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    Research Update 585


    Save our Sight (SOS): a collective call-to-action for enhanced retinal care across health systems in high income countries.

    Eye (London, England). 2023 Jun 6.

    Loewenstein A, Berger A, Daly A, Creuzot-Garcher C, Gale R, Ricci F, Zarranz-Ventura J, Guymer R.

    With a growing aging population, the prevalence of age-related eye disease and associated eye care is expected to increase. The anticipated growth in demand, coupled with recent medical advances that have transformed eye care for people living with retinal diseases, particularly neovascular age-related macular degeneration (nAMD) and diabetic eye disease, has presented an opportunity for health systems to proactively manage the expected burden of these diseases. To do so, we must take collective action to address existing and anticipated capacity limitations by designing and implementing sustainable strategies that enable health systems to provide an optimal standard of care. Sufficient capacity will enable us to streamline and personalize the patient experience, reduce treatment burden, enable more equitable access to care and ensure optimal health outcomes. Through a multi-modal approach that gathered unbiased perspectives from clinical experts and patient advocates from eight high-income countries, substantiated perspectives with evidence from the published literature and validated findings with the broader eye care community, we have exposed capacity challenges that are motivating the community to take action and advocate for change. Herein, we propose a collective call-to-action for the future management of retinal diseases and potential strategies to achieve better health outcomes for individuals at-risk of, or living with, retinal disease.

    DOI: 10.1038/s41433-023-02540-w


    Efficacy, durability, and safety of faricimab in patients from Asian countries with neovascular age-related macular degeneration: 1-Year subgroup analysis of the TENAYA and LUCERNE trials.

    Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 2023 Jun 9

    Takahashi K, Cheung CMG, Iida T, Lai TYY, Ohji M, Yanagi Y, Kawano M, Ohsawa S, Suzuki T, Kotecha A, Lin H, Patel V, Swaminathan B, Lee WK; TENAYA, LUCERNE Investigators.

    Purpose: To evaluate 1-year efficacy, durability, and safety of faricimab among patients from Asian countries in the TENAYA/LUCERNE trials of neovascular age-related macular degeneration (nAMD).

    Methods: Treatment-naïve patients with nAMD were randomly assigned (1:1) to faricimab 6.0 mg up to every 16 weeks (Q16W), based on disease activity at weeks 20 and 24, or aflibercept 2.0 mg Q8W. The primary endpoint was change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48.

    Results: In the pooled TENAYA/LUCERNE trials, there were 120 (9.0%) and 1209 (91.0%) patients in the Asian (faricimab n = 61; aflibercept n = 59) and non-Asian country (faricimab n = 604; aflibercept n = 605) subgroups, respectively. In the Asian country subgroup, mean BCVA change from baseline at the primary endpoint visits was 7.1 (95% CI, 4.3-9.8) letters with faricimab and 7.2 (4.4-10.0) letters with aflibercept. In non-Asian country patients, mean vision gains were 6.1 (5.2-7.1) and 5.7 (4.8-6.7) letters with faricimab and aflibercept, respectively. At week 48, 59.6% of Asian country patients in the faricimab group achieved Q16W dosing (vs. 43.9% non-Asian) and 91.2% achieved ≥ Q12W dosing (vs. 77.5% non-Asian). Central subfield thickness reductions were similar between the subgroups, with meaningful and similar reductions from baseline observed at the primary endpoint visits and over time. Faricimab was well tolerated in both subgroups, with an acceptable safety profile.

    Conclusion: Consistent with the global TENAYA/LUCERNE findings, faricimab up to Q16W showed sustained visual and anatomical benefits in patients with nAMD from Asian and non-Asian countries.

    DOI: 10.1007/s00417-023-06071-8


    Foveal Eversion is Associated with High Persistence of Macular Edema and Visual Acuity Deterioration in Retinal Vein Occlusion.

    Ophthalmology and therapy. 2023 Jun 9.

    Arrigo A, Aragona E, Antropoli A, Bianco L, Rosolia A, Saladino A, Bandello F, Battaglia Parodi M.

    Introduction: Foveal eversion (FE) is a recently described optical coherence tomography (OCT) finding associated with negative outcome in diabetic macular edema. The main goal of the present study was to investigate the role of the FE metric in the diagnostic workup of retinal vein occlusion (RVO).

    Methods: This study was a retrospective, observational case series. We included 168 eyes (168 patients) affected by central RVO (CRVO) and 116 eyes (116 patients) affected by branch (RVO). We collected clinical and imaging data from CRVO and BRVO eyes affected by macular edema with a minimum follow-up of 12 months. On structural OCT, we classified FE as pattern 1a, characterized by thick vertical intraretinal columns, pattern 1b, presenting thin vertical intraretinal lines, and pattern 2, showing no signs of vertical lines in the context of the cystoid macular edema. For statistical purposes, we considered data collected at baseline, after 1 year and at the last follow-up.

    Results: The mean follow-up was 40 ± 25 months for CRVO eyes and 36 ± 24 months for BRVO eyes. We found FE in 64 of 168 CRVO eyes (38%) and in 25 of 116 BRVO eyes (22%). Most of the eyes developed FE during the follow-up. For CRVO eyes, we found 6 eyes (9%) with pattern 1a, 17 eyes (26%) with pattern 1b and 41 eyes (65%) with pattern 2. Of those BRVO eyes with FE, we found 8 eyes (32%) with pattern 1a + 1b and 17 eyes (68%) with pattern 2. In both CRVO and BRVO the presence of FE was significantly associated with higher persistence of macular edema and worse outcome, with FE pattern 2 representing the most severe condition. Remarkably, FE patterns 1a and 1b were characterized by BCVA stability over the follow-up, whereas FE pattern 2 showed significant bestcorrected visual acuity (BCVA) worsening at the end of the follow-up.

    Conclusions: FE can be considered a negative prognostic biomarker in RVO, associated with higher persistence of macular edema and worse visual outcome. Müller cell impairment might represent the pathogenic mechanism leading to the loss of macular structural support and impairment of fluid homeostasis.

    DOI: 10.1007/s40123-023-00734-9


    Progression of Geographic Atrophy: Retrospective Analysis of Patients from the IRIS® Registry (Intelligent Research in Sight).

    Ophthalmology science. 2023 Apr 19;

    Rahimy E, Khan MA, Ho AC, Hatfield M, Nguyen TH, Jones D, McKeown A, Borkar D, Leng T, Ribeiro R, Holekamp N.

    Purpose: To evaluate disease progression and associated vision changes in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) in 1 eye and GA or neovascular AMD (nAMD) in the fellow eye using a large dataset from routine clinical practice.

    Design: Retrospective analysis of clinical data over 24 months. SUBJECTS: A total of 256 635 patients with GA from the American Academy of Ophthalmology (Academy) IRIS® Registry (Intelligent Research in Sight) Registry (January 2016 to December 2017).

    Methods: Patients with ≥ 24 months of follow-up were grouped by fellow-eye status: Cohort 1, GA:GA; Cohort 2, GA:nAMD, each with (subfoveal) and without subfoveal (nonsubfoveal) involvement. Eyes with history of retinal disease other than AMD were excluded. Sensitivity analysis included patients who were managed by retina specialists and had a record of imaging within 30 days of diagnosis.

    Main Outcome Measures: Change in visual acuity (VA), occurrence of new-onset nAMD, and GA progression from nonsubfoveal to subfoveal.

    Results: In total, 69 441 patients were included: 44 120 (64%) GA:GA and 25 321 (36%) GA:nAMD. Otherwise eligible patients (57 788) were excluded due to follow-up < 24 months. In both GA:GA and GA:nAMD cohorts, nonsubfoveal study eyes had better mean (standard deviation) VA at index (67 [19.3] and 66 [20.3] letters) than subfoveal eyes (59 [23.9] and 47 [26.9] letters), and 24-month mean VA changes were similar for nonsubfoveal (-7.6 and -6.2) and subfoveal (-7.9 and -6.5) subgroups. Progression to subfoveal GA occurred in 16.7% of nonsubfoveal study eyes in the GA:GA cohort and 12.5% in the GA:nAMD cohort. More new-onset study-eye nAMD was observed in the GA:nAMD (21.6%) versus GA:GA (8.2%) cohorts. Sensitivity analysis supported the robustness of the observations in the study.

    Conclusions: This retrospective analysis describes the natural progression of GA lesions and the decline in VA associated with the disease.

    DOI: 10.1016/j.xops.2023.100318

    Reticular Pseudodrusen: Inter-reader Agreement of Evaluation on OCT Imaging in Age-Related Macular Degeneration.

    Ophthalmology science. 2023 May 5;

    Wu Z, Schmitz-Valckenberg S, Blodi BA, Holz FG, Jaffe GJ, Liakopoulos S, Sadda SR, Bonse M, Brown T, Choong J, Clifton B, Corradetti G, Corvi F, Dieu AC, Dooling V, Pak JW, Saßmannshausen M, Skalak C, Thiele S, Guymer RH.

    Purpose: To determine the interreader agreement for reticular pseudodrusen (RPD) assessment on combined infrared reflectance (IR) and OCT imaging in the early stages of age-related macular degeneration across a range of different criteria to define their presence.

    Design: Interreader agreement study. PARTICIPANTS: Twelve readers from 6 reading centers.

    Methods: All readers evaluated 100 eyes from individuals with bilateral large drusen for the following: (1) the presence of RPD across a range of different criteria and (2) the number of Stage 2 or 3 RPD lesions (from 0 to ≥ 5 lesions) on an entire OCT volume scan and on a selected OCT B-scan. Supportive information was available from the corresponding IR image.

    Main Outcome Measures: Interreader agreement, as assessed by Gwet’s first-order agreement coefficient (AC1).

    Results: When evaluating an entire OCT volume scan, there was substantial interreader agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions, and ≥ 5 definite lesions on en face IR images corresponding to Stage 2 or 3 lesions (AC1 = 0.60-0.72). On selected OCT B-scans, there was also moderate-to-substantial agreement for the presence of any RPD, any or ≥ 5 Stage 2 or 3 lesions (AC1 = 0.58-0.65) and increasing levels of agreement with increasing RPD stage (AC1 = 0.08, 0.56, 0.78, and 0.99 for the presence of any Stage 1, 2, 3, and 4 lesions, respectively). There was substantial agreement regarding the number of Stage 2 or 3 lesions on an entire OCT volume scan (AC1 = 0.68), but only fair agreement for this evaluation on selected B-scans (AC1 = 0.30).

    Conclusions: There was generally substantial or near-substantial-but not near-perfect-agreement for assessing the presence of RPD on entire OCT volume scans or selected B-scans across a range of differing RPD criteria. These findings underscore how interreader variability would likely contribute to the variability of findings related to the clinical associations of RPD. The low levels of agreement for assessing RPD number on OCT B-scans underscore the likely challenges of quantifying RPD extent with manual grading. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references.

    DOI: 10.1016/j.xops.2023.100325

    Hyperreflective material in patients with non-neovascular pachychoroid disease.

    BMC Ophthalmology. 2023 Jun 6;

    Maruyama-Inoue M, Yanagi Y(, Mohamed S, Inoue T, Kitajima Y, Ikeda S, Kadonosono K.

    Background: This study aimed to report eleven cases of non-neovascular pachychoroid disease with hyperreflective material (HRM) that occurred in Japanese patients.

    Methods: A retrospective review of data from eleven patients who had non-neovascular retinal pigment epithelium (RPE) protrusion with HRM in the neurosensory retina between March 2017 and June 2022 was conducted. Clinical examination, color fundus photography, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and OCT angiography data were analyzed. Main outcome measures were patient characteristics, changes in SD-OCT findings, and symptom outcomes.

    Results: All cases had RPE protrusion and HRM with dilated choroidal veins, which were characteristic of pachychoroid disease. However, none of the cases had macular neovascularization (MNV). In 9 eyes (81.8%), HRM improved spontaneously without intervention and resulted in alterations in RPE, referred to as pachychoroid pigment epitheliopathy (PPE) or focal choroidal excavation (FCE). In these cases, symptoms such as metamorphopsia and distortion improved without treatment. In the remaining two cases (18.2%), HRM still persisted during the follow-up period.

    Conclusion: There are some cases of non-neovascular pachychoroid disorder with HRM, which might be a new entity of pachychoroid spectrum disease or an early stage of PPE or FCE. These cases should not be misdiagnosed as MNV, and careful observation is necessary.

    DOI: 10.1186/s12886-023-03011-2

    Association of OCT and OCT angiography measures with the development and worsening of diabetic retinopathy in type 2 diabetes.

    Eye (London, England). 2023 Jun 6. doi:

    Srinivasan S, Sivaprasad S, Rajalakshmi R, Anjana RM, Malik RA, Kulothungan V, Raman R, Bhende M.

    Objective: To assess if optical coherence tomography (OCT) and OCT angiography (OCTA) measures are associated with the development and worsening of diabetic retinopathy (DR) over four years.

    Methods: 280 participants with type 2 diabetes underwent ultra-wide field fundus photography, OCT and OCTA. OCT-derived macular thickness measures, retinal nerve fibre layer and ganglion cell-inner plexiform layer thickness and OCTA-derived foveal avascular zone area, perimeter, circularity, vessel density (VD) and macular perfusion (MP) were examined in relation to the development and worsening of DR over four years.

    Results: After four years, 206 eyes of 219 participants were eligible for analysis. 27 of the 161 eyes (16.7%) with no DR at baseline developed new DR, which was associated with a higher baseline HbA1c and longer diabetes duration. Of the 45 eyes with non-proliferative DR (NPDR) at baseline, 17 (37.7%) showed DR progression. Baseline VD (12.90 vs. 14.90 mm/mm2, p = 0.032) and MP (31.79% vs. 36.96%, p = 0.043) were significantly lower in progressors compared to non-progressors. Progression of DR was inversely related to VD ((hazard ratio [HR] = 0.825) and to MP (HR = 0.936). The area under the receiver operating characteristic curves for VD was AUC = 0.643, with 77.4% sensitivity and 41.8% specificity for a cut-off of 15.85 mm/mm2 and for MP it was AUC = 0.635, with 77.4% sensitivity and 25.5% specificity for a cut-off of 40.8%.

    Conclusions: OCTA metrics have utility in predicting progression rather than the development of DR in individuals with type 2 diabetes

    DOI: 10.1038/s41433-023-02605-w


    The macular retinal ganglion cell layer as a biomarker for diagnosis and prognosis in multiple sclerosis: A deep learning approach.

    Acta Ophthalmologica. 2023 Jun 10.

    Montolío A, Cegoñino J, Garcia-Martin E, Pérez Del Palomar A.

    Purpose: The macular ganglion cell layer (mGCL) is a strong potential biomarker of axonal degeneration in multiple sclerosis (MS). For this reason, this study aims to develop a computer-aided method to facilitate diagnosis and prognosis in MS.

    Methods: This paper combines a cross-sectional study of 72 MS patients and 30 healthy control subjects for diagnosis and a 10-year longitudinal study of the same MS patients for the prediction of disability progression, during which the mGCL was measured using optical coherence tomography (OCT). Deep neural networks were used as an automatic classifier.

    Results: For MS diagnosis, greatest accuracy (90.3%) was achieved using 17 features as inputs. The neural network architecture comprised the input layer, two hidden layers and the output layer with softmax activation. For the prediction of disability progression 8 years later, accuracy of 81.9% was achieved with a neural network comprising two hidden layers and 400 epochs.

    Conclusion: We present evidence that by applying deep learning techniques to clinical and mGCL thickness data it is possible to identify MS and predict the course of the disease. This approach potentially constitutes a non-invasive, low-cost, easy-to-implement and effective method.

    DOI: 10.1111/aos.15722


    Tyrosine Kinase Inhibitors and their role in treating neovascular age-related macular degeneration and diabetic macular oedema.

    Eye (London, England). 2023 Jun 7.

    Chandra S, Tan EY, Empeslidis T, Sivaprasad S.

    The advent of intravitreal anti-VEGF injections has revolutionised the treatment of both neovascular age-related macular degeneration (nAMD or wet AMD) and diabetic macular oedema (DMO). Despite their efficacy, anti-VEGF injections precipitate significant treatment burden for patients, caregivers and healthcare systems due to the high frequency of injections required to sustain treatment benefit. Therefore, there remains an unmet need for lower-burden therapies. Tyrosine kinase inhibitors (TKI) are a novel class of drugs that may have considerable potential in addressing this issue. This review will summarise and discuss the results of various pilot studies and clinical trials exploring the role of TKIs in treatment of nAMD and DMO, highlighting promising candidates and possible challenges in developments.

    DOI: 10.1038/s41433-023-02610-z