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    Research Update 566


    Investigation of Incidence and Causes of Acute Vision Loss During Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration During a 4-Year Follow-Up.

    Retina (Philadelphia, Pa.) 2023 Jan 18.

    Machida A, Oishi A, Tsuiki E, Maekawa Y, Kurihara J, Hirata Y, Machida E, Kitaoka T.

    Purpose: To investigate the incidence, risk factors, and outcomes of patients with age-related macular degeneration (AMD) who experienced acute vision loss despite periodic injections of anti-vascular endothelial growth factor (VEGF) treatment for 4 years.

    Methods: This retrospective cohort study included patients who were diagnosed with treatment-naïve neovascular AMD and completed a 4-year follow-up. The incidence and risk factors for the occurrence of three or more lines of visual loss at every check-up were investigated.

    Results: The analysis included 76 eyes of 76 patients. Acute vision loss occurred in 30 eyes (39.5%) over 4 years. Lower baseline best collected visual acuity (BCVA) and disrupted ellipsoid zone were independent predictors of vision loss occurrence. Although the causes and timing of visual acuity loss varied, retinal pigment epithelium tears were observed only in the first year. Most (86.7%) patients who experienced vision loss recovered their vision to pre-loss levels at least once; however, the final BCVA was worse than that in the group that did not experience acute vision loss.

    Conclusion: Approximately half of the patients with AMD experienced acute vision loss during a 4-year, despite continuous anti-VEGF treatment. Most patients recovered from vision losses temporarily; however, they experienced worse visual outcomes subsequently.

    DOI: 10.1097/IAE.0000000000003740


    Evaluation of Standard-Of-Care Intravitreal Aflibercept Treatment Practices in Patients with Diabetic Macular Oedema in the Uk: DRAKO Study Outcomes.

    Eye (London, England). 2023 Jan 18.

    Sivaprasad S, Ghanchi F, Kelly SP, Kotagiri A, Talks J, Scanlon P, McGoey H, Nolan A, Saddiq M, Napier J, Morgan-Warren P.

    Background/Objectives: DRAKO (NCT02850263) was a 24-month, prospective, non-interventional, multi-centre cohort study enrolling patients with diabetic macular oedema (DMO) including central involvement. The study evaluated UK standard-of-care intravitreal aflibercept (IVT-AFL) treatment. This analysis describes the treatment pathway and service provision for the anti-vascular endothelial growth factor (VEGF) treatment-naïve (C1) and non-naïve patients (C2) who received prior anti-VEGF treatment for DMO other than IVT-AFL.

    Methods: Mean changes in best-corrected visual acuity and central subfield thickness were measured and stratified by baseline factors, including ethnicity and administration of five initial monthly injections within predefined windows. Clinic visits were classified as treatment only (T1), monitoring assessment only (T2), combined visits (T3) or post-injection visits with no treatment or assessment (T4).

    Results: Median time from decision to treat to treatment was 6 days. As a percentage of total visits, T1, T2, T3 and T4 were 7%, 42%, 48% and 3% for C1 and 11%, 39%, 48% and 2% for C2. Most IVT-AFL injections were administered by healthcare professionals (HCPs) other than doctors (C1, 57.4%; C2, 58.5%). The percentage of treatments associated with a procedure-related adverse event where at least 75% of injections were completed by the same injector role were similar for doctors and other HCPs (C1, 1.1% and 0.8%; C2, 0.7%, and 1.0%).

    Conclusions: Results indicate that upon DMO diagnosis, patients were treated promptly, and most visits were combined (treatment and assessment) or monitoring only. Most IVT-AFL was administered by non-physicians with a similar treatment-related safety profile as IVT-AFL administered by physicians.

    DOI: 10.1038/s41433-022-02367-x

    Effect Of Age on Response to Anti-VEGF Agents in Patients with Center Involving Diabetic Macular Edema in a Tertiary Hospital.

    International Journal of Retina and Vitreous. 2022 Dec 13.

    Alshalan HA, Arevalo JF, Alomary SI, Ardah HI, Hazzazi MA

    Purpose: The aim of the current study is to evaluate the effect of age as an independent factor for the response to two anti-VEGF agents, intravitreal ranibizumab and intravitreal aflibercept, among patients presented with central-involving DME in one tertiary care center in Riyadh, Saudi Arabia.

    Methods: Retrospective cohort study.

    Results: A total of 210 eyes of 121 patients were included in the study. The mean age was 61.2 ± 11.40 years, 50.4% were males. On characterizing groups based on age, the group of patients 60 years or younger are 48 patients (mean age 51.5 ± 9.92) and 52.1% of them are females. On the other hand, the group of patients older than 60 years are 73 patients (mean age 67.6 ± 6.85) and 52.1% of them are males. The two anti-VEGF agents used were aflibercept (88.1%) and ranibizumab (11.9%). The mean BCVA using ETDRS letter score improved after treatment (5.55238095 ± 15.9538695) and the mean change in CST decreased after treatment (- 106.91 ± 117.385 μm). Regarding age, we found that there is no significant difference in mean improvement of BCVA in patients according to their age (p = 0.5429), patients younger than 60 years old gained 5.64 ETDRS letter score and those older than 60 years old gained 5.49 improvement. Similarly, mean improvement in CST was different between patients younger than 60 years old (- 125.1 μm) and those who were older than 60 years old (- 94 μm) with a trend favoring younger patients but this difference was not statistically significant (p = 0.08).

    Conclusion: Age is a clinically significant factor affecting the outcome of anti-VEGF injections. Patients’ CST had a difference of > 30 μm on average between the two age groups favoring younger patients. However, it was not statistically significant, maybe a bigger sample size is needed to prove statistical significance.

    DOI: 10.1186/s40942-022-00434-9


    Incidence and Progression of Chorioretinal Folds During Long-Duration Spaceflight.

    JAMA Ophthalmology. 2023 Jan 5.

    Ferguson CR, Pardon LP, Laurie SS, Young MH, Gibson CR, Brunstetter TJ, Tarver WJ, Mason SS, Sibony PA, Macias BR.

    Importance: The primary contributing factor for development of chorioretinal folds during spaceflight is unknown. Characterizing fold types that develop and tracking their progression may provide insight into the pathophysiology of spaceflight-associated neuro-ocular syndrome and elucidate the risk of fold progression for future exploration-class missions exceeding 12 months in duration.

    Objective: To determine the incidence and presentation of chorioretinal folds in long-duration International Space Station crew members and objectively quantify the progression of choroidal folds during spaceflight.

    Design, Setting, And Participants: In this retrospective cohort study, optical coherence tomography scans of the optic nerve head and macula of crew members completing long-duration spaceflight missions were obtained on Earth prior to spaceflight and during flight. A panel of experts examined the scans for the qualitative presence of chorioretinal folds. Peripapillary total retinal thickness was calculated to identify eyes with optic disc edema, and choroidal folds were quantified based on surface roughness within macular and peripapillary regions of interest.

    Interventions Or Exposures: Spaceflight missions ranging 6 to 12 months.

    Main Outcomes And Measures: Incidence of peripapillary wrinkles, retinal folds, and choroidal folds; peripapillary total retinal thickness; and Bruch membrane surface roughness. RESULTS: A total of 36 crew members were analyzed (mean [SD] age, 46 [6] years; 7 [19%] female). Chorioretinal folds were observed in 12 of 72 eyes (17%; 6 crew members). In eyes with early signs of disc edema, 10 of 42 (24%) had choroidal folds, 4 of 42 (10%) had inner retinal folds, and 2 of 42 (5%) had peripapillary wrinkles. Choroidal folds were observed in all eyes with retinal folds and peripapillary wrinkles. Macular choroidal folds developed in 7 of 12 eyes (4 of 6 crew members) with folds and progressed with mission duration; these folds extended into the fovea in 6 eyes. Circumpapillary choroidal folds developed predominantly superior, nasal, and inferior to the optic nerve head and increased in prevalence and severity with mission duration.

    Conclusions And Relevance: Choroidal folds were the most common fold type to develop during spaceflight; this differs from reports in idiopathic intracranial hypertension, suggesting differences in the mechanisms underlying fold formation. Quantitative measures demonstrate the development and progression of choroidal folds during weightlessness, and these metrics may help to assess the efficacy of spaceflight-associated neuro-ocular syndrome countermeasures.

    DOI: 10.1001/jamaophthalmol.2022.5681


    Two Potentially Distinct Pathways to Geographic Atrophy in Age-Related Macular Degeneration Characterized by Quantitative Fundus Autofluorescence.

    Eye (London, England). 2023 Jan 9.

    Wei W, Mazzola M, Otero-Marquez O, Tong Y, Souied E, Querques G, Bailey Freund K, Theodore Smith R.

    Background/Aims: To demonstrate two distinct pathways to geographic atrophy (GA) that originate from soft drusen/ pigment epithelial detachments (PEDs) and subretinal drusenoid deposits (SDDs), respectively, and are characterized by their final quantitative autofluorescence (qAF) levels.

    Methods: 23 eyes of 18 patients with GA underwent spectral-domain optical coherence tomography (SD-OCT) and qAF imaging on the qAF-ready Heidelberg Spectralis. 52 GA Regions-of-interest (ROIs), or clusters of adjacent lesions, were selected, and the ROIs were divided into groups by the dominant iAMD precursors on prior serial tracked SD-OCT scans. Mean qAF values and structural SD-OCT findings of groups were compared.

    Results: Group 1 lesions (soft drusen/PED precursors, 18/52) were isolated, with lower mean qAF (35.88 ± 12.75 units); group 3 lesions (SDD precursors, 12/52) were multilobular, with significantly higher mean qAF (71.62 ± 12.12 units, p < 0.05). Group 2 lesions, (mixed precursors, 22/52) had intermediate mean qAF (58.13 ± 67.92 units). Significantly greater prevalence of split RPE/ Bruch’s membrane complex in SDD-associated GA, suggesting basal laminar deposit (BLamD), than in drusen-associated lesions was the major structural difference.

    Conclusion: Quantitative autofluorescence (qAF) of GA lesions may reflect two distinct pathogenic pathways and structural outcomes, originating from soft drusen/PED and subretinal drusenoid deposits (SDDs), with the final qAF values lower or higher, respectively. Basal laminar deposit specifically in and adjacent to SDD-associated lesions may account for their greater autofluorescence. The potential importance of this paradigm is that it could direct, simplify and facilitate research on geographic atrophy by dividing the disease into two components that may be studied separately.

    DOI: 10.1038/s41433-022-02332-8


    Increased End-Stage Renal Disease Risk in Age-Related Macular Degeneration: A Nationwide Cohort Study With 10-Year Follow-Up.

    Scientific Reports. 2023 Jan 5.

    Jung W, Park J, Jang HR, Jeon J, Han K, Kim B, Yoon JM, Lim DH, Shin DW.

    Common etiologies between age-related macular degeneration (AMD) and kidney disease advocate a close link between AMD and end-stage renal disease (ESRD). However, the risk of ESRD in people with AMD was not reported. Here, we investigated the association between AMD and the risk of ESRD by using a nationwide, population-based cohort data in Korea. 4,206,862 participants aged 50 years or older were categorized by presence of AMD and visual disability. Risk of ESRD was the primary outcome. Cox regression hazard model was used to examine the hazard ratios (HRs) with adjustment for potential confounders. Stratified analyses by age, sex, baseline kidney function, and cardiometabolic comorbidities were performed. During the mean 9.95 years of follow-up, there were 21,759 incident ESRD events (0.52%). AMD was associated with 33% increased risk of ESRD (adjusted HR [aHR] 1.33, 95% confidence interval [CI] 1.24-1.44), and the risk was even higher when accompanied by visual disability (aHR 2.05, 95% CI 1.68-2.50) than when not (aHR 1.26, 95% CI 1.17-1.37). Age, baseline kidney function, and cardiometabolic comorbidities significantly interact between AMD and the risk of ESRD. Our findings have clinical implications on disease prevention and risk factor management of ESRD in patients with AMD.

    DOI: 10.1038/s41598-022-26964-8


    The Effect on Patients’ Visual Acuity and Grade, Secondary to Non-Attendance at Treatment Centers, Post Referral from Diabetic RetinaScreen Ireland.

    Clinical Ophthalmology (Auckland, N.Z.). 2023 Jan 11;

    Harmon J, Kelly S, Acheson R, Keegan D, McMahon S, Kavanagh H, O’Toole L.

    Background: Patient non-attendance following referral to hospital is a significant challenge, in particular, for persons with diabetes.

    Aim: We sought to determine the impact on both visual acuity and the subsequent follow-up retinopathy grade of patients when they fail to attend Diabetic Retinopathy Treatment (DRT) Centers following referral from Diabetic RetinaScreen (DRS).

    Methods: A retrospective analysis of patients discharged from DRT due to multiple consecutive missed appointments between January 2016 and June 2021. Patients discharged for non-attendance were compared with patients discharged from completed treatment.

    Results: Of the 24,945 NEC patients referred to DRT, 5900 (24%) and 9345 (37%) were discharged back to DRS due to non-attendance and completed treatment, respectively. Those discharged for non-attendance were younger (60.7 v 63.4, p < 0.001) and had higher proportions of males (67% v 63%, p < 0.001) and people with type 1 diabetes (27% v 18%, p < 0.001). After attending rescreening after discharge, those discharged for non-attendance were significantly more likely to have a worsening of DR grade (26% v 8%, p < 0.001).

    Conclusion: Despite being notified that further investigation (with possible treatment) was required post DRS, many diabetic patients failed to attend for further management of their eye care in DRT. These patients had worse visual outcomes compared to those that attended. Improved patient education and communication are required to mitigate against the consequences of non-attendance.

    DOI: 10.2147/OPTH.S388988


    Association Between Fatty Acid Intakes and Age-Related Macular Degeneration in a Japanese Population: JPHC-NEXT Eye Study.

    Translational Vision Science & Technology. 2023 Jan 3

    Yasukawa T, Sasaki M, Motomura K, Yuki K, Kurihara T, Tomita Y, Mori K, Ozawa N, Ozawa Y, Yamagishi K, Hanyuda A, Sawada N, Tsubota K, Tsugane S, Iso H.

    Purpose: To determine the associations between fatty acid intakes and the prevalence of age-related macular degeneration (AMD) under a population-based cross-sectional study.

    Methods: Residents of Chikusei City aged ≥40 years underwent systemic and eye screening. AMD was graded according to a modified version of the Age-Related Eye Disease Study classification. Dietary intake was assessed using a food frequency questionnaire and was adjusted for total energy intake.

    Results: Altogether, 10,788 eyes of 5394 participants, 2116 men (mean [standard deviation (SD)] age, 62.4 [9.4] years) and 3278 women (60.6 [9.5] years), were included. The mean daily total fat intakes were 52.8 g and 59.0 g in men and women, respectively. After adjustments for potential confounders, saturated fatty acid (SFA) intake was inversely associated with the prevalence of any AMD in men (for each energy-adjusted 1-SD increase: odds ratio [OR], 0.86; 95% confidence interval [CI], 0.74-1.00). Significant trends were found for decreasing odds ratios of AMD with increasing SFA, monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) intake (P for trend = 0.02, 0.04, and 0.04, respectively). In women, only a significant association was observed between the second quartile of linolenic acid intake and the prevalence of any AMD (OR, 0.78; 95% CI, 0.62-0.99).

    Conclusions: We found an inverse association of SFA intake and a weak inverse association of MUFA and PUFA intakes with the prevalence of any AMD in a Japanese population.

    Translational Relevance: Adequate fatty acid intake may be necessary to prevent or decelerate AMD.

    DOI: 10.1167/tvst.12.1.3


    Optical Coherence Tomography Imaging Biomarkers Associated with Neovascular Age-Related Macular Degeneration: A Systematic Review.

    Eye (London, England). 2022 Dec 16.

    Hanson RLW, Airody A, Sivaprasad S, Gale RP.

    The aim of this systematic literature review is twofold, (1) detail the impact of retinal biomarkers identifiable via optical coherence tomography (OCT) on disease progression and response to treatment in neovascular age-related macular degeneration (nAMD) and (2) establish which biomarkers are currently identifiable by artificial intelligence (AI) models and the utilisation of this technology. Following the PRISMA guidelines, PubMed was searched for peer-reviewed publications dated between January 2016 and January 2022.

    Population: Patients diagnosed with nAMD with OCT imaging.

    Settings: Comparable settings to NHS hospitals.

    Study Designs: Randomised controlled trials, prospective/retrospective cohort studies and review articles. From 228 articles, 130 were full-text reviewed, 50 were removed for falling outside the scope of this review with 10 added from the author’s inventory, resulting in the inclusion of 90 articles. From 9 biomarkers identified; intraretinal fluid (IRF), subretinal fluid, pigment epithelial detachment, subretinal hyperreflective material (SHRM), retinal pigmental epithelial (RPE) atrophy, drusen, outer retinal tabulation (ORT), hyperreflective foci (HF) and retinal thickness, 5 are considered pertinent to nAMD disease progression; IRF, SHRM, drusen, ORT and HF. A number of these biomarkers can be classified using current AI models. Significant retinal biomarkers pertinent to disease activity and progression in nAMD are identifiable via OCT; IRF being the most important in terms of the significant impact on visual outcome. Incorporating AI into ophthalmology practice is a promising advancement towards automated and reproducible analyses of OCT data with the ability to diagnose disease and predict future disease conversion.

    DOI: 10.1038/s41433-022-02360-4