Cause Of Vision Loss Research Articles

Artificial Intelligence Applications in Diabetic Retinopathy: What We Have Now and What to Expect in the Future.

Diabetic retinopathy (DR) is a major complication of diabetes mellitus and is a leading cause of vision loss globally. A prompt and accurate diagnosis is crucial for ensuring favorable visual outcomes, highlighting the need for increased access to medical care. The recent remarkable advancements in artificial intelligence (AI) have raised high expectations for its role in disease diagnosis and prognosis prediction across various medical fields. In addition to achieving high precision comparable to that of ophthalmologists, AI-based diagnosis of DR has the potential to improve medical accessibility, especially through telemedicine. In this review paper, we aim to examine the current role of AI in the diagnosis of DR and explore future directions.

Enhanced Ocular Delivery of Beva via Ultra-Small Polymeric Micelles for Noninvasive Anti-VEGF Therapy.

Pathological ocular neovascularization resulting from retinal ischemia constitutes a major cause of vision loss. Current anti-VEGF therapies rely on burdensome intravitreal injections of Bevacizumab (Beva). Herein ultrasmall polymeric micelles encapsulating Beva (P@Beva) are developed for noninvasive topical delivery to posterior eye tissues. Beva is efficiently loaded into 11nm micelles fabricated via self-assembly of hyperbranched amphiphilic copolymers. The neutral, brush-like micelles demonstrate excellent drug encapsulation and colloidal stability. In vitro, P@Beva enhances intracellular delivery of Beva in ocular cells versus free drug. Ex vivo corneal and conjunctival-sclera-choroidal tissues transport after eye drops are improved 23-fold and 7.9-fold, respectively. Anti-angiogenic bioactivity is retained with P@Beva eliciting greater inhibition of endothelial tube formation and choroid sprouting over Beva alone. Remarkably, in an oxygen-induced retinopathy (OIR) model, topical P@Beva matching efficacy of intravitreal Beva injection, is the clinical standard. Comprehensive biocompatibility verifies safety. Overall, this pioneering protein delivery platform holds promise to shift paradigms from invasive intravitreal injections toward simplified, noninvasive administration of biotherapeutics targeting posterior eye diseases.

Causes of Vision Loss Associated with Dengue Fever in Bihar, India - A Case Series.

The incidence and geographic distribution of dengue has increased dramatically in recent years across various parts of the world. Previously, ocular findings in dengue fever were considered rare. We report a spectrum of ocular manifestations presenting with vision loss in the last dengue epidemic in an eastern state of India. This is a retrospective interventional case series of patients with vision loss who were diagnosed with dengue eye disease in the 2022 epidemic. Systemic and ophthalmic examinations were completed on all patients and were analyzed. Fifteen patients had presented with vision loss. The mean age was 41.7 ± 10.8 years, and patients were mostly males. Three patients presented with panophthalmitis and orbital cellulitis. Eight patients were diagnosed with optic neuropathy. Four patients had macular involvement: macular chorioretinitis, macular subhyaloid hemorrhage, and macular hemorrhages in two patients. All patients with optic neuropathy gave a history of mild fever and had remained undiagnosed. The rest had been diagnosed with the more severe dengue hemorrhagic fever. Vision recovered partially or fully in patients with optic neuropathy and macular disease. No eye could be salvaged in any panophthalmitis patients. Thrombocytopenia (platelet count <100 × 109 per liter of blood) was significantly associated with ocular hemorrhage and panophthalmitis, but thrombocytopenia was not significantly seen in optic neuropathy. We conclude that optic neuropathy may be an underreported cause of vision loss in dengue fever. An eye examination is advocated in all patients with dengue eye disease.

Advancements in Imaging and Therapeutic Options for Dry Age-Related Macular Degeneration and Geographic Atrophy.

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, with dry AMD (d-AMD) leading to geographic atrophy (GA) and significant visual impairment. Multimodal imaging plays a crucial role in d-AMD diagnosis and management, allowing for detailed classification of patient phenotypes and aiding in treatment planning and prognosis determination. Treatment approaches for d-AMD have recently witnessed profound change with the development of specific drugs targeting the complement cascade, with the first anticomplement agents recently approved for GA treatment. Additionally, emerging strategies such as gene therapy and laser treatments may offer potential benefits, though further research is needed to fully establish their efficacy. However, the lack of effective therapies capable of restoring damaged retinal cells remains a major challenge. In the future, genetic treatments aimed at preventing the progression of d-AMD may emerge as a powerful approach. Currently, however, their development is still in the early stages.

Challenges and opportunities of developing small-molecule therapies for age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of vision loss in senior adults. The disease can be categorized into two types: wet AMD and dry AMD. Wet AMD, also known as exudative or neovascular AMD, is less common but more severe than dry AMD and is responsible for 90% of the visual impairment caused by AMD and affects 20 million people worldwide. Current treatment options mainly involve biologics that inhibit the vascular endothelial growth factor or complement pathways. However, these treatments have limitations such as high cost, injection-related risks, and limited efficacy. Therefore, new therapeutic targets and strategies have been explored to improve the outcomes of patients with AMD. A promising approach is the use of small-molecule drugs that modulate different factors involved in AMD pathogenesis, such as tyrosine kinases and integrins. Small-molecule drugs offer advantages, such as oral administration, low cost, good penetration, and increased specificity for the treatment of wet and dry AMD. This review summarizes the current status and prospects of small-molecule drugs for the treatment of wet AMD. These advances are expected to support the development of effective and targeted treatments for patients with AMD.

Cystoid Macular Edema (CME)

Cystoid Macular Edema (CME) is one of the most common causes of vision loss in postoperative cataract patients. CME occurs due to fluid accumulation in the subretinal space due to increased permeability of perifoveal capillaries and intra-ocular vascular instability which is a consequence of disruption or damage to the blood barrier layer of the retina. This condition occurs in 20% after cataract surgery, 1% of whom have clinical symptoms in the form of a significant decrease in vision. Provision of medicamentose therapy after surgery can optimize sharp vision and treat CME. The patient who entered from the poly RSUDZA was an 82-year-old man with complaints of blurred left eye and winding vision since the patient sneezed 1 week after cataract surgery. Patients are given artificial tears eye drops and topical NSAIDs as well as education for drug adherence. The response to therapy is quite good where there is improvement in vision and on OCT examination there is a reduction in macular thickness.

Clinical characteristics and associated factors of diabetic retinopathy in Sudanese patients

Background: Diabetic retinopathy (DR) is a leading cause of vision loss and preventable blindness, particularly in middle- and high-income countries.Aim: This study aimed to assess the characteristics and associated factors of DR in Sudanese patients with type 2 diabetes mellitus (DM).Setting: A cross-sectional hospital-based study included 119 patients with type 2 DM was conducted at EL-Walidain Eye Hospital, Khartoum, Sudan, from February 2021 to May 2021.Methods: A non-mydriatic digital fundus camera was used for fundus photography, and Scottish Diabetic Retinopathy Grading Scheme was used for the final classification of DR.Results: Females comprised 53.8% of patients, mean age of 58.8 ± 8.5 years. Uncontrolled DM was found in 37.8% with a mean duration of 10.5 ± 4.8 years. Myopia was the most common refractive error found in 57.8% of the uncontrolled group, followed by emmetropia (17.8%). Whereas in the controlled group, 47.3% were hyperopic and 39.2% were myopic. Maculopathy grade M1 was found to be 37.8% in the uncontrolled group and 18.9% in the controlled group, with no significant difference (p = 0.361). Conversely, the difference in retinopathy between the two groups was statistically significant (p = 0.043).Conclusion: Decreased vision and increased retinopathy were associated with an increase in patients’ age. More widespread diabetes awareness and screening programmes to improve diabetes management and control in Sudan and other developing countries.Contribution: This study observed maculopathy grade M1 and myopia were more common in uncontrolled DM, and vision function was inversely correlated with age (p 0.05).

Efficacy of Ranibizumab in the Treatment of Macular Edema Secondary to Retinal Vein Occlusion

Objective: Branch retinal vein occlusion (BRVO), a major cause of vision loss, is a significant ocular health concern. The frequency of macular edema due to BRVO is a critical area of study because of its profound impact on patient quality of life. This study investigated the effectiveness of ranibizumab, a monoclonal antibody fragment and VEGF inhibitor, in the treatment of macular edema in patients with BRVO. Material and Methods: Twelve patients (12 eyes) diagnosed with macular edema secondary to BRVO were included in this study. Patients were selected on the basis of specific visual acuity and macular thickness criteria, excluding those with other ocular conditions or systemic diseases. 0.05 milligrams of ranibizumab was administered intravitreally to each patient. Ophthalmological assessments were conducted both before and after the injection and at 1, 2, 3, and 6-month intervals following medication administration. Results: The average follow-up duration was 5.5±1.16 months (ranging from 2 to 6 months). The average central macular thickness before the injection was 542.66±191.44 µm, which decreased to 320.50±101.44 µm at 1-month post-injection, 283.66±125.01 µm at 2 months, 299.40±91.52 µm at 3 months, and 260.90±144.97 µm at 6 months. The reduction in central macular thickness at all time points was statistically significant (p&lt;0.01). The mean Early Treatment Diabetic Retinopathy Study (ETDRS) letter score was 55.83±23.91 before the injection and improved to 71.25±17.07 at 1 month, 74.33±15.97 at 2 months, 66.7±21.60 at 3 months, and 71.2±17.38 at 6 months post-injection. The increase in visual acuity at 1, 2, 3, and 6 months after the injection was statistically significant compared to the pre-injection ETDRS letter scores (p&lt;0.05). An improvement of two or more lines in visual acuity was observed in 58.3% of cases at 1 month, 58.3% at 2 months, 50% at 3 months, and 80% at 6 months (one line equivalent to five letters). Conclusion: Intravitreal Ranibizumab injections have been found to be effective and reliable in the early stages of treating macular edema due to branch retinal vein occlusion.

Effects of Nox4 upregulation on PECAM-1 expression in a mouse model of diabetic retinopathy.

Diabetic Retinopathy (DR) is the leading cause of vision loss in working-age adults. The hallmark features of DR include vascular leakage, capillary loss, retinal ischemia, and aberrant neovascularization. Although the pathophysiology is not fully understood, accumulating evidence supports elevated reactive oxygen species associated with increased activity of NADPH oxidase 4 (Nox4) as major drivers of disease progression. Previously, we have shown that Nox4 upregulation in retinal endothelial cells by diabetes leads to increased vascular leakage by an unknown mechanism. Platelet endothelial cell adhesion molecule 1 (PECAM-1) is a cell surface molecule that is highly expressed in endothelial cells and regulates endothelial barrier function. In the present study, using endothelial cell-specific human Nox4 transgenic (TG) mice and endothelial cell-specific Nox4 conditional knockout (cKO) mice, we investigated the impact of Nox4 upregulation on PECAM-1 expression in mouse retinas and brain microvascular endothelial cells (BMECs). Additionally, cultured human retinal endothelial cells (HRECs) transduced with adenovirus overexpressing human Nox4 were used in the study. We found that overexpression of Nox4 increases PECAM-1 mRNA but has no effect on its protein expression in the mouse retina, BMECs, or HRECs. Furthermore, PECAM-1 mRNA and protein expression was unchanged in BMECs isolated from cKO mice compared to wild type (WT) mice with or without 2 months of diabetes. Together, these findings do not support a significant role of Nox4 in the regulation of PECAM-1 expression in the diabetic retina and endothelial cells. Further studies are warranted to elucidate the mechanism of Nox4-induced vascular leakage by investigating other intercellular junctional proteins in endothelial cells and their implications in the pathophysiology of diabetic retinopathy.

Ultrasmall copper nanodots eye drops for microenvironment regulation of diabetes retinopathy by relieving hypoxia and inhibiting HIF-1α/VEGF signaling pathway

Diabetic retinopathy (DR) is the main cause of visual loss among blinding diseases. The pathological microenvironment, characterized by hypoxia, reactive oxygen species (ROS) accumulation and oxidative stress, is critical to the onset and progression of DR. In this study, an ultrasmall (4–6 nm) copper nanodots was developed as nanozyme (Cu NZs) and dispersed in 2 % Methocel to formulate Cu NZs eye drops to relieve hypoxia and scavenge excrescent ROS for the effective treatment of DR. Due to its smaller size and higher specific surface area, Cu NZs exposes more active sites and can guarantee excellent antioxidant activity. The results of in vitro studies indicated that Cu NZs had biocompatible and protective effects on human retinal microvascular endothelial cells (HRMECs), alleviating hypoxia in HRMECs, reducing oxidative stress, and inhibiting hypoxia-inducing factor-1α (HIF-1α)/ vascular endotheliogenesis factor (VEGF) signaling pathway. In an animal model of streptozotocin (STZ)-induced DR, Cu NZs eye drops have been shown to greatly relieve the hypoxic microenvironment of DR and inhibit the expression of HIF-1α and VEGF. CuNZs eye drops reduced inflammatory factors in the DR microenvironment, significantly reducing the progression of neovascularization and vascular leakage. And the nano-enzyme eye drops have no toxic side effects on the eyes and important organs of the whole body. This treatment mode based on the nano enzyme cascade reaction from comprehensive microenvironment regulation (hypoxia relief, free radical scavenging, anti-inflammatory), has excellent ability to treat DR. Although the nanoparticle is effective against DR in the short term at the cellular and animal levels, the long-term efficacy and safety remains to be evaluated.

Genetic Association between Lipid-Regulating Drug Targets and Diabetic Retinopathy: A Drug Target Mendelian Randomization Study.

Diabetic retinopathy (DR) is a diabetic microvascular complication and a leading cause of vision loss. However, there is a lack of effective strategies to reduce the risk of DR currently. The present study is aimed at assessing the causal effect of lipid-regulating targets on DR risk using a two-sample Mendelian randomization (MR) study. Genetic variants within or near drug target genes, including eight lipid-regulating targets for LDL-C (HMGCR, PCSK9, and NPC1L1), HDL-C (CETP, SCARB1, and PPARG), and TG (PPARA and LPL), were selected as exposures. The exposure data were obtained from the IEU OpenGWAS project. The outcome dataset related to DR was obtained from the FinnGen research project. Inverse-variance-weighted MR (IVW-MR) was used to calculate the effect estimates by each target. Sensitivity analyses were performed to verify the robustness of the results. There was suggestive evidence that PCSK9-mediated LDL-C levels were positively associated with DR, with OR (95% CI) of 1.34 (1.02-1.77). No significant association was found between the expression of HMGCR- and NPC1L1-mediated LDL-C levels; CETP-, SCARB1-, and PPARG-mediated HDL-C levels; PPARA- and LPL-mediated TG levels; and DR risk. This is the first study to reveal a genetically causal relationship between lipid-regulating drug targets and DR risk. PCSK9-mediated LDL-C levels maybe positively associated with DR risk at the genetic level. This study provides suggestive evidence that PCSK9 inhibition may reduce the risk of DR.

Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.

Observation on the changes of visual field and optic nerve fiber layer thickness in patients with early diabetic retinopathy

BackgroundDiabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) and is a leading cause of vision loss. Early detection of DR-related neurodegenerative changes is crucial for effective management and prevention of vision loss in diabetic patients. MethodsIn this study, we employed spectral-domain polarization-sensitive optical coherence tomography (SD PS-OCT) to assess retinal nerve fiber layer (RNFL) changes in 120 eyes from 60 types 1 DM patients without clinical DR and 60 age-matched healthy controls. Visual field testing was performed to evaluate mean sensitivity (MS) and mean defect (MD) as indicators of visual function. ResultsSD PS-OCT measurements revealed significant reductions in RNFL birefringence, retardation, and thickness in type 1 DM patients compared to healthy controls. Visual field testing showed decreased MS and increased MD in DM patients, indicating functional impairment correlated with RNFL alterations. ConclusionOur findings demonstrate early neurodegenerative changes in the RNFL of type 1 DM patients without clinical DR, highlighting the potential of SD PS-OCT as a sensitive tool for early detection of subclinical DR-related neurodegeneration. These results underscore the importance of regular ophthalmic screenings in diabetic patients to enable timely intervention and prevent vision-threatening complications.

Deciphering novel TCF4-driven mechanisms underlying a common triplet repeat expansion-mediated disease.

Fuchs endothelial corneal dystrophy (FECD) is an age-related cause of vision loss, and the most common repeat expansion-mediated disease in humans characterised to date. Up to 80% of European FECD cases have been attributed to expansion of a non-coding CTG repeat element (termed CTG18.1) located within the ubiquitously expressed transcription factor encoding gene, TCF4. The non-coding nature of the repeat and the transcriptomic complexity of TCF4 have made it extremely challenging to experimentally decipher the molecular mechanisms underlying this disease. Here we comprehensively describe CTG18.1 expansion-driven molecular components of disease within primary patient-derived corneal endothelial cells (CECs), generated from a large cohort of individuals with CTG18.1-expanded (Exp+) and CTG 18.1-independent (Exp-) FECD. We employ long-read, short-read, and spatial transcriptomic techniques to interrogate expansion-specific transcriptomic biomarkers. Interrogation of long-read sequencing and alternative splicing analysis of short-read transcriptomic data together reveals the global extent of altered splicing occurring within Exp+ FECD, and unique transcripts associated with CTG18.1-expansions. Similarly, differential gene expression analysis highlights the total transcriptomic consequences of Exp+ FECD within CECs. Furthermore, differential exon usage, pathway enrichment and spatial transcriptomics reveal TCF4 isoform ratio skewing solely in Exp+ FECD with potential downstream functional consequences. Lastly, exome data from 134 Exp- FECD cases identified rare (minor allele frequency <0.005) and potentially deleterious (CADD>15) TCF4 variants in 7/134 FECD Exp- cases, suggesting that TCF4 variants independent of CTG18.1 may increase FECD risk. In summary, our study supports the hypothesis that at least two distinct pathogenic mechanisms, RNA toxicity and TCF4 isoform-specific dysregulation, both underpin the pathophysiology of FECD. We anticipate these data will inform and guide the development of translational interventions for this common triplet-repeat mediated disease.

Two case reports of a novel missense mutation in the PNPLA6 gene in two siblings with chorioretinal dystrophy, hypogonadotropic hypogonadism, and cerebellar ataxia.

Boucher Neuhäuser Syndrome (BNS) is a rare disease with autosomal recessive inheritance defined by the classical triad; early-onset ataxia, hypogonadism and chorioretinal dystrophy. We present two siblings diagnosed with BNS at midlife, identified with homozygous state of a novel PNPLA6 missense mutation. One healthy sibling and the mother were heterozygous carriers of the mutation. The proband presented with the classical triad and the other sibling presented with visual problems at first. The proband was referred to our department by a private Neurologist, in early adulthood, because of hypogonadism, cerebellar ataxia, axonal neuropathy, and chorioretinal dystrophy for further evaluation. The sibling was referred to our department for evaluation, at childhood, due to visual problems. Later, the patient displayed the triad of ataxia, hypogonadotropic hypogonadism, and chorioretinal dystrophy. The unusual medical history of the two siblings led to further examinations and eventually the diagnosis of the first BNS cases in Cyprus. WES-based ataxia in silico gene panel analysis revealed 15 genetic variants and further filtering analysis revealed the PNPLA6 c.3323G > A variant. Segregation analysis in the family with Sanger sequencing confirmed the PNPLA6 homozygous variant c.3323G > A, p.Arg1108Gln in exon 29. This highlights the importance of considering rare inherited causes of visual loss, spinocerebellar ataxia, or/and HH in a neurology clinic and the significant role of genetic sequencing in the diagnostic process.

Современные аспекты патогенеза, диагностики и лечения диабетической ретинопатии

The article discusses current ideas about the pathogenesis, risk factors, and new methods of diagnosis and treatment of diabetic retinopathy. This disease is a specific microvascular ocular complication of diabetes mellitus and is part of the group of ischemic retinopathies, which are characterized by a significant violation of capillary perfusion, the development of intraocular newly formed vessels and retinal edema. Statistics show that almost 366 million people in the world suffer from diabetes mellitus (IDF Atlas, 2011). According to forecasts, this number is expected to double by 2030, and this global growth will have a huge impact on the prevalence of diabetic retinopathy. Over the past decade, advances in medical technology and the development of new treatment methods have significantly improved the diagnosis and treatment of patients, but nevertheless, diabetic macular edema and proliferative diabetic retinopathy remain the leading causes of vision loss.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy

BackgroundDiabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME.MethodsA retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated.ResultsThe logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson’s R = 0.44, p < 0.001).ConclusionThe developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model’s robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Metabolic reprogramming of the retinal pigment epithelium by cytokines associated with age-related macular degeneration.

The complex metabolic relationship between the retinal pigment epithelium (RPE) and photoreceptors is essential for maintaining retinal health. Recent evidence indicates the RPE acts as an adjacent lactate sink, suppressing glycolysis in the epithelium in order to maximize glycolysis in the photoreceptors. Dysregulated metabolism within the RPE has been implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of vision loss. In the present study, we investigate the effects of four cytokines associated with AMD, TNFα, TGF-β2, IL-6, and IL-1β, as well as a cocktail containing all four cytokines, on RPE metabolism using ARPE-19 cells, primary human RPE cells, and ex vivo rat eyecups. Strikingly, we found cytokine-specific changes in numerous metabolic markers including lactate production, glucose consumption, extracellular acidification rate, and oxygen consumption rate accompanied by increases in total mitochondrial volume and ATP production. Together, all four cytokines could potently override the constitutive suppression of glycolysis in the RPE, through a mechanism independent of PI3K/AKT, MEK/ERK, or NF-κB. Finally, we observed changes in glycolytic gene expression with cytokine treatment, including in lactate dehydrogenase subunit and glucose transporter expression. Our findings provide new insights into the metabolic changes in the RPE under inflammatory conditions and highlight potential therapeutic targets for AMD.

Corneal ulcers and the risk of visual impairment in a matched cohort study in Nepal

PurposeWe estimated the association between corneal ulcer and two outcomes: visual impairment and vision-related quality of life. We investigated for differential effects by rural/urban location. DesignPopulation-based matched prospective cohort study. MethodsWe followed 540 incident corneal ulcer cases identified in a cluster randomized trial in Nepal. Cases were pair-matched to individuals without incident corneal ulcers by age, sex and location using incidence density sampling. Clinical examinations were performed to assess outcomes in both groups after 12 months, which included visual acuity and a modified version of the Hong Kong vision-related quality of life questionnaire. Results392 matched pairs had complete outcome data and were included in the analyses. Median age was 42 years (interquartile range [IQR]: 28, 53) and 63.8 % were female. After controlling for education and occupation, corneal ulcer was associated with an approximately 1-line reduction in visual acuity (0.11 logMAR units, 95 % CI 0.06 to 0.15, P < 0.001), and with an increased risk of low vision/blindness (adjusted risk ratio 1.89, 95 % CI 1.44 to 2.48, P < 0.001). Corneal ulcer was associated with lower vision-related quality of life on the 20-question questionnaire (adjusted mean difference in score -1.69, 95 % CI -2.78 to -0.61, P = 0.002). We were unable to demonstrate effect modification for any outcome by rural/urban status. ConclusionsWe observed worse visual acuity and lower vision-related quality of life among those with incident corneal ulcers compared to those without. The population-based design, which captured the full spectrum of disease, confirms that corneal ulcers are an important cause of vision loss in the general population of Nepal and highlights the need for effective community-based corneal ulcer prevention interventions.

Two-Year Follow-up of Necrotic Herpetic Retinopathy in a Renal Transplant Recipient

Visual disturbances are common in patients who received renal transplant. Visual acuity is reduced in 60% of renal transplant patients after 10-year posttransplant. The most common causes are cataracts, diabetic retinopathy, and hypertensive retinopathy. However, infectious causes of visual loss are rare and most commonly associated with cytomegalovirus and toxoplasmosis infections. Here, we report a 32-year-old male who developed visual loss 6 months after receiving a live-related kidney transplant. The patient had a history of varicella infection in the immediate posttransplant period. The visual loss was secondary to acute retinal necrosis probably secondary to a Varicella infection. This rare manifestation is even more unique in a posttransplant scenario which is usually associated with progressive outer retinal necrosis. The patient had developed irreversible visual loss secondary to the retinal necrosis. Here, we report this rare association as well as 2-year ophthalmological follow-up of this patient.