No abstract

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina occurring principally in new born preterm infants. It is an avoidable cause of childhood blindness. With the increase in the survival of preterm babies, ROP has become the leading cause of preventable childhood blindness throughout the world. A simple screening test done within a few weeks after birth by an ophthalmologist can avoid this preventable blindness. Although screening guidelines and protocols are strictly followed in the developed nations, it lacks in developing economies like India and China, which have the highest number of preterm deliveries in the world. The burden of this blindness in these countries is set to increase tremendously in the future, if corrective steps are not taken immediately. ROP first emerged in 1940s and 1950s, when it was called retrolental fibroplasia. Several epidemics of this disease were and are still occurring in different regions of the world and since then a lot of research has been done on this disease. However, till date very few comprehensive review articles covering all the aspects of ROP are published. This review highlights the past, present and future strategies in managing this disease. It would help the pediatricians to update their current knowledge on ROP.

Background: Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis. Methods: Adults with non-high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks). The primary end point was placebo-adjusted percentage change from baseline in non-HDL-C at 24 weeks. Secondary end points included placebo-adjusted percentage changes from baseline in triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and ANGPTL3. Results: Two hundred eighty-six subjects were randomized: 44 to placebo and 242 to vupanorsen. The median age was 64 (interquartile range, 58-69) years, 44% were female, the median non-HDL-C was 132.4 (interquartile range, 118.0-154.1) mg/dL, and the median triglycerides were 216.2 (interquartile range, 181.4-270.4) mg/dL. Vupanorsen resulted in significant decreases from baseline over placebo in non-HDL-C ranging from 22.0% in the 60 mg every 2 weeks arm to 27.7% in the 80 mg every 2 weeks arm (all P <0.001 for all doses). There were dose-dependent reductions in triglycerides that ranged from 41.3% to 56.8% (all P <0.001). The effects on LDL-C and ApoB were more modest (7.9%-16.0% and 6.0%-15.1%, respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance. ANGPTL3 levels were decreased in a dose-dependent manner by 69.9% to 95.2% (all P <0.001). There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen. Injection site reactions and >3x elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively), and there was a dose-dependent increase in hepatic fat fraction (up to 76%). Conclusions: Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non-HDL-C and additional lipid parameters. Injection site reactions and liver enzyme elevations were more frequent at higher doses, and there was a dose-dependent increase in hepatic f at fraction.

Features of severe capillary bed loss in the vascularised retina were seen in our cases. Oxygen could be a precipitating factor in causing this retinopathy of prematurity in large babies.

More bigger and mature babies are developing severe ROP in South India than in industrialized countries. The characteristics of babies affected are similar to those seen during the first epidemic of ROP which occurred during the 1950s in Europe and North America. Guidelines on oxygenation and screening policies should be jointly developed by pediatricians and ophthalmologists to end this epidemic of avoidable blindness in India.