Mutation spectrum of the Norrie disease pseudoglioma (NDP) gene in Indian patients with FEVR.

PURPOSE: Mutations in the Norrie disease pseudoglioma (NDP; Xp11.3) gene have been involved in retinal blood vessel formation and neural differentiation and are implicated in familial exudative vitreoretinopathy (FEVR) cases. However, the role of the gene has not been explored in the Indian context. Thus, this study was designed to understand the involvement of NDP among Indian patients with FEVR. METHODS: The study cohort comprised 225 subjects, including unrelated patients with FEVR (n = 110) and ethnically matched healthy subjects (n = 115) recruited from a tertiary eye care center in India. The entire coding regions, intron-exon boundaries, along with the 5' and 3' untranslated regions of NDP were screened with resequencing following standard protocols. The spectrum of the observed variants was analyzed in conjunction with data available from other populations. RESULTS: Eight potentially pathogenic mutations (p.His4ArgfsX21, p.Asp23GlufsX9, p.Ile48ValfsX55, p.His50Asp, p.Ser57*, p.Gly113Asp, p.Arg121Gln, and p.Cys126Arg, including five novel ones), were observed in the coding region of the NDP gene in ten unrelated FEVR probands (9%). The novel changes were not observed in the control subjects and were unavailable in the dbSNP, ESP5400, NIEHS95, and ExAC databases. All probands with NDP mutations exhibited classical features of the disease as observed among patients with FEVR worldwide. CONCLUSIONS: This is perhaps the first study to demonstrate the involvement of NDP among patients with Indian FEVR that further expands its mutation spectrum. The data generated could have broad implications in genetic counseling, disease management, and early intervention for a better prognosis in FEVR.

Variants in the 10q26 gene cluster (LOC387715 and HTRA1) exhibit enhanced risk of age-related macular degeneration along with CFH in Indian patients.

PURPOSE: Single nucleotide polymorphisms (SNPs) in the LOC387715 (rs10490924), HTRA1 (rs11200638), and CFH (rs1061170) genes have been implicated in age-related macular degeneration (AMD). The present study was undertaken to determine the involvement of the LOC387715 and HTRA1 in an AMD cohort from India. METHODS: The coding region of LOC387715 (exon 1) and the promoter of HTRA1 were screened by resequencing in AMD cases and normal controls. Odds ratios were calculated to assess the risk of individual genotypes. Linkage disequilibrium (LD) and haplotype frequencies were estimated with Haploview software. Population attributable risk (PAR %) for the associated SNPs and their combined effects were calculated. RESULTS: Resequencing revealed seven different SNPs in these genes, of which significant associations were noted with the risk alleles of rs10490924 (T allele; P = 5.34 x 10(-12)) in LOC387715, and rs11200638 (A allele; P = 4.32 x 10(-12)) and rs2672598 (C allele; P = 3.39 x 10(-11)) in HTRA1 among the cases. Correspondingly, the homozygous risk genotypes TT, AA, and CC in these SNPs exhibited higher disease odds and PAR %. rs10490924 and rs11200638 were in tight LD (D', 0.90; 95% CI, 0.84-0.93). G-C-T-A-C was the risk haplotype (P = 8.04 x 10(-15)), whereas the G-C-G-G-T haplotype was protective (P = 2.01 x 10(-4)). The combined effect of the CFH (CC) and LOC387715 (TT) risk genotypes exhibited a PAR of 93.7% (OR, 73.89; 95% CI, 8.69-628.13). CONCLUSIONS: The present data provided an independent validation of the association of LOC387715 and HTRA1 SNPs, along with their risk estimates among Indian patients with AMD. These associations underscore their significant involvement in AMD susceptibility, which may be useful for predictive testing.

Favorable outcome after choroidal drainage for postoperative kissing suprachoroidal hemorrhage following trabeculectomy in a high myopic vitrectomised eye.

A 39-year-old lady with past history of vitreoretinal surgery for retinal detachment and cataract surgery with Intraocular lens implantation was diagnosed as uncontrolled glaucoma. She had high myopia. She underwent Trabeculectomy and following which she presented with massive suprachoroidal hemorrhage in the first postoperative day with severe loss of vision. This case depicts the risk of suprachoroidal hemorrhage in a high myopic vitrectomised eye following glaucoma filtration surgery. It also demonstrates a favorable outcome following intervention for postoperative Suprachoroidal hemorrhage. At present, there is no evidence in literature of such event in a high myopic Vitrectomised eye following Trabeculectomy.

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.

Measurement of greatest linear diameter for choroidal neovascular membrane using optical coherence tomography.

PURPOSE: Correlation of greatest linear diameter (GLD) of choroidal neovascularization (CNV) measured by fundus fluorescein angiography (FA) with optical coherence tomography (OCT). DESIGN: Retrospective noninterventional observational case series. METHODS: Patients who underwent verteporfin therapy for subfoveal classic CNV were assessed. GLD of CNV was calculated manually from mean of 6 line scans. GLD measured on OCT and FA was correlated by assessing the agreement of the two techniques by interclass correlation and Bland and Altman technique. RESULTS: Twenty-seven eyes of 27 patients with subfoveal classic CNV were included. The mean age was 49.3 +/- 18.6 years. The mean GLD calculated on FA was 1973.3 microm and OCT was 2024.2 microm. Substantial agreement was observed between GLD measured on FA and OCT (Inter-Class Correlation [ICC] = 0.77%; 95% confidence interval, 0.56 to 0.89). CONCLUSIONS: GLD measured on OCT correlates to FA measurement. This method could be beneficial where FA is contraindicated while contemplating photodynamic therapy (PDT).

Analysis of CFH, TLR4, and APOE polymorphism in India suggests the Tyr402His variant of CFH to be a global marker for age-related macular degeneration.

PURPOSE: To screen polymorphisms in complement factor-H (CFH), toll-like receptor 4 (TLR4), and APOE genes as potential risk factors for age-related macular degeneration (AMD) in Indian patients. METHODS: One hundred patients with AMD and 120 normal control subjects were screened for the polymorphisms by restriction digestion and resequencing. Five intragenic SNPs in CFH were screened to generate haplotype data in cases and controls. The data were analyzed in conjunction with data from other populations based on genotype and haplotype frequencies, and odds ratios were computed to estimate the risk of AMD in the different genotypes. RESULTS: Significant association was noted with the CFH variant (Tyr402His) among AMD cases (P = 1.19 x 10(-7)). Individuals homozygous for the mutant genotype CC had a significantly higher risk (P < 0.0001) of AMD (OR = 11.52; 95% CI 5.05-26.28) than those carrying a single copy of the C allele (OR = 1.51; 95% CI 0.82-2.80), after adjusting for age, gender, and diabetes. Linkage disequilibrium and haplotype analysis at the CFH locus indicated the C-G-T-C-A-G to be a risk haplotype (P = 0.0003). No significant differences were observed in the genotype frequencies of APOE polymorphisms among patients and control subjects (P = 0.76). The carriers of epsilon4 allele had a reduced risk (P = 0.03) of AMD (OR = 0.42, 95% CI 0.19-0.91). TLR4 did not exhibit any association with AMD. CONCLUSIONS: The CFH polymorphism Tyr402His appears indicative of AMD pathogenesis. Diabetes, age, and gender in the presence of the homozygous "CC" genotype in CFH carry an increased risk of AMD. Hence this polymorphism could be used as a potential marker for predictive testing across continents.

Modification of screening criteria for retinopathy of prematurity in India and other middle-income countries.

PURPOSE: To determine the gestational age and birth weight of premature babies who developed vision-threatening severe retinopathy of prematurity. DESIGN: Prospective observational study of babies at risk of blindness due to retinopathy of prematurity. METHODS: Data pertaining to all babies who underwent laser treatment or surgery for acute retinopathy of prematurity and those who had cicatricial retinopathy of prematurity were prospectively collected. The gestational age and birth weight were evaluated to establish screening criteria. RESULTS: In 120 babies, the mean gestational age was 29.6 weeks (range 26 to 36 weeks). The birth weight of 115 babies ranged from 710 to 2000 g (mean 1254.5 g, SD 280.8). Birth weight was not available for five babies. Only one baby had a gestational age of >35 weeks. CONCLUSIONS: Ocular morbidity related to retinopathy of prematurity was seen in bigger and more mature babies. This study provides a scientific basis for establishing screening criteria for retinopathy of prematurity in South India and other middle-income countries.

Diametric measurement of foveal avascular zone in healthy young adults using optical coherence tomography angiography.

BACKGROUND: The objective of this study is to measure the diameter size of foveal avascular zone (FAZ) in both eyes of healthy young adults using optical coherence tomography (OCT) angiography. METHODS: A cross sectional study to measure the foveal avascular zone in healthy young adults. Subjects underwent OCT angiography using Zeiss AngioPlex OCT angiography in both eyes. RESULTS: 30 eyes of 15 healthy young adults were evaluated. The mean horizontal FAZ diameter of superficial vascular plexus was 661.166 ± 119.99 microns and mean vertical FAZ diameter was 660.033 ± 96.169 microns (P = 0.9442). The mean horizontal FAZ diameter of deep vascular plexus was 1011.2 ± 154.526 microns and the mean vertical FAZ diameter of deep vascular plexus was 818.033 ± 102.108 microns. There was no difference between the contralateral eyes of subjects in FAZ diameter of both superficial and deep capillary plexuses. CONCLUSION: The mean diametric size of FAZ in superficial capillary plexus is 660.599 ± 0.801 microns and deep capillary plexus is 914.616 ± 136.589 microns. There was no significant difference with the contralateral eyes.

Successful closure of treatment-naïve, flat edge (Type II), full-thickness macular hole using inverted internal limiting membrane flap technique.

OBJECTIVE: The objective of this study was to present the outcome of the internal limiting membrane (ILM) peeling flap technique for a treatment-naïve, flat edge (Type II), full-thickness macular hole (MH). METHODS: A 52-year-old man presented with complaints of decreased vision and seeing black spot. He was diagnosed to have a flat edge, full-thickness MH, which was confirmed by optical coherence tomography (OCT). He underwent 23G vitrectomy with brilliant blue G-assisted inverted ILM peeling with an inverted flap over the hole followed by fluid gas exchange. RESULTS: Postoperative follow-up until 3 months showed successful closure of the MH, which was confirmed by OCT. The best-corrected visual acuity improved from baseline 6/60 to 6/12 at the final follow-up. CONCLUSION: Using the inverted ILM flap technique, a treatment-naïve, flat edge (Type II), full thickness MH achieved successful anatomical and functional outcomes.

Indocyanine green dye enhanced laser photocoagulation for juxtafoveal choroidal neovascularisation.

PURPOSE: To evaluate the initial results of pilot study of indocyanine green dye enhanced laser photocoagulation for juxtafoveal choroidal neovascularisation (CNV). MATERIALS AND METHODS: The study was conducted on eleven eyes of 11 patients of CNV during the period 2001 and 2002. Two to three minutes after the injection of 5 ml of 25 mgm of indocyanine green (ICG) dye, 810 nm diode laser was used to treat the choroidal neovascular lesions. RESULTS: The age of the patients ranged from 45 to 80 years. All patients completed 12 months of follow-up. Eight eyes (72.7%) had neovascular age related macular degeneration, 2 eyes (18.2%) had myopic CNV and one eye (9.09%) had CNV secondary to angioid streak. The presenting visual acuity was or=6/12 in three patients. The final visual acuity at the end of at least 12 months follow-up was 6/12 or better in one eye (9%); 6/18-6/36 in 3 eyes (27.27%) and

Role of photodynamic therapy in polypoidal choroidal vasculopathy.

PURPOSE: To evaluate photodynamic Therapy (PDT) with Verteporfin for polypoidal choroidal vasculopathy (PCV) involving the fovea in Indian eyes, through a retrospective interventional case series. MATERIALS AND METHODS: We retrospectively reviewed the records of 9 patients (9 eyes) diagnosed to have PCV with foveal involvement between September 2001 and October 2002. RESULTS: Nine eyes underwent PDT for PCV. Follow-up ranged from 12 to 16 months. Initial visual acuity (VA) ranged from 1/60 to 6/12 and final VA varied from 1/60 to 6/9 at the end of follow-up. VA improved in 4/9 eyes (44.4%) by one line and remained unchanged in 5/9 eyes (55.6%), hence it was considered stabilized in all eyes. No adverse effects or events were observed during or after treatment with verteporfin. CONCLUSION: PDT may be beneficial for PCV with foveal involvement. Its long-term efficacy requires to be evaluated.

Optical coherence tomographic evaluation of foveal pseudocyst in the formation of macular hole.

Optical coherence tomographic documented progression of foveal pseudocyst in a vitrectomised eye to full thickness macular hole is reported. Muller cell alteration and other centrifugal forces are possible pathomechanisms.

Retino-choroidal ischemia in central retinal vein occlusion.

A 41-year-old gentleman with insulin dependent diabetes had decreased vision in the right eye due to non-ischemic central retinal vein occlusion with macular edema. One month following intravitreal ranibizumab, he developed retino-choroidal ischemia with further loss of vision. Authors show the fluorescein angiographic transition from non-ischemic central retinal vein occlusion to retino-choroidal ischemia.

Case control analyses of acute endophthalmitis after cataract surgery in South India associated with technique, patient care, and socioeconomic status.

Purpose. We investigated acute endophthalmitis incidence following cataract surgery vis-a-vis the current technological and postoperative care changes in higher and lower socioeconomic categories of patients in South India. Methods. In a retrospective case control study, we analyzed 62 cases of acute endophthalmitis and 5 controls for each endophthalmitis case from 46,095 cataract surgeries done between years 1993 and 1998. The time period covered the transition of surgical technique and after care. In addition, we analyzed systemic diseases, surgeon factor, habitat, and socioeconomic status. Results. Clinical and culture positive endophthalmitis incidence were 0.13% and 0.07%, respectively. Differential incidence of 0.10% and 0.17% for in- and ambulatory care surgeries, respectively, was close to statistical significance (P = 0.054). Lower economy category ambulatory patients had higher risk of infection. Conclusion. Ambulatory cataract surgery carried additional risk for post-operative infection in lower socioeconomic group. Improved health education could ensure greater safety.

Outcomes of a protocol-based management for zone 1 retinopathy of prematurity: the Indian Twin Cities ROP Screening Program report number 2.

PURPOSE: To report the outcomes of zone 1 aggressive posterior retinopathy of prematurity (ROP) treated with aggressive laser photocoagulation by a protocol-based approach over a 10-year period. DESIGN: Prospective, interventional case series. SETTING: Tertiary eye institute and neonatal intensive care units in the twin cities of Hyderabad and Secunderabad in South India. STUDY POPULATION: Babies screened under the Indian Twin Cities Retinopathy of Prematurity Screening (ITCROPS) program between January 1, 1997 and March 31, 2007. INTERVENTION: Multiple sessions of laser photocoagulation at any sign of plus disease with abnormal shunt vessels with or without neovascularization in zone 1. OUTCOME MEASURE: Based on the anatomic status of the retina at the final follow-up, the outcome was classified into good (completely regressed with no vitreoretinal changes), fair (regression with vitreoretinal distortion), or poor (progression into partial or total retinal detachment involving macula). Descriptive statistics (mean and range) were used for gestational age at birth, birth weight, and post-conceptional age at first presentation and at the first intervention. Trends in incidence of zone 1 ROP over 1 decade were analyzed. Outcomes were expressed in terms of proportions and 95% confidence interval (CI). RESULTS: Of the 3654 babies screened, 227 eyes of 115 babies were detected to have zone 1 aggressive disease, defined as zone 1 retinal vessels having abnormal closed-loop shunts, dilation and tortuosity, flat new vessels, or rapid progression. Laser was performed in 169 eyes. Disease regressed with good outcome in 142 eyes (84%) (95% CI, 77.6-89.2) and progressed to poor outcome in 13 eyes (7.69%) (95% CI, 4.1-12.8), while fair outcome was seen in 6 eyes (3.55%) (95% CI, 1.3-7.5). Thus 148 babies (87.5%) (95% CI, 81.6-92.14) had a favorable outcome. The outcomes in 8 treated eyes (4.7%) lost to follow-up were unknown. CONCLUSIONS: Zone 1 aggressive ROP has a good outcome if the screening is done early; intervention is prompt and adequate, with frequent follow-up until complete regression is achieved.

Transpupillary thermotherapy for chronic central serous chorioretinopathy.

PURPOSE: To determine whether transpupillary thermotherapy (TTT) causes resolution of neurosensory detachment associated with chronic central serous chorioretinopathy (CSCR). METHODS: The study was a prospective interventional pilot study. All patients underwent Snellen visual acuity measurement (converted to LogMAR for analysis), slitlamp biomicroscopy, fundus examination, colour fundus photography, fluorescein and indocyanine green (ICG) angiography and optical coherence tomography (OCT). Follow-up was scheduled at 1, 2 and 3 months. Success was defined as resolution of neurosensory detachment on OCT at 3 months, and failure as persistence of the same. The primary outcome measure was resolution of OCT-measured neurosensory detachment and secondary outcome measure was change in visual acuity at the end of 3 months. RESULTS: Fourteen eyes of 13 patients were included in the study. Twelve patients were male. The left eye was affected in seven of 14 eyes. The patients' mean age was 42.7+/-4.5 years (range 38-54 years). TTT parameters were as follows: power 156+/-47.8 mW; spot size 2.2+/-1.1 mm; duration 39.6+/-7.5 s. Following treatment, complete resolution of neurosensory detachment on OCT was seen in nine eyes (64.3%) at month 1 (P=0.004) and 11 eyes (78.6%) at months 2 and 3 (P=0.001). Three eyes (21.4%) had persistent subretinal fluid at month 3. Eight eyes (52.7%) had >or=3 lines of improvement (two eyes: five lines and six eyes three lines) at the final visit. CONCLUSION: Transpupillary thermotherapy could be a therapeutic option in patients with chronic CSCR.

Comparison of mean macular thickness using optical coherence tomography and visual acuity in diabetic retinopathy.

BACKGROUND: The purpose of the present study was to quantitatively assess the mean macular thickness in diabetic patients using optical coherence tomography and its correlation with visual acuity. METHODS: A prospective case series study was undertaken of consecutive diabetic patients referred to a tertiary eye care centre for an eye check up from January 2003 to June 2003. One hundred and five eyes from 55 patients with varying degree of diabetes underwent optical coherence tomography examination. The study patients were divided into four groups: group I, non-proliferative diabetic retinopathy (NPDR); group II, NPDR with clinically significant macular oedema (CSME); group III, proliferative diabetic retinopathy (PDR); and group IV, PDR with CSME. RESULTS: The mean macular thickness of the entire group was 256.0 +/- 129.7 microm. A positive correlation (r = 0.424, P < 0.0001) was evident between mean macular thickness and visual acuity. CONCLUSION: Optical coherence tomography is a useful tool for objectively monitoring macular thickness in patients with diabetic retinopathy. Mean macular thickness correlates with visual acuity.