Next-generation sequencing-based genetic testing and phenotype correlation in retinitis pigmentosa patients from India

Purpose: Inherited retinal dystrophies (IRD) are a heterogeneous group of retinal diseases leading to progressive loss of photoreceptors through apoptosis. Retinitis pigmentosa (RP) is considered the most common form of IRD. Panel?based testing in RP has proven effective in identifying the causative genetic mutations in 70% and 80% of the patients. This is a retrospective, observational, single?center study of 107 RP patients who had undergone next?generation sequencing?based targeted gene panel testing for IRD genes. These patients were inspected for common phenotypic features to arrive at meaningful genotype–phenotype correlation. Methods: Patients underwent complete ophthalmic examination, and blood was collected from the proband for DNA extraction after documenting the pedigree. Targeted Next Generation Sequencing (NGS) was done by panel?based testing for IRD genes followed by co?segregation analysis wherever applicable. Results: Of the 107 patients, 72 patients had pathogenic mutations. The mean age of onset of symptoms was 14 ± 12 years (range: 5–55). Mean (Best Corrected Visual Acuity) BCVA was 6/48 (0.9 logMAR) (range 0.0–3.0). At presentation, over one?third of eyes had BCVA worse than 6/60 (<1 logMAR). Phenotype analysis with the gene defects showed overlapping features, such as peripheral well?defined chorioretinal atrophic patches in patients with CERKL, PROM1, and RPE65 gene mutations and large macular lesions in patients with RDH12 and CRX gene mutations, respectively. Nummular or clump?like pigmentation was noted in CRB1, TTC8, PDE6A, and PDE6B. Conclusion: NGS?based genetic testing can help clinicians to diagnose RP more accurately, and phenotypic correlations can also help in better patient counselling with respect to prognosis and guidance regarding ongoing newer gene?based therapies.

Updated guidelines for the management of polypoidal choroidal vasculopathy: Recommendations from the Indian Polypoidal Choroidal Vasculopathy Panel and the Vitreoretinal Society of India

In Asians, polypoidal choroidal vasculopathy (PCV) is becoming more widely recognized as a significant cause of exudative maculopathy. The previous set of Indian guidelines on the management of PCV were published in 2018, with a literature search updated up to November 2015. As the treatment of PCV evolves, retinal physicians must constantly modify their current practice. The current guidelines are based on the most up-to-date information on PCV and are an update to the previous set of guidelines. These guidelines were developed by a panel of Indian retinal experts under the aegis of the Vitreoretinal Society of India (VRSI), based on a comprehensive search and assessment of literature up to September 2021. The final guidelines i) provide the updated nomenclature in PCV; ii) discusses the newer diagnostic imaging features of PCV, especially in the absence of indocyanine green angiography (ICGA); and iii) recommends the best possible therapeutic approach in the management of PCV, including the choice of anti-vascular endothelial growth factor (anti-VEGF) agents, treatment regimen, and the role of switching between the anti-VEGF agents. In the face of non-availability of photodynamic therapy (PDT) in India, we constructed practical recommendations on anti-VEGF monotherapy in PCV. The current updated recommendations would provide a broader framework to the treating retinal physician for the diagnosis and management of PCV for optimal therapeutic outcomes.

Genetic testing in four Indian families with suspected Stickler syndrome

Purpose: Stickler syndrome is associated with the development of rhegmatogenous retinal detachment (RRD), and often presents with ocular, auditory, skeletal, and orofacial abnormalities. Molecular analysis has proven effective in diagnosis, confirmation and classification of the disease. We aimed to describe the utility of next?generation sequencing (NGS) in genetic analysis of four Indian families with suspected Stickler syndrome. Methods: The index cases presented with retinal detachment with family history. Genetic analysis in the index case was performed by next?generation sequencing of inherited retinal degeneration genes, and validated by Sanger sequencing followed by co?segregation analysis in the other family members. Results: Twenty patients were included for the genetic analysis (15 males and 5 females from four families). Clinical details were available for 15 patients (30 eyes). Fourteen eyes (11 patients) developed RRD. In the 16 eyes without RRD, 8 underwent barrage laser to lattice degeneration and 8 were under observation. Disease segregating heterozygous mutations with pathogenic/likely pathogenic effect was identified in COL2A1 (c.4318?1G>A, c.141G>A, c.1221+1G>A for 3 families) and COL11A1 (c.1737+1 G>A for 1 family) gene. In addition to the mutation in the COL2A1 gene, a pathogenic heterozygous variant associated with risk for arrhythmogenic right ventricular cardiomyopathy (ARVC) was identified in one member. Conclusion: NGS testing confirmed the presence of the causative gene for Stickler syndrome in the index case followed by evaluation of family members and confirmation of genetic and ocular findings. We believe that this may be the first such report of families with RRD from India

Effect of ocular magnification on macular measurements made using spectral domain optical coherence tomography.

Aim: The aim of the present study was to study the effect of ocular magnification on macular measurements made using spectral domain optical coherence tomography (OCT). Materials and Methods: One hundred and fifty-one subjects were included from the normative study of foveal morphology carried out at our hospital. Subjects underwent comprehensive eye examination and macular scanning using Cirrus highdefinition OCT and axial length (AXL) measurement. Macular cube 512 × 128 scan protocol was used for scanning the macula. Automated measurements of the fovea namely foveal diameter, foveal slope (lateral measurements) and foveal depth (axial measurement) were taken. A correction factor for ocular magnification was done using the formula t = p × q × s, where “t” is the corrected measurement, “p” is the magnification of OCT, “q” is the ocular magnification, and “s” is the measurement on OCT without correction. The difference between corrected and uncorrected measurements was evaluated for statistical significance. Results: Mean AXL was 22.95 ± 0.78 mm. Refractive error ranged from −3D to +4D. Mean difference between measured and corrected foveal diameter, slope and depth was 166.05 ± 95.37 μm (P < 0.001), 0.81° ± 0.53° (P < 0.001) and 0.05 ± 0.49 μm (P = 0.178) respectively. AXL lesser than the OCT calibrated value of 24.46 mm showed an increased foveal diameter (r = 0.961, P < 0.001) and a reduced foveal slope (r = −0.863, P < 0.001) than the corrected value. Conclusion: Lateral measurements made on OCT varied with AXL s other than the OCT calibrated value of 24.46 mm. Therefore, to estimate the actual dimensions of a retinal lesion using OCT, especially lateral dimensions, we recommend correction for the ocular magnification factor.

Epiretinal membrane removal in patients with Stargardt disease.

Epiretinal membranes (ERMs) in Stargardt disease have been known to undergo spontaneous separation in children. Results of surgical intervention in adult patients with Stargardt disease have rarely been reported. A retrospective review of results of surgical intervention for ERM causing visual impairment in two adult patients of Stargardt disease was carried out. Both patients developed ERM in one eye during their follow‑up period with the resultant drop in their preexisting visual acuity. Postsurgery, restoration of foveal contour with some improvement in visual acuity was observed in both patients. No adverse effect of surgery was noted.

Linguatula serrata in the anterior chamber of the eye.

We report a case of intraocular Linguatula in healthy young female who presented with a history of trivial trauma, dislocated lens, inflammation and secondary glaucoma. A mobile worm was seen in the anterior chamber. Pars plana lensectomy and vitrectomy was planned to remove both the cataractous lens and the parasite during which the worm disappeared from view but was later recovered from the cassette fluid. It was identified as the nymphal form of Linguatula serrata (tongue worm).

High altitude retinopathy.

High altitude retinopathy is a condition often seen among mountain climbers or among persons who reach high altitudes rapidly. In this report, we describe a case of a 57 year old healthy gentleman who presented with diminution of vision in both the eyes associated with retinal hemorrhages and the spontaneous resolution of the same.

Photodynamic monotherapy or combination treatment with intravitreal triamcinolone acetonide, bevacizumab or ranibizumab for choroidal neovascularization associated with pathological myopia.

This retrospective, interventional case series analyses treatment outcomes in eyes with choroidal neovascularization (CNV) secondary to pathological myopia, managed with photodynamic therapy, (PDT), (Group 1, N = 11), PDT and intravitreal triamcinolone acetonide (4 mg/0.1ml) (Group 2, N = 3), PDT and intravitreal anti-vascular endothelial growth factor (anti-VEGF) bevacizumab 1.25 mg/0.05 ml, ranibizumab 0.5 mg/0.05 ml and reduced-fluence PDT and intravitreal ranibizumab 0.5 mg/0.05 ml (Group 3, N=12). All the patients underwent PDT. Intravitreal injections were repeated as required. SPSS 14 software was used to evaluate the data. Wilcoxon signed ranks test was used to evaluate pre- and post-treatment vision. The Kruskal-Wallis test was used for comparison between the groups. All the groups were statistically comparable. All the eyes showed complete regression of CNV, with a minimum follow-up of six months. All groups had visual improvement; significantly in Group 3 (P = 0.003). Combination PDT with anti-VEGF agents appeared to be efficacious in eyes with myopic CNV. However, a larger study with a longer follow-up is required to validate these results.

Choroidal neovascularization associated with coloboma of the choroid: A series of three cases.

Choroidal neovascularization (CNV) is a rare complication associated with coloboma of the choroid. We describe three cases of coloboma choroid where there was loss of vision due to CNV development at the edge of the coloboma. One was managed by photodynamic therapy alone and two were managed by a combination of reduced fluence PDT and intravitreal bevacizumab. Significantly we noted that one treatment session was sufficient to achieve regression of the CNV and improvement in visual acuity.

Blow-in fracture of the orbital roof presenting as a case of non-resolving choroidal effusion.

A 34-year-old male patient was referred to us as a case of non-resolving suprachoroidal hemorrhage. History revealed decrease in right eye vision following trauma to forehead. B scan ultrasonography (USG) of the right eye showed a high-reflective structure indenting the globe. It turned out to be an inferiorly displaced fracture fragment from the orbital roof on computerized tomography (CT) scan. The choroidal elevation disappeared after open reduction of the fracture fragment and patient had good recovery of vision. USG and CT scan were helpful in the diagnosis and management of this case.

Coats' disease: An Indian perspective.

Aim: To describe the clinical features, treatment and outcome patterns in 307 eyes with Coats' disease. Materials and Methods: Retrospective chart review of patients diagnosed with Coats' disease between January 1996 and January 2006 from a single referral center in southern India. Results: Two hundred and eighty patients (307 eyes) with mean age of 15.67 years (range: Four months-80 years) were included. Decreased vision (77%), unilateral affection (90%) and male preponderance (83.4%) were chief presenting features. Anterior segment involvement was seen in 67 (21.8%) eyes. Retinal telangiectasia were seen in 302 (99%) eyes, exudation in 274 (89%) eyes and retinal detachment in 158 (51.5%) eyes. Four-quadrant disease was seen in 207 (67.2 %) eyes. Visual acuity was < 20/200 in 249 (80.9%) eyes. One hundred and nine of 176 treated eyes (61.93%) had favorable anatomical outcome; 207 of 280 eyes (74%) had an optimal structural outcome. Seventeen (5.3%) eyes were enucleated. Complications following treatment included phthisis bulbi (7%), neovascular glaucoma (5%), epiretinal membrane (4.4%) and rubeosis iridis (4.4%). Conclusion: Indian patients with Coats' disease have a high male predominance, the majority of whom present with severe visual impairment and extensive four-quadrant exudation. Unusual presentations such as pain, vitreous hemorrhage and a high incidence of anterior segment involvement are distinctive to Indian eyes.

Transpupillary thermotherapy for choroidal neovascular membrane in age related macular degeneration.

PURPOSE: To evaluate the efficacy of transpupillary thermotherapy (TTT) in choroidal neovasularisation (CNVM) secondary to age related macular degeneration (AMD). MATERIAL AND METHODS: Retrospective, non-randomized study of 28 eyes of 28 patients with subfoveal CNVM (classic, occult or mixed) secondary to AMD. RESULTS: Fifteen patients (53.57%) maintained their pre-treatment vision, 2 (7.14%) patients showed improvement of more than 2 lines and 11 (39.28%) patients showed deterioration of vision by >2 lines. Angiographic and clinical regression of CNVM was noted in 19 patients (67.8%) on an average follow up of 15.32 +/- 3.31 months. CONCLUSION: TTT leads to stabilisation of vision in 60% of treated eyes with CNVM due to AMD.

Endophthalmitis caused by Acinetobacter calcoaceticus. A profile.

PURPOSE: To report the clinical and microbiological profile of endophthalmitis caused by Acinetobacter calcoaceticus. METHODS: A retrospective study of case series of Acinetobacter calcoaceticus endophthalmitis. Outcome measures included ability to sterilise the eye, anatomical result (clear media and attached retina) and visual recovery (visual acuity > 6/60). RESULTS: Of the 20 cases studied, 10 were cases of postoperative endophthalmitis, 3 were posttraumatic, 6 were endogenous and one was bleb-related endophthalmitis. Specific features of interest observed were relative chronicity of presentation and absence of any obvious predisposing factor in endogenous endophthalmitis cases. All cases could be sterilised except one, which needed evisceration. Cases with postoperative endophthalmitis had better anatomical outcome (7/10 with attached retina and clear media) and visual outcome (4/10 regained vision > 6/18). Higher smear positivity was seen in vitreous samples (72.2%) compared to aqueous samples (37.5%). Culture positivity was higher from the vitreous cavity compared to aqueous. The organism was sensitive to ciprofloxacin in a high percentage (88.9%) of cases. CONCLUSIONS: Visual recovery in Acinetobacter calcoaceticus endophthalmitis is modest. Ciprofloxacin is the antibiotic of choice.