Efficacy and Safety of Biosimilar FYB201 Compared with Ranibizumab in Neovascular Age-Related Macular Degeneration.

Abstract Purpose This trial was conducted to investigate the clinical equivalence of the proposed biosimilar FYB201 and reference ranibizumab in patients with treatment-naive, subfoveal choroidal neovascularization caused by neovascular age-related macular degeneration (nAMD). Design This was a prospective, multicenter, evaluation-masked, parallel-group, 48-week, phase III randomized study. Participants A total of 477 patients were randomly assigned to receive FYB201 (n = 238) or reference ranibizumab (n = 239). Methods Patients received FYB201 or ranibizumab 0.5 mg by intravitreal injection in the study eye every four weeks. Main Outcome Measures The primary end point was change from baseline in best corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 8 weeks prior to the third monthly intravitreal injection. Biosimilarity of FYB201 to its originator was assessed via a two-sided equivalence test, with an equivalence margin in BCVA of 3 ETDRS letters. Results BCVA improved in both groups, with a mean improvement of +5.1 (FYB201) and +5.6 (reference ranibizumab) ETDRS letters at week 8. The analysis of covariance (ANCOVA) least squares mean difference for the change from baseline between FYB201 and reference ranibizumab was –0.4 ETDRS letters with a 90% confidence interval (CI) of –1.6 to 0.9. Primary end point was met as the 90% CI was within the predefined equivalence margin. Adverse events were comparable between treatment groups. Conclusions FYB201 is biosimilar to reference ranibizumab in terms of clinical efficacy and ocular and systemic safety in the treatment of patients with nAMD

The impact of successful cataract surgery on quality of life, household income and social status in South India.

BACKGROUND: To explore the hypothesis that sight restoring cataract surgery provided to impoverished rural communities will improve not only visual acuity and vision-related quality of life (VRQoL) but also poverty and social status. METHODS: Participants were recruited at outreach camps in Tamil Nadu, South India, and underwent free routine manual small incision cataract surgery (SICS) with intra-ocular lens (IOL) implantation, and were followed up one year later. Poverty was measured as monthly household income, being engaged in income generating activities and number of working household members. Social status was measured as rates of re-marriage amongst widowed participants. VRQoL was measured using the IND-VFQ-33. Associations were explored using logistic regression (SPSS 19). RESULTS: Of the 294 participants, mean age ± standard deviation (SD) 60 ± 8 years, 54% men, only 11% remained vision impaired at follow up (67% at baseline; p<0.001). At one year, more participants were engaged in income generating activities (44.7% to 77.7%; p<0.001) and the proportion of households with a monthly income <1000 Rps. decreased from 50.5% to 20.5% (p<0.05). Overall VRQoL improved (p<0.001). Participants who had successful cataract surgery were less likely to remain in the lower categories of monthly household income (OR 0.05-0.22; p<0.02) and more likely to be engaged in income earning activities one year after surgery (OR 3.28; p = 0.006). Participants widowed at baseline who had successful cataract surgery were less likely to remain widowed at one year (OR 0.02; p = 0.008). CONCLUSION: These findings indicate the broad positive impact of sight restoring cataract surgery on the recipients' as well as their families' lives. Providing free high quality cataract surgery to marginalized rural communities will not only alleviate avoidable blindness but also - to some extent - poverty in the long run

Confocal Blue Reflectance Imaging in Type 2 Idiopathic Macular Telangiectasia

PURPOSE. To report the characteristics of confocal blue reflectance imaging in type 2 idiopathic macular telangiectasia (type 2 IMT). METHODS. In a prospective observational cross-sectional study, both eyes of 33 patients with type 2 IMT were examined by means of fundus biomicroscopy, fundus photography, fluorescein angiography, and optical coherence tomography (OCT). Confocal blue reflectance (CBR) imaging was performed using a confocal scanning laser ophthalmoscope (HRA2; Heidelberg Engineering, Heidelberg, Germany). To compare the results derived from different imaging modalities, an analysis was performed using image analysis software (Heidelberg Eye Explorer; Heidelberg Engineering). RESULTS. CBR imaging revealed a parafoveal area of increased reflectance that was slightly larger than the area of hyperfluorescence in late-phase fluorescein angiography. The area usually encompassed an oval parafoveal area, but sectors could be spared. A parafoveal area of increased CBR was detected in 98% of eyes that showed angiographic evidence for type 2 IMT. CONCLUSIONS. CBR imaging is a new, noninvasive, and sensitive method that may contribute to differentiate type 2 IMT from other diseases. Abnormalities of macular pigment distribution and Miiller cell pathology may contribute to the phenomenon of increased CBR and thus the pathophysiology of type 2 IMT

España y la República Romana

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Patients with Neovascular Age-Related Macular Degeneration Requiring Intensive Intravitreal Aflibercept Treatment: An ARIES Post Hoc Analysis.

INTRODUCTION The aim of this post hoc analysis of the ARIES study is to explore the requirement for intravitreal aflibercept (IVT-AFL) treatment intervals of < 8 weeks (w) in patients with neovascular age-related macular degeneration (nAMD), and to assess vision and anatomic outcomes in such patients who require more intensive treatment. METHODS ARIES was a multicenter, randomized, phase 3b/4 study that investigated the efficacy of two IVT-AFL proactive, individualized, treat-and-extend regimens over 2 years in treatment-naïve patients with nAMD. Patients were determined as injection-intensive if the study investigator identified that a treatment interval of < 8 w was needed and if they had ≥ 1 interval of < 8 w after three initial monthly doses. Treatment intervals could be extended subsequently if extension criteria were met. This is a post hoc analysis of patients enrolled in ARIES and statistical analysis is descriptive. RESULTS Of 269 patients in the combined treatment arms, 23.0% (n = 62) were injection-intensive (Year 1: 13.8% [n = 37]; Year 2: 9.3% [n = 25]). Time from IVT-AFL initiation to injection-intensive determination varied (range, 16-100 w; median: 43.2 w). Mean treatment interval was 8.4 w before and 6.1 w after injection-intensive determination. Overall, 59.7% achieved treatment intervals of ≥ 8 w following injection-intensive determination. Vision improvements from baseline to Week 104 were smaller for injection-intensive patients than non-injection-intensive patients (mean [SD] best-corrected visual acuity change: + 2.3 [15.6] vs.  + 5.9 [12.3] letters). Anatomic outcomes were similar between injection-intensive and non-injection-intensive patients (central retinal thickness change from baseline to Week 104: - 160 [154] vs.  - 167 [136] µm). CONCLUSIONS In ARIES, 23% of treatment-naïve patients with nAMD experienced at least one treatment interval of < 8 w. Injection-intensive patients showed improved vision and anatomic outcomes. For most, treatment intervals could be extended to ≥ 8 w following injection-intensive determination. CLINICALTRIALS gov Identifier: NCT02581891

Integrated results from the COPERNICUS and GALILEO studies.

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. RESULTS: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in CONCLUSION: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO

The relative impact of vision impairment and cardiovascular disease on quality of life: the example of pseudoxanthoma elasticum

<p>Abstract</p> <p>Objective</p> <p>To investigate the impact of pseudoxanthoma elasticum (PXE), a rare hereditary disease of concurrent vision impairment (VI) and cardiovascular complications (CVCs), on vision-related (VRQoL) and health-related quality of life (HRQoL).</p> <p>Methods</p> <p>VRQoL and HRQoL were assessed using the Impact of Vision Impairment (IVI) questionnaire and the Short Form Health Survey (SF-36) in 107 PXE patients. Patients were stratified into four groups: A = no VI or CVC; B = CVCs only; C = VI only; and D = both VI and CVCs.</p> <p>Results</p> <p>Following Rasch analysis, the IVI was found to function as a vision-specific functioning and emotional well-being subscale, and the SF-36 as a health-related physical functioning and mental health subscale. The presence of VI and CVC were significant predictors of vision-specific functioning and emotional well-being (p < 0.001), with a clinically meaningful decrement in vision-specific functioning in patients with VI. No associations were found for the SF-36 Physical Functioning and Mental Health scores between any groups.</p> <p>Conclusions</p> <p>Vision impaired patients with PXE report significantly poorer vision-specific functioning than PXE patients without VI. In contrast, the relative impact of PXE on reported general HRQoL was much less. Our results suggest that vision impairment has the larger impact on QoL in this sample.</p

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

INTRODUCTION Recently, 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. METHODS ARIES (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. RESULTS In 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. CONCLUSION In 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 Abstract (MP4 308264 KB)