IMAGING PREDICTORS OF FUNCTIONAL OUTCOMES AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To evaluate the microstructural optical coherence tomography and fundus autofluorescence imaging predictors of visual acuity, metamorphopsia, and aniseikonia following rhegmatogenous retinal detachment repair. METHODS: This is a multicenter retrospective study of patients with primary rhegmatogenous retinal detachment who underwent repair. Best-corrected visual acuity, metamorphopsia, and aniseikonia were formally tested at 3 months postoperatively. Metamorphopsia and aniseikonia were quantitatively assessed with M-CHARTS and the New Aniseikonia Test, respectively. High-resolution spectral-domain optical coherence tomography and fundus autofluorescence images were obtained at 3 months postoperatively. Images were assessed for discontinuity of the outer retinal bands on optical coherence tomography and retinal displacement detected by retinal vessel printings on fundus autofluorescence by two masked graders with disagreements adjudicated by a third senior masked grader. Multiple linear regression models were used to determine the predictors of postoperative visual acuity, metamorphopsia, and aniseikonia. RESULTS: Six hundred fourteen eyes of 614 patients were included in this study. Regression analysis indicated that significant early postoperative (at 3 months) imaging predictors of visual acuity were discontinuity of the external limiting membrane (P = 0.001) and the presence of retinal vessel printings on fundus autofluorescence (P = 0.033). Discontinuity of interdigitation zone was a significant predictor of metamorphopsia [horizontal metamorphopsia (P =0.004); vertical metamorphopsia (P = 0.056); average of horizontal metamorphopsia + vertical metamorphopsia (P = 0.008)], and presence of retinal vessel printings was a significant predictor of aniseikonia (P = 0.04). CONCLUSION: Discontinuity of the external limiting membrane and retinal displacement were significant predictors of postoperative visual acuity following rhegmatogenous retinal detachment repair. Discontinuity of the interdigitation zone and retinal displacement were significant predictors of metamorphopsia and aniseikonia, respectively.

Integrated Assessment of OCT, Multimodal Imaging, and Cytokine Markers for Predicting Treatment Responses in Retinal Vein Occlusion Associated Macular Edema: A Comparative Review of Anti-VEGF and Steroid Therapies.

Retinal vein occlusion (RVO) is a significant cause of vision loss, characterized by the occlusion of retinal veins, leading to conditions such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). Macular edema (ME), a prevalent consequence of RVO, is the primary cause of vision impairment in affected patients. Anti-VEGF agents have become the standard treatment, showing efficacy in improving visual acuity (VA) and reducing ME. However, a subset of patients exhibit a suboptimal response to anti-VEGF therapy, necessitating alternative treatments. Corticosteroids, which address inflammatory pathways implicated in ME, have shown promise, particularly in cases resistant to anti-VEGF. This review aims to identify biomarkers that predict treatment response to corticosteroids in RVO-associated ME, utilizing multimodal imaging and cytokine assessments. Baseline imaging, including SD-OCT and OCT-A, is essential for evaluating biomarkers like hyperreflective foci (HRF), serous retinal detachment (SRF), and central retinal thickness (CRT). Elevated cytokine levels, such as IL-6 and MCP-1, correlate with ME severity and poor anti-VEGF response. Early identification of these biomarkers can guide timely transitions to corticosteroid therapy, potentially enhancing treatment outcomes. The practical conclusion of this review is that integrating biomarker assessment into clinical practice enables personalized treatment decisions, allowing for earlier and more effective management of RVO-associated ME by transitioning patients to corticosteroid therapy when anti-VEGF agents are insufficient. Advanced diagnostics and machine learning may further refine personalized treatment strategies, improving the management of RVO-associated ME.

Harvesting Magneto-Acoustic Waves Using Magnetic 2D Chromium Telluride (CrTe3).

A vast majority of electrical devices have integrated magnetic units, which generate constant magnetic fields with noticeable vibrations. The majority of existing nanogenerators acquire energy through friction/mechanical forces and most of these instances overlook acoustic vibrations and magnetic fields. Magnetic two-dimensional (2D) tellurides present a wide range of possibilities for devising a potential flexible energy harvester. 2D chromium telluride (2D CrTe3) is synthesized, which exhibits ferromagnetic behavior with a higher T c of ≈224 K. The structure exhibits stable high remnant magnetization, making 2D CrTe3 a potential material for harvesting magneto-acoustic waves. A magneto-acoustic nanogenerator (MANG) is fabricated and the basic mechanical stability and sensitivity of the device with change in load conditions are tested. A high surface charge density of 2.919 mC m-2 is obtained for the device. The thermal strain created in the lattice structure is examined using in-situ Raman spectroscopy. The magnetic anisotropy energy (MAE) responsible for long-range FM ordering is calculated by theoretical modelling with insights into opening of electronic bandgap which enhances the flexoelectric effects. The MANG can be a potential NG to synergistically tap into the magneto-acoustic vibrations generated from the frequency changes of a vibrating device such as loudspeakers.

Reattachment rate with pneumatic retinopexy versus pars plana vitrectomy for single break rhegmatogenous retinal detachment.

AIM: To assess the primary reattachment rate (PARR) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD) meeting the Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomised Trial (PIVOT) criteria with a single break in detached retina. METHODS: A post hoc analysis of two clinical trials. To be included, patients with primary RRD had to meet PIVOT criteria but could have only one break in the detached retina. Patients with additional pathology in the attached retina were included in a secondary analysis. The primary outcome was PARR following PnR versus PPV at 1-year postoperatively. RESULTS: 162 patients were included. 53% (86/162) underwent PnR and 47% (76/162) had a PPV. 99% (85/86) and 86.8% (66/76) completed the 1-year follow-up visits in the PnR and PPV groups, respectively. PARR was 88.2% (75/85) in the PnR group and 90.9% (60/66) in the PPV group (p=0.6) with a mean postoperative logMAR best-corrected visual acuity of 0.19±0.25 versus 0.34±0.37 (Snellen 20/30 vs 20/44) (p=0.01) each in the PnR and PPV groups, respectively.In an additional analysis of patients who were also allowed to have any pathology in the attached retina, the PARR was 85% (91/107) and 91.6% (66/72) in the PnR and PPV groups, respectively (p=0.18). CONCLUSIONS: PnR and PPV provide similar long-term PARR in a substantial proportion of patients meeting PIVOT criteria with only a single break in the detached retina. Therefore, in patients meeting these specific criteria, PnR is an appropriate first-line therapy as it offers superior functional outcomes without compromising PARR.

Facedown Positioning in Macular Hole Surgery: A Systematic Review and Individual Participant Data Meta-Analysis.

TOPIC: To assess the anatomical and visual effects of facedown positioning (FDP) advice in patients undergoing vitrectomy with gas tamponade for idiopathic full-thickness macular holes (FTMHs), and to explore differential treatment effects by macular hole size and FDP duration. CLINICAL RELEVANCE: The necessity and duration of FDP for FTMH closure remain contentious, with no consensus guidelines. METHODS: Prospectively registered systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials comparing FDP to no FDP (nFDP) across the MEDLINE, Embase, and Cochrane Library databases and clinical trial registries from January 2000 to March 2023 (CRD42023395152). All adults with idiopathic FTMHs undergoing vitrectomy with gas tamponade were included. The main outcomes were primary macular hole closure and post-operative visual acuity at 6 months or nearest time point. RESULTS: Of 8 eligible trials, 5 contributed IPD for 379 eyes and were included in our analysis. The adjusted odds ratio (OR) for primary closure with FDP versus nFDP was 2.41 (95% CI 0.98 to 5.93, P = 0.06) [GRADE: Low], translating to a relative risk (RR) of 1.08 (1.00 to 1.11) and a number needed to treat (NNT) of 15. The FDP group exhibited a mean improvement in post-operative visual acuity of -0.08 logMAR (-0.13 to -0.02, P = 0.006) [GRADE: Low] compared to the nFDP group. Benefits were more certain in participants with larger holes of minimum linear diameter ≥ 400 µm: adjusted OR for closure ranged from 1.13 to 10.12 (P = 0.030) (NNT 12), with a mean visual acuity improvement of -0.18 to -0.01 logMAR (P = 0.022). Each additional day of FDP was associated with improved odds of anatomical success (adjusted OR 1.02 to 1.41, RR 1.00 to 1.02, P = 0.026) and visual acuity improvement (-0.02 logMAR, -0.03 to -0.01, P = 0.002), possibly plateauing at 3 days. CONCLUSION: This study provides low certainty evidence that FDP improves the anatomical and visual outcomes of macular hole surgery modestly and indicate that the effect may be more substantial for macular holes exceeding 400 µm. The findings support recommending FDP for patients with macular holes exceeding 400 µm pending further investigation.

Duration of face down positioning following full-thickness macular hole repair: A protocol for a randomized pilot study.

OBJECTIVE: Full-thickness macular holes (FTMH) are defects in the fovea involving all neural retinal layers. They reduce patients' visual acuity (VA) and impact their quality of life. FTMHs are repaired with pars plana vitrectomy (PPV) with intraocular gas tamponade and post-operative face-down positioning (FDP). There is no consensus regarding the ideal positioning requirements following FTMH repair and there lacks clear guidelines on the topic. While analysis of global practice patterns indicates that between 5-7 days is the most common duration suggested by surgeons, there is significant heterogeneity in surgeon preferences. There is, however, biological plausibility to support minimal or even no FDP following surgery and given the disabling nature of FDP for patients, there is a need to better assess key patient outcomes with different FDP durations. As such, this prospective randomized controlled pilot trial will compare 3-days of FDP to 7-days of FDP following PPV for FTMH. METHODS: This single-centered, parallel-group randomized controlled pilot trial will randomize patients 1:1 following PPV to 3 days or 7 days of FDP. This investigation has been approved by the local ethics board (HiREB # 16100) and has been registered on clinicaltrials.gov (NCT06000111). The primary objective will be focused on assessing the feasibility of a larger trial; this will be determined through an assessment of the recruitment rate, retention rate, completion rate and recruitment time. The secondary outcomes involve assessment of the following patient-important outcomes a) macular hole closure rate, b) best-recorded VA, c) a general quality of life measure and vision-specific quality of life measure, d) patient compliance and e) complication rates. Outcomes will be evaluated at 3 months following surgery. DISCUSSION: The results of this pilot study will determine the feasibility of a larger-scale trial that will answer a patient important question with clinical equipoise.

Impact of COVID-19 on a real-world treat-and-extend regimen with aflibercept for neovascular age-related macular degeneration.

OBJECTIVE: To assess the effect of the COVID-19 pandemic on injection intervals among patients treated for neovascular age-related macular degeneration. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients treated at a single practice using a treat-and-extend regimen with intravitreal aflibercept between December 2018 and April 2021. METHODS: The primary outcome was the change in injection intervals. Secondary outcomes included differences in best-recorded visual acuity (BRVA) and central subfield thickness (CST). Associations were evaluated with linear mixed-effects modelling. RESULTS: This study included 1839 injections from 185 eyes (141 patients). The median (interquartile range) injection intervals in the pre-COVID-19 and COVID-19 periods were 60 (42-70) and 70 (49-90) days, respectively. The pandemic was associated with a mean injection interval lengthening of 7.2 days (P < 0.001), a decrease in BRVA of 3.1 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and a reduction in CST of 14.7 µm (P = 0.003). The presence of exudative intraretinal fluid was associated with a reduction in treatment intervals of 11.1 days (P < 0.001), a reduction in BRVA of 1.9 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and an increase in CST of 52.4 µm (P < 0.001). The presence of subretinal fluid was associated with a reduction in treatment intervals of 8.5 days (P < 0.001) and an increase in CST of 21.6 µm (P < 0.001). CONCLUSIONS: This real-world study estimated that the severe acute respiratory syndrome coronavirus 2 pandemic resulted in an injection extension of 7.2 days with associated decreases in BRVA and CST that are unlikely clinically significant on a population basis. This builds on evidence suggesting that long-term vascular endothelial growth factor suppression can facilitate meaningful interval extensions while maintaining visual acuity.

Exploring the fragility of meta-analyses in ophthalmology: a systematic review.

OBJECTIVE: The fragility index (FI) of a meta-analysis evaluates the extent that the statistical significance can be changed by modifying the event status of individuals from included trials. Understanding the FI improves the interpretation of the results of meta-analyses and can help to inform changes to clinical practice. This review determined the fragility of ophthalmology-related meta-analyses. METHODS: Meta-analyses of randomized controlled trials with binary outcomes published in a journal classified as 'Ophthalmology' according to the Journal Citation Report or an Ophthalmology-related Cochrane Review were included. An iterative process determined the FI of each meta-analysis. Multivariable linear regression modeling evaluated the relationship between the FI and potential predictive factors in statistically significant and non-significant meta-analyses. RESULTS: 175 meta-analyses were included. The median FI was 6 (Q1-Q3: 3-12). This meant that moving 6 outcomes from one group to another would reverse the study's findings. The FI was 1 for 18 (10.2%) of the included meta-analyses and was ≤5 for 75 (42.4%) of the included meta-analyses. The number of events (p < 0.001) and the p-value (p < 0.001) were the best predictors of the FI in both significant and non-significant meta-analyses. CONCLUSION: The statistical significance of meta-analyses in ophthalmology often hinges on the outcome of a few patients. The number of events and the p-value are the most important factors in determining the fragility of the evidence. The FI is an easily interpretable measure that can supplement the reader's understanding of the strength of the evidence being presented. PROSPERO REGISTRATION: CRD42022377589.

Outcomes of Postcataract Surgery Endophthalmitis Managed Without Microbial Cultures.

PURPOSE: To evaluate outcomes of eyes with postcataract surgery endophthalmitis that were managed without microbial cultures. DESIGN: This retrospective, single-center comparative cohort study identified all cases of endophthalmitis after cataract surgery presenting between February 1, 2014, and November 1, 2022. SUBJECTS: All eyes presenting with presumed endophthalmitis requiring in-office treatment with intravitreal antibiotics and either a vitreous or aqueous tap were included. METHODS: Endophthalmitis cases were divided into the "culture group," if the vitreous or aqueous specimens were sent for microbiologic sampling, or into the "no culture group" if an aqueous or vitreous tap was performed but not sent for microbiologic sampling. MAIN OUTCOME MEASURES: Best-corrected visual acuity (VA) 12 months after endophthalmitis presentation, incidence of retinal detachment, and need for subsequent procedures. RESULTS: Of the 232 endophthalmitis cases identified, 196 (85%) were in the "culture group" and 36 (15%) were in the "no culture group." At endophthalmitis presentation, eyes in the "culture group" had a mean (standard deviation [SD]) logarithm of the minimum angle of resolution (logMAR) VA (Snellen equivalent) of 2.14 (0.8) (20/2760) and mean (SD) logMAR VA in the "no culture group" was 1.93 (0.8) (20/1702) (P = 0.185). At 12-month follow-up, mean (SD) logMAR VA for the "culture group" was 0.80 (1.0) (20/126) and 0.41 (0.5) (20/50) in the "no culture group" (adjusted difference = 0.41, 95% confidence interval = -0.043 to 0.857, P = 0.076). Twenty of 196 (10%) eyes in the "culture group" developed secondary retinal detachments within 12 months of presentation compared with 0 in the "no culture group" (P = 0.045). CONCLUSIONS: Eyes with endophthalmitis after cataract surgery managed without microbiologic cultures have similar visual outcomes to eyes managed with microbiologic cultures and may be less likely to develop secondary retinal detachments. This may be an acceptable strategy to manage endophthalmitis after cataract surgery when prompt access to a microbiologic facility is unavailable. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Experimentally validated inverse design of multi-property Fe-Co-Ni alloys.

This study presents a machine learning (ML) framework aimed at accelerating the discovery of multi-property optimized Fe-Ni-Co alloys, addressing the time-consuming, expensive, and inefficient nature of traditional methods of material discovery, development, and deployment. We compiled a detailed heterogeneous database of the magnetic, electrical, and mechanical properties of Fe-Co-Ni alloys, employing a novel ML-based imputation strategy to address gaps in property data. Leveraging this comprehensive database, we developed predictive ML models using tree-based and neural network approaches for optimizing multiple properties simultaneously. An inverse design strategy, utilizing multi-objective Bayesian optimization (MOBO), enabled the identification of promising alloy compositions. This approach was experimentally validated using high-throughput methodology, highlighting alloys such as Fe66.8Co28Ni5.2 and Fe61.9Co22.8Ni15.3, which demonstrated superior properties. The predicted properties data closely matched experimental data within 14% accuracy. Our approach can be extended to a broad range of materials systems to predict novel materials with an optimized set of properties.

Outcomes of Eyes Lost to Follow-up After Treatment With Intraocular or Periocular Steroid Injections.

Purpose: To evaluate the visual, intraocular pressure (IOP), and anatomic outcomes of eyes with loss to follow-up (LTFU) after intravitreal or periocular steroid injections. Methods: Patients receiving intraocular or periocular steroid injections and with LTFU for at least 180 days were included in this retrospective cohort study. Charts were reviewed for the visual acuity (VA), IOP, and central foveal thickness at the visit before LTFU, the first return visit, and 3, 6, and 12 months after return. Results: Fifty-three eyes of 47 patients were identified. The mean (±SD) age was 62.3 ± 14.9 years, the mean LTFU time was 295 ± 181.2 days (range, 182-1101), and the mean follow-up after return was 354 ± 339.3 days (range, 32-1141). The overall mean number of steroid injections was 5.2 ± 3.9 (range, 1-18). Compared with the mean logMAR VA at the visit before LTFU (0.59 [Snellen 20/77]), the mean VA remained stable at all timepoints after return as follows: return visit (0.62 [20/83]; P = .6), month 3 (0.55 [20/70]; P = .6), month 6 (0.55 [20/70]; P = .5), month 12 (0.64 [20/87]; P = .6), and final visit (0.69 [20/97]; P = .2). At the first return visit, 8 (15%) of 53 patients had an IOP of 21 mm Hg or higher (range, 21-31); 2 required treatment with a new antihypertensive medication (latanoprost and timolol, respectively). Conclusions: Patients with LTFU after receiving steroid injections maintained their VA. No patient required incisional glaucoma surgery. Compared with other etiologies, eyes with diabetic macular edema had a greater increase in IOP.

Understanding network meta-analysis methodology for the ophthalmologist.

PURPOSE OF REVIEW: Over the past decade, the number of studies published using network meta-analyses (NMAs) has rapidly increased, and there have been continued advancements to further advance this analysis approach. Due to the fast moving and changing landscape in the infancy of NMA methodology, there is a lack of consistency and standardization for this approach. This article aims to summarize the crucial components of an NMA for both future readers, and for potential NMA authors. RECENT FINDINGS: Key components of NMAs include, but are not limited to, reporting the proposed analysis methods, assessment of risk of bias within the included studies, reporting the overall quality of the available evidence, and defining the parameters in which the results will be presented. Although NMA allows for a comprehensive evaluation of all available treatment options for a given condition, we believe that there is importance in ensuring clear understanding and appropriate interpretation of results to inform clinical practice. SUMMARY: While many components of NMA mirror those of traditional pairwise meta-analysis, there are many novel methodologies that are specific to this approach. It is imperative that future NMAs follow guidance from key methodology groups, as these provide valuable tools for conducting and reporting NMAs.

Rationale and Design of VOYAGER: Long-term Outcomes of Faricimab and Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Clinical Practice.

Purpose: To describe the rationale and design of the VOYAGER (NCT05476926) study, which aims to investigate the safety and effectiveness of faricimab and the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) in clinical practice. VOYAGER also aims to understand drivers of clinical practice treatment outcomes by gaining novel insight into the intersection of treatment regimens, decisions, anatomic outcomes, and vision. Design: Primary data collection, noninterventional, prospective, multinational, multicenter clinical practice study. Participants: At least 5000 patients initiating/continuing faricimab or PDS for nAMD/DME (500 sites, 31 countries). Methods: Management will be per usual care, with no mandated scheduled visits/imaging protocol requirements. Using robust methodologies, relevant clinical and ophthalmic data, including visual acuity (VA), and data on treatment clinical setting/regimens/philosophies, presence of anatomic features, and safety events will be collected. Routinely collected fundus images will be uploaded to the proprietary Imaging Platform for analysis. An innovative investigator interface will graphically display the patient treatment journey with the aim of optimizing treatment decisions. Main Outcome Measures: Primary end point: VA change from baseline at 12 months per study cohort (faricimab in nAMD and in DME, PDS in nAMD). Secondary end points: VA change over time and per treatment regimens (fixed, treat-and-extend, pro re nata, and other) and number. Exploratory end points: VA change in relation to presence/location of anatomic features that impact vision (fluid, central subfield thickness, fibrosis, atrophy, subretinal hyperreflective material, diabetic retinopathy severity, and disorganization of retinal inner layers) and per treatment regimen/philosophies. The impact of regional and practice differences on outcomes will be assessed as will safety. Results: Recruitment commenced in November 2022 and will continue until late 2027, allowing for up to 5 years follow-up. Exploratory interim analyses are planned annually. Conclusions: VOYAGER is an innovative study of retinal diseases that will assess the effectiveness and safety of faricimab and PDS in nAMD and DME and identify clinician- and disease-related factors driving treatment outcomes in clinical practices globally to help optimize vision outcomes. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Maintenance of proteostasis by Drosophila Rer1 is essential for competitive cell survival and Myc-driven overgrowth.

Defects in protein homeostasis can induce proteotoxic stress, affecting cellular fitness and, consequently, overall tissue health. In various growing tissues, cell competition based mechanisms facilitate detection and elimination of these compromised, often referred to as 'loser', cells by the healthier neighbors. The precise connection between proteotoxic stress and competitive cell survival remains largely elusive. Here, we reveal the function of an endoplasmic reticulum (ER) and Golgi localized protein Rer1 in the regulation of protein homeostasis in the developing Drosophila wing epithelium. Our results show that loss of Rer1 leads to proteotoxic stress and PERK-mediated phosphorylation of eukaryotic initiation factor 2α. Clonal analysis showed that rer1 mutant cells are identified as losers and eliminated through cell competition. Interestingly, we find that Rer1 levels are upregulated upon Myc-overexpression that causes overgrowth, albeit under high proteotoxic stress. Our results suggest that increased levels of Rer1 provide cytoprotection to Myc-overexpressing cells by alleviating the proteotoxic stress and thereby supporting Myc-driven overgrowth. In summary, these observations demonstrate that Rer1 acts as a novel regulator of proteostasis in Drosophila and reveal its role in competitive cell survival.