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To evaluate the anatomic and visual outcomes of patients with idiopathic epiretinal membranes (ERM) complicated by schisis of the retinal nerve fiber layer (sRNFL) in routine clinical practice.Retrospective case control study.Patients undergoing idiopathic ERM surgery at Cole Eye Institute from 2013-2021.Patients were grouped by the presence of absence of sRNFL prior to surgery. Preoperative and postoperative data was collected regarding VA, changes in central subfield thickness (CST) over time, and presence of cystoid macular edema (CME).Frequency of sRNFL in patients undergoing idiopathic ERM surgery.48 of 89 patients (53.9%) presented with sRNFL. sRNFL patients presented with significantly decreased VA compared to those without (58.63 ± 12.48 vs 67.68 ± 7.84 ETDRS letters, p0.001 respectively). At final follow-up after ERM removal, there was no significant difference in final VA in sRNFL patients compared to those without (71.16±2.93 vs 74.11±2.76, p=0.467). At presentation, sRNFL patients had greater CST than those without (454±10.01 vs 436±0.23, p=0.23). This difference persisted at 90-day follow-up after ERM removal (402 ± 8.08 vs 375± 10.19 μm, p=0.043). Resolution of sRNFL was reported at post-operative week 1 in 30 of 31 cases (96.7%).SRNFL is a microstructural feature in greater than 50% of idiopathic ERMs in routine clinical practice and carries visual significance on presentation and anatomic significance postoperatively.

Purpose: Oxidative stress-induced mitochondrial dysfunction is implicated in the pathogenesis of age-related macular degeneration (AMD). Oxidized mitochondrial flavoprotein fluorescence (FPF) may serve as a quantifiable biomarker of oxidative stress, reported as either mean score for the entire image (intensity) or variability (heterogeneity). This study examines FPF intensity and heterogeneity across a large patient cohort of various Beckman stages of AMD. Methods: This study enrolled patients with isolated AMD and healthy control patients with no retinopathy between 2018 and 2021. Multivariate logistic regression analysis included stage of AMD, age, gender, ethnicity, and smoking status. Analysis of Variance test compared mean FPF intensity and heterogeneity between disease states. Results: Four hundred fifty-six eyes (228 AMD eyes, 228 age-matched control eyes) were included in the final multivariate analysis. Intermediate, geographic atrophy (GA), and neovascular AMD correlated with significantly increased FPF intensity ( P < 0.001, respectively), while all AMD stages correlated with increased FPF heterogeneity ( P < 0.001, respectively). FPF intensity and heterogeneity were significant negative predictors of visual acuity ( P = 0.018 and 0.024, respectively). Conclusions: This prospective observational study further implicates mitochondrial damage in AMD pathophysiology. Long-term clinical trials will be needed to examine the predictive role of FPF imaging in patients over time. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:24–31.]

Background and Objective: Rhegmatogenous retinal detachment (RRD) requires urgent surgical intervention. The effect of travel distance on RRD outcomes is unclear. Patients and Methods: This retrospective cohort study included 642 patients who underwent RRD repair at Cole Eye Institute from 2012 to 2020. Google Maps was used to calculate the travel distance in miles from the residential zip code to the presenting and surgery location addresses. Multivariable logistic and bivariate linear regressions were used to compare macula-off status and best-corrected visual acuity (BCVA) in ETDRS letters at presentation and at 6-month follow-up, with patient travel distance divided into < 25 miles, 25 to 50 miles, and > 50 miles. Results: Four hundred sixty-two patients were examined in the final cohort. The retinal reattachment rate was 94.3% for less than 25 miles, 96.3% for 25 to 50 miles, and 95.9% for greater than 50 miles ( P = 0.63). In multivariable analysis, distance to presenting location was not associated with macula-off status ( P = 0.69) or BCVA at follow-up ( P = 0.27). Oneway analysis of distance and time from presentation to surgery in days revealed that distance to surgical site was associated with longer time to surgery ( P = 0.003). Subset analysis of patients with income less than $25,520 ( n = 18) revealed greater distance to presenting and surgical location was associated with longer time to surgery ( P < .0001), but was not associated with BCVA at follow-up ( P = 0.53). Conclusions: This data suggests that patients who live further from the hospital achieve equivalent outcomes from RRD repair, despite delays in surgery. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:666–672.]

Whether by indirect oxidative stress or direct genetic defect, various genetic retinal dystrophies involve mitochondrial stress. Mitochondrial flavoprotein fluorescence (FPF), reported as either average signal intensity or variability (heterogeneity), may serve as a direct, quantifiable marker of oxidative stress.This observational study enrolled patients with genetically confirmed retinal dystrophies between January and December 2021. Patients with concomitant maculopathy and ocular hypertension were excluded. Patients were FPF imaged with OcuMet BeaconThe final analysis cohort included 242 images from 157 patients. Mean FPF intensity was significantly increased between age matched controls and patients with confirmed rod-cone dystrophy, Stargardt disease, Bardet-Biedl syndrome (BBS), and Mitochondrial ATP synthase mutation (FPF intensity and heterogeneity significantly increased in patients with retinal dystrophies. The correlation of FPF lesions with FAF lesions implies FPF may be a clinically useful biomarker in patients with IRDs.This study found increases in flavoprotein fluorescence signal in patients with genetically confirmed inherited retinal dystrophies compared to age matched controls. Flavoprotein fluorescence signal correlated with fundus autofluorescence findings, suggesting clinical utility of novel signal.

A case study on a challenging industrial crystallization is presented. The crystallization under investigation was prone to oiling-out, which led to agglomeration and stalling of crystallization. A...

BACKGROUND AND OBJECTIVE: To report the time in which patients with panretinal photocoagulation (PDR) progress to vision-threatening retinopathy (VTR) complications after receiving PRP, and risk factors in routine clinical practice. PATIENTS AND METHODS: Records of patients with complete PRP for PDR were retrospectively reviewed for up to 3.5 years after PRP. Two hundred twenty eyes were selected. RESULTS: Time from PRP to VTR was 1.25 ± 0.82 years. Age, Black race, neovascularization of the disc on examination, diabetic foot disease (DFD), and high-risk PDR characteristics on fluorescein angiography were identified as significant risk factors. Half of patients with DFD on examination developed a VTR within 1.5 years after PRP ( P < .001). CONCLUSION: In clinical practice, providers may consider DFD and Black race as predictors of time to VTR event within 4 years after PRP in patients with PDR. [ Ophthalmic Surg Lasers Imaging Retina . 2022;53(4):186–193.]

PurposeLoss to follow-up or fragmented follow-up episodes (LTFU) may contribute to suboptimal clinical outcomes, especially when comparing real world data to clinical trials. This systemic review gathers available evidence around interventions meant to decrease the LTFU in AMD, RVO, and DME patientsPatients and methodsPubMed was queried using a literature search strategy and reviewed by the authors. Studies with interventions aimed at reducing lost to follow up were included.ResultsTen studies were extracted from 89 candidate publications.DiscussionTelephone interventions featuring assistance in scheduling in improving LTFU in urban, African American populations over 50 years old with diabetic retinopathy. The same interventions have shown promise in glaucoma, but remain understudied in AMD, RVO, and other geographic, ethnic, and socioeconomic demographics.ConclusionNo sole intervention with efficacy in improving LTFU has been developed. A standardized definition of LTFU, as well as testing interventions across broad age, geography, ethnic, racial, and socioeconomic lines. Longitudinal data would also add credence to the efficacy of purported interventions.OtherNo sources of funding for this article.

Dendrobatid frogs sequester alkaloid defenses from dietary arthropods. Here, we provide experimental evidence that mother strawberry poison frogs (Oophaga pumilio) provision alkaloids to tadpoles. Captive-raised females were fed the synthetic alkaloid decahydroquinoline (DHQ), which we subsequently quantified in their skin, eggs, and developing tadpoles. DHQ quantity was positively associated with tadpole mass/development, suggesting high sequestration rates by tadpoles. These data confirm that tadpoles obtain nutrition and alkaloids by feeding exclusively on maternally provisioned eggs.

The Ang/Tie2 pathway complements VEGF-mediated activity in retinal vascular diseases such as DME, AMD, and RVO by decreasing vascular integrity, increasing neovascularization, and increasing inflammatory signaling. Faricimab is a bispecific antibody that has been developed as an inhibitor of both VEGF and Ang2 that has shown positive results in phase I, II and III trials. Recent Year 1 data from phase III clinical trials YOSEMITE, RHINE, TENAYA, and LUCERNE have confirmed the efficacy, safety, durability, and superiority of faricimab in patients with DME and nAMD. Faricimab, if approved, may significantly decrease treatment burden in patients with retinal vascular diseases to a greater extent than would current standard of care anti-VEGF injections.

Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite that enhances both platelet responsiveness and in vivo thrombosis potential in animal models, and TMAO plasma levels predict incident atherothrombotic event risks in human clinical studies. TMAO is formed by gut microbe-dependent metabolism of trimethylamine (TMA) moiety-containing nutrients, which are abundant in a Western diet. Here, using a mechanism-based inhibitor approach targeting a major microbial TMA-generating enzyme pair, CutC and CutD (CutC/D), we developed inhibitors that are potent, time-dependent, and irreversible and that do not affect commensal viability. In animal models, a single oral dose of a CutC/D inhibitor significantly reduced plasma TMAO levels for up to 3 d and rescued diet-induced enhanced platelet responsiveness and thrombus formation, without observable toxicity or increased bleeding risk. The inhibitor selectively accumulated within intestinal microbes to millimolar levels, a concentration over 1-million-fold higher than needed for a therapeutic effect. These studies reveal that mechanism-based inhibition of gut microbial TMA and TMAO production reduces thrombosis potential, a critical adverse complication in heart disease. They also offer a generalizable approach for the selective nonlethal targeting of gut microbial enzymes linked to host disease limiting systemic exposure of the inhibitor in the host.