Retina and Omega-3

Over the last decade, several epidemiological studies based on food frequency questionnaires suggest that omega-3 polyunsaturated fatty acids could have a protective role in reducing the onset and progression of retinal diseases. The retina has a high concentration of omega-3, particularly DHA, which optimizes fluidity of photoreceptor membranes, retinal integrity, and visual function. Furthermore, many studies demonstrated that DHA has a protective, for example antiapoptotic, role in the retina. From a nutritional point of view, it is known that western populations, particularly aged individuals, have a higher than optimal omega-6/omega-3 ratio and should enrich their diet with more fish consumption or have DHA supplementation. This paper underscores the potential beneficial effect of omega-3 fatty acids on retinal diseases

Choroidal neovascularisation complicating geographic atrophy in age-related macular degeneration.

Abstract OBJECTIVE: To investigate the morphological and functional outcomes after intravitreal ranibizumab injections for choroidal neovascularisation (CNV) complicating geographic atrophy (GA). DESIGN: Retrospective, interventional, consecutive case series. METHODS: We reviewed the charts of all consecutive patients with GA due to age-related macular degeneration (AMD), who received intravitreal ranibizumab injections for the development of CNV at least 24 months earlier. RESULTS: 21 treatment-naive eyes of 21 consecutive patients (4 men, 17 women, mean age 86.9±1.6 years) were included. In 95.2% of eyes a type 2 CNV was present, extrafoveal in 42.8% of cases. After a mean of 5.0±0.87 (range 1-20) intravitreal ranibizumab injections, best-corrected visual acuity (BCVA) significantly worsened at the 24-month follow-up visit (0.73±0.05 vs 0.88±0.08 logMAR, respectively; p=0.01). A significant reduction of intraretinal cystic lesions, subretinal fluid and pigment epithelium detachment (p<0.001) and a significant increase of GA area (p=0.003) were present at last visit. CONCLUSIONS: Ranibizumab treatment of GA-associated CNVs provides no BCVA improvement at 24 months follow-up despite an anatomic response of CNV. Low effectiveness of ranibizumab in these cases is likely due to GA progression

Toward a Specific Classification of Polypoidal Choroidal Vasculopathy: Idiopathic Disease or Subtype of Age-Related Macular Degeneration

PURPOSE To suggest a clinical distinction between idiopathic polypoidal choroidal vasculopathy (PCV) and secondary polyps associated with neovascular age-related macular degeneration (NV-AMD). METHODS The study was a retrospective case series of 52 eyes of 52 consecutive patients (31 females and 21 males) diagnosed with PCV. Initial diagnosis was based on scanning laser ophthalmoscope-indocyanine green angiography (SLO-ICGA) in association with fluorescein angiography (FA) and optical coherence tomography (OCT). All the data and images were analyzed in a masked fashion by four experienced examiners in two different sessions: the first, to classify patients into the two hypothesized groups (idiopathic polyps or NV-AMD-related polyps); the second, following a predetermined scheme, to describe objective features. The results obtained in each session underwent a cross multivariate analysis to identify statistically significant differences (P ≤ 0.05) between the two groups. RESULTS The two groups were clinically different on the basis of FA (leakage origin [P = 0.001] and presence of drusen [P = 0.001]), ICGA (evidence of choroidal neovascularization [CNV; P = 0.001] and/or branching vascular network [BVN; P = 0.001]), OCT imaging (type of pigmented epithelium detachment [P = 0.001], presence of BVN [P = 0.001], and subfoveal choroidal thickness [P = 0.001]). Further significant differences were observed according to the location of lesion (uni- or multifocal) (P = 0.001), type of CNV (P = 0.001), and best-corrected visual acuity (P = 0.001). CONCLUSIONS Our study demonstrated clinical and statistically significant differences between idiopathic PCV and NV-AMD-related polyps that could be considered as distinct entities. Although they share some similarities, mainly the sub-RPE location, the ability to identify a specific clinical pattern suggests a more specific therapeutic approach for these two entities

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

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)

Parafoveal OCT Angiography Features in Diabetic Patients without Clinical Diabetic Retinopathy: A Qualitative and Quantitative Analysis

Purpose. To evaluate the capacity of OCT angiography (OCTA) for detecting infraclinical lesions in parafoveal capillaries in diabetic patients without diabetic retinopathy (DR). Methods. This prospective observational cross-sectional case-control study analyzed the superficial and deep capillary plexuses (SCP and DCP) on macular OCTA scans (3 × 3 mm) centered on the fovea. We compared 22 diabetic patients (34 eyes included) without DR diagnosis on color fundus photographs, with 22 age- and gender-matched nondiabetic controls (40 eyes included). Qualitative analysis concerned morphological ischemic capillary alterations. Quantitative analysis measured foveal avascular zone (FAZ) size, parafoveal capillary density, and enlargement coefficient of FAZ between SCP and DCP. Results. Neither the qualitative nor quantitative parameters were significantly different between both groups. No microaneurysms or venous tortuosity was observed in any of the analyzed images. On the SCP, the mean FAZ area was 0.322 ± 0.125 mm2 in diabetic patients and 0.285 ± 0.150 mm2 in controls, P=0.31. On the DCP, the mean FAZ area was 0.444 ± 0.153 mm2 in cases and 0.398 ± 0.138 mm2 in controls, P=0.20. Conclusion. OCTA did not detect infraclinical qualitative or quantitative differences in parafoveal capillaries of diabetic patients without DR in comparison with nondiabetic controls

Treatment of Exudative Age-Related Macular Degeneration with a Designed Ankyrin Repeat Protein that Binds Vascular Endothelial Growth Factor: a Phase I/II Study

PURPOSE: To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN: Phase I/II, open-label, multicenter, dose-escalation study. METHODS: Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS: Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for &gt;= 4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS: A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. larger-scale studies are warranted to confirm these observations. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).PURPOSE: To evaluate the safety, tolerability and bioactivity of ascending doses of MP0112, a designed ankyrin repeat protein (DARPin) that binds with high affinity to vascular endothelial growth factor-A (VEGF-A), in treatment-naive patients with exudative age-related macular degeneration (AMD). DESIGN: Phase I/II, open-label, multicenter, dose-escalation study. METHODS: Patients were to receive a single intravitreal injection of MP0112 at doses ranging from 0.04 to 3.6 mg and be monitored for 16 weeks for safety, efficacy, pharmacokinetics, and dose response. RESULTS: Altogether, 32 patients received a single injection of MP0112. The maximum tolerated dose was 1.0 mg because of a case of endophthalmitis in the 2.0 mg cohort. Drug-related adverse events were reported by 13 (41%) of 32 patients; they included ocular inflammation in 11 patients (7 mild, 4 moderate in severity). Visual acuity scores were stable or improved compared with baseline for &gt;= 4 weeks following injection; both retinal thickness and fluorescein angiography leakage decreased in a dose-dependent manner. Rescue therapy was administered to 20 (91%) of 22 patients who received 0.04-0.4 mg MP0112 compared with 4 of 10 (40%) patients who received 1.0 or 2.0 mg. Of patients in the higher-dose cohorts who did not require rescue treatment, 83% (5/6) maintained reductions in central retinal thickness through week 16. CONCLUSIONS: A single injection of 1.0 or 2.0 mg MP0112 resulted in mean decreases in retinal thickness and leakage area despite ocular inflammation. larger-scale studies are warranted to confirm these observations. (C) 2014 The Authors. Published by Elsevier Inc. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/)