Atypical Refractory Macular Edema: Are We Missing Something?

Purpose: To report a case of bilateral refractory macular edema in a diabetic macular edema in a diabetic with an underlying systemic illness. Case Report: A 65-year-old male presented with the symptom of blurred vision in both eyes for three months. He was a known diabetic patient and was also hypertensive for the last 10 years. The corrected distance visual acuity was 20/120 in the right eye and 20/80 in the left eye. Fundus examination revealed multiple deep and superficial retinal hemorrhages, cystoid macular edema, and serous macular detachment in both eyes. With a diagnosis of diabetic macular edema in both eyes, the patient was treated with multiple intravitreal injections of anti-vascular endothelial growth factor and steroids. Since he did not show a favorable response, the patient was further investigated and diagnosed with multiple myeloma. After undergoing treatment for the same, the patient was seen a year later and noted to have significant resolution of the macular edema and subretinal fluid in both eyes. Conclusion: In patients who suffer with atypical macular edema that is resistant to conventional treatment, it is imperative to look for underlying systemic illnesses such as immunoproliferative disorders and hematologic malignancies

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

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 mm(3)). 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 mm(3)) and lowest (1.6 mm(3)) in the treatment naïve group. Responders and non-responders groups had median values of 3.65 and 3.93 mm(3), respectively. This trend was not observed with CFV, CFT, and TRV. A linear regression yielded threshold values of CFV (~0.3 mm(3)), CFT (~386 µm), and TRV (~9.06 mm(3)), 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

South Asian Patient Population Genetics Reveal Strong Founder Effects and High Rates of Homozygosity – New Resources for Precision Medicine

AbstractPopulation-scale genetic studies can identify drug targets and allow disease risk to be predicted with resulting benefit for management of individual health risks and system-wide allocation of health care delivery resources. Although population-scale projects are underway in many parts of the world, genetic variation between population groups means that additional projects are warranted. South Asia has a population whose genetics is the least characterized of any of the world’s major populations. Here we describe GenomeAsia studies that characterize population structure in South Asia and that create tools for economical and accurate genotyping at population-scale. Prior work on population structure characterized isolated population groups, the relevance of which to large-scale studies of disease genetics is unclear. For our studies we used whole genome sequence information from 4,807 individuals recruited in the health care delivery systems of Pakistan, India and Bangladesh to ensure relevance to population-scale studies of disease genetics. We combined this with WGS data from 927 individuals from isolated South Asian population groups, and developed a custom SNP array (called SARGAM) that is optimized for future human genetic studies in South Asia. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that approach 100 times that seen in outbred populations. We describe founder effects that increase the power to associate functional variants with disease processes and that make South Asia a uniquely powerful place for population-scale genetic studies

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

Acknowledgements: We thank Abhijit Chowdhury, Anamitra Barik, Rajesh Kumar Rai, the Birbhum Health and Demographic Surveillance System, the Parkinson Research Alliance of India (PRAI), Syed Qasim Mehdi (deceased), and Partha Majumder for providing samples and sample metadata. J.D.W., J.R., and D.S. were supported in part by NIH grant R01 HG010689. A.V.K. was supported in part by NIH grants 1K08HG010155 and 1U01HG011719. Sequence data collection was supported by NIH grant 5UM1HG008895 to S.K. and by Genentech Research. We are grateful to all of our colleagues for their support and discussions throughout the course of this work and to all of the participants in this study.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

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

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

Abstract 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

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