Divya Balakrishnan

Serious adverse events and visual outcomes of rescue therapy using adjunct bevacizumab to laser and surgery for retinopathy of prematurity. The Indian Twin Cities Retinopathy of Prematurity Screening database Report number 5

Aim To report serious adverse events and long-term outcomes of initial experience with intraocular bevacizumab in retinopathy of prematurity (ROP). Methods Consecutive vascularly active ROP cases treated with bevacizumab, in addition to laser and surgery, were analysed retrospectively from a prospective computerised ROP database. Primary efficacy outcome was regression of new vessels. Secondary outcomes included the anatomic and visual status. Serious systemic and ocular adverse events were documented. Results 24 ROP eyes in 13 babies, received single intraocular bevacizumab for severe stage 3 plus after failed laser (seven eyes), stage 4A plus (eight eyes), and stage 4B/5 plus (nine eyes). Drug was injected intravitreally in 23 eyes and intracamerally in one eye. New vessels regressed in all eyes. Vision salvage in 14 of 24 eyes and no serious neurodevelopmental abnormalities were noted up to 60 months (mean 30.7 months) follow-up. Complications included macular hole and retinal breaks causing rhegmatogenous retinal detachment (one eye); bilateral, progressive vascular attenuation, perivascular exudation and optic atrophy in one baby, and progression of detachment bilaterally to stage 5 in one baby with missed follow-up. One baby who received intracameral injection developed hepatic dysfunction. One eye of this baby also showed a large choroidal rupture. Conclusions Though intraocular bevacizumab, along with laser and surgery salvaged vision in many otherwise progressive cases of ROP, vigilance and reporting of serious adverse events is essential for future rationalised use of the drug. We report one systemic and four ocular adverse events that require consideration in future use of the drug.

Unusual Adverse Choroidal Reaction to Intravitreal Bevacizumab in Aggressive Posterior Retinopathy of Prematurity: The Indian Twin Cities ROP Screening (ITCROPS) Data Base Report Number 7*

Abstract Purpose: To describe a case of choroidal ischemia in a neonate after single, bilateral, intravitreal bevacizumab (IVB) injection for severe zone 1 aggressive posterior retinopathy of prematurity (AP-ROP). Methods: A six-week-old baby, born at a gestation age of 28 weeks and birth weight of 1.08 kg, presented at a postconceptional age of 34 weeks for ROP screening. On examination, both eyes revealed engorged iris new vessels with poorly dilating pupils. Retinal examination showed media haze, severe zone 1 APROP with confluent new vessels, severe plus disease, and early vitreous condensation at the edge of new vessels for 12 clock hours. The child was treated bilaterally, with single IVB injection before laser. After 16 hours, hypotony and exudative retinal detachment with patches of choroidal whitening suggestive of choroidal ischemia were seen. Results: The child was treated with topical steroids and cycloplegic drops and exudative retinal detachment resolved on the tenth day. Initial resolution of new vessels showed recurrence after two weeks and was treated with laser photocoagulation. Stable retinopathy status was noted up to six months follow-up. Conclusion: Choroidal ischemia secondary to a single IVB injection for the treatment of AP-ROP could be an unusual complication which raises the concern of its use as a monotherapy in neonates.

Impact of the day-30 screening strategy on the disease presentation and outcome of retinopathy of prematurity. The Indian twin cities retinopathy of prematurity report number 3

Context: Outcomes of various screening strategies in retinopathy of prematurity are not well reported. Aim: To assess the impact of a city-wide, ROP screening strategy, on the disease presentation and treatment outcome. Materials and Methods: A retrospective case-control study from a prospectively collected ROP data-base was analyzed. Cases (group 1a) included ROP babies that were screened directly in neonatal intensive care units, and controls (group 1b) were babies referred directly to the institute from other neonatal centers during the same period. Historical controls (group 2) were ROP cases seen in the years preceding establishment of this ROP program and database. Primary outcome measure was the risk of eyes presenting with stage 4 or worse ROP, and main secondary outcome measure was the final anatomic outcome. Results: Of the 643 cases screened, 322 eyes of 161 babies had ROP. The median age of 7.19 months at presentation for the 46 patients (92 eyes) in group 2 was higher than the median age of 1.29 months for the 115 patients (230 eyes) in group 1. Within the group 1, group 1a had lower median age at presentation than group 1b (0.91 months versus 2.30 months). The relative risk of an eye presenting in the stage 4 and 5 in group 2 was 4.7 times higher (95% confidence interval 3.07 -7.32) than in group 1. Eyes that could be given treatment in group 2 were significantly less (P < 0.0005) than in group 1. The relative risk of poor outcome in group 2 was 3.83 times higher (95% confidence interval 2.75 -5.34) than in group 1. Group 1a eyes had the best outcomes. Conclusion: Early screening before one month of age in neonatal centers detects the disease early where prompt treatment can lead to favorable outcomes. The study provides early results of a model strategy for ROP screening.

Mutation spectrum of NDP, FZD4 and TSPAN12 genes in Indian patients with retinopathy of prematurity

Aim Retinopathy of prematurity (ROP) is a vasoproliferative eye disease in preterm infants. Based on its phenotypic similarities with familial exudative vitreo retinopathy (FEVR), the present study was conducted to screen the Norrin signalling pathway genes (already been implicated in FEVR) for understanding their involvement among Indian patients with ROP. Methods The study cohort consisted of patients with ROP (n=246) and controls (n=300) that included full term (n=110) and preterm babies devoid of ROP (n=190). Screening of the NDP, FZD4, TSPAN12 genes were accomplished by resequencing the entire coding and untranslated regions (UTR). The genotype data of the patients with ROP were analysed in the background of their clinical manifestations and further analysed in conjunction with other available data on these genes worldwide. Results Two novel variants in intron 1 (IVS1 +16A>G) and 3′UTR (c.5 22T>C) along with a previously reported change in the 5′UTR (c.395_409del14bp) were observed in the NDP gene in three patients with ROP. Screening of the FZD4 revealed four heterozygous variants, p.(Pro33Ser), p.(Pro168Ser), p.(Ile192Ile) and p.(Ile360Val), a compound heterozygous (p.(Pro33Ser)/p.(Pro168Ser)) and a 3′UTR (c*G>T) variants in the study cohort. Variants p.(Pro33Ser) and p.(Pro168Ser) were found to be significantly associated with ROP. A heterozygous variant p.(Leu119Arg) in TSPAN12 gene was observed in a patient with threshold ROP. However, a formal genotype–phenotype correlation could not be established due to the low frequencies of the variant alleles in these genes. Conclusions This is a first study that revealed association of few variants in Norrin signalling genes among Indian patients with ROP that warrants further detailed investigation worldwide.

Cataract surgery in children with retinopathy of prematurity (ROP): surgical outcomes

Purpose To report the outcomes of cataract surgery in children with retinopathy of prematurity (ROP). Methods A retrospective case review of all children diagnosed with ROP from January 2001 to December 2014 was done and those who underwent cataract surgery were included in the study. Details of ROP and cataract treatment, postoperative complications and outcomes were analysed. Results Of the 2258 children diagnosed to have ROP, 28 eyes of 22 children were included, 14 boys and 8 girls. Mean age at cataract surgery was 18.9 months (range 2 months to 12 years). Most common grade of ROP was stage 4 (13 eyes). Nineteen eyes underwent retinal surgery, scleral buckle (one eye) and laser (three eyes). Five eyes showed spontaneous regression. Mean duration for the development of cataract postretinal surgery was 7.76 months (range 2–32 months). Nine eyes did not receive a primary intraocular lens (IOL). Intraoperative posterior capsular rupture occurred in two eyes. Postoperative complications included visual axis opacification (four), secondary glaucoma (two) and IOL capture (one). Postoperative visual acuity assessment was possible in 23 eyes, 11 had better than 20/200 vision. Eleven patients had a follow-up of at least 2 years and the mean myopic shift at 2 years was −3.07 D in pseudophakes and −8.75 D in aphakes. Conclusions Cataracts may develop in children with ROP regardless of the modality of intervention. Postoperative complications and refractive changes are similar to those in eyes without ROP.

Serpiginous Choroiditis with Atypical Presentation Treated with Intravenous Methyl Prednisolone

Abstract Purpose: The purpose of this study is to report a case of atypical serpiginous choroiditis presenting with disc edema and exudative retinal detachment, treated successfully with intravenous methyl prednisolone. Methods: A 45-year-old male patient presented with sudden decrease of vision in his left eye. On examination, left eye showed disc edema, exudative retinal detachment, and active serpiginous choroiditis. He was treated with intravenous methyl prednisolone followed by oral steroids and Azathioprine. Results: At six weeks of follow-up, the choroiditis resolved completely with improvement of visual acuity. Conclusion: Atypical presentations of serpiginous choroiditis can cause diagnostic dilemma, but prompt diagnosis and immediate treatment can result in good visual recovery.

Role of Tamponade in Vitrectomy for Proliferative Diabetic Retinopathy with Vitreous Hemorrhage

ABSTRACT Aim: To analyze the role of tamponade in vitrectomy for proliferative diabetic retinopathy with vitreous hemorrhage. Methods: A retrospective chart analysis of patients who underwent vitrectomy for proliferative diabetic retinopathy (PDR) between 2006 and 2013, with a minimum follow-up of six months, was done. The data collected included age, gender, control of diabetes, pre- and postoperative best-corrected visual acuity (BCVA), retinal detachment, type of tamponade, and recurrence of vitreous hemorrhage (VH). Statistical analysis was done using SPSS software version 2.0 and p values <0.05 were taken as significant. Results: A total of 73 eyes of 73 patients were included. The patients were analyzed in four groups: Group 1: no tamponade; Group 2: air; Group 3: gas; Group 4: silicone oil (SO). Eighteen (24.7%), 18 (24.7%), 15 (20.5%), and 22 (30.1%) patients were in the four groups, respectively. The mean preoperative BCVA in logMAR was 1.61, 1.84, 2.25, and 2.03 and the mean change in BCVAs at six months was –0.98, –0.94, –0.97, and –0.19 in four groups, respectively. Recurrent vitreous hemorrhage was noted in 11.1%, 11.1%, 6.7%, and 9.5% of patients of four groups; it was not statistically significant. The retina remained attached in 100%, 100%, 93%, and 90% of patients in the four groups, respectively, at six months. Conclusion: The use of an intraocular tamponade in eyes with vitreous hemorrhage due to PDR was not found to be superior to no tamponade in reducing recurrent vitreous hemorrhage. Therefore, the use of a tamponade in eyes without retinal break is not beneficial.

Abnormal Complement Activation and Inflammation in the Pathogenesis of Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a neurovascular complication in preterm babies, leading to severe visual impairment, but the underlying mechanisms are yet unclear. The present study aimed at unraveling the molecular mechanisms underlying the pathogenesis of ROP. A comprehensive screening of candidate genes in preterms with ROP (n = 189) and no-ROP (n = 167) was undertaken to identify variants conferring disease susceptibility. Allele and genotype frequencies, linkage disequilibrium and haplotypes were analyzed to identify the ROP-associated variants. Variants in CFH (p = 2.94 × 10−7), CFB (p = 1.71 × 10−5), FBLN5 (p = 9.2 × 10−4), CETP (p = 2.99 × 10−5), and CXCR4 (p = 1.32 × 10−8) genes exhibited significant associations with ROP. Further, a quantitative assessment of 27 candidate proteins and cytokines in the vitreous and tear samples of babies with severe ROP (n = 30) and congenital cataract (n = 30) was undertaken by multiplex bead arrays and further validated by western blotting and zymography. Significant elevation and activation of MMP9 (p = 0.038), CFH (p = 2.24 × 10−5), C3 (p = 0.05), C4 (p = 0.001), IL-1ra (p = 0.0019), vascular endothelial growth factor (VEGF) (p = 0.0027), and G-CSF (p = 0.0099) proteins were observed in the vitreous of ROP babies suggesting an increased inflammation under hypoxic condition. Along with inflammatory markers, activated macrophage/microglia were also detected in the vitreous of ROP babies that secreted complement component C3, VEGF, IL-1ra, and MMP-9 under hypoxic stress in a cell culture model. Increased expression of the inflammatory markers like the IL-1ra (p = 0.014), MMP2 (p = 0.0085), and MMP-9 (p = 0.03) in the tears of babies at different stages of ROP further demonstrated their potential role in disease progression. Based on these findings, we conclude that increased complement activation in the retina/vitreous in turn activated microglia leading to increased inflammation. A quantitative assessment of inflammatory markers in tears could help in early prediction of ROP progression and facilitate effective management of the disease, thereby preventing visual impairment.

Systemic steroids as an aid to the management of Idiopathic Polypoidal Choroidal Vasculopathy (IPCV): A descriptive analysis

Purpose To determine the role of systemic steroids in improving visual acuity, preventing recurrence and hastening pigment epithelial detachment resolution in IPCV patients. Methods Retrospective computer assisted comparative case series of consecutive patients with documented IPCV who did and did not receive systemic steroids as part of their treatment regimen between 2007 and 2012. Patients who had systemic contraindication to steroid therapy were excluded from the steroid arm. Data collected included demographics, the best corrected visual acuity, details of the ocular and systemic exam, the treatment offered, the follow-up period and the final visual and anatomic outcomes. Outcome measures included the final BCVA, the time to resolution of the associated pigment epithelial detachment (PED, if present), the recurrence rate and the associated side effects, if any. Appropriate statistical analysis was done. Statistical significance: p < 0.05. Results 14 patients (14 eyes) had received systemic steroids in the stated period; these were compared with 26 consecutive patients (26 eyes) who did not. Mean age: 59.24 vs 62.38 years (A vs B). Mean baseline BCVA: 1.86 ± 1.24 logMAR vs 2.12 ± 1.48 logMAR (A vs B). 8 females in Group A and 14 in Group B. 11 patients in group A and 19 in group B had associated systemic hypertension. Therapy consisted of laser photocoagulation, anti-vascular endothelial growth factor therapy, photodynamic therapy or a combination of these. Mean follow-up: 43.21 ± 11.32 months (Group A) vs 48.24 ± 9.75 months (Group B). BCVA at three months was significantly better (0.84 ± 0.74 logMAR vs 1.16 ± 0.89 (p = 0.039). Final BCVA: 0.86 ± 0.78 logMAR (Group A) vs 1.29 ± 0.92 (Group B, p = 0.042). 7 patients in group A and 12 in Group B had a recurrence (insignificant difference). 1 patient in Group A and 7 in Group B had unresolved disease (persistent PED) at the end of follow-up (OR: 4.60; 95% CI 1.7–11.10). Conclusion Steroids appear to improve visual acuity and accelerate the resolution of the PEDs in patients with IPCV and large PEDs, but do not seem to influence recurrence.

A Comparative Study on Surgical Outcomes of Glued Intraocular Lens and Sutured Scleral Fixated Intraocular Lens Implantation

ABSTRACT Purpose: To compare the surgical outcomes of glued intraocular lens (GIOL) and sutured scleral fixated intraocular lens (SFIOL) implantation. Methods: A retrospective, interventional case series of 60 patients (68 eyes) who underwent GIOL (28 eyes: 11 primary; 17 secondary) and SFIOL (40 eyes: 24 primary; 16 secondary) in a tertiary eye care institute was done. The main outcome measures were complications, time taken for surgery, postoperative refractive outcomes, and final best-corrected visual acuity (BCVA). Results: The mean final BCVA was 0.42 (20/40) (+/– SD 0.29) in the GIOL group and 0.57 (20/50) (+/– SD 0.48) in the SFIOL group (p=0.08). The time taken for primary GIOL (mean+/– SD: 66+/–19 minutes) was significantly lower than primary SFIOL (means+/–SD: 94+/–34 minutes) (p=0.006). The complications were comparable between the GIOL (25%) and SFIOL (15%) groups (p=0.30). The most common complication noted was transient vitreous hemorrhage (GIOL 17%, SFIOL 5%). The only sight-threatening complication seen was retinal detachment, with one eye in each group. The mean follow-up was 20 (GIOL) and 20.4 weeks (SFIOL). Conclusion: Both glued intraocular lens and sutured scleral fixated intraocular lens are safe and effective procedures in cases of insufficient capsular support. In view of the shorter surgical time with similar outcomes, primary GIOL can be considered as a preferred surgical option over primary SFIOL.