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Vitreo Retinal Diseases-I Free Papers

Contents

VITREO RETINAL DISEASES - I


Effect of Intravitreal Bevacizumab on Choroidal Neovasular Membrane Secondary to Choroidal Osteoma................................................................ 1026
Dr. Ankur Gupta, Dr. Ajay Sharma, Dr. Tandava Krishnan Panakanti, Dr. Muhammad Moniruzzaman

Burkholderia Cepacia Endophthalmitis A Losing Battle ....................... 1028


Dr. Shalabh Sinha

Retinopathy of Prematurity: Analysis of Screening, Incidence and Risk Factors............................................................................................................. 1030


Dr. V. K. Dhull, Dr. Anugya Agrawal, Dr. Geeta Gathwala, Dr. Manisha Nada

A Retrospective Review of Vision Threatening Complications Post Intravitreal Bevacizumab in CRVO.................................................................................... 1033
Dr. Narendra G. Venkata, Dr. Sambasiva Rao Velagapudi

Is Elevated Plasma Homocysteine in Patients With Retinal Veinous Occlusion A Indicator for Severe Macular Edema?....................................................... 1036
Dr. Poninder Kumar Dogra, Dr. Sqn Ldr Avdesh Oli, Dr. Brig Ajay Banarji, Dr. Brig T. S. Ahluwalia

Associations of AMD in Central India. The Central India Eye and Medical Study (CIEMS) ................................................................................................ 1039
Dr. Nangia Vinay Kumar B., Dr. Jost Jonas, Dr. Arshia Matin, Dr. Maithili Kulkarni Dr. Maneesh M. Bapaye, Dr. Meena M. Bapaye, Dr. Charuta M. Bapaye

Recording Posterior Segment Surgery with Handycam............................ 1044 Our 5 Years Experiences with 102 Intravitreal Injections of Avastin as Primary Therapy for ROP............................................................................... 1047
Dr. Rohan Chauhan, Dr. Banker Alay S.

Clinical Features Diagnosis and Management of Choroidal Neovascular Membrane in Pediatric Population............................................................... 1054
Dr. Jyoti Prakash Vyas, Dr. Giridhar A., Dr. Thomas Thachil

APROP: A Case Series .................................................................................. 1060

Dr. Sucheta Kshirsagar, Dr. Pravin Narwadkar, Col.M.Deshpande, Dr. Nilesh Kakade

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VITREO RETINAL DISEASES - I


Chairman: Dr. Chandran Abraham ; Co-Chairman: Dr. Meena Chakrabarti Convenor: Dr. Narendran V.; Moderator: Dr. Tushar Kanti Sinha

Effect of Intravitreal Bevacizumab on Choroidal Neovasular Membrane Secondary to Choroidal Osteoma


Dr. Ankur Gupta, Dr. Ajay Sharma, Dr. Tandava Krishnan Panakanti, Dr. Muhammad Moniruzzaman

he term choroidal osteoma was coined by Gass in 1978.1 These tumors demonstrate evidence of bone formation in the choroid and are believed to be choristomatous in origin.2 In a follow-up study of 36 patients, the probability of loss of visual acuity (20/200 or worse) was more than 50% over 10 years.3 Choroidal neovascularization (CNVM) is the most frequent cause of visual loss (>50%) in choroidal osteoma.4

MATERIALS AND METHODS


We report a case of a 21 year old lady of choroidal osteoma with CNVM presenting with complaints of defective vision OD for past 6 months. Her past ocular, medical, and family histories were noncontributory. On examination, her best-corrected visual acuity was 6/18 N8 in OD and 6/6 N6 in OS. Her anterior segment evaluation was within normal limits in OU. Fundus examination OD showed an elevated, yellowish lesion on the posterior pole having a smooth surface with slight elevation with associated subretinal haemorrhage. B scan ultrasound showed high surface reflectivity with posterior shadowing suggestive of ossification. CT scan showed a radio opaque plaque of bone density at the level of posterior pole in OD. FFA showed a large area of early patchy hyperfluorescence with late staining in the area of lesion with an area of blocked fluorescence in area of sub retinal haemorrhage to it suggestive of a CNVM. Spectral domain OCT (Cirrus, Carl Zeiss) showed a high reflective sub retinal lesion with posterior shadowing with adjacent area of sub foveal sub retinal fluid. A diagnosis of choroidal osteoma with secondary CNVM was made. A treatment option of anti VEGF (Vascular Endothelial Growth Factor) injection was offered to the patient after explaining its roles and limitations for which the patient consented. The patient was given 3 intravitreal bevacizumab injections (1.25 mg in 0.05 mL) at monthly intervals. Visual acuity improved to 6/6; N 6 and CNVM showed signs of regression, with resolution of sub retinal hemorrhage and fluid confirmed on OCT and FFA. 2 months after third

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injection, recurrence of CNVM was noticed on OCT and a repeat bevacizumab injection was given. Two months after the last injection (7 months), CNVM was inactive with a visual acuity of 6/6; N 6 which was also noted on OCT and FFA.

DISCUSSION
LASER photocoagulation was initially used for Choroidal osteoma with extrafoveal secondary CNVM.5 Aylward et. al. found the success rate in such cases to be only 25%.2 Nearly half of Choroidal osteoma related CNVM were subfoveal, which could only be observed. Extrafoveal CNVM too was poorly responsive to laser photocoagulation, probably due to depigmentation of RPE and degenerated RPE/Bruchs membrane complex, resulting in the reduced laser uptake. Surgical removal of subfoveal CNV has been performed successfully; however, the visual result has been poor.6 Reports of PDT for osteoma-related CNVM have been published. However, issues related to cost, risk of vision loss and need for multiple retreatments have been raised.7 TTT has also been tried in this condition but there is lack of visual recovery.8 Bevacizumab has been used successfully for the treatment of CNVM due to neovascular AMD.9 We used intravitreal bevacizumab for the treatment of Choroidal osteoma related CNV and observed rapid regression of CNV with a marked improvement of visual acuity. Marked improvement of visual acuity and rapid regression of CNVM was observed in our patient following 3 intravitreal injections of bevacizumab. However, recurrence was seen two months later which was treated with one more injection after which CNVM got stabilised and patient is maintaining a visual acuity of 6/6. Narayanan R et. al. reported prompt visual recovery and rapid CNVM regression following bevacizumab injection for Choroidal osteoma related CNVM.10 Similar finding were noticed by Ahmadieh H et. al.11 This treatment modality may be superior to previous methods in terms of anatomic and visual results. This dramatic effect may be attributable to the very thinned and degenerated RPE/Bruchs membrane complex, resulting in the better penetration of bevacizumab into the underlying subretinal space. In conclusion: 1. Intravitreal bevacizumab may be an effective treatment modality in management of CNVM secondary to choroidal osteoma. 2. Larger series of such cases need to be studied to further validate our findings.

REFERENCES
1. Gass J D, Guerry RK, Jack RL, Harris G. Choroidal Osteoma. Arch Ophthalmol 1978;96:428-35.

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2. Aylward GW, Chang TS, Pautler SE, Gass JD. A long-term follow-up of choroidal osteoma. Arch Ophthalmol 1998;116:1337-41. 3. Shields CL, Shields JA, Augsburger JJ. Choroidal osteoma. Surv Ophthalmol 1988;33:17-27. 4. 5. Kadrmas EF, Weiter JJ. Choroidal osteoma. Int Ophthalmol Clin 1997;37:171-82. Rose SJ, Burke JF, Brockhurst RJ. Argon laser photoablation of a choroidal osteoma. Retina 1991;11:224-8.

6. Foster BS, Fernandez-Suntay JP, Dryja TP, Jakobiec FA, DAmico DJ. Clinicopathologic reports, case reports, and small case series: Surgical removal and histopathologic findings of a subfoveal neovascular membrane associated with choroidal osteoma. Arch Ophthalmol 2003;121:273-6. 7. Singh AD, Talbot JF, Rundle PA, Rennie IG. Choroidal neovascularization secondary to choroidal osteoma: successful treatment with photodynamic therapy. Eye (Lond) 2005;19:482-4. 8. Shukla D, Tanawade RG, Ramasamy K. Transpupillary thermotherapy for subfoveal choroidal neovascular membrane in choroidal osteoma. Eye (Lond) 2006;20:845-7. 9. Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration. Ophthalmology 2006;113:363-72. 10. Narayanan R, Shah VA. Intravitreal bevacizumab in the management of choroidal neovascular membrane secondary to choroidal osteoma. Eur J Ophthalmol 2008;18:466-8. 11. Ahmadieh H, Vafi N. Dramatic response of choroidal neovascularization associated with choroidal osteoma to the intravitreal injection of bevacizumab (Avastin). Graefes Arch Clin Exp Ophthalmol 2007;245:1731-3.

Burkholderia Cepacia Endophthalmitis A Losing Battle

Dr. Shalabh Sinha


50 years old male was referred with post phacoemulsification and intraocular lens implantation surgery endophthalmitis in his left eye. The infection occurred within 1 week of the intraocular surgery. He gave history of intravitreal injection of vancomycin, ceftazidime and dexamethasone. On examination he was found to have subconjunctival triamcinolone crystals, infinity corneal suture, corneal edema, hypopyon, mid dilated pupil, cortex was present inferonasally, and posterior capsular rent. He was advised vitrectomy with repeat intravitreal injection. The patient chose to go to a tertiary eye centre, where a pars plana bimanual vitrectomy with intravitreal

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antibioctics was done 15 days after the patient had presented to me. He gave history of 4 intravitreal injections in the post operative period. Oral ciprofloxacin was given along with topical ciprofloxacin to the patient at the tertiary centre. The patient again presented 10 days following his discharge to me with a bloody hypopyon, exudative membrane and yellow glow. IOL explantation along with capsular bag was done with vitreous lavage and intravitreal injection of vancomycin (1mg/0.1 ml) and ceftazidime (2.25 mg /0.1 ml). The IOL capsular bag complex grew bulkholderia cepacia on culture. The organism was resistant to vancomycin and only weakly sensitive to ceftazidime, pippercillin +tazobactum was strongly sensitive. Patient again presented 20 days later with a hypopyon and faint yellow glow. Intravitreal pippercilin /tazobactum (250 microgram / 0.1 ml) was injected every 48 hours for 4 days. Patient again presented 13 days later with an increase in pain and a hypopyon, which was blood tinged. Pippercillin/tazobactum and ceftazidime was once again injected intravitreally every 48 hours for the next 4 days, where the hypopyon was found to reduce, but rubeosis could now be seen. He once again presented 9 days later with increase in anterior chamber exudation and hyphema, after which he was lost to follow-up. Burkholderia cepacia complex is a group of catalase producing, non-lactose fermenting gram negative organisms. 17 different species are known of which b cepacia is the most important and causes lung involvement in patients with cystic fibrosis. Person to person spread has been documented and patients with this disease are strictly isolated from other uninfected patients in hospitals and clinics. Burkholderia cepacia is naturally resistant to common antibiotcics, including aminoglycosides, quinolones, B lactum, and polymixins. B cepacia has been found in commercially available betadine and chlorhexidine mouthwash. It has also been reported in pharmacy compounded trypan blue. The organism is sensitive to ceftazidime, pipercillin, doxycycline, cotriamoxazole, meropenem and chloramphenicol. There are only five reports of endophthalmitis occurring due to burkholderia cepacia and only one from India. Avinash et. al. had published their single patient report in IJO in 2005. Recently the largest series of endophthalmitis due to the same organism has been reported from southern India by Sachdeva et. al. in 2011 Retina Volume X, Number X. A poor outcome and recurrence was reported secondary to this organism. Rubeosis has not been reported in any series or case reports, as was seen in our case. The use of pipercillin as a broad spectrum antibiotic and its dose was described by Abdullah et. al. The successful use of intravitreal pipercillin /tazobactum was described by Annie Mithai et. al. in a patient with pseudomonas aureginosa post operative endophthalmitis. Another report of pipercillin /tazobactum use intravitreally has been reported by Trehan Hemant Singh et. al. in post traumatic endophthalmitis secondary to enterobacter.

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Rare and difficult to treat organisms being grown in culture in patients with post operative endophthalmitis, are making the successful treatment of these patients exceedingly difficult. Vitreo-retinal surgeons would have to become familiar with lesser known agents for the treatment of endophthalmitis.

Retinopathy of Prematurity: Analysis of Screening, Incidence and Risk Factors

Dr. V. K. Dhull, Dr. Anugya Agrawal, Dr. Geeta Gathwala, Dr. Manisha Nada
etinopathy of prematurity (ROP) is one of the leading causes of blindness and marked visual impairment among premature and low birth weight neonates. The rate of blindness caused by ROP varies greatly among countries and different regions within countries depending on their level of development, standard of neonatal care, neonatal outcomes and whether effective screening and treatment programs exist. That is why, screening guidelines must not be generalized and must take into account regional differences. As screening criteria differ across different units and time-periods, overall incidence of ROP varies from 20% to 52% with more recent studies reporting lower rates of ROP ranging from 20% to 30%.1-4 An important lesson is learnt from units reporting ROP in different time periods. Initial low incidence of ROP rises with better screening protocols, availability of assisted ventilation services and survival of sicker, smaller neonates. In this phase even sick but relatively mature (late preterm) neonates have been reported to develop ROP. This period is followed by gradual decline in incidence of ROP especially of more severe variety. Different studies have reported various risk factors. Some of them are debatable, but most established among them are low gestation age, low birth weight and unmonitored supplemental oxygen administration. 5-7 Treatment includes cryotherapy/laser photocoagulation of avascular retina and recently intravitreal injections of anti-VEGF agents for threshold disease and vitreoretinal surgery for advanced stages with variable visual outcomes. Considering so much of diversity in incidence, risk factors and treatment outcomes of this disease, we realised that guidelines and screening programs that take into consideration the characteristics of local populations should be designed. So, we decided to conduct a prospective study in our region, in order to design a better and more efficient screening program and analyse risk factors and efficacy of latest treatment modality using anti VEGF agents.

MATERIALS AND METHODS


This prospective, unmasked study was conducted in a tertiary care hospital in

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Northern India among the premature neonates admitted in Neonatal intensive Care Units (NICU), from September, 2009 to August, 2010. Patients with birth weight 1500 grams and/or Gestational age 32 weeks and selected patients with birth weight between 1500 and 2000 grams or gestational age > 32 weeks but 35 weeks with unstable clinical course or neonatologists concern over high risk factors were included. Patients with major congenital malformations, chromosomal anomalies, ocular anomalies and patients who died or lost to follow up were excluded from the study. All subjects underwent thorough history taking from parents, data recording from available records. Complete Ophthalmologic examination including fundus examination was done with Binocular Indirect Ophthalmoscope using +20 D or +30 D lens and scleral indentation using a small muscle hook. Standard procedure and precautions described in literature were employed for fundus dilatation, local anaesthesia and examination. For each infant with ROP, the age at which it was first detected, the location (zones), severity and extent of ROP, exposure to any risk factors were recorded on a prescribe format and analysed statistically regarding factors such as gestation age, birth weight, gender, period of supplemental oxygenation, apgar score, history of blood transfusion, total parenteral nutrition, surfactant used, respiratory distress, documented sepsis, metabolic acidosis, seizures, neonatal jaundice, intracranial haemorrhage, apnoeic attacks, necrotizing enterocolitis, multiple gestation and some prenatal maternal factors such as mothers age at the time of conception, diabetes, smoking, preeclampsia and maternal bleeding etc. ETROP recommendations were adhered to whenever treatment was necessary.

RESULTS
In total 207 surviving preterm neonates who met inclusion criteria were screened. Subjects were finally divided in two groups. In group I: ROP was present while in group II: ROP was absent. At the completion of follow-up, 44 (21.26%) were diagnosed to have developed some degree of ROP in at least one eye on at least one occasion. Gender was not found to significantly influence the frequency of ROP in the study (p=0.124). The mean birth weight of group I was 1284.66 209.144 grams and of group II was 1396.04 188.237 grams. This difference was statistically significant using independent sample t-test (p =0.001). The mean period of gestation in group I was 31.095 1.856 weeks and of group II was 32.207 1.545 weeks. This was highly significant using independent sample t-test (p< 0.001). Among the 44 ROP patients, 2(4.54%) cases of unilateral and 6(13.62%) cases of bilateral stage 3 with plus disease, extending over > 6 contiguous/ 8 cumulative clock hours were found. Bilateral cases underwent nonconfluent green laser peripheral retinal ablation using

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the indirect ophthalmoscope. The 2 cases with U/L disease were treated with intravitreal injection of 125 g (0.05 cc) of Intravitreal Bevacizumab (Avastin, Zentech) once in involved eye. Regression occurred in all cases. We observed 16 cases (36.32%) of stage 2 retinopathy occurring in zone III or zone II and 20 cases (45.40%) of stage 1 retinopathy in zone III or zone II, all of which regressed during without any intervention during the observation period. Although 37.3% of neonates with a birth weight 1,250 g had ROP, only 14.9% of neonates with a birth weight > 1,250 g had ROP. This was statistically significant (p = .001). The rate of ROP between neonates with a birth weight 1,500 g and those with a birth weight > 1,500 g was also statistically significant (p < .001). The rate of ROP was also higher in neonates with a gestational age of 32 weeks or less (29.9%) compared to neonates with a gestational age > 32 weeks (10.0%) (P = 0.001). The mean gestational ages were 31.31 1.692 weeks for mild disease and 29.40 2.408 weeks for severe disease. This difference was statistically significant (p=0.028). While, on univariate analysis respiratory distress, use of surfactant, sepsis, low Apgar score, metabolic acidosis, blood transfusion and pregnancy induced hypertension were found to be significant, only exposure to unmonitored oxygen was significant on multivariate analysis.

DISCUSSION
In our study, incidence of ROP (21.26%) is similar to more recent studies... Our incidence of 14.9% in babies with birth weight >1250 gm. is greater than a report from USA (2006) in which Yanovitch et. al. found 4.2% in babies weighing between 12501800 grams.8 Our study has revealed 10 risk factors that portend the development of ROP in preterm babies in our region. This is comparable to other studies.2,9,10 When these significant factors were analysed using multivariate logistic regression, it was found that oxygen exposure (p< 0.001) was the only independent risk factor, which is a well-established risk factor in the development of ROP including severe ROP, in VLBW and LBW babies.7 A recent study in India with similar screening criteria and similar overall incidence (22.3%) found that 33.6 % babies with ROP required treatment.4 This was greater than that found in our study (11.36%). This difference may be explained by better NICU facilities in our institute. Though the incidence of ROP is significantly greater below the 1500 mark but the fact that 8.1% of high risk babies weighing >1500 grams have ROP, cannot be ignored. The need of the hour is to establish sickness criteria so that only those with significant risk factors in the heavy cohort are screened.

REFERENCES
1. Charan R, Dogra MR, Gupta A, Narang A. The incidence of retinopathy of prematurity in a neonatal care unit. Indian J Ophthalmol 1995;43:123-6.

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2. Maheshwari R, Kumar H, Paul VK, Singh M, Deorari AK, Tiwari HK. Incidence and risk factors of retinopathy of prematurity in a tertiary care new born unit in New Delhi. Natl Med J India 1996;9:211-4. 3. Aggarwal R, Deorari AK, Azad RV, Kumar H, Talwar D, Sethi A et. al. Changing profile of retinopathy of prematurity. J Trop Pediatr 2002;48:239-42. 4. Chaudhari S, Patwardhan V, Vaidya U, Kadam S, Kamat A. Retinopathy of prematurity in a tertiary care center--incidence, risk factors and outcome. Indian Pediatr 2009;46:219-24. 5. Campbell K. Intensive oxygen therapy as a possible cause of retrolental fibroplasias: a clinical approach. Med J Aust 1951;2:48-50.

6. Seiberth V, Linderkamp O. Risk factors in retinopathy of prematurity. A multivariate statistical analysis. Ophthalmologica 2000;214:131-5. 7. 8. Patz A, Hoeck LE, de la Cruz E. Studies on the effect of high oxygen administration in retrolental fibroplasia: I. Nursery observations. Am J Ophthalmol 1952;35:1248-53. Yanovitch TL, Siatkowski RM, McCaffree M, Corff KE. Retinopathy of prematurity in infants with birth weight > or =1250 grams- incidence, severity, and screening guideline cost-analysis. J AAPOS 2006;10:128-34. Charles JB, Ganthier R Jr, Appiah AP. Incidence and characteristic of retinopathy of prematurity in a low income inner city population. Ophthalmology 1991;88:14-7.

9.

10. Jandeck C, Kellner U, Kossel H, Bartsch M, Versmold HT, Foerster MH. Retinopathy of prematurity in infants of birth weight > 2000g after hemorrhagic shock at birth. Br J Ophthalmol 1996;80:728-31.

A Retrospective Review of Vision Threatening Complications Post Intravitreal Bevacizumab in CRVO

Dr. Narendra G. Venkata, Dr. Sambasiva Rao Velagapudi


entral retinal vein occlusion (CRVO) causes vision loss as a result of macular edema and / or retinal ischemia. The Central Vein Occlusion study failed to demonstrate a statistically significant visual acuity benefit from grid laser photocoagulation, for macular edema. New modalities have been explored in the treatment of macular edema secondary to CRVO, among which, both intravitreal triamcinolone acetonide and intravitreal bevacizumab have shown a marked reduction in macular edema, also accompanied by improvement in visual acuity. Both drugs differ in the spectrum of side effects and potentially in the magnitude and duration of their effect. The aim of the current study is to assess primarily the complications,changes in visual acuity and macular thickness on optical coherence tomography (OCT) in patients

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with CRVO receiving 1.25 mg monthly intravitreal bevacizumab for 3 months atleast and then on PRN scheduling. This retrospective case series included 68 eyes (68 patients) with CRVO presenting with 6/24 or worse visual acuity, which consecutively underwent intravitreal injection of bevacizumab (1.25 mg, 68 eyes) with at least 12 months of follow-up. After the use of intraocular bevacizumab was approved in the hospital, bevacizumab was injected between January 2010 and Jamuary 2011. The study had informed consent was obtained from all patients. The inclusion criteria were as follows: The patients had to be with perfused CRVO confirmed by fluorescein angiography, with central macular thickness 250 m, and baseline visual acuity of 20/200 or worse. Perfused CRVO was defined as lacking evidence of neovascularization in the retina or iris and having no obvious macular ischemia. The exclusion criteria were previous treatment for CRVO, such as intravitreal injection, subtenon injection, or laser photocoagulation, since the time of onset of CRVO, a history of glaucoma, macular edema secondary to other causes, such as age-related macular degeneration and diabetic retinopathy. At baseline, all the patients underwent a thorough ophthalmological examination, including best-corrected visual acuity measurement with a Snellen chart, applanation tonometry, ophthalmoscopy, fluorescein angiography, and OCT. 1.25 mg (0.05 ml) of bevacizumab (Avastin; Genentech) was injected into the vitreous cavity under sterile conditions. After the injection, a topical antibiotic was applied and the patients were monitored for potential injection-related complications. The patients were initially followed up at the first week post-injection, and twice at two-week intervals, and then at routine monthly intervals. The main primary outcome measures studied were potential vision threatening complications, visual acuity and central macular thickness on OCT at one, three, six, and twelve months after the initial injection. The complications during follow-up were also noted. Repeated intravitreal injections were carried out when the central macular thickness appeared to be more than 250 m on OCT. Repeat injections were performed at intervals of at least six weeks. Post injection FFA was done in select cases,OCT was done as a routine after every injection. IOP measurement,detailed anterior segment evaluation and biomicroscopy,gonioscopy. Vision improvement and macular thickness, ocular and nonocular adverse events (AE and SAEs) are documented. All 68 eyes received a minimum of 3 injections, 54 eyes received 3 injections, 8 eyes received 4 injections, 5 eyes received 5 injections, 1 eye

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received 6 injections. Mean interval between injection was 30 days,Mean pre inj IOP: 12 mm Hg, Mean pre inj IOP: 14 mm Hg. Most of the study eyes (64 of 68) had final successful, favourable anatomical and functional outcomes which translated to significant visual improvements.Mean Preop vision: 2/60, Mean postop vision: 6/36. Mean Pre inj CFT: 520 microns,Mean Post inj CFT: 190 microns. Host of rather vision threatening complications (n=8) like: Endothelitis, TASS like syndrome, Glaucoma, Noninfectious Endophthalmitis, Branch Retinal Arterial occlusion, Multiple capillary non perfusion areas, Presumed conversion to Ischaemic CRVO, Vitreous Haemorrhage are noted. Out of 8 eyes who had these complications, 4 eyes with TASS, Endothelitis, Glaucoma, noninfectious endophthalmitis did recover well and regained final favorable functional outcome. Mean Preinj Vision in these 4 eyes: 3/60, Mean Postinj Vision in these 4 eyes: 6/60. All these 4 were managed medically. Eyes with BRAO, CNP areas, Ischaemic CRVO conversion, Vitreous haemorrhage had less favourable final functional outcome. Mean Preinj Vision in these 4 eyes: 3/60,Mean Postinj Vision in these 4 eyes: 2/60. Except with eye which developed arterial occlusion,rest of the 3 eyes were lasered. Anti-VEGF agents, such as bevacizumab, exert direct, strong inhibition of VEGF. Several studies involving a reduction in macular edema due to CRVO with bevacizumab have revealed promising results, but only few reported such vision threatening complications. Therefore, the overall results suggest that intravitreal bevacizumab is associated with the anatomic resolution of macular edema, functional improvement, but some alarming complications in subset of patients. The two major side effects of intravitreal steroids are a steroid-induced increase in intraocular pressure and development of cataracts. In contrast, intravitreal bevacizumab has been seen to be free of complications in many studies. But, in view of the potential complications of intravitreal bevacizumab in our study a word of caution is warranted, for intravitreal use in CRVO.

REFERENCES
1. Priglinger SG, Wolf AH, Kreutzer TC, Kook D, Hofer A, Strauss RW, et. al. Intravitreal bevacizumab injections for treatment of central retinal vein occlusion: Six-month results of a prospective trial. Retina. 2007;27:100412. 2. Ferrara DC, Koizumi H, Spaide RF. Early bevacizumab treatment of central retinal vein occlusion. Am J Ophthalmol. 2007;144:86471.

3. Retinal vascular events after intravitreal bevacizumab. (Mansour AM Acta Ophthalmol. 2010;88:730-5.

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Is Elevated Plasma Homocysteine in Patients With Retinal Veinous Occlusion A Indicator for Severe Macular Edema?
Dr. Poninder Kumar Dogra, Dr. Sqn Ldr Avdesh Oli, Dr. Brig Ajay Banarji, Dr. Brig T. S. Ahluwalia

etinal vein occlusions can be either central retinal vein occlusions (CRVO), hemi retinal vein occlusions (HCRVO) or branch retinal vein occlusions (BRVO).1,2 It is second only to diabetic retinopathy as a retinal vascular cause of visual loss, and the effect of this condition has on the visual acuity and visionrelated quality of life can be significant.2 Although the pathogenesis is still not fully understood, some of the common factors associated are age, hypertension, atherosclerotic retinal vessel changes, diabetes, hyperhomocystinaemia and open angle glaucoma. CRVO/HCRVO/BRVO seem to have a comparable risk profile.1 In various studies on cardio vascular diseases it has been found that homocysteine (HCy) is an important risk factor for various atherosclerotic related diseases. The exact mechanism of Homocysteine related damage to blood vessels is not known. Homocysteine is a sulfur-containing nonprotein amino acid that is either metabolized to cystathionine by the transsulfuration pathway, requiring B6, or it is converted back to methionine by B12 and folate, requiring transmethylation.3 The accepted normal range of fasting plasma homocysteine ranges between 5-15 micro mol/litre. Hyperhomocysteinemia is an independent risk factor for atherosclerosis in the coronary, cerebral, and peripheral vasculature4 and increased incidence of myocardial infarction is seen in hyperhomocysteinemia.5 Homocysteine causes oxidative injury to the endothelial cells and enhances the peroxidation of low density lipoprotein, thereby promoting the atheromatous process. Despite the existence of studies pointing to mild hyperhomocysteinemia6 as a risk factor for systemic occlusive vascular disease, thrombosis, and stroke, the question as to whether Hcy is responsible for these events or if it is just an atherosclerosis marker remains to be answered. The relationship, if any, with retinal vein occlusion remains unclear. Till date none of the studies have found any correlation between plasma homocysteine levels and macular edema based on central macular thickness.

MATERIALS AND METHODS


A cross sectional study of 59 consecutive patients attending the Armed Forces Medical College (AFMC) Pune, Eye OPD with retinal vein occlusion (CRVO/ HCRVO or BRVO) were enrolled for the study.

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Screened patients were then subjected to comprehensive ocular examination. A detailed questionnaire on family history, social status, dietary habits, other risk factors for systemic diseases including other ocular diseases and drug history was completed. This comprehensive ophthalmic evaluation included Best corrected visual acuity (BCVA), relative afferent pupillary defect, fundus picture, Fluorescein angiography and OCT* (Spectral domain 3D Optical Coherence Tomography) which were basis for diagnosis of RVO. The patients also underwent systemic evaluation in the form of blood pressure recording, blood sugar fasting and post prandial, lipid profile and ECG. After a complete ocular and systemic evaluation, the cases of recent unstable angina, myocardial infarction, renal failure, CVAs and those on current supplemental therapy with multivitamins, Vit B6, folic acid, Vit B12 as well as those with diabetic retinopathy and age related macular degeneration were excluded. A total of 59 patients formed the study group who underwent OCT and FFA. Plasma homocysteine levels were then estimated in all these patients. As the main outcome measure, hyperhomocysteinemia was defined as a plasma homocysteine level of 15 micromol/litre (umol/l) or more. The results were collected, tabulated and analysed.

RESULTS
A total of 59 patients of retinal vein occlusion were included in the study. Mean age of patients was 61.45 years with a range of 37 to 82 yrs. 54.23 % of patients were males while females were 45.76 %. 28 eyes had CRVO/HCRVO (47.45 %) and 31 had BRVO (52.55%). Right eye was involved in 59.32% and left eye was involved in 40.67%. Out of 59 patients, 42 (71.18%) had raised plasma homocysteine. The mean value of plasma homocysteine was 35.72 mol /l with a range 7.6 to 147.53 mol /l, SD 29.196. Mean CMT at presentation was 651.28 in patients with hyperhomocysteinemia. In patients with normal homocysteine mean CMT was 319.11 with mean homocysteine level of 9.86 mol/l. Elevated homocysteine clinically and statistically correlated with severe macular edema based on CMT( p value <0.001) as in Fig 1. In conclusion increased homocysteine may also augment thrombotic events, as it inhibits the expression of thrombomodulin secreted by the endothelial cells to prevent the activation of protein C. Homocysteine enhances the activity of factors V and VII and the adhesion of platelets to the endothelium. In addition,the toxicity of homocysteine to the vascular endothelium may also

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account for its association with retinal vein occlusion. Possibly the above mechanism is responsible for the raised homocysteine levels seen in 42 out of 59 patients and lead a severe macular edema by altering the vascular cell function. The increased resistance of choroidal vessels and decreased choroidal perfusion may also cause Figure 1: Homocysteine v/s Central Macular thickness retinal pigment epithelial atrophy and stimulate the growth of vascular endothelial growth factor for neovascularization.7 Several studies have demonstrated that HCy can also cause direct cytotoxic effects by forming disulfide protein derivatives, thereby modifying vascular cell function.8 Other mechanisms reported include homocysteine-induced oxidative stress (redox stress)9 and decreased bioavailability of nitric oxide.10 In literature there are few reports which do not support the association between hyperhomocysteinemia and RVO.11 In recent past several studies12 have found correlation between hyperhomocysteinemia and CRVO.13 Angayarkanni Narayanasamy et. al.14, found that elevated Hcy and low methionine were risk factors for CRVO in an Indian population. In this study we found that plasma homocysteine levels were raised in 71.8% of patients with retinal vascular occlusions which is rather high. In addition there is a significant correlation between plasma homocysteine level and macular edema in patients with RVO. Patients with greater level of plasma homocysteine had more severe macular edema as compared to those with normal homocysteine levels. Elevated homocysteine clinically and statistically strongly correlated with severe macular edema based on CMT (p value <0.001) In addition, significant number of patients had systemic co morbidities which could be a confounding factor for elevated plasma level of homocysteine. The response to intervention in group with elevated homocysteine is also another aspect which needs further detailed study. In every case of RVO, plasma homocystiene should be checked as the treatment of this entity is very cheap and simple. Also RVO could be a warning for further more sinister vascular events like heart attack and stroke.

REFERENCES
1. Hayreh, S.S., Retinal vein occlusion. Indian journal of Ophthalmology, 1994;42:109-32. 2. G.:, C.J., ed. Central retinal vein occlusion. R. SJ. Mosby St Louis. 2001;3:1368-75.

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3. JD, F., Inborn errors of sulfur-containing amino acid metabolism. J Nutr., 2006;136:1750S-54S. 4. Genser D, P.H., Hauer R, Halbmayer WM, Mlczoch J, Elmadfa Homocysteine, folate and vitamin B12 in patients with coronary heart disease. Ann Nutr Metab., 2006;50:413-9. 5. Brown BA, M.J., Ward TP, Hollifield RD, Dick JS, Brozetti JJ, Howard RS, Thach AB., Homocysteine: a risk factor for retinal venous occlusive disease. Ophthalmology. 2002;109:28790.

6. Lattanzio R, S.F., Ramoni A, Fattorini A, Brancato R, DAngelo A. 80. , Moderate hyperhomocysteinemia and early-onset central retinal vein occlusion. Retina, 2006;26:65-70. 7. Brown BA, M.J., Ward TP, Hollifield RD, Dick JS, Brozetti JJ, Howard RS, Thach AB, Homocysteine: a risk factor for retinal venous occlusive disease. Ophthalmology., 2002;109:287-90.

8. J, S., The many facets of hyperhomocysteinemia: studies from the Framingham cohorts. J Nutr., 2006;136:1726S-30S. 9. Tyagi N, S.K., Steed M, Ovechkin AV, Moshal KS., Mechanisms of homocysteineinduced oxidative stress. Am J Physiol, 2005;289:H2649-56.

10. N, W., Mechanisms of increased vascular oxidant stress in hyperhomocysteinemia and its impact on endothelial function. Curr Drug Metab, 2005;6:27-54. 11. Di Crecchio L, P.M., Sanguinetti G, Iacono P, Ravalico G, Hyper homocysteinemia and the methylenetetrahydrofolate reductase 677C-T mutation in patients under 50 years of age affected by central retinal vein occlusion. Ophthalmology. 2004;111:940-5. 12. Chua B, K.A., Wong TY, Mitchell P Homocysteine and retinal emboli the blue mountain eye study. Am J Ophthalmol, 2006;142:322-4. 13. Chau B, K.A., Wong TY, Mitchell P, Homocysteine and retinal vein occlusion: population based study. Am J Ophthalmol. 2005;139:181-2. 14. Angayarkanni Narayanasamy, B.S., Coral Karunakaran,, Hyperhomocysteinemia and Low Methionine Stress Are Risk Factors for Central Retinal Venous Occlusion in an Indian Population. Investigative Ophthalmology and Visual Science, 2007;48:1441-6.

Associations of AMD in Central India. The Central India Eye and Medical Study (CIEMS)
Dr. Nangia Vinay Kumar B., Dr. Jost Jonas, Dr. Arshia Matin, Dr. Maithili Kulkarni

ge-related macular degeneration (AMD) is one of leading causes of visual impairment and blindness in elderly subjects worldwide.1-6 The list of risk factors for AMD include many parameters, such as smoking, family history and ethnic background.7-25 Since these parameters differ between

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populations of various continents, and because the previous investigations did not include all basic ocular parameters, in particular biometric measurements, and because population-based data for the Indian population are scarce, it was the purpose of our investigation to evaluate associations of early AMD with a relatively large number of ocular and systemic factors in an Indian population group.

MATERIALS AND METHODS


The Central India Eye and Medical Study (CIEMS) is a population-based cross-sectional study in rural Central India. It was carried out in 8 villages in the rural region of Central Maharashtra at a distance of about 40 km from Nagpur.26-28 The Medical Ethics Committee of the Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg and the ethical committee of Suraj Eye Institute / Nagpur approved the study and all participants gave informed consent. Inclusion criterion was an age of 30+ years. Out of total population of 13,606 villagers, 5885 subjects were eligible, out of whom 4711 people participated (response rate: 80.1%). There were 2520 (53.5%) women. The mean age was 49.513.4 years (median: 47 years; range: 30-100 years). All examinations were carried out in the hospital. Trained social workers filled out a questionnaire including 200 questions on the socioeconomic background and living conditions, on the daily food, smoking or other types of tobacco consumption, alcohol consumption, amount and type of daily physical activity, known diagnosis of major systemic diseases, on the intake of oral medication, on the psychiatric status (questions on psychiatric depression including thoughts of suicide), on wearing and availability of glasses, and on the family history of eye diseases. The ophthalmic examinations included measurements of visual acuity, refractometry, keratometry, frequencydoubling perimetry (program C-20-1; Zeiss-Humphrey, Dublin, California, USA), slit lamp biomicroscopy, Goldmann applanation tonometry, corneal pachymetry and ocular biometry (Pacscan; Sonomed, Lake Success, NY), and after pupillary dilatation, digital photography of the lens, optic disc (20 degree) and of the disc and macula (50 degree) (ZeisFF450 telecentric fundus camera; Zeiss Meditec Co. Oberkochen, Germany). For the assessment of AMD, the Wisconsin Age-Related Maculopathy Grading system was used. 5,21,29 Early AMD was present if late AMD was absent and if there were signs of soft drusen (>63 m) or any drusen (except small hard drusen) combined with retinal pigment epithelium changes in the macular area. In all subjects, the pulse, arterial blood pressure, body height, weight, chest X-ray and electrocardiogram were recorded. One and a half hours after a standardized lunch, blood and urine samples were taken. The blood examination consisted of a complete blood count including measurement of

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hemoglobin and erythrocyte sedimentation rate. Blood glucose, glycosylated hemoglobin, lipid profile, urea and creatinine were also measured. Urine samples underwent microscopic examination and testing for albuminuria. Selection criteria for the present study were the availability of assessable fundus photographs. Statistical analysis was performed using a commercially available statistical software package (SPSS for Windows, version 17.0, SPSS, Chicago, IL). Only one eye per subject was taken for statistical analysis.

RESULTS
Fundus photographs were available for 4542 (96.4%) subjects. Early AMD was present in 215/4542 subjects (4.70.3%), and late AMD was detected in 8/4542 (0.20.03%) subjects. After adjustment for age, prevalence of AMD was significantly associated with hyperopic refractive error (P=0.001), shorter axial length (P=0.01), and higher corneal refractive power (P=0.02). Each diopter increase in hyperopic refraction or each mm decrease in axial length was associated with an 15% (odds ratio (OR):1.15; 95% confidence interval (CI):1.06,1.24) and 19% (OR:0.81; 95%CI:0.69,0.95) increased probability of early AMD, respectively. AMD was not significantly associated with blood pressure, serum concentration of cholesterol, glycosylated haemoglobin Hb1Ac, highdensity lipoproteins and postprandial glucose, gender, level of education, any parameter of smoking, alcohol consumption, psychiatric depression or of daily activities, anterior chamber depth, lens thickness, intraocular pressure, size of the optic disc, neuroretinal rim and parapapillary atrophy, nor amount of nuclear cataract and status after cataract surgery. If the statistical analysis was adjusted for age and refractive error, age-related macular degeneration was marginally significantly associated with a low intake of fruits (P=0.06).

DISCUSSION
The data from this population-based study demonstrated the expected association between age and age-related macular degeneration. After adjustment for age, hyperopic refractive error, and parallel to it, short axial length, was the single most important associated factor for the disease in adult Indians. The findings of previous studies on that topic have been inconsistent and inconclusive so far. The Rotterdam Study,17 the French DMLA Study,26 the Age-Related Eye Disease Study,14 and the Beijing Eye Study21 found a correlation between hyperopia and AMD. In contrast, the Beaver Dam study did not report on an association between refractive errors and either the 5-year.27 In contrast to previous population-based studies in Western countries as well as in South India, age-related macular degeneration in adult Indians living in rural Central India was not associated with any parameter of smoking, and

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diagnosis of arterial hypertension or diabetes mellitus. It is in contrast to most population-based studies which have described an association between smoking and AMD.9,10,11,23 In summary, hyperopia or short axial length besides age was the single most important associated factor for AMD in adult Indians. There was a statistically marginal association between AMD and low intake of fruits. The prevalence of AMD was independent of arterial blood pressure, diabetes mellitus, blood lipid status, gender, level of education, smoking, alcohol consumption, and daily activities nor of the amount of cataract or status after cataract surgery.

REFERENCES
1. Kawasaki R, Yasuda M, Song SJ, et al. The prevalence of age-related macular degeneration in Asians: A systematic review and meta-analysis. Ophthalmology 2010;117:921-7. 2. Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of age-related maculopathy in Australia: the Blue Mountains Eye Study. Ophthalmology 1995;102:145060. 3. Vingerling JR, Dielemans I, Hofman A, et al. The prevalence of age-related maculopathy in the Rotterdam Study. Ophthalmology 1995;102:20510. 4. Krishnaiah S, Das T, Nirmalan PK, et al. Risk factors for age-related macular degeneration: findings from the Andhra Pradesh eye disease study in South India. Invest Ophthalmol Vis Sci 2005;46:4442-9. 5. Li Y, Xu L, Jonas JB, Yang H, Ma Y, Li J. Prevalence of age-related maculopathy in adult Chinese. The Beijing Eye Study. Am J Ophthalmol 2006;142:788-93. Correction: Am J Ophthalmol 2008;146:329. 6. Gupta SK, Murthy GV, Morrison N, et al.: Prevalence of early and late age-related macular degeneration in a rural population in northern India: the INDEYE feasibility study. Invest Ophthalmol Vis Sci. 2007;48:1007-11. 7. Bker T, Fang T, Steinmetz R. Refractive error and choroidal perfusion characteristics in patients with choroidal neovascularization and age-related macular degeneration. Ger J Ophthalmol 1993;2:1013. 8. Sandberg MA, Tolentino MJ, Miller S, et al. Hyperopia and neovascularization in age-related macular degeneration. Ophthalmology 1993;100:100913. 9. Vingerling JR, Hofman A, Grobbee DE, et al. Age-related macular degeneration and smoking. The Rotterdam Study. Arch Ophthalmol 1996;114:1193-6. 10. Smith W, Mitchell P, Leeder SR. Smoking and age-related maculopathy; the Blue Mountain Eye Study. Arch Ophthalmol 1996;114:151823. 11. Delcourt C, Diaz JL, Ponton-Sanchez A, et al. Smoking and age-related macular degeneration. The POLA Study. Pathologies Oculaires Liees a lAge. Arch Ophthalmol 1998;116:1031-5. 12. Wang JJ, Mitchell P, Smith W. Refractive error and age-related macular degeneration: the Blue Mountains Eye Study. Invest Ophthalmol Vis Sci 1998;39:216771.

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13. Wang JJ, Mitchell PG, Cumming RG, et al. Cataract and age-related maculopathy: the Blue Mountains Eye Study. Ophthalmic Epidemiol 1999;6:31726. 14. Age-Related Eye Disease Study Research Group. Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: Age- Related Eye Disease Study Report Number 3. Ophthalmology. 2000;107:222432. 15. McCarty CA, Mukesh BN, Fu CL, et al. Risk factors for age-related maculopathy. The Visual Impairment Project. Arch Ophthalmol 2001;119:1455-62. 16. Wong TY, Klein R, Klein BE, Tomany SC. Refractive errors and 10-year incidence of age-related maculopathy. Invest Ophthalmol Vis Sci. 2002;43:2869-73. 17. Ikram MK, van Leeuwen R, Vingerling JR, et al. Relationship between refraction and prevalent as well as incident age-related maculopathy: The Rotterdam Study. Invest Ophthalmol Vis Sci. 2003;44:377882. 18. Wang JJ, Klein R, Smith W, et al. Cataract surgery and the 5-year incidence of latestage age-related maculopathy: pooled findings from the Beaver Dam and Blue Mountains eye studies. Ophthalmology 2003;110:1960-7. 19. Wang JJ, Jakobsen KB, Smith W, Mitchell P. Refractive status and the 5-year incidence of age-related maculopathy: The Blue Mountains Eye Study. Clin Experiment Ophthalmol. 2004;32:2558. 20. Tomany SC, Wang JJ, van Leeuwen R, et al. Risk factors for incident age-related macular degeneration: pooled findings from three continents. Ophthalmology 2004;111:1280-7. 21. Xu L, Li Y, Zheng Y, Jonas JB. Associated factors for age-related maculopathy in the adult population in China. The Beijing Eye Study. Br J Ophthalmol. 2006;90:1087-90. 22. Xu L, Wang S, Li Y, Jonas JB. Retinal vascular abnormalities and prevalence of age-related macular degeneration in adult Chinese. The Beijing Eye Study. Am J Ophthalmol 2006;142:688-9. 23. Cackett P, Wong TY, Aung T et al. Smoking, cardiovascular risk factors, and agerelated macular degeneration in Asians: the Singapore Malay Eye Study. Am J Ophthalmol 2008;146:960-7. 24. Seddon JM, Reynolds R, Maller J, et al. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci. 2009;50:2044-53. 25. Tao Y, Jonas JB. Refractive error and smoking habits in exudative age-related macular degeneration in a hospital-based setting. Eye 2010;24:648-52. 26. Chaine G, Hullo A, Sahel J, et al. Case control study of the risk factors for agerelated macular degeneration. Br J Ophthalmol 1998;82:9961002. 27. Klein R, Klein BE, Jensen SC, Cruickshanks KJ. The relationship of ocular factors to the incidence and progression of age-related maculopathy. Arch Ophthalmol 1998;116:50613.

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Recording Posterior Segment Surgery with Handycam

Dr. Maneesh M. Bapaye, Dr. Meena M. Bapaye, Dr. Charuta M. Bapaye


ecording a good quality surgical video is essential for documentation of surgeons surgical skill. Creating a quality video is an important tool for educating not just postgraduate students and colleagues but also patients. Creation of a surgical video involves recording the surgical procedure, editing it to highlight important aspects and then storing it in suitable format for later viewing. Recording of posterior segment surgery remains a challenge due to low resolution of single chip CCD (Charge Coupled Device) cameras that are commonly used in anterior segment surgery recording. The high resolution 3-chip CCD cameras that are used with C-mount on beam splitter are costly and system remains cumbersome. There have been reports where handheld digital video camera (camcorder) has been manually placed on one of the eyepieces of assistant scope to record the surgery.1 We describe a system using FlexioMotionTM adapter by Carl Zeiss Inc and Sony HandycamTM to record the posterior segment surgery with good resolution and ease of archiving the videos.

Recording the video

In the OR we use OPMI MDO (Carl Zeiss Inc.) microscope with S5 stand for posterior segment surgery. The microscope has X-Y and zoom functions. Non contact wide angle viewing system Binocular Indirect Ophthalmomicroscope (BIOM IV) (Occulus, GmBH, Germany) is used for posterior segment visualization. For macula work we use Flat lens of Landers lens system with self stabilizing ring. Flexio MotionTM adapter developed by Carl Zeiss Inc is connected to one port of dual port beam splitter. This adapter can be connected to a wide range of handheld digital camcorders commercially available. We use Sony HDR XR-500E HandycamTM. The handycam records videos in Full HD AVCHD format having resolution of 1080i. The camera has hard disc with 120GB capacity. It records videos for approximately 1200 minutes before hard disc is entirely occupied. The camcorder has automatic functions for focussing, adjusting white balance and illumination. These functions can be changed manually if required though we prefer to use autofocus function as we can avoid manual adjustment during critical stages of surgery. Camera zoom can be adjusted separately using camera controls. Once desired level of magnification is achieved, it further varies proportionately with microscope zoom function. The camera comes with video output cable which is connected to external monitor for real-time viewing.

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The handycam can also be used to take still pictures intraoperatively by switching the mode from video to picture mode. The images are stored in JPEG format.

Transferring and storing the video to external device


The video files can be stored on camcorder hard disc and transferred periodically. A HDMI USB2.0 cable provided with the camcorder can be used to transfer the video in AVCHD format to the computer or external hard disc for storage. We use HP laptop computer with Intel i5 coreTM processor as it offers excellent speed in transferring the video files. It takes approximately one and half hours to transfer 120GB of video data into storage device. We use external hard disc of 1terabyte storage capacity (Buffalo MinistationTM). Alter

Editing the Video

For editing the video we use Windows movie maker software preloaded with the Windows office. It is possible to precisely edit the video, blend subsequent clips, add voiceover as well as text where required.

DISCUSSION
Video recording using analog CCD cameras had been a preferred mode for past 20 to 25 years. But in last 4 to 5 years, recording of surgical videos directly into digital formats is preferred. Analog video formats have much lesser resolution (230 lines) as compared to digital formats (720 or 1080 lines in HD format). Further it has to be converted to digital format before editing and archiving. Process of conversion causes further loss of resolution.2 The process of conversion into digital format is cumbersome and time consuming. Hence digital formats have become more popular. The video recording system we describe here consists of FlexioMotionTM adapter by Carl Zeiss Inc. attached onto one of the ports of dual port beam splitter. This adapter supports wide range of handheld digital camcorders. We use Sony HandycamTM HDR XR 500E, which has hard disc which can store 120GB of data. This camcorder records videos in Full HD which has resolution of 1080i. It uses AVCHD format which was developed by Sony and Panasonic. AVCHD format compresses video to a great extent without losing quality. Audio format used to compress the audio data supports 8 channel surround sound without loss of quality. During edition if the video this format can be stored in different resolutions without losing video and audio quality. The difficulties that we faced during use of this system were mostly related to autofocus function. As the camcorder is designed to focus at closest object, an air bubble in anterior vitreous leads to loss of focus of posterior structures. In the psedophakic eyes these bubbles can be easily removed with vitrectomy

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cutter, but poses a challenge in phakic eye. To avoid this problem it is necessary to remove air completely from infusion line. We have also found difficulty in getting good focus with Landers lens system, which is used for macular work. The field of interest keeps getting defocused. It usually happens as instruments like ILM peeling forceps get greatly enlarged with Landers flat lens and camcorder tends to focus at the shaft of such instruments rather than tip, which is area of interest. This problem can be corrected by shifting to manual mode of focussing while doing macula work. With manual mode, retinal plane remains in focus. The focus doesnt change with movement of instruments. One more difficulty that we noticed was difficulty generated due to shining of instruments with light from light pipe. The surgical field also gets very bright, blocking view of surgical focus when working close to retina, as one tends to move light pipe inadvertently close to area of interest during such manoeuvre. One has to get used to keeping light pipe farther away, closer to sclerotomy to avoid this problem. Use of Chandelier light pipe give excellent view with bright illumination and overcomes these problems easily. A Vast number of video editing softwares are available. While some like Windows movie maker come preloaded with most of laptop computers, other open source softwares like Lightworks is available online for free download. Other editing softwares like Kaltura can be purchased online. Finally cost of the system. The cost of FlexioMotionTM adapter is about Euro 1950 (approximately INR 1,30,000/-). The model of HandycamTM used by us costs INR 53,000/-. The external hard disc of 1 terabyte costs approximately INR 5000/-. Laptop used doesnt require any special video grab card or additional soft ware. Thus the cost of setting up the system comes about INR 1,88,000/-. This cost is much lesser than other systems used for video recording of posterior segment surgery. Traditionally 3 chip CCD digital cameras have been mounted on C-mounts connected to beam splitter. An elaborate set up is required involving controller unit to manually alter various parameters, servers with large storage capacity to store data in digital format as the signal compression is less. These videos have to be transferred by burning them on a DVD or high capacity pen drive devices. All these methods add to physical space occupied and expenses involved. In the literature, the cost of set described is INR 4,25,000/-2. Alternatively Zeiss Inc. provides option of customary integrated digital video system, Medilive Trio eyeTM, along with latest generation microscopes. The quoted cost of system is Euro 17000/- (approx INR 11,47,500/-).

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In conclusion, FlexioMotionTM adapter with handheld digital camcorder provides extremely user friendly and economical method of recording high quality videos of posterior segment surgery.

REFERENCES
1. Ankur Sinha, Rohit Saxena, H S Sethi, Kiran Turaka. Hand held digital camera for digital video recording of ophthalmic surgery. Indian J Ophthalmol 2006;54:209. 2. Raju B, Raju NSD, Raju AS, Sudhakaran CP, Razak A. Digital video recording and archiving in ophthalmic surgery. Indian J Ophthalmol 2006;54:53-7.

Our 5 Years Experiences with 102 Intravitreal Injections of Avastin as Primary Therapy for ROP

Dr. Rohan Chauhan, Dr. Banker Alay S.


etinopathy of prematurity (ROP) continues to be a major cause of blindness in children. Although ablation of the retina with laser or cryotherapy reduces the incidence of blindness by suppressing the neovascular phase of ROP the visual outcomes after treatment are often remains poor. After destructive treatment of avascular retina with the laser and cryotherapy the baby faces many side effects of the treatment e.g. high myopia and astigmatic refractive errors and peripheral visual field loss. So the ultimate visual outcome after ROP treatment remains guarded and poor. Vascular endothelial growth factor (VEGF) has an important role in the pathogenesis of ROP. In humans, cat, rat and mouse retina astrocytes migrate into the developing retina in front of the forming vasculature. A physiologic hypoxia develops, due to the increased metabolic demands of the differentiating neural retina; leading to up regulation of astrocyte VEGF production, the gradient of VEGF produced mediates continued vascularization of the ganglion cell layer. Synthesis of VEGF by the Muller cells, also stimulated by a local oxygen deficit, induces the sprouting of the vasculature downward into the inner nuclear layer. Once metabolic demands are met, hypoxia subsides and VEGF expression declines. It is hypothesized that when premature infants are placed in high oxygen, the physiologic hypoxia signal is overridden and astrocyte VEGF synthesis is suppressed. The lack of VEGF leads to the regression of immature vessels (vaso-obliteration), which during their development are dependent on VEGF for their continued survival. Once the infant is returned to room air, nonperfused retina becomes ischemic and the hypoxic environment up regulates VEGF synthesis in astrocytes and other neural cells. The global nature of the VEGF

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production by a significant area of nonperfused retina, compared to the local release by a limited number of astrocytes, leads to uncontrolled, abnormal vessel growth.1 Which in turn leads to the progression of ROP and tractional retinal detachment and the eye is lost in very short period of time. Inhibition of VEGF expression in the neovascular phase might prevent destructive neovascularization in ROP. Compared to pegaptanib which is a modified 28-base ribonucleic acid aptamer that selectively binds VEGF165, bevacizumab is a humanized monoclonal antibody that inhibits all active isoforms of VEGF. Intravitreal bevacizumab is a treatment modality which is currently being tried out for use in macular edema following wet age-related macular degeneration (ARMD), branch retinal vein occlusion (BRVO), central retinal vein occlusion (CRVO), rubeosis irides, proliferative diabetic retinopathy (PDR), for post-laser photocoagulation anterior segment ischemia in aggressive posterior retinopathy of prematurity2,3 and for many other vaso proliferative diseases causing macular edema. Although intravitreal use of bevacizumab is an off-label option and it has many so called safety concerns regarding the thrombo embolic events after its use, still the use has risen exponentially in the last few months mainly due to its efficacy and economic considerations.4 Recently, Hugo3 et. al. published a short series showing the excellent structural outcomes following the intravitreal bevacizumab in severe ROP. There are many isolated case reports of using intravitreal bevacizumab in ROP.5,6,7,8. Kusaka9 et. al. showed bevacizumab is beneficial for treating severe ROP refractory to conventional laser therapy. Our study aimed to evaluate the efficacy of intravitreal bevacizumab in treatment of aggressive retinopathy of prematurity.

MATERIALS AND METHODS


Retrospective analysis of 102 eyes of 58 patients with severe ROP, who received single IB (0.025cc) injection. Inclusion Criteria: We included only those babies in whom complete pretreatment and treatment information could be retrieved from the hospital records regarding period of gestation, birth weight, duration of oxygen exposure, associated systemic illness, stage, zone, extent and severity of the disease. The disease was documented as per the international ROP classification.11 The treatment was carried out only after detailed written informed consent regarding the off label use of bevacizumab, intravitreal injection10 and the fear of unknown systemic side effects in a child. All babies received 0.5 mg intravitreal bevacizumab injection to one or both eyes for severe ROP. (Stage III

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ROP with high-risk pre-threshold or threshold with plus disease). Before the procedure 4% xylocaine drops and povidone iodine was put in babys eyes for the topical anaesthesia and antisepsis. In the operating room, baby was held by anaesthetist and the eyelid speculam was put, after the anterior chamber paracentesis with sterile 31 Guage insulin syringe, bevacizumab was injected into the vitreous cavity with a 30-gauge needle inserted through the pars plana 1.5 mm posterior to the limbus. General anaesthesia was avoided in respect to poor general condition of the premature babies. Patients were instructed to put one drop of 0.3% ciprofloxacin in combination with 0.1% dexamethasone into the injected eye four times daily for 1 week after the procedure. Repeat examinations were done at day 1 and weekly thereafter for one month and then monthly. All patients were carefully monitored for vital signs and complete physical and ocular monitoring was performed during the entire follow-up period the response to treatment was observed in the form of degree of dilatation of pupil and regression of ROP following the treatment. All the patients were observed continuously by the internist for the fear of possible unknown adverse events following intra vitreal bevacizumab. Follow-up examination included evaluation of anterior segment abnormalities like iris atrophy, anterior chamber depth and cataract with the help of magnification offered by + 28 D lens and indirect ophthalmoscope or slit lamp examination wherever possible. Dilated posterior segment examination was done by direct and indirect ophthalmoscopy for any posterior pole abnormalities or peripheral fundus changes. All the recorded changes at follow-up were correlated with period of gestation, birth weight, oxygen exposure, severity and extent of ROP, myopia and strabismus. All babies were followed for the period up to 5 years. Neuro developmental analysis was carried out by the expert pediatric neurologist at the end of 1 year post avastin injection with (Development Quotient - DQ). Functional outcome was assessed by the electo physiologist with the ElectoRetinogram (ERG) and Visually Evoked Potential (VEP) at the end of 1 year post avastin injection to assess the functional outcome.

RESULTS
Retrospective analysis of 102 eyes of 58 patients with severe ROP who received single IB (0.025cc) injection. Baseline characteristics : 102 eyes (58 patients), (OD :49, OS :53), 39 males and 16 females with birth weight and gestational age ranging from 25-36 weeks (Mean 28 weeks) and 820-1900 grams (Mean 1241 grams), respectively, were included in the study. The follow-up ranged from 3 to 5 years, with a mean follow up

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of 4 years. Mean time interval from birth to injection was 9.18 weeks (3 to 16 weeks). Prospective study of 18 eyes with ROP treated with IB (0.625mg/0.05ml) with/without laser. Following injection, there was a dramatic response in the dilatation of the pupil with the pupil not able to dilate previously in all eyes. There was regression of neovascularization in all eyes. Reinjection was not required in any eyes. No eyes had any progression in any disease or required any more intervention. There was complete disappearance of rubeosis in all eyes following a single injection of Avastin. Regression of persistent foetal vasculature was also observed in 2 eyes. All patients were subjected to Neuro developmental analysis by the expert pediatric neurologist at the end of 1 year post avastin injection with (Development Quotient - DQ). Functional outcome was assessed by the electo physiologist with the Electo-Retinogram (ERG) and Visually Evoked Potential (VEP) at the end of 1 year post avastin injection to assess the functional outcome. 17 eyes (16.6%) had local adverse events: 8 eyes (8%) had self-resolving subconjunctival hemorrhage, 6 eyes (6%) had persistent peripheral avascular retina, 2 eyes (2%) had transient vitreous hemorrhage and 1 eye (1%) had peripheral fibrous avascular membrane. 1 patient had some degree of psychomotor developmental delay in D-Q Analysis.

DISCUSSION
Laser or cryotherapy has been the gold standard in treating severe ROP. However even following optimal treatment there are many eyes that have a very poor visual prognosis. Recently, VEGF has been recognized to play a role in the pathogenesis of severe ROP. The safety and efficacy of intravitreal anti-VEGF drugs like bevacizumab (AvastinTM), pegaptanib (MacugenTM) and ranibizumab (LucentisTM) in various retinal vascular diseases have been established. The choice of bevacizumab was deliberate to try to minimize the possibility of systemic complications. The molecular weight of bevacizumab is 149 kd, that of VEGF-trap (investigational) is 110 kd, and that of ranibizumab (Lucentis; Genentech, Inc.) is 48 kd. It is especially undesirable to inject a small molecule that might easily penetrate into the undifferentiated peripheral retina and cause local damage. In addition, a small molecule could potentially traverse the retinal barrier completely and escape into the circulation in amounts more likely to cause systemic complications. Only 1:1,000 of the bevacizumab level in the treated eye has been shown (in rabbits) to be present in the nontreated eye or in the blood. In adults, the intravitreal half-life of bevacizumab is 5.6 days, that of VEGF-trap is 4.4 days, and that of ranibizumab is 3.2 days. Injection of substances into the preterm vitreous, which is very viscous compared with the more liquefied aging vitreous, likely increases this half-life considerably

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The choice to refrain from laser therapy also was deliberate to try to minimize the possibility of systemic complications. Laser therapy to destroy the natural barrier of the full thickness retina with an intact Bruch membrane would likely increase the exit of bevacizumab via the larger choroidal vessels into the blood. This case series deliberately included patients with ROP in posterior zone II to have a better chance to identify central nervous system complications in those infants without intraventricular hemorrhage. Similarly, the decision to give bilateral intravitreal injections was deliberate to avoid creating a case series of amblyopic eyes due to the unilateral visual deprivation caused by the inflammatory response, cataract, hemorrhage, or other complications after laser therapy. Another favorable circumstance is that vascularization of the preterm peripheral retina is a finite process. Vascularization only progresses in the retina to the extent of the astrocytes (called spindle cells) present in the preterm retina at the time of birth. Vascularization does not necessarily extend to the ora serrata especially in infants with a low gestational age at birth. Once inner retinal vascularization proceeds in an orderly fashion to its embryonic destination determined by gestational age (without the formation of tractional membranes), the disease process does not recur and should not cause late retinal detachments, which have been reported in the months and years after both cryotherapy and laser therapy. Recently, Chung12 et. al. reported that in a baby with aggressive stage 3 zone I ROP, the combination of indirect laser photocoagulation and intravitreal bevacizumab injection was well tolerated and induced prompt regression of aggressive zone I ROP. Honda13 et. al. Acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity. Quiroz-Mercado14 et. al. also reported one patient with stage IVa ROP had spontaneous retinal reattachment after an intravitreal injection of bevacizumab. Our series also indicate that intravitreal bevacizumab followed by laser for severe ROP resulted in ROP regression, prompt resolution of plus signs and neovascular proliferation. Also, no signs of systemic or ocular adverse events were observed. There are many advantages with treatment in that it can be given even in very severe disease where laser or cryo would not be very helpful. Also it can be given even in eyes where the pupils do not dilate and also would do away with the side effects of laser and cryo. The time taken for the treatment is also very less and would avoid interventions in very sick babies. However, further studies need to be performed in order to determine the safety and long term efficacy of intravitreal Bevacizumab for the treatment of ROP either as first line therapy or after failure of conventional therapy. However, our study has found the BENEFITS of using intravitreal

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Bevacizumab with or without laser to be substantial: 1. The complications of laser are prevented completely. Ablation of the entire avascular peripheral retina is avoided. Cataracts, angle closure glaucoma, anterior segment necrosis, phthisis, and high myopia do not occur. Strabismus related to too little field to sustain binocular vision is prevented. 2. Fewer patients need to be treated. Bevacizumab offers a larger window of treatment so one can observe a few days to be sure that ROP is advancing and really needs to be treated. 3. The disease stops almost immediately. The anti- VEGF therapy not only inactivates the VEGF in the retina, but also that already in the vitreous. Plus disease is uniformly gone within 48 hours. 4. No potential complications of anti-VEGF therapy have been observed. a) Bevacizumab administration for ROP Stage 3 at the same time or immediately following laser therapy might permit the drug to escape the natural retinal barrier despite its large molecular weight (149 KD). b) Bevacizumab administration for ROP Stages 4 and 5 (following retinal detachment) is usually administered to eyes that have had laser therapy. This may permit the drug to escape the natural retinal barrier. Advanced disease itself with retinal detachment is associated with high vitreous levels of VEGF.3 Further, Bevacizumab at these late stages of ROP can trigger contraction of membranes and accelerate retinal detachment.4 Despite these arguments which favor the use of intravitreal Bevacizumab without laser therapy for vision threatening ROP Stage 3, we still realize the need to gather evidence based data to confirm a favourable RISKBENEFIT ratio before recommending its wide use for ROP in the NICU. Thus, the BEAT-ROP (Bevacizumab Eliminates the Angiogenic Threat of Retinopathy Of Prematurity) prospective, randomized, controlled, multicenter clinical trial has begununder the watchful eye of the FDA-IND (NCT 00622726). We believe that no laser therapy is needed in combination with Bevacizumab for the angiogenic component of ROP and that Bevacizumab has no favourable effect on the tractional component of ROP. Treatment for ROP has evolved from later, more destructive (cryotherapy) to earlier, less destructive (LASER therapy) peripheral retinal ablation. If evidence-based data supports early findings, the use of Avastin may be recommended without the need for ablative LASER therapy and before retinal detachment develops. Avastin will be especially useful for ROP stage 3 cases with hemorrhage decreasing retinal visualization, rigid pupils, intravitreal neovascularization with early or developing (minimal) fibrous membranes, or aggressive posterior retinopathy of prematurity (AP-ROP). These cases all continue to have poor outcomes with LASER therapy.15 Sato16 et. al. showed the elevated level of erythropoietin and its correlation with the VEGF level in eyes with stage 4 ROP suggest that not only VEGF but also erythropoietin may contribute to the pathogenesis of ROP.

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Intravitreal bevacizumab could prove to be safe and extremely efficacious treatment for severe ROP (Stage III ROP with high-risk pre-threshold or threshold with plus disease).

REFERENCES
1. Quiroz-Mercado H, Ustariz-Gonzalez O, Martines-Castellanos MA, et al. Our experience after 1765 intravitreal injections of bevacizumab: the importance of being part of a developing story. Semin Ophthalmol. 2007;22:109-25. 2. Sangtam T, Vinekar A, Maheshwar B, Dogra MR, Eong KA. Intravitreal bevacizumab (Avastin) for post-laser photocoagulation anterior segment ischemia in aggressive posterior retinopathy of prematurity. Indian J Ophthalmol 2007;55:317. 3. Shah PK, Narendran V, Tawansy KA, et al. Intravitreal bevacizumab (Avastin) for post laser anterior segment ischemia in aggressive posterior retinopathy of prematurity. Indian J Ophthalmol. 2007;55:75-6. 4. Quiroz-Mercado H, Ustariz-Gonzalez O, Martines-Castellanos MA, et al. Our experience after 1765 intravitreal injections of bevacizumab: the importance of being part of a developing story. Semin Ophthalmol. 2007;22:109-25. 5. Azad R, Chandra P. Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Indian J Ophthalmol 2007;55:319.

6. Travassos A, Teixeira S, Ferreira P, Regadas I, Travassos AS, Esperancinha FE, Prieto I, Pires G, van Velze R, Valido A, Machado Mdo C.Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging. 2007;38:233-7. 7. Lalwani GA, Berrocal AM, Murray TG, Buch M, Cardone S, Hess D, Johnson RA, Puliafito CA. Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity. Retina. 2008;28(3 Suppl):S13-8. 8. Mintz-Hittner HA, Kuffel RR Jr. Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina. 2008;28:831-8. 9. Kusaka S, Shima C, Wada K, Arahori H, Shimojyo H, Sato T, Fujikado T. Efficacy of intravitreal injection of bevacizumab for severe retinopathy of prematurity: a pilot study. Br J Ophthalmol. 2008;92:1450-5. Epub 2008 Jul 11.

10. Jager RD, Aiello LP, Patel SC, Cunningham ET Jr. Risks of intravitreous injection: a comprehensive review. Retina. 2004;24:676-98. 11. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity Revisited [published correction appears in: Arch Ophthalmol. 2006;124(11):1669-1670]. Arch Ophthalmol. 2005;123:991-9. 12. Chung EJ, Kim JH, Ahn HS, Koh HJ. Combination of laser photocoagulation and intravitreal bevacizumab (Avastin) for aggressive zone I retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2007;245:1727-30. Epub 2007 Aug 10. 13. Honda S, Hirabayashi H, Tsukahara Y, Negi A. Acute contraction of the proliferative

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membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2008;246:1061-3. Epub 2008 Mar 5. 14. Quiroz-Mercado H, Martinez-Castellanos MA, Hernandez-Rojas ML, SalazarTeran N, Chan RV. Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity. Retina. 2008;28(3 Suppl):S19-25. 15. Mintz-Hittner HA, Best LM. Antivascular endothelial growth factor for retinopathy of prematurity. Curr Opin Pediatr. 2009;21:182-7. 16. Sato T, Kusaka S, Shimojo H, Fujikado T. Vitreous Levels of Erythropoietin and Vascular Endothelial Growth Factor in Eyes with Retinopathy of Prematurity. Ophthalmology. 2009;Apr 14.

Clinical Features Diagnosis and Management of Choroidal Neovascular Membrane in Pediatric Population

Dr. Jyoti Prakash Vyas, Dr. Giridhar A., Dr. Thomas Thachil
ubfoveal choroidal neovascularization in children is a rare event, typically occurring as a complication of inflammatory or infectious chorioretinal disease. Visual acuity may be compromised by the subfoveal location of the choroidal neovascular complex, exudative macular detachment, subretinal or subretinal pigment epithelial hemorrhage, and cystoid degenerative changes of the neurosensory retina. Wilson and Mazur and Goshorn et. al. reported that 58% of subretinal neovascular membranes in children and adolescents undergo spontaneous involution, with 29% achieving a final visual acuity of 20/50.The prognosis for subfoveal neovascularization in children is reportedly more favorable than for adult neovascularization from either exudative agerelated macular degeneration (AMD) or presumed ocular histoplasmosis (POHS). Intravitreal injection of anti VEGF agents is the current standard of care treatment in treatment of neovascular age related macular degeneration(AMD). Intravitreal anti-VEGF therapy is also being used increasingly in cases of retinal veno occlusive disease, proliferative diabetic retinopathy and non AMD related CNV from causes like myopia, idiopathic, postinflammatory.

MATERIALS AND METHODS


The charts of patients with angiographically documented choroidal neovascular membrane in patients below the age of 18 years, from 2004 to 2010 were reviewed. Inclusion Criteria: All patients <18 years with angiographically proven choroidal neovascular membrane were included.

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Exclusion Criteria: All patients < 18 years of age with a previous history of laser, clinical features of CSR, old trauma, coexisting retinal disease, recent ocular surgery clinical features of anterior or posterior uveitis. Patients without a minimum follow up of 6 months. Outcome Measures: The BCVA at presentation and at the end of treatment. For assessing the change in BCVA, a 2 line drop was considered as a drop in BCVA, while a gain of 1 line was considered as gain. If the BCVA remained the same, it was considered to be stabilized. [NB: BCVA <6/60 was considered to be the same level, i.e. CF improving to 5/60 was considered as stabilization and not improvement]. Baseline evaluation: All patients had their BCVA assessment by Snellenss chart, slit lamp biomicroscopic examination and dilated fundus examination. Fluorescein angiography and Optical Coherence Tomography were done. Treatment Modalities: The various treatment modalities used in our series included loading dose of Bevacizumab, PRN dosing of Bevacizumab, combination therapy PDT with Visudyne with anti VEGF agents, IVTA and thermal laser. Loading dose of Bevacizumab included 3 monthly injections of Bevacizumab followed by repeat angiogram at the end of the 4th month. Residual activity on angiogram warranted further injections. Retreatment was based on demonstration of serous macular detachment on OCT. The antiVEGF intravitreal therapy was repeated at a 4-week interval if OCT showed serous macular detachment. The patient was subsequently reviewed at monthly intervals. In case of PRN dosing of Bevacizumab, serial OCTs at monthly intervals were performed and at the evidence of membrane activity, as evidenced by serous macular detachment, the patient was treated with Bevacizumab injections till the complete resolution was achieved. In combination therapy with PDT with Visudyne and anti-VEGF agents, the lesion size was assessed angiographically. PDT was given with a 689 nm diode laser for 83 seconds with a laser spot size 1000 microns larger than the greatest linear dimension of the lesion. Anti VEGF injection was given on the following day. A repeat angiogram was done at the end of 3 months to look for signs of closure of CNV. In case of residual activity of CNV additional cycle of PDT with anti-VEGF agents was given. Thermal laser was used in cases of a small extrafoveal lesion. IVTA was used in cases presenting in the pre anti-VEGF era.

RESULTS
16 eyes of 16 patients were enrolled of which 14 eyes with adequate follow up were analyzed. The mean age of the patients was 14.5 years (Range 7-18 years) with a mean period of follow up of 27.5 months (Range 6-89 months). The sex distribution was equal. All patients except one had unilateral disease. The patient with the bilateral disease had CNV secondary to Bests disease. The etiologies included post inflammatory in 48.57%, posttraumatic in 7.1%

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and CNV secondary to Bests disease in 7.1% and idiopathic in 48.57%.[Table 2]. The median baseline BCVA was 6/36. In terms of BCVA change at the end of the treatment, 35.7%(five patients) achieved stabilization of visual acuity, 28.6% (four) showed an improvement in visual acuity while 35.7%(five) showed a drop in visual acuity. [Table 1] Angiographic characteristics of the choroidal neovascular membrane included 78.57 % predominantly classic in 78.57% and occult in 21.4%. Location was subfoveal in 50%, juxtafoveal in 42.87% and peripapillary in 7.1%. The treatment modalities included loading dose Bevacizumab in 35.7%, combination therapy with PDT and anti VEGF in 14.28%, thermal laser with IVTA in 7.1%, Bevacizumab on PRN basis in 14.28%, IVTA in 14.28%. In two patients (14.28%) no treatment specific to CNV was given, these patients developed scarring of the CNV while only on antitoxoplasma medications. In the patients who were treated with loading dose of Bevacizumab, the mean number of injections was 2.4[ range 3-5]. Two patients had a residual CNV on angiogram at the end of initial loading regime and were advised 2 more injections. Out of these 2 only one patient (representative case no. 1) took the additional injections. Repeat angiogram showed no residual activity of the membrane. In the prn dosing group one patient received three doses of Bevacizumab while another patient received only one injection along with antitoxopalsma therapy. Both of these patients developed scarring of the membrane. Amongst the patients treated with IVTA, only one patient developed raised IOP which was successfully managed medically with topical antiglaucoma medications. Of the patients treated combination therapy, both patients received one cycle of PDT with anti VEGF agent on the subsequent day. One of these patients developed recurrence and was managed with 2 additional doses of Bevacizumab. Only one patient underwent combination with thermal laser and IVTA. Apart from one instance of raised IOP none of the patients developed any complications to the therapies instituted.

Representative Cases

Case No. 1: A 17 year old male developed diminution of vision OD to 6/60 N36. Ocular examination, fundus photography, FA and OCT showed subfoveal active CNV (Fig 1a). Loading dose of Bevacizumab was given at monthly intervals. Repeat FA (Fig 1b) showed residual activity so two additional doses of Bevacizumab were given at monthly intervals. BCVA was 6/9 N6 at 6 months and repeat FA showed scar with staining. (Fig 1c). Case No. 2: A 12year old female developed diminution of vision OS to 6/36 N36. Ocular examination, fundus photography, FA and OCT showed subfoveal active CNV (Fig 1a). Combination therapy with IVTA and thermal laser was done. Repeat FA showed total resolution. BCVA was 6/6 N 8p at 6 months. The BCVA improved to 6/6 N6 at 1 year and she has maintained the same BCVA till her last follow up (38 months).

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1(a) 1(b) 1(c) Figure 1: (a) Shows the pretreatment FA showing a subfoveal predominantly classic CNV and OCT shows a fibrovascular PED with serous macular detachment; (b) Post loading dose of Bevacizumab residual activity of the CNV on FA and minimal serous macular detachment with fibrovascular PED on OCT. (c) Final FA and OCT after 2 additional doses of Bevacizumab, showing RPE window defects and FVPED. OCT shows no residual serous macular detachment. Figure 2: (a) Shows the pre treatment FA showing juxtafoveal classic CNV and the OCT showing a pre RPE fusiform lesion. (b) Post treatment with IVTA with thermal laser, FA showing scarring of the CNV with no residual activity. OCT shows hyperreflectivity in the juxtafoveal region with no residual intraretinal edema or serous macular detachment. 2(a)

2(b)

DISCUSSION
Although the clinical course of subfoveal CNV secondary to AMD is well documented in the literature, sparse information exists on both the natural history and treatment of CNV in the pediatric age group. Due to the rare occurrence of this entity, there are not many published reports in the available literature; it poses challenges in the management. Von Eiken et. al. reported photodynamic therapy to be successful in 1 case of a 5-year-old girl with subfoveal CNVM. The successful use of anti-VEGF therapies in younger patients, most notably in neonates with retinopathy of prematurity, has allowed for application of this treatment to other pediatric conditions. Cakir and colleagues reported two children with choroidal neovascular membrane that regressed following treatment with bevacizumab with documented

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improvement in visual acuity. Avery has discussed the potential uses of antiVEGF agents in pediatric diseases. He also raised concern and demanded caution in the use of these powerful agents, especially bevacizumab, which has a long systemic half-life. In our series however none of the patients developed any adverse effect. Adverse effects are typically uncommon and therefore unlikely to be seen with relatively small numbers of patients. In our series 64.28% of the total patients achieved stabilization or improvement of vision. As this result includes all the treatment groups in the study, compounded with the small sample size and the substantial lack of literature, these results cannot be overtly generalized. However it seems that pediatric CNV fare off better than its age related counterparts. Amongst the patients who received Bevacizumab, the improvement in visual acuity could have been attributed to the dose used in our series (2.5mg/0.1ml). However, Bashshur et. al. administered 3 injections of 2.5 mg/0.1 mL every 4 weeks as per their protocol in CNV from AMD. Still this is just an extrapolation and it is wise to be exert caution for the overzealous in the use of these agents in pediatric cases. This series suffers from many shortcomings. One is that it is retrospective. Another is that it is not a randomized treatment trial so the inherent weaknesses in the article cannot be avoided. Visual acuity was measured in a non standardized fashion using the Snellen chart. Since no single treatment protocol was followed the data from our series cannot be directly extrapolated to other available data. Table 1: Change in the BCVA in patients (Parentheses show the LogMAR equivalent as per the AJO guidelines)
Patients 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Baseline Final BCVA BCVA 6/18 (0.5) 6/60 (1) 6/18 (0.5) CF 1 (2.7) 6/12 (0.3) 6/18 (0.5) CF 1 (2.7) 6/9 (0.2) 6/18 (0.5) 6/60 (1) 6/36 (0.8) 1/60 (2.7) 6/36 (0.8) 4/60 (2.7) 6/18 (0.5) 6/9 (0.2) CF 1 (2.7) 5/60 (1) 6/60 (1) 6/36 (0.8) 6/36 (0.8) 6/9 (0.2) 6/6 (0) 5/60 (2.7) 6/6p (0) 5/60 (2.7) 3/60 (2.7) 3/60 (2.7) Change in BCVA 0 8 -6 0 -7 -3 3 0 5 -1 2 0 -3 0 Follow Up (Months) 53 7 16 6 27 89 42 7 6 6 38 7 30 84

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In conclusion choroidal Table 2: Graph showing the incidence of neovascular membrane various etiologies in the series in pediatric age is a potentially treatable but rare entity and in the lack sufficient trial and guidelines for the management, treating this subgroup of diseases is challenging. The treatment options which include PDT, thermal laser, IVTA and anti-VEGF agents have their own benefits and risks. Various investigators have shown the results of treatment with various modalities to be favorable. Timely and judicious management yields good visual outcomes.

REFERENCES
1. 2. Wilson ME, Mazur DO. Choroidal neovascularization in children: report of five cases and literature review. J Pediatr Ophthalmol Strabismus 1988;25:239. Goshorn EB, Hoover DL, Eller AW, et. al. Subretinal neovascularization in children and adolescents. J Pediatr Ophthalmol Strabismus 1995;32:17882.

3. Surgical Management of Subfoveal Neovascularization in Children J Sears, A Capone, Jr,.T Aaberg, Sr. H Lewis, H Grossniklaus, P Sternberg, Jr,. E DeJuan, Ophthalmology 1999;106:9204 4. Rosenfeld PJ, Brown DM, Heier JS et. al. MARINA Study Group, NEJM 2006; 355:1419-1431,,, Avery RL, Pieramici JD, Rabena MD, Castellarin AA, Nasir MA, Giust MJ, IVA for NVAMD, Ophthalmology; 2006;113:363-72. 5. 6. Buch H, Nielsen NV,Copenhagen City Eye Study, Ophthalmology 2005;112:787-78. Campochiaro PA, Hafiz G, Intravitreal ranibizumab for macular edema due to retinal vascular occlusion, implication of VEGF as a critical stimulator. Mol Ther 2008;16:791-799, Rodriguez- Fontal M IVL for DR Curr Diabetes Rev. 2009;5:47-51

7. von Eiken J, Hoh H, Rehfeldt K. Photodynamic therapy for choroidal neovascularization due to choroidal coloboma in a 512 -year-old child. Klin Monatsbl Augenheilkd 2007;22:140-45. 8. Cakir M, Cekic O, Yilmaz OF. Intravitreal bevacizumab for idiopathic choroidal neovascularization. J AAPOS 2009;13:296-8. 9. Cakir M, Cekic O, Yilmaz OF. Intravitreal bevacizumab and triamcinolone treatment for choroidal neovascularization in Best disease. J AAPOS 2009;13:94-6.

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10. Avery RL. Extrapolating anti-vascular endothelial growth factor therapy into pediatric ophthalmology: Promise and concern. J AAPOS 2009;13:329-31. 11. Ferris FL III, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research. Am J Ophthalmol 1982;94:916.

APROP: A Case Series


Dr. Sucheta Kshirsagar, Dr. Pravin Narwadkar, Col.M.Deshpande, Dr. Nilesh Kakade

etinopathy of Prematurity (ROP) is a disease peculiarly occurring in preterm neonates. It is a retinal vascular disease which, if left untreated can lead to irreversible blindness or severe visual impairment in babies. ROP is of particular significance for country like ours due to high number of preterm births .In last decade or two, modern neonatal care has been hugely responsible for survival of extremely premature babies. Currently developing countries like India are facing Third Epidemic of ROP1. Aggressive Posterior ROP (APROP) is a particularly aggressive form of the disease seen extremely preterm babies born before 30 weeks of gestational age or born with less than 1200 grams of birth weight 2. APROP starts earlier and progress very fast to blinding sequelae as compared to classical ROP.

Rationale

There have been very few publications discussing the spectrum of APROP. One study published from North India analyses the spectrum of APROP and outcome after laser treatment.3 Another study by Drenser et. al., analyses the anatomic and functional outcome after treatment of APROP.4 There has been no published data from western India. We conducted this study to find out clinical spectrum, anatomical outcome of treatment and also the correlation of occurrence of APROP with risk factors. To analyses the clinical presentation of aggressive Posterior retinopathy of prematurity cases, there correlation with risk factors and anatomical treatment outcome.

Objective
1. 2.

To study the clinical signs. To study various risk factors present in the neonates.

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3. Anatomocal treatment outcome in the form of regression or worsening of the disease. Study design: This is a retrospective chart review of 26 eyes of 13 babies diagnosed to have APROP.

MATERIALS AND METHODS


Records of all 669 babies who underwent ROP screening examination between July 2009 to April 2011 over a period of 22 months were reviewed. Totally 13 babies were diagnosed as having APROP. All babies had undergone ROP screening examination using Retcam shuttle (Clarity MSI, CA, USA). The criteria for diagnosis of APROP were, presence of capillary shunts in zone I or posterior zone II with or without presence of plus disease (vascular dilatation and tortuosity in posterior pole). These cases underwent aggressive laser treatment in one or multiple sessions. The eyes which did not respond to laser treatment were treated with intravitreal anti VEGF (Avastin ) injection. The eyes which deteriorated to stage 4B or stage 5 ROP despite medical treatment, underwent vitrectomy. The data about risk factors for ROP, including gestational age, birth weight, oxygen supplementation, RDS, intraventricular hemorrhage, sepsis, blood transfusions etc. which was noted, was analyzed.

RESULT
The mean Birth weight of babies was 1238 grams (Range 750 gm to 1742 gm). The mean gestational age was 30.6 weeks (range 28 weeks to 34 weeks). Six babies were above 1251 gms of birth weight, 4 were between 1000 to 1250 gms of Birth weight, 3 were of < 1000 gms. Other risk factors which were observed in these babies were ventricular support in 7(53.5%) babies, oxygen supplementation 9(69.2%). 14 eyes regressed after laser treatment alone, 8 eyes needed subsequent Inj. Avastin for non regressing ROP, 4 eyes were treated primarily with inj. Avastin; one eye developed stage 4B ROP even after laser and avastin and underwent lens sparing vitrectomy.

DISCUSSION
For our case series it is evident that APROP occurs in more mature and bigger babies in India .We had a baby with birth weight as higher as 1742 gms presenting with APROP. Recent neonatal forum of India (NNFI) guidelines recommend ROP screening of babies with birth weight < 1750 gms.5 We agree with recommendation that babies above this criteria but having strong neonatal course should be referred for ROP screening .

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Ventilator support and oxygen supplementation were amongst most common risk factors observed in these babies. In Indian set up, all NICUs specially the ones in government sector may not be well equipped to monitor oxygen levels during supplementation. Equipments like oxygen level monitors may help further in reducing the incidence of APROP in these vulnerable population of babies. Two babies whose eyes were treated with primary Inj. Avastin had small pupil with neovascularization of Iris and media haze at the time of presentation. Hence laser treatment was not possible. One of these was referred late (9 weeks chronological age) for ROP screening. Out of the 11 babies that were treated with laser, 3 babies were of less than 3 weeks chronological age at the time of treatment. One baby was just 2 weeks old at the time of treatment. This proves that Earlier screening for extremely premature babies may help in early diagnosis and better treatment outcome.2 One eye which progressed to stage 4B despite multiple laser sessions and inj. Avastin was treated with lens sparing vitrectomy and retina was anatomically settled at last follow up 6 weeks after surgery. In conclusion aggressive posterior ROP (APROP) is an entity which has to be looked into with positive suspicion as diagnosis can be missed due to subtle clinical features like lack of presence of classical ROP stage, deceptive junction between avascular and vascular retina and choroidal vessels which can be confused with retinal vessels. In India even bigger babies (> 1250gms) are prone to develop APROP. ROP screening should be planned earlier for these babies and they should be treated aggressively.

REFERENCES
1. Gilbert C, Retinopathy of prematurity : A global perspective of the epidemics, population of babies at risk and implications for control, Early Human Development 2008;84:77-82. 2. Jalali S, Anand R, Kumar H, Dogra M R, Azad R, Gopal L, Programme planning and screening strategy in Retinopathy of prematurity. Indian J of Ophthalmol 2003;51:89-97. 3. Sanghi, Gaurav MS*; Dogra , Mangatr. MS*;Das, Pranab MS*; Vinekar, Ananad MS, FRCS*; Gupta, Amod MS*;Dutta, Saurabh MD. Aggressive Posterior Retinopathy of Prematurity in Asian Indain Babies: Spectrum of Disease and Outcome After Laser Treatment.

4. Drenser, Kimberly A. MD, Phd. Trese, Michael T. MD, Capone, Antonio Jr. MD, Aggressive Posterior Retinopathy of Prematurity. 5. Chairperson: Ranjan Kumar Pejaver ; Members: Archana P Bilagi, Anand Vinekar; Reviewers: Ashok K Deorari, Subhadra Jalali :NNF Clinical Practice Guidelines 2010.

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