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Lipid nanoparticles (LNPs) have emerged as a promising platform for retinal genetic therapy, offering a non-viral alternative to adeno-associated viruses. Although LNPs can transfect outer retinal cells, their transfection profile across inner retinal cell types remains insufficiently characterized. Here, we systematically assessed the cell-type transfection profile of conventional LNPs encapsulating chemically modified mRNA encoding mCherry in murine retinal explants, complemented by experiments in dissociated retinal cell cultures. We compared quasi-subretinal and quasi-intravitreal administrations and evaluated how retinal degeneration and inner limiting membrane (ILM) integrity influence LNP-mediated transfections. We observed that LNPs efficiently transfected Müller glia under all experimental conditions. In addition, LNPs transfected several other retinal cell types, including neurons in dissociated cells and explants, and vascular cells exclusively in explants. Subretinal delivery resulted in higher transfection rates than intravitreal administration, and overall efficiency was higher in degenerate as compared to non-degenerate healthy retinas. In healthy retinas, removal of ILM increased transfection efficiency following intravitreal administration. Together, these findings demonstrate that conventional LNPs can transfect a broader range of retinal cell types than previously recognized and highlight LNPs as a tool for mRNA delivery to the retina, with applications in gene supplementation, editing, and regenerative therapies for inner retinal disorders.
To evaluate the effect of epiretinal membrane (ERM)-induced retinal traction on functional and anatomical changes of lamellar macular hole (LMH). This retrospective study included patients with LMH followed for at least 12 months without surgery. Best-corrected visual acuity (BCVA), M-CHARTS-assessed metamorphopsia, and optical coherence tomography (OCT) parameters were evaluated. ERM-induced retinal traction was assessed using B-scan and en face OCT images, with maximum depth of retinal folds (MDRF) quantified as an indicator of retinal traction strength. Annual rates of change in visual function and OCT parameters were compared between eyes with and without ERM-induced retinal traction. Thirty-six eyes were analyzed. During a mean follow-up of 46.4 ± 28.4 months, BCVA and metamorphopsia worsened, accompanied by foveal cavity enlargement, increased epiretinal proliferation thickness and ellipsoid zone disruption length, and decreased minimum retinal thickness (all P < 0.05). Eyes with ERM-induced retinal traction demonstrated significantly faster functional and anatomical deterioration than those without traction. MDRF showed significant correlations with worsening rates of BCVA, metamorphopsia, foveal cavity enlargement, and retinal thinning. ERM-induced retinal traction was associated with accelerated functional and anatomical deterioration in LMH. Quantitative assessment of retinal traction may facilitate the identification of LMH at higher risk of progression.
To evaluate the time-adjusted economics of retinal and cataract surgery in order to clarify how the dynamics of ambulatory surgery centers influence access to urgent care. A time-driven activity-based costing model integrating Centers for Medicare & Medicaid Services ambulatory surgery center reimbursement, intraservice times, and cost data from a provider was applied to 18 421 retinal and 880 448 cataract procedures (2021-2024). Reimbursement, cost, and profit were converted to per-minute values, and a financial efficiency coefficient was used to quantify time-adjusted profitability. Variation in time and overhead allocation was assessed with sensitivity analyses. Retinal procedures required 76.1 minutes vs 20.8 minutes for cataract surgery (ratio, 3.65). Time-normalized metrics favored cataract surgery, with reimbursement, cost, and profits per minute of $52.63, $29.28, and $23.35, compared with retinal procedures' $24.61, $16.22, and $8.40. The profit per minute for retinal procedures was 36% of the cataract profit. The financial efficiency coefficient was 0.098, indicating retinal surgery was less than 10% efficient after adjusting for operative duration. Parity would require reducing operative time to 7.5 minutes or increasing reimbursement by $61.05 per minute (~71%). No retinal Current Procedural Terminology code achieved a financial efficiency coefficient ≥1. Block modeling showed adding 2 retinal cases to a cataract block converted a margin to a loss, with retinal blocks generating losses approaching $5,908. Although ambulatory surgery center reimbursement was higher for retinal than cataract surgery and the cost per minute was lower for retinal surgery, cataract surgery was more profitable per minute. These findings underscore the need for reform of time-based reimbursement that reflects the complexity of retinal surgery.
Background: Amyotrophic lateral sclerosis (ALS) is increasingly recognized as a multisystem disorder involving neurovascular dysfunction. The retina allows in vivo assessment of neurovascular changes. This study evaluated retinal structural and microvascular alterations in ALS using optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A). Methods: This cross-sectional study included 46 participants with ALS and 19 healthy controls. Retinal thickness and vascular density in the superficial and deep retinal capillary plexuses and the choriocapillaris were quantified using OCT and OCT-A. Group comparisons and logistic regression analyses were performed to assess associations with ALS. Subgroup analyses were conducted according to clinical phenotype. Results: In total, 124 eyes were analyzed. ALS was associated with increased average retinal thickness (p = 0.023) and reduced vascular density in the superficial retinal capillary plexus (p = 0.005), deep retinal capillary plexus (p < 0.001), and choriocapillaris (p = 0.004). In logistic regression analyses, retinal thickness was positively associated with ALS status (OR = 1.42, p = 0.023), whereas higher vascular density in the superficial plexus, deep plexus, and choriocapillaris was associated with lower odds of ALS. No significant differences were observed between bulbar- and spinal-onset ALS phenotypes. Conclusions: ALS is associated with structural and microvascular retinal alterations detectable by OCT and OCT-A. These findings support the presence of systemic neurovascular dysfunction and highlight retinal imaging as a promising, non-invasive approach for investigating disease mechanisms and developing potential biomarkers.
Sirt1 is of main importance in vascular homeostasis maintenance and in the protection of microcirculatory function during pathology. However, the exact mechanisms underlying the protective effects of Sirt1 on retinal vasculature are still not fully understood. Here, we analyse the effects of Sirt1 overexpression in the retina of transgenic mice. Mice retinas were studied by means of PCR, western blot and immunohistochemistry to assess the expression of Sirt1, VEGF-A, and the PDGF-B/PDGFR-β pathway. Retinal vasculature was deeply analysed by immunohistochemistry, trypsin digestion, and transmission electron microscopy. Our results showed that Sirt1-tg mice exhibited a moderate retinal Sirt1 overexpression throughout the retinal parenchyma, mainly at the nuclei of vascular retinal cells. This Sirt1 overexpression led to an increased expression of retinal VEGF-A. In addition, our results suggested that the expected VEGF-driven angiogenesis was prevented in Sirt1-tg mice retinas by two vessel stabilization mechanisms: increased pericyte coverage, and focal increased collagen IV deposition in blood vessel basement membrane. Altogether, our findings may indicate a possible role for Sirt1 in modulating VEGF angiogenic effects, potentially being associated with changes in pericyte coverage and basement membrane protein deposition in retinal blood vessels.
Strabismus surgery may lead to haemodynamic changes in the retina and optic nerve head which could affect eye function. To investigate the possible haemodynamic changes of the retina and optic disc after horizontal strabismus surgery using optical coherence tomography angiography (OCTA). 37 eyes of 20 patients who underwent horizontal rectus muscle recession surgery were included to this prospective study. Demographic features, ophthalmological exam including strabismus findings were noted. OCTA examinations were performed preoperatively, postoperative first week and first month. OCTA measurements, including vessel density of the superficial and the deep capillary plexus, optic nerve head, foveal retinal thickness, peripapillary retinal nerve fibre layer thickness, were compared among the study periods. The median age of subjects was 9 (5-45) years. Ten subjects (50%) with esotropia underwent bilateral medial rectus recession, and 10 subjects (50%) with exotropia underwent bilateral lateral rectus recession. Postoperative first week and first month superficial whole image and parafoveal capillary plexus vessel density were significantly lower than preoperative values (p = 0.010, p = 0.008, respectively). However, no significant difference was found regarding deeper capillary and optic disc vessel density, foveal retinal thickness, and retinal nerve fibre layer thickness. Although recession surgery did not significantly influence the microcirculation of the deeper retina and optic disc in the early postoperative period, it seemed to be associated with decreased superficial vessel density which could be suggesting a possible link to hypoperfusion and ischaemia. Further studies are needed to investigate the long-term effects of bilateral symmetric recession surgery for horizontal strabismus on the microcirculation of the retina and optic nerve head.
Retinal and choroidal structural alterations have increasingly been recognized in individuals with human immunodeficiency virus (HIV) infection, although findings from optical coherence tomography (OCT) studies remain inconsistent. We evaluated retinal and choroidal thickness changes measured by OCT in HIV-infected individuals compared with healthy controls. A comprehensive literature search was conducted in PubMed, Scopus, Web of Science, and Embase from database inception to April, 2025. Studies reporting OCT-based measurements of retinal layer or choroidal thickness (CT) in HIV-infected individuals and healthy controls were included. Standardized mean differences (SMD) were pooled using fixed- or random-effects models. 21 studies involving HIV-infected individuals and healthy controls were included. HIV infection was associated with significant thinning of the macular ganglion cell-inner plexiform layer (SMD -0.55; 95% CI -0.80 to -0.29;P < 0.001), foveal inner plexiform layer (SMD -0.36; 95% CI -0.62 to -0.10;P = 0.006), temporal peripapillary retinal nerve fiber layer (pRNFL) (SMD -0.21; 95% CI -0.40 to -0.02; P = 0.03), and global pRNFL (SMD -0.20; 95% CI -0.38 to -0.02; P = 0.03). Peripheral macular ganglion cell layer (SMD 0.17; 95% CI 0.01-0.32;P = 0.034) and outer plexiform layer thickness (SMD 0.35; 95% CI 0.18-0.52;P < 0.001) were significantly increased. CT was comparable between HIV-infected individuals and healthy controls (SMD 0.15; 95% CI -0.28-0.58;P = 0.49). Overall, HIV infection appears to be associated with selective, layer-specific retinal structural alterations, predominantly affecting inner retinal layers, while CT remains largely preserved. These findings support the concept of HIV-related neuroretinal involvement and suggest that OCT-derived retinal parameters may serve as noninvasive biomarkers for detecting neurodegenerative changes in individuals with HIV infection.
Bipolar disorder and depression are associated with structural and functional changes in the retina, including a thinner retinal nerve fibre layer (RNFL). Lithium is widely considered the most effective treatment for bipolar disorder, but its mechanism of action is not fully understood. We assessed research looking at the effect of lithium on structural or functional retinal outcomes in humans. Searches using the terms 'Lithium' AND 'retina' were carried out to identify peer reviewed studies assessing the impact of lithium on retinal structure or function. These included those with or without a control group comparison, pre- and post- lithium comparisons and observational studies. There were no exclusions based on the quantity or preparation of lithium administered, or the length of administration. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tool for Analytical Cross Sectional Studies, and a narrative synthesis and tabulated summary of the included studies was completed. Seven studies assessing structural outcomes and 10 reporting functional ones were identified, all highly heterogenous and with multiple limitations. Structural outcomes were derived exclusively from optical coherence tomography (OCT) with retinal nerve fibre layer (RNFL) being the most common measurement. There was no evidence of differences in the RNFL between participants with bipolar disorder taking lithium and healthy controls in two larger studies. In six studies looking at differences in those with bipolar disorder taking lithium and those taking valproate, two showed no signs of difference and four showed evidence of thicker RNFL in the lithium group. Studies reporting functional outcomes reported a statistically significant effect of lithium on at least one functional measure, derived from electrooculography, electroretinography, and dark adaptation thresholds. Current evidence suggests that lithium is likely to have an effect on the retina but limitations in all studies mean better designed and adequately powered prospective studies are required. PROSPERO database (Number-CRD42024516635).
Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, yet the cell-type-specific molecular alterations associated with disease progression remain incompletely understood. This study aimed to characterize transcriptional changes across retinal cell types in diabetes and DR and identify candidate disease-associated biomarkers using single-cell transcriptomics and machine-learning approaches. We generated a single-cell RNA sequencing (scRNA-seq) atlas comprising 297 121 high-quality retinal cells from 20 eyes of 13 Chinese donors, including non-diabetic controls (NON), diabetes without retinopathy (DM), and DR samples. Following quality control, batch correction, clustering, and cell-type annotation, differential expression analyses were performed across disease states within each retinal cell type. Candidate biomarkers were further prioritized using a machine-learning framework incorporating L1-regularized logistic regression, recursive feature elimination with cross-validation, and stability selection. We identified 10 major retinal cell populations and characterized extensive cell-type-specific transcriptional alterations associated with diabetes and DR. Pathway enrichment analyses consistently highlighted immune activation, oxidative stress, neurodegeneration, and synaptic dysfunction across multiple retinal cell types. A total of 707 cell-type-specific candidate marker genes were identified, providing a comprehensive resource for investigating disease-associated molecular mechanisms and potential therapeutic targets. This study establishes a single-cell transcriptomic atlas of the Chinese diabetic retina and reveals cell-type-specific molecular signatures associated with DR progression. These findings provide biological insights into retinal disease mechanisms and nominate candidate biomarkers for future functional and translational studies.
To characterize the topography of hyperreflective spots (HRSs) and hard exudates (HEs) and to analyze their association with localized retinal sensitivity in diabetic retinal disease (DRD). In this prospective cross-sectional study, diabetic patients (type I/II) underwent increased axial resolution optical coherence tomography (OCT) and mesopic microperimetry. HRSs (<30 µm, without back shadowing) and HEs (>30 µm, with back shadowing) were annotated in OCT scans and spatially matched to microperimetry test points across Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. Eyes with confounding OCT biomarkers (disorganization of the retinal inner layers, ellipsoid zone/external limiting membrane disruption, vitreomacular traction) were excluded. Linear mixed-effects models were used to evaluate the associations between lesion types and localized retinal sensitivity. Fifty-one eyes of 51 patients were included (mean age, 55.9 ± 14.8 years; diabetic retinopathy severity scale, 3.3 ± 1.6; hemoglobin A1c, 7.6% ± 2.0%). HRSs (n = 2308) were present in all study eyes, while HEs (n = 1222) were present in 21 eyes. Normalized to ETDRS subfield area, both HRSs (229.2 /mm2) and HEs (82.8 /mm2) showed the highest densities in the central subfield. Higher HRS load was independently associated with reduced retinal sensitivity (β = -0.06, P = 0.011), whereas no significant association was observed for HEs (P = 0.461); this finding should be interpreted with caution given the limited number of eyes with HEs. HRSs and HEs demonstrate distinct spatial distributions and functional associations in DRD, with HRSs independently linked to localized sensitivity loss. HRSs may serve as an accessible biomarker of early neuroretinal impairment and could improve patient stratification and treatment evaluation in clinical trials.
To describe how optical coherence tomography (OCT) is used in retinal disease management to aid in decision-making, including whether to treat or observe, extend or shorten dosing intervals, switch therapy, and plan or assess surgical care. Pivotal randomized clinical trials and designs in neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were reviewed to characterize how OCT is used within evidence-based retreatment and monitoring strategies, including newer faricimab and aflibercept 8 mg trial programs. These decision strategies were translated into scenario-based clinical guidance for real-world decision-point use. Where randomized evidence is limited, particularly for selected surgical retina decision points, guidance reflects the authors' expert opinion as informed by available literature and common retina practice. OCT is used in trial protocols as an anatomic biomarker for nAMD, DME, and RVO to assess disease activity, treatment response and recurrence, and to determine individualized follow-up and retreatment intervals. OCT was often obtained at protocol visits during active therapy phases and at key reassessment points. When new symptoms, suspected recurrence, incomplete response, diagnostic uncertainty, or high-risk features are present, shorter assessment intervals may be appropriate. OCT-guided, decision-linked monitoring is supported by contemporary randomized clinical trials as integral to the management of nAMD, DME, and RVO, while recognizing that OCT frequency is generally not randomized as an isolated variable. The risk of avoidable vision loss can be reduced with scenario-based retina clinical guidance that emphasizes OCT at clinical decision points, improving patient safety and enhancing individualized care.
Subretinal fibrosis, a major cause of irreversible vision loss in neovascular age-related macular degeneration (nAMD), is driven by excessive deposition of extracellular matrix such as collagens. While proline metabolism is known to play a critical role in collagen biosynthesis and fibrosis, its involvement in subretinal fibrosis remains unclear. Here, we characterized the progression of fibrovascular lesions in JR5558 mice, observing significant molecular alterations as early as 4 weeks of age and phenotypic changes by 8 weeks. Transcriptomic and metabolomic analyses revealed elevated levels of 4-hydroxyproline, an essential component of collagen, alongside significant alterations of other fibrosis-related pathways. P4HA1, a catalytic subunit of prolyl-4-hydroxylase essential for 4-hydroxyproline biosynthesis, was prominently expressed in fibrotic lesions in retinas of JR5558, laser-induced murine models and human eyes with nAMD. Targeting P4HA1 with the small-molecule inhibitor diethyl pythiDC significantly attenuated fibrovascular lesion expansion in the JR5558 mouse model and reduced collagen turnover in human retinal pigment epithelium cells. Treatment responses in JR5558 mice were lesion-cluster dependent, with the combination of diethyl pythiDC with aflibercept showing selective antifibrotic benefit in moderate lesion cluster. These findings support a potential role of proline metabolism, particularly proline hydroxylation, in subretinal fibrosis. Inhibiting P4HA1 with diethyl pythiDC inhibited fibrosis in the models we studied, highlighting a potential therapeutic strategy.
In retinal neurodegenerative disorders, the initial degeneration of primary target cells is frequently followed by a phenomenon known as the bystander effect, wherein neighboring, initially unaffected cells also undergo degeneration. This secondary cell death can exceed the number of directly insulted cells (Frantseva et al. 2002a,b; de Rivero Vaccari et al. 2007; Wang et al. 2010; Park et al. 2011; Akopian et al. 2014; O'Brien and Bloomfield 2018). Although the precise mechanisms underlying the bystander effect remain incompletely understood, gap junctions (GJs) have been implicated in mediating the spread of pro-death signals from injured to adjacent cells. Consequently, GJs have become a focal point in recent research, with GJ blockade proposed as a neuroprotective strategy in progressive retinal diseases, such as diabetic retinopathy, ischemia, and glaucoma. However, GJs are essential in physiological neuronal communication, and their prolonged inhibition may disrupt visual processing (Bloomfield and Völgyi 2009; Völgyi et al. 2013; O'Brien and Bloomfield 2018), thereby limiting the therapeutic utility of GJ blockades in the treatment of chronic retinal conditions. Considering this, we propose an alternative hypothesis: rather than solely contributing to neurodegeneration, GJs may also support cell survival by facilitating the intercellular transmission of protective molecules (termed here as 'health-signals') that counteract apoptotic cascades and possibly attenuate the primary insult itself. In this framework, GJs could disseminate "health signals" across the retinal network, suggesting that co-administering neuroprotective agents with GJ permeability enhancers might amplify their therapeutic reach. While this hypothesis assumes that key endogenous molecules can cross GJs, their specific properties and transjunctional dynamics remain poorly understood. This review consolidates current knowledge on GJ-mediated communication and explores its clinical utility in retinal neuroprotection.
Background/Objectives: To determine the incidence of persistent avascular retina (PAR) and identify associated risk factors in patients with a history of retinopathy of prematurity (ROP) evaluated with ultra-widefield imaging. Methods: A retrospective case-control study was conducted on patients with a history of ROP evaluated with ultra-widefield imaging at a tertiary care center in Mexico. Clinical variables were analyzed, with PAR as the primary outcome. Associations were assessed using binary logistic regression models. Results: Ninety-two patients were included, of whom 12 (13.0%) presented with PAR. Receiving ≥2 anti-VEGF injections was significantly associated with PAR (OR 4.48; 95% CI 1.21-16.64; p = 0.032), an association that remained consistent after adjustment for gestational age and maternal factors. Additionally, maternal preeclampsia and chorioamnionitis were independently associated with PAR. Conclusions: Persistent avascular retina appears to result from a complex interplay of prenatal and postnatal factors affecting retinal vascular development. Patients requiring repeated anti-VEGF treatment and those exposed to adverse maternal conditions may represent a subgroup at increased risk for incomplete peripheral retinal vascularization, supporting the need for long-term retinal surveillance after ROP regression.
To characterize longitudinal patterns of intraretinal (IRF) and subretinal fluid (SRF) dynamics using AI-assisted optical coherence tomography (OCT) biomarker quantification and to evaluate their association with long-term visual outcomes in eyes with central retinal vein occlusion (CRVO). Patients with previously treatment-naïve CRVO and a documented 24-month follow-up were retrospectively included. All eyes received intravitreal aflibercept administered according to a treat-and-extend protocol. Spectral-domain OCT scans were analyzed at baseline, and after 3 and 24 months. IRF and SRF volumes were quantified using RetinAI Discovery OCT Biomarker Detector (Ikerian AG). Linear regression models were used to assess the association between fluid volumes and 24-month corrected distance visual acuity (CDVA). Patients were clustered according to their IRF trajectories over time to identify distinct fluid-response phenotypes. Out of 173 patients, 64 eyes (64 patients) were included. Baseline IRF and SRF volumes showed no significant association with 24-month CDVA. Cluster analysis of longitudinal IRF trajectories identified four distinct fluid-response patterns. Eyes with low or rapidly resolving IRF achieved the best long-term visual outcomes (median CDVA 73 letters), whereas those with persistent or recurrent IRF showed poorer outcomes (median 53 letters; p=0.008). Early IRF resolution tended to predict superior visual recovery at 24 months. AI-based volumetric OCT analysis suggests that distinct retinal fluid trajectories in CRVO may have prognostic implications for long-term visual acuity, though these findings are preliminary and require validation. Dynamic IRF resolution patterns are more informative than static fluid volumes for predicting functional outcomes following anti-VEGF therapy.
To assess the geographic coverage of U.S. medical and surgical retina specialists and identify community-level sociodemographic factors associated with reduced access. For this population-based, cross-sectional study, fellowship-trained retina specialists were identified using professional society membership databases, private practice websites, academic department profiles, and Centers for Medicare and Medicaid Services data. Practice addresses were geocoded, and 15-, 30-, and 60-min drive-time service areas were generated. U.S. Census tracts enriched with 2019-2023 American Community Survey sociodemographic data were overlaid, with tract proximity defined by the shortest service area capturing the tract centroid. Multivariable logistic regression was used to identify tract-level sociodemographic characteristics associated with inadequate access to care (i.e., >60-min). Odds ratios (ORs) were scaled per 10-percentage point increase in each predictor. Approximately 5.0% of U.S. residents lived >60-min from the nearest retina specialist. After adjusting for urbanicity, higher odds of inadequate access were observed amongst tracts with higher proportions of Medicare-aged residents (OR 1.61 [95% confidence interval, 1.58-1.64]) and greater racial homogeneity (1.15 [1.14-1.16]). Higher proportions of college-educated residents were associated with reduced odds of inadequate access (0.89 [0.88-0.90]). Weaker associations were observed between inadequate access and higher proportions of uninsured (1.05 [1.02-1.08]) and Hispanic/Latino residents (1.08 [1.07-1.09]). No association was observed for proportion very low-income residents (1.00 [0.99-1.02]). Approximately 1 in 20 U.S. residents lived >60-min from a retina specialist, with several sociodemographic characteristics associated with reduced access. These findings highlight specific communities that may benefit most from targeted interventions.
It is our purpose to address concerns regarding visual field loss as a barrier to optimal performance of encircling laser retinopexy as a prophylaxis for retinal detachment, especially when extended posteriorly, as in prophylaxis for retinal detachment in Stickler syndrome (SS). We retrospectively analyzed visual field and visual acuity changes after encircling laser prophylaxis extending to the posterior edge of the vortex vein ampullae (ora secunda cerclage/Stickler syndrome, OSC/SS) in our first four SS patients who underwent such prophylaxis. We then used disability tables and validated patient questionnaires to characterize the extent of visual disability and/or symptoms resulting from such encircling prophylaxis. The reduction in peripheral visual field from OSC/SS posterior prophylaxis (to an average diameter of approximately 100 degrees in five treated eyes) was a far smaller percentage impairment (0-21% by various estimations) than the 85% impairment from loss of both visual acuity and visual field after RD in the primary eye of a typical SS patient prior to fellow eye prophylaxis. Turano and NEI VFQ-25 Questionnaires both indicated that everyday mobility and travel visual tasks were not significantly affected by the laser prophylaxis. Encircling laser retinopexy, extending posteriorly to and between the vortex vein ampullae, did not cause significant visual disability or any symptomatic visual field loss in an initial cohort of four patients with SS. Nor did we encounter any symptomatic visual field loss in 22 patients so treated subsequently. OSC/SS encircling laser prophylaxis safety and effectiveness is now being prospectively studied in a larger clinical trial (NCT07146516). Encircling laser treatment to the peripheral retina for prevention of retinal detachment modestly reduces the peripheral visual field and in return substantially increases security for the central visual field. In an initial sample, peripheral visual field loss even for the maximal form of laser prevention (as needed for Stickler syndrome) was minimal and asymptomatic. A prospective clinical trial (NCT07146516) of such prophylaxis will continue monitoring for symptomatic visual field changes.
Glaucoma is the leading cause of irreversible blindness globally. Chronic neuroinflammation drives progressive retinal ganglion cell (RGC) loss independent of intraocular pressure, yet safe, sustained and precise neuroprotective modulation of the retinal inflammatory microenvironment remains a significant challenge. We developed an injectable fibrin gel delivery system loaded with ginseng-derived exosomes (GE-fibrin gel, GE-gel) to modulate microglial polarization, reduce retinal inflammation and promote RGC survival. In vitro, GE showed strong antioxidant and anti-apoptotic effects by getting rid of reactive oxygen species caused by oxidative stress and lowering apoptosis in R28 cells. Both GE and GE-gel stopped lipopolysaccharide from causing pro-inflammatory M1 polarization of microglia and increased anti-inflammatory M2 phenotypic change. Intravitreal injection of GE-gel suppressed pro-inflammatory microglial activation, diminished neuroinflammation and improved the survival of RGCs in a chronic ocular hypertension rat model. These results show that GE-gel could promote microglial polarization, change the immune environment in the retina and protect RGCs functionally over the long term. This approach may hopefully provide promising solutions for rapid and effective glaucoma therapy.
To evaluate retinal structural parameters and layer-specific microvascular perfusion using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) in patients with chronic methamphetamine use disorder. This prospective, cross-sectional study included 45 patients with methamphetamine use disorder and 45 age-and sex-matched healthy controls. All participants underwent comprehensive ophthalmologic examination and standardized OCT and OCTA imaging. Central macular thickness, peripapillary retinal nerve fiber layer (RNFL) thickness, and subfoveal choroidal thickness were assessed by OCT. OCTA was used to quantify foveal avascular zone (FAZ) area, vessel density of the superficial and deep capillary plexuses (SCP and DCP), and flow areas of the outer retina and choriocapillaris. Correlations with duration and cumulative methamphetamine exposure were analyzed. Total and superior quadrant RNFL thicknesses were significantly higher in the methamphetamine group(p=0.039 and p=0.030, respectively). Although SCP-VD was lower in the methamphetamine group, this difference did not reach statistical significance(p>0.05). In contrast, DCP-VD was significantly reduced in the methamphetamine group across total, parafoveal, and perifoveal regions(all p<0.001). Choriocapillaris flow area was also significantly lower in methamphetamine users(p=0.001). No clinical signs of retinopathy were observed in the patient group. Total and superior RNFL thicknesses were positively correlated, and outer retinal flow was negatively correlated, with both duration and cumulative methamphetamine exposure(p<0.05). Chronic methamphetamine use was associated with reduced DCP vessel density and decreased choriocapillaris flow despite the absence of clinically apparent retinopathy. These findings suggest layer-specific subclinical microvascular alterations detectable by OCTA. Longitudinal studies are needed to determine their progression and clinical relevance.
To evaluate the temporal association between treatment of retinal breaks (RBs) without detachment using laser retinopexy or cryotherapy and the development of epiretinal membrane (ERM), including ERM peel. Retrospective cohort study. After propensity score matching (PSM) and applying inclusion/exclusion criteria, 20,191 patients undergoing laser retinopexy (treatment cohort) and 730 patients undergoing cryotherapy (treatment cohort) were each compared with matched untreated RB controls. Data were extracted from a national clinical database (TriNetX). Patients with RBs without detachment treated with laser retinopexy or cryotherapy were compared with individuals with untreated RBs (control cohort) to examine the incidence of ERM formation and ERM peel from three months to five years. A secondary analysis compared laser retinopexy with cryotherapy cohorts directly. During the five-year study period, both treatment cohorts demonstrated the highest risk for ERM formation early after intervention. In the laser retinopexy cohort, ERM risk was increased at three months (2.88% vs 0.94%; RR, 3.06) and remained elevated at one year (6.27% vs 2.26%; RR, 2.77), with higher ERM peel rates persisting through five years. In the cryotherapy cohort, ERM risk was increased at six months (5.34% vs 1.92%; RR, 2.79) and one year (8.63% vs 2.60%; RR, 3.32). Rates of ERM requiring surgical peeling were low and not estimable at several time points in the cryotherapy cohort due to small event counts. In direct comparison, no significant differences were observed between laser retinopexy and cryotherapy cohorts across all time points. Treatment of RBs without detachment with either laser retinopexy or cryotherapy is associated with an increased risk of ERM formation compared with untreated RBs, with risk peaking early following treatment and persisting over time. No significant difference in ERM risk was observed between treatment modalities, suggesting that ERM development may occur as a response to vitreoretinal disruption and inflammation regardless of the specific intervention performed.