, potential for optic nerve transplantation and fast progressing technology for artificial vision. References 1. Lee AG, Chau FY, Golnik KC, Cardon RH, Wall M. The diagnostic yield of the evaluation for isolated unexplained optic atrophy. Ophthalmology 2005:112:757-59. 2. Behbehani R. Clinical approach to optic neuropathies. Clin Ophthalmol. 2007:1(3):233-46. 3. Lee AG, Brazis PW (eds). Clinical pathways in NeuroOphthalmology: An Evidence based approach. Thieme Medical Publishers. 2003:1-35. 4. Brazis PW, Masdeu JC, Biller J(eds).Localization in clinical neurology. Lippincott Williams & Wilkins. 2007:131-69. 5. Mansoui AM, Hamed LM. Racial variation of optic nerve disease. Neuro-Ophthalmology.1991:11:319-23. 6. Teymoorian S. Examination of the optic nerve at the slit lamp biomicroscope with a handheld lens. http://eyewiki.aao.org. Accessed on 2nd January 2011. 7. O’Neill EC, Danesh-Meyer HV, Connell PP et al. The optic nerve head in acquired optic neuropathies. Nat rev neurol. 2010:6(3):221-36.

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Case Reports

Bilateral Mooren’s Ulcer with perforation and Iris prolapse Uday Gajiwala1, Jyotsom Ganatra2, Rajesh Patel1, Parin Shah1, Rohan Chariwala1 1. SEWA Rural, Jhagadia-393110, Dist.-Bharuch, Gujarat, INDIA, Phone-(02645)220021, 2. Department of Ophthalmology, Kaiser-Permanente Medical Center, San Rafael, California 94903- USA Mooren’s Ulcer is an idiopathic, rapidly progressive, painful peripheral ulcerative keratitis with no associated scleritis. It’s a diagnosis of exclusion which means all other diagnosable systemic disorders that could be responsible for the progressive destruction of cornea must be ruled out. The etiology of Mooren’s Ulcer remains uncertain. However, recent studies indicate that it is an autoimmune disease directed against a specific target molecule in the corneal stroma, triggered in genetically susceptible individuals by one of several possible mechanisms. A 40 years old female presented to us on 25th January 2008 from rural tribal area of Sagbara with bilateral peripheral ulcerative keratitis with perforation and iris prolapse in right eye. She is known case of diabetes mellitus for last seven years. Diagnosis of Mooren’s ulcer was made after she underwent extensive medical and laboratory testing to rule out an infectious or systemic cause of corneal melt. She benefited by right eye patch graft, left eye tissue adhesive with BCL application, Both eyes conjunctival peritomy and immunosuppressive drugs along with control of diabetes. This case report aims to highlight the diagnosis and treatment of Mooren’s ulcer.

Case Report A 40 year old female from rural tribal area of Sagbara with low socio economical status presented to us on 25th January 2008 with complaint of decreased vision, redness, watering, ocular pain and photophobia in both eyes for last 2 months more so in right eye for last one week. She was having diabetes mellitus for last seven years which was controlled by medication. There was no history of trauma, joint pain. On examination, best corrected visual acuity in right eye was 6/36 and in left eye, it was 6/24. There was inferior crescent of corneal thinning involving 6 clock hours (3-9 o’clock) with limbal involvement but no associated scleritis. In right eye, there was a perforation with Iris prolapse at 6-7 o’clock position. In both eyes, there was overhanging edge infiltrated with white cells and spreading towards centrally and circumferentially. It was positive for fluorescein stain indicating overlying epithelial defect. The pupil was peaked inferotemporally in right eye due to perforation and in left eye due to impending perforation. There were no signs of secondary infection and/or Iritis on examination. Dilated Indirect ophthalmoscopy was normal in both eyes. (No diabetic retinopathy)

Presentation She was investigated to rule out systemic disease causing peripheral ulcerative keratitis. RBS was 301 mg/kg showing

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uncontrolled diabetes mellitus on the day of presentation. Investigations done – Hemogram with ESR, Urine routine and microscopy, VDRL, RA factor, HCV, X- ray chest and Joints, SGPT, ANCA, ANA, HBsAg, Scraping of the ulcer are done, which were normal. She was referred to her physician to control diabetes mellitus as well as to rule out systemic disorders causing peripheral ulcerative keratitis. She was placed on Insulin Injections to control DM. After excluding systemic diseases associated with peripheral ulcerative keratitis, A diagnosis of Bilateral Mooren’s ulcer was made and systemic immunosuppressive therapy was started with oral methotrexate 10 mg once a week and oral systemic steroids at a dose of 1.5 mg / kg / day. Right eye Iris abscission (of prolapsed part) with patch graft (free Hand) was done after controlling diabetes mellitus. Tissue adhesive with Bandage Contact Lens Application with conjunctival peritomy was done in left eye. Locally she was started on Prednisolone eye drops 2 hourly, Ofloxacin eye drops 4 times a day, timolol maleate eye drops twice a day, 2 % HPMC eye ointment three times a day. Tissue Adhesive and Bandage Contact Lens were removed

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Bilateral Mooren’s Ulcer with perforation and Iris prolapse

RE-After 6 Months Follow Up: Right Eye:

LE-After 6 Months Follow Up: Left Eye:

after 6 weeks in left eye. It was nicely epithelialized and scarred without any overhanging edge. Right eye patch graft is doing well after 6 months. Best corrected visual acuity in right eye 6/18 and left eye 6/18 after 6 months follow up.

Discussion Although the diagnosis of Mooren’s ulceration may be difficult when a patient first presents with PUK the clinical appearance is characteristic. However, a thorough medial history, physical examination and appropriate laboratory investigations must be performed to rule out underlying systemic conditions causing PUK, since Mooren’s Ulcer is a diagnosis of exclusion. Mooren’s ulcer was first described by Bowman in 1849[1] and then by McKenzie in 1854 as “Chronic serpiginous ulcer of cornea or ulcus roden”[2]. Mooren’s name, however, became attached to this rare disorder because of his publication of cases in 1863 and 1867[3]. He was the first to clearly describe this insidious corneal problem and define it as a clinical entity. Nettleship[4] summarized the accumulated reported experience with the disorder in a classic article.

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Mooren’s ulcer is idiopathic by definition, occurring in complete absence of any diagnosable systematic disorder that could be responsible for progressive destruction of the cornea with no associated scleritis. Its exact pathophysiology remains uncertain, although a growing body of evidence indicates that it is an autoimmune disease directed against a specific target molecule in the corneal stroma resulting in its destruction by degradative enzymes, which are released primarily by neurotrophils attracted into the area by diverse stimuli [12,13], probably triggered in genetically susceptible individual by one or several mechanisms. Wood and Kaufman having reported 9 cases concluded that there were two clinical types of Mooren’s ulcer[5]. The first limited type, is usually unilateral, with mild to moderate symptoms, generally responds well to medical and surgical treatment. This type is believed to occur in older patients and has become known as typical or benign Mooren’s ulcer. In contrast, the second type is bilateral, with relatively more pain and generally a poor response to therapy in younger patients, became known as atypical or malignant, Mooren’s ulcer. The benign type is bilateral in 25% of patients and the malignant type is bilateral in 75 % of Patients.

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Bilateral Mooren’s Ulcer with perforation and Iris prolapse

Keitzman[6] published a series of 37 cases of progressive Mooren’s ulcer in Nigeria affecting primarily healthy men between age of 20 and 30 yrs and the clinical course was very rapid. Perforation occurred in 36% of the patients. As a result, the generalized belief has developed that the progressive and relentless atypical form of Mooren’s ulcer has A predilection for young men of African origin. Lewallen and courtright[7], in their published series of Mooren’s ulcer, suggest that younger patients had bilateral disease less frequently than older patients (1.5:1) regardless of race. Although they found that men were 1.6 times more likely to have Mooren’s ulcer than were women. Different entities have been associated with Mooren’s ulcer, often leading to conjecture that there may be a causal relationship. An association with helminthiasis has been suggested in Nigeria[8], Schanzlinp[9] speculated that the antigen antibody reaction to helminth toxin deposited in peripheral cornea provoked the inflammation and ulceration. Recently in 2 patients with bilateral Mooren’s ulcers chronic hepatitis with infection C was documented[10,11] and they improved after treatment of the hepatitis C with interferon α2β. The authors proposed that molecular mimicry may be involved, with the hepatitis C virus stimulating an autoimmune response to corneal antigens through cross reacting epitopes. Based on the clinical presentation[20] and the low dose anterior segment fluorescein angiographic findings, there seem to be three distinct varieties of Mooren’s ulceration 1. Unilateral Mooren’s ulceration (UM), characterized by an excessively painful progressive corneal ulceration in one eye in elderly patients, associated with non perfusion of the superficial vascular plexus of the anterior segment. 2. Bilateral aggressive Mooren’s ulceration (BAM), which occurs in young patients, progresses circumferential and only later, centrally in the cornea. Angiography shows vascular leakage and new vessel formation which extends into the base ulcer. 3. Bilateral indolent Mooren’s ulceration (BIM), which usually occurs in middle aged patients presenting with progressive peripheral corneal guttering in both eyes, with little inflammatory response. There is no change from the normal vascular architecture on angiography except an extension of new vessels into the ulcer.

DD • •

Rheumatoid arthritis Wagener’s Granulomatosis

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• • • • • • • • •

Polyarteritis Nodosa Other collagen vascular diseases Inflammatory bowel disease Giant cell Arteritis Staphylococcal Marginal Keratitis Local infections causes Terrien’s degeneration Pellucid degeneration Ocular Rosacea

Treatment Today, most experts agree on stepwise approach in management of Mooren’s ulcer[19]]. 1. Topical Steroids 2. Conjunctival Resection 3. Systemic immuno suppressive 4. Additional Surgical Procedure 5. Rehabilitation

Goals To arrest the destructive process and to promote healing and re-epithelialization of the corneal surface[15-18].

Steroids Initially: Intensive topical steroids Prednisolone acetate 1% eye drop One hourly

In association with Topical Cycloplegics Prophylactic Antibiotics If epithelial healing does not occur within 2-3 days, the frequency of tropical steroids can be increased to every half hour. Once healing occurs, the frequency can be reduced and tapered slowly over a period of several months. Such management, especially in unilateral, benign form has met with good results. Topical cyclosporine-A therapy (0.5% solution) also found useful in some studies.

Systemic steroids Oral pulse therapy 60-100 mg daily of oral Prednisolone is indicated when topical therapy is ineffective after 7-40 days. When topical steroids may be dangerous because of precariously deep ulcer or infiltrate [[14, 22]. Topical tetracycline may be used for anticollagenolytic properties. A therapeutic soft contact lens or patching of eye may be

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Bilateral Mooren’s Ulcer with perforation and Iris prolapse

beneficial when ulcer is deep.

When a perforation is too large for tissue adhesive to seal the leak, some type of patch graft will be necessary. This may range from a small tapered plug of corneal tissue to a penetrating keratoplasty.

Conjunctival Resection • If ulcer progresses despite steroid regimen, conjunctival resection should be performed [15-18]. • Under topical or sub conjunctively anesthesia, this consists of conjunctival excision to bare sclera extending at least 2 clock hours to either side of peripheral ulcer and approximately 4 mm posterior to the corneoscleral limbus and parallel to the ulcer[23]. The overhanging lip of ulcerating corneas may also be removed. Post operatively a firm pressure dressing should be used.

The rationale of this procedure Conjunctiva adjacent to the ulcer contains inflammatory cells that may be producing antibodies against the cornea and cytokines which amplify the inflammation and recruit additional inflammatory cells. Multiple resections may be necessary.

Systemic immuno suppressive therapy Indication Bilateral or progressive Mooren’s ulcer that fails to preceding therapeutic attempts will require systemic cytotoxic theory to bring a half to the progressive corneal destruction

Commonly used agents Cyclophosphamide – 2 mg / kg / day Methotrexate (7.5 – 15 mg once a week) Azathioprine (2 mg / kg body weight / day) The degree of fall in white blood cell count is considered as the most reliable indicator of immunosuppression produced by cyclophosphacomide. Most authors believe that the evidence for the efficacy of systematic immune suppressive chemotherapy for progressive bilateral Mooren’s ulcer is quite strong, and further believe that such treatment should be employed sooner rather than later in the care of such patients, before the corneal destruction, has become too extensive to need for surgery. Adverse effects of these cytotoxic and immunosuppressive medications, such as anemia, alopecia, nausea, nephrotoxicity, are likely and it must be administer in close observation of physician.

Additional surgical procedures Small perforations / Impending perforation may be treated with application of tissue adhesive – isobutyl cyanoacrylate and placement of a soft contact lens to provide comfort and to prevent dislodging of the glue.

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Rehabilitation Once the active ulceration has stopped and the remaining cornea has been completely opacified, it is possible perform PK on these patients, even in the face of a thinned and vascularized cornea. Because of the immune systems remarkable memory, surgical attempts at rehabilitation in Mooren’s ulceration, should be done only with concurrent immunosuppressant, even when the active disease has been arrested, or is burnt out because attempts at penetrating keratoplasty often are associated with recurrence and graft failure.

Conclusion Bilateral Mooren’s ulcer in young patients can progress rapidly in a circumferential fashion towards the center of the cornea and can present with perforation and Iris prolapse early in a course of disease. Though clinical appearance is characteristics, Mooren’s Ulcer remains a diagnosis of exclusion and systemic diseases associated with PUK must be ruled out. Current treatment options and work up have resulted in a significant improvement in the prognosis of patients with Mooren’s Ulcer. With appropriate management, the eyes can usually be salvaged and visual loss can be minimized.The keys to appropriate treatment are early diagnosis, judicious use of topical as well as systemic steroids, immunosuppressives, and the use of tissue glue and patch grafting as indicated by the clinical scenario. References 1. Bowman W: Case 12, pll2 in the parts concerned in the operations of the eye (1849), cited by Nettleship E: Chronic Serpiginous Ulcer of the Cornea (Mooren’s ulcer). Trans Ophthalmol Soc UK 22:103-144,1902 2. McKenzie H: Disease of the Eye. 1854, p 631. 3. Mooren A: Ulcus Rodens. Ophthalmiatrische Beobachtungen. Berlin, A. Hirschwald:107-110, 1867 4. Nettleship A, Brkic S, Vackonic S: Chronic Serpiginous Ulcer of the Cornea (Mooren’s ulcer). Trans Ophthalmol Soc UK 22:103 - 144, 1902 5. Wood T, Kaufman H: Mooren’s ulcer. Am J Ophthalmol 71:417422, 1971 6. Keitzman B. Mooren’s ulcer in Nigeria. Am J Ophthalmol 65:679-685, 1968 7. Lewallen S, Courtright P: Problems with current concepts of the epidemiology of Mooren’s corneal ulcer. Ann Ophthalmol 22:5255, 1990 8. Majekodunmi AA. Ecology of Mooren’s ulcer in Nigeria. Doc Ophthalmol 49:211-219, 1980

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Bilateral Mooren’s Ulcer with perforation and Iris prolapse 9.

Schanzlin D: Mooren’s Ulceration. In: Smolin G, Thoft R, eds. The cornea. Boston. Little brown 1994, pp 408-414. 10. Wilson S, Lee W, Murakami C et al. Mooren’s type Hepatitis C virus-associated corneal ulceration. Ophthalmology 101:736745, 1994 11. Moazami G, Auran J, Florakis G et al: Interferon treatment of Mooren’s ulcers associated with hepatitis C. Am J Ophthalmol 119:365-366, 1995 12. Brown S. Mooren’s ulcer: Histopathology and proteolytic enzymes of adjacent conjunctiva. Br J Ophthalmol 59:670-674, 1975 13. Young R, Watson P: Light and electron microscopy of corneal melting syndrome (Mooren’s Ulcer). Br J Ophthalmol 66:341356,1982 14. Ferguson E III, Carreno O: Mooren’s ulcer and delimiting keratotomy. South Med J 62:1170-1175, 1969

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Delhi Journal of Ophthalmology 15. Chow C, Foster CS: Mooren’s ulcer. Int Ophthalmol Clin 36:113, 1996 16. Dinzis P, Mondino B: Management of non-infectious corneal ulcers. Surv Ophthalmol 32:94-110, 1987 17. Mondino B: Inflammatory diseases of the peripheral cornea. Ophthalmology 95:463-472, 1988 18. Robin G, Schanzlin D, Verity S et al. Peripheral corneal disorders. Surv Ophthalmol 31:1-36, 1986 19. Sangwan VS, Zafirakis P, Foster CS. Mooren’s ulcer: Current concepts in management. Indian J Ophthalmol 1997;45:7-17 20. Watson PG. Eye. 1997; 11 (Pt 3):349-56. 21. Seino JY, Anderson SF. Optom Vis Sci 1998 Nov; 75(11):783-90. 22. Frangieh T, Kenyon K: Mooren’s ulcer. In: Brightbill FS, ed. Corneal Surgery: Theory, technique, and tissue, ed 2. St Louis: Mosby 1993, pp 328-335. 23. Foster CS: Immunologic disorders of the conjunctiva, cornea and sclera. In: Albert DA & Jakobiec FA, eds. Principles and Practice of Ophthalmology. Philadelphia: Saunders: 1994, pp 200-203.

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Case Reports

Acute Onset Myopia and Angle Closure Glaucoma after Topiramate Administration Nidhi Verma, Ashok Kumar Glaucoma Services, Nidhi Eye Hospital, Bijnor, Uttar Pradesh, India. Topiramate is a new anti-convulsant which is used for the prophylaxis of migraine and cluster headache. We report a 17 year old male with bilateral induced acute onset myopia and secondary angle closure glaucoma following topiramate intake. In cases of bilateral acute angle closure glaucoma and induced myopia , drug induced ciliary body rotation should be excluded.

Introduction

Discussion

Topiramate is a sulfamate substituted monosaccharide, new anti epileptic drug used both as mono therapy and as an adjunct in the control of partial and primary generalized epilepsy. It is also effective in migraine prophylaxis, trigeminal neuralgia and bipolar disorders. We report the case of a adolescent with topiramate induced acute onset myopia and secondary angle closure glaucoma.

Acute Myopia, a rare idiosyncratic reaction to sulphonamides, was first described in 1938.[2] Banta et al [1] reported the first case of topiramate ( Topomax, Ortho-McNeil) induced angle glaucoma in a 51 year old man who recently initiated the medication for mood stabilization. Case reports on ocular side – effects of this drug date back to 2001.[1,3,4] In the “certain” category of WHO classification system, adverse ocular side effects associated with topiramate include abnormal vision, acute IOP elevation, acute myopia ( upto 8.75 dioptres), diplopia, nystagmus and shallow anterior chamber with angle closures. High frequency UBM, AS- OCT and B-Scan ultrasound have helped establish and document the patho-physiology of the myopia and angle closure glaucoma[5-7] – uveal effusions and ciliary body oedema resulting in antero-lateral rotation of the ciliary body, anterior displacement of lens iris diaphragm which contributes to the myopic shift, anterior chamber shallowing and secondary appositional angle closure. Though the exact mechanism is unclear, the fluid movement leading to effusion is thought to be related to drug induced changes in membrane potential.[8] The management of topiramate related acute rise of IOP requires stopping the drug in concert with the prescribing physician. Medical therapy such as aqueous suppressants should be given. Laser peripheral iridotomy are not helpful as angle closure is not pupillary – block related. Topical miotis are usually contra-indicated as they could precipitate relative pupil block. Ophthalmologist should be cautious with acetazolamide as it is also a sulpha- based drug and has been reported to cause angle – closure glaucoma in a similar manner to topiramate.[9] Topiramate is rapidly absorbed ( serum levels peak after oral dose in 1-4 hours), has good bio- availability , a relatively long half- life ( 20 – 30 hours), and is predominantly excreted

Case Report A 17 year old boy presented to our out patient department with complaint of sudden diminition of distance vision in both eyes since morning. We noted induced myopia from previous emmetropic state to – 3.5 Dsph in right eye and -4.0 Dsph in left eye. Anterior segment examination showed white and quiet (both) eyes, but anterior chambers were shallow and the iris and lens were bowed forward.(figure 1) IOP measured by goldmann applanation tonometry were 36mmHg in right eye and 28mm Hg in left eye. Gonioscopy revealed 360′ appositional angle closure in both eyes. Fundus examination revealed normal optic nerve with a cup disc ratio of 0.4 in both eyes and bilateral retinal striae radiating from the fovea.[fig 2] B-Scan ultra sound revealed annular peripheral choroidal effusion in both eyes.[fig 3] Oral topiramate treatment had been commenced for migraine prophylaxis 10 days prior to the onset of his symptoms at a dose of 25 mg once daily. He had no known previous drug allergies. Topiramate was stopped immediately. Topical ‘Timolol + Brimonidine’ combination eye drop twice daily in both eyes was started & continued for 3 days. Four days after stopping topiramate, visual acuity returned to normal with no refractive error, IOP was 10 mm Hg in both eyes, anterior chamber depth was normal and anterior chamber angles were open on gonioscopy. Two weeks later, repeat B-Scan ultra sound showed resolution of choroidal effusion.

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Acute Onset Myopia and Angle Closure Glaucoma after Topiramate Administration

in urine. If unrecognized as a drug related event, serious outcomes could occur ( 7 cases of permanent visual loss following angle closure glaucoma have been reported ).[10] Ocular examination before starting topiramate cannot identify eyes at risk. It is suggested that if the patient needs topiramate, it should be started with low doses and increased slowly with regular ocular examination. Patients, who are on topiramate therapy should be warned and advised to report immediately any symptoms of eye – pain or blurred vision especially in the first few weeks of treatment. Ophthalmologist need to be aware of the potential ocular side effects of topiramate. Although relatively rare, early recognition is key to appropriate management and maximised visual outcomes.

Figure 1: Representative slitlamp photograph of the both eyes demonstrating the following: A, shallow anterior chambers ; B, Forward bowing of lens-iris diaphragm

Delhi Journal of Ophthalmology

References 1. Banta JT, Hoffman K, Budenz DL, Ceballos E, Greenfield DS. Presumed Topiramate-induced Bilateral Acute Angle-closure Glaucoma. Am J Ophthalmol. 2001;132:112–4. doi: 10.1016/S00029394(01)01013-3. [PubMed] [Cross Ref] 2. Berns W. Proceedings of the Meeting of the Swedish Ophthalmological Society, 3rd December, 1938. Acta Ophthalmol. 1940;18:96-98. 3 Sen HA, O’Halloran HS, Lee WB. Case reports and small case series: topiramate-induced acute myopia and retinal striae. Arch Ophthalmol. 2001;119:775–777. [PubMed] 4. Sankar PS, Pasquale LR, Grosskreutz CL. Uveal effusion and secondary angle-closure glaucoma associated with topiramate use. Arch Ophthalmol. 2001;119:1210–1211. [PubMed 5. Shams P. 2007 Alcon Glaucoma Case Study Competition. Pinpoint Scotland Ltd; 9 Gayfield Square, Edinburgh EH1 3NT, UK: pp. 10–13. SUPP:1107:PINSCOT. 6. Levy J, Yagev R, Petrova A, Lifshitz T. Topiramate-induced bilateral angle-closure glaucoma. Can J Ophthalmol. 2006;41:221–225. doi: 10.1139/I06-012. [PubMed] [Cross Ref] 7. Chalam KV, Tillis T, Syed F, Agarwal S, Brar VS. Acute bilateral simultaneous angle closure glaucoma after topiramate administration: a case report. J Med Case Reports. 2008;2 doi: 10.1186/1752-1947-2-1. [PMC free article] [PubMed] [Cross Ref] 8. Levy J, Yagev R, Petrova A, Lifshitz T. Topiramate-induced bilateral angle-closure glaucoma. Can J Ophthalmol. 2006;41:221–225. doi: 10.1139/I06-012. [PubMed] [Cross Ref] 9. Fan JT, Johnson DH, Burk RR. Transient myopia, angle-closure glaucoma, and choroidal detachment after oral acetazolamide. Am J Ophthalmol. 1993;115:813–814. [PubMed 10. Fraunfelder FW, Fraunfelder FT, Keates EU. Topiramateassociated acute, bilateral, secondary angle-closure glaucoma. Ophthalmology. 2004;111:109–111. doi: 10.1016/j. ophtha.2003.04.004. [PubMed] [Cross Ref]

Figure 2. Representative fundus photograph of the right eye demonstrating retinal striae radiating from the fovea

Figure 3. Representative B-mode ultrasound image of the both eyes demonstrating: Choroidal Effusion

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Instrument Scan

Understanding your Direct Ophthalmoscope Digvijay Singh, Rohit Saxena, Pradeep Sharma, Vimla Menon Dr. R.P. Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

The direct ophthalmoscope is an extremely important examination tool not only for ophthalmologists but for physicians as well. It is probably the only tool in ophthalmology that can help perform a complete ocular examination. This article highlights the development, functioning and use of direct ophthalmoscopes.

A peak in the past Scientists had tried to peer into the then unknown back of the eye in the 18th and 19th century but were unsuccessful in understanding and establishing a coaxial illumination observation system. Then in the mid 19th century, several scientists noticed that if they kept a light source (pointed at the subject) very near their eye, then in some cases (emmetropes) they could view the red reflex and retina. It was in 1849 that Charles Babbage made what was probably the first practical ophthalmoscope.[1] (Figure 1). It was a simple piece of mirror with a silver patch rubbed off from the centre to make it see-through. Shortly afterwards, in 1851, Hermann Von Helmholtz published a monograph describing in detail the optical working of an ophthalmoscope and a designed a practical ophthalmoscope very similar to the ones used today. (Figure 2) Helmholtz is recognized as the inventor of the direct ophthalmoscope. An anecdote in this regard is that when Helmholtz tried to interest the king’s physician in his newly invented ophthalmoscope, he was told that it had no value as every known disease of the eye could already be diagnosed without it. Around the same time, the ophthalmoscope gave Helmholtz an instant global fame in the field of optics.

Figure 1: Babbage and his ophthalmoscope

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Figure 2: Helmholtz and his ophthalmoscope

Instrument detailing Currently, the ophthalmoscope comes in various sizes and modifications though all follow the same optical principle. Initially we describe in detail a standard direct ophthalmoscope and later look at the variants available with their specific advantages[2]. (Figure 3)

Figure 3: Detailed instrument scheme for the direct ophthalmoscope

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Understanding your Direct Ophthalmoscope

The ophthalmoscope consists of a metallic optical tube, usually made of a durable light weight metal such as chromeplated brass for proper alignment of the contents. Inside this tube, glass condensing lens, objective lens, mirror/prism aperture dial assembly, red-free/polarizer assembly and lamp are sealed. The aperture dial is mounted such that it maintains alignment despite a fall/accidental drop from a reasonable height.

as a clinical science existed well before the development of the ophthalmoscope as is exemplified by the founding of Moorfields eye hospital in 1804 and many others[3].

Illumination system • Incandescent lamp: This is usually a xenon halogen bright white lamp powered by a 2.5V non-rechargeable or 3.5V [NiMH (Nickel Metal Hydride) or LiION(Lithium ion)] rechargable battery. • Condensing lens: There are two condensing lens, one on either side of the aperture dial which focus the light onto the mirror/prism. • Aperture dial: This has got various apertures such as cobalt blue filter, fixation star, small spot, large spot, pinhole, hemispot and alit. These have a specific function each. • Reflecting mirror/prism: This is a mirror angled at 45 degrees which is partially reflecting or has a central peephole. It makes the light cone projected upon the patients eye appear as if it has originated from the mirror itself. Most modern ophthalmoscopes utilize a prism in place of a mirror for this purpose.

Apertures

Viewing system • Condensing Lens: These are aspheric lens with ranges varying with every ophthalmoscope model. Eg. +1-10, +15, +20,+40 and -1-10,-15,-20,-25,-35 in the Heine beta 200. • Viewing window: Recessed, antireflective coated to avoid glare. • Polarizing/red free filter: This is mounted on a separate dial and enables green, red free image viewing of the fundus or a polarized view to detect nerve fibre layer.

The why, what and how of direct ophthalmoscopy? Why? Why direct? It is a direct ophthalmoscope as the image forms directly on the retina and there is no intermediate image akin to that seen in an indirect ophthalmoscope. Why ophthalmoscope? It is indeed interesting to wonder why this instrument came to be called as an ophthalmoscope since the term ophthalmology was coined a good deal after the invention of the ophthalmoscope by Helmholtz in 1851. It is quite clearly argued in essays written in the nineteenth century that instruments and developing technology such as ophthalmoscope and laryngoscopes actually led to the development of the respective specializations. Of course eye Vol. 21, No. 3, January-March, 2011

What are all the knobs for? Light intensity adjustment dial: This helps provide an illumination of variable intensity for eliminating the corneal reflex and patient comfort.

Small spot This provides approximately a five degrees cone and is used for a small pupil. It also helps decrease corneal reflexes and increases patient comfort. Large spot This provides an approximately eight to ten degrees illuminated circle (though highly dependent on the refractive status and papillary diameter). Macular spot/pinhole This provides a small spot to observe only the fovea/macula without any undue light thereby minimizing patient discomfort and enabling viewing through a 1-2mm pupil. Hemi-spot Reduces corneal reflex and provides retinal depth perception. Slit Accurate assessment of retinal elevations and depressions. Assessment of anterior chamber depth. Cobalt blue spot Examination of corneal abrasions and scarring Fixation star (with polar coordinates) Accurate eccentric fixation testing, disc assessment and retinal mapping. Red free filter This may be combined with all filters. Contrasts features by removing red colour and thus betters visualization of blood vessels, hemorrhages and nerve fibre layer. Some ophthalmoscopes may have a polarized filter to better evaluate nerve fibre defects. Condensing/focusing lens They help focus the image onto the observers retina. Need to be selected based on the subjects refractive status and distance at which ophthalmoscopy is done. What are the image properties? The image formed by an ophthalmoscope is virtual, erect and magnified. The area of retina imaged varies between 6.5 to 10 degrees. (Average area subtended by disc is 7 degrees vertical and 5.5 degrees horizontal; thus an average sized disc should just fit the 5 degree cone of ophthalmoscope)

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How does the ophthalmoscope function? Fundamental Optics The ray diagram of the direct ophthalmoscope is shown below. It also depicts the usage of condensing lenses for eyes with refractive error[2]. (Figure 4)

Understanding your Direct Ophthalmoscope

When the ophthalmoscopy is being done from very close to the eye, the distance is less than f causing a virtual erect image to be seen. Magnification To understand how the ophthalmoscope magnifies, we take the example of an emmetropic eye. First we examine a small segment of a retinal vessel from 25 cm (the comfortable near vision distance). Let us suppose it subtended an angle of q0. We now view the same vessel segment from very close to the eye. Assuming the eye as a reduced lens of power 60D, we now are seeing from within the focal length of this lens thus we see a virtual erect image. On extrapolating this image to 25cm distance, you can observe that it is much larger and subtends an angle of q10. Thus we observe an angular magnification and no linear magnification. M ang= q10/ q0 = distance(d) × power(D)= 0.25 × 60.This is equal to 15. (Figure 7)

Figure 4: Ray diagram depicting optics of ophthalmoscope

Image Properties The image properties depend on the working distance used for ophthalmoscopy. When done at a distance of 25 cm for distant direct examination, we observe a real inverted unmagnified image of the fundus as shown in Figure5.

1

A object (upright arrows) at 25 cm subtends angle q at unaided observer’s eye. B Virtual Image (Large grey Arrow) of the same object subtends angle

Figure 5: Image properties during distant direct ophthalmoscopy

When the fundoscopy is done from a very near distance to the subject’s eye, the image is a virtual erect one.(Figure 6)

Figure 6: Image properties while viewing fundus during close range ophthalmoscopy.

This image changes from a real to virtual may be understood with a basic knowledge of optics. The focal length of the reduced eye model is 1.67 cm. The retina therefore lies between f and 2f. When we do a distant direct ophthalmoscopy, we are observing the image from distance between 2f and infinity as also, the light source is originating from this point. This thus gives a real inverted image forming on the observer’s eye.

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q1 when viewed.

Figure 7: Image depicting magnification property of ophthalmoscope

Field of view The field of view seen in a direct ophthalmoscope varies with the distance at which the examination is carried out and the pupil diameter. For example, if we observe the fundus from a distance of 15 cm in a 2mm pupil, then we can only see an area of about 200-300µ or a short segment of a vessel. In contrast on observing from very close to the eye in a well dilated pupil (8mm), we can see more than 10degrees of field. Theoretically it may be possible to see up to the equator in a fully dilated pupil in a cooperative patient on moving the ophthalmoscope and patients eyes appropriately.

How to perform a complete ophthalmoscopic examination? Steps Before proceeding, it is important to understand the instrument well. The first step in the use of an ophthalmoscope is to do Vol. 21, No. 3, January-March, 2011

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Understanding your Direct Ophthalmoscope

examination at 1m distance. This sheds light on any abnormalities of the eyelids, orbit and periorbita as well as highlights any obvious ocular deviations. This should be followed by a distant direct examination at 22-25cm( a comfortable near vision distance). Some ophthalmologists prefer to do this at a closer distance of 10cm as it gives better details. If the examination is done at 10cm, we should select a +10D condensing lens to view the best glow. At 25 cm, a +4D lens may be used. This examination shows a red reflex and highlights any opacities in the media as black images. The patient may then be asked to look in the four cardinal gazes and the movement of the opacity noted. Movement against the ocular movement means the opacity is behind the nodal point of the eye (i.e. in the lens or vitreous) while a movement with would indicate corneal or anterior segment opacity. The distant direct examination is also used to examine the lens, iris, cornea and adnexa. Any squint in a child may be picked up due to an unequal reflex (Bruckner’s test). The presence of an RAPD can also come forth in this step. The third step involves moving closer to the patient and correspondingly increasing the power in the condensing lens to examine in detail the magnified anterior segment structures. The fourth step entails reducing the condensing lens power such that any part of the retina comes into focus. While reducing the power, the vitreous cavity will come into focus and any pathology in it may be seen. Once the retina is focused, we may localize any blood vessel and follow it backwards against the branching pattern to reach the optic disc. Then move temporally from the disc to reach the macula. We can ask the patient to look into the light and the fovea will come into focus. The blood vessels can be traced into the periphery from the disc to reach second and third order vessels. This completes the posterior pole examination to examine the periphery, we ask the patient to look in the four cardinal gazes while continuing to focus the retina. The ophthalmoscope illuminated cone may be moved to further our view into the peripheral retina.

Practical tips •

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•

To eliminate the irritating corneal reflex, one can slightly tilt the ophthalmoscope and view obliquely. One can also decrease the illumination intensity and use a smaller aperture. Corneal reflex is also negated if the patient is approached from 15 degrees rather than from straight ahead. Use a small aperture for a smaller pupil as only an illuminated cone equal to the size of the pupil can enter or exit the eye while the rest will reflect off the iris creating unnecessary glare and poor contrast. The fovea lies 3 degrees temporal to the optical axis of the eye, the disc lies 10 degrees nasal and the peripheral

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• • •

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•

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retina commences about 16 degrees temporal to it. Thus, if the patient is seeing straight ahead, then we know how much to tit the ophthalmoscope to view these landmarks. The patient should be asked to look straight ahead into the distance or preferably to a target on a far off wall. The patient should be instructed to stay steady and frequently blink during the examination. The examiner should use his right eye to view the patient’s right eye and vice versa. They should keep their opposite hand on the patient’s forehead to support and steady it. The examiner should keep both their eyes open during examination and imagine as if the retina is at 6 meters to prevent accommodation. Normally, the examiner should continue to wear his glasses while the patient has to remove his. The field of view decreases if the examiner wears his glasses therefore for low myopes or hyperopes (± 3Ds) and astigmats (below 2.5Dc) may remove their glasses especially in a small pupil. A trick to decide the appropriate selection of the condensing lens is described as follows. Observe the light reflex on the retinal vessels. If a white line is seen then either the patient is emmtropic or hyperopic. In that case, add plus lens and the highest plus when the line reflex disappears is the appropriate power. This would also be the approximate refractive error of the patient if the examiner had not accommodated. If there is no line of light reflex on the vessels, then the patient is myopic. Add minus power and the smallest minus lens when the reflex appears is the refractive error of the patient. The lenses of the ophthalmoscope can be used to focus variously the apex and base of any intraocular mass and thus helps determine its height in dioptres.

How to select an appropriate ophthalmoscope? The ophthalmoscope selection should be guided by a number of factors. Prime among these is the intended clinical role. For a physician who needs to evaluate whether a fundus is normal or abnormal, a basic design should suffice while an ophthalmologist should look for one with highest quality optics and maximum functionality for accurate diagnosis. The ophthalmoscope should have apertures such as the small and large spot, cobalt blue filter, slit and the fixation star. Presence of a green filter is mandatory for diagnostic purposes. The instrument should contain adequate number of focusing lenses with a 1 dioptre minimum count for fine focusing. The battery should preferably be rechargeable Li ion or NiMH which provide extended power. Beyond this minimum specifications, any of the advanced machines may be used.

How to Care for the direct ophthalmoscope? The direct ophthalmoscope is a sturdy built instrument for

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heavy handling but requires proper care for its longevity. The following precautions should be observed: • The battery should be fully discharged and recharged once every few months to maximize battery life. • After fully charging the battery, the bulb should first be switched on at sub-maximal illumination for 1-2 cases before employing full illumination to maximize bulb life. • Use only genuine bulbs and replace in accordance with the owner’s manual instructions. • The condensing lenses are stuck to the dial using glue which is soluble in acetone and related solvents. Therefore never use these to clean your ophthalmoscope. • The ophthalmoscope may be cleaned using mild alcohol or detergent and a soft cloth. • A cotton bud should be used to clean the viewing window and aperture window in a circular sweeping manner. • Ophthalmoscopes come with twist and fit as well as automatic lock heads. Ascertain the head connector in the scope and fix head accordingly. • Always store the ophthalmoscope in ints case when not in use. If it will be unused for a long time, remove the battery and store. • Dispose the NiMH or Li ion battery appropriately.

possible but not mutually interfering. This gives a larger view in smaller pupils as well as eliminates corneal reflex artifacts. Apart from this the incorporation of aspheric designs in lenses has led to decreased aberrations and reflex artifacts. Battery life has been greatly enhanced with the modern NiMH or Li ion batteries while their size and weight has more than halved. This has enabled manufacture of Pocket sized or mini ophthalmoscopes which have an added convenience factor. Further advancements are underway to add better and more functionality to this principal tool of every clinician.

Conclusion

Innovations in direct ophthalmoscopes

The direct ophthalmoscope has an immense contribution in furthering the development of ophthalmology as a specialty science. Familiarity with the use of this instrument would go a long way in aiding the diagnosis of diseases by physicians and ophthalmologists alike. Although technology has brought the ophthalmoscope a long way from its humble beginnings, one should realize that like every instrument, it too has its limitations. These include the limited field of view, poor image visibility through hazy media, inability to appreciate the full picture, a high need for patient cooperation and non stereoscopic viewing among others. If we works bearing these in mind, we are unlikely to get mislead by false signs and would gain a lot more from this brilliant instrument.

The direct ophthalmoscope has come a long way from the polished mirror made by Babbage or the more practical model of Helmholtz. Illumination technology has shifted from the use of a gas flame as an external source of illumination to the first directly illuminated ophthalmoscope made in 1915 to the current day instruments using halogen and xenon bulbs. The viewing systems have improved drastically over time. The latest innovations include the panoptic ophthalmoscope which uses axial point source optics whereby the light is focused at a point on the cornea before moving onwards into the eye. This enables a wider field of view (up to 5 times wider) in smaller pupils. Another leap forward is the use of advanced coaxial optics where the illumination and viewing is done along the same path of light keeping them as close as

References 1. Keeler CR. Babbage the Unfortunate..Br J Ophthalmol 2004;88:730-732. 2. Timberlake GT, Kennedy M.The Direct Ophthalmoscope:How it Works and How to Use It. 2005. University of Kansas Press. 3. Silvester A. The emergence of medical specialties in the nineteenth century: a discussion of the historiography. History of Medicine online 2010 Priory.com publication 4. Instruction user manual of Heine Beta200 ophhalmoscope. 5. Ghosh S, Collier A, Varikarra M, Palmer S. Fundoscopy made easy. 2010. Churchill livingstome Elsevier. 1-21. 6. Fisher WA. Ophthalmoscopy, Retinoscopy and Refracion. 1937:1-34.

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Understanding your Direct Ophthalmoscope

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Delhi Journal of Ophthalmology

Origial Article

Study of Colour Blindness in Tibetan Population Navjot Kaur, Avinash Kumar, Gurinder Kaur, Jasjeet Kaur Dhillon, K.D.Singh Government Medical College & Hospital, Chandigarh, India Of the 1210 male and 800 female Tibetan population in Northern India between the age group of 11-60 years, 51 males and no female were found to be having colour blindness, showing an incidence of 4.21 % and 0% respectively. The study was done with the help of Ishihara charts and Pickford Nicolson’s anomaloscope. The type of colour blindness in males in its descending order of occurrence was simple deuteranomaly 27.45% protanopia 17.64%, deuteranopia 17.64%, extreme deuteranomaly 15.68%, protanomaly 13.72%, extreme protanomaly 5.88% and tritanopia 1.96%. None of the female was colour blind. The incidence and type of colour blidness found in males is within the range of other Indian samples. Nevertheless the incidence is much lower than the values reported in European populations but is much higher than the values reported in African populations.

Introduction Sir John Dalton was the first scientist to give a clear description of his own colour blindness in 1794. This publication stimulated much subsequent research into the pathophysiology and genetics of the condition (1). In 1801-1802, Thomas Young postulated the existence of three “principal” colours (red, green and violet) from which all colours and white light can be obtained, (2). Von Helmholtz (1866) suggested that there are three types of cones containing three photochemical substances corresponding to the three fundamental colour sensations (3). In 1881, Lord Rayleigh introduced anomaloscope for scientific analysis of colour defects (4). Since then many scientists have worked on the incidence of colour blindness in different parts of India and the world. But very few studies are available on the use of anomaloscope in India. The present study was conducted to find out the incidence of congenital colour blindness in the Tibetan population and to find out the type and degree of colour blindness with the help of anomaloscope. A comparison witl1 other studies is made. Persons with defective colour vision are at a disadvantage especially for employment purposes eg: as pilots, drivers, in defence services and in technical fields like engineering and medical profession.

Method 2010 Tibetees of either sex between the age group of 11-60 years from Patiala, Ambala, Zirakpur, Mohali, Bhuppur camp and Puruwala camp were investigated for colour vision by the means of Ishihara charts and the anomaloscope. Not much work has been undertaken in this group of population in this region of the country therefore, the Tibetan population was selected in the present study. In addition to the tests of colour vision, all the subjects were tested for acuity of vision by using Snellen’s test chart for distant vision and Jaeger’s chart for near vision. The 15th edition of Ishihara plates (1960) was used and tests were conducted in accordance with instructions accompanying Vol. 21, No. 3, January-March, 2011

the plates (5). Ishihara plates consist of a series of cards on which a coloured background is printed in spots of different sizes. A letter, figure or a number is printed against this background in spots of the same size. To a normal subject the figure or letter at once becomes clear, but the colour blind subject fails to distinguish it from the background. It is easy, quick to perform and type of colour defect can be ascertained with a fair degree of accuracy. The detection of Tritan defect is not possible using this test. First 25 plates were used in the present study as all the individuals were educated. The plates from 26 to 38 are meant for illiterate persons, so these were not used.The Pickford Nicolson Anomaloscope (6) is a simple colorimeter based on the use of integrating boxes. The outside dimensions of the apparatus are about 10”X 10 ½ “X5”. The instrument has color chances optical glass filters. It is manually operated. With the anomaloscope three tests were performed in which a red / green, a green / blue and a yellow / blue Rayleigh equation were used respectively. The Rayleigh equation used is: Red (642nm) + Green (555nm) = Yellow (585nm).The wavelengths of the primary filters (Red and Green) used are 642nm and 555nm, to produce a yellow with a wavelength of 585 nm. Both eyes were tested separately using different equations. It is the only instrument by means of which colour blindness can be correctly classified

Results All healthy subjects with no history of chronic disease or long term medication were selected for the present study. Out of 2010 individuals (1210 males and 800 females) 51 males and no female was found to be having colour blindness (Table 1) The age range of 51 colour blind males is 11-60. (Table II) The type of colour blindness in males by using Ishihara charts only is shown in Table III. The results of the Ishihara chart tests show that 51 individuals were protan/deutan type and only one individual was of tritan

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type. Out of 51 protan/deutan type of individuals, 18 were of protan type, 32 were of detuan type. Another observation was that out of 50 protan/deutan type of individuals there were only 2 whose readings were resembling the test figures totally. All other protan/deutan type did not show a typical resemblance in total, but a sum total of their readings show that they were of protan/deutan type. This shows that there are individual differences in the degree of colour blindness. The reading of one tritan type of individual resembled the test figures completely. The results also show that the deutan type of colour blindness is the most frequent type. The acuity of vision with or without glasses in all these affected individuals was found to be normal. The type of degree of colour blindness in males as tested by the anomaloscope are shown in Table IV. As most of these affected individuals are of protan/deutan type, the results of the red/green equation are plotted graphically (Fig 1) . No monochromat was found in the present study. In all the affected individuals both eyes were defective, on testing each eye separately. An interesting observation in the study was that most of the affected individuals did not know that they had any defect regarding their colour vision.

Discussion The incidence of colour blindness is much more in males as compared to females. The results of the present study with anomaloscope show that the frequency of trichromatism was much more as compared to dichromatism and among trichomats, the frequency of deuteranomaly is more than that of protanomaly. This can be explained by the heredity of colour blindness (7). As colour blindness is a hereditory defect, the incidence in different age groups is statistically insignificant. In the present study the incidence of colour blindness in males was 4.21 %. A comparison with the other studies show that there is less variation of the incidence of colour blindness in different parts and communities of India as shown in Table V than in other parts of the world as shown in Table VI. This comparison gives support to the selection relaxation hypothesis of Post (14) and Pickford (22). As shown in Table VII no female was found to be colour blind. It is not possible to conclude regarding the incidence of colour blindness in females from the present data. To find the exact incidence of colour blindness in females, a further study with a large sample is required. References 1. Emery AE, John Dalton (1766-1844). J Med Genet 1988; 25 (6) :422-426. 2. Young: Theory of colour vision. Phil Trans 1801 ; 91: 23-A. A course of lectures on natural physiology and the mechanical arts, London 18-07. Quoted by Duke Elder. The Physiology of eye and vision 1968; iv: 643. 3. Von Helmholtz: Ann Phys (LPZ) 1852; 87: 45. Quoted from Duke

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Study of Colour Blindness in Tibetan Population Elder. Physiology of the eye and vision. System of ophthalmology 1968; 4:620. 4. Rayleigh L. Colour equations. Nature 1881; 25: 64-66. 5. Ishihara S. Test for colour blindness. 15th complete edition with 38 plates 1960; H.K. Lewis Co. Ltd., London. 6. Pickford RW, Lackowski R. Anomaloscope. Brit J Physiol Optics 1961; 17: 131-134, 7. William F Ganong . Vision. Review of medical physiology 2003; 21: 168. 8. Dutta PC, Kumar GO. The incidence of inherited defects of colour vision in MP. Acta Genet Med Gen 1966 ; 15(4) 364-369. 9. Bansal IJS. The frequency of colour blindness among the Punjabis of India. J Genet Hum 1967; 16 (1-2) : 1-5. 10. Parikh NP, Baxi AJ and Jhala HI. Incidence of colour blindness among three groups from Gujarat. The Indian Journal of Medical Sciences 1968 ; 334-7. 11. Bhasin MK. The frequency of colour blindness in Newars of Nepal valley. Acta Genet Basel 1967; 17: 454-458. 12. Clements F. Racial differences in colour blindness. Amer J Phys Anthrop 1961 ; 4: 189-204. 13. Vries-de Mol EC de, Went LN. Frequency of different type s of colour vision defects in Netherlands. Human Heredity 1978 ;28: 301-317. 14. Post RH. Natural selection and colour blindness. Eug Quart 1962 ; 9: 131-146. 15. Rebato E and Calderon R. Incidence of red-green colour blindness in the Basque population. Anthropol Anz 1990 ; 48 (2) : 148-5 . 16. Sato H. Frequency of colour defects among Japnese. Acta Soc Opthal Jap 1935 ; 38: 2227-2239. 17. Chan F, Mao J. Colour blindness among Chinese. Brit J Opthal 1950 ; 34 : 744-748. 18. Zein ZA. Gene frequency and types of colour blindness In Ethiopians. Ethiop Med J 1990 ; 28 (2) : 73-75. 19. Applemans M. Colour defects among the natives of Congo.Bull Soc Belge Opthal 1953 ; 103: 226-229. 20. Simon T. Colour defects among natives of Uganda. E Afr Med J 1951 ; 28 :75-78. 21. Oppolzer A and Winkler EM. The incidence of colour blindness in East African Negores. Anthropol Anz 1980 ; 38 (2) : 117-20. 22. Pickford RW. Natural selection and colour blindness. Eugen Rev 1963 ; 55 : 97-101. 23. Tiwari SC. The incidence of colour blindness among the Tibetans. J Genet Hum 1969; 17 (1-2) : 95-99. 24. Mahajan OP, Gogna RS. Study of colour blindness in school children. Indian J Physiol Pharmacol 1977; 21 (1) : 59-62. 25. Manibabu, Mayanglambam. Colour blindness amongst the Maring Nagas of Manipur. Journal of Human Ecology Delhi; 1998 ; 9 (2) : 199-200. 26. Naresh S. Study of colour blindness in Jat Sikhs Indian J. Physiol Pharmacol Apr 1995 ; 38 (2) : 127-130. 27. Dhillon JK: Study of colour blindness in Mohammadans MD Thesis of Punajbi University 1979.

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Study of Colour Blindness in Tibetan Population Table I Showing the incidence of colour blindness In 2010 Tibetees

Delhi Journal of Ophthalmology

Table V Comparison of incidence of color blindness in males in different Part of India

Table II Showing Age Range of 51 colour blind males.

Table III Showing type of colour blindness in 1210 males by Using Ishihara Chart Test

Table VI Comparison of incidence of color blindness in males in different Part of India

Table IV Showing type of colour blindness in 1210 males by Using Ishihara Chart Test Table VII Comparison of incidence of color blindness in females in different Part of India

Vol. 21, No. 3, January-March, 2011

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Origial Article

Manual Sutureless Small Incision Technique for Exchange of dislocated Posterior Chamber IOL Lakshminarayana Pasumala ESIC Hospital , Noida (Delhi/NCR) Dislocation of Posterior Chamber Intra Ocular Lenses(PC IOL) into posterior segment with complete rupture of posterior capsule is a well known complication of Phacoemulsification with Foldable IOL implantation which can be managed by various techniques such as repositioning of the IOL in the ciliary sulcus by suturing to sclera or iris fixation and IOL exchange with either a iris claw lens or Anterior Chamber(AC) IOL.Suturing techniques result in complications like vitreous hemorrhage and IOL re-dislocation and exchange with iris claw lens and AC IOL requires large limbal corneal incisions which need suturing and result in significant astigmatism and complications like iris prolapse,hyphema and iris atrophy.To obviate these problems we describe a series of 7 cases in which we have used the incision design of Manual Small Incision Cataract Surgery for exchange of dislocated PC IOL’s with AC IOL’s through a Manual Sclero Corneal Sutureless Small Incision (Manual SI) route in cases with absent capsular support.Though this route is being used in such cases there is no study till today describing it’s effectiveness and pitfalls if any in a series of cases.

Introduction The advent of Phacoemulsification has rendered the incision for cataract surgery smaller, compact and self sealing, facilitating use of foldable intraocular lens (IOL).Insertion of foldable IOLs through these compact incisions carries with it high risk of PC IOL dislocation in case of tears in lens capsule. Dislocated IOL needs to be removed and requires either repositioning or exchange. Various techniques described for repositioning or exchange of dislocated IOL in the absence of capsular support include repositioning of the PC IOL in the ciliary sulcus by suturing to the sclera [1] and iris fixation. IOL can be exchanged with either iris claw lens or Anterior chamber lens(AC IOL) via a large limbal incision. [2] AC IOL implantation is technically easier but it requires an additional large limbal incision and carry with it intraoperative problems like iris prolapse, iris atrophy, hyphema. To obviate the problems of large uncontrolled limbal incisions in these cases the sclerocorneal sutureless small incision design of manual SICS surgery is being used as an effective alternative with excellent results but a systematic case series describing it’s use is lacking.Hence we describe in a series of 7 patient’s, the technique for exchange of dislocated PC IOL with AC IOL through a Manual Sutureless Small Incision(manual SI) route which avoids large uncontrolled limbal incisons and results in quick and effective visual rehabilitation to the patient. Materials and Methods We have operated on 7 patients using this technique between Sep 2009 and July 2010 in our hospital, all surgeries being performed by a single surgeon. All the patients have previously undergone phacoemulsification with foldable IOL

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implantation with complication of dislocated PC IOL into vitreous with complete capsular rupture, 2 operated in our center and 5 being referral patients. In all the 7 patients the IOL was completely dislocated into vitreous. Complete Ocular examination and detailed Indirect Ophthalmoscopy(I/O) examination was normal in all patients. Two patients had mild vitreous haze but no vitreous hemorrhage. In all the patients a peribulbar block was administered after dilating the pupil. Superior rectus bridle suture applied, conjuctival peritomy done and scleral bed blanched with cautery. A 6mm sclerocorneal tunnel carved as in manual SICS procedure described by Sanduk Ruit et al with a crescent knife. At this time no entry is made into the anterior chamber. After this a standard 3 port pars plana vitrectomy (PPV) procedure done and IOL is gently prolapsed into the AC and placed above the iris (Fig 1, Fig 2). Pupil constricted with 0.5% pilocarpine (Fig 3) and AC washed with saline. Visco Elastic Device is injected below and above the IOL through a clear corneal side port incision. Superior vitrectomy ports closed with 6-0 vicryl suture. Valvular entry is made into the AC through the already created tunnel with a keratome knife. Leading haptic of the PC-IOL is held with a vitreous forceps and IOL explanted through the tunnel incision (Fig 4). Infusion of saline through the vitrectomy cannula is kept on during the entire procedure to maintain good AC pressure. Kelman style, PMMA AC IOL is implanted in the AC after closing the infusion port of vitrectomy cannula (Fig 5). Peripheral iridectomy done and sclerocorneal lip is hydrated with saline and AC made water tight. Conjuctival edges are cauterised and subconjuctival injection of a antibiotic-steroid mixture given.

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Manual Sutureless Small Incision Technique for Exchange of dislocated Posterior Chamber IOL

Results In all the 7 cases foldable acrylic IOL’s were explanted by PPV and Kelman style AC IOL’s of optic diameter 6 mm implanted in the AC. None had any contraindication for AC IOL implantation. Pre-op visual acuity (VA) with aphakic correction ranged from 20/80 to 20/40. All the patients had excellent post operative visual recovery and at 8 week examination minimal refractive error noted in all (range -0.25 DS to- 1.00 DS spherical and astigmatism range from -0.25 DC to -0.75 DC) (table 1).Post operative VA ranged from 20/30 to 20/20.The wound was self sealing in all the patients and required no suture. Post-operatively none developed any retinal tears, choroidal effusions, supra choroidal hemorrhage or vitreous hemorrhage. Corneal clarity were normal pre and post operative in all the patients.

Delhi Journal of Ophthalmology

incision route in a series of 7 patient’s which results in less post operative astigmatism, quick visual rehabilitation and with additional benefit of decreased iris related complications. The technique is easy to apply as it is an extension of incision design of manual SICS surgery and requires less technical expertise, saves time and can be practiced on a wide scale.To the best of our knowledge this is the first study describing the use of incison design of manual SICS surgery for exchange of posteriorly dislocated IOL’s in a case series of 7 patients.

Discussion Dislocation of PC IOL into vitreous with complete capsular rupture is an often encountered problem in modern cataract surgery and can be managed with either repositioning or exchange of the IOL. Exchange with a AC IOL is a simple technique and the procedure requires less time unlike suture fixation which is a technically demanding procedure [3] and it cannot be universally applied to all designs of IOLs. [2] IOL exchange with iris claw lens and AC IOLs require large limbal incisions of 7-7.5 mm with associated risk of choroidal effusions and supra choroidal hemorrhage [4,5] and also the incision requires suturing. In contrast our technique involves exchange of IOL through a self sealing sutureless sclerocorneal incision route which is routinely used for manual SICS and we did not encounter any of the problems seen with large limbal incisions. Harry S Geggel [6] has described a simplified technique for acrylic foldable IOL explantation through a scleral frown incision of 3.5-4 mm and exchanged it for another foldable IOL. In our cases we have explanted the IOLs through a self sealing 6 mm incision and implanted a AC IOL. As manual SICS’s are widely performed in developing countries we have applied its incision technique in our cases with good result. On Literature search we did not find any systematic study reported for exchange of dislocated PC IOL with AC IOL through a manual SICS route so far and with this technique we encountered minimal astigmatism. Sanduk Ruit et al [7] compared Phaco with manual SICS and reported minimal astigmatism difference between Phaco and manual SICS group (0.18 D). Our technique involves a valvular self sealing incision and has decreased incidence of iris prolapse, iris atrophy. Using this technique we have explanted 4 single piece foldable acrylic IOL’s and 3 multipiece IOL’s. In conclusion we have described a useful technique for exchange of dislocated PC IOL with a AC IOL through a manual sutureless small Vol. 21, No. 3, January-March, 2011

Figure 1: PC IOL is being brought into AC with vitreous forceps after PPV.

Figure 2: PC IOL prolapsed into AC and resting above iris.VED is injected above and below the IOL.

Figure 3: Iris constricted with 0.5% pilocarpine nitrate to prevent the IOL from falling back into the vitreous.

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Delhi Journal of Ophthalmology

Manual Sutureless Small Incision Technique for Exchange of dislocated Posterior Chamber IOL

Figure 4: PC IOL is being explanted through the small incision route with vitreous forceps. Note no iris prolapse.

References 1. Pang MP, Ilar M. A Modified technique for the management of completely dislocated posterior chamber intraocular lenses in the absence of capsular support. Retina 2003; 23: 861-63. 2. Flynn HW Jr. Pars plana vitrectomy in the management of subluxed and posteriorly dislocated intraocular lenses. Graefes Arch Clin Exp Ophthalmol 1987; 225: 169-72. 3. Wagoner MD, Cox TA, Ariyasu RG, Jacobs DS, Karp CL. Intraocular lens implantation in the absence of capsular support: a report by the American Academy of Ophthalmology. Ophthalmol 2003; 110: 840-59. 4. Sabti K, Lindley SK, Mansour M, Discepola M. Uveal effusion after cataract surgery: an echographic study. Ophthalmol 2001; 108:100-3. 5. Beatty S, Lotery A, Kent D, O’Driscoll A, Kilmartin DJ, Wallace D, et al. Acute intraoperative suprachoroidal haemorrhage in ocular surgery. Eye (Lond) 1998; 12:81520. 6. Geggel HS. Simplified technique for acrylic intraocular lens explantation. Ophthalmic Surg Lasers. 2000; 31: 506-7. 7. Ruit S, Tabin G, Chang D, Bajracharya L, Kline DC, Richheimer W, et al. A prospective randomized clinical trial of phacoemulsification vs manual sutureless smallincision extracapsular cataract surgery in Nepal. Am. J. Ophthalmol 2007; 143: 32-38.

Figure 5: AC IOL in place .Wound self sealed requiring no suture.

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Delhi Journal of Ophthalmology

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