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Fitch TC, Frank SI, Li YK, Saint-Geniez M, Kim LA, Shu DY. Real-Time Analysis of Bioenergetics in Primary Human Retinal Pigment Epithelial Cells Using High-Resolution Respirometry. J Vis Exp 2023;(192)Abstract
Metabolic dysfunction of retinal pigment epithelial cells (RPE) is a key pathogenic driver of retinal diseases such as age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Since RPE are highly metabolically-active cells, alterations in their metabolic status reflect changes in their health and function. High-resolution respirometry allows for real-time kinetic analysis of the two major bioenergetic pathways, glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), through quantification of the extracellular acidification rate (ECAR) and oxygen consumption rate (OCR), respectively. The following is an optimized protocol for conducting high-resolution respirometry on primary human retinal pigment epithelial cells (H-RPE). This protocol provides a detailed description of the steps involved in producing bioenergetic profiles of RPE to define their basal and maximal OXPHOS and glycolytic capacities. Exposing H-RPE to different drug injections targeting the mitochondrial and glycolytic machinery results in defined bioenergetic profiles, from which key metabolic parameters can be calculated. This protocol highlights the enhanced response of BAM15 as an uncoupling agent compared to carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) to induce the maximal respiration capacity in RPE. This protocol can be utilized to study the bioenergetic status of RPE under different disease conditions and test the efficacy of novel drugs in restoring the basal metabolic status of RPE.
Carelli V, Newman NJ, Yu-Wai-Man P, Biousse V, Moster ML, Subramanian PS, Vignal-Clermont C, Wang A-G, Donahue SP, Leroy BP, Sergott RC, Klopstock T, Sadun AA, Fernández GR, Chwalisz BK, Banik R, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel J-A, the LHON Group S. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation. Ophthalmol Ther 2023;12(1):401-429.Abstract
INTRODUCTION: Lenadogene nolparvovec is a promising novel gene therapy for patients with Leber hereditary optic neuropathy (LHON) carrying the m.11778G>A ND4 mutation (MT-ND4). A previous pooled analysis of phase 3 studies showed an improvement in visual acuity of patients injected with lenadogene nolparvovec compared to natural history. Here, we report updated results by incorporating data from the latest phase 3 trial REFLECT in the pool, increasing the number of treated patients from 76 to 174. METHODS: The visual acuity of 174 MT-ND4-carrying patients with LHON injected in one or both eyes with lenadogene nolparvovec from four pooled phase 3 studies (REVERSE, RESCUE and their long-term extension trial RESTORE; and REFLECT trial) was compared to the spontaneous evolution of an external control group of 208 matched patients from 11 natural history studies. RESULTS: Treated patients showed a clinically relevant and sustained improvement in their visual acuity when compared to natural history. Mean improvement versus natural history was - 0.30 logMAR (+ 15 ETDRS letters equivalent) at last observation (P < 0.01) with a maximal follow-up of 3.9 years after injection. Most treated eyes were on-chart as compared to less than half of natural history eyes at 48 months after vision loss (89.6% versus 48.1%; P < 0.01) and at last observation (76.1% versus 44.4%; P < 0.01). When we adjusted for covariates of interest (gender, age of onset, ethnicity, and duration of follow-up), the estimated mean gain was - 0.43 logMAR (+ 21.5 ETDRS letters equivalent) versus natural history at last observation (P < 0.0001). Treatment effect was consistent across all phase 3 clinical trials. Analyses from REFLECT suggest a larger treatment effect in patients receiving bilateral injection compared to unilateral injection. CONCLUSION: The efficacy of lenadogene nolparvovec in improving visual acuity in MT-ND4 LHON was confirmed in a large cohort of patients, compared to the spontaneous natural history decline. Bilateral injection of gene therapy may offer added benefits over unilateral injection. TRIAL REGISTRATION NUMBERS: NCT02652780 (REVERSE); NCT02652767 (RESCUE); NCT03406104 (RESTORE); NCT03293524 (REFLECT); NCT03295071 (REALITY).
Rong SS, Yu XT. Phenotypic and Genetic Links between Body Fat Measurements and Primary Open-Angle Glaucoma. Int J Mol Sci 2023;24(4)Abstract
The phenotypic and genetic links between body fat phenotypes and primary open-angle glaucoma (POAG) are unclear. We conducted a meta-analysis of relevant longitudinal epidemiological studies to evaluate the phenotypic link. To identify genetic links, we performed genetic correlation analysis and pleiotropy analysis of genome-wide association study summary statistics datasets of POAG, intraocular pressure (IOP), vertical cup-to-disc ratio, obesity, body mass index (BMI), and waist-to-hip ratio. In the meta-analysis, we first established that obese and underweight populations have a significantly higher risk of POAG using longitudinal data. We also discovered positive genetic correlations between POAG and BMI and obesity phenotypes. Finally, we identified over 20 genomic loci jointly associated with POAG/IOP and BMI. Among them, the genes loci CADM2, RP3-335N17.2, RP11-793K1.1, RPS17P5, and CASC20 showed the lowest false discovery rate. These findings support the connection between body fat phenotypes and POAG. The newly identified genomic loci and genes render further functional investigation.
Singh RB, Parmar UPS, Kahale F, Agarwal A, Tsui E. Vaccine-Associated Uveitis after COVID-19 Vaccination: Vaccine Adverse Event Reporting System Database Analysis. Ophthalmology 2023;130(2):179-186.Abstract
PURPOSE: To assess the risk of vaccine-associated uveitis (VAU) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and evaluate uveitis onset interval and clinical presentations in the patients. DESIGN: A retrospective study from December 11, 2020, to May 9, 2022, using the Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. PARTICIPANTS: Patients diagnosed with VAU after administration of BNT162b2 (Pfizer-BioNTech, Pfizer Inc/BioNTech SE), mRNA-1273 (Moderna, Moderna Therapeutics Inc), and Ad26.COV2.S (Janssen, Janssen Pharmaceuticals) vaccine worldwide. METHODS: A descriptive analysis of the demographics, clinical history, and presentation was performed. We evaluated the correlation among the 3 vaccines and continuous and categorical variables. A post hoc analysis was performed between uveitis onset interval after vaccination and age, dose, and vaccine type. Finally, a 30-day risk analysis for VAU onset postvaccination was performed. MAIN OUTCOME MEASURES: The estimated global crude reporting rate, observed to expected ratio of VAU in the United States, associated ocular and systemic presentations, and onset duration. RESULTS: A total of 1094 cases of VAU were reported from 40 countries with an estimated crude reporting rate (per million doses) of 0.57, 0.44, and 0.35 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The observed to expected ratio of VAU was comparable for BNT162b2 (0.023), mRNA-1273 (0.025), and Ad26.COV2.S (0.027). Most cases of VAU were reported in patients who received BNT162b2 (n = 853, 77.97%). The mean age of patients with VAU was 46.24 ± 16.93 years, and 68.65% (n = 751) were women. Most cases were reported after the first dose (n = 452, 41.32%) and within the first week (n = 591, 54.02%) of the vaccination. The onset interval for VAU was significantly longer in patients who received mRNA-1273 (21.22 ± 42.74 days) compared with BNT162b2 (11.42 ± 23.16 days) and rAd26.COV2.S (12.69 ± 16.02 days) vaccines (P < 0.0001). The post hoc analysis revealed a significantly shorter interval of onset for the BNT162b2 compared with the mRNA 1273 vaccine (P < 0.0001). The 30-day risk analysis showed a significant difference among the 3 vaccines (P < 0.0001). CONCLUSIONS: The low crude reporting rate and observed to expected ratio suggest a low safety concern for VAU. This study provides insights into a possible temporal association between reported VAU events and SARS-CoV-2 vaccines; however, further investigations are required to delineate the associated immunological mechanisms.
Eslami M, Kazeminasab S, Sharma V, Li Y, Fazli M, Wang M, Zebardast N, Elze T. PyVisualFields: A Python Package for Visual Field Analysis. Transl Vis Sci Technol 2023;12(2):6.Abstract
PURPOSE: Artificial intelligence (AI) methods are changing all areas of research and have a variety of capabilities of analysis in ophthalmology, specifically in visual fields (VFs) to detect or predict vision loss progression. Whereas most of the AI algorithms are implemented in Python language, which offers numerous open-source functions and algorithms, the majority of algorithms in VF analysis are offered in the R language. This paper introduces PyVisualFields, a developed package to address this gap and make available VF analysis in the Python language. METHODS: For the first version, the R libraries for VF analysis provided by vfprogression and visualFields packages are analyzed to define the overlaps and distinct functions. Then, we defined and translated this functionality into Python with the help of the wrapper library rpy2. Besides maintaining, the subsequent versions' milestones are established, and the third version will be R-independent. RESULTS: The developed Python package is available as open-source software via the GitHub repository and is ready to be installed from PyPI. Several Jupyter notebooks are prepared to demonstrate and describe the capabilities of the PyVisualFields package in the categories of data presentation, normalization and deviation analysis, plotting, scoring, and progression analysis. CONCLUSIONS: We developed a Python package and demonstrated its functionality for VF analysis and facilitating ophthalmic research in VF statistical analysis, illustration, and progression prediction. TRANSLATIONAL RELEVANCE: Using this software package, researchers working on VF analysis can more quickly create algorithms for clinical applications using cutting-edge AI techniques.
Al-Khersan H, Sengillo J, Fan KC, López-Cañizares A, da Cruz NFS, Patel NA, Berrocal AM. Widefield Fluorescein Angiography Findings in Pediatric Patients with X-Linked Retinoschisis. Ophthalmol Retina 2023;7(7):639-643.Abstract
PURPOSE: To evaluate the retinal vasculature in pediatric patients with X-linked retinoschisis (XLRS). DESIGN: Retrospective consecutive case series. SUBJECTS: Pediatric patients with a diagnosis of XLRS who had undergone widefield fluorescein angiography (FA). METHODS: The electronic medical records of pediatric patients with XLRS at a tertiary referral eye center were reviewed from January 2015 to December 2021. Fluorescein angiography images were reviewed for anomalies of the retinal vasculature. MAIN OUTCOMES MEASURES: Vascular anomalies on FA were recorded, including capillary dropout/ischemia, terminal supernumerary vessels, vascular leakage, abnormal vascular loops, straightening of vessels, aberrant circumferential vessels, and neovascularization. RESULTS: In total, 29 eyes of 15 patients were included in the study (1 patient had a phthisical eye). On FA, the most common findings were capillary dropout/ischemia (21 of 29 eyes, 72.4%), terminal supernumerary vessels (21 eyes, 72.4%), abnormal vascular loops (20 eyes, 69%), and vascular leakage (17 eyes, 58.6%). Of the 17 eyes with leakage, the most posterior zone of involvement was zone 1 in 11 eyes (64.7%) and zone 2 in 6 eyes (35.3%). All eyes demonstrated ≥ 1 vascular anomaly on FA. Among the 29 eyes, 23 (79.3%) demonstrated peripheral bullous schisis or retinal detachment (RD) with a mean of 5.6 clock hours of involvement. The presence of either RD or bullous retinal schisis was associated with the incidence of capillary dropout (91.3% in schisis/RD eyes vs. 0% in nonschisis/RD eyes, P < 0.001). Among those with RD or bullous schisis, a higher degree of involvement correlated with more severe capillary dropout (Pearson 0.49, P = 0.025). CONCLUSION: The present study demonstrates consistent vascular changes in pediatric patients with XLRS using widefield FA. Although the presence of capillary ischemia was associated with the severity of bullous schisis or RD, other vascular anomalies were observed in patients both with and without peripheral schisis. Although further research is needed to understand the etiology of these vascular anomalies, FA should be considered in the evaluation of these patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Torm MWE, Dorweiler TF, Fickweiler W, Levine RS, Fort PE, Sun JK, Gardner TW. Frontiers in diabetic retinal disease. J Diabetes Complications 2023;37(2):108386.Abstract
Diabetic retinal disease (DRD) remains a leading cause of vision loss and blindness globally. Although treatments can be effective when given at vision-threatening stages of DRD, there is a lack of knowledge about the earliest mechanisms leading to the development of clinically evident DRD. Recent advances in retinal imaging methods for patients with diabetes allow a more precise and granular characterization of the different stages of DRD than is provided by the classic Diabetic Retinopathy Severity Scale based on fundus photographs. In addition, recent clinical studies have yielded more information on how to adjust blood glucose levels, lipid levels and blood pressure to minimize the risk of DRD. Given the incomplete success of current therapies, there is a critical need for better understanding of the mechanisms underlying DRD and novel treatment targets that address the entire neurovascular retina. Moreover, the causes for interindividual variability in the development of DRD in patients with similar glycemic history and other metabolic factors are not yet clarified either. Finally, greater focus on patients' experience with visual disabilities and treatment effects should be addressed in research in this field.
Righetto GM, de Lopes JLS, Martins Bispo PJ, André C, Souza JM, Andricopulo AD, Beltramini LM, da Camargo ILBC. Antimicrobial Activity of an Fmoc-Plantaricin 149 Derivative Peptide against Multidrug-Resistant Bacteria. Antibiotics (Basel) 2023;12(2)Abstract
Antimicrobial resistance poses a major threat to public health. Given the paucity of novel antimicrobials to treat resistant infections, the emergence of multidrug-resistant bacteria renewed interest in antimicrobial peptides as potential therapeutics. This study designed a new analog of the antimicrobial peptide Plantaricin 149 (Pln149-PEP20) based on previous Fmoc-peptides. The minimal inhibitory concentrations of Pln149-PEP20 were determined for 60 bacteria of different species and resistance profiles, ranging from 1 mg/L to 128 mg/L for Gram-positive bacteria and 16 to 512 mg/L for Gram-negative. Furthermore, Pln149-PEP20 demonstrated excellent bactericidal activity within one hour. To determine the propensity to develop resistance to Pln149-PEP20, a directed-evolution in vitro experiment was performed. Whole-genome sequencing of selected mutants with increased MICs and wild-type isolates revealed that most mutations were concentrated in genes associated with membrane metabolism, indicating the most likely target of Pln149-PEP20. Synchrotron radiation circular dichroism showed how this molecule disturbs the membranes, suggesting a carpet mode of interaction. Membrane depolarization and transmission electron microscopy assays supported these two hypotheses, although a secondary intracellular mechanism of action is possible. The molecule studied in this research has the potential to be used as a novel antimicrobial therapy, although further modifications and optimization remain possible.
Geoffrion D, Melki S, Harissi-Dagher M. Correspondence. Retina 2023;43(5):e30-e31.
Aboobakar IF, Kinzy TG, Zhao Y, Fan BJ, Pasquale LR, Qassim A, Kolovos A, Schmidt JM, Craig JE, Bailey JCN, Wiggs JL, Wiggs JL. Mitochondrial TXNRD2 and ME3 genetic risk scores are associated with specific primary open-angle glaucoma phenotypes. Ophthalmology 2023;Abstract
PURPOSE: Genetic variants in regions that include the mitochondrial genes TXNRD2 and ME3 are associated with primary open-angle glaucoma (POAG) in genome-wide association studies (GWAS). To assess their clinical impact, we investigated whether TXNRD2 and ME3 genetic risk scores (GRSs) are associated with specific glaucoma phenotypes. DESIGN: Cross-sectional study PARTICIPANTS: 2617 POAG cases and 2634 controls from the NEIGHBORHOOD consortium. METHODS: All POAG-associated single nucleotide polymorphisms (SNPs) in the TXNRD2 and ME3 loci were identified using GWAS data (p<0.05). Of these, 20 TXNRD2 and 24 ME3 SNPs were selected after adjusting for linkage disequilibrium. The correlation between SNP effect size and gene expression levels was investigated using the Gene-Tissue Expression (GTEx) database. GRSs were constructed for each individual using the unweighted sum of TXNRD2, ME3, and TXNRD2+ME3 combined risk alleles. Age and gender-adjusted odds ratios (ORs) for POAG diagnosis were calculated per decile for each GRS. Additionally, the clinical features of POAG cases in the top 1, 5, and 10% of each GRS were compared to the bottom 1, 5, and 10%, respectively. MAIN OUTCOME MEASURES: POAG OR per GRS decile; maximal treated intraocular pressure (IOP) and prevalence of paracentral visual field loss among POAG cases with high vs. low GRSs. RESULTS: Increased SNP effect size strongly correlated with higher TXNRD2 and lower ME3 expression levels (r=0.95 and -0.97, respectively, p<0.05 for both). Individuals in decile 10 of TXNRD2+ME3 GRS had the highest odds of POAG diagnosis (OR=1.79 compared to decile 1, p<0.001). POAG cases in the top 1% of TXNRD2 GRS had higher mean maximal treated IOP compared to the bottom 1% (19.9 mmHg vs 15.6 mmHg, adjusted p=0.03). POAG cases in the top 1% of ME3 and TXNRD2+ME3 GRS had a higher prevalence of paracentral field loss compared to the bottom 1% (72.7-88.9% vs 14.3-33.3%; adjusted p=0.03 for both). CONCLUSIONS: POAG patients with higher TXNRD2 and ME3 GRSs had higher treated IOP and a greater prevalence of paracentral field loss. Functional studies exploring how these variants impact mitochondrial function in glaucoma patients are warranted.
Franco JJ, Nagata T, Okamoto T, Mukai S. An ultralow-cost portable centrifuge from discarded materials for medical applications. Sci Rep 2023;13(1):3081.Abstract
Reliable centrifugation for medical applications has historically required access to expensive, bulky, and electricity-dependent commercial devices, which are generally unavailable in resource-poor settings. Although several portable, low-cost, non-electric centrifuges have been described, these solutions have predominately been designed for diagnostic applications requiring sedimentation of relatively small volumes. Moreover, construction of these devices frequently requires access to specialized materials and tools that are often unavailable in underserved areas. Herein, we describe the design, assembly, and experimental validation of the CentREUSE-an ultralow-cost, portable, discarded material-based, human-powered centrifuge for use in therapeutic applications. The CentREUSE demonstrated a mean centrifugal force of 10.5 relative centrifugal force (RCF) ± 1.3. Sedimentation of 1.0 mL triamcinolone acetonide suspension for intravitreal use after 3 min of CentREUSE centrifugation was comparable to that achieved after 12 h of gravity-mediated sedimentation (0.41 mL ± 0.04 vs. 0.38 mL ± 0.03, p = 0.14). Sediment compactness after 5 min and 10 min of CentREUSE centrifugation was similar to that observed after centrifugation with a commercial device for 5 min at 10 RCF (0.31 mL ± 0.02 vs. 0.32 mL ± 0.03, p = 0.20) and 50 RCF (0.20 mL ± 0.02 vs. 0.19 mL ± 0.01, p = 0.15), respectively. Templates and instructions for construction of the CentREUSE are included as part of this open-source publication.
Ahmed I, Hoyek S, Patel NA. Global Disparities in Retinopathy of Prematurity: A Literature Review. Semin Ophthalmol 2023;38(2):151-157.Abstract
PURPOSE: To provide an overview of the impact of retinopathy of prematurity (ROP), and the challenges in the screening, diagnosis, and treatment of ROP worldwide. METHODS: A comprehensive search was conducted using the PubMed database from January 2011 to October 2021 using the following keywords: retinopathy of prematurity, laser, and anti-vascular endothelial growth factor (VEGF). Data on patient characteristics, ROP treatment type, and recurrence rates were collected. The countries included in these studies were classified based on 2021-2022 World Bank definitions of high, upper-middle, lower-middle, and low-income groups. Moreover, a search for surgical outcomes for ROP and screening algorithms and artificial intelligence for ROP was conducted. RESULTS: Thirty-nine studies met the inclusion criteria. ROP treatment and outcomes showed a trend towards intravitreal anti-VEGF injections as the initial treatment for ROP globally and the treatment of recurrent ROP in high-income countries. However, laser remains the treatment of choice for ROP recurrence in middle-income countries. Surgical outcomes for ROP stage 4A, 4B and 5 are similar worldwide. The incidence of ROP and ROP-related visual impairment continue to increase globally. Although telemedicine and artificial intelligence offer potential solutions to ROP screening in resource-limited areas, the current models require further optimization to reflect the global diversity of ROP patients. CONCLUSION: ROP screening and treatment paradigms vary widely based on country income group due to disparities in resources, limited access to care, and lack of universal guidelines.
Singh T, Ichhpujani P, Singh RB, Arya S, Kumar S. Is ultra-thin Descemet stripping automated endothelial keratoplasty a viable alternative to Descemet membrane endothelial keratoplasty? A systematic review and meta-analysis. Ther Adv Ophthalmol 2023;15:25158414221147823.Abstract
BACKGROUND: Ultra-thin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) is a recently developed surgical procedure that has shown promising results for the management of various corneal endothelial diseases. OBJECTIVES: To evaluate the outcomes of the UT-DSAEK to the Descemet membrane endothelial keratoplasty (DMEK). DESIGN: A systematic analysis of the studies comparing UT-DSAEK with DMEK by evaluating one or more outcomes (vision, complications, and post-operative endothelial cell counts) was performed. The meta-analysis was done if two or more studies reported a common outcome. METHODS: We used PubMed, EMBASE, and SCOPUS databases to identify articles comparing the outcomes of UT-DSAEK with DMEK and performed a meta-analysis using RevMan, version 5.4. RESULTS: A total of six studies were included in this review (two randomized clinical trials and four non-randomized comparative studies). Our analysis showed the patients who underwent DMEK cases showed better visual outcomes with a mean difference of 0.06 LogMAR (95% CI: 0.04-0.09) in BCVA, albeit with i 2 of 52% (heterogenous values). The evidence was weak, with the most weightage on retrospective studies. UT-DSAEK showed significantly fewer complications such as graft dislocations, with an odds ratio of 0.25 (95% CI: 0.13-0.48). There was no significant difference in the endothelial cell counts with a mean difference of 86.34 (95%CI: -133.09 to -305.77). CONCLUSION: Although the literature is limited on UT-DSAEK with post-operative visual acuity that could be practically at par with DMEK, lesser complication rates and comparable post-operative endothelial cells could be a suitable alternative to DMEK for corneal endothelial pathologies.
Maturi RK, Glassman AR, Josic K, Baker CW, Gerstenblith AT, Jampol LM, Meleth A, Martin DF, Melia M, Punjabi OS, Rofagha S, Salehi-Had H, Stockdale CR, Sun JK, Sun JK. Four-Year Visual Outcomes in the Protocol W Randomized Trial of Intravitreous Aflibercept for Prevention of Vision-Threatening Complications of Diabetic Retinopathy. JAMA 2023;329(5):376-385.Abstract
IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) injections in eyes with nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) reduce development of vision-threatening complications from diabetes over at least 2 years, but whether this treatment has a longer-term benefit on visual acuity is unknown. OBJECTIVE: To compare the primary 4-year outcomes of visual acuity and rates of vision-threatening complications in eyes with moderate to severe NPDR treated with intravitreal aflibercept compared with sham. The primary 2-year analysis of this study has been reported. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 64 clinical sites in the US and Canada from January 2016 to March 2018, enrolling 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study [ETDRS] severity level 43-53; range, 0 [worst] to 100 [best]) without CI-DME. INTERVENTIONS: Eyes were randomly assigned to 2.0 mg aflibercept (n = 200) or sham (n = 199). Eight injections were administered at defined intervals through 2 years, continuing quarterly through 4 years unless the eye improved to mild NPDR or better. Aflibercept was given in both groups to treat development of high-risk proliferative diabetic retinopathy (PDR) or CI-DME with vision loss. MAIN OUTCOMES AND MEASURES: Development of PDR or CI-DME with vision loss (≥10 letters at 1 visit or ≥5 letters at 2 consecutive visits) and change in visual acuity (best corrected ETDRS letter score) from baseline to 4 years. RESULTS: Among participants (mean age 56 years; 42.4% female; 5% Asian, 15% Black, 32% Hispanic, 45% White), the 4-year cumulative probability of developing PDR or CI-DME with vision loss was 33.9% with aflibercept vs 56.9% with sham (adjusted hazard ratio, 0.40 [97.5% CI, 0.28 to 0.57]; P < .001). The mean (SD) change in visual acuity from baseline to 4 years was -2.7 (6.5) letters with aflibercept and -2.4 (5.8) letters with sham (adjusted mean difference, -0.5 letters [97.5% CI, -2.3 to 1.3]; P = .52). Antiplatelet Trialists' Collaboration cardiovascular/cerebrovascular event rates were 9.9% (7 of 71) in bilateral participants, 10.9% (14 of 129) in unilateral aflibercept participants, and 7.8% (10 of 128) in unilateral sham participants. CONCLUSIONS AND RELEVANCE: Among patients with NPDR but without CI-DME at 4 years treatment with aflibercept vs sham, initiating aflibercept treatment only if vision-threatening complications developed, resulted in statistically significant anatomic improvement but no improvement in visual acuity. Aflibercept as a preventive strategy, as used in this trial, may not be generally warranted for patients with NPDR without CI-DME. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02634333.
Lee HJ, Alipour F, Cruzat A, Posarelli M, Zheng L, Hamrah P. Utility of In Vivo Confocal Microscopy in Diagnosis of Acanthamoeba Keratitis: A Comparison of Patient Outcomes. Cornea 2023;42(2):135-140.Abstract
PURPOSE: The aim of this study was to compare outcomes between cases of Acanthamoeba keratitis (AK) diagnosed and treated with or without the use of in vivo confocal microscopy (IVCM). METHODS: We performed a retrospective comparative case series of 26 eyes of 23 patients diagnosed with AK at the Massachusetts Eye and Ear Infirmary over a 5-year period. The characteristics of all identified cases were summarized. We compared the time from presentation to diagnosis of AK (primary outcome), visual acuity, and rates of therapeutic penetrating keratoplasty between eyes diagnosed by culture-only group (n = 8) and by IVCM to diagnose AK (n = 9) and later confirmed by culture (IVCM/C group). RESULTS: The diagnostic delay was significantly longer in the culture only group (25 ± 29 days) compared with the IVCM/C group (3 ± 3 days, P < 0.01). At 6 months, there was a significant difference in best-corrected visual acuity between the culture-only group (1.46 ± 1.07, n = 7) and the IVCM/C group (0.22 ± 0.22, n = 8), after adjusting for initial baseline visual acuity (P = 0.02). Therapeutic penetrating keratoplasty was performed in 50% of culture-only (n = 7) and 11% of IVCM/C group eyes (n = 9), but this was not statistically significant (P = 0.13). CONCLUSIONS: IVCM can expedite the diagnosis of AK, and its use as an adjunct tool in the diagnosis of AK may result in better patient outcomes compared with basing treatment decisions on corneal cultures alone.

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