South Asian medical cohorts reveal strong founder effects and high rates of homozygosity.

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Diabetic Retinopathy and Diabetic Macular Edema in People With Early-Onset Diabetes.

This study examined the clinical profile, treatment profile, and vision outcomes of people ≤40 years of age with diabetes and diabetic macular edema (DME). Within this age-group, the prevalence of center-involving DME was 16%, with 74% of eyes showing cystoid edema, 37% showing spongiform edema, and 41% having neurosensory detachment. Longer diabetes duration (P = 0.001) and greater severity of diabetic retinopathy (P <0.001) were associated with DME prevalence. Thus, regular and more frequent follow-up, as well as early and aggressive treatment of diabetic eye disease, are required in people diagnosed early with diabetes.

Neovascular glaucoma following Nd:YAG laser capsulotomy: a rare complication in a postvitrectomised patient with diabetes.

To describe a case of acute-onset neovascular glaucoma (NVG) after a neodymium:yttrium-aluminium-garnet (Nd:YAG) capsulotomy in a diabetic vitrectomized eye of a patient with severe systemic and ocular comorbidities. A man in his 50s underwent a Nd:YAG capsulotomy for visually significant posterior capsular opacification with a previous history of vitrectomy with silicone oil in situ for diabetic retinopathy. He had systemic and ocular comorbidities implicating an advanced ischaemic status, both systemically and locally. Five days post Nd:YAG capsulotomy, extensive neovascularisation of the iris and angles was noted. Despite maximum antiglaucoma medication, an evisceration ensued due to intractable NVG. This case report highlights the importance of irreversible complications after a seemingly simple capsulotomy in eyes with advanced ocular conditions and systemic comorbidities necessitating extreme caution.

Merits of multicolor imaging for tractional retinal detachment.

PURPOSE: To compare multicolor imaging (MCI) with Optos color fundus photography (OCFP) for the evaluation of morphology and extent of preretinal membranes in diabetic tractional retinal detachments (TRD). METHODS: In this retrospective study, 30 eyes with diabetic TRDs were imaged using the MCI feature of the Heidelberg Spectralis Spectral-domain optical coherence tomography (SD-OCT) and color photo using the Optos Daytona ultra-widefield fundus camera. Two investigators independently graded and determined the agreeability between the two modalities with respect to the extent of the TRD and preretinal membranes on the SD-OCT B-scan images. RESULTS: The MCI provided better visualization of the attachments and traction points of the posterior hyaloid face and preretinal membranes and is comparable to the SD-OCT B-scan images. The inter-rater agreeability rates for OCFP had a Kappa (κ) value of 0.37, while the MCI had a κ value of 0.46. When comparing between images of different wavelengths, grading using infrared reflectance (IR) had a poor agreement (-0.04 ± 0.04) while green reflectance (GR) (0.46 ± 0.32) and blue reflectance (BR) (0.53 ± 0.19) had a moderate agreement. The composite MCI and GR images also had comparatively higher intraclass coefficient when compared to the OCFP (0.25 [-0.09-0.55]) and IR (-0.03 [-0.39-0.34]) images. CONCLUSION: MCI is more sensitive for determining the extent of TRDs and for the detection of secondary membranes when compared to OCFP, thus, aiding in better surgical planning.

Bilateral Sequential Acute Macular Neuroretinopathy in an Asian Indian Female with ß Thalassemia Trait following (Corona Virus Disease) COVID-19 Vaccination and Probable Recent COVID Infection - Multimodal Imaging Study.

INTRODUCTION: Corona virus disease (COVID-19) has been associated with a variety of ophthalmic manifestations including acute macular neuroretinopathy and paracentral middle maculopathy. Posterior segment manifestations after post COVID-19 vaccinations have been reported. CASE REPORT: A 25- year-old Asian Indian female developed sequential bilateral AMN following a single dose of COVISHIELD™ vaccine. On investigations she was found to have a ß thalassemia trait. Presentation started unilaterally and progressed to the other eye after a month. On clinical examination, the fundus was apparently normal in both eyes. Significant changes suggestive of AMN were seen on multimodal imaging of the posterior segment of the respective eye at the time of involvement which resolved spontaneously in due course. CONCLUSION: We report a temporal association of COVID-19 vaccination and AMN.

Correlation of Volume of Macular Edema with Retinal Tomography Features in Diabetic Retinopathy Eyes.

Optical coherence tomography (OCT) enables the detection of macular edema, a significant pathological outcome of diabetic retinopathy (DR). The aim of the study was to correlate edema volume with the severity of diabetic retinopathy and response to treatment with intravitreal injections (compared to baseline). Diabetic retinopathy (DR; n = 181) eyes were imaged with OCT (Heidelberg Engineering, Germany). They were grouped as responders (a decrease in thickness after intravitreal injection of Bevacizumab), non-responders (persistent edema or reduced decrease in thickness), recurrent (recurrence of edema after injection), and treatment naïve (no change in edema at follow-up without any injection). The post-treatment imaging of eyes was included for all groups, except for the treatment naïve group. All eyes underwent a 9 × 6 mm raster scan to measure the edema volume (EV). Central foveal thickness (CFT), central foveal volume (CFV), and total retinal volume (TRV) were obtained from the early treatment diabetic retinopathy study (ETDRS) map. The median EV increased with DR severity, with PDR having the greatest EV (4.01 mm3). This correlated positively with TRV (p < 0.001). Median CFV and CFT were the greatest in severe NPDR. Median EV was the greatest in the recurrent eyes (4.675 mm3) and lowest (1.6 mm3) in the treatment naïve group. Responders and non-responders groups had median values of 3.65 and 3.93 mm3, respectively. This trend was not observed with CFV, CFT, and TRV. A linear regression yielded threshold values of CFV (~0.3 mm3), CFT (~386 µm), and TRV (~9.06 mm3), above which EV may be detected by the current scanner. In this study, EV provided a better distinction between the response groups when compared to retinal tomography parameters. The EV increased with disease severity. Thus, EV can be a more precise parameter to identify subclinical edema and aid in better treatment planning.

Optical coherence tomography angiography (OCTA) of retinal vasculature in patients with post fever retinitis: a qualitative and quantitative analysis.

Post fever retinitis is a heterogenous entity that is seen 2-4 weeks after a systemic febrile illness in an immunocompetent individual. It may occur following bacterial, viruses, or protozoal infection. Optical coherence angiography (OCTA) is a newer non-invasive modality that is an alternative to fundus fluorescein angiography to image the retinal microvasculature. We hereby describe the vascular changes during the acute phase of post fever retinitis on OCTA. Imaging on OCTA was done for all patients with post fever retinitis at presentation with 3 × 3 mm and 8 × 8 mm scans centred on the macula and corresponding enface optical coherence tomography (OCT) scans obtained. A qualitative and quantitative analysis was done for all images. 46 eyes of 33 patients were included in the study. Salient features noted were changes in the superficial (SCP) and deep capillary plexus (DCP) with capillary rarefaction and irregularity of larger vessels in the SCP. The DCP had more capillary rarefaction when compared to the SCP. The foveal avascular zone (FAZ) was altered with an irregular perifoveal network. Our series of post fever retinitis describes the salient vascular features on OCTA. Although the presumed aetiology was different in all our patients, they developed similar changes on OCTA. While OCTA is not useful if there is gross macular oedema, the altered FAZ can be indicative of macular ischemia.

Intracystic hyperreflective material in centre-involving diabetic macular oedema.

PURPOSE: To report evolution and predictive value of intracystic hyperreflective material (ICHRM) on optical coherence tomography (OCT) in centre-involving diabetic macular oedema (CI-DME). METHODS: Demographic and OCT features of patients with treatment-naïve CI-DME were analysed retrospectively. OCT parameters noted were macular oedema type, ICHRM presence, presence of hyperreflective spots, disorganised inner retinal layers and outer retinal layers integrity. Eyes were grouped into group 1 CI-DME without ICHRM and group 2 CI-DME with ICHRM. Univariate and multivariate linear regression analyses were done to study the correlation between various OCT features and final vision. RESULTS: In this study, 62 eyes of 50 patients were included in group 1 and 61 eyes of 51 patients in group 2. Mean presenting logMAR vision in groups 1 and 2 was 0.374 ± 0.346 and 0.523 ± 0.369 respectively. Poor final visual acuity was noted in CI-DME with ICHRM group (p = 0.015). On linear regression analysis, 3 OCT features, namely, ICHRM presence (p = 0.034), inner segment-outer segment layer disruption (p = 0.001) and ellipsoid zone defects (p = 0.003), were associated with poor final vision. More intravitreal anti-VEGF (2.98 vs 0.629) and steroid (1.51 vs 0.242) injections were required for macular oedema resolution in ICHRM group. CONCLUSION: This study is the first to assess the ICHRM on OCT as predictor for treatment outcome in DME eyes. We described its evolution during the DME management and its plausible influence on intravitreal therapy. We believe that this finding has the potential to become a novel biomarker for predicting the visual outcome in DME.

ßA1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity.

ßA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as ßA3 and ßA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that ßA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of ßA3/A1-crystallin in metabolism of retinal astrocytes. We found that ßA1-crystallin acts as an uncompetitive inhibitor of PTP1B, but ßA3-crystallin does not. Loss of ßA1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR/cas9 gene-edited ßA1-knockdown (KD) mice, but not in ßA3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified ßA1-crystallin as a regulator of PTP1B; loss of this regulation may be a new mechanism by which astrocytes contribute to DR. Interestingly, proliferative diabetic retinopathy (PDR) patients showed reduced ßA1-crystallin and higher levels of PTP1B in the vitreous humor.

Impact of sub-foveal choroidal thickness on clinical features and long-term clinical outcomes in polypoidal choroidal vasculopathy.

PURPOSE: To study the clinical features and long-term clinical outcomes in polypoidal choroidal vasculopathy (PCV) in eyes with different sub-foveal choroidal thickness (SFCT). METHODS: In this retrospective, observational comparative study, treatment-naïve eyes diagnosed with PCV using the 'EVEREST-2' study criteria were included. The eyes were divided into three groups of thin, medium and thick choroids, based on the SFCT data of total study eyes. Demographic, clinical, imaging features and treatment outcomes between the 3 groups were compared. RESULTS: Sixty-three eyes in 63 patients were included. Right eye was involved in 39 (61%) cases and left eye in 24 (39%) cases. Mean age was 68.3 ± 6.82 years (range 54-85 years). Mean SFCT was 274 µm (median = 269 µm), and one standard deviation was 79.2 µm. Totally, 11, 43 and 9 eyes were included in the thin, medium and thick choroid groups, respectively. The mean SFCT was 161 ± 24.1 µm, 275 ± 39.6 µm and 412 ± 26.2 µm in the thin, medium and thick choroid groups, respectively. There was no statistically significant difference in the clinical and imaging features and treatment outcomes between eyes with thin, medium and thick SFCT. CONCLUSION: Eyes with PCV can have a choroid of varying thicknesses. Clinical, imaging and treatment responses were similar between the three sub-foveal choroidal thickness groups in this study. In future, more studies are required to evaluate the role of the choroidal thickness and its relationship to treatment in PCV.

Foveal cyst: Unknown etiology and unexplained response to treatment.

BACKGROUND: Foveal cysts have been associated with vitreous traction due to a taut posterior hyaloid. These eyes may progress to become a full-thickness macular hole, remain stable, or resolve after a posterior vitreous detachment. A foveal cyst in an eye with a complete posterior vitreous detachment and no other obvious pathology is unusual. CASE PRESENTATION: A 21-year-old male presented with blurred vision in the left eye of 1-month duration. On examination his left-eye vision was 20/60, and anterior segment examination was normal. Fundus examination showed internal limiting membrane folds with a suspected lamellar macular hole. A spectral domain optical coherence scan showed a thin dome-like cyst in the sub foveal region involving the outer retinal layer with a detached posterior hyaloid face. A trial of intravitreal dexamethasone implant was given, following which there was improvement in vision and resolution of the foveal cyst. At the third-month follow-up, the patient presented with a stellate pattern of hyporeflectivity in the macular area both on spectral domain optical coherence scan and multicolor imaging with no change in visual acuity. CONCLUSION: The presence of a foveal cyst in a young male without any risk factors is peculiar, and the rapid response to intravitreal dexamethasone implant raises questions about the pathogenesis. The stellate pattern of hyporeflectivity on spectral domain optical coherence scan imaging with an intraretinal "filling defect"-like picture on fluorescein angiography suggests a possible ongoing ischemic pathology.

Solar retinopathy-correlation between adaptive optics and spectral domain optical coherence tomography with visual acuity.

BACKGROUND: To study the characteristics of photoreceptors on adaptive optics (AO) in patients of solar retinopathy and its correlation to changes in spectral domain optical coherence tomography (SDOCT) and visual acuity. METHODS AND MATERIAL: This is a cross-sectional observational study of six eyes of five patients with clinically diagnosed solar retinopathy. Five age-matched controls were included for comparison. A flood-illuminated adaptive optics retinal camera (AO; rtx1, Imagine Eyes, Orsay, France) was used to image the photoreceptors and a spectral domain optical coherence tomography (SDOCT; Spectralis™ Heidelberg Engineering, Germany) was used to study the retinal layers in these patients. The corrected distance visual acuity (CDVA) was assessed using Snellen's chart. RESULTS: Defects on the SDOCT were smaller (0.25 to 0.75°) at the fovea compared with AO (more than 1°). The cone mosaic was preserved beyond 1°. The cone count from the foveal center at 0.75, 1, 2, and 3° was decreased in all patients of solar retinopathy (mean value 5352) compared with age-matched controls (mean value 15693). A corresponding increase in spacing (mean value 19.13) compared with controls (mean value 9.34) was also observed. The CDVA ranged from 20/30 to 20/80. There was no statistically significant relationship between cone density, at any of the eccentricities measured, with CDVA or OCT defect (p > 0.05, for all). CONCLUSIONS: Adaptive optics is a sensitive and accurate tool to analyze photoreceptor damage in solar maculopathy. It can be used as an adjunct for better understanding of the pathology and to observe or predict changes in these patients.

Macular tractional retinal detachment: A rare complication of blunt trauma.

Traumatic rhegmatogenous retinal detachment after blunt ocular trauma is a known entity. A tractional macular detachment occurring posttrauma without a retinal break is a unique presentation. A 25-year-old gentleman after blunt ocular trauma with a ball presented a week later with a vision of 20/800, large subretinal bleed and resolving vitreous hemorrhage in the right eye. Three weeks later, an extensive glial proliferation at the posterior pole and macular tractional retinal detachment was noted with the worsening of visual acuity. A vitrectomy, membrane peeling, and silicone oil tamponade with a subsequent silicone oil removal at 6 months stabilized the macula, and vision improved to 20/120. A tractional macular detachment post blunt trauma is rare albeit an interesting occurrence, which can be effectively managed with vitrectomy and allied procedures.