Treatment Diabetic Retinopathy Study Letters Research Articles

Vision loss reduction with avacincaptad pegol for geographic atrophy: a 12-month post hoc analysis of the GATHER1 and GATHER2 trials

To evaluate the impact of reduction in geographic atrophy (GA) lesion growth on visual acuity in the GATHER trials using categorical outcome measures. Randomized, double-masked, sham-controlled phase 3 trials. Aged ≥50 years with non-center point involving GA and best corrected visual acuity (BCVA) of 25-80 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye. GATHER1 consisted of 2 parts. In Part 1, 77 patients were randomized 1:1:1 to avacincaptad pegol (ACP) 1 mg, ACP 2 mg, and sham. In Part 2, 209 patients were randomized 1:2:2 to ACP 2 mg, ACP 4 mg, and sham. In GATHER2, patients were randomized 1:1 to ACP 2 mg (n=225) and sham (n=223). A post hoc analysis of 12-month data for pooled ACP 2 mg and sham groups is reported. Proportion of study eyes that experienced ≥10-, ≥15-, or ≥20-BCVA ETDRS letter loss from baseline to month 12; time-to-event analysis of persistent vision loss of ≥10-, ≥15-, or ≥20-BCVA letters from baseline at ≥2 consecutive visits over 12 months; proportion of study eyes with BCVA loss to a level below driving eligibility threshold at month 12 among those eligible to drive at baseline. Lower proportions of study eyes experienced ≥10-, ≥15-, or ≥20-BCVA letter loss from baseline over 12 months with ACP 2 mg (11.6%, 4.0%, and 1.6%, respectively) vs sham (14.1%, 7.6%, and 4.5%, respectively). There was a reduction in the risk of persistent loss of ≥15-BCVA ETDRS letters with ACP 2 mg (3.4%) vs sham (7.8%) through 12 months. A lower proportion of study eyes treated with ACP 2 mg reached the threshold for driving ineligibility vs sham by 12 months. Treatment with ACP 2 mg delayed the risk of progression to persistent vision loss (ie, ≥10-, ≥15-, and ≥20-BCVA letter loss or BCVA loss to a level below driving eligibility threshold) vs sham over 12 months.

The Reinforced Treat-and-Extend Protocol for Exudative Age-Related Macular Degeneration: Retrospective Assessment of 24-Month Real-World Outcomes in France.

The aim of this work is to evaluate the real-world outcomes of the reinforced treat-and-extend (RTE) protocol for the treatment of exudative age-related macular degeneration with intravitreal injections of aflibercept or ranibizumab (anti-vascular endothelial growth factor therapies). This was a retrospective review of patients from two tertiary ophthalmology centers in France initiating the RTE protocol between February 2018 and June 2021. The primary outcome was change in best-corrected visual acuity (BCVA) after 24months. Secondary outcomes were change in central retinal thickness (CRT), recurrence, and management-related factors (injection interval, number of injections/consultations). Outcomes were additionally evaluated after protocol changes (strict versus modified RTE protocol groups). Sixty-eight patients (72 eyes) were included (68% females; mean age 82.2 ± 7.8years). After 24months, mean BCVA significantly improved (65.22 ± 14 vs. 71.96 ± 13 Early Treatment Diabetic Retinopathy Study letters; p < 0.001) and CRT significantly decreased (388.6 ± 104 vs. 278.8 ± 51μM; p < 0.001) with 21% of eyes showing signs of exudation. Over the 24months, a mean total of 14.9 ± 4.0 injections and 8.6 ± 1.4 consultations were performed. Mean 24-month injection interval was 7.9 ± 2.3weeks. Initial and 24-month ophthalmic outcomes for eyes in the strict (47%) versus modified (53%) groups were not significantly different, but mean time interval to first recurrence of disease activity was significantly shorter for the modified group (7.3 ± 2.4 vs. 9.9 ± 2.5weeks; p < 0.001). Patients in the strict RTE group received significantly less injections (13.9 ± 3.6 vs. 16.5 ± 3.9; p = 0.006) and mean 24-month injection interval was significantly longer (9.5 ± 2.7 vs. 6.5 ± 2.1weeks; p < 0.001). Consultation number was similar (8.5 ± 1.9 vs. 8.8 ± 1.6; p = 0.93). Treatment with aflibercept versus ranibizumab did not influence ophthalmic or management outcomes. The RTE protocol, even when modified, reduced consultations but improved ophthalmic outcomes. The RTE protocol could reduce hospital visits and overall burden while also encouraging better patient compliance. Video Abstract available for this article. Vincent Soler and François-Philippe Roubelat summarize the Reinforced Treat-and-Extend Protocol and main results (MP4 225022 KB).

The Natural History of Retinal Sensitivity Loss in Diabetic Macular Ischemia over One Year Evaluated by Microperimetry.

Background/Objectives: This one-year prospective observational study, conducted at two centers, aimed to report the natural history of retinal sensitivity (RS) loss in diabetic macular ischemia (DMI). Methods: Patients with stable-treated proliferative diabetic retinopathy (PDR) were recruited if there was evidence of DMI on optical coherence tomography angiography, defined as a foveal avascular zone ≥ 0.5 mm2 or parafoveal capillary dropout ≥ 1 quadrant. The minimal visual acuity required for performing microperimetry (MP) was ≥54 Early Treatment Diabetic Retinopathy Study letters (Snellen equivalent 20/80). The overall RS (oRS) and pointwise sensitivity (PWS) within the 3 × 3 mm macula were assessed at baseline and twelve months. A value <25 decibels (dB) was defined as impaired RS, and a decrease of 2 and 7 dB was regarded as mild and severe loss, respectively. Results: A total of 88 patients (97 eyes) were included. No statistically significant MP changes were detected at one year. However, 10% of the cohort lost oRS ≥ 2 dB, and 73% lost ≥2 dB PWS in ≥5 loci, whereas 1% lost oRS ≥ 7 dB, and 4% lost ≥7 dB PWS in ≥5 loci. The foveola and temporal parafovea were the most vulnerable to severe RS loss. Compared to their counterpart, eyes with baseline oRS ≥ 25 dB had significantly more RS loss in the macula and superior parafovea (55% versus 32% and 53% versus 28%, both p = 0.01). Conclusions: Rather than oRS loss, ≥2 dB loss in PWS in ≥5 loci is a more feasible outcome measure for clinical trials in DMI.

Clinical effects of atorvastatin combined with conbercept in the treatment of patients with macular edema secondary to retinal vein occlusion and carotid plaque: study protocol for a prospective randomized controlled trial.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs have been widely used in patients with macular edema (ME) secondary to retinal vein occlusion (RVO); however, recurrence is a major concern. This study aims to observe the clinical effects of atorvastatin and intravitreal therapy in the treatment of patients with branch or central RVO-ME and coexistent carotid plaques (CP). A prospective randomized controlled clinical trial will be conducted. Sixty-four patients diagnosed with branch or central RVO-ME and coexistent CP will be enrolled and randomly allocated in a 1:1 ratio to the control and experimental groups. The control group will be treated with intravitreal conbercept monthly for 3 months, followed by monthly evaluation and injection of pro re nata (PRN) for 12 months, while the experimental group will be treated with oral atorvastatin 20 mg daily combined with the control group treatment. If a drop of best-corrected visual acuity (BCVA) is more than five Early Treatment Diabetic Retinopathy Study (ETDRS) letters (one line) or an increment in central subfield thickness (CSFT) of 100 μm (or a 10% increment from the previous visit), intravitreal re-treatment will be performed. Outcome measurements include CSFT, BCVA, number of injections, and incidence of adverse events during the 12-month follow-up period. Differences between groups will be evaluated using Student's t-test, and comparisons between groups will be evaluated using repeated-measures analysis of variance. The study has been approved by the Institutional Review Board of Nanjing Lishui People's Hospital, Nanjing, China (approval number 2023KY0418-12, dated 18 April 2023), and has been registered on chictr.org.cn. Written informed consent will be collected from each patient and the results of this trial will be submitted to a peer-reviewed journal. Chinese Clinical Trial Registry ChiCTR2300071359. Registered on 12 May 2023.

REDUCING TREATMENT BURDEN FOR AGE-RELATED MACULAR DEGENERATION PATIENTS: A SYSTEMATIC REVIEW OF RANIBIZUMAB PORT DELIVERY SYSTEM

Introduction and Objective: Ranibizumab port delivery system (PDS) is a newly developed method that provides a continuous, long-term supply of ranibizumab into the vitreous, reducing the burden of monthly intravitreal injection visits for neovascular age-related macular degeneration (nAMD) patients. This review aims to evaluate the efficacy and safety of ranibizumab PDS in nAMD. &#x0D; Methods: An extensive literature search was performed on 4 online databases: PubMed, Cochrane, ProQuest, and ScienceDirect. The inclusion criteria are human studies comparing ranibizumab port delivery system and intravitreal ranibizumab, English language, with full-text journal available. The main outcome measurements are best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters, central foveal thickness (CFT), and adverse events.&#x0D; Result: Two randomized controlled trials (RCTs) with a total of 635 adults were evaluated. At week 96, ranibizumab PDS reported observed mean BCVA changes from baseline (-1.0; +4.2; ETDRS letters) compared to monthly intravitreal ranibizumab (-1.1; +6.1; ETDRS letters). However, there was an increase in mean CFT changes from baseline (+9.9; -15.3 vs ?1.3; -21.3, µm) and more severe adverse events frequency (22; 4 vs 4; 0) with ranibizumab PDS versus monthly intravitreal ranibizumab, respectively. &#x0D; Conclusion: Ranibizumab PDS showed comparable visual outcomes to intravitreal ranibizumab while demonstrating marginally inferior anatomical outcomes and higher incidence of severe adverse effects. Despite this, with fewer treatment visits required for up to 24 weeks, ranibizumab PDS can potentially reduce the treatment burden in nAMD patients with poor compliance. Further studies are needed to provide better patient eligibility guidelines and recommendations for adverse event management of ranibizumab PDS.

A Prospective, Observational, Non-interventional Clinical Study of Participants With Choroideremia: The NIGHT Study

The NIGHT study aimed to assess the natural history of choroideremia (CHM), an X-linked inherited chorioretinal degenerative disease leading to blindness, and determine which outcomes would be the most sensitive for monitoring disease progression. A prospective, observational, multicenter cohort study. Males aged ≥18 years with genetically confirmed CHM, visible active disease within the macular region, and best-corrected visual acuity (BCVA) ≥34 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline were assessed for 20 months. The primary outcome was the change in BCVA over time at Months 4, 8, 12, 16, and 20. A range of functional and anatomical secondary outcome measures were assessed up to Month 12, including retinal sensitivity, central ellipsoid zone (EZ) area, and total area of fundus autofluorescence (FAF). Additional ocular assessments for safety were performed. A total of 220 participants completed the study. The mean BCVA was stable over 20 months. Most participants (81.4% in the worse eye and 77.8% in the better eye) had change from baseline > -5 ETDRS letters at Month 20. Interocular symmetry was low overall. Reductions from baseline to Month 12 were observed (worse eye, better eye) for retinal sensitivity (functional outcome; -0.68 dB, -0.48 dB), central EZ area (anatomical outcome; -0.276 mm2, -0.290 mm2), and total area of FAF (anatomical outcome; -0.605 mm2, -0.533 mm2). No assessment-related serious adverse events occurred. Retinal sensitivity, central EZ area, and total area of FAF are more sensitive than BCVA in measuring the natural progression of CHM.

Assistance Burden Comparison Between Age-Related Macular Degeneration and Retinal Angiomatous Proliferation Over a Three-Year Follow-up.

We compared assistance burden between neovascular age-related macular degeneration (nAMD) and retinal angiomatous proliferation (RAP) under intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment on a treat-and-extend (T&E) regimen in a third-level hospital in a developed country. This retrospective study using data from the Fight Retinal Blindness! Registry included patients treated between January 2016 and December 2020. Final event was established as best corrected visual acuity (BCVA) lower than 20 Early Treatment Diabetic Retinopathy Study letters. According to choroidal neovascularization (CNV), three different study groups were established: type 1, 2, and 3. A total of 285 eyes of 227 patients were included. Mean age was 80.1 ± 6.5, 79.1 ± 7.9, and 81.2 ± 7.2 years, for the three study groups, respectively. Mean injections were 16.0 ± 4.8, 16.5 ± 4.1, and 14.1 ± 5.7, respectively; and mean number of visits were 17.9 ± 4.3, 18.2 ± 3.1, and 16.8 ± 5.3, respectively. No differences were found (P > 0.05). Survival curves and log-rank analysis also showed no differences (P = 0.344). Cox proportional hazard models showed that a lower baseline BCVA, subfoveal geographic atrophy (GA), and subfoveal fibrosis (SF) were associated with a higher risk of reaching ≤ 20 letters. nAMD and RAP under a T&E regimen indicate a high assistance burden during the first three years. The presence of subfoveal GA or SF are associated with a BCVA lower than 20 letters. [Ophthalmic Surg Lasers Imaging Retina 2024;55:197-203.].

Implementation of a retinal stroke-code protocol results in visual recovery in patients receiving reperfusion therapies.

Reperfusion therapies represent promising treatments for patients with Central Retinal Artery Occlusion (CRAO), but access is limited due to low incidence and lack of protocols. We aimed to describe the benefit of implementing a Retinal Stroke-Code protocol regarding access to reperfusion, visual acuity and aetiological assessment. Prospective cohort study performed at a Comprehensive Stroke Centre. Criteria for activation were sudden monocular, painless vision loss within 6 h from onset. Eligible patients received IAT when immediately available and IVT otherwise. All patients were followed by ophthalmologists to assess best-corrected visual acuity (BCVA) and visual complications, and by neurologists for aetiological workup. Visual amelioration was defined as improvement of at least one Early Treatment Diabetic Retinopathy Study (ETDRS) letter from baseline to 1 week. Of 49 patients with CRAO, 15 (30.6%) received reperfusion therapies (12 IVT, 3 IAT). Presentation beyond 6 h was the main contraindication. Patients receiving reperfusion therapies had better rates of visual improvement (33.3% vs 5.9%, p = 0.022). There were no complications related to reperfusion therapies. Rates of neovascular glaucoma were non-significantly lower in patients receiving reperfusion therapies (13.3% vs 20.6%, p = 0.701). Similar rates of atherosclerotic, cardioembolic and undetermined aetiologies were observed, leading to 10 new diagnosed atrial fibrillation and five carotid revascularizations. A comprehensive acute management of CRAO is feasible despite low incidence. In our study, reperfusion therapies were safe and associated with higher rates of visual recovery. A similar etiological workup than ischemic stroke led to of high proportion of underlying aetiologies.

Safety Results for Geographic Atrophy Associated with Age-Related Macular Degeneration Using Subretinal Cord Blood Platelet-Rich Plasma

PurposeTo evaluate the safety of subretinal injection of cord blood platelet-rich plasma (CB-PRP) and its possible effect in eyes affected by geographic atrophy (GA) associated with dry age-related macular degeneration (d-AMD). DesignInterventional, open-label study started in January 2021 with at 12 months of follow-up (the Si.Cord Study). This study was a single-center, nonrandomized, sequential-assigned clinical trial conducted in Rome, Italy, at Fondazione Policlinico Universitario Agostino Gemelli IRCCS (ClinicalTrials.gov_NCT04636853). Subjects, Participants, and ControlsThirteen patients (26 eyes) with bilateral d-AMD-related GA were enrolled. One eye from each patient (with more advanced GA) underwent CB-PRP treatment, and the fellow eye was considered the control. All patients participated in follow-up at 12 months. InterventionAll 13 eyes received 23-gauge (G) vitrectomy and subretinal injection of CB-PRP using a 41-G needle. Main Outcomes and MeasuresBest corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study (ETDRS) letters, central macular thickness using optical coherence tomography (OCT) and atrophic area measured on en-face OCT images were assessed at baseline, 1, 3, 6 and 12 months. ResultsThe BCVA in the treated group was 34.46 ± 20.8 ETDRS at baseline; 40.84 ± 20.52 at 1 month; 40.07 ± 20.34 at 3 months; 39.38 ± 19.84 at 6 months and 35.84 ± 18.38 at 12 months. In the untreated group, the BCVA was 53 ± 21.1 ETDRS letters at baseline; 51.54 ± 20.99 at 1 month; 46.62 ± 19.47 at 3 months; 46.85 ± 18.58 at 6 months and 43.92 ± 17.97 at 12 months (two-way ANOVA: interaction of treatment by eye or time, p= -0.084). Central macular thickness (CMT) did not show a significant inter-eye difference at 12 months (p=0.97). The atrophic geographic areas tended to increase in both treated and fellow eyes at 12 months (p<0.0001). No inflammatory reaction, endophthalmitis, retinal detachment, uveitis, or other complications due to the subretinal injection of CB-PRP were observed during the follow-up. ConclusionsSubretinal injection of CB-PRP could be safely used for d-AMD in its GA form. Despite its safety, a larger cohort of patients, and probably a new way of administration, will be needed in order to understand whether the CB-PRP could have a role in the GA treatment.

Face-down positioning or posturing after macular hole surgery.

Face-down positioning or posturing after macular hole surgery.

Efficacy and Safety of Brolucizumab for Diabetic Macular Edema

Despite the effectiveness of existing anti-vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME). To evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME. This 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021. Brolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks. Participants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52. A total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, -0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, -237.8 μm; aflibercept, -196.5 μm; difference, -41.4; 95% CI, -58.9 to -23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion. In these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified. ClinicalTrials.gov Identifier: NCT03917472.

Maintenance of Vision Needed to Drive after Intravitreal Anti-VEGF Therapy in Patients with Neovascular Age-related Macular Degeneration and Diabetic Macular Edema

To evaluate the association between intravitreal anti-VEGF therapy and visual acuity (VA)/driving vision maintenance over 4 years in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME). Retrospective, observational, clinical practice cohort study using data from the Vestrum Health database. Initial diagnosis (January 1, 2014 to June 30, 2019) of nAMD or DME and ≥ 1 year of treatment/follow-up history. The VA analysis required 4 years of treatment/follow-up history. For the driving vision maintenance analysis, patients required Snellen VA of 20/40 or better at baseline and for ≥ 6 months during year 1 after index intravitreal anti-VEGF treatment in the better-seeing eye. A loss-of-driving event was the first clinic visit with VA worse than 20/40 sustained for ≥ 6 consecutive months. Kaplan-Meier analyses estimated the probability of maintaining driving vision over 4 years stratified by year-1 injection number. Cox proportional hazard models examined associations between baseline clinical characteristics and year-1 injection frequency and the risk of losing driving vision. Mean change in VA over time and by baseline VA, driving vision maintenance probability over time and stratified by anti-VEGF injection frequency, and baseline factors predictive of driving vision maintenance. In year 1, the nAMD and DME cohorts gained 8.5 and 9.5 ETDRS letters, respectively. Between years 1 and 4, patients with nAMD and DME lost 6.6 and 2.7 ETDRS letters, respectively. The probability of maintaining driving vision over 4 years was 56% (nAMD) and 72% (DME); among patients who received 1 to 5, 6 to 7, and ≥ 8 anti-VEGF injections in year 1, corresponding probabilities were 50%, 56%, and 65% (nAMD; P < 0.001) and 63%, 72%, and 77% (DME; P < 0.001). Baseline factors associated with driving vision loss included older age, worse index VA, geographic atrophy (nAMD), and worsening baseline diabetic retinopathy (DME). Older age and worse index VA were risk factors for driving vision loss, whereas a greater year-1 injection number was associated with driving vision maintenance through year 4, supporting early initiation and frequent anti-VEGF injections for maintaining driving vision in nAMD or DME. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Use of Adjunctive Corticosteroid With Antivascular Endothelial Growth Factor Agents in the Treatment of Choroidal Neovascular Membrane Associated With Presumed Ocular Histoplasmosis

Purpose: To evaluate the impact of combination treatment of antivascular endothelial growth factor (anti-VEGF) intravitreal injections and corticosteroids in patients with choroidal neovascularization (CNV) secondary to presumed ocular histoplasmosis syndrome (POHS). Methods: A retrospective multicenter study was conducted in a cohort from Illinois and Missouri. Patients were identified over an 8-year period, and data were evaluated over a 1-year study window commencing with treatment initiation. Group 1 included patients treated with intravitreal injections of anti-VEGF, and group 2 included those who received intravitreal injections of anti-VEGF and adjuvant corticosteroids. Optical coherence tomography (OCT) measurements and increases in Early Treatment Diabetic Retinopathy Study (ETDRS) letter score were compared between each group. Results: Using the method of last visit carried forward, the visual acuity (VA) in group 2 was 6.42 ETDRS letters better than the VA in group 1 at the final assessment. Patients in group 2 had a mean ETDRS letter gain of 21.50 ( P = .06) from the initial baseline vision. The average amount of decrease in OCT central subfield thickness compared with baseline was lower in group 1 (80.9 ± 129.8 µm) vs group 2 (102.8 ± 90.40 µm) at the 1-year follow-up visit ( P = .25). Conclusions: Approved treatment of CNV secondary to POHS is limited. Adjuvant corticosteroid treatment in patients with CNV secondary to POHS may provide better long-term vision and OCT outcomes than anti-VEGF alone and may offer an additional therapy option for these patients.

Clinical Correlation of Retinal Fluid Fluctuation Represented by Fluctuation Index in Wet Age-Related Macular Degeneration: TOWER Study Report 2.

To explore outcomes and biomarkers associated with retinal fluid instability represented by a new parameter in neovascular age-related macular degeneration (nAMD). Patients with treatment-naïve nAMD receiving anti-vascular endothelial growth factor (VEGF) injections for a duration of 1 to 3 years were consecutively reviewed. Fluctuation Index (FI) of each eye, calculated by averaging the sum of differences in 1-mm central subfield thickness between each follow-up from months 3 to 24, was arranged into ascending order from the lowest to the highest and split equally into low, moderate, and high fluctuation groups. Outcomes were analyzed at 24 months. Of 558 eyes, FI values showed a negative correlation with a degree-response gradient with 24-month visual improvement. After controlling for baseline best-corrected visual acuity and potential confounders, eyes with low fluctuation gained more Early Treatment Diabetic Retinopathy Study letters than those in the moderate and high fluctuation group (Δ, 10.1 and 14.0 letters, respectively). Significant best-corrected visual acuity improvement from baseline to month 24 (11.8 letters) was observed exclusively in the low fluctuation group despite the indifference in the number of injections and types of anti-VEGF drug used among groups. Patients presenting with central subfield thickness of ≥405 µm or intraretinal fluid coinciding with subretinal fluid showed a significant association with foveal thickness instability during the maintenance phase. Apart from the central subfield thickness values, unstable macular thickening represented by the FI was associated with some baseline features and may contribute to substandard visual outcomes. FI may be a valuable tool for assessing therapeutic adequacy in the treatment of nAMD.

Validation of the Waterloo Differential Visual Acuity Test (WatDAT) and Comparison With Existing Pediatric Tests of Visual Acuity.

The new Waterloo Differential Acuity Test (WatDAT) is designed to allow recognition visual acuity (VA) measurement in children before they can typically undertake matching tests. The study purpose was to validate WatDAT in adults with normal and reduced VA. Eighty adults (18 to <40 years of age) participated (32 normal VA, 12 reduced VA, and 36 simulated reduced VA). Monocular VA was measured on two occasions in random order for WatDAT (versions with 3 and 5 distractors for Faces and Patti Pics house among circles), Lea Symbols, Kay Pictures and Patti Pics matching tests, Teller Acuity Cards, Cardiff Acuity Test, and Early Treatment Diabetic Retinopathy Study (ETDRS) letter chart. Pediatric tests were validated against ETDRS using limits of agreement (LoA), sensitivity, and specificity. The LoA for repeatability were also determined. WatDAT showed minimal bias compared with ETDRS, and LoAs, which were similar to pediatric matching tests (0.241-0.250). Both preferential looking tests showed higher bias and LoAs than ETDRS. Matching tests showed good agreement with ETDRS, except for Kay Pictures and Lea Uncrowded test, which overestimated VA. WatDAT showed high sensitivity (>0.96) and specificity (>0.79), which improved with criterion adjustment and were significantly higher than for the preferential looking tests. LoA for repeatability for WatDAT 3 Faces and WatDAT 5 Faces were comparable with the ETDRS. WatDAT demonstrates good agreement and repeatability compared with the gold-standard ETDRS letter chart, and performed better than preferential looking tests, the alternative until a child can undertake a matching VA test. Good validity of the Waterloo Differential Acuity Test was demonstrated in adults as a first step to showing its potential for detecting childhood visual disorders.

Topographic Correlation of Microperimetry With Structural Characteristics in Diabetic Macular Ischemia

This study aimed to determine the threshold for defining abnormal retinal sensitivity (RS) that correlates with structural changes in diabetic macular ischemia (DMI) patients with stable treated proliferative diabetic retinopathy (PDR). Prospective cross-sectional study. In a single center, we recruited 85 eyes (67 patients) with stable treated PDR with best-corrected visual acuity (BCVA) ≥54 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (Snellen equivalent 20/80) and optical coherence tomography angiography evidence of DMI. The function-function and function-structure correlation were assessed. Two pre-selected thresholds in overall RS (oRS), 25 decibels (dB) and age-matched normative data (AMND), were tested on their ability to reflect abnormal anatomy in DMI. Finally, a multivariable regression model was established to depict the relationship between the oRS and various parameters. The oRS showed only a modest correlation with BCVA and low-luminance visual acuity (LLVA). The whole image deep vessel density (wiDVD) was the most reliable vascular metric correlated with RS. For every 1% decline in the wiDVD, the oRS decreased by 0.37 dB (P < .001) after multivariable adjustment. Furthermore, both a reduction of oRS to <25 dB or < AMND could differentiate eyes with FAZ ≥0.5 mm2, whole image superficial vessel density (wiSVD) <37.7%, wiDVD <41.9%, and the presence of disorganization of the retinal inner layers (DRIL) from their counterparts. The absolute value of 25 dB in oRS is worth considering as a trial endpoint as it does not require complex calculation and closely reflects the structural abnormalities in DMI.

Comparative assessment of subretinal hyper-reflective material in patients treated with brolucizumab versus aflibercept in HAWK and HARRIER

PurposePost hoc analysis of the phase III HAWK and HARRIER studies to compare the reductions in subretinal hyper-reflective material (SHRM) thickness following brolucizumab 6 mg or aflibercept 2 mg treatment...

Ten-year real-world outcomes of antivascular endothelial growth factor therapy in neovascular age-related macular degeneration using pro re nata regimen

Background/aimsTo analyse long-term outcomes of antivascular endothelial growth factor (anti-VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD) using pro re nata (PRN) regimen in a single-centre clinical...

Trends in Secondary Intraocular Lens Surgery among Vitreoretinal Surgeons

To identify changes in secondary lens techniques over time and to determine common complications of each technique. Retrospective cohort study. All patients in the database from January 2015-December 2021 who underwent secondary lens placement (anterior chamber IOL, scleral fixated IOL, or scleral sutured IOL). Rates of secondary IOL surgery technique were analyzed in 3597 participants in a nationwide aggregated electronic health care database using 2 sample independent T-tests. Rates of post-operative rhegmatogenous retinal detachment (RRD) following secondary IOL surgery were assessed using chi square test of proportion. Post-operative visual acuity was assessed using 2 sample independent T-tests. The primary outcome was change in IOL technique over time. Secondary datapoints examined were the development of post-operative rhegmatogenous retinal detachment (RRD) following secondary IOL surgery, visual acuity changes, the development of endophthalmitis, suture erosion, haptic erosion, or corneal edema following IOL surgery. ACIOL use decreased over the 7-year period from 93% of cases to 36% of cases (p<0.0001), while SFIOL use increased from 3% to 34% (p<0.0001), and SSIOL use increased from 4% to 30% (p<0.0001). Visual acuity increased for each surgical technique (ACIOL: 44.1 vs. 49.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, p<0.001; SFIOL: 48.7 vs. 57.6 letters, p<0.001; SSIOL: 51.5 vs. 61.2 letters, p<0.001), with larger visual acuity gains seen in SFIOL and SSIOL use (ACIOL vs. SFIOL, p=0.004; ACIOL vs. SSIOL, p=0.002; SFIOL vs. SSIOL, p=0.64). Average RRD rates did not significantly differ between techniques. Rates of endophthalmitis, haptic erosion, and suture erosion were low and did not significantly differ between techniques. Rates of corneal edema were significantly higher in ACIOL cases (vs. SFIOL, p<0.0001; vs. SSIOL, p<0.0001). Rates of ACIOL implantation performed by vitreoretinal surgeons have decreased over time with more vitreoretinal surgeons electing to place either a SFIOL or SSIOL towards the end of the study period; complication profiles among the three techniques may be similar.

LONG-TERM PROGNOSIS OF CHOROIDAL NEOVASCULARIZATION COMPLICATING ANGIOID STREAKS.

To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era. Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak-associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum ("PXE" or "no PXE") and between eyes previously treated or not with photodynamic therapy ("PDT" or "no PDT"). Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47-175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively. Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks.