Best-corrected Visual Acuity Letter Score Research Articles

Association of Retinal Thickness at Month 1 Post-Treatment 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.

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.

Machine Learning to Predict Faricimab Treatment Outcome in Neovascular Age-Related Macular Degeneration

To develop machine learning (ML) models to predict, at baseline, treatment outcomes at month 9 in patients with neovascular age-related macular degeneration (nAMD) receiving faricimab. Retrospective proof of concept study. Patients enrolled in the phase II AVENUE trial (NCT02484690) of faricimab in nAMD. Baseline characteristics and spectral domain-OCT (SD-OCT) image data from 185 faricimab-treated eyes were split into 80% training and 20% test sets at the patient level. Input variables were baseline age, sex, best-corrected visual acuity (BCVA), central subfield thickness (CST), low luminance deficit, treatment arm, and SD-OCT images. A regression problem (BCVA) and a binary classification problem (reduction of CST by 35%) were considered. Overall, 10 models were developed and tested for each problem. Benchmark classical ML models (linear, random forest, extreme gradient boosting) were trained on baseline characteristics; benchmark deep neural networks (DNNs) were trained on baseline SD-OCT B-scans. Baseline characteristics and SD-OCT data were merged using 2 approaches: model stacking (using DNN prediction as an input feature for classical ML models) and model averaging (which averaged predictions from the DNN using SD-OCT volume and from classical ML models using baseline characteristics). Treatment outcomes were defined by 2 target variables: functional (BCVA letter score) and anatomical (percent decrease in CST from baseline) outcomes at month9. The best-performing BCVA regression model with respect to the test coefficient of determination (R2) was the linear model in the model-stacking approach with R2 of 0.31. The best-performing CST classification model with respect to test area under receiver operating characteristics (AUROC) was the benchmark linear model with AUROC of 0.87. A post hoc analysis showed the baseline BCVA and the baseline CST had the most effect in the all-model prediction for BCVA regression and CST classification, respectively. Promising signals for predicting treatment outcomes from baseline characteristics were detected; however, the predictive benefit of baseline images was unclear in this proof-of-concept study. Further testing and validation with larger, independent datasets is required to fully explore the predictive capacity of ML models using baseline imaging data. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Visual acuity time in range: a novel concept to describe consistency in treatment response in diabetic macular oedema

ObjectiveTo assess ‘time in range’ as a novel measure of treatment response in diabetic macular oedema (DMO).MethodsThis post hoc analysis of the Protocol T randomised clinical trial included 660 individuals with centre-involved DMO and best-corrected visual acuity (BCVA) letter score ≤78–≥24 (approximate Snellen equivalent 20/32–20/320). Study participants received intravitreal aflibercept 2.0 mg, repackaged (compounded) bevacizumab 1.25 mg, or ranibizumab 0.3 mg given up to every 4 weeks using defined retreatment criteria. Mean time in range was calculated using a BCVA letter score threshold of ≥69 (20/40 or better; minimum driving requirement in many regions), with sensitivity analyses using BCVA thresholds from 100 to 0 (20/10 to 20/800) in 1-letter increments.ResultsTime in range was defined as either the absolute or relative duration above a predefined BCVA threshold, measured in weeks or as a percentage of time, respectively. Using a BCVA letter score threshold of ≥69 (20/40 or better), the least squares mean time in range (adjusted for baseline BCVA) in Year 1 was 41.2 weeks with intravitreal aflibercept, 4.0 weeks longer (95% CI: 1.7, 6.3; p = 0.002) than bevacizumab and 3.6 weeks longer (1.3, 5.9; p = 0.004) than ranibizumab. Overall, mean time in range was numerically longer for intravitreal aflibercept for all BCVA letter score thresholds between 92 and 30 (20/20 to 20/250). In the Day 365–728 analysis, time in range was 3.9 (1.3, 6.5) and 2.4 (0.0, 4.9) weeks longer with intravitreal aflibercept vs bevacizumab and vs ranibizumab (p = 0.011 and 0.106), respectively.ConclusionBCVA time in range may represent another way to describe visual outcomes and potential impact on vision-related functions over time for patients with DMO and provide a better understanding, for physicians and patients, of the consistency of treatment efficacy.

Two-Year Outcomes After Variable Duration of Drug Cessation in Patients With Maculopathy Associated With Pentosan Polysulfate Use

Prior retrospective studies have provided limited evidence on disease progression following drug cessation in patients with maculopathy associated with pentosan polysulfate (PPS). To evaluate the 2-year evolution of maculopathy associated with PPS use after drug cessation. This cohort study prospectively evaluated the natural history of patients with maculopathy associated with PPS use. Participants seen at the Emory Eye Center were enrolled between December 1, 2018, and December 1, 2019, and data were collected through November 30, 2021. The main outcomes were changes in visual function and structure. Visual function was assessed annually with refraction and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), mesopic microperimetry, and dark adaptometry. Structural outcomes included presence and extent of complete retinal pigment epithelium and outer retinal atrophy (cRORA), macular central subfield thickness (CST), and subfoveal choroidal thickness (SFCT). Of the 12 participants (23 eyes), 11 (91.7%) were female (1 [8.3%] male), 11 (91.7%) were White (1 [8.3%] Black), and median (IQR) age at enrollment was 58 (47-64) years. Median (IQR) time from PPS discontinuation to initial visit was 0.6 (0.4-1.9) years. Median baseline ETDRS BCVA letter score was 83 (Snellen equivalent, 20/20) (IQR, 80-86.5 [20/25-20/20]), with a median 2-year change of -3 (IQR, -6 to -0.5; P = .08). Four eyes (17.4%) had a letter score decline of 15 or more, all associated with progressive cRORA. Median change in microperimetry average threshold was -3.5 dB (IQR, -4.1 to -2.5 dB; P = .001), and percent reduced threshold was 32.5% (IQR, 20.3%-52.8%; P = .004). Nine eyes (39%) had macular cRORA at baseline, with a median linearized growth rate of 0.23 mm/y (IQR, 0.22-0.25 mm/y). Two eyes (8.7%) without atrophy at baseline developed new-onset cRORA. Median baseline CST was 284 μm (IQR, 253-291 μm), with a median 2-year change of -5 μm (IQR, -13 to 0.5 μm; P = .0497). Median 2-year change in SFCT was 1 μm (IQR, -18 to 16 μm; P = .91). The findings of this cohort study suggest that functional and structural deficits continue to progress in PPS-associated maculopathy even after drug cessation. Additional study is needed to determine whether these findings can be generalized to other patients with PPS-associated maculopathy and whether longer follow-up could determine subsequent disease course.

Visual function correlates with neurodevelopment in a population cohort of school-aged children born extremely preterm.

To investigate visual function and neurodevelopment in a geographically defined population cohort of school-aged children born extremely preterm. All children born extremely preterm in Central Norway between 2006 and 2011 (n=65) were identified, and 36 (median age, min/max: 13, 10/16) were included. Best-corrected visual acuity (BCVA), contrast sensitivity (four spatial frequencies), parent-reported challenges and neuropsychological testing in learning, executive functions, motor skills, perception, reaction time, working and visual memory, processing speed, and pattern separation were measured. Brain MRI (3T) was acquired and read by a neuroradiologist. Median (min/max) BCVA letter score was 85 (35/91) in the better and 82 (13/89) in the worse eye. ROP participants (n=7) had lower contrast sensitivity in the two highest spatial frequencies (p= 0.024 and p= 0.004). Parent-reported challenges correlated negatively with BCVA (learning: p= 0.014; executive functions: p= 0.002; motor skills: p= 0.000; and perception: p= 0.001), while motor skills correlated negatively with one (p= 0.010) and perception with two (p= 0.003 and p= 0.009) of four spatial frequencies. Neuropsychological tests were reduced relative to norms. None had MRI-verified preterm brain injury. Visual function was subnormal and correlated with parent-reported challenges in a small cohort of extremely preterm school-aged children, indicating that visual function may be a marker of neurodevelopmental outcomes.

Efficacy and safety of intravitreal HLX04-O, an anti-VEGF monoclonal antibody, for the treatment of wet age-related macular degeneration.

To evaluate the efficacy and safety of HLX04-O, an investigational ophthalmic formulation of HLX04 (bevacizumab biosimilar) for intravitreal injection, as a treatment for wet age-related macular degeneration (wAMD) in a phase 1/2 clinical trial (NCT04993352). Eligible patients with wAMD were enrolled to receive HLX04-O intravitreal injections at a dose of 1.25 mg/0.05 mL every four weeks. Efficacy and adverse events were evaluated every month during study visits. A 76-year-old male with wAMD in his left eye participated in the trial and completed six cycles of HLX04-O intravitreal injections. Changes were observed in macular center point thickness (baseline vs last study visit, 437 vs 255 µm) and best-corrected visual acuity letter score (baseline vs last study visit, 36 vs 77) of the affected eye, which indicated an improvement in wAMD over treatment. No adverse events were reported by the data cutoff date. HLX04-O at 1.25 mg/0.05 mL every four weeks is well tolerated in this patient, demonstrating promising safety and efficacy in wAMD treatment. Large-scale studies are required to confirm the outcomes.

Association Between Visual Acuity and Fluid Compartments with Treat-and-Extend Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis.

IntroductionRecently, there has been growing interest in exploring the relationship between visual acuity and fluid localization in different retinal compartments. This post hoc analysis of the ARIES study explores the relationship between the presence of intraretinal fluid (IRF) and subretinal fluid (SRF), both at baseline and throughout treatment, and best-corrected visual acuity (BCVA) in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in a treat-and-extend regimen.MethodsARIES (NCT02581891) was a multicenter, randomized, phase 3b/4 study comparing the efficacy of two IVT-AFL treat-and-extend regimens over 2 years in patients with treatment-naïve nAMD. This post hoc analysis explores the relationship between the presence of SRF/IRF and absolute BCVA (letter score) at baseline and fixed visits.ResultsIn 210 patients (treat-and-extend treatment arms combined), SRF presence at baseline was associated at every time point with a numerically higher mean BCVA than if absent, with 10 more letters at week 104. IRF presence at baseline was associated at all but one time point with a numerically lower mean BCVA than if absent (week 104, 8-letter difference). Baseline SRF+IRF was associated with lower BCVA (week 104, 7-letter difference) than if only SRF was present, but higher BCVA (week 104, 8-letter difference) than if only IRF was present. Absence of SRF+IRF was not associated with better BCVA at any time point during the study.ConclusionIn ARIES, in patients with nAMD treated with IVT-AFL, the presence of SRF was associated with better visual acuity, whereas IRF was associated with poorer visual acuity. The findings of this post hoc analysis suggest that differentiating IRF from SRF may offer better prognostic value in guiding treatment-extension decisions than the use of combined or “any” IRF and SRF. Prospective trials are needed to validate these results and determine their clinical relevance.Trial registration number (ClinicalTrials.gov)NCT02581891. Association between Visual Acuity and Fluid Compartments with Treat-and-Extend Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis: A Video (MP4 308264 KB)Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00491-1.

Response to 1-Year Fixed-Regimen Bevacizumab Therapy in Treatment-Naïve DME Patients: Assessment by OCT Angiography.

Purpose To evaluate the effectiveness of intravitreal bevacizumab treatment in patients with diabetic macular edema (DME) by assessing retinal changes using optical coherence tomography angiography (OCT-A). Methods This prospective study was performed in patients with treatment-naïve DME. The eyes of patients were imaged using a swept-source OCT system with a scan area of 6 × 6 mm. The DME patients with a central macular thickness (CMT) of ≥300 μm received nine bevacizumab injections within 12 months. The demographic, systemic, and ocular parameters, including the best-corrected visual acuity (BCVA), CMT, microaneurysm (MA) count, and foveal avascular zone (FAZ) area in both superficial capillary plexus (SCP) and deep capillary plexus (DCP), as well as vessel density in SCP, were assessed in the patients. In addition, the response (good or poor) of the DME eyes to bevacizumab treatment and the final visual acuity (BCVA of 75 letters) were analyzed. Results Seventy-seven eyes of DME patients were subjected to the final analysis. Bevacizumab treatment reduced CMT from 425.06 μm (±77.15) to 350.25 μm (±82.04) and improved BCVA by about 8.61 letters (from 64.73 to 73.34) in the patients. The mean number of MAs in SCP decreased from 3.51 ± 2.07 to 2.31 ± 1.15 (p < 0.001) and in DCP from 17.12 ± 11.56 to 12.21 ± 6.99 (p < 0.001), whereas the area of FAZ increased in SCP from 328.22 ± 131.38 to 399.70 ± 156.98 (p < 0.001) and in DCP from 571.13 ± 396.01 to 665.89 ± 412.77 (p = 0.001). The final BCVA letter score and CMT were statistically significant in both poor and good responders, as well as in BCVA < 75 and BCVA ≥ 75 groups. Conclusion The fixed-regimen intravitreal bevacizumab therapy was effective in treating DME. Apart from noninvasive visualization of microvascular damage, OCT-A showed limited usefulness in predicting treatment response. Although the study showed that the number of MAs was significantly reduced during treatment, which is an OCT-A predictor of a good response to bevacizumab treatment at a 12-month visit, commonly observed artifacts may reduce the usefulness of OCT-A.

Early effect of simultaneous intravitreal dexamethasone and bevacizumab combination treatment in patients with persistent diabetic macular edema

To report the early effect of simultaneous intravitreal dexamethasone and bevacizumab combination treatment in patients with persistent diabetic macular edema (DME). In this single-center prospective non-randomized study, 65 eyes of 59 patients with persistent DME were included. In the combined group (Group 1), we treated 35 eyes of 29 persistent DME patients with a simultaneous combination of intravitreal dexamethasone and bevacizumab, and in the control group (Group 2), we treated 30 eyes of 30 patients with intravitreal bevacizumab. Changes in Best Corrected Visual Acuity (BCVA), Central Macular Thickness (CMT) and Intraocular Pressure (IOP) from the initial visit to each subsequent follow-up visit (1st, 2nd and 3rd months) were recorded. In Group 1, the mean baseline Early Treatment Diabetic Retinopathy (ETDRS) BCVA letter score was 44.1±19.3 (range 20-51), improving significantly to 58.8±18.2 (range 42-73) in the first month (P<0.05), 57±19.2 (range 40-72) in the second month (P<0.05) and 55.4±18.4 (range 34-71) in the third month (P<0.05). In Group 2, the mean pre-injection BCVA ETDRS letter score was 43.3±18.8 (range 20-56) and did not improve significantly; the letter score was 44.3±18.1 (range 20-49) in the third month. In Group 1, the mean BCVA change from baseline to the 3rd month was 11.3 ETDRS letters. In Group 2, the mean BCVA change from baseline to the 3rd month was 1 ETDRS letter. In Group 1, the mean reduction in CMT from baseline was -142.25μm. In Group 2, the mean reduction in CMT from baseline was -17.30μm. In Group 1 at the third month, 12 (34.2%) eyes with a CMT>300μm needed an additional injection. No serious ocular or systemic side effects occurred in any patient. Simultaneous intravitreal dexamethasone and bevacizumab combination treatment is effective and can be used safely in persistent DME.

Alone laser versus bevacizumab plus laser for diffuse diabetic macular edema (ALBA randomized trial).

Purpose:To report the 12-month results of laser (treatment G1) versus intravitreal bevacizumab combined with laser (treatment G2) in patients with diffuse diabetic macular edema (DME).Methods:In this single-center randomized independent controlled trial, 32 patients were randomized to G1 (n = 15) or G2 (n = 17). In G1, laser was given at baseline and then pro re nata (PRN). In G2, three intravitreal bevacizumab (1.25 mg) injections were given once every 6 weeks, then laser and then PRN. Analysis was performed by treatment as administered. This study was registered in clinicaltrials.gov as NCT01572350 and EU Clinical Trial Registry as 2009-014654-15.Results:G2 was superior to G1 improving best corrected visual acuity (BCVA) with respect baseline (+8.0 vs + 3.0; p < 0.01). At month 12, a significantly greater proportion of patients had a BCVA letter score >15 and >73 in G2 (3 of 15 (20%) and 8 of 15 (53%), respectively) versus G1 (1 of 17 (6%) and 4 of 18 (23%), respectively). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire, at 12 months was statistically indistinguishable between both groups.Conclusion:G2 provided superior visual acuity gains over G1 in patients with visual impairment due to center-involving diffuse DME, associated with significant gains in VFQ-25 scores.

Effectiveness of 190 µg Fluocinolone Acetonide and 700 µg Dexamethasone Intravitreal Implants in Diabetic Macular Edema Using the Area-Under-the-Curve Method: The CONSTANT Analysis.

PurposeCalculations of area-under-the-curve (AUC) provide the average letters gained across the entire treatment period, which may be a better estimate of long-term effectiveness than single time-point outcomes, particularly when it comes to sustained-release therapies.Materials and MethodsThe AUC method was used to compare the efficacy of the 0.2 µg/day fluocinolone acetonide (total dose of 0.19 mg; FAc) and dexamethasone (DEX) 700 µg implants based on published data from their respective Phase 3 FAME (Fluocinolone Acetonide for Macular Edema) and MEAD pivotal clinical trials in diabetic macular edema (DME). Best-corrected visual acuity (BCVA) letter scores were collated from the FAME trial and compared with those reported in MEAD. The trapezoidal rule was then used to calculate AUC, based on BCVA letter score, from baseline to Month 36 (FAME)/Month 39 (MEAD) and presented as an overall mean visual acuity change per day.ResultsTreatment with either the FAc or DEX implant resulted in an improved BCVA over the treatment period compared with sham. This effect was statistically greater (p=0.029) for the FAc implant than the DEX implant (5.2 vs 3.5 letters/day, respectively) and even greater in the recurrent DME subgroup (p<0.001; 6.9 vs 3.5 letters/day, respectively).ConclusionAlthough direct comparisons between trial cohorts cannot be performed, this analysis indicated that, in their respective pivotal clinical trial cohorts, treatment with the FAc implant provides better long-term visual acuity outcomes and a lower treatment burden than achieved with the DEX implant.

Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion

The comparative clinical effectiveness of ranibizumab, aflibercept, and bevacizumab for the management of macular edema due to central retinal vein occlusion (CRVO) is unclear. To determine whether intravitreal aflibercept or bevacizumab compared with ranibizumab results in a noninferior mean change in vision at 100 weeks for eyes with CRVO-related macular edema. This prospective, 3-arm, double-masked, randomized noninferiority trial (Lucentis, Eylea, Avastin in Vein Occlusion [LEAVO] Study) took place from December 12, 2014, through December 16, 2016, at 44 UK National Health Service ophthalmology departments. Inclusion criteria included age 18 years or older, visual impairment due to CRVO-related macular edema of less than 12 months with best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score (approximate Snellen equivalent) in the study eye between 19 (20/400) and 78 (20/32), and spectral domain optical coherence tomography imaging central subfield thickness of 320 μm or greater. Data were analyzed from March 4, 2019, to April 26, 2019. Participants were randomized (1:1:1) to receive repeated intravitreal injections of ranibizumab (0.5 mg/0.05 mL) (n = 155), aflibercept (2.0 mg/0.05 mL) (n = 154), or bevacizumab (1.25 mg/0.05 mL) (n = 154) for 100 weeks. Adjusted mean change in BCVA in the study eye at 100 weeks wherein noninferiority was concluded if the lower bounds of the 95% CI of both the intention-to-treat and the per protocol analyses were above -5 letters. Of 463 participants, 265 (57.2%) were male, with a mean (SD) age of 69.1 (13.0) years. The mean (SD) gain in BCVA letter score was 12.5 (21.1) for ranibizumab, 15.1 (18.7) for aflibercept, and 9.8 (21.4) for bevacizumab at 100 weeks. Aflibercept was noninferior to ranibizumab (intention-to-treat-adjusted mean BCVA difference, 2.23 letters; 95% CI, -2.17 to 6.63 letters; P < .001). Bevacizumab was not noninferior to ranibizumab (intention-to-treat-adjusted mean BCVA difference, -1.73 letters; 95% CI, -6.12 to 2.67 letters; P = .07). The per protocol analysis conclusions were similar. Fewer mean injections were given in the aflibercept group (10.0) than in the ranibizumab (11.8) group (mean difference at 100 weeks, -1.9; 95% CI, -2.9 to -0.8). Mean changes in vision after treatment of macular edema due to CRVO were no worse using aflibercept compared with ranibizumab. Mean changes in vision using bevacizumab compared with ranibizumab were inconclusive regarding vision outcomes (ie, the change in visual acuity from baseline, on average, may be worse or may not be worse when using bevacizumab compared with ranibizumab). ISRCTN13623634.

Effect of Ranibizumab and Aflibercept on Best-Corrected Visual Acuity in Treat-and-Extend for Neovascular Age-Related Macular Degeneration

To our knowledge, this is the first randomized clinical trial to compare visual outcomes and injection loads between ranibizumab and aflibercept using an identical treat-and-extend (TE) regimen for neovascular age-related macular degeneration (nAMD). To report the results of the preplanned 12-month interim analysis of 2 predefined secondary efficacy end points of a randomized clinical trial. The Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients (RIVAL) trial was conducted in 24 sites in Australia and included 281 treatment-naive eyes from 281 participants with active choroidal neovascularization secondary to nAMD and a visual acuity letter score of 23 or greater who were recruited between April 11, 2014, and October 31, 2015. A preplanned interim analysis was performed at month 12. Best-corrected visual acuity (BCVA) assessors and the central reading center, which determined treatment intervals, were masked to treatment assignments. Participants were randomized (1:1) to receive intravitreal injections of 0.5 mg of ranibizumab or 2.0 mg of aflibercept. After receiving 3 initial monthly injections, participants entered the TE phase. Mean change in BCVA and the number of injections from baseline to month 12. Of 281 participants, 148 (52.7%) were women and the mean (SD) age was 77.7 (8.1) years. The baseline mean BCVA letter score (approximate Snellen equivalent) was 65.3 (20/50) in the ranibizumab arm and 65.1 (20/50) in the aflibercept arm. One hundred twenty-seven ranibizumab participants (90.1%) and 121 aflibercept participants (88.3%) completed month 12 with a mean (SD [Snellen equivalent]) BCVA letter score of 72.9 (15.5 [20/32]) and 70.5 (14.6 [20/40]), respectively. The mean change in BCVA letter scores from baseline to month 12 was 7.2 (95% CI, 5.5-8.9) for ranibizumab and 4.9 (95% CI, 3.1-6.6) for aflibercept (letter score difference, 2.3; 95% CI, -0.1 to 4.7; P = .06). The mean number of injections from baseline to month 12 was 9.7 in both the ranibizumab (SD, 2.8) and aflibercept (SD, 2.6) arms with a rate ratio of 1.00 (95% CI, 1.0-1.1; P = .86). Our findings suggest that neither aflibercept nor ranibizumab for nAMD are superior to the other regarding the average visual acuity gains and number of injections during 1 year in a TE regimen. Further follow-up to 2 years may determine if advantages of one over the other can be identified. Clinicaltrials.Gov identifier: NCT02130024.

Efficacy and safety of ranibizumab monotherapy versus ranibizumab in combination with verteporfin photodynamic therapy in patients with polypoidal choroidal vasculopathy: 12-month outcomes in the Japanese cohort of EVEREST II study.

PurposeTo compare the efficacy and safety of ranibizumab 0.5 mg with or without verteporfin photodynamic therapy in Japanese patients with polypoidal choroidal vasculopathy over 12 months.Study designEVEREST II was a 24-month, Phase IV, multicenter, randomized, double-masked study in Asian patients with symptomatic macular polypoidal choroidal vasculopathy.MethodsOf the 322 enrolled patients, 84 patients, including 46 patients who received ranibizumab + verteporfin photodynamic therapy (combination therapy arm) and 38 patients who received ranibizumab/sham PDT (monotherapy arm), were Japanese who were evaluated in this subanalysis. Mean change in best-corrected visual acuity (BCVA) and complete polyp regression at Month 12, ranibizumab treatment exposure, and safety over 12 months were assessed.ResultsBaseline demographics were well balanced between the arms. At Month 12, mean change in BCVA letter score was +8.5 with combination therapy versus +6.4 with monotherapy. Complete polyp regression was higher with combination therapy than with monotherapy at Month 12 (70.5% vs 27.3%). Over 12 months, patients in the combination arm received a median of 4.0 ranibizumab injections vs 7.0 in the monotherapy arm. Serious adverse events were generally low in both arms, and retinal hemorrhage, an adverse event, was reported in one patient (2.2%).ConclusionThe results from the Japanese cohort were in agreement with the EVEREST II study. Combination therapy was effective in improving BCVA and achieving a higher rate of complete polyp regression with a lower number of ranibizumab injections than monotherapy. No new safety signals were reported, and safety events were comparable between both arms over 12 months.

Conbercept for Treatment of Neovascular Age-related Macular Degeneration: Results of the Randomized Phase 3 PHOENIX Study

Age-related macular degeneration (AMD) can cause irreversible vision loss leading to blindness. We aim to evaluate the efficacy and safety of intravitreal injections of 0.5mg conbercept, a new anti-vascular endothelial growth factor (anti-VEGF) drug, for treatment of AMD on a schedule more manageable for patients. A prospective, double-masked, multicenter, sham-controlled, phase III randomized trial. Patients: Patients with choroidal neovascularization (CNV) secondary to AMD were enrolled and randomized to the conbercept group or the sham control group. The conbercept group received intravitreal injections of conbercept (0.5mg) once monthly for the first 3months, then once quarterly until month 12 (3+ Q3M). The sham group received first 3monthly sham injections and then 3monthly injections of conbercept (0.5mg) followed by quarterly administrations until month 12. The primary endpoint was mean change from baseline in best-corrected visual acuity (BCVA) at month 3. A total of 114 patients (91.9%) from 9 sites in China completed the 12-month study. At the 3-month primary endpoint, the mean changes in BCVA from baseline were+9.20 letters in the conbercept group and+2.02 letters in the sham group, respectively (P< .001). At 12months, the mean changes from baseline in BCVA letter score were+9.98 letters in the conbercept group and+8.81 letters in the sham group(P= .64). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival hemorrhage, and increased intraocular pressure. A conbercept dosing regimen of 3 initial monthly administrations followed by quarterly treatments is effective for treatment of AMD. In previous reports, other anti-VEGF agents were unable to maintain similar clinical benefits with the same regimen.

PREDICTIVE VALUE OF OPTICAL COHERENCE TOMOGRAPHIC FEATURES IN THE BEVACIZUMAB AND RANIBIZUMAB IN PATIENTS WITH DIABETIC MACULAR EDEMA (BRDME) STUDY.

To establish the predictive value of specific optical coherence tomography retinal features on visual outcomes and retinal thickness during anti-vascular endothelial growth factor treatment in patients with diabetic macular edema. Post hoc analysis of compound data of a prospective, 6-month, multicenter, randomized controlled trial of 119 patients with diabetic macular edema receiving either intravitreal bevacizumab or ranibizumab were analyzed to assess the associations between baseline retinal morphologic parameters and change in best-corrected visual acuity and central subfield thickness. Based on the study protocol of the core study, best-corrected visual acuity and central subfield thickness were obtained before each mandatory monthly injection during 6 months. The presence of serous retinal detachment at baseline was associated with significant improvement in best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.001 and P = 0.01, respectively). In addition, the presence of disorganization of retinal inner layers was associated with lower best-corrected visual acuity letter score at Month 3 and Month 6 (P < 0.05 and P = 0.01, respectively). This study found that serous retinal detachment and disorganization of retinal inner layers were associated with different treatment responses to anti-vascular endothelial growth factor therapy in patients with diabetic macular edema.

Comparison of 12-month therapeutic effect of conbercept and ranibizumab for diabetic macular edema: a real-life clinical practice study

BackgroundTo compare the efficacy of intravitreal conbercept and ranibizumab in the treatment of diabetic macular edema (DME) in a real-life clinical practice.MethodsThis was a retrospective study. Among 62 Chinese patients with DME, 32 patients (36 eyes) received intravitreal conbercept (IVC) injections and 30 patients (32 eyes) received intravitreal ranibizumab (IVR) injections, once a month for 3 months followed by as needed therapy. All participants had at least 12 months of follow-up. We compared the changes in best-corrected visual acuity (BCVA) letter score and central retinal thickness (CRT) between groups, as well as the number of intravitreal injections delivered. Safety was assessed with the incidence of adverse events (AEs).ResultsAt month 12, the mean BCVA letter score improved by 9.3 ± 5.2 with conbercept, and by 8.9 ± 4.4 with ranibizumab, the mean CRT reduction was 138.4 ± 97.7 μm and 145.2 ± 72.5 μm, respectively. There was no statistically significant difference of improvement in BCVA (P = 0.756) and decrease in CRT (P = 0.748) between the two groups. The number of intravitreal injections delivered was significantly higher (P = 0.027) in the IVR group (7.2 ± 1.0 per eye) than in the IVC group (6.6 ± 0.9 per eye). There were no severe ocular adverse reactions or systemic adverse events.ConclusionsBoth conbercept and ranibizumab are effective in the treatment of DME, achieving the similar clinical efficacy. In comparison to ranibizumab, conbercept shows a longer treatment interval and fewer intravitreal conbercept injections are needed.

The Clinical Importance of Changes in Diabetic Retinopathy Severity Score

To investigate the clinical importance of changes in diabetic retinopathy severity score (DRSS) in patients with diabetic macular edema (DME) treated with intravitreal ranibizumab. Post hoc analysis of the phase III RIDE and RISE studies of ranibizumab for treatment of DME. Four hundred sixty-eight eyes treated with ranibizumab from randomization with gradable DRSS on baseline fundus photographs. Visual and anatomic outcomes were examined in eyes grouped according to DRSS change from baseline to month24. Mean best-corrected visual acuity (BCVA) letter score change, proportion of patients with 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letter score change, mean contrast sensitivity change, proportion of patients with resolved macular edema, and leakage on fluorescein angiography. Most (56.8%) patients treated with ranibizumab experienced 1-step or more improvement in DRSS from baseline to month 24; 40.0% had no change, and 3.2% experienced DRSS worsening. Patients with DRSS stability or improvement had greater mean BCVA letter score changes (+15.1,+14.2,+11.3, and+11.2 letters for ≥3-step improvement, ≥2-step improvement, 1-step improvement, and no DRSS change, respectively) compared with+5.0 letters in patients who had any DRSS worsening. Best-corrected visual acuity letter score gain of 15 letters or more was more common in patients with 2-step or 3-step or more DRSS improvement (51.9% and 44.6%, respectively) compared with those with a 1-step DRSS improvement, no change, or worsening (37.9%, 39.6%, and 26.7%, respectively). A loss of 15 letters or more in BCVA was more common in patients with any DRSS worsening (13.3%) compared with patients who had stable or improved DRSS (0%-2.8%). Resolution of macular edema was more common in patients with DRSS improvement: 84.2%, 87.7%, and 92.3% of patients with 1-step, 2-step or more, and 3-step or more improvement in DRSS achieved central foveal thickness of 250μm or less, compared with 65.2% and 53.3% of patients who had no DRSS change or any DRSS worsening. These findings provide further support that improvement in DRSS is a clinically important outcome that should be evaluated as a measure of treatment effectiveness in future studies of diabetic eye disease.

Test-Retest Variability of Functional and Structural Parameters in Patients with Stargardt Disease Participating in the SAR422459 Gene Therapy Trial.

PurposeThe goal of this analysis was to determine the test–retest variability of functional and structural measures from a cohort of patients with advanced forms of Stargardt Disease (STGD) participating in the SAR422459 (NCT01367444) gene therapy clinical trial.MethodsTwenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic ABCA4 mutation on each chromosome participating in the SAR422459 (NCT01367444) gene therapy clinical trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, semiautomated kinetic perimetry (SKP) using isopters I4e, III4e, and V4e, hill of vision (HOV) calculated from static visual fields (SVF) by using a 184n point centrally condensed grid with the stimulus size V test target. Retinal structural changes such as central macular thickness and macular volume were assessed by spectral-domain optical coherence tomography (SD-OCT). Repeatability coefficients (RC) and 95% confidential intervals (CI) were calculated for each parameter using a hierarchical mixed-effects model and bootstrapping.ResultsCriteria for statistically significant changes for various parameters were found to be the following: BCVA letter score (8 letters), SKP isopters I4e, III4e, and V4e (3478.85; 2488.02 and 2622.46 deg2, respectively), SVF full volume HOV (VTOT, 14.62 dB-sr), central macular thickness, and macular volume (4.27 μm and 0.15 mm3, respectively).ConclusionsThis analysis provides important information necessary to determine if significant changes are occurring in structural and functional assessments commonly used to measure disease progression in this cohort of patients with STGD. Moreover, this information is useful for future trials assessing safety and efficacy of treatments in STGD.Translational RelevanceDetermination of variability of functional and structural measures in participants with advanced stages of the STGD is necessary to assess efficacy and safety in treatment trials involving STGD patients.