Deletion involving exon 18 of RPGRIP1 is a major cause of achromatopsia.

P-219: Relationship between corneal exam findings, best-corrected visual acuity, and ocular symptoms in patients with relapsed or refractory multiple myeloma receiving belantamab mafodotin

Introduction: The Canadian Treat-and-Extend Analysis Trial with Ranibizumab (CANTREAT) was a 2-year, multicentred, randomized clinical trial to evaluate treat-and-extend (T&E) relative to monthly administration of ranibizumab in neovascular age-related macular degeneration (nAMD). This post hoc analysis of the CANTREAT trial explores the relationship between the maximal extension interval tolerated by patients receiving T&E ranibizumab and visual acuity outcomes. Methods: Treatment-naïve patients with nAMD were randomized to receive either a once-monthly dosing or T&E regimen of ranibizumab across 27 treatment centres in Canada and were followed for 24 months. For this post hoc analysis, patients in the T&E cohort were subdivided into the following groups based on maximum extension interval: 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks. The primary outcome was the change in ETDRS best-corrected visual acuity (BCVA) from baseline to month 24 while secondary outcomes included change in central retinal thickness (CRT). All results were reported using descriptive statistics. Results: A total of 285 participants undergoing T&E were enrolled in this post hoc analysis. At month 24, the change in BCVA from baseline was +8.5 ± 9.3, +7.7 ± 13.8, +4.4 ± 9.6, +4.4 ± 18.5, and +7.8 ± 14.8 letters in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. The change in CRT at month 24 was −79.2 ± 95.0, −143.9 ± 128.9, −97.7 ± 101.1, −120.9 ± 105.3, and −133.2 ± 108.8 μm in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. Conclusion: The capacity to extend does not necessarily associate with improved visual acuity outcomes, with the poorest change in BCVA seen in those extended 8–10 weeks. The highest change in BCVA and lowest decrease in CRT was in the group maximally extended for 4 weeks. There was a correlation between change in BCVA and change in CRT for other extension groups. Future studies should establish the predictive factors for successful extension in patients undergoing T&E in nAMD.

Background: Correlation of abnormal fundus autofluorescence (FAF) patterns with best-corrected visual acuity (BCVA).Aim: This study aims to evaluate FAF patterns in eyes with early dry age-related macular degeneration (AMD) and correlate these patterns with logarithm of minimum angle of resolution (logMAR) BCVA. Settings and Design: Institutional, descriptive prospective cohort study. Subjects and Methods: One hundred fifty-nine eyes of 103 patients with early dry AMD were recruited. FAF imaging was done for all patients with the aid of confocal scanning laser ophthalmoscopy (cSLO). BCVA was recorded for all patients using logMAR BCVA. Statistical Analysis Used: Data were fed to the computer and analyzed using IBM SPSS software package Version 20.0 (Armonk, NY, USA: IBM Corp). Kruskal–Wallis test for abnormally quantitative variables, to compare between more than two studied groups and post hoc (Dunn's multiple comparisons test) for pairwise comparisons. The significance of the obtained results was judged at the 5% level. Results: Seven FAF patterns have been identified (normal, minimal change, focal increased, linear, patchy, reticular, and speckled pattern). The mean logMAR BCVA among eyes with different FAF patterns was significantly variable. Eyes with patchy FAF pattern had the best mean BCVA (0.15 ± 0.0), while eyes with linear FAF pattern had the worst mean BCVA (0.52). Conclusions: The mean logMAR BCVA was statistically significant variable among different FAF patterns in eyes with early AMD suggesting a possible link between each FAF pattern and the visual prognosis. This finding can aid in determining the visual potential of eyes with early AMD according to FAF pattern in large samples studies.

8033 Background: Belantamab mafodotin (GSK2857916; belamaf; BLENREP) is a B-cell maturation antigen (BCMA)-targeting antibody–drug conjugate approved in the US and EU as a monotherapy for the treatment of adult patients with RRMM. Ocular events (OEs) during the pivotal DREAMM-2 trial (NCT03525678) included corneal exam findings (punctate keratopathy and microcyst-like epithelial changes), BCVA changes, and ocular symptoms. Dose reductions or delays based on corneal exam findings and BCVA were used to manage OEs. Here we performed a post hoc investigation of relationships between corneal exam findings, BCVA changes, and patient-reported ocular symptoms to explore if BCVA changes and symptoms could guide dosing, rather than corneal exams. Methods: Eye evaluations (including a corneal exam and BCVA assessment of Snellen visual acuity) were performed on all patients receiving single-agent belamaf (2.5 mg/kg) by ophthalmologists at baseline and prior to each belamaf dose. Changes in the corneal epithelium (Ker) and BCVA were both assessed as per protocol-defined criteria and assessment of grade (Gr) was based on the worse eye. BCVA grading was relative to baseline. Patient-reported ocular symptoms were reported as per the Common Terminology Criteria for Adverse Events. Results: In 12.5% of eye evaluations Gr 3–4 Ker was associated with minimal or no (Gr ≤1) BCVA changes. When patient-reported ocular symptoms were also considered, only 7.5% of evaluations found Gr 3–4 Ker with Gr ≤1 BCVA changes or ocular symptoms. Mild or no (Gr ≤2) Ker was associated with Gr ≤1 BCVA changes in 59.5% of evaluations, or in 38.8% of evaluations with no ocular symptoms reported. Overall, Gr 3–4 Ker were found in 24.9% of evaluations; by contrast, patients had Gr 2–4 BCVA changes or ocular symptoms in 53.7% of evaluations. Association of corneal epithelium changes (Ker) with BCVA changes and ocular symptoms. Conclusions: These findings highlight that BCVA changes and ocular symptoms should be further investigated to determine if they can be used as alternatives (eg, frequency of eye examinations based on symptoms) for the management of belamaf dosing to potentially reduce the burden on patients and healthcare professionals. Clinical trial information: NCT03525678. [Table: see text]

To evaluate the efficacy and safety of ranibizumab 0.5mg in Japanese patients with visual impairment due to macular oedema secondary to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) and to support the applicability of the phase III results from Caucasian to Japanese populations. This is a 3-month, open-label, single-arm, multicentre, phase III study. Thirty-one patients (15 BRVO and 16 CRVO) aged ≥18years with a best-corrected visual acuity (BCVA) letter score of 19-73 (BRVO) or 24-73 (CRVO) were included. The primary end-point was the mean average change in BCVA from baseline to month 1 through month 3 after three consecutive monthly intravitreal injections of ranibizumab 0.5mg. Secondary end-points were mean change in BCVA and central subfield thickness (CSFT), categorized BCVA, and safety over 3months. At month 3, the mean average change in BCVA improved substantially from baseline for BRVO (11.3 letters, p=0.001) and CRVO (6.7 letters, p=0.019). The mean BCVA improved (12.8 and 9.1 letters) and the mean CSFT decreased (212.5 and 442.1μm) from baseline to month 3. At month 3, 26.7% (BRVO) and 31.3% (CRVO) of the patients had a gain of ≥15 letters from baseline. Safety findings in this study were similar to those reported in the previous clinical trials. Ranibizumab was effective in improving BCVA and was well tolerated in Japanese patients with BRVO and CRVO. The findings from this study were consistent with those reported in the Caucasian population.

ObjectivesThe aim of this study was to obtain real-world clinical data on the safety and efficacy of ranibizumab treatment for myopic choroidal neovascularization (CNV) due to pathologic myopia.MethodsThis was a prospective, observational, post-marketing surveillance study in ranibizumab-naive Japanese patients with myopic CNV. Patients who initiated ranibizumab treatment were registered and prospectively observed over 12 months. Safety endpoints were the incidence of ocular and non-ocular adverse drug reactions (ADRs) and serious adverse events (SAEs). The efficacy endpoint included the average change in best-corrected visual acuity (BCVA) in logarithm of the minimal angle of resolution (logMAR) units (logMAR BCVA) from baseline to the last observation.ResultsThree hundred and eighteen patients were included in the safety analysis population. Of these 79.9% were female and the mean age was 65.5 years. The incidences of SAEs and ADRs were 0.6 and 0.3%, respectively. A total of 268 patients (84.0%) completed the 12-month study period. The mean (±SD) and median number of ranibizumab injections were 2.0 ± 1.5 and 1.0 during the 12-month study period, respectively. The number of ranibizumab injections received was one in 52.2% of patients and less than or equal to three in 89.2%. The mean change in logMAR BCVA from baseline to month 12 was −0.193, and the mean logMAR BCVA improved from 0.517 to 0.319 between baseline and month 12.ConclusionsThis study showed that ranibizumab is generally well tolerated, and that a minimum number of injections were necessary to produce a therapeutic effect in Japanese myopic CNV patients in a real-world setting.

MM-103: Relationship Between Corneal Exam Findings, Best-Corrected Visual Acuity (BCVA), and Ocular Symptoms in Patients with Relapsed or Refractory Multiple Myeloma (RRMM) Receiving Belantamab Mafodotin (GSK2857916; Belamaf)

Purpose Retinitis pigmentosa (RP) shows great diversity between genotypes and phenotypes, and it is important to identify the causative genes. This study aimed to analyze the molecular profiles, associated ocular characteristics, and progression of RP in Korean patients. Methods All the genetic variants in patients with RP, identified using targeted next-generation sequencing (NGS) with a panel of 88 RP-related genes between November 2018 and November 2019, were retrospectively reviewed. All the patients underwent comprehensive ophthalmological evaluations, and their clinical and family histories were recorded. The best-corrected visual acuity (BCVA) deterioration and photoreceptor disruption progression rates were determined based on the major causative mutational genes using nonlinear mixed models, and the differences among them were investigated using the interaction effect. Results Among the 144 probands, 82 variants in 24 causative genes were identified in 77 families (53.5%). Most of the RP cases were associated with autosomal recessive variants (N = 64 (44.4%)), followed by autosomal dominant (N = 10 (6.9%)) and X-linked variants (N = 3 (2.1%)). The four most frequently affected genes were EYS (N = 15 (10.4%)), USH2A (N = 12 (8.3%)), PDE6B (N = 9 (6.3%)), and RP1 (N = 8 (5.6%)). Epiretinal membranes and cystoid macular edema were frequently noted in the patients with USH2A (75.0%) and PDE6B (50.0%) variants, respectively. During the follow-up period, the BCVA and photoreceptor disruption changes were significantly different among the patients carrying the four common causative genes (P=0.014 and 0.034, resp.). Patients with PDE6B variants showed faster BCVA changes (0.2 LogMAR/10 years), and those with USH2A variants showed the fastest ellipsoid zone disruptions (−170.4 µm/year). Conclusion In conclusion, our genetic analysis using targeted NGS provides information about the prevalence of RP-associated mutations in Korean patients. Delineating clinical characteristics according to genetic variations may help clinicians identify subtype features and predict the clinical course of RP.

BackgroundTo evaluate the correlation between visual acuity improvement and vision-related QOL after ranibizumab treatment in Japanese patients with AMD.MethodsIn this one-year prospective, interventional, open-label, multicenter study involving four sites, patients with neovascular AMD were enrolled and observed for 12 months. Treatment-naïve patients received 0.5 mg ranibizumab as needed after three initial monthly doses. The best corrected visual acuity (BCVA) and central macular thickness (CMT) were measured at every visit. Evaluations with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and patient satisfaction questionnaire were performed at baseline and 3 and 12 months after initial treatment. The primary endpoint was change in BCVA and QOL 3 months after ranibizumab treatment. QOL outcomes were also assessed in the better and poor BVCA subgroups.ResultsThe study enrolled 100 patients. The mean logMAR BCVA after treatment improved significantly from 0.43 to 0.30 at 3 months (p< 0.0001), and 0.28 at 12 months (p< 0.0001). The mean NEI-VFQ-25 composite scores improved from 79.48 to 84.13 at 3 months (p< 0.0001), and 86.0 at 12 months (p< 0.0001). The 3 and 12-month changes in NEI-VFQ-25 score and BCVA showed significant correlation. In the poor baseline visual acuity group (decimal BCVA ≤0.5), there was a significant correlation between the changes in the NEI-VFQ-25 score and BCVA (p=0.02) but not in the better baseline visual acuity group (decimal BCVA > 0.6, p=0.1) at 3 months. There were no significant differences in the satisfaction questionnaire score from baseline to at 3 months (p=0.54) and 12 months (p=0.23). The average CMT improved significantly from 340 to 264 μm at 3 months (p< 0.0001) and to 268 μm at 12 months (p< 0.0001).ConclusionsIntravitreal ranibizumab treatment resulted in improvement in visual acuity, anatomical change, and visual function change in Japanese AMD patients. Significant improvement was seen in patient visual function, and this was correlated with changes in VA, except immediately after loading dose treatment in patients with higher baseline VA. The patients’ satisfaction with the treatment remained unchanged during the study period.Trial registrationThis study is registered at UMIN Clinical Trials Registry (UMIN000012013). Registered October 10, 2013, as prospective study.

PurposeTo investigate the long-term natural history of retinal function of achromatopsia (ACHM).MethodsSubjects with molecularly confirmed ACHM were recruited in a prospective cohort study of mesopic microperimetry. Coefficient of repeatability and intraclass correlation coefficient (ICC) of mean sensitivity (MS) were calculated. Best-corrected visual acuity (BCVA), bivariate contour ellipse area (BCEA), contrast sensitivity (CS), MS, total volume (VTOT), and central field volume (V5°) from volumetric and topographic analyses were acquired. Correlation of functional parameters with structural findings from optical coherence tomography (OCT) was performed.ResultsEighteen subjects were recruited. Mean follow-up was 7.2 years. The MS test–retest repeatability coefficient was 1.65 decibels (dB), and the ICC was 0.973 (95% confidence interval, 0.837–0.98). Mean MS was similar for right and left eyes (16.97dB and 17.14dB, respectively). A negative significant correlation between logMAR BCVA and the retinal sensitivity indices (MS, VTOT, V5°) was found. A significant negative correlation between logCS and MS, VTOT, and V5° was also observed. BCVA and BCEA improved during follow-up. Mean CS, MS, VTOT, and V5° at final follow-up were similar to baseline. MS was similar between CNGA3- and CNGB3-ACHM. Patients with and without the presence of a foveal ellipsoid zone on OCT had similar MS (16.64 dB and 17.17 dB, respectively).ConclusionsWe demonstrate a highly reproducible assessment of MS. Retinal function including MS, volumetric indices, and CS are stable in ACHM. Improvement of fixation stability and small changes of BCVA over time may be part of the natural history of the disease.

PURPOSE:: To compare the effect of intravitreal diclofenac (IVD) versus intravitreal triamcinolone (IVT) on refractory uveitic cystoid macular edema. METHODS:: In this pilot, randomized, clinical trial, 15 eyes were randomly assigned to IVD group, patients (8 eyes) who received a single intravitreal injection of diclofenac (500 μg/0.1 mL), and IVT group (7 eyes) patients who received a single intravitreal injection of triamcinolone (2 mg). Change in best-corrected visual acuity in logarithm of the minimum angle of resolution at Week 36 was the primary outcome measure. Secondary outcomes included changes in best-corrected visual acuity (BCVA) at 12 weeks and 24 weeks, central macular thickness, macular leakage, and potential injection-related complications. RESULTS:: In the IVD group, BCVA was more than the baseline values in 4 eyes at 36 weeks; however, within-group analysis disclosed no statistically significant changes in the mean BCVA in this group. Nonetheless, in the IVT group, mean BCVA improved significantly at 12, 24, but not at 36 weeks compared with the baseline values. It was 0.86 ± 0.37 at baseline and 0.63 ± 0.48, 0.62 ± 0.42, and 0.43 ± 0.49 logarithm of the minimum angle of resolution at 12, 24, and 36 weeks, respectively. Mean central macular thickness diminished also significantly only in the IVT group. Nevertheless, comparing the mean BCVA and central macular thickness changes, macular leakage, and the occurrence of any injection-related complications, no significant difference was observed between the groups at any of the follow-up visits. CONCLUSION:: This pilot study demonstrated the superiority of IVT over IVD in the treatment of refractory uveitic cystoid macular edema regarding both functional and anatomical outcomes. Further studies are warranted to confirm potential benefit of IVD observed in this study.

Intravitreal Bevacizumab for Diabetic Macular Edema Associated With Severe Capillary Loss: One-Year Results of a Pilot Study

Fundus Autofluorescence Patterns in Best Vitelliform Macular Dystrophy

Prediction for 2-Year Vision Outcomes Using Early Morphologic and Functional Responses in the Comparison of Age-related Macular Degeneration Treatments Trials

To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM. The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study. Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing: PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the 6 causative variants that are known to cause ACHM, or the 275 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C. The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in whole-exome sequencing suggests the presence of unique hotspots in Japanese patients with ACHM that were not detectable via ordinal whole-exome sequencing.