Letter Score Research Articles

Visual acuity, full-field stimulus thresholds and electroretinography for 4 years in USH2A-associated retinal degeneration RUSH2A study

PurposeTo describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the RUSH2A study and to assess their suitability as clinical trial endpoints. DesignProspective natural history study. ParticipantsParticipants (n=105) with biallelic disease-causing sequence variants in USH2A and BCVA letter score of ≥54 were included. MethodsBCVA, FST, fundus-guided microperimetry, static perimetry and spectral domain optical coherence tomography were performed annually and ERG at baseline and 4 years only. Mixed effects models were used to estimate annual rates of change with 95% confidence intervals (CI). Associations of change from baseline to 4 years between BCVA, FST, ERG and other metrics were assessed with Spearman correlation coefficients (rs). Main Outcome MeasuresBCVA, FST, ERG. ResultsThe annual rate of decline in BCVA was 0.83 (95% CI: 0.65, 1.02) letters/year. For FST, the change was 0.09 (0.07, 0.11) log cd.s/m2/year for white threshold, 0.10 (0.08, 0.12) log cd.s/m2/year for blue threshold and 0.05 (0.04, 0.06) log cd.s/m2/year for red threshold. Changes were 22.6 (17.4, 28.2) %/year for white threshold, 26.0 (20.3, 32.1) %/year for blue threshold, and 12.3 (8.7, 16.0) %/year for red threshold. The high percentage of eyes with undetectable ERGs at baseline limited assessment of change. ConclusionBCVA was not a sensitive measure of progression over 4 years. FST was a more sensitive measure; however, additional information on the clinical relevance of changes in FST is needed before this test can be adopted as an endpoint for clinical trials.

Evaluation of the Effectiveness of Virtual Telephone Consultations Against Traditional Face-to-Face Consultations in Spine Surgery Using an Objective Metric.

Coronavirus disease 2019 (COVID-19) proved to be a catalyst in the paradigm change from face-to-face (F2F) to virtual consultations in trauma and orthopaedics. This study evaluates the efficacy of telephone consultations versus F2F reviews in an elective spine clinic. In this retrospective study, the clinic lettersfrom elective spinal clinics were conducted over one month.Patients with lumbar spine pathology were included, divided into telephone and F2F groups, and further categorized into new referrals and follow-ups. The Ashford Clinic Letter Score (ACLS) was used to assess the efficacy of consultations. Results: Out of 126 spinal patients reviewed, 92 met the inclusion criteria. Of these, 47 were F2F and 45 were telephone consultations. The mean satisfaction scores for all patients were 7.60 for F2F and 7.42 for telephone consultations, with no significant difference (p=0.202). New patient satisfaction scores were 7.64 for F2F and 7.35 for telephone (p=0.284), and follow-up scores were 7.58 for F2F and 7.48 for telephone (p=0.530). The results showed that there was no difference between face-to-face and virtual consultations. Telephone consultations are nearly as effective as F2F consultations in elective spine clinics, particularly for follow-up patients. The findings support the viability of telemedicine as an economical and efficient alternative method instead of traditional F2F consultations in orthopaedic practice. Further research is needed to explore patient satisfaction and outcomes in other spinal pathologies and to optimise patient stratification for telemedicine.

Aflibercept Biosimilar MYL-1701P vs Reference Aflibercept in Diabetic Macular Edema

Biosimilars may be lower-cost alternatives to originator biologic products, potentially offering expanded access or reduced economic burden, but have not been evaluated with aflibercept in diabetic macular edema (DME). To compare efficacy and safety of MYL-1701P, an aflibercept biosimilar, with reference aflibercept (Eylea [Regeneron]) in DME. This was a double-masked, randomized clinical trial that included participants at 77 centers across the US, Europe, Japan, and India. Included in the analysis were individuals 18 years and older with type 1 or type 2 diabetes with central DME and best-corrected visual acuity (BCVA) letter score of 73 to 38 in the study eye using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Study data were analyzed from October to December 2021. Formulations of MYL-1701P (0.5-mg vial) or reference aflibercept every 4 weeks for 5 consecutive intravitreal injections, followed by every 8 weeks through week 52. The primary outcome was the adjusted difference in least squares mean (SE) change from baseline BCVA letter score at week 8 with an equivalence margin of -3 to +3 letters. Secondary outcomes included change in central subfield thickness (CST), BCVA, number of injections over 52 weeks, incidence of adverse events (AEs), and antidrug antibodies (ADAs). A total of 355 participants (mean [SD] age, 62.2 [9.2] years; 216 male [60.8%]) were randomized to MYL-1701P (179 participants [50.4%]) and aflibercept (176 participants [49.6%]). At week 8, mean (SE) change in BCVA was 6.60 (0.55) letters vs 6.56 (0.55) letters in the MYL-1701P vs aflibercept groups. The adjusted mean difference of 0.04 letters (90% CI, -1.16 to 1.24 letters) met the primary outcome. At week 8, mean (SE) change in CST was -112 (7) μm vs -124 (7) μm in the MYL-1701P vs aflibercept groups (adjusted mean difference, 12 μm; 90% CI, -3 to 26 μm). The incidence of treatment-emergent AEs in the MYL-1701P and aflibercept arms were ocular (30.9% [55 of 178] vs 29.5% [52 of 176]), serious ocular (0.6% [1 of 178] vs 1.1% [2 of 176]), nonocular (65.2% [116 of 178] vs 65.3% [115 of 176]), and serious nonocular (16.9% [30 of 178] vs 11.9% [21 of 176]). The mean (SD) total number of injections was 8.4 (2.1) vs 8.7 (1.8) in the MYL-1701P vs aflibercept groups. The incidence of treatment-induced or treatment-boosted ADAs was 2.8% (5 of 177) vs 5.7% (10 of 176) in the MYL-1701P vs aflibercept arms. MYL-1701P demonstrated clinical equivalence in regard to efficacy, with comparable safety and immunogenicity, to reference aflibercept. These findings support use of MLY-1701P as an alternative to reference aflibercept. ClinicalTrials.gov Identifier: NCT03610646.

Vitrectomy as an Adjunct to Treat-and-Extend Anti-VEGF Injections for Diabetic Macular Edema

There are reported benefits from vitrectomy for diabetic macular edema (DME); however, data precede anti-vascular endothelial growth therapy (VEGF) therapy, supporting a need to assess the current role of vitrectomy. To determine rates of recruitment and efficacy outcomes of vitrectomy plus internal limiting membrane (ILM) peeling adjunctive to treat-and-extend (T&E) anti-VEGF injections for diabetic macular edema (DME). This was a single-masked, multicenter randomized clinical trial at 21 sites in the United Kingdom from June 2018 to January 2021, evaluating single eyes of treatment-naive patients with symptomatic vision loss from DME for less than 1 year. Inclusion criteria were best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score greater than 35 (approximate Snellen equivalent, 20/200 or better) and central subfield thickness (CST) greater than 350 μm after 3 monthly intravitreal injections of ranibizumab or aflibercept. Data analysis was performed in July 2023. Patients were randomized 1:1 into vitrectomy plus standard care or standard care alone and further stratified into groups with vs without vitreomacular interface abnormality. Both groups received a T&E anti-VEGF injection regimen with aflibercept, 2 mg, or ranibizumab, 0.5 mg. The vitrectomy group additionally underwent pars plana vitrectomy with epiretinal membrane or ILM peel within 1 month of randomization. Rate of recruitment and distance BCVA. Secondary outcome measures were CST, change in BCVA and CST, number of injections, rate of completed follow-up, and withdrawal rate. Over 32 months, 47 of a planned 100 patients were enrolled; 42 (89%; mean [SD] age, 63 [11] years; 26 [62%] male) completed 12-month follow-up visits. Baseline characteristics appeared comparable between the control (n = 23; mean [SD] age, 66 [10] years) and vitrectomy (n = 24; mean [SD] age, 62 [12] years) groups. No difference in 12-month BCVA was noted between groups, with a 12-month median (IQR) BCVA letter score of 73 (65-77) letters (Snellen equivalent, 20/40) in the control group vs 77 (67-81) letters (Snellen equivalent, 20/32) in the vitrectomy group (difference, 4 letters; 95% CI, -8 to 2; P = .24). There was no difference in BCVA change from baseline (median [IQR], -1 [-3 to 2] letters for the control group vs -2 [-8 to 2] letters for the vitrectomy group; difference, 1 letter; 95% CI, -5 to 7; P = .85). No difference was found in CST changes (median [IQR], -94 [-122 to 9] μm for the control group vs -32 [-48 to 25] μm for the vitrectomy group; difference, 62 μm; 95% CI, -110 to 11; P = .11). Enrollment goals could not be attained. However, with 47 participants, evidence did not support a clinical benefit of vitrectomy plus ILM peeling as an adjunct to a T&E regimen of anti-VEGF therapy for DME. isrctn.org Identifier: ISRCTN59902040.

Design and Validation of Endophthalmitis Infectivity Measurement Algorithm in Post Cataract Acute Endophthalmitis: EMS Report No. 6.

We constructed a clinical clue-based algorithm to identify the microbiology-positive post-cataract surgery endophthalmitis. The Endophthalmitis Infectivity Measurement Algorithm (EIMA) was constructed using presenting Snellen vision (Letter score [LS]) and Inflammation Score (IS, from the cornea, anterior chamber, iris, and vitreous). Retrospective data (70% for training; 30% for testing) was fitted into CHAID (Chi-squared Automatic Interaction Detection). EIMA was validated with prospective data. EIMA-categorized disease severity was weighed against the symptom duration to detect infecting micro-organisms. EIMA was constructed from 1444 retrospective data. The average LS was 6.03 ± 12.11, median IS was 14 (8-24), and culture positivity was 38%. The accuracy and area under the curve of CHAID were 66.36% and 0.642, respectively. EIMA was validated with 175 prospectively collected data. Microbiology positivity (culture + sequencing) was 58.9%. EIMA sensitivity, specificity, and accuracy against microbiology-positive endophthalmitis were 73.7 (95% confidence interval [CI], 64.19-81.96), 81.9 (95% CI, 71.1-90.02), 77.1 (95% CI, 70.20-83.14), respectively. The positive and negative likelihood ratios were 4.08 (95% CI, 2.46-6.67) and 0.32 (95% CI, 0.22-0.45), respectively. There was higher microbial growth in two days or less than in three- to six-day symptom duration (69.9% vs. 28.2%; P = 0.018) endophthalmitis. Gram-negative infection was higher in two days or less (55.6% vs. 20.2%; P = 0.014), and gram-positive infection was higher in three- to six-day endophthalmitis (62.1% vs. 27.7%; P = 0.027). EIMA identified microbiology-positive endophthalmitis three-quarters of the time. EIMA suggested infectivity and the class of microbial infection could help targeted management of endophthalmitis after cataract surgery.

Safety and Efficacy of Multiple Escalating Doses of RC28-E for Neovascular Age-Related Macular Degeneration: A Phase 1b Trial.

To assess the safety and efficacy of repeated intravitreal injections of RC28-E, a novel bispecific antibody that simultaneously binds vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with neovascular age-related macular degeneration (AMD). This was a prospective, multicenter, open-label clinical trial; 37 patients with choroidal neovascularization secondary to AMD and best-corrected visual acuity (BCVA) letter scores between 73 and 34 were enrolled. Treatment regimens consisted of a 3-month loading phase and a pro re nata (PRN) maintenance phase. This study included three treatment groups: the 0.5, 1.0, and 2.0mg RC28-E groups, with escalating doses ranging from 0.5 to 2.0mg. Patients were evaluated monthly for 48weeks. Safety was assessed based on ocular and systemic adverse events (AEs), pharmacokinetic characteristics, and the presence of anti-RC28-E antibodies. Efficacy was assessed using the mean change in BCVA and central subfield thickness (CST) from baseline to week 48. Most AEs were mild or moderate. The most common AE was a minor injection-related subconjunctival hemorrhage (16.2%). The AEs did not increase with dose or repeated injections. At week 48, mean improvements in BCVA from baseline in the 0.5, 1.0, and 2.0mg groups were 6.1 ± 8.3, 9.9 ± 10.7, and 7.6 ± 9.38 letters, respectively; mean reductions in CST in the three groups were 112.1 ± 160.5, 175.1 ± 212.4, and 128.7 ± 145.8μm, respectively. The serum RC28-E concentrations in 95% of the patients were below the quantification limit of the assay. No significant change from baseline was observed in the mean plasma concentrations of VEGF or FGF over the 48weeks of treatment. Pre-treatment antibodies to RC28-E were detected in 1 of the 37 patients. Antibodies to RC28-E were detected in two patients after dosing with RC28-E for 48weeks. RC28-E was well tolerated and exhibited an overall favorable safety profile with evidence of improvements in BCVA and anatomical parameters.

ROBIN: a randomised, double-masked, placebo-controlled Phase IIa study of the AOC3 inhibitor BI 1467335 in diabetic retinopathy

ObjectiveTo evaluate the safety and efficacy of BI 1467335 in patients with non-proliferative diabetic retinopathy (NPDR).MethodsROBIN is a Phase IIa, double-masked, randomised, placebo-controlled study (NCT03238963). Patients with NPDR and without centre-involved diabetic macular oedema were included; all had a best corrected visual acuity letter score of ≥70 Early Treatment Diabetic Retinopathy Study letters in the study eye at screening. Patients received oral BI 1467335 10 mg or placebo once daily for 12 weeks. Post-treatment follow-up was 12 weeks. The primary endpoint was the proportion of patients over the 24 weeks with ocular adverse events (AEs). Secondary endpoints were the proportion of patients with ≥2-step improvement from baseline in DRSS severity level at Week 12 and the proportion of patients with non-ocular AEs at 24 weeks.ResultsSeventy-nine patients entered the study (BI 1467335, n = 40; placebo, n = 39). The proportion of patients with ocular AEs over 24 weeks was greater in the BI 1467335 versus the placebo group (35.0% vs 23.1%, respectively). Treatment-related AEs were reported for similar numbers of patients in the placebo and BI 1467335 group (7.7% vs 7.5%, respectively). At Week 12, 5.7% (n = 2) of patients in the BI 1467335 group had a 2-step improvement in DRSS severity level from baseline, compared with 0% in the placebo group.ConclusionsBI 1467335 was well tolerated by patients with NPDR. There was a high variability in DRSS levels for individual patients over time, with no clear efficacy signal.

Efficacy of Ranibizumab in the Treatment of Macular Edema Secondary to Retinal Vein Occlusion

Objective: Branch retinal vein occlusion (BRVO), a major cause of vision loss, is a significant ocular health concern. The frequency of macular edema due to BRVO is a critical area of study because of its profound impact on patient quality of life. This study investigated the effectiveness of ranibizumab, a monoclonal antibody fragment and VEGF inhibitor, in the treatment of macular edema in patients with BRVO. Material and Methods: Twelve patients (12 eyes) diagnosed with macular edema secondary to BRVO were included in this study. Patients were selected on the basis of specific visual acuity and macular thickness criteria, excluding those with other ocular conditions or systemic diseases. 0.05 milligrams of ranibizumab was administered intravitreally to each patient. Ophthalmological assessments were conducted both before and after the injection and at 1, 2, 3, and 6-month intervals following medication administration. Results: The average follow-up duration was 5.5±1.16 months (ranging from 2 to 6 months). The average central macular thickness before the injection was 542.66±191.44 µm, which decreased to 320.50±101.44 µm at 1-month post-injection, 283.66±125.01 µm at 2 months, 299.40±91.52 µm at 3 months, and 260.90±144.97 µm at 6 months. The reduction in central macular thickness at all time points was statistically significant (p<0.01). The mean Early Treatment Diabetic Retinopathy Study (ETDRS) letter score was 55.83±23.91 before the injection and improved to 71.25±17.07 at 1 month, 74.33±15.97 at 2 months, 66.7±21.60 at 3 months, and 71.2±17.38 at 6 months post-injection. The increase in visual acuity at 1, 2, 3, and 6 months after the injection was statistically significant compared to the pre-injection ETDRS letter scores (p<0.05). An improvement of two or more lines in visual acuity was observed in 58.3% of cases at 1 month, 58.3% at 2 months, 50% at 3 months, and 80% at 6 months (one line equivalent to five letters). Conclusion: Intravitreal Ranibizumab injections have been found to be effective and reliable in the early stages of treating macular edema due to branch retinal vein occlusion.

Association of Retinal Thickness at Month 1 Postrandomization With Later Thickness and Visual Acuity in Central Vein Occlusion

Purpose: To investigate the association of retinal thickness 1 month post-randomization (1 month after first study injection with aflibercept or bevacizumab) with later retinal thickness, visual acuity, and number of treatments in eyes with central or hemiretinal vein occlusion enrolled in the SCORE2 trial. DesignCohort study using data from a randomized multicenter clinical trial. MethodsAnalysis included 350 SCORE2 participants through 2 years of follow-up. Main outcome measures are central subfield thickness (CST) on spectral domain optical coherence tomography, best-corrected visual acuity letter score (VALS), and number of treatments for macular edema. CST was classified as thin (≤216µm), medium (>216µm and ≤300µm), or thick (>300µm). ResultsAt Month 1, 15% (51/350) of study eyes were in the thin CST class, 57% (199/350) in the medium CST class, and 29% (100/350) in the thick CST class. Of eyes with thin CST at Month 1, 89-96% were also thin during Months 2-12. Over all visits studied, the VALS of eyes in the medium Month 1 CST class was significantly greater than the Month 1 thin class. During Months 6-12 (p<0.001) and 12-24 (p <0.001), but not during Months 0-6 (p=0.36) when monthly treatment was protocol-specified, the mean number of treatments for macular edema per study eye was highest in the thick CST class and lowest in the thin CST class. The thin CST class is significantly more likely to have disorganization of the retinal inner layers inside the central subfield, more paracentral acute middle maculopathy at Month 1, and a history of anti-VEGF treatment prior to trial enrollment. ConclusionsEyes with a thin CST at Month 1 were more likely to be in their Month 1 CST class during Months 2-12 than eyes in the thick or medium Month 1 CST classes. Eyes in the medium CST class had the best VALS, with fewest treatments in the thin class after Month 6. These findings suggest that having a post-treatment thin CST can be as detrimental to visual acuity as having a post-treatment thick CST.

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial

Concerns remain over the long-term safety of vascular endothelial growth factor (VEGF) inhibitors to treat retinopathy of prematurity (ROP). RAINBOW is an open label randomised trial comparing intravitreal ranibizumab (in 0.2mg and 0.1mg doses) with laser therapy in very low birthweight infants (<1500g) with ROP. Of 201 infants completing RAINBOW, 180 were enrolled in the RAINBOW Extension Study. At 5 years, children underwent ophthalmic, development and health assessments. The primary outcome was visual acuity in the better-seeing eye. The study is registered with ClinicalTrial.gov, NCT02640664. Between 16-6-2016 and 21-4-2022, 156 children (87%) were evaluated at 5 years. Of 32 children with no acuity test result, 25 had a preferential looking test, for 4 children investigators reported low vision for each eye, and in 3 further children no vision measurement was obtained. 124 children completed the acuity assessment, the least square mean (95% CI) letter score in the better seeing eye was similar in the three trial arms-66.8 (62.9-70.7) following ranibizumab 0.2mg, 64.6 (60.6-68.5) following ranibizumab 0.1mg and 62.1 (57.8-66.4) following laser therapy; differences in means: ranibizumab 0.2mg v laser: 4.7 (95% CI:-1.1, 10.5); 0.1mg v laser: 2.5 (-3.4, 8.3); 0.2mg v 0.1mg: 2.2 (-3.3, 7.8). High myopia (worse than-5 dioptres) in at least one eye occurred in 4/52 (8%) children following ranibizumab 0.2mg, 8/55 (15%) following ranibizumab 0.1mg and 11/45 (24%) following laser therapy (0.2mg versus laser: odds ratio: 3.99 (1.16-13.72)). Ocular and systemic secondary outcomes and adverse events were distributed similarly in each trial arm. 5-year outcomes confirm the findings of the original RAINBOW trial and a planned interim analysis at 2 years, including a reduced frequency of high myopia following ranibizumab treatment. No effects of treatment on non-ocular outcomes were detected. Novartis Pharma AG.

Phase 2 Trial Evaluating Minocycline for Geographic Atrophy in Age-Related Macular Degeneration

Existing therapies to slow geographic atrophy (GA) enlargement in age-related macular degeneration (AMD) have relatively modest anatomic efficacy, require intravitreal administration, and increase the risk of neovascular AMD. Additional therapeutic approaches are desirable. To evaluate the safety and possible anatomic efficacy of oral minocycline, a microglial inhibitor, for the treatment of GA in AMD. This was a phase 2, prospective, single-arm, 45-month, nonrandomized controlled trial conducted from December 2016 to April 2023. Patients with GA from AMD in 1 or both eyes were recruited from the National Institutes of Health (Bethesda, Maryland) and Bristol Eye Hospital (Bristol, UK). Study data were analyzed from September 2022 to May 2023. After a 9-month run-in phase, participants began oral minocycline, 100 mg, twice daily for 3 years. The primary outcome measure was the difference in rate of change of square root GA area on fundus autofluorescence between the 24-month treatment phase and 9-month run-in phase. Of the 37 participants enrolled (mean [SD] age, 74.3 [7.6] years; 21 female [57%]), 36 initiated the treatment phase. Of these participants, 21 (58%) completed at least 33 months, whereas 15 discontinued treatment (8 by request, 6 for adverse events/illness, and 1 death). Mean (SE) square root GA enlargement rate in study eyes was 0.31 (0.03) mm per year during the run-in phase and 0.28 (0.02) mm per year during the treatment phase. The primary outcome measure of mean (SE) difference in enlargement rates between the 2 phases was -0.03 (0.03) mm per year (P = .39). Similarly, secondary outcome measures of GA enlargement rate showed no differences between the 2 phases. The secondary outcome measures of mean difference in rate of change between 2 phases were 0.2 letter score per month (95% CI, -0.4 to 0.9; P = .44) for visual acuity and 0.7 μm per month (-0.4 to 1.8; P = .20) for subfoveal retinal thickness. Of the 129 treatment-emergent adverse events among 32 participants, 49 (38%) were related to minocycline (with no severe or ocular events), including elevated thyrotropin level (15 participants) and skin hyperpigmentation/discoloration (8 participants). In this phase 2 nonrandomized controlled trial, oral minocycline was not associated with a decrease in GA enlargement over 24 months, compared with the run-in phase. This observation was consistent across primary and secondary outcome measures. Oral minocycline at this dose is likely not associated with slower rate of enlargement of GA in AMD.

Risk Factors for Meeting Criteria for Switching from Bevacizumab to Aflibercept When Treating Eyes with Diabetic Macular Edema and Visual Acuity of < 20/40

ObjectiveTo identify factors for meeting prespecified criteria for switching from bevacizumab to aflibercept in eyes with center-involved diabetic macular edema (CI-DME) and moderate vision loss initially treated with bevacizumab in DRCR Retina Network Protocol AC. DesignPost hoc analysis of data from a randomized clinical trial Participants270 participants with one or both eyes with CI-DME and visual acuity (VA) letter score of 69 to 24 (Snellen equivalent 20/50-20/320) MethodsEligible eyes were assigned to receive intravitreal aflibercept monotherapy (N=158) or bevacizumab followed by aflibercept if prespecified criteria for switching were met between 12 weeks and 2 years (N=154). Main Outcome MeasuresMeeting switching criteria: 1) at any time, 2) at 12 weeks, and 3) after 12 weeks. Associations between meeting the criteria for switching and factors measured at baseline and 12 weeks were evaluated in univariable analyses. Stepwise procedures were used to select variables for multivariable models. ResultsIn the bevacizumab first group, older participants had higher risk of meeting the switching criteria at any time, with a hazard ratio (HR) for a 10-year increase in age (95% confidence interval) of 1.32 (1.11 – 1.58). Male participants or eyes with worse baseline VA were more likely to switch at 12 weeks (HR for male vs. female = 4.84 [1.32 – 17.81]; HR for 5-letter lower baseline VA: 1.30 [1.03 – 1.63]). Worse 12-week CST (HR for 10-μm greater = 1.06 [1.04 – 1.07]) was associated with increased risk for switching after 12 weeks. The mean (SD) improvement after completing the switch to aflibercept was 3.7 (4.9) letters. ConclusionsThe identified factors can be used to refine expectations regarding the likelihood that an eye will meet protocol criteria to switch to aflibercept when treatment is initiated with bevacizumab. Older patients are more likely to be switched. At twelve weeks, thicker central subfield thickness was predictive of eyes most likely to be switched in the future.

Enhancing the Functional Performance of Patients with Late-Stage Age-Related Macular Degeneration Implanted with a Miniature Telescope using Rehabilitation Training.

In this work, our aim is to report the functional outcomes of cataract surgery with smaller-incision new-generation miniature telescope (SING IMT) implantation followed by rehabilitation training in patients with central visual loss due to late-stage age-related macular degeneration (AMD). This retrospective study included patients who were monocularly implanted with SING IMT and then followed a rehabilitation program based on 6 biweekly sessions focused on visual abilities, reading, writing, visual motor integration and mobility. A total of 11 participants were included in this study. Reading acuity (RA), reading speed (RS), and fixation stability (FS) were assessed biweekly at 6-, 8-, 10-, 12-, 14-, and 16-week follow-up visits after SING IMT implantation and at a final assessment at 24weeks. Best-corrected distance visual acuity (BCDVA) was also measured at baseline and at the same postoperative timepoints. Mean baseline BCDVA was 12.5 ± 8.6 letter score. Both RA and RS were found to be significantly improved from the first rehabilitation session (6weeks after surgery) to the last session (24weeks after surgery). At the end of the rehabilitation program, mean RA was 0.45 ± 0.19 LogMAR and mean RS was 30.9 ± 17.6 words per minute. Moreover, all patients achieved a FS of 15s or more after the last rehabilitation session. Most patients (55%) achieved an improvement of 15 letters in BCDVA at the end of the study. This study suggests that rehabilitation training can improve visual functions of patients with late-stage AMD implanted with SING IMT in real-world tasks such as reading skills.

Real-world visual acuity outcomes for patients with naïve neovascular age-related macular degeneration treated with aflibercept, ranibizumab, or bevacizumab in the Republic of Korea.

To compare the visual outcomes of different anti-vascular endothelial growth factor (VEGF) drugs, including aflibercept, ranibizumab, and bevacizumab, in a real-world setting in Korea. We collected data from patients who received monotherapy using one of these three anti-VEGF drugs as naïve treatment after being diagnosed with neovascular age-related macular degeneration. The number of injections and visual acuity (VA) outcomes of each cohort were obtained and pairwise comparisons were performed using propensity score matching. A total of 254 aflibercept, 238 ranibizumab, and 282 bevacizumab treatment-naïve eyes were included. The mean VA change at 3 years for all cohorts combined was -1.8 letters, and the mean number of injections was 9.4. In the direct comparison of the three drugs, the mean change in the VA letter score was +2.0 letters for aflibercept and -11.7 letters for bevacizumab (P < 0.001). The number of aflibercept injections was significantly higher than the number of bevacizumab injections (P = 0.002). The visual outcomes for aflibercept and ranibizumab were +4.7 letters and -1.9 letters, respectively, and comparable results were obtained (P = 0.13). The VA outcomes for ranibizumab and bevacizumab were also not significantly different (P = 0.09). The numbers of injections for aflibercept, ranibizumab, and bevacizumab were 10.8, 6.7, and 8.8, respectively. Significant differences were observed between the injection frequencies comparisons of aflibercept and ranibizumab and ranibizumab and bevacizumab (P < 0.001 and P = 0.002, respectively). In the Korean clinical medical environment, which included various confounding factors, especially socioeconomic ones, the aflibercept VA outcome was significantly better than that of bevacizumab, and aflibercept injections were the most numerous. These real-world data imply that the drug effect as well as the environment in which the drug can be sufficiently used affected patient final VA scores.

DISPARITIES IN MOCA AND MMSE SCORES AMONG DIVERSE OLDER ADULTS: A CASE ANALYSIS OF CREOLE-SPEAKING PARTICIPANTS

Abstract Almost 11% of older adults in the US have Alzheimer’s or related dementia. Most studies suggest that those who are Black or Hispanic are at higher risk. A culturally diverse sample, including Haitian older adults, was recruited from South Florida communities to participate in a longitudinal study, “In-Vehicle Sensors to Detect Change in Cognition of Older Drivers.” An extensive cognitive battery was administered for comparison with driving behaviors. No validated translations in Creole were available, so three Haitian-born examiners translated and back-translated test items into Creole. Two additional bilingual examiners verified the results. An analysis of variance (ANCOVA) comparing Haitian participants (N=12) and European Americans (N=135) on the MoCA controlling for age and education indicated the European American group scored higher (M = 25.78, SD = 2.57) than the Haitian Group (M =24.17, SD = 3.01), a significant difference in test performance, F (1, 124) = 6.11, P= .015. Results on four subscales of the MoCA evidenced significantly higher scores for the European American group: Visual EX Total, F (1, 124) = 22.52, p &amp;lt; .001; Serial-7, F (1, 124) = 12.09, p &amp;lt;.001; Attention Total, F (1, 124) = 5.10, p &amp;lt;.001; Letter Score F (1, 124) = 13.09, p &amp;lt;.001. No differences in language, abstract, delayed recall, or orientation were found. These preliminary results suggest cultural influences may account for differences in test performance. Further investigation with a larger sample of Haitian older adults is needed to explain differences in performance on this widely used test.

Efficacy and Safety of Biosimilar QL1207 vs. the Reference Aflibercept for Patients with Neovascular Age-Related Macular Degeneration: A Randomized Phase 3 Trial.

This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73-34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2mg (0.05ml) in the study eye every 4weeks for the first 3months, followed by 2mg every 8weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. A total of 366 patients were enrolled (QL1207 group, n = 185; aflibercept group, n = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changeswas - 1.1 letters(95% confidence interval - 3.0 to 0.7; P = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

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.

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.

Long-Term Control of Retinal Thickness Variability and Vision Following the 0.19 mg Fluocinolone Acetonide Implant.

Purpose: To assess the impact of retinal thickness variability (RTV) control on visual and treatment burden outcomes in patients with diabetic macular edema (DME) who received the 0.19 mg fluocinolone acetonide (FAc) intravitreal implant (Iluvien, Alimera Sciences). Methods: This post hoc analysis examined the outcomes of a 3-year, phase 4, nonrandomized, open-label observational study. Retinal thickness was measured as central subfield thickness (CST). RTV was quantified by CST area under the curve (CST-AUC), retinal thickness amplitude (RTA), and retinal thickness standard deviation (RTSD). Visual outcomes were measured as best-corrected visual acuity (BCVA), and treatment burden was measured as the number of yearly supplemental DME treatments. Results: The percentage of eyes with a CST ≤300 µm fluctuated throughout the study but was significantly increased relative to baseline at 36 months (baseline: 32.9% vs 36 months: 46.8%; P < .05). FAc significantly reduced RTV in all measures more than 36 months (P < .0001). When divided into quartiles, eyes with the best RTV control post FAc had the greatest BCVA gains and improved disease control (ie, reduced need for supplemental therapy). The last-observed BCVA letter score exhibited linear correlations with CST-AUC (R2 = -0.100), RTA (R2 = -0.125), and RTSD (R2 = -0.162). A multivariate linear regression with baseline BCVA as a covariate displayed improved correlations with the last-observed BCVA, CST-AUC (R2 = -0.448), RTA (R2 = -0.432), and RTSD (R2 = -0.436). Conclusions: The sustained corticosteroid release of the 0.19 mg FAc implant reduced RTV in patients with DME, which directly correlated with significantly improved vision and a reduced supplemental treatment burden.

Revisiting the relationships of n-gram measures to L2 writing proficiency: Comparisons between genres and connections to vocabulary levels

The effect of multiword sequences on L2 writing proficiency among different genres and their relations to vocabulary levels are understudied. In this study 60 indices of bigrams and trigrams related to frequency, association, range and proportion of frequent n-grams were employed to analyze 600 rated English essays and 600 rated English request letters composed by Chinese high school students. We investigated whether there were similar or varied n-gram measures predictive of their holistic scores among the two genres and the relationship between specific multiword combinations connected to the n-gram measures predictive of writing scores and their vocabulary levels in the Chinese national English curriculum. The results showed that three pairs of similar n-gram measures predicted the holistic scores among these two types of writings, but five indices were uniquely associated with letter scores. Additionally, in both genres, higher mean MI associations in more proficient compositions were significantly correlated to more multiword combinations containing words from college and graduate levels in advanced writings than in intermediate writings. This study contributed to a better understanding of the relations among word associations, vocabulary levels and writing proficiency among high school student English writings.