SCORE2 Report 13: Intraretinal Hemorrhage Changes in Eyes with Central or Hemiretinal Vein Occlusion Managed with Aflibercept, Bevacizumab or Observation. Secondary Analysis of the SCORE and SCORE2 Clinical Trials
Am J Ophthalmol. 2020 Aug 20;S0002-9394(20)30459-1.
Andrew Hendrick, Paul C VanVeldhuisen, Ingrid U Scott, Jacquie King, Barbara A Blodi, Michael S Ip, Rahul N Khurana, Neal L Oden, SCORE2 Investigator Group
PMID: 32828880 DOI: 10.1016/j.ajo.2020.08.030
Purpose: To investigate the relationship between intraretinal macular hemorrhage and visual acuity outcomes in eyes with CRVO or HRVO managed with aflibercept, bevacizumab, or observation.
Design: Retrospective analysis of data from two randomized clinical trials.
Methods: 362 participants were randomized in the Study of COmparative Treatments for REtinal Vein Occlusion 2 and 88 participants randomized to observation in the Standard Care versus COrticosteroid in REtinal Vein Occlusion Study. Participants received monthly intravitreal aflibercept or bevacizumab through Month 6 or observation through Month 8. Main outcome was visual acuity letter score (VALS).
Results: Reduced area of hemorrhage by Month 6 was observed in 70.7% (116/164) of aflibercept-treated eyes, 63.8% (104/163) of bevacizumab-treated eyes, and 42.2% (27/64) of observation eyes by Month 8 (P<0.01). Relative to eyes with hemorrhage during follow-up: aflibercept-treated eyes without hemorrhage at Month 6 had a mean VALS improvement of 8.0 (99% CI: 1.9, 14.2); bevacizumab-treated eyes without hemorrhage at Month 6 had a mean VALS improvement of 3.2 (99% CI: -4.6, 11.0); observation eyes without hemorrhage at Month 8 had a mean VALS improvement of 13.5 (99% CI: 0.4, 26.5). At Month 6, presence of hemorrhage and change in central subfield thickness (CST) were significantly associated with change in VALS; however, CST was a more important predictor.
Conclusion: Improvement in hemorrhage during follow-up was associated with visual acuity improvements and predicted visual acuity changes beyond what was explained by CST. These findings suggest intraretinal macular hemorrhage is an important indicator of disease severity in retinal vein occlusion.
The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration
Int J Retina Vitreous. 2020 Aug 20;6:39.
Emily S Levine, Eugenia Custo Greig, Luísa S M Mendonça, Shilpa Gulati, Ivana N Despotovic, A Yasin Alibhai, Eric Moult, Nora Muakkassa, Maddalena Quaranta-El Maftouhi, Adil El Maftouhi, Usha Chakravarthy, James G Fujimoto, Caroline R Baumal, Andre J Witkin, Jay S Duker, M Elizabeth Hartnett, Nadia K Waheed
PMID: 32844038 PMCID: PMC7441632 DOI: 10.1186/s40942-020-00242-z
Background: The short-term effects of anti-vascular endothelial growth factor (anti-VEGF) treatment on macular neovascularization (MNV) morphology is well described, but long-term studies on morphologic changes and correlation of such changes to the type of MNV have not been conducted. This study aims to determine if different types of MNVs in neovascular AMD (nAMD) behave differently with anti-VEGF treatment as visualized on optical coherence tomography angiography (OCTA).
Methods: Treatment-naïve nAMD patients were retrospectively screened for baseline and follow-up OCTA imaging 10 or more months after initial treatment. Images were graded for MNV type, area, activity, mature versus immature vessels, vessel density, presence of atrophy, atrophy location and area. Growth rate was calculated as the percent change in lesion area from baseline over the years of follow-up. In addition, the occurrence of complete regression and the percent of lesions that grew, remained stable, and shrunk per type was also evaluated.
Results: Forty-three eyes from 43 patients with a mean follow-up of 2 years were evaluated. On structural OCT, 26 lesions were classified as pure type 1 MNVs, 12 MNVs had a type 2 component, and 5 MNVs had a type 3 component. Of these cases, 2 mixed-type MNVs were considered to have completely regressed. There was no significant differences in MNV area and growth rate between type 1 and type 2 lesions, but all cases of type 3 lesions shrunk in the follow-up period. There was no correlation between the number of injections per year and growth rate, endpoint MNV area or endpoint activity status for any MNV type. There was no significant association between the development of atrophy and the number of injections, baseline MNV area, baseline vessel density, or lesion growth rate.
Conclusions: In nAMD, complete regression of an MNV network exposed to anti-VEGF is rare. This work emphasizes the role of anti-VEGF as anti-leakage rather than vascular regression agents in nAMD.
Virtual Reality Becomes a Reality for Ophthalmologic Surgical Clinical Trials
Transl Vis Sci Technol. 2020 Jun 3;9(7):1.
Dante J Pieramici, Felix Heimann, Raymond Brassard, Giulio Barteselli, Shrirang Ranade
PMID: 32832208 PMCID: PMC7414641 DOI: 10.1167/tvst.9.7.1
The Port Delivery System with ranibizumab (PDS) is an innovative, investigational drug delivery system designed for continuous delivery of ranibizumab into the vitreous to maintain therapeutic drug concentrations for extended durations. The phase 2 Ladder trial (NCT02510794) tested the efficacy of three customized formulations of ranibizumab in patients with neovascular age-related macular degeneration, and the phase 3 Archway trial (NCT03677934) will further assess the safety and efficacy of PDS 100 mg/mL with fixed 24-week refills. The insertion of the PDS implant into the vitreous cavity and subsequent refill-exchange of the drug require procedural skills that are not directly transferable from everyday experience for most eye surgeons today. Preoperative practice for the PDS implant insertion and refill-exchange procedures is therefore critical for achieving optimal surgical outcomes. Virtual reality (VR) as a training tool has long been used by the aeronautic industry and more recently adapted for physician training in medicine and surgery, with encouraging results. Besides the primary use of traditional training tools, physicians participating in Archway have an option to practice in computer-simulated environments provided by VR simulators before performing their first PDS implant insertion and refill-exchange procedures on patients. This Perspective article describes the unique advantages and technologic challenges that practice on VR simulators has to offer, and the experience of Archway physicians with VR technology as a first in any ophthalmic clinical trial.
Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study
Br J Ophthalmol. 2020 Aug 22;bjophthalmol-2020-316952.
Amy Babiuch, Charles Clifton Wykoff, Jenna Hach, Sunil Srivastava, Katherine E Talcott, Hannah J Yu, Muneeswar Nittala, SriniVas Sadda, Michael S Ip, Thuy Le, Ming Hu, Jamie Reese, Justis P Ehlers
PMID: 32829304 DOI: 10.1136/bjophthalmol-2020-316952
Background/aims: Quantifying microaneurysms (MAs) turnover may be an objective measure for therapeutic response in diabetic retinopathy. This study assesses changes in MA counts on ultra-widefield fluorescein angiography (UWFA) in subjects undergoing treatment with intravitreal aflibercept injection (IAI) for proliferative diabetic retinopathy (PDR) in the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy(RECOVERY) study using an automated MA detection platform.
Methods: RECOVERY is a prospective study that enrolled 40 subjects with PDR randomised 1:1 to receive 2 mg IAI every 4 weeks(q4wk) or every 12 weeks (q12wk). UWFA images were obtained at baseline, 6 months and 1 year. Images were analysed using an automated segmentation platform to detect and quantify MAs. Zones 1, 2 and 3 correspond to the macula, mid-periphery and far-periphery, respectively.
Results: The q4wk cohort demonstrated a significant decline in MAs in all zones and panretinally at baseline versus month 6, baseline versus year 1, and month 6 versus year 1 (-20.0% to -61.8%; all p<0.001). In the q12wk cohort, baseline versus month 6 showed a significant decline panretinally (mean: -34.2%; p<0.001) and in zone 3 (mean -44.18%; p<0.001). Addiitonally, baseline to year 1 in the q12wk group demonstrated significant decline panretinally (mean: -47.7%; p<0.001) and in zone 3 (mean: -59.8%; p<0.001). All zones demonstrated significantly decline from month 6 to year 1 in the q12wk group.
Conclusion: Therapy with IAI demonstrates significantly reduced panretinal MA counts in PDR at 1 year in both treatment groups. The use of automated platforms to detect and quantify MAs may provide a novel imaging marker for evaluating disease activity and therapeutic impact.
Trial registration number: NCT02863354..
Comparison of the Effect of Ranibizumab and Aflibercept on Changes in Macular Choroidal Thickness in Patients Treated for Diabetic Macular Edema
J Ophthalmol. 2020 Aug 11;2020:5708354.
Valérie Sarda, Pauline Eymard, Linda Hrarat, Franck Fajnkuchen, Audrey Giocanti-Aurégan
PMID: 32850142 PMCID: PMC7441456 DOI: 10.1155/2020/5708354
Purpose: The aim of this study was to assess the effect of intravitreal injections (IVI) of ranibizumab and aflibercept on the choroidal thickness (CT) in patients with treatment-naive diabetic macular edema (DME) before and after monthly IVI.
Patients and Methods. Prospective monocenter study. Inclusion criteria were treatment-naive DME eyes without concomitant panretinal photocoagulation, associated with a decrease in best-corrected visual acuity ≤75 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. DME was defined by a central retinal thickness ≥300 μm on swept-source OCT (Triton DRI OCT, Topcon Corporation, Itabashi, Japan). Patients received 5 IVI of ranibizumab or aflibercept. The primary endpoint was the change in the central subfield CT (CSCT) between inclusion (M0) and 1 month after the fifth IVI (M5). The secondary endpoint was the CT changes between M0 and M5 in other locations of the macular ETDRS grid.
Results: Twenty-four eyes of 24 patients with a mean age of 61.1 years were included. Eleven and 13 patients were, respectively, treated with ranibizumab and aflibercept, and 86.4% had type 2 diabetes. The overall CSCT decreased significantly by -12 μm between M0 and M5 (231.7 μm at M0 and 219.7 μm at M5) (p=0.03). It decreased by -15.2 μm (p=0.02) in the aflibercept group (206.9 μm at M0 and 191.7 μm at M5) and by -7.3 μm (p=0.4) in the ranibizumab group (267.5 μm at M0 and 260.2 μm at M5). The CSCT decreased by -4.9 μm in noninjected contralateral eyes (242.3 μm at M0 and 237.4 μm at M5). CT changes between M0 and M5 in the superior, temporal, inferior, and nasal macular inner ring were significant in the aflibercept group but not in the ranibizumab and control groups.
Conclusion: In DME patients, the CSCT decreases after 5 IVI of anti-VEGF, especially after aflibercept treatment.
DIAGNOSIS & IMAGING
Comparison of macular neovascularization lesion size by the use of Spectral-Domain Optical Coherence Tomography Angiography and Swept-Source Optical Coherence Tomography Angiography versus Indocyanine Green Angiography
Acta Ophthalmol. 2020 Aug 24.
Anna-Maria Haas, Daniel Ahmed, Martin Stattin, Alexandra Graf, Katharina Krepler, Siamak Ansari-Shahrezaei
PMID: 32833284 DOI: 10.1111/aos.14572
Purpose: To compare the lesion sizes of macular neovascularization (MNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) as well as indocyanine green angiography (ICGA).
Methods: In this prospective, observational case series, patients showing a secured diagnosis of MNV on ICGA or Fluorescein Angiography, were imaged by SD-OCTA and SS-OCTA on the same day. Lesion size was measured on 3 × 3-mm2 and 6 × 6-mm2 scans using the Maestro 2 SD-OCTA (Topcon Corporation, Tokyo Japan) and the Triton SS-OCTA device (Topcon Corporation, Tokyo Japan) and compared to ICGA (Spectralis HRA, Heidelberg, Germany).
Results: Twenty eyes from 20 patients (11 females, 55%) were enrolled. The neovascularization area measured on 6 × 6-mm2 SD-OCTA was lower compared to that outlined on SS-OCTA, however, not reaching statistical significance (p = 0.094). Regarding 3 × 3-mm2 measurements, the median lesion sizes between the two OCTA devices were comparable (p = 0.492). Indocyanine green angiography depicted a larger lesion area than both OCTA devices, however, not reaching statistical significance.
Conclusion: SD-OCTA tends to show smaller areas of MNV extension than SS-OCTA regarding 6 × 6 mm2 scans. The lesion size of MNV can be very well compared between the different devices, emphasizing the use of OCTA for monitoring neovascular area. Lesion measurements on SS-OCTA correlate better with ICGA than SD-OCTA.
Patterns and Determinants of Choroidal Thickness in a Multiethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study
Ophthalmol Retina. 2020 Aug 25;S2468-6530(20)30340-7.
Youngseok Song, Yih-Chung Tham, Crystal Chong, Ricardo Ong, Beau J Fenner, Kai Xiong Cheong, Kengo Takahashi, Janice Marie Jordan-Yu, Kelvin Yi Chong Teo, Anna C S Tan, Ching-Yu Cheng, Tien Yin Wong, Usha Chakravarthy, Yasuo Yanagi, Gemmy Chui Ming Cheung
PMID: 32858246 DOI: 10.1016/j.oret.2020.08.012
Purpose: To describe the distribution and determinants of choroidal thickness (CT) in participants in a population study based on spectral-domain optical coherence tomography (SD-OCT) measurements.
Design: Population-based, cross-sectional study.
Subjects: Ethnic Chinese, Indian, and Malay adults older than 50 years without any retinal diseases (e.g., diabetic retinopathy, macular edema, age-related macular degeneration, central serous chorioretinopathy, etc.) that might affect the CT were recruited from the Singapore Epidemiology of Eye Diseases Study.
Methods: Choroidal imaging was performed by SD-OCT (Spectralis, Heidelberg Engineering, Germany) in enhanced-depth imaging (EDI) mode. Subfoveal choroidal thickness (SFCT) was measured on the foveal line scan by two retinal experts independently (YS and KT) and the average used in the analyses. In Chinese and Indian cohorts in whom macular raster scans were captured, the manufacturer supplied research software (Heyex SP-X version 126.96.36.199; Heidelberg Engineering) was used to obtain automated segmentation yielding mean choroidal thickness in each of the 9 ETDRS grid sectors.
Main outcome measures: SFCT and regional CT in the 9 ETDRS grid sectors.
Results: For the SFCT analysis 2,794 eyes from 1,619 participants (Chinese, Indian and Malay ) were included. The mean age was 60.9 years (SD 7.7), and 797 (49.2%) were male. Mean SFCT was 255.2 μm (SD 102.6). The normal range of SFCT was 106 to 447 μm (corresponding to 5th and 95th percentile limit of SFCT, respectively). In multivariable models, thinner SFCT was associated with older age, female, longer axial length, and Malay (vs Chinese) ethnicity. In the subset of Chinese and Indian eyes (n=1,842) in whom regional variation was evaluated the choroid was thickest at the superior and temporal sectors and thinner at inferior and nasal sectors.
Conclusions: SFCT is influenced by age, gender and ethnicity along with regional differences even within individual eyes. SFCT also shows a wide range in physiological limits. These data may be used as a reference in future studies.
Variations and trends in global disease burden of age-related macular degeneration: 1990-2017
Acta Ophthalmol. 2020 Aug 24.
Minjie Zou, Yichi Zhang, Aiming Chen, Charlotte Aimee Young, Yi Li, Danying Zheng, Guangming Jin
PMID: 32833305 DOI: 10.1111/aos.14589
Purpose: To evaluate the disease burden of age-related macular degeneration (AMD) and to evaluate the risk factors of disability-adjusted life years (DALY) caused by AMD.
Methods: Country-specific DALY number, rate and age-standardized rate of AMD were acquired from the Global Burden of Disease Study 2017 database. The Socio-demographic Index (SDI), Human Development Index (HDI), Inequality-adjusted Human Development Index (IA-HDI) and other related data were obtained from published data or shared databases. Regression analysis was conducted to evaluate the correlations between the potential risk factors and the age-standardized DALY rate of AMD.
Results: The DALY number doubled from 1990 to 2017, and DALY rate increased from 4.73 (95% CI: 3.19-6.54) to 6.95 (95% CI: 4.76-9.54). However, change was small after standardizing. Females tended to have severer burden. Disability-adjusted life years (DALY) rates were correlated to annual PM2.5 concentration, gross domestic product (GDP) per capita, population with at least some secondary education (secondary education), glaucoma prevalence and gross national income (GNI) per capita. In SDI model, glaucoma, GDP, healthcare access and quality index (HAQ) and secondary education were associated with disease burden (p < 0.001). In IA-HDI model, cataract, glaucoma, PM2.5, GDP and secondary education were correlated to DALY rates (p < 0.001). In model included four components of HDI, glaucoma, PM2.5, GDP, secondary education, expected years of schooling and life expectancy at birth were associated (p < 0.001).
Conclusion: Being female, older age, poor socioeconomic status and less educated are associated with a heavier disease burden of AMD. These findings would provide a basic understanding for policy making on AMD prevention and treatment.
Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease
BMC Med Genomics. 2020 Aug 26;13(1):120.
Thomas W Winkler, Felix Grassmann, Caroline Brandl, Christina Kiel, Felix Günther, Tobias Strunz, Lorraine Weidner, Martina E Zimmermann, Christina A Korb, Alicia Poplawski, Alexander K Schuster, Martina Müller-Nurasyid, Annette Peters, Franziska G Rauscher, Tobias Elze, Katrin Horn, Markus Scholz, Marisa Cañadas-Garre, Amy Jayne McKnight, Nicola Quinn, Ruth E Hogg, Helmut Küchenhoff, Iris M Heid, Klaus J Stark, Bernhard H F Weber
PMID: 32843070 PMCID: PMC7449002 DOI: 10.1186/s12920-020-00760-7
Background: Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD.
Methods: To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for > 170,000 photographs from UKBB. We searched for early AMD loci via GWAS and via a candidate approach based on 14 previously suggested early AMD variants.
Results: Altogether, we identified 10 independent loci with statistical significance for early AMD: (i) 8 from our GWAS with genome-wide significance (P < 5 × 10- 8), (ii) one previously suggested locus with experiment-wise significance (P < 0.05/14) in our non-overlapping data and with genome-wide significance when combining the reported and our non-overlapping data (together 17,539 cases, 105,395 controls), and (iii) one further previously suggested locus with experiment-wise significance in our non-overlapping data. Of these 10 identified loci, 8 were novel and 2 known for early AMD. Most of the 10 loci overlapped with known advanced AMD loci (near ARMS2/HTRA1, CFH, C2, C3, CETP, TNFRSF10A, VEGFA, APOE), except two that have not yet been identified with statistical significance for any AMD. Among the 17 genes within these two loci, in-silico functional annotation suggested CD46 and TYR as the most likely responsible genes. Presence or absence of an early AMD effect distinguished the known pathways of advanced AMD genetics (complement/lipid pathways versus extracellular matrix metabolism).
Conclusions: Our GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. Our data provide a resource comparable in size to the existing IAMDGC data on advanced AMD genetics enabling a joint view. The biological relevance of this joint view is underscored by the ability of early AMD effects to differentiate the major pathways for advanced AMD.
Functional Analysis and Classification of Homozygous and Hypomorphic ABCA4 Variants Associated with Stargardt Macular Degeneration
Hum Mutat. 2020 Aug 26.
Susan B Curtis, Laurie L Molday, Fabian A Garces, Robert S Molday
PMID: 32845050 DOI: 10.1002/humu.24100
Stargardt macular degeneration (STGD1) is caused by mutations in the gene encoding ABCA4, an ATP-binding cassette protein that transports N-retinylidene-phosphatidylethanolamine (N-Ret-PE) across photoreceptor membranes. Reduced ABCA4 activity results in retinoid accumulation leading to photoreceptor degeneration. The disease onset and severity vary from severe loss in visual acuity in the first decade to mild visual impairment late in life. We determined the effect of 22 disease-causing missense mutations on the expression and ATPase activity of ABCA4 in the absence and presence of N-Ret-PE. Three classes were identified that correlated with the disease onset in homozygous STGD1 individuals: Class 1 exhibited reduced ABCA4 expression and ATPase activity that was not stimulated by N-Ret-PE; individuals homozygous for these variants had an early disease onset (≤ 13 yr); Class 2 showed reduced ATPase activity with limited stimulation by N-Ret-PE; these correlated with a moderate disease onset (14 - 40 yr); Class 3 displayed high expression and ATPase activity that was strongly activated by N-Ret-PE; these were associated with a late disease onset (> 40 yr). Based on our results, we introduce a functionality index for gauging the effect of missense mutations on STGD1 severity. Our studies support the mild phenotype exhibited by the p.Gly863Ala, p.Asn1868Ile, and p.Gly863Ala/p.Asn1868Ile variants. This article is protected by copyright. All rights reserved.
NUTRITION & LIFESTYLE
Dietary nutrient intake and progression to late age-related macular degeneration in the Age-Related Eye Disease Studies 1 and 2
Ophthalmology. 2020 Aug 25;S0161-6420(20)30836-8.
Elvira Agrón, Julie Mares, Traci E Clemons, Anand Swaroop, Emily Y Chew, Tiarnan D L Keenan, AREDS and AREDS2 Research Groups
PMID: 32858063 DOI: 10.1016/j.ophtha.2020.08.018
Purpose: To analyze associations between the dietary intake of multiple nutrients and risk of progression to late age-related macular degeneration (AMD) and its subtypes. Additional objectives were to analyze progression to large drusen and interactions with AMD genotype.
Design: Post hoc analysis of two controlled clinical trial cohorts: Age-Related Eye Disease Study (AREDS; recruitment 1992-8) and AREDS2 (recruitment 2006-8).
Participants: Eyes with no late AMD at baseline in AREDS participants (n=4,504) and AREDS2 participants (n=3,738): total of 14,135 eyes. Mean age was 71.0 years (SD 6.7); 56.5% were female.
Methods: Fundus photographs were collected at annual study visits and graded centrally for late AMD. Dietary intake of multiple nutrients was calculated for each participant from food frequency questionnaires.
Main outcome measures: Progression to late AMD, geographic atrophy (GA), neovascular AMD, and (separate analyses) large drusen.
Results: Over median follow-up of 10.2 years, of the 14,135 eyes, 32.7% progressed to late AMD. For nine nutrients, intake quintiles 4 or 5 (versus 1) were significantly (P≤0.0005) associated with decreased risk of late AMD: vitamins A, B6, and C, folate, β-carotene, lutein/zeaxanthin, magnesium, copper, and alcohol. For three nutrients, quintiles 4 or 5 were significantly associated with increased risk: saturated fatty acid, monounsaturated fatty acid, and oleic acid. Similar results were observed for GA. Regarding neovascular AMD, nine nutrients were nominally associated with decreased risk (vitamins A and B6, β-carotene, lutein/zeaxanthin, magnesium, copper, docosahexaenoic acid, omega-3 fatty acid, and alcohol) and three with increased risk (saturated fatty acid, monounsaturated fatty acid, and oleic acid). In separate analyses (n=5,399 eyes of 3,164 AREDS participants), 12 nutrients were nominally associated with decreased risk of large drusen.
Conclusions: Higher dietary intake of multiple nutrients, including minerals, vitamins, and carotenoids, is associated with decreased risk of progression to late AMD. These associations are stronger for GA, for which no treatments are available, than for neovascular AMD. The same nutrients tend also to have protective associations against large drusen development. Strong genetic interactions exist for some nutrient-genotype combinations, particularly omega-3 fatty acids and CFH. These data may justify further research into underlying mechanisms and randomized trials of supplementation.
The Association of Ideal Cardiovascular Health and Ocular Diseases Among U.S Adults
Am J Med. 2020 Jul 21;S0002-9343(20)30540-4.
Noah De La Cruz, Obadeh Shabaneh, Duke Appiah
PMID: 32828726 DOI: 10.1016/j.amjmed.2020.06.004
Background: Globally, about 2.2 billion people have a vision impairment or blindness and approximately half of them could have been prevented. Several ocular diseases share common characteristics that overlap with risk factors for cardiovascular diseases. The aim of this study was to evaluate the relation between the American Heart Association's prescription for health called the Life's Simple 7 (LS7) metrics and the occurrence of ocular diseases.
Methods: Data were from 6118 adults aged ≥40 years who participated in the 2005-2008 National Health and Nutrition Examination Survey. LS7 metrics consisted of information on smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. Scores were summed for a maximum of 14 (most ideal cardiovascular health). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).
Results: The average age of participants was 57 years with 53% of them being women. A one-unit increase in LS7 scores was associated with reduced odds for age-related macular degeneration (OR: 0.95, 95% CI: 0.90-0.99), diabetic retinopathy (OR: 0.68, 95% CI: 0.64-0.73), cataract (OR: 0.94, 95% CI: 0.90-0.98), and glaucoma (OR: 0.94, 95% CI: 0.88-0.99). After multivariable adjustment, the association was limited to only diabetic retinopathy (OR: 0.69, 95% CI: 0.64-0.74). This association persisted when diabetic retinopathy was limited to only diagnosis by retinal imaging.
Conclusions: In this study, ideal cardiovascular health which is indicative of a healthy lifestyle was associated with lower odds for ocular diseases especially diabetic retinopathy. These findings suggest that interventions to prevent cardiovascular diseases may also hold promise in preventing ocular diseases.
The Efficacy of Conbercept in Polypoidal Choroidal Vasculopathy: A Systematic Review
J Ophthalmol. 2020 Aug 13;2020:4924053.
Yimin Wang, Mengxi Shen, Jinwei Cheng, Xiaodong Sun, Peter K Kaiser
PMID: 32855818 PMCID: PMC7442996 DOI: 10.1155/2020/4924053
Methods: Thirty studies with 1308 eyes were identified and included in this study. The primary outcome measures were best-corrected visual acuity (BCVA), and secondary outcomes were optical coherence tomography characteristics and polyp regression rates. The pooled results were calculated by the random-effect or fixed-effect model according to the heterogeneity of the data.
Results: Despite a large standard deviation in means (SMD) improvement for BCVA and central retinal thickness (CRT) in the conbercept group, there was no statistically significant difference in the other outcomes compared to ranibizumab and aflibercept. However, there was a greater polyp regression rate in the conbercept group at 12 months.
Conclusions: This systematic review indicates that conbercept may achieve similar BCVA and CRT improvements as ranibizumab and aflibercept, with a superior rate of polyp regression at 12 months.
Radiotherapy for neovascular age-related macular degeneration
Cochrane Database Syst Rev. 2020 Aug 26;8:CD004004.
Jennifer R Evans, Chinedu Igwe, Timothy L Jackson, Victor Chong
PMID: 32844399 DOI: 10.1002/14651858.CD004004.pub4
Background: Radiotherapy has been proposed as a treatment for new vessel growth in people with neovascular age-related macular degeneration (AMD).
Objectives: To examine the effects of radiotherapy on neovascular AMD.
Search methods: We searched CENTRAL, MEDLINE, Embase, LILACS and three trials registers and checked references of included studies. We last searched the databases on 4 May 2020. SELECTION CRITERIA: We included all randomised controlled trials in which radiotherapy was compared to another treatment, sham treatment, low dosage irradiation or no treatment in people with choroidal neovascularisation (CNV) secondary to AMD.
Data collection and analysis: We used standard procedures expected by Cochrane. We graded the certainty of the evidence using GRADE. We considered the following outcomes at 12 months: best-corrected visual acuity (BCVA) (loss of 3 or more lines, change in visual acuity), contrast sensitivity, new vessel growth, quality of life and adverse effects at any time point. MAIN RESULTS: We included 18 studies (n = 2430 people, 2432 eyes) of radiation therapy with dosages ranging from 7.5 to 24 Gy. These studies mainly took place in Europe and North America but two studies were from Japan and one multicentre study included sites in South America. Three of these studies investigated brachytherapy (plaque and epimacular), the rest were studies of external beam radiotherapy (EBM) including one trial of stereotactic radiotherapy. Four studies compared radiotherapy combined with anti-vascular endothelial growth factor (anti-VEGF) with anti-VEGF alone. Eleven studies gave no radiotherapy treatment to the control group; five studies used sham irradiation; and one study used very low-dose irradiation (1 Gy). One study used a mixture of sham irradiation and no treatment. Fifteen studies were judged to be at high risk of bias in one or more domains. Radiotherapy versus no radiotherapy There may be little or no difference in loss of 3 lines of vision at 12 months in eyes treated with radiotherapy compared with no radiotherapy (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.64 to 1.04, 811 eyes, 8 studies, I2 = 66%, low-certainty evidence). Low-certainty evidence suggests a small benefit in change in visual acuity (mean difference (MD) -0.10 logMAR, 95% CI -0.17 to -0.03; eyes = 883; studies = 10) and average contrast sensitivity at 12 months (MD 0.15 log units, 95% CI 0.05 to 0.25; eyes = 267; studies = 2). Growth of new vessels (largely change in CNV size) was variably reported and It was not possible to produce a summary estimate of this outcome. The studies were small with imprecise estimates and there was no consistent pattern to the study results (very low-certainty evidence). Quality of life was only reported in one study of 199 people; there was no clear difference between treatment and control groups (low-certainty evidence). Low-certainty evidence was available on adverse effects from eight of 14 studies. Seven studies reported on radiation retinopathy and/or neuropathy. Five of these studies reported no radiation-associated adverse effects. One study of 88 eyes reported one case of possible radiation retinopathy. One study of 74 eyes graded retinal abnormalities in some detail and found that 72% of participants who had radiation compared with 71% of participants in the control group had retinal abnormalities resembling radiation retinopathy or choroidopathy. Four studies reported cataract surgery or progression: events were generally few with no consistent evidence of any increased occurrence in the radiation group. One study noted transient disturbance of the precorneal tear film but there was no evidence from the other two studies that reported dry eye of any increased risk with radiation therapy. None of the participants received anti-VEGF injections. Radiotherapy combined with anti-VEGF versus anti-VEGF alone People receiving radiotherapy/anti-VEGF were probably more likely to lose 3 or more lines of BCVA at 12 months compared with anti-VEGF alone (RR 2.11, 95% CI 1.40 to 3.17, 1050 eyes, 3 studies, moderate-certainty). Most of the data for this outcome come from two studies of epimacular brachytherapy (114 events) compared with 20 events from the one trial of EBM. Data on change in BCVA were heterogenous (I2 = 82%). Individual study results ranged from a small difference of -0.03 logMAR in favour of radiotherapy/anti-VEGF to a difference of 0.13 logMAR in favour of anti-VEGF alone (low-certainty evidence). The effect differed depending on how the radiotherapy was delivered (test for interaction P = 0.0007). Epimacular brachytherapy was associated with worse visual outcomes (MD 0.10 logMAR, 95% CI 0.05 to 0.15, 820 eyes, 2 studies) compared with EBM (MD -0.03 logMAR, 95% CI -0.09 to 0.03, 252 eyes, 2 studies). None of the included studies reported contrast sensitivity or quality of life. Growth of new vessels (largely change in CNV size) was variably reported in three studies (803 eyes). It was not possible to produce a summary estimate and there was no consistent pattern to the study results (very low-certainty evidence). For adverse outcomes, variable results were reported in the four studies. In three studies reports of adverse events were low and no radiation-associated adverse events were reported. In one study of epimacular brachytherapy there was a higher proportion of ocular adverse events (54%) compared to the anti-VEGF alone (18%). The majority of these adverse events were cataract. Overall 5% of the treatment group had radiation device-related adverse events (17 cases); 10 of these cases were radiation retinopathy. There were differences in average number of injections given between the four studies (1072 eyes). In three of the four studies, the anti-VEGF alone group on average received more injections (moderate-certainty evidence).
Authors' conclusions: The evidence is uncertain regarding the use of radiotherapy for neovascular AMD. Most studies took place before the routine use of anti-VEGF, and before the development of modern radiotherapy techniques such as stereotactic radiotherapy. Visual outcomes with epimacular brachytherapy are likely to be worse, with an increased risk of adverse events, probably related to vitrectomy. The role of stereotactic radiotherapy combined with anti-VEGF is currently uncertain. Further research on radiotherapy for neovascular AMD may not be justified until current ongoing studies have reported their results.
Trial registration: ClinicalTrials.gov
NEI-Supported Age-Related Macular Degeneration Research: Past, Present, and Future
Transl Vis Sci Technol. 2020 Jun 30;9(7):49.
Charles Wright, Anna E Mazzucco, Steven M Becker, Paul A Sieving, Santa J Tumminia
PMID: 32832254 PMCID: PMC7414643 DOI: 10.1167/tvst.9.7.49
Purpose: To review past and current National Eye Institute (NEI)-supported age-related macular degeneration (AMD) activities and initiatives and preview upcoming coordinated efforts for studying AMD.
Methods: We conducted and summarized a portfolio analysis and literature review of NEI intramural and extramural AMD activities.
Results: The NEI supports a broad range of AMD research, both by individual independent investigators as well as through networks and consortia. The International AMD Genomics Consortium, Age-Related Eye Disease Study, Age-Related Eye Disease Study 2 (AREDS2), and Comparison of AMD Treatments Trial legacy work probed the complex genetics, clinical presentation, and standards of patient care, respectively. The NEI AMD Pathobiology Working Group identified gaps and opportunities for future research efforts. The AMD Ryan Initiative Study and clinical trials testing the efficacies of minocycline to modulate retinal microglia activity and induced pluripotent stem cells-derived retinal pigmented epithelium (RPE) patch implants to rescue photoreceptor cell death are among the future directions for NEI-supported AMD research. Finally, NEI commissioned the creation of AREDS2 participant-derived induced pluripotent stem cell (iPSC) lines linked to their associated genomic and phenotypic datasets. These datasets will also be linked to the data obtained using their associated iPSC-derived cells (RPE, retina, choroid) and made publicly available.
Conclusions: Investments by NEI for AMD research will continue to provide invaluable resources to investigators committed to addressing this complex blinding disease and other retinal degenerative diseases.
Translational relevance: NEI now stands poised to expand the resources available to clinical investigators to uncover disease mechanisms and move experimental therapies into clinical trials.
Peripapillary pachychoroid neovasculopathy: A novel entity
Eur J Ophthalmol. 2020 Aug 25;1120672120953071.
Javier Montero Hernández, Lidia Remolí Sargues, Clara Monferrer Adsuara, Verónica Castro Navarro, Catalina Navarro Palop, Enrique Cervera Taulet
PMID: 32842763 DOI: 10.1177/1120672120953071
Purpose: Peripapillary pachychoroid syndrome is a new variant of pachychoroid disease recently described. It is important to establish the features and pathogenic mechanisms of this novel entity and its possible association with type 1 neovascularization. The aim of this study is to report a case of peripapillary pachychoroid neovasculopathy, a novel entity of pachychoroid spectrum disease.
Case report: A 51-year-old woman was referred to our macula service due to macular pigmentary changes in her right eye. On examination, best corrected visual acuity was 20/20 Snellen equivalent in both eyes. Funduscopy revealed pigmentary changes in the papillonasal bundle in her right eye with mottled autofluorescence in the same area where pigmentary changes. Spectral-domain optical coherence tomography illustrated a shallow irregular pigment epithelium detachment (PED) which appears as "double layer sign" overlying pachyvessels, with hyper-flow signal beneath it and a large network of neovascularization revealed by cross-sectional optical coherence tomography angiography. Indocyanine green angiography confirmed the pachyvessels and choroidal hyper-permeability in the peripapillary region. A diagnosis of peripapillary pachychoroid neovasculopathy was made and good visual and anatomical outcomes were achieved with a treat-and-extend regimen with intravitreal aflibercept.
Conclusion: We report a novel entity within the pachychoroid spectrum disease, the peripapillary pachychoroid neovasculopathy, which could improve our understanding of the pathogenic mechanism of choroidal neovascularization in pachychoroid disorders.