Outcomes of vitreoretinal surgery in eyes with retinitis pigmentosa without retinal detachment.

PURPOSE: Outcomes of retinal detachment (RD) have been discussed in detail in many reports of patients with retinitis pigmentosa (RP). This study tries to understand the outcomes of vitreoretinal (VR) surgery for indications other than RD in the eyes with RP. METHODS: This is a retrospective study that includes clinical data from January 2013 to December 2021. Patients with RP who were treated with a VR surgical intervention were included in the study. The primary outcome of the study was to assess the changes in best-corrected visual acuity. RESULTS: Forty-four eyes of 40 patients with RP were included in the study. Nearly half of the eyes (43%, 19/44) presented from 1 month to 1 year after the onset of diminished vision, with or without floaters. The mean ± standard deviation (SD) best-corrected visual acuity (BCVA) at presentation was 1.30 ± 0.79 logMAR (20/400 ± 20/125). The major surgical indications were vitreous opacities (43.2%, 19/44) and subluxated/dislocated cataractous lenses (25%, 11/44). The median follow-up duration was 8 months (interquartile range (IQR): 1.5-27). Approximately 77% (34/44) of the eyes had improvement in vision. The mean postoperative BCVA at the last follow-up was 0.95 ± 0.73 logMAR (p-value: 0.03). CONCLUSIONS: Most eyes with RP recovered well after VR surgical interventions, with short-term improvements in visual acuity. It may be crucial to address the vitreous opacities and membranes as they hinder the residual central island of vision in RP. However, appropriate counselling is required regarding the progressive nature of retinal neuronal degeneration.

OUTCOME OF EYES TREATED FOR RETINOPATHY OF PREMATURITY IN POSTERIOR ZONE I: An Eastern India Study.

PURPOSE: To analyze the outcomes of eyes treated for retinopathy of prematurity in posterior Zone I. METHODS: In a part retrospective (9 years) and part prospective (1 year) interventional study, we analyzed eyes treated for retinopathy of prematurity in posterior Zone I with a minimum follow-up for 6 months. RESULTS: This study included 109 eyes of 56 infants; mean gestational age and birth weights were 29.3 (±2.1) weeks and 1112.5 (±381.9) g, respectively. The treatment included intravitreal anti-vascular endothelial growth factor as the initial treatment modality in 101 eyes (92.6%), either alone (27 eyes) or combined with laser or vitreous surgery (73 eyes). Laser was the initial treatment modality in eight eyes, either alone (n = 3) or in combination with surgery (n = 5). With anti-vascular endothelial growth factor alone, 30.68% (n = 27) eyes responded favorably, and the remaining 69.32% (n = 59) eyes needed retreatment (laser in the majority). At the final follow-up, 89.9% (out of 109) of eyes did well anatomically. Good outcome was significantly linked to no detachment at presentation ( P < 0.0001) and the presence of well-defined central vascular trunks ( P = 0.001). CONCLUSION: Treating the eyes before retinal detachment with bevacizumab followed by laser (and surgery, if needed) results in a favorable outcome in babies with posterior Zone I retinopathy of prematurity.

Tablet-based 'ON/OFF' pathway test can distinguish between rod- and cone-dominated diseases.

INTRODUCTION: The photopic ON pathway defect is associated with nocturnal vision loss. However, the measurement of ON function to detect a rod-dominated disease (rods affected more than cones) has not been explored. We evaluated whether the psychophysical evaluation of ON/OFF pathways can be used to distinguish cone-dominated from rod-dominated diseases. METHODS: Thirty-seven patients with inherited retinal diseases were tested using the 'EyeSpeed' [iOS application] on an iPad. The test displayed a random number (1-3) of light or dark targets on a black-and-white noise background. Participants responded on a touch screen indicating the correct number of targets displayed. The outcome variables-reaction time, accuracy and performance index (speed [1/reaction time] * accuracy) to both light and dark targets were assessed for diagnostic ability using standard receiver-operating characteristic (ROC) analysis. RESULTS: Mean ± standard deviation age and visual acuity for the cone- and rod-dominated groups were 25.15 ± 11.74 years, 0.80 ± 0.25 logMAR and 28.3 ± 14.29 years, 0.48 ± 0.26 logMAR, respectively. The median reaction time to light targets in rod-dominated disease [interquartile range] was 5.28 s [3.17], significantly greater than for patients with cone-dominated disease (2.07 s [0.93]; Mann-Whitney U test, p < 0.001). Amongst all of the outcome variables evaluated, the reaction time to light targets (criterion of ≥2.98 s) exhibited the highest area under the ROC curve (area = 0.89 ± 0.11; p < 0.001), with a sensitivity and specificity of 82.4% and 85% respectively. CONCLUSIONS: Reaction time to light targets using the ON/OFF pathway paradigm is a valid marker to differentiate between rod- and cone-dominated retinal dystrophies. ON pathway function measured using a tablet-based test could act as a supplemental test in the diagnosis of challenging photoreceptor-specific inherited retinal diseases.

Coats disease in India: clinical presentation and outcome in 675 patients (690 Eyes).

PURPOSE: To study the clinical profile, treatment, and visual outcome of patients with Coats disease in India. METHODS: This was a cross-sectional, observational hospital-based study of patients diagnosed with Coats disease during a 10-year period using an electronic medical record system. RESULTS: We identified 675 patients with Coats disease with a prevalence rate of 0.025%. The mean age of the patients was 16.8 years (median, 12 years). Majority were males (75%) with unilateral presentation (98%) in first decade of life (n = 309, 46%). The most common presentation was foveal exudation (stage 2B, n = 161, 23.3%), followed by exudative retinal detachment-extrafoveal (stage 3A1, n = 143, 20.7%), and extrafoveal exudation (stage 2A, n = 136, 19.7%). Treatment modalities included observation (48 eyes, 17%), laser photocoagulation ± intravitreal bevacizumab/triamcinolone acetonide (n = 82, 29%), cryotherapy ± intravitreal bevacizumab/triamcinolone acetonide (n = 64, 23%), and surgical intervention (n = 86, 31%). Despite appropriate treatment, at mean follow-up of 16 months, there was no significant difference between presenting and final visual acuity (48% vs. 48%, p > 0.05). Using multivariate regression analysis, factors associated with poor visual outcome were younger age (< 0.001; - 0.02 to - 0.1), unilateral disease (0.04; - 0.68 to - 0.01), cataract (0.004; 0.13 to 0.69), retinal detachment (< 0.001; 0.49 to 0.82), and glaucoma (< 0.001; 0.34 to 0.94). CONCLUSION: The most common clinical presentation of Coats disease in India is foveal exudation in first and second decade. At initial presentation, about half of the affected eyes had blindness and one-third underwent surgical intervention.

Electronic medical records driven big data analytics in retinal diseases, report number 1: non-oncological retinal diseases in children and adolescents in India.

PURPOSE: To describe the spectrum and demographic distribution of non-oncological retinal diseases in children and adolescents presenting to a multi-tier ophthalmic hospital network in India. METHODS: This is a cross-sectional hospital-based retrospective study over nine years (March 2011-March 2020) from a pyramidal eye care network in India. The analysis included 477,954 new patients (0-21 years), collected from an International Classification of Diseases (ICD) coded electronic medical record (EMR) system. Patients with a clinical diagnosis of retinal disease (non-oncological) in at least one eye were included. Age-wise distribution of these diseases in children and adolescents was analysed. RESULTS: In the study, 8.44% (n = 40,341) of new patients were diagnosed with non-oncological retinal pathology in at least one eye. The age group-specific distribution of retinal diseases was 47.4%, 11. 8%, 5.9%, 5.9%, 6.4%, 7.6% in infants (< 1 year), toddlers (1-2 years), early childhood (3-5 years), middle childhood (6-11 years), early adolescents (12-18 years) and late adolescents (18-21 years), respectively. 60% were male, and 70% had bilateral disease. The mean age was 9.46 ± 7.52 years. The common retinal disorders were retinopathy of prematurity (ROP, 30.5%), retinal dystrophy (19.5%; most commonly, retinitis pigmentosa), and retinal detachment (16.4%). Four-fifth of the eyes had moderate to severe visual impairment. Nearly one-sixth of patients needed low vision and rehabilitative services, and about 1 in 10 patients required surgical intervention (n = 5960, 8.6%). CONCLUSION AND RELEVANCE: About 1 in 10 children and adolescents seeking eye care in our cohort had non-oncological retinal diseases; the common ones were ROP (in infants) and retinitis pigmentosa (in adolescents). This information would help future strategic planning of eye health care in the institution in pediatric and adolescent age groups.

Clinical characteristics of comorbid retinal dystrophies and primary angle closure disease.

PURPOSE: To assess the clinical characteristics of comorbid retinal dystrophies and primary angle closure disease. DESIGN: Retrospective study from January 1992 to June 2020. METHODS: This descriptive study included 92 eyes of 46 patients with comorbid retinal dystrophies and primary angle closure disease (PACD) that included eyes with primary angle closure suspect, primary angle closure and primary angle closure glaucoma. Demographic profile, clinical characteristics of PACD and its association with retinal dystrophies are described. RESULTS: The study included 46 patients (92 eyes). Males were majority, 63%. Mean (± standard deviation) age when retinal dystrophy was diagnosed was 29.6 ± 9.4 years and PACD was diagnosed at 32.23 ± 7.92 years. Mean BCVA at presentation was 1.07 ± 0.87 log MAR [95% confidence interval (CI) 0.87, 1.26]. Mean Intraocular pressure at diagnosis of glaucoma was 27 ± 16 mmHg (95% CI 23.5, 31.5 mmHg). The most common retinal dystrophy associated with PACD was retinitis pigmentosa (RP) followed by RP with retinoschisis. The hospital-based prevalence of PACD among all patients with RP and retinoschisis was 0.19% and 0.15% respectively. Laser peripheral iridotomy was performed in 74 eyes (80.5%). Glaucoma was managed medically in majority of the eyes (58 eyes, 63.04%) and minority required surgical management with trabeculectomy (11, 11.9%). CONCLUSION: Retinitis pigmentosa is the most common retinal dystrophy associated with PACD. Comorbid PACD in eyes with retinal dystrophies was observed in second to third decade of life. This calls for screening for angle closure in eyes with retinal dystrophies from second decade onwards to identify the comorbid PACD and treat or refer them appropriately.

Evaluation of photoreceptor function in inherited retinal diseases using rod- and cone-enhanced flicker stimuli.

PURPOSE: Clinical assessment of rod and cone photoreceptor sensitivity often involves the use of extended dark adaptation times to minimise cone involvement or the use of bright adapting backgrounds to saturate rods. In this study we examine a new rod/cone sensitivity test, which requires minimal dark adaptation. The aim was to establish whether rod/cone sensitivity losses could be measured reliably in patients with retinal diseases that selectively affect rods or cones when compared to age-matched subjects with normal vision. METHODS: Flicker modulation thresholds (FMTs) were measured psychophysically, using cone- and rod-enhanced stimuli located centrally, and in four quadrants, at 5° retinal eccentricity in 20 patients (age range: 10-41 years) with cone-dominated (Stargardt's disease or macular dystrophy; n = 13) and rod-dominated (retinitis pigmentosa; n = 7) disease. These data were compared against age-matched normals tested with identical stimuli. RESULTS: Across all retinal locations, cone FMTs in cone-dominated diseases (Median ± IQR: 32.32 ± 28.15% for central location) were greater than a majority (83%; 49/59) of corresponding rod FMTs (18.7 ± 3.29%; p = 0.05) and cone FMTs of controls (4.24 ± 2.00%). Similarly, rod FMTs in rod-dominant disease (14.99 ± 22.58%) were greater than a majority (88%; 29/39) of the corresponding cone FMTs (9.09 ± 10.33%) (p = 0.13) and rod FMT of controls (6.80 ± 2.60 %). CONCLUSIONS: Cone-specific deficits were larger than rod-specific deficits in cone-dominated diseases, and vice versa in rod-dominated disease. These results suggest that the new method of assessing photoreceptor sensitivity has potential application in detecting specific rod/cone losses without the need for dark adaptation.

ENTEROCOCCUS ENDOPHTHALMITIS: Clinical Settings, Antimicrobial Susceptibility, and Management Outcomes.

PURPOSE: To report the clinical presentation and management outcome of patients with endophthalmitis caused by Enterococcus species and to report the susceptibility profile of the isolates. METHODS: Twenty-nine cases with culture-proven Enterococcus endophthalmitis from January 2005 to May 2018 underwent vitrectomy/vitreous biopsy, intravitreal antibiotic with or without additional procedures. The undiluted vitreous was subjected to microbiologic evaluation. A favorable anatomical outcome was defined as preservation of the globe, absence of hypotony, attached retina, and absence of active inflammation at the last visit. Favorable visual outcome was final visual acuity ≥20/400. RESULTS: There were 24 men (82.8%). Mean age at presentation was 32.89 ± 25.25 years (median 24 years). Inciting event was open globe injury in 18 (62%), endogenous in 5 (17.24%), postcataract surgery in 3 (10.34%), postscleral buckling in 2 (6.89%), and postkeratoplasty in 1 (3.44%). Enterococcus casseliflavus was the commonest species isolated (14/29, 48.27%) followed by E. faecalis (9/29, 31%). Susceptibility to vancomycin was seen in 27/29 isolates (93%). Visual acuity was ≤20/400 in all eyes at presentation and ≥20/400 in 10/29 cases (34.48%) at final visit. Anatomical success was seen in 18/29 eyes (62%). Corneal involvement was high at 24/29 eyes (82.75%). CONCLUSION: Enterococcus is not an uncommon organism in the setting of endophthalmitis after open globe injury. Resistance to vancomycin is rare. Multidrug resistance pattern is restricted to E. faecalis. Visual outcome is poor despite early and appropriate therapy due to inherent organism virulence.

Prospective clinical study of two different treatment regimens of combined laser photocoagulation and intravitreal bevacizumab for retinopathy of prematurity: the Indian Twin Cities ROP Study (ITCROPS) database report number 9.

PURPOSE: To evaluate, in a combined treatment strategy for treatment-warranted retinopathy of prematurity (ROP), which of the two is a better treatment sequence, peripheral laser photocoagulation (LPC-IVB) first or intravitreal bevacizumab (IVB-LPC) first. METHODS: Twenty-two babies (44 eyes) with ROP were recruited from 1 July 2014 to 30 March 2016. All the right eyes received LPC on day one followed by IVB on day four (LPC-IVB group). In all left eyes, IVB was injected on day one followed by LPC on day four (IVB-LPC group). The primary outcome measure was the proportion of eyes that had complete ROP regression with no additional treatment within 2 weeks of the onset of therapy. Retinal photography and drawings were used at each visit to document disease course. RESULTS: In LPC-IVB group, 72.7% (16/22) eyes had complete ROP regression with no additional treatment within 2 weeks of the onset of therapy. In the IVB-LPC group, 95.5% (21/22 eyes) had complete regression within 2 weeks. Additional laser had complete regression in all eyes in each group. One baby (two eyes, one from each group) had late recurrence at 5 months. CONCLUSION: The combined therapy strategy was successful for ROP management. Administration of anti-vascular endothelial growth factor injection before the peripheral laser was better than the reverse strategy of laser first. Late recurrences and adverse events were low.

Characteristics of 'sawtooth shunt' following anti-vascular endothelial growth factor for aggressive posterior retinopathy of prematurity.

OBJECTIVE: To explore the characteristics of 'sawtooth shunts (STS)' following intravitreal anti-vascular endothelial growth factors (anti-VEGF) for aggressive posterior retinopathy of prematurity (AP-ROP). DESIGN: Prospective observational study. METHODS: In a prospective observational study, 45 eyes of 24 babies receiving intravitreal anti-VEGF for AP-ROP or hybrid ROP were analyzed. Anti-VEGF molecule and doses: bevacizumab (0.62 mg or ½ IVB, n = 30 eyes; 0.25 mg or 1/5IVB, n = 9 eyes; 0.12 mg or 1/10 IVB, n = 1 eye); or ranibizumab (0.25 mg or ½IVR, n = 3 eyes; 0.1 mg or 1/5IVR, n = 2 eyes). They were followed every 1-2 week till disease regression with or without laser treatment. Development of STS, its variants, characteristics, timeline, and final outcomes was analyzed. RESULTS: STS occurred in 26 (57.7%) eyes at 1-6 weeks following anti-VEGF injections and persisted for 1-14 weeks. While the shunt regressed spontaneously in half of the treated eyes (n = 13) with anti-VEGF alone, the other half (n = 13) required additional laser because of either non-compliance (n = 9) or recurrence (n = 4). CONCLUSION: The STS was observed to be an important retinal vascular change seen in infants treated with intravitreal anti-VEGF at half adult doses. It warrants further studies to explore the association between STS and its association with disease recurrence or regression.

ISCEV guide to visual electrodiagnostic procedures.

Clinical electrophysiological testing of the visual system incorporates a range of noninvasive tests and provides an objective indication of function relating to different locations and cell types within the visual system. This document developed by the International Society for Clinical Electrophysiology of Vision provides an introduction to standard visual electrodiagnostic procedures in widespread use including the full-field electroretinogram (ERG), the pattern electroretinogram (pattern ERG or PERG), the multifocal electroretinogram (multifocal ERG or mfERG), the electrooculogram (EOG) and the cortical-derived visual evoked potential (VEP). The guideline outlines the basic principles of testing. Common clinical presentations and symptoms are described with illustrative examples and suggested investigation strategies.

CLINICAL PRESENTATION, MICROBIOLOGIC PROFILE AND FACTORS PREDICTING OUTCOMES IN BACILLUS ENDOPHTHALMITIS.

PURPOSE: To describe the clinical presentation, microbiologic profile, and factors predicting outcomes in Bacillus endophthalmitis. METHODS: Retrospective interventional case series. Eighty-six patients with culture-proven Bacillus endophthalmitis, from January 2001 to December 2015, underwent vitrectomy/vitreous biopsy and intravitreal antibiotic with or without steroid as appropriate. The undiluted vitreous biopsy was subjected to microbiologic evaluation. The duration of symptoms, presenting visual acuity, organisms isolated, influence of intravitreal dexamethasone with intravitreal antibiotics, and type of initial intervention were examined for any clinical and statistical correlation in terms of odds ratio with the final visual outcome. RESULTS: Trauma was the commonest etiology (n = 75; 87.2%). Mixed infection with other bacteria was seen in 11 patients. All Bacillus species were sensitive to gentamicin followed by ciprofloxacin (n = 85; 98.83%) and vancomycin (n = 81; 94.18%). Odds in favor of a favorable visual outcome were seen with clinical treatment within 48 hours of the symptoms (OR 25.47, 95% CI 2.45-254.16, P = 0.006), better presenting vision (OR 31.21, 95% CI 2.96-323.64, P = 0.004), and absence of polymicrobial infection (OR 18.03, 95% CI 0.9-344.4, P = 0.05). Only 20% of all treated patients regained ambulatory vision, and one fifth of all of them developed phthisis. CONCLUSION: Patients diagnosed with Bacillus endophthalmitis merit aggressive vitreous intervention guided by the culture-sensitivity report. Despite early and appropriate treat ment, the outcomes are generally poor.

Correlation of macular structure and function in a boy with primary foveomacular retinitis and sequence of changes over 5 years.

PURPOSE: To describe the clinical characteristics, macular structure and function, and to document sequential changes over 5 years in a 10-year-old boy with bilateral primary foveomacular retinitis. METHODS: A 10-year-old boy presented with sudden onset scotoma in both eyes, experienced after getting up from bed on a non-eclipse day. He persistently denied direct sun-gazing. He neither had any significant systemic illness, nor was using any medications. In addition to a detailed examination at presentation that included fundus fluorescein angiogram (FFA), electroretinogram (ERG), pattern ERG and electrooculogram (EOG), he was examined periodically for 5 years with Humphrey visual field (HVF), spectral domain optical coherence tomogram (SDOCT), Amsler grid charting and multifocal ERG. The macular structure and functions were analyzed over the years and correlated with the symptoms. RESULTS: All findings were bilaterally symmetrical at each visit. At presentation, his corrected visual acuity was 20/25 with subfoveal yellow dot similar to solar retinopathy, central scotoma with reduced foveal threshold in HVF 24-2, micropsia in Amsler grid, missing of two plates on Ishihara color vision chart, transfoveal full thickness hyper-reflective band on SD OCT, unremarkable FFA and normal foveal peak in mfERG. The flash ERG and EOG were unremarkable. A month later, his VA improved to 20/20, he had relative scotoma in Amsler grid, no scotoma in HVF (10-2), restoration of the inner segment of the photoreceptors with sharp defect involving ellipsoid and photoreceptor interdigitation zone in SDOCT and blunting of foveal peaks in mfERG. Three months later, his corrected VA was 20/20 with relative scotoma in Amsler grid, normal color vision, no scotoma in HVF 10-2 and unchanged SDOCT findings. In subsequent examinations at 6, 9, 14, 29, 39 and 60 months, he was symptomless with VA 20/20, unremarkable fundus, normal Amsler grid and HVF (normal foveal threshold), unchanged SDOCT findings and the reduced foveal peaks on mfERG in both eyes got normalized only at 60 months. CONCLUSION: Presented here is a case of bilaterally symmetrical idiopathic foveomacular retinitis that had a clinical appearance similar to solar retinopathy. The fundus changes persisted for 4 weeks, the symptoms and changes in Amsler grid lasted for 3 months, and the foveal threshold in visual fields normalized within 3 months. Maximum change in the SDOCT defect occurred within a month, and the extrafoveal defect in the ellipsoid and photoreceptor interdigitation line persisted despite resolution of symptoms and resolution of the visual field defect and normal distance vision. Probably, the foveal lesion detected on SDOCT was too small to cause a reduction in the distance visual acuity or show up in the visual field and mfERG later.

Clinical presentations, risk factors and outcomes of ceftazidime-resistant Gram-negative endophthalmitis.

BACKGROUND: To describe the clinical features and outcomes of patients diagnosed with ceftazidime-resistant Gram-negative endophthalmitis and the role of intravitreal imipenem in these cases. DESIGN: Retrospective consecutive interventional case series at a tertiary eye care centre in South India. PARTICIPANTS: Consecutive cases of ceftazidime-resistant Gram-negative endophthalmitis from April 2010 to December 2014. Fifty-six cases diagnosed during this time period were included. METHODS: All cases were managed with vitreous biopsy/vitrectomy, microscopy and undiluted vitreous culture, antimicrobial susceptibility of bacterial isolates and received intravitreal antibiotics. MAIN OUTCOME MEASURES: Anatomic and visual outcome of these cases, antimicrobial susceptibility pattern of intravitreal imipenem and outcome of cases injected with it. RESULTS: Commonest presentation was acute endophthalmitis following cataract surgery (27 eyes, 48.21%). Pseudomonas aeruginosa was isolated in 33 eyes (58.93%; 95% CI 46.05-71.81%). Nineteen eyes (34%; 95% CI 21.59-46.41%) developed phthisis; 14 eyes (25%; 95% CI 13.66-36.34%) had vision <20/200; 17 eyes (30.35%; 95% CI 18.31-42.39%) eyes had an ambulatory vision >20/200 (logMAR 1); 6 eyes (10.71%; 95% CI 2.61-18.81%) had a reading vision >20/40 (logMAR 0.3). Trend was towards better anatomic (72.73% vs. 40%) (P = 0.05) and visual improvement in the imipenem group (logMAR 3.94 + 0.21 to 2.43 + 1.4; P = 0.002), as compared with non-imipenem group (logMAR 2.99 + 1.3 to 2.55 + 1.4; P = 0.13). CONCLUSIONS: Outcome of ceftazidime-resistant Gram-negative endophthalmitis is poor. P. aeruginosa is the commonest isolated organism. All cases were sensitive to imipenem. There was a trend towards better anatomic outcome in imipenem-treated eyes.

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.

CLINICAL PRESENTATIONS AND OUTCOMES OF RHEGMATOGENOUS RETINAL DETACHMENT IN RETINITIS PIGMENTOSA.

PURPOSE: To describe the clinical presentations and outcomes of rhegmatogenous retinal detachments (RRD) in eyes with retinitis pigmentosa. METHODS: A retrospective review of all patients of retinitis pigmentosa with RRD from January 1990 to December 2013 at a tertiary eye care institute. RESULTS: Of total 28,622 patients of retinitis pigmentosa over a 23-year period, 17 eyes of 17 patients had RRD. Mean age at presentation was 34.53 ± 16.42 years (median 32 years). Median duration of decreased vision attributed to RRD was 6 months. Ten eyes (59%) had cataract and 3 eyes (18%) had history of cataract surgery. Thirteen eyes (76%) had inferior retinal detachment; 9 eyes (53%) had lattice with retinal holes; and 8 eyes (47%) had atrophic retinal holes. There were no horse-shoe tears, giant retinal tears, dialysis, and macular holes related RRD. Majority (82%) of retinal breaks were in the inferotemporal quadrant. Only 3 eyes (18%) had proliferative vitreoretinopathy at presentation. Twelve eyes at presentation had best-corrected visual acuity <20/200 and 6 eyes had only light perception. The macula was involved by the detachment in all cases. Mean preoperative visual acuity was 1.4 ± 0.88 logarithm of the minimum angle of resolution (median 1.3, range 3-0.1; 20/502). Surgery was not advised in 6 eyes (35% patients); 5 eyes (30%) underwent scleral buckling and 6 eyes (35%) underwent vitrectomy. Median follow-up was 5 months. Reattachment rate at last follow-up was 91% (15 eyes). Mean postoperative best-corrected visual acuity recorded was 1.06 ± 0.8 (median 1, range 3-0.1; 20/229) (P = 0.15). Eight eyes at last visit had best-corrected visual acuity <20/200. Of the 11 eyes operated, 4 improved in vision and 7 retained the preoperative vision. CONCLUSION: The incidence of RRD in retinitis pigmentosa is very low. Presentation, although delayed, is at a younger age. Horse-shoe tears and proliferative vitreoretinopathy are uncommon; cataract is a common coexisting pathology. Surgical reattachment rates appear high and recurrent RRD is uncommon. However, visual gain is limited by the underlying retinal degenerative condition.

Mutation spectrum of the FZD-4, TSPAN12 AND ZNF408 genes in Indian FEVR patients.

BACKGROUND: Mutations in candidate genes that encode for a ligand (NDP) and receptor complex (FZD4, LRP5 and TSPAN12) in the Norrin ß-catenin signaling pathway are involved in the pathogenesis of familial exudative vitreoretinopathy (FEVR, MIM # 133780). Recently, a transcription factor (ZNF408) has also been implicated in FEVR. We had earlier characterized the variations in NDP among FEVR patients from India. The present study aimed at understanding the involvement of the remaining genes (FZD4, TSPAN12 and ZNF408) in the same cohort. METHODS: The DNA of 110 unrelated FEVR patients and 115 unaffected controls were screened for variations in the entire coding and untranslated regions of these 3 genes by resequencing. Segregation of the disease-associated variants was assessed in the family members of the probands. The effect of the observed missense changes were further analyzed by SIFT and PolyPhen-2 scores. RESULTS: The screening of FZD4, TSPAN12 and ZNF408 genes identified 11 different mutations in 15/110 FEVR probands. Of the 11 identified mutations, 6 mutations were novel. The detected missense mutations were mainly located in the domains which are functionally crucial for the formation of ligand-receptor complex and as they replaced evolutionarily highly conserved amino acids with a SIFT score < 0.005, they are predicted to be pathogenic. Additionally 2 novel and 16 reported single nucleotide polymorphisms (SNP) were also detected. CONCLUSIONS: Our genetic screening revealed varying mutation frequencies in the FZD4 (8.0 %), TSPAN12 (5.4 %) and ZNF408 (2.7 %) genes among the FEVR patients, indicating their potential role in the disease pathogenesis. The observed mutations segregated with the disease phenotype and exhibited variable expressivity. The mutations in FZD4 and TSPAN12 were involved in autosomal dominant and autosomal recessive families and further validates the involvement of these gene in FEVR development.

Characteristics and outcomes of anterior hyaloidal fibrovascular proliferation in lasered retinopathy of prematurity. The Indian Twin Cities Retinopathy of Prematurity Study (ITCROPS) report number 4.

To describe the characteristics and treatment outcomes of an unreported, late vitreous hemorrhage due to anterior hyaloidal fibrovascular proliferation in laser-regressed retinopathy of prematurity (ROP). Interventional case series. In the ongoing Indian Twin Cities ROP study database, consecutive cases with isolated late vitreous hemorrhage at least one year after laser-regressed disease were analyzed retrospectively. Anterior hyaloidal fibrovascular proliferation was diagnosed primarily using scleral depression. Anterior retinal cryopexy with adjunctive treatments was performed. The main outcome measure was clinical resolution of new vessels with no recurrent hemorrhage over a 1-year period. Vitreous hemorrhage, at two to eight years of age, developed in three eyes of three children out of 1,168 ROP lasered eyes. All had received laser for zone I disease as neonates, with no subsequent sequelae. Evaluation revealed filiform new vessels at the posterior vitreous base involving inferior 180° with absence of any other source of hemorrhage. All underwent anterior retinal cryopexy to the affected area. Simultaneous additional treatment, based on intraoperative findings, included one case each of peripheral laser photocoagulation, lens-sparing vitrectomy and intravitreal bevacizumab. All three showed successful regression and non-recurrence of vitreous hemorrhage with improvement of vision >20/40 at an intermediate follow-up of two years. Anterior hyaloidal fibrovascular proliferation is an unreported and rare cause of vitreous hemorrhage, appearing years after laser-regressed ROP. It has a good response to interventional treatment. Meticulous scleral depression of the vitreous base under anesthesia is useful to detect this rare source of vitreous hemorrhage.

Petaloid-pattern pigmentary retinopathy: a novel case report.

We report the case of a 6-year-old girl with an unusual petaloid-pattern pigmentary retinopathy associated with nyctalopia and reduction of vision which had been invariably static over the past 5 years. We performed a comprehensive ophthalmic examination including fundoscopy, autofluorescent imaging, electroretinography and optical coherence tomography. There were diffuse retinal pigment epithelium (RPE) washout areas with blotches of pigment distributed in the pattern of a petal with marked chorioretinal atrophy and scar at the fovea. The arterial caliber was normal. Investigations ruled out intrauterine and neonatal infection. Systemically, she was healthy with normal intellect but with 3-month delayed milestones of development. She had used valproic acid for seizure disorder (without any organic central nervous system lesion) from 2-5 years of age. Electroretinography showed extinguished scotopic responses with slight reduction in cone responses. Optical coherence tomography showed a scar with attenuated RPE-choriocapillary complex at the macula. Her clinical profile did not fully match with any previously described pigmentary retinopathies except rod-cone dystrophy and choroidal dystrophy to a certain extent. The pigmentary retinopathy reported here is a combination of a petaloid pattern of pigmentary disturbance, stationary reduction of vision, nyctalopia, normal intellect and marginal delayed milestones. In the absence of such a description in the literature we named this disorder as petaloid-pattern pigmentary retinopathy.