Efficacy of lenadogene nolparvovec gene therapy versus idebenone in Leber hereditary optic neuropathy due to the m.11778G>A MT-ND4 variant: two matching adjusted indirect comparisons.

Analysis of a 3-year, Phase 4, open-label, observational study evaluating the association of baseline best-corrected visual acuity (BCVA) with visual, treatment burden, and retinal thickness variability (RTV) outcomes and intraocular pressure (IOP)-related events after the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant. Data from patients with diabetic macular edema (DME) who did not have a clinically significant rise in IOP after previous corticosteroid treatment (N = 202 eyes from 159 patients) were segregated by baseline BCVA of ≥20/40 or <20/40 and analyzed for BCVA, number of yearly supplemental DME treatments, RTV, and incidence of IOP-related events. At 36 months post-FAc, eyes with better baseline BCVA (≥20/40) maintained baseline BCVA, whereas vision in eyes with worse baseline BCVA (<20/40) increased by approximately 7 letters to 61.34 letters (Snellen equivalent approximately 20/60; P < 0.05). Treatment burden and RTV decreased post-FAc regardless of baseline BCVA. Eyes with better baseline BCVA (≥20/40) had numerically fewer IOP-related events post-FAc versus eyes with worse baseline BCVA (<20/40), including a lower incidence of incisional IOP-lowering surgery. The 0.19-mg FAc implant improved RTV and treatment burden regardless of baseline BCVA. Better baseline BCVA (≥20/40) was associated with long-term BCVA maintenance. Although eyes with worse baseline BCVA (<20/40) experienced significantly improved BCVA, it never rose to the level of those with better baseline BCVA. These data indicate that early, effective intervention in DME, before significant vision loss occurs, is key to maintaining visual outcomes.

This study aimed to assess the safety and efficacy of a rAAV2 carrying normal ND4 (rAAV2-ND4) (NR082) in individuals with visual loss due to LHON carrying the m.11778G>A mutation. Additionally, it aimed to determine a safe dose of NR082 for intravitreal injection. This was a single-arm, open-label, dose-finding clinical trial. A total of 12 participants with the m.11778G>A mitochondrial DNA mutation and vision loss exceeding 6 months in both eyes were enrolled in this trial. The participants received NR082 by unilateral intravitreal injections. 6 participants received 1.5 × 109 vg, 0.05 mL (Group I), and 6 participants received 4.5 × 109 vg, 0.05 mL (Group II) and were followed for 52 weeks and underwent safety assessments, with visual structure and function examinations. No serious ocular or systemic adverse events or dose-limiting toxicity were reported. Adverse events possibly related to treatment included uveitis, subconjunctival haemorrhage, vitreous opacity and keratic precipitates. In Group I, the mean baseline best-corrected visual acuity (BCVA) in injected eyes improved from 1.86 ± 0.36 LogMAR at baseline to 1.59 ± 0.10 LogMAR in week 52 post intravitreal rAAV2-ND4. In Group II, baseline BCVA was 2.15 ± 0.23 LogMAR, improving to 1.92 ± 0.32 LogMAR in week 52. Two eyes in Group I and four eyes in Group II showed significant improvement (at least 0.3 LogMAR BCVA improvement) after 52 weeks. This Phase 1/2 trial demonstrated no serious safety concerns among the 12 participants. And dose of 4.5 × 109 vg, 0.05 mL was to be used in future Phase 3 study.

BackgroundThis study aimed to elucidate visual benefits of ranibizumab in patients with neovascular age-related macular degeneration (nAMD) compared with control arms and identify factors affecting response.MethodsThis is a post-hoc pooled...

Intravitreal injections with anti-vascular endothelial growth factor (anti-VEGF) for the treatment of subfoveal diabetic macular oedema (DMO) were approved in Denmark in 2011 but were used off-label at our centre 2008–2011 (Brynskov et al., 2013). We hereby report real-world experiences with intravitreal ranibizumab and aflibercept for DMO in the Zealand Region (836 000 inhabitants) 2008–2021. We retrospectively analysed all eyes that received at least 1 injection for DMO. Almost all eyes were treatment-naïve. Eyes with no follow-up visits or no recorded baseline visual acuity were excluded (n = 125). We initiated treatment with 1–3 monthly or bimonthly injections followed by observation and decision to re-treat based on disease activity. Outcomes were similar for patients receiving a loading dose versus a non-loading dose (Lindboe et al., 2021). Re-admitted eyes were included, counting the intermediate period as an observation period. We included 1083 eyes of 728 patients treated with a total of 8790 anti-VEGF injections. A mean of 4.1 injections were given per eye in the first year and 0.9 injections were given in the following years up to discontinuation. Baseline best corrected visual acuity (BCVA) was 67.8 (±0.4) ETDRS letters and improved by a mean of 2.5 (±0.3) letters at the first follow-up visit and gradually declined by a mean of 0.8 letters per year thereafter. Only 22 eyes completed 8 years of follow-up, and in these eyes, BCVA had decreased by 8.6 (±19.7) letters compared with baseline (Figure 1). The yearly proportion of eyes with an increase of at least 10 letters up to 7 years of follow-up was 13%–16%. However, the yearly proportion of eyes with a loss of more than 10 letters increased gradually from 5% after the first follow-up visit to 32% after 7 years. After 7 years 42% of eyes maintained BCVA ≥69 letters. The eyes with the poorest baseline BCVA experienced the largest gain in BCVA at the first follow-up visit, but the eyes with low baseline BCVA did not catch up with the eyes that started with better baseline BCVA. Baseline mean central retinal thickness (CRT) was 432 μm and declined to a mean of 68 μm (±101 μm) at the first follow-up visit and decreased by a mean of 9 μm per year until year 7 (n = 58). Lower baseline BCVA (p < 0.0001), younger age (p < 0.0001), and lower HbA1c at baseline (p = 0.01) were associated with a better BCVA at 2 years after baseline (multiple linear regression). Sex (p = 0.75), diabetes type (p = 0.83), diabetes duration (p = 0.28), previous central laser treatment (p = 0.80), previous pan-retinal laser photocoagulation (PRP) (p = 0.24), baseline CRT (p = 0.68), pure ranibizumab versus pure aflibercept (p = 0.92) failed to reach statistical significance. Similar results were seen at the first follow-up visit, at 1 year and for all discontinued patients at the time of discontinuation—both collectively and for patients discontinued before 3 years, after 3–4 years and after more than 4 years. The only exception was prior PRP, which was associated with better BCVA at the first follow-up visit (p = 0.01). Our results reflect a real-world setting and only eyes in need of continuous treatment were analysed as eyes with stable or intractable disease were discontinued. In most other long-term studies for the anti-VEGF treatment of DMO, BCVA stabilizes around 70 ETDRS letters, regardless of treatment regimen (Dugel et al., 2016) using a higher number of yearly injections than in our cohort. In a real-world setting, anti-VEGF treatment can initially improve BCVA followed by a gradual yearly decline around a mean of 0.8 letters with a modest number of yearly injections. Lower baseline BCVA, younger age and lower baseline HbA1c were consistently associated with a better outcome.

Background/aimsTo report the clinical course of patients with idiopathic epiretinal membranes (iERMs) and good baseline best-corrected visual acuity (BCVA) managed without surgical treatment.MethodsRetrospective, observational case series of patients with iERMs and 20/50 or better BCVA who did not undergo surgery between January 2014 and December 2017 with a 1-year follow-up. Secondary epiretinal membranes were excluded. iERMs were stratified into two groups: Group I (BCVA 20/30 or better) and Group II (BCVA 20/40 to 20/50). The main outcome measures included baseline and final follow-up BCVA, central macular thickness (CMT) on OCT.ResultsThe study included 174 eyes (145 patients): 139 eyes (79.8%) had typical iERMs and 35 eyes (18%) had LMH. For Group I typical iERMs, the logMAR baseline and final mean BCVA were 0.09 ± 0.1 (Snellen equivalent 20/25) and 0.10 ± 0.1 (20/25+) respectively (p = 0.22). In this group, the baseline and final mean CMT were 335 ± 73µm and 342 ± 78µm, respectively (p = 0.47). For Group II typical iERMs, the logMAR baseline and final mean BCVA were 0.3 ± 0.1 (20/44) and 0.4 ± 0.2 (20/45) respectively (p = 0.31). In this group, the baseline and final mean CMT were 386 ± 95µm and 391 ± 93µm, respectively (p = 0.84).ConclusionThe clinical course of patients with iERM and good baseline BCVA is generally favorable without surgery and includes stable BCVA and OCT measurements after at least one year.

To evaluate predictive factors for postoperative visual function of primary chronic rhegmatgenous retinal detachment (RRD) after sclera buckling (SB). Totally 48 patients (51 eyes) with primary chronic RRD were included in this prospective interventional clinical cases study, which underwent SB alone from June 2008 to December 2014. Age, sex, symptoms duration, detached extension, retinal hole position, size, type, fovea on/off, proliferative vitreoretinopathy (PVR), posterior vitreous detachment (PVD), baseline best corrected visual acuity (BCVA), operative duration, follow up duration, final BCVA were measured. Pearson correlation analysis, Spearman correlation analysis and multivariate linear stepwise regression were used to confirm predictive factors for better final visual acuity. Student's t-test, Wilcoxon two-sample test, Chi-square test and logistic stepwise regression were used to confirm predictive factors for better vision improvement. Baseline BCVA was 0.8313±0.6911 logMAR and final BCVA was 0.4761±0.4956 logMAR. Primary surgical success rate was 92.16% (47/51). Correlation analyses revealed shorter symptoms duration (r=0.3850, P=0.0053), less detached area (r=0.5489, P<0.0001), fovea (r=0.4605, P=0.0007), no PVR (r=0.3138, P=0.0250), better baseline BCVA (r=0.7291, P<0.0001), shorter operative duration (r=0.3233, P=0.0207) and longer follow up (r=-0.3358, P=0.0160) were related with better final BCVA, while independent predictive factors were better baseline BCVA [partial R-square (PR(2))=0.5316, P<0.0001], shorter symptoms duration (PR(2)=0.0609, P=0.0101), longer follow up duration (PR(2)=0.0278, P=0.0477) and shorter operative duration (PR(2)=0.0338, P=0.0350). Patients with vision improvement took up 49.02% (25/51). Univariate and multivariate analyses both revealed predictive factors for better vision improvement were better baseline vision [odds ratio (OR) =50.369, P=0.0041] and longer follow up duration (OR=1.144, P=0.0067). Independent predictive factors for better visual outcome of primary chronic RRD after SB are better baseline BCVA, shorter symptoms duration, shorter operative duration and longer follow up duration, while independent predictive factors for better vision improvement after operation are better baseline vision and longer follow up duration.

Spectral-Domain OCT Predictors of Visual Outcomes after Ranibizumab Treatment for Macular Edema Resulting from Retinal Vein Occlusion

To evaluate the baseline spectral-domain optical coherence tomography (SD-OCT) characteristics of macular edema (ME) due to branch retinal vein occlusion (BRVO) for visual outcome after intravitreal bevacizumab injection. Fifty-nine patients treated in one eye with intravitreal bevacizumab for ME due to BRVO were retrospectively reviewed. Stepwise multiple regression analysis was used to evaluate the relative contribution of several variables, including SD-OCT characteristics such as photoreceptor inner segment/outer segment (IS/OS) integrity and external limiting membrane (ELM status), baseline best-corrected visual acuity (BCVA), and baseline central retinal thickness (CRT) with final visual outcome. Thirty-one patients (52.5 %) had disrupted photoreceptor IS/OS integrity. The mean BCVA improved significantly from 0.50 logMAR (20/63 Snellen equivalent) to 0.10 logMAR (20/25 Snellen equivalent) in the intact photoreceptor group (p = 0.000, paired t-test). However, the mean BCVA was improved in the disrupted photoreceptor group, from 1.10 logMAR (20/252 Snellen equivalent) to 0.94 logMAR (20/174 Snellen equivalent), which was not statistically significant (p = 0.177, paired t-test). ELM was disrupted in 23 patients (39.0 %). The mean BCVA improved significantly from 0.63 logMAR (20/85 Snellen equivalent) to 0.26 logMAR (20/36 Snellen equivalent) in the intact ELM group (p = 0.000, paired t-test), however, not significantly improved in the disrupted ELM group, from 1.09 logMAR (20/246 Snellen equivalent) to 1.01 logMAR (20/205 Snellen equivalent) (p = 0.563, paired t-test). The strongest individual predictor of final BCVA among patients with ME due to BRVO was the integrity of photoreceptor IS/OS layer on SD OCT (r (2) = 0.514, p = 0.000, stepwise multiple regression), but the most efficient model was the combination of the photoreceptor IS/OS integrity, ELM status, and baseline BCVA (r(2) = 0.671, p = 0.000, stepwise multiple regression). The strongest predictor of final BCVA was the status of photoreceptor IS/OS integrity (β = 0.532, p = 0.000, stepwise multiple regression), followed by ELM status (β = 0.325, p = 0.006, stepwise multiple regression), and the baseline BCVA (β = 0.238, p = 0.013, stepwise multiple regression). Our results suggest that baseline SD-OCT characteristics, the status of photoreceptor IS/OS and ELM can be helpful in predicting the final visual outcome after intravitreal bevacizumab injection in these patients.

ImportanceFactors affecting visual acuity prognosis after gene therapy in Leber's hereditary optic neuropathy (LHON) patients with mutation at site 11 778 are unknown.BackgroundTo analyse correlations between visual acuity prognosis and baseline characteristics of LHON after rAAV2‐ND4 gene therapy.DesignRetrospective study.ParticipantsFifty‐three LHON patients with a mutation at site 11 778.MethodsSingle‐eye intravitreal injection of rAAV2‐ND4.Main Outcome MeasuresSex, onset age, duration of disease, best‐corrected visual acuity (BCVA), visual field index (VFI) and mean deviation (MD) were recorded for all patients at baseline. BCVA was recorded at 1‐ and 3‐month follow‐up visits after gene therapy. Correlations between BCVA prognosis and baseline characteristics were analysed by univariate analysis. Logistic regression analysis was performed on independent factors affecting BCVA prognosis.ResultsUnivariate analysis showed significant differences in the VFI and MD of the injected eye between BCVA improvement and non‐improvement groups after 3 months of treatment, with greater VFI and smaller absolute MD in the BCVA improvement group. Logistic regression showed that VFI and baseline BCVA were independent prognostic factors for visual acuity. The correlation between VFI and MD was statistically significant.Conclusions and RelevanceVFI and baseline BCVA were correlated with the visual acuity prognosis of LHON patients receiving gene therapy, with greater baseline VFI and better baseline BCVA predicting better visual acuity prognosis. MD was strongly correlated with VFI and might be correlated with gene therapy prognosis. This finding may form a basis for predicting the efficacy of gene therapy in these patients and guiding subsequent treatment.

Introduction: The objective of this study was to evaluate the impact of unplanned treatment gap, secondary to COVID-19 pandemic lockdowns, on visual acuity in previously treated diabetic macular edema (DME) patients. Methods: A multicenter, retrospective study of DME patients, previously treated with anti-VEGF injections, who were followed up during COVID-19 pandemic (2020) compared to pre-CO­VID-19 period (2019). Results: A total of 634 DME patients with a mean age of 68.4 years met the inclusion criteria, 385 were assessed in 2019 (pre-COVID-19) and 239 patients assessed in 2020 (COVID-19). Baseline best corrected visual acuity (BCVA) among patients in 2019 and 2020 was 0.52 ± 0.44, 0.45 ± 0.43 (logarithm of the minimal angle of resolution, respectively). There was no significant difference between the years 2020 and 2019 in baseline BCVA (p = 0.07). Mean number of anti-VEGF injections was significantly lower (5 vs. 6, p < 0.01), with a major lower ratio of injections per patient in the COVID-19 first lockdown period (March–June 2020) in the COVID-19 group. Baseline BCVA (p < 0.01) was the only significant predictor of final BCVA. Number of injections, age, gender, and the year were not found as predictors of final BCVA. Conclusions: In a large cohort of DME patients, an unplanned delay in treatment with anti-VEGF injections for 2–3 months, due to COVID-19 pandemic lockdown, had no significance impact on visual acuity. For most patients, returning to routine treatment regimen was sufficient for maintaining BCVA.

PurposeTo evaluate the 12-month outcome of intravitreal anti-vascular endothelial growth factor therapy in eyes with bilateral retinal angiomatous proliferation (RAP).MethodsThis retrospective observational study included 38 eyes of 19 patients with stage 1 or 2 bilateral RAP at diagnosis. The eyes of patients who exhibited different baseline best-corrected visual acuity (BCVA) values in both eyes were assigned to one of two groups—the better (n=13) and worse (n=13) visual acuity groups. The BCVA values in both groups were compared to those at baseline and at 12 months. In addition, the 12-month changes in BCVA were compared between the two groups. The association between the optical coherence tomography findings at diagnosis and the 12-month BCVA was also analyzed.ResultsThe values of mean baseline and 12-month BCVA in the better visual acuity group (13 eyes) were 0.48 ± 0.19 and 0.58 ± 0.29, respectively, and those in the worse visual acuity group (13 eyes) were 0.83 ± 0.20 and 0.90 ± 0.31. The 12-month changes in BCVA were not significantly different between the two groups (p=0.786). Among the six patients with equivalent baseline BCVA in both eyes, four patients (66.7%) exhibited 1 to 2 lines or ≥3 lines of difference in BCVA between eyes at 12 months. Eyes without pigment epithelial detachment (PED) at diagnosis exhibited significantly better BCVA at 12 months than eyes with PED (p=0.021).ConclusionsBetter baseline visual acuity was associated with better BCVA at 12 months posttreatment in patients with bilateral RAP. However, equivalent baseline visual acuity in both eyes might not guarantee similar treatment outcomes. In addition, the absence of PED is predictive of better visual outcome.

OCT Predictors of 3-Year Visual Outcome for Type 3 Macular Neovascularization

Effects of Time From Diagnosis to Treatment and Baseline Vision on Retinal Vein Occlusion Outcomes in Aflibercept 2 mg Phase 3 Trials.

BackgroundTo compare the efficacy of pars plana vitrectomy (PPV) at different time points to treat acute retinal necrosis (ARN) and to investigate the necessity of PPV for ARN.MethodsA retrospective review of the treatment options and outcomes of the ARN patients was performed. Thirty ARN patients (34 eyes) were included in this study. The eyes were divided into 3 groups depending on the treatment administered. In the medically treated group, there was no retinal detachment (RD) at the first visit. The routine group patients were treated with systemic antiviral medications, as well as with intravitreal antiviral injections. In the early PPV treatment group, there was no RD at the first visit. The early PPV treatment group patients were treated with systemic antiviral medications and PPV plus silicone oil tamponade and intravitreal injection. In the PPV group, there was RD at the first visit. The PPV group patients were treated with systemic antiviral medications and PPV plus silicone oil tamponade and intravitreal injection.ResultsIn the medically treated group, the mean baseline best corrected visual acuity (BCVA) (logMAR) was 1.38 ± 0.35. The BCVA was 1.21 ± 0.36 at the last visit for the medically treated group. In this group, one eye (12.5%) developed RD after 1 month of treatment. In the early PPV treatment group, the mean BCVA (logMAR) was 1.68 ± 0.26. The BCVA was 1.83 ± 0.21 at the last visit for the early PPV group. In this group, five eyes (29.4%) had recurrent RD before silicone oil removal. In the PPV group, the mean BCVA (logMAR) was 2.0 ± 0.35. The BCVA was 1.72 ± 0.34 at the last visit for the PPV group. In this group, one eye (11.1%) had recurrent RD before silicone oil removal. There were no significant differences among the three groups in the baseline BCVA and the BCVA at the last visit (p>0.05). There were no significant differences between the early PPV group and the PPV group in the recurrent RD rates (p = 0.38).ConclusionsProphylactic PPV showed no difference in recurrent RD rates or better BCVA. Therefore, prophylactic vitrectomy cannot prevent RD nor improve the prognosis of ARN based on our research.

Latent, acute, and chronic Leber's hereditary optic neuropathy