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Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1–53.0)/(22.6–32.9), Portugal (39.0–74.4)/(21.4–38.9), Netherlands (40.6–66.3)/(25.3–38.8) and UK (37.5–62.4)/(23.3–34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2–12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8–19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR.

Retinal photoreceptor degeneration occurs frequently in several neurodegenerative retinal diseases such as age-related macular degeneration, retinitis pigmentosa, or genetic retinal diseases related to the photoreceptors. Despite the impact on daily life and the social and economic consequences, there is no cure for these diseases. Considering this, cell-based therapy may be an optimal therapeutic option. This study evaluated the neuroprotective in vitro potential of a secretome of human bone marrow mesenchymal stem cells (MSCs) for retinal photoreceptors in vitro. We analyzed the photoreceptor morphologic changes and the paracrine factors secreted by human bone marrow MSCs in a physically separated co-culture with degenerated neuroretinas, using organotypic neuroretinal cultures. The results showed that the secretome of human bone marrow MSCs had a neuroprotective effect over the neuroretinal general organization and neuropreserved the photoreceptors from degeneration probably by secretion of neuroprotective proteins. The study of the expression of 1,000 proteins showed increased paracrine factors secreted by MSCs that could be crucial in the neuroprotective effect of the stem cell secretome over in vitro retinal degeneration. The current results reinforce the hypothesis that the paracrine effect of the human bone marrow MSCs may slow photoreceptor neurodegeneration and be a therapeutic option in retinal photoreceptor degenerative diseases.

Silicone oil (SO) still represents the main choice for long‐term intraocular tamponade in complicated vitreoretinal surgery. This review compared the complications associated with the use of SO and other vitreous substitutes after pars plana vitrectomy in patients with different underlying diseases. Meta‐analysis was conducted in accordance with PRISMA guidelines. We retrieved randomized clinical trials (RCTs), retrospective case–control and cohort studies evaluating the risk of using SO, published between 1994 and 2020, conducting a computer‐based search of the following databases: PubMed, Web of Science, Scopus and Embase. Primary outcome was the rate of complications such as intraocular hypertension, retinal re‐detachment, unexpected vision loss or hypotony. Secondary outcome was to compare the rate of adverse events of different SO viscosities, especially emulsification. Forty‐three articles were included. There were significant differences in intraocular hypertension (p = 0.0002, OR = 1.66; 95% CI = 1.27–2.18) and the rate of retinal re‐detachment (p < 0.0009, OR = 0.65; 95% CI = 0.50–0.64) between SO and other agents, including placebo. However, there were no differences in other complication rates. Silicone oil (SO)‐emulsification rate was non‐significantly higher in low than high SO viscosity, and results from other complications were comparable in both groups. The high quality of most of the studies included in this study is noteworthy, which provides some certainty to the conclusions. Among them is the high variability of the SO residence time. The fact that ocular hypertension and not hypotension is related to SO use. A clear relationship is not found for the so‐called unexplained vision loss, which affects a significant percentage of eyes. Re‐detachment cases are less if SO is used and that surprisingly there does not seem to be a relationship in the percentage of emulsification between the low‐ and high‐viscosity silicones. All these data warrant more standardized prospective studies.

ABSTRACT.Purpose: To compare the distribution of BCL-2 -938C>A (rs2279115) and BAX -248G>A (rs4645878) genotypes among European subjects undergoing rhegmatogenous retinal detachment (RRD) surgery in relation to the further development of proliferative vitreoretinopathy (PVR). Methods: A case-control gene association study, as a part of Retina 4 project, was designed. rs2279115 and rs4645878 polymorphisms were analysed in 555 samples from patients with RRD (134 with PVR secondary to surgery). Proportions of genotypes and AA homozygous groups of BCL-2 and BAX polymorphisms between subsamples were analysed in two phases. Genotypic and allelic frequencies were compared in global sample and in subsamples. Results: BAX: Differences were observed in the genotype frequencies and in AA carriers between controls and cases in the global series. The odds ratio (OR) of A carriers in the global sample was 1.7 (95% CI: 1.23-2.51). Proportions of genotypes in Spain + Portugal were significant different. The OR of A carriers from Spain and Portugal was 1.8 (95% CI: 1.11-2.95). BCL-2: No significant differences were observed in genotype frequencies. However, proportions of genotypes in Spain + Portugal were significant. A protective effect (OR: 0.6 95% CI: 0.43-0.96) was found in A carriers from Spain and Portugal. Conclusions: Results suggest that A allele of rs4645878 could be a biomarker of high risk of developing PVR in patients undergoing RD surgery. The possible role of BCL-2 (inhibitor of necroptosis pathway) as a possible new target in PVR prophylaxis should be investigated.

Objectives To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes.

PurposeThe objective of this study is to determine the expression and localization of lymphotoxin alpha (LTA) in human retinas and the functionality of one of its polymorphisms rs2229094 (C13R) (T>C), previously associated with proliferative vitreoretinopathy (PVR) development.Materials and methodsTotal RNA from three healthy human retinas were extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis, using flanking primers of LTA cDNA. In addition, three human eyes with retinal detachment (RD) and three healthy control eyes were subjected to immunohistochemistry (IHC) with a specific antibody against LTA. The functionality of T and C alleles was assessed by using pCEFL-Flag expression vector and transient transfection assays in COS-1 cell line. In addition, expression analysis by RT-PCR, Western blot and subcellular localization of both alleles and by immunofluorescence assay was performed.ResultsRT-PCR analysis revealed no significant levels of messenger RNA (mRNA) LTA in healthy human retinas. Sequential IHC staining showed differences between healthy human and RD retinas. No differences in mRNA and protein expression levels and in subcellular localization between both alleles were found. Both alleles were located in the cytoplasm of COS-1 cells.ConclusionAlthough results suggest lack of functionality, the differences found in IHC study and its strong association with PVR and its relationship with tumor necrosis factor locus, warrant further studies and could justify the use of this polymorphism as a valid biomarker to identify high-risk patients to develop PVR after RD.

Summary Background We undertook a Grand Challenges in Global Eye Health prioritisation exercise to identify the key issues that must be addressed to improve eye health in the context of an ageing population, to eliminate persistent inequities in health-care access, and to mitigate widespread resource limitations. Methods Drawing on methods used in previous Grand Challenges studies, we used a multi-step recruitment strategy to assemble a diverse panel of individuals from a range of disciplines relevant to global eye health from all regions globally to participate in a three-round, online, Delphi-like, prioritisation process to nominate and rank challenges in global eye health. Through this process, we developed both global and regional priority lists. Findings Between Sept 1 and Dec 12, 2019, 470 individuals complete round 1 of the process, of whom 336 completed all three rounds (round 2 between Feb 26 and March 18, 2020, and round 3 between April 2 and April 25, 2020) 156 (46%) of 336 were women, 180 (54%) were men. The proportion of participants who worked in each region ranged from 104 (31%) in sub-Saharan Africa to 21 (6%) in central Europe, eastern Europe, and in central Asia. Of 85 unique challenges identified after round 1, 16 challenges were prioritised at the global level; six focused on detection and treatment of conditions (cataract, refractive error, glaucoma, diabetic retinopathy, services for children and screening for early detection), two focused on addressing shortages in human resource capacity, five on other health service and policy factors (including strengthening policies, integration, health information systems, and budget allocation), and three on improving access to care and promoting equity. Interpretation This list of Grand Challenges serves as a starting point for immediate action by funders to guide investment in research and innovation in eye health. It challenges researchers, clinicians, and policy makers to build collaborations to address specific challenges. Funding The Queen Elizabeth Diamond Jubilee Trust, Moorfields Eye Charity, National Institute for Health Research Moorfields Biomedical Research Centre, Wellcome Trust, Sightsavers, The Fred Hollows Foundation, The Seva Foundation, British Council for the Prevention of Blindness, and Christian Blind Mission. Translations For the French, Spanish, Chinese, Portuguese, Arabic and Persian translations of the abstract see Supplementary Materials section.