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    Research update: Issue 498

    The latest research highlights for 10 May 2021.

    10 May 2021


    Visual Acuity, Vitreous Hemorrhage, and Other Ocular Outcomes After Vitrectomy vs Aflibercept for Vitreous Hemorrhage Due to Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial

    JAMA Ophthalmol. 2021 May 6.

    Adam R Glassman, Wesley T Beaulieu, Maureen G Maguire, Andrew N Antoszyk, Clement C Chow, Michael J Elman, Lee M Jampol, Hani Salehi-Had, Jennifer K Sun, DRCR Retina Network

    PMID: 33956075 DOI: 10.1001/jamaophthalmol.2021.1110

    Importance: Although there were no differences in mean visual acuity (VA) over 24 weeks after vitrectomy with panretinal photocoagulation (PRP) vs aflibercept in a randomized clinical trial among eyes with vitreous hemorrhage due to proliferative diabetic retinopathy (PDR), post hoc analyses may influence treatment choices.

    Objective: To compare exploratory outcomes between treatment groups that may affect treatment choices for patients with vitreous hemorrhage due to PDR.

    Design, setting, and participants: This post hoc analysis of a randomized clinical trial conducted at 39 DRCR Retina Network sites included adults with vision loss due to PDR-related vitreous hemorrhage for whom vitrectomy was considered. Data were collected from November 2016 to January 2020.

    Interventions: Random assignment to 4 monthly injections of aflibercept vs vitrectomy with PRP. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol-specific criteria.

    Main outcomes and measures: Visual acuity area under the curve (adjusted for baseline VA) and clearance of vitreous hemorrhage.

    Results: A total of 205 eyes were included in the analysis (115 male [56%] and 90 [44%] female participants; mean [SD] age, 57 [11] years). Among 89 eyes with a baseline VA of 20/32 to 20/160 (47 receiving aflibercept, including 4 [9%] that had undergone vitrectomy; 42 undergoing vitrectomy, including 3 [7%] that had received aflibercept), the adjusted mean difference in VA letter score over 24 weeks between the aflibercept and vitrectomy groups was -4.3 (95% CI, -10.6 to 1.9) compared with -16.7 (95% CI, -24.4 to -9.1) among 59 eyes with baseline VA worse than 20/800 (P = .02 for interaction; 26 in the aflibercept group, including 6 [23%] that had undergone vitrectomy; 33 in the vitrectomy group, including 8 [24%] that had received aflibercept). In the full cohort, the median time to clearance of the initial vitreous hemorrhage was 36 (interquartile range [IQR], 24-52) weeks in the aflibercept group vs 4 (IQR, 4-4) weeks in the vitrectomy group (difference, 32 [95% CI, 20-32] weeks; P < .001).

    Conclusions and relevance: Both initial aflibercept and vitrectomy with PRP are viable treatment approaches for PDR-related vitreous hemorrhage. Although this study did not find a significant difference between groups in the primary outcome of mean VA over 24 weeks of follow-up, eyes receiving initial vitrectomy with PRP had faster recovery of vision over 24 weeks when baseline VA was worse than 20/800 and faster vitreous hemorrhage clearance. Approximately one-third of the eyes in each group received the alternative treatment (aflibercept or vitrectomy with PRP). These factors may influence treatment decisions for patients initiating therapy for PDR-related vitreous hemorrhage.

    Trial registration: Identifier: NCT02858076.

    Clinical Features, Prognosis, and Long-Term Response to Ranibizumab of Macular CNVs in Pattern Dystrophies Spectrum: A Pilot Study

    J Ophthalmol. 2021 Apr 16;2021:6698522

    Lorenzo Casillo, Stefano Tricarico, Laura Contento, Enzo M Vingolo  

    PMID: 33953968 PMCID: PMC8068556 DOI: 10.1155/2021/6698522

    Introduction: To analyze the morphological and functional features of choroidal neovascularizations (CNVs) in eyes affected by pattern dystrophies (PD), evaluating their long-term response to intravitreal ranibizumab, and comparing them with CNVs in age-related macular degeneration (AMD). The mean goal is to identify possible disease biomarkers and to evaluate the long-term prognosis of CNVs in PD.

    Materials and methods: A retrospective study of 42 patients with naïve CNV (26 PD and 16 AMD), for a total of 47 eyes (29 eyes in the PD group and 18 eyes in the AMD group). Each patient received a loading dose of ranibizumab (one monthly for three months) followed by pro re nata (PRN) reinjection protocol for a period of at least three years. Morphological OCT parameters (CRT, central retinal thickness; SRF, subretinal fluid; IRF, intraretinal fluid; SHRM, subretinal hyperreflective material; HRF, hyperreflective foci; HCD, hyperreflective crystalline deposits; cCT, central choroidal thickness; slCT, sublesional choroidal thickness; EZd, ellipsoid zone disruption; and best corrected visual acuity (BCVA in logMAR scale)) were reported at baseline and last follow-up.

    Results: At baseline, no significant differences were found between the two groups, except for choroidal thickness parameters that were significantly greater in the PD group (p = 0.009). Longitudinal PD analysis demonstrated reduction in BCVA (p = 0.009), decrease in CRT (p = 0.046), resolution of SRF in 61.6% of cases (p = 0.004) and SHRM in 30% (p = 0.034), and choroidal thinning both centrally (p = 0.004) and sublesional (p = 0.011) compared to baseline. At 3 years, the PD group received significantly more injections than the AMD (p = 0.011) and showed significantly thicker choroid (p = 0.033) and more frequent HRF (p = 0.006). Regarding the PD group, we found a negative correlation between age and choroidal thicknesses at baseline and at 3 years (p < 0.05); significant positive correlations were found between baseline BCVA and at 3 years (p < 0.001), BCVA at 3 years and IRF (p = 0.003) and SHRM at 3 years (p = 0.003); CRT baseline and CRT 3 years (p = 0.017); HCD at 3 years was associated with greater CRT (p = 0.04) and IRF at 3 years (p = 0.019).

    Conclusions: Early and long-term morphofunctional features of CNVs in PD and in AMD are overlapping. CNVs in PD have poorer long-term response to ranibizumab and higher choroidal thickness suggesting different pathogenetic and evolutionary mechanisms.

    One year outcomes of treat and extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy

    Eur J Ophthalmol. 2021 May 5;11206721211014717.

    Alexandros Rouvas, Nikolaos Gouliopoulos, Maria Douvali, Georgios Koutsocheras, Maria Theodorou, Nikolaos Bouratzis, Panagiota Bougatsou, Panagiotis Theodossiadis 

    PMID: 33951982 DOI: 10.1177/11206721211014717

    Purpose: To compare the 1-year outcomes of treat-and-extend and pro re nata (PRN) treatment regimens with aflibercept for polypoidal choroidal vasculopathy (PCV), by the means of visual acuity (VA), frequency of recurrence of polypoidal lesions and developed fibrosis, and the number of intravitreal injections, and thus to determine which one is preferable in the maintenance phase in PCV.

    Methods: In our prospective study, only naive and previously untreated PCV patients were included. Initially one session of photodynamic therapy (PDT) and three monthly intravitreal injections of 2.0 mg aflibercept (IAIs) were applied in 38 eyes. After this loading phase, they were re-examined and 30 PCV eyes with no exudative phenomena were included in the study. They were divided in two groups; in the first one (16 patients) the PRN treatment modality of IAIs was applied, while in the second one (14 patients) the treat-and-extend regimen was applied.

    Results: Over a 12-month period, VA significantly improved in treat-and-extend group (logMAR BCVA 0.41 ± 0.15 vs 0.57 ± 0.24 at baseline, p = 0.044), while in the PRN group VA remained stable (logMAR BCVA 0.70 ± 0.36 vs 0.65 ± 0.18 at baseline, p = 0.61). During the maintenance phase, the patients of treat-and-extend group did not encounter development/progression of fibrosis or any recurrent episodes, whereas the patients of PRN group had significantly more recurrent episodes (0 vs 1.37 ± 0.5, p < 0.001) and the frequency of development/progression of fibrosis was significantly higher (0% vs 44%, p = 0.02). However, the treat-and-extend treatment regimen was accompanied by significantly more administered IAIs (6 ± 0 vs 5.13 ± 1.08, p = 0.006).

    Conclusion: We highlighted the superiority of treat-and-extend regime with IAIs, which seems to yield better functional outcomes by preventing recurrence and subfoveal fibrosis, although a greater number of injections is required.

    Comparing Effectiveness of Three Different Anti-VEGF Treatment Regimens for Neovascular Age-Related Macular Degeneration: Two Years’ Real-World Clinical Outcomes

    Clin Ophthalmol. 2021 Apr 23;15:1703-1713.

    Faye Horner, Peck Lin Lip, Bashar R Mohammed, William Fusi-Rubiano, Eesha Gokhale, Bushra Mushtaq, Randhir Chavan

    PMID: 33935487 PMCID: PMC8080302 DOI: 10.2147/OPTH.S305141

    Purpose: To compare and report the 2-year treatment outcomes from 3 different anti-VEGF treatment regimens in treating neovascular aged-related macular degeneration (nAMD): Ranibizumab pro re nata (Ranibizumab-PRN); Ranibizumab treat and extend (Ranibizumab-T&E); Aflibercept fixed first year dosing (7 injections) with treat and extend in subsequent year (Aflibercept-Fixed).

    Methods: All treatment-naïve nAMD patients who completed 24 months of monitoring from a single treatment center were included. Patients received the initial loading dose of three injections (4-weekly interval), followed by one of the 3 treatment regimens. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcome was number of injections required in each year. Data analysis included last observation carried forward (LOCF) for patients with incomplete year-2 follow-up.

    Results: A total of 249 eyes (230 patients) were studied: 121 Ranibizumab-PRN; 65 Ranibizumab-T&E, and 63 Aflibercept-Fixed. Baseline median VA (ETDRS letters) for Ranibizumab-PRN, Ranibizumab-T&E, and Aflibercept-Fixed was 53.9, 61.1, and 54.9 letters, achieving final VA of 54.9, 65.1, and 65.1 letters, respectively. Hence, the number of letters increased at the end of 24 months for each group was +1.0 (Ranibizumab-PRN), +4.0 (Ranibizumab-T&E), highest +10.2 in Aflibercept-Fixed group. Median number of injections over 2 years (year-1/year-2) was 5/1 for Ranibizumab-PRN, 9/6 for Ranibizumab-T&E, and 7/5 for Aflibercept-Fixed. Both Ranibizumab-T&E and Aflibercept-Fixed also shared the same reduction of median CRT (115 µm), higher than Ranibizumab-PRN (83 µm).

    Conclusion: We report VA improvement from all three different treatment regimens with both Aflibercept-Fixed and Ranibizumab-T&E regimens achieving the same higher final VA. Aflibercept-Fixed dosing may have more favorable efficacy with the highest VA gain and comparatively lower dosing frequency whereas Ranibizumab-T&E may be more efficient than Ranibizumab-PRN regimen, according to our study.


    The Progression of Stargardt Disease using Volumetric Hill of Vision Analyses Over 24 Months: ProgStar Report No.15

    Am J Ophthalmol. 2021 May 2;S0002-9394(21)00214-2.

    Etienne M Schönbach, Lucas Janeschitz-Kriegl, Rupert W Strauss, Marco E G V Cattaneo, Kaoru Fujinami, David G Birch, Artur V Cideciyan, Janet S Sunness, Richard G Weleber, Michael S Ip, SriniVas R Sadda, Hendrik P N Scholl, ProgStar Study Group

    PMID: 33951446 DOI: 10.1016/j.ajo.2021.04.015

    Purpose: To report the yearly rate of change in macular function in patients with Stargardt disease type 1 (STGD1) over 24 months and to establish a new volumetric visual function index for use in clinical trials investigating the efficacy on retinal sensitivity.

    Design: International, multicenter, prospective cohort study with five study visits every 6 months over 24 months.

    Participants and main outcome measures: A total of 233 individuals with genetically confirmed STGD1 (≥ 1 disease-causing ABCA4 variant). The total volume (VTOT) beneath the sensitivity surface of a 3-D model of the hill of vision and mean sensitivity (MS) derived from mesopic microperimetry performed with a white stimulus. Changes of VTOT over time and its correlation with the ABCA4 genotype and baseline features.

    Results: At baseline, 440 eyes (233 patients) with a mean (SD) age of 33.7 (15.0) years, mean (SD) visual acuity of 46.08 (16.03) ETDRS letters were analyzed with an average VTOT of 0.91 dB-sr and an MS of 10.73 dB. The overall mean rate of decrease in sensitivity [95% CI] was 0.077 [0.064, 0.090] dB-sr/yr for VTOT and 0.87 [0.72, 1.02] dB/year for MS. The progression rate of VTOT depended on baseline visual function (0.029 dB-sr/year for low and 0.120 dB-sr/year for high baseline VTOT; p<0.001) and exhibited a difference in the first vs. second year of follow up (0.065 dB-sr/year vs. 0.089 dB-sr/year, respectively; p<0.001). The absence of pigmentary abnormalities of the retinal pigment epithelium at baseline was found to be associated with a faster progression rate (p<0.001), whereas a significant association with the genotype was not detected (p=0.7).

    Conclusion: In STGD1, both microperimetric outcomes demonstrate statistically significant and clinically meaningful changes after relatively short follow-up periods. Volumetric modeling may be useful in future interventional clinical trials that aim to improve retinal sensitivity or to slow down its decline and for structure-function correlations.

    Portable Diagnostic System for Age-Related Macular Degeneration Screening Using Visual Evoked Potentials

    Eye Brain. 2021 Apr 29;13:111-127.

    Craig Versek, S Mohammad Ali Banijamali, Peter Bex, Kameran Lashkari, Sagar Kamarthi, Srinivas Sridhar  

    PMID: 33953628 PMCID: PMC8092944 DOI: 10.2147/EB.S295745

    Background: Delayed Dark-Adapted vision Recovery (DAR) is a biomarker for Age-related Macular Degeneration (AMD), however its measurement is burdensome for patients and examiners.

    Methods: In this study, we developed a portable, wireless and user-friendly system that employs a headset with a smartphone to deliver controlled photo-bleach and monocular pattern reversal stimuli, while using custom electroencephalography (EEG) electrodes and electronics in order to measure Dark-Adapted Visual Evoked Potentials (DAVEP) objectively and separately at the peripheral and central visual field. This is achieved in one comfortable 20-minute session, without requiring subject reporting. DAVEP responses post photo-bleach for up to 15 minutes were measured concurrently from both eyes in 12 AMD-patients, 1 degenerative myopia patient, and 8 controls who had no diagnosed macular vision loss.

    Results: Robust positive polarity DAVEP responses were observed at 200-500 ms from stimulus onset to scotopic stimuli that have been seldom reported and analyzed previously. The amplitude recovery of the DAVEP response was significantly delayed in AMD patients as compared to controls. We developed DAVEP1 scores, a simple metric for DAR, which classified 90% of subject eyes correctly, indicating the presence of AMD in at least one eye of all pre-confirmed subjects with this diagnosis.

    Conclusion: We developed a user-friendly, portable VEP system and DAVEP1 metric, which show a high potential to identify DAR-deficits in AMD-patients. This novel technology could aid in early diagnosis of AMD.

    Untargeted metabolomics for uncovering plasma biological markers of wet age-related macular degeneration

    Aging (Albany NY). 2021 May 4;13.

    Yanhui Deng, Ping Shuai, Haixin Wang, Shanshan Zhang, Jie Li, Mingyan Du, Peirong Huang, Chao Qu, Lulin Huang 

    PMID: 33946050 DOI: 10.18632/aging.203006

    Wet age-related macular degeneration (wAMD) causes central vision loss and represents a major health problem in elderly people. Here we have used untargeted metabolomics using UHPLC-MS to profile plasma from 127 patients with wAMD (67 choroidal neovascularization (CNV) and 60 polypoidal choroidal vasculopathy (PCV)) and 50 controls. A total of 545 biochemicals were detected. Among them, 17 metabolites presented difference between patients with wAMD and controls. Most of them were oxidized lipids (N=6, 35.29%). Comparing to controls, 28 and 18 differential metabolites were identified in patients with CNV and PCV, respectively. Two metabolites, hyodeoxycholic acid and L-tryptophanamide, were differently distributed between PCV and CNV. We first investigated the genetic association with metabolites in wet AMD (CFH rs800292 and HTRA1 rs10490924). We identified six differential metabolites between the GG and AA genotypes of CFH rs800292, five differential metabolites between the GG and AA genotypes of HTRA1 rs10490924, and four differential metabolites between the GG and GA genotypes of rs10490924. We selected four metabolites (cyclamic acid, hyodeoxycholic acid, L-tryptophanamide and O-phosphorylethanolamine) for in vitro experiments. Among them, cyclamic acid reduced the activity, inhibited the proliferation, increased the apoptosis and necrosis in human retinal pigment epithelial cells (HRPECs). L-tryptophanamide affected the proliferation, apoptosis and necrosis in HRPECs, and promoted the tube formation and migration in primary human retinal endothelial cells (HRECs). Hyodeoxycholic acid and O-phosphorylethanolamine inhibited the tube formation and migration in HRECs. The results suggested that differential metabolites have certain effects on wAMD pathogenesis-related HRPECs and HRECs.


    Vascular endothelial growth factor inhibitors for predominantly Caucasian myopic choroidal neovascularization: 2-year treatment outcomes in clinical practice: data from the Fight Retinal Blindness! Registry

    Acta Ophthalmol. 2021 May 6.

    Pierre-Henry Gabrielle, Vuong Nguyen, Catherine Creuzot-Garcher, Lucia Miguel, Socorro Alforja, Laura Sararols, Ricardo P Casaroli-Marano, Javier Zarranz-Ventura, Mark Gillies, Jennifer Arnold, Daniel Barthelmes  

    PMID: 33960115 DOI: 10.1111/aos.14893

    Purpose: To report the 24-month outcomes of vascular endothelial growth factor (VEGF) inhibitors for myopic choroidal neovascularization (mCNV) in predominantly Caucasian eyes in routine clinical practice.

    Methods: Retrospective analysis of treatment-naïve eyes starting intravitreal injection of VEGF inhibitors of either bevacizumab (1.25 mg) or ranibizumab (0.5 mg) for mCNV from 1 January 2006 to 31 May 2018 that were tracked in the Fight Retinal Blindness! registry.

    Results: We identified 203 eyes (bevacizumab-85 and ranibizumab-118) of 189 patients. The estimated mean (95% CI) change in VA over 24 months for all eyes using longitudinal models was +8 (5, 11) letters with a median (Q1, Q3) of 3 (2, 5) injections given mostly during the first year. The estimated mean change in VA at 24 months was similar between bevacizumab and ranibizumab [+9 (5, 13) letters for bevacizumab versus +9 (6, 13) letters for ranibizumab; p = 0.37]. Both agents were also similar in the mCNV activity outcomes, treatment frequency and visit frequency.

    Conclusions: The 24-month treatment outcomes of VEGF inhibitors for mCNV were favourable in this largest series yet reported of predominantly Caucasian eyes in routine clinical practice, with approximately two lines of visual gain and a median of three injections given mostly during the first year. These outcomes are similar to those reported for predominantly Asian eyes. Bevacizumab appeared to be as safe and effective as ranibizumab.

    Increased risk of Alzheimer’s disease among patients with age-related macular degeneration: A nationwide population-based study

    PLoS One. 2021 May 7;16(5):e0250440.

    Li-Yen Wen, Lei Wan, Jung-Nien Lai, Chih Sheng Chen, Jamie Jiin-Yi Chen, Ming-Yen Wu, Kai-Chieh Hu, Lu-Ting Chiu, Peng-Tai Tien, Hui-Ju Lin  

    PMID: 33961642 DOI: 10.1371/journal.pone.0250440

    Objective: This study aimed to investigate the risk of Alzheimer’s disease among patients with age-related macular degeneration and its association with confounding comorbidities.

    Method: This was a population-based, retrospective cohort study. By accessing data from the National Health Insurance Research Database of Taiwan, we identified 10,578 patients aged 50-100 years who were newly diagnosed with age-related macular degeneration between 2000 and 2012 and 10,578 non- age-related macular degeneration individuals. The comorbidities assessed were osteoporosis, diabetes, cirrhosis, cerebrovascular disease, chronic kidney disease, hypertension, hyperlipidemia, coronary artery disease, and chronic obstructive pulmonary disease.

    Results: Patients with age-related macular degeneration had a 1.23-fold increased risk of their condition advancing to Alzheimer’s disease (aHR = 1.23, 95% CI = 1.04-1.46). The younger patients were diagnosed with age-related macular degeneration, the more likely patients got Alzheimer’s disease (50-64 age group: aHR = 1.97, 95% CI = 1.04-3.73; 65-79 age group: aHR = 1.27, 95% CI = 1.02-1.58; 80-100 age group: aHR = 1.06, 95% CI = 0.78-1.45). In addition, there were significantly higher risks of Alzheimer’s disease for patients with cirrhosis (aHR = 1.50, 95% CI = 1.09-2.06) in the age-related macular degeneration cohort than in the non-age-related macular degeneration cohort.

    Conclusion: Patients with age-related macular degeneration may exhibit a higher risk of Alzheimer’s disease than people without age-related macular degeneration.

    Eyes that Do Not Meet the Eligibility Criteria of Clinical Trials on Age-Related Macular Degeneration: Proportion of the Real-World Patient Population and Reasons for Exclusion

    J Ophthalmol. 2021 Apr 17;2021:6635467.

    Jae Hui Kim, Jong Woo Kim, Chul Gu Kim 

    PMID: 33953966 PMCID: PMC8068537 DOI: 10.1155/2021/6635467

    Background: To evaluate the proportion of eyes that do not meet the eligibility criteria of clinical trials on neovascular age-related macular degeneration (AMD) and the reasons for exclusion.

    Methods: This retrospective, observational study included 512 eyes of 463 patients diagnosed with treatment-naïve neovascular AMD. The proportion of eyes that did not meet the eligibility criteria of the Vascular Endothelial Growth Factor Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies were evaluated. The two most common reasons for exclusion were also evaluated in each subtype of neovascular AMD (typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), and type 3 neovascularization).

    Results: Among the 512 eyes, 229 (44.7%) did not meet the eligibility criteria. In all the included eyes, the most common reasons for exclusion were good or poor visual acuity (169 eyes, 33.0%), followed by the presence of subretinal hemorrhage (47 eyes, 9.5%). Moreover, good or poor visual acuity was the most common reason for exclusion in all three subtypes of neovascular AMD. The second most common reason was a fovea-involving scar or fibrosis in typical neovascular AMD, subretinal hemorrhage in PCV, and other vascular diseases affecting the retina in type 3 neovascularization.

    Conclusions: Among the included cases, 44.7% did not meet the eligibility criteria for VIEW study, suggesting that the conclusion derived from clinical trials may not directly reflect the real-world outcomes. Additionally, the reasons for ineligibility differed among the different subtypes of neovascular AMD.

    Long-term outcomes of intravitreal therapy for symptomatic diabetic macular oedema in a real-world setting in Switzerland

    Graefes Arch Clin Exp Ophthalmol. 2021 May 4.

    Johanna J Zirpel, Isabel B Pfister, Christin Gerhardt, Justus G Garweg

    PMID: 33942162 DOI: 10.1007/s00417-021-05187-z

    Objective: To assess the long-term visual outcomes in eyes with symptomatic diabetic macular oedema (DME) under intravitreal treatment (IVT) in a clinical routine setting.

    Methods: Patients with newly diagnosed DME were included in this retrospective study if they had received at least three IVTs and a follow-up period ≥ 2 years. Due to altered treatment patterns since the approval of ranibizumab for DME in 2012, patients were subdivided according to their first IVT before 2013 (group 1) or thereafter (group 2). The primary outcome measure was the evolution of best-corrected visual acuity (BCVA) over time.

    Results: Of 217 eyes (191 patients) with DME, 151 eyes (117 patients) fulfilled the inclusion criteria (63 eyes in the first period, 88 in the second period). Mean follow-up time was 7.9 ± 3.1 (group 1) and 4.1 ± 1.4 years (group 2; p < 0.001). Visual gains were similar in the first year (group 1: + 5.3 ± 15.5, group 2: + 7.3 ± 12.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters; p = 0.44), but not thereafter (after 2 years in group 1: + 4.4 ± 15.0, group 2: + 8.3 ± 13.0 ETDRS letters; p = 0.038). During the first year, group 1 patients received less clinical examinations (group 1: 6.6 ± 3.3, group 2: 7.5 ± 2.1; p = 0.007) and less injections (group 1: 3.6 ± 2.7, group 2: 6.1 ± 2.7; p < 0.001).

    Conclusion: A greater visual gain, in response to more intensive treatment during the first year, was maintained for at least 5 years in group 2 subjects. Our data confirm that in a real-world setting, early intensive treatment results in satisfying long-term visual outcomes.


    IL-9 and IL-10 Single-Nucleotide Variants and Serum Levels in Age-Related Macular Degeneration in the Caucasian Population

    Mediators Inflamm. 2021 Apr 12;2021:6622934.

    Alvita Vilkeviciute, Dzastina Cebatoriene, Loresa Kriauciuniene, Reda Zemaitiene, Rasa Liutkeviciene    

    PMID: 33953642 PMCID: PMC8057879 DOI: 10.1155/2021/6622934

    Considering the immunological impairment in age-related macular degeneration (AMD), we aimed to determine the associations of IL-9 rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884 and IL-10 rs1800871, rs1800872, and rs1800896 polymorphisms and their haplotypes, as well as the serum levels of IL-9 and IL-10 with AMD. 1209 participants were enrolled in our study. SNPs were genotyped using TaqMan SNP genotyping assays by real-time PCR method. IL-9 and IL-10 serum levels were evaluated using ELISA kits. Our study results have shown that haplotypes A-G-C-G-G and G-A-T-A-T of IL-9 SNPs are associated with the decreased odds of early AMD occurrence (p = 0.035 and p = 0.015, respectively). A set of rare haplotypes was associated with the decreased odds of exudative AMD occurrence (p = 0.033). Also, IL-10 serum levels were lower in exudative AMD than in controls (p = 0.049), patients with early AMD (p = 0.017), and atrophic AMD (p = 0.008). Furthermore, exudative AMD patients with IL-10 rs1800896 CT and TT genotypes had lower IL-10 serum concentrations than those with wild-type (CC) genotype (p = 0.048). In conclusion, our study suggests that IL-10 serum levels can be associated with a minor allele at IL-10 rs1800896 and exudative AMD. The haplotypes of IL-9 SNPs were also associated with the decreased odds of early and exudative AMD.

    Longitudinal phenotypic study of late-onset retinal degeneration due to a founder variant c.562C>A p.(Pro188Thr) in the C1QTNF5 gene

    Ophthalmic Genet. 2021 May 5;1-12.

    Julie De Zaeytijd, Frauke Coppieters, Marieke De Bruyne, Jasper Van Royen, Dimitri Roels, Rani Six, Caroline Van Cauwenbergh, Elfride De Baere, Bart P Leroy 

    PMID: 33949280 DOI: 10.1080/13816810.2021.1923041

    Background: Late-onset retinal degeneration (L-ORD) is a rare autosomal dominant retinal dystrophy related to C1QTNF5 gene variants.

    Materials and methods: Twenty-six patients (21-81 years) with L-ORD due to c.562C>A p.(Pro188Thr) with a mean follow-up time of 8 years (range 1-37 years) underwent an extensive ophthalmic work-up.

    Results: Best-corrected visual acuity (BCVA) and visual fields were maintained up to 50 to 55 years (n = 8), with a gradual decline, but conservation of functional central vision between 55 to 65 years (n = 15), followed by a steep decrease in overall visual function beyond 65 years (n = 9). Classic anterior segment findings in L-ORD of abnormally long, anteriorly inserted lens zonules were absent in most patients (n = 24/26). In contrast, findings of iris transillumination and sphincter pupillae atrophy with poor dilation were novel. Patients presented with three completely different initial fundus phenotypes: adjoining pavingstone-like atrophic patches (type 1) (n = 6/20); tiny yellow-white subretinal dots (type 2) (n = 8/20); or larger yellow, thick, round sub-RPE drusenoid deposits (type 3) (n = 4/20). Two patients had a mixed phenotype. Although different in presentation phenotype, patients eventually all progressed to a common panretinal atrophy with diffuse intraretinal pigment migration beyond the age of 65. Progression pace, and thus visual prognosis, differed depending on presentation phenotype. Specifically, type 2 appears to have a more benign course.

    Conclusions: Phenotypic analysis showed three distinct presenting phenotypes with a considerable intrafamilial variability both in age of onset of clinical signs and in disease progression, with a fair visual potential (>20/40) until the seventh decade.


    Diagnostic accuracy of current machine learning classifiers for age-related macular degeneration: a systematic review and meta-analysis

    Eye (Lond). 2021 May 6.

    Ronald Cheung, Jacob Chun, Tom Sheidow, Michael Motolko, Monali S Malvankar-Mehta

    PMID: 33958739 DOI: 10.1038/s41433-021-01540-y

    Background and objective: The objective of this study was to systematically review and meta-analyze the diagnostic accuracy of current machine learning classifiers for age-related macular degeneration (AMD). Artificial intelligence diagnostic algorithms can automatically detect and diagnose AMD through training data from large sets of fundus or OCT images. The use of AI algorithms is a powerful tool, and it is a method of obtaining a cost-effective, simple, and fast diagnosis of AMD.

    Methods: MEDLINE, EMBASE, CINAHL, and ProQuest Dissertations and Theses were searched systematically and thoroughly. Conferences held through Association for Research in Vision and Ophthalmology, American Academy of Ophthalmology, and Canadian Society of Ophthalmology were searched. Studies were screened using Covidence software and data on sensitivity, specificity and area under curve were extracted from the included studies. STATA 15.0 was used to conduct the meta-analysis.

    Results: Our search strategy identified 307 records from online databases and 174 records from gray literature. Total of 13 records, 64,798 subjects (and 612,429 images), were used for the quantitative analysis. The pooled estimate for sensitivity was 0.918 [95% CI: 0.678, 0.98] and specificity was 0.888 [95% CI: 0.578, 0.98] for AMD screening using machine learning classifiers. The relative odds of a positive screen test in AMD cases were 89.74 [95% CI: 3.05-2641.59] times more likely than a negative screen test in non-AMD cases. The positive likelihood ratio was 8.22 [95% CI: 1.52-44.48] and the negative likelihood ratio was 0.09 [95% CI: 0.02-0.52].

    Conclusion: The included studies show promising results for the diagnostic accuracy of the machine learning classifiers for AMD and its implementation in clinical settings.

    Focus on Survival Analysis for Eye Research

    Invest Ophthalmol Vis Sci. 2021 May 3;62(6):7.

    Myra B McGuinness, Jessica Kasza, Zhichao Wu, Robyn H Guymer

    PMID: 33950248 DOI: 10.1167/iovs.62.6.7

    Analysis of time-to-event data, otherwise known as survival analysis, is a common investigative tool in ophthalmic research. For example, time-to-event data is useful when researchers are interested in investigating how long it takes for an ocular condition to worsen or whether treatment can delay the development of a potentially vision-threatening complication. Its implementation requires a different set of statistical tools compared to those required for analyses of other continuous and categorial outcomes. In this installment of the Focus on Data series, we present an overview of selected concepts relating to analysis of time-to-event data in eye research. We introduce censoring, model selection, consideration of model assumptions, and best practice for reporting. We also consider challenges that commonly arise when analyzing time-to-event data in ophthalmic research, including collection of data from two eyes per person and the presence of multiple outcomes of interest. The concepts are illustrated using data from the Laser Intervention in Early Stages of Age-Related Macular Degeneration study and statistical computing code for Stata is provided to demonstrate the application of the statistical methods to illustrative data.

    Retinal Fluid and Thickness as Measures of Disease Activity in Neovascular Age-Related Macular Degeneration

    Retina. 2021 May 3.

    Peter K Kaiser, Charles C Wykoff, Rishi P Singh, Arshad M Khanani, Diana V Do, Hersh Patel, Nikhil Patel

    PMID: 33949342 DOI: 10.1097/IAE.0000000000003194

    Purpose: Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration (nAMD), as evidenced by clinical trials that have used these features for inclusion criteria, re-treatment criteria, and outcome measures of the efficacy of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents.

    Methods: A literature review of anatomical measures of disease activity was conducted.

    Results: Treatment goals for nAMD include improving/maintaining vision by drying the retina, and several analyses have evaluated the relationship between visual function and anatomy. Change in retinal thickness has been found to correlate with change in visual acuity, and variation in retinal thickness may predict visual acuity outcomes. In addition, specific fluid compartments may have different prognostic values. For example, the presence of intraretinal fluid has been associated with poorer visual acuity while the presence of subretinal fluid has been associated with better visual acuity. Retinal fluid and thickness are important for selecting dosing interval durations in clinical trials and clinical practice.

    Conclusions: Retinal thickness and retinal fluid are common anatomical measures of disease activity in nAMD. Further research is required to fully elucidate the relationship between anatomical features and visual outcomes in nAMD.