Indian Journal of Ophthalmology最新文献

Purpose: Posterior polar cataract (PPC), a rare congenital cataract, is characterized by subcapsular opacities in the lens affecting vision and posing surgical challenges. Genetic heterogeneity exists, though several genes are implicated in its pathogenesis. This study reports on the genetic profile of late-onset PPC cases and identifies variations specific to posterior capsular rupture (PCR) during surgery.

Methods: Detailed clinical and genetic history was documented from 100 clinically diagnosed PPC patients and 100 controls. Whole-exome sequencing (WES) was performed in 30 patients and 15 controls, and pathogenic variants were validated in 70 patients and 85 controls by Sanger sequencing.

Results: Bilateral PPC was seen in 58%, sporadic cases were 61%, while 39% had a family history. Phacoemulsification was performed on 89 patients, with 12 patients experiencing PCR. Analysis revealed novel and reported variations in the genes - CRYAB (c.328T>G; p.C110G), CRYGB - (c.331A>C; p.I111L), (c.44G>A; p.R15H), CRYBG3 - (c.1115C>T; p.S372F), CRYBA1- (c.516A>C; p.G172H), along with EPHA2 (c.1114 G>A; p.E372K), GJA3-(c.895C>A; p.L299M), and PITX3 (c.285C>T; p.I95I). CRYBG3 and GJA3 variations were common among the PCR cases.

Conclusion: Results indicate genetic heterogeneity with no mutation hotspots, and the absence of PITX3 variations in our patient cohort is interesting. The study highlights the importance of mutation screening and genotype-phenotype relationships and underscores the importance of accurate diagnosis for enhanced cataract care and management. Subsequent functional studies on the role of these genes may help in understanding normal lens development and provide insights for advanced surgical approaches.

Abstract: Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has transformed the management of retinal and choroidal vascular diseases, delivering substantial and sustained visual benefits across neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. As treatment paradigms have evolved toward chronic, often lifelong therapy with repeated injections, attention has increasingly shifted from short-term procedural safety to a broader evaluation of ocular and systemic adverse events. Among these, intraocular inflammation (IOI) has emerged as the most debated ocular safety signal, ranging from mild, self-limited sterile inflammation to rare but vision-threatening occlusive retinal vasculitis. At the same time, systemic adverse events remain biologically plausible yet uncommon in the general population. This review provides a contemporary, clinically oriented synthesis of anti-VEGF safety, emphasizing that IOI and systemic events are not uniform drug effects but reflect complex interactions among drug-specific properties, delivery factors, disease substrate, patient susceptibility, and immunogenicity. We outline a mechanistic framework distinguishing acute sterile inflammation driven by innate immune activation from delayed vasculitic phenotypes associated with adaptive immune responses and anti-drug antibodies. A structured five-pillar susceptibility model is proposed to contextualize risk modifiers, alongside phenotype-driven management and prevention strategies. Systemic safety considerations are reviewed with attention to agent-specific pharmacokinetics, high-risk patient phenotypes, and cumulative exposure. By integrating mechanistic insights with clinical phenotyping, risk stratification, and preventive strategies, this review aims to support informed, individualized decision-making. A balanced, prevention-focused approach enables clinicians to preserve the transformative benefits of anti-VEGF therapy while maintaining a high standard of long-term ocular and systemic safety.

Purpose: To evaluate the causal effects of coffee-related circulating biomarkers on myopia and to nominate plausible biological mechanisms.

Design: Leveraging a two-sample Mendelian randomization (MR) framework, this study integrated in silico network pharmacology, gene-level MR, and computational structure-based modeling to investigate the relationship.

Methods: We performed MR for 11 coffee-associated biomarkers using summary-level genome-wide association data. Predicted targets of 7-methylxanthine (7-MX) were intersected with myopia-associated genes to construct a protein-protein interaction network, identify hub genes, and conduct GO/KEGG enrichment. Gene-level MR was applied to prioritize causal candidates. The interaction between 7-MX and the key target was evaluated by molecular docking and explored by molecular dynamics (MD) simulations.

Results: Genetically predicted 7-MX showed a protective association with myopia (OR 0.77; 95% CI 0.62-0.95; P = 0.014), whereas other biomarkers were null. Overlapping genes were enriched in angiogenic and signaling pathways, including VEGF and PI3K-Akt. Among hub genes, EPHB4 was prioritized; higher genetically predicted EPHB4 expression was associated with a lower myopia risk (OR 0.90; 95% CI 0.84-0.97; P = 0.005). Docking indicated stable 7-MX binding within the EPHB4 ATP pocket, which was supported by MD trajectories.

Conclusions: Convergent genetic, network, and computational evidence suggests a protective role of 7-MX against myopia, potentially mediated by direct engagement of EPHB4 and modulation of angiogenic signaling. These findings are hypothesis-generating and warrant replication in larger genome-wide association studies and functional validation in ocular models.

Background: Over the past few decades, children from the south eastern regions of India presented with anterior chamber angle granulomas and/or subconjunctival granulomas or a retro corneal membrane with nodules at the advancing edge. These lesions were initially considered as tuberculous in origin and were referred as "conglomerate tubercles" for several years. Subsequent investigations identified the true etiology as trematode eye disease.

Purpose: To analyze the epidemiological, geographical, and clinical characteristics of pediatric patients diagnosed with ocular granuloma caused by trematode infection.

Methods: A retrospective review was conducted on medical records of pediatric patients with the diagnosis of anterior chamber granuloma or subconjunctival granuloma seen between 1997 and 2017. Data were compiled and analyzed descriptively.

Results: A total of 269 children were diagnosed with trematode granuloma. Among them, 216 were boys and 53 were girls, with the age ranging from 3 to 16 years and a mean age of 10.13 years ± (3.01) years. The majority of cases were reported from Tamil Nadu. Of 269 children, 171 received medical treatment, and 98 children underwent surgical removal of the granuloma. Visual prognosis was generally favorable, when the visual axis was spared.

Conclusion: Trematode-induced ocular granuloma is a distinct parasitic condition predominantly affecting children in specific geographical areas, especially in those living near trematode larva contaminated water bodies. Accurate identification of the etiology is essential to ensure effective management and to prevent vision loss.

Purpose: The purpose of this study is to analyze the genetic polymorphisms of specific genes- VEGF +936T/C, ACE ID, TNF 308G/A, and GSTP1-on the progression or regression of retinopathy of prematurity (ROP) in premature infants. The goal is to determine how these genetic variations influence the development of ROP and assess their potential as biomarkers for the disease.

Methods: This study is a genetic association study focused on identifying the relationship between genetic polymorphisms and ROP progression in a cohort of premature infants. The study involves genotyping 12 polymorphisms in four genes (VEGF, ACE, TNF, and GSTP1) in a sample of 100 premature infants diagnosed with ROP. A total of 100 premature infants diagnosed with ROP, without any other ophthalmologic disease, were included in the study. Twelve genetic polymorphisms in the genes VEGF (+936T/C), ACE (Insertion/ Deletion), TNF (308G/A), and GSTP1 were genotyped using standard molecular techniques. The frequencies of these polymorphisms in the ROP-positive group were compared, and their association with ROP progression or regression was evaluated using statistical tests such as Chi-square or Fisher's exact test. P values less than 0.05 were considered statistically significant.

Results: Out of the 12 polymorphisms studied, only two showed statistically significant associations with ROP progression or regression.The ACE insertion allele was associated with ROP regression and VEGF +936T/C polymorphism was found to increase the risk of ROP, with the C allele being a potential risk factor for the progression of the disease. The other polymorphisms in the TNF 308G/A and GSTP1 genes did not show a statistically significant influence on ROP progression or regression.

Conclusion: The ACE ID polymorphism appears to provide a protective effect against the development of ROP. Premature infants with the insertion allele of the ACE gene may be at lower risk for ROP progression,suggesting a potential role for ACE gene variation in influencing disease outcomes. The VEGF +936T/C polymorphism seems to increase the risk of ROP development, with the C allele possibly contributing to the progression of the disease.This study emphasizes the potential genetic factors involved in ROP, which could pave the way for personalized approaches in monitoring and managing ROP in premature infants,particularly in resource-limited settings. Further research with larger sample sizes is needed to confirm these findings and explore the underlying mechanisms of these genetic polymorphisms in ROP.

Abstract: Infectious uveitis is a significant cause of ocular morbidity and visual impairment worldwide, especially in developing regions, where it commonly leads to intraocular inflammation. However, in recent years, cases of infectious uveitis have been rising even in the developed world. Due to the considerable variation in the causes of infectious uveitis globally, this review concentrates on epidemiological aspects. Ophthalmologists should become familiar with the patterns of infectious uveitis in their area to enable early diagnosis and prevent blindness from these treatable conditions. The incidence of tuberculosis disease remains very high in low- and middle-income regions, including India. Although there is emerging consensus that tubercular uveitis (TBU) is a significant cause of uveitis in TB-endemic areas, the lack of microbiological evidence in most cases poses a major diagnostic challenge. Polymerase chain reaction (PCR) detection of the MTB genome in ocular fluids from several centers in India has shown low sensitivity and cannot definitively exclude TB infection. Conversely, nearly all intraocular viral infections can be diagnosed with high sensitivity and specificity using standard PCR techniques. The advent of mNGS as a diagnostic tool has shown great promise, with reports uncovering previously undetected pathogens. However, interpreting mNGS results remains complex. Serology continues to be a valuable method for diagnosing systemic viral infections that cause infectious uveitis, particularly syphilis and parasitic infections. Effective antimicrobial treatments have been available for many years. Recurrences, especially in viral and toxoplasmosis-related uveitis, are common, necessitating a cautious approach to prophylactic therapy.

Purpose: This study was designed to investigate the primary targets and possible mechanisms of ranitidine (Ra) against diabetic retinopathy (DR).

Methods: Single-cell sequencing technology and the SPIED3 platform were employed to characterize key genes in retinal Müller cells (RMCs) of diabetic mice and identify potential small-molecule compounds separately. The effects of small-molecule compounds on the cell viability and proliferative capacity of mouse retinal Müller cells (rMC-1) cultured in high-glucose (HG) were evaluated using the cell counting kit-8 (cck-8) and 5-ethyl-2-deoxyuridine (Edu) assay. Glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), and Fe2+ were identified as indicators of ferroptosis. Then, network pharmacology was used to predict specific targets for Ra. Western blotting was used to identify ferroptosis-related proteins, including glutathione peroxidase 4 (GPX4), cystine/glutamate transporter (xCT), serine/threonine-protein kinase AKT1, and glycogen synthase kinase-3β (GSK3β).

Results: The predicted results suggested that the potential mechanism of RMCs damage in diabetic mice is associated with ferroptosis. The cck-8 results indicated Ra played a regulatory role in HG-induced rMC-1 by enhancing cell viability. Besides, Edu results showed that Ra promoted the proliferation of rMC-1 cells. Network pharmacological analyses predicted a potential mechanism of Ra effect in HG-induced rMC-1, mainly associated with the AKT1 and GSK3β genes. Phenotypically, Ra elevated intracellular GSH levels, while reducing MDA, Fe²⁺, and ROS concentrations. Mechanistically, Ra increased xCT and GPX4 expression through the promotion of AKT1/GSK3β phosphorylation, thereby alleviating ferroptosis in HG-induced rMC-1 cells.

Conclusions: The study highlighted that the mechanism of DR is closely associated with ferroptosis and demonstrated that Ra inhibits HG-induced ferroptosis of rMC-1 cells by regulating the AKT1/GSK3β signaling pathway, thereby providing a theoretical basis for using Ra in managing DR.

Purpose: Fusion transcripts have been reported as biomarkers for several diseases; however, a fusion gene has not been reported in ophthalmic disease. To the best of our knowledge, the discovery of fusion transcript in Behcet's disease (BD), a noninfectious uveitis, is reported for the first time. We generated complete transcript data for BD subtape and discovered fusion transcripts specific to BD patients.

Methods: We sequenced total RNA from peripheral blood mononuclear cells isolated from clinically characterized BD patients and controls and generated BAM files, which served as input data for predicting fusion transcripts. We used Arriba, a computational tool for the detection of fusion transcripts. Arriba is fast and accurate for the identification of gene fusions from RNA sequencing data. It is specifically designed for high-throughput RNA-seq data, leveraging STAR-aligned chimeric BAM files to detect fusion events with high sensitivity.

Results: The Arriba tool identified a set of fusion transcripts specific to BD patients. One of the fusion transcripts was characterized and validated, which represents the read-through fusion with a product size of 421 bp consisting of a part of exon 2 of NFATC2 (112bp) and a part of exon 28 of ATP9A (309 bp); these are adjacent genes in chromosome 20.

Conclusion: This paper reports the discovery of fusion transcript in uveitis-BD subtype and is also the first report for any ophthalmic disease. Such fusion transcript is absent in controls and other subtypes of uveitis. It may be a possible biomarker for the noninfectious BD patients.