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    Research Update 589


    Integrating Macular Optical Coherence Tomography with Ultrawide Field Imaging in a Diabetic Retinopathy Telemedicine Program Using a Single Device.

    Retina (Philadelphia, Pa.) 2023 Jul 4.

    Aiello LP, Jacoba CMP, Ashraf M, Cavallerano JD, Tolson AM, Tolls D, Sun JK, Silva PS.

    Purpose: To determine the effect of combined macular optical coherence tomography (SD-OCT) and ultrawide field retinal imaging (UWFI) within a telemedicine program.

    Methods: Comparative cohort study of consecutive patients with both UWFI and SD-OCT. UWFI and SD-OOCT were independently evaluated for diabetic macular edema (DME) and non-diabetic macular pathology. Sensitivity and specificity were calculated with SD-OCT as gold standard.

    Results: 422 eyes from 211 diabetic patients were evaluated. DME severity by UWFI: no DME 93.4%, non-center involved DME (nonciDME) 5.1%, ciDME 0.7%, ungradable DME 0.7%. SD-OCT was ungradable in 0.5%. Macular pathology was identified in 34 (8.1%) eyes by UWFI and in 44 (10.4%) eyes by SD-OCT. DME represented only 38.6% of referable macular pathology identified by SD-OCT imaging. Sensitivity/specificity of UWFI compared to SD-OCT was 59%/96% for DME and 33%/99% for ciDME. Sensitivity/specificity of UWFI compared to SDOCT was 3%/98% for ERM.

    Conclusions: Addition of SD-OCT increased the identification of macular pathology by 29.4%. Over 58.3% of the eyes thought to have any DME on UWF imaging alone were false positives by SD-OCT. The integration of SD-OCT with UWFI markedly increased detection and reduced false positive assessments of DME and macular pathology in a teleophthalmology program.

    DOI: 10.1097/IAE.0000000000003883


    Efficacy, Durability and Safety of Faricimab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Oedema: Lessons Learned from Registration Trials.

    Ophthalmology & therapy. 2023 Jul 6.

    Larsen HO, Grauslund J, Vergmann AS.

    Introduction: This review aims to assess the efficacy, durability and safety of faricimab-a dual vascular endothelial growth factor and angiopoietin 2 inhibitor-in patients with neovascular age-related macular degeneration (nAMD) and diabetic macula oedema (DMO). It summarises the findings of current studies on faricimab and discusses whether this new drug may fill a gap in current treatment options.

    Methods: We performed a search of the PubMed, Cochrane, Web of Science and EMBASE databases for publications on faricimab between 29 November 2022 and 10 May 2023, and a search of for the protocols on clinical trials for this review. We included clinical trials, case-control studies and observational studies.

    Results: In phase 3 trials of nAMD, the efficacy of faricimab was non-inferior to aflibercept (+ 5.8-6.6 vs. + 5.1-6.6 Early Treatment Diabetic Retinopathy Study [ETDRS] letters). At study end, 80% of faricimab-treated patients were on ≥ 12-week dosing intervals, and 44.9-45.7% of faricimab-treated patients were on 16-week dosing intervals. Total adverse events, as well as serious ocular adverse events, were comparable between groups. In phase 3 trials of DMO, efficacy of faricimab was non-inferior to aflibercept (+ 10.7-11.8 vs. + 10.3-10.9 ETDRS letters). At study end, > 70% of patients in the personalised treatment interval faricimab group were on ≥ 12-week dosing intervals, and 51-53% were on 16-week dosing intervals. Total adverse events were comparable between groups, although the rate of serious ocular adverse events was higher in the faricimab groups than in the aflibercept groups (1.9-3.1% vs. 0.6-1.9%, respectively). In real-world studies of treatment-resistant nAMD or DMO, faricimab demonstrated superior efficacy compared to aflibercept. In a real-world study of mostly previously treated nAMD, faricimab demonstrated some efficacy.

    Conclusion: Faricimab demonstrated non-inferior to superior efficacy, strong durability and acceptable safety in treatment-naïve nAMD and mostly treatment-naïve DMO, as well as superior efficacy in treatment-resistant nAMD and DMO. However, further research is needed on faricimab in real-world settings.

    DOI: 10.1007/s40123-023-00753-6

    Long-term efficacy and complications of intravitreal anti-vascular endothelial growth factor agents combined with ablative therapies in juvenile Coats disease: a five year follow-up study.

    Graefe’s archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 2023 Jul 8.

    Li L, Li S, Liu J, Deng G, Ma J, Lu H.

    Purpose: To evaluate the long-term safety and efficacy of adjuvant intravitreal anti-VEGF therapy in juvenile Coats disease.

    Methods: This retrospective, observational study included a total of 62 eyes in 62 pediatric patients with juvenile Coats disease treated with intravitreal anti-VEGF agents followed for a mean of 67.08 months (ranged from 60 to 93 months). All affected eyes were managed initially with one session of ablative treatment plus adjuvant intravitreal anti-VEGF agent (0.5 mg/0.05 ml ranibizumab or conbercept). Ablative treatment was repeated if telangiectatic retinal vessels were not completely regressed or recurred. Anti-VEGF therapy was repeated if subretinal fluid or macular edema still existed. Treatments above were repeated every 2 to 3 months. We reviewed clinical and photographic records of patients including the demographics, clinical characteristics and interventions.

    Results: At final visit, all 62 affected eyes had partially or completely disease resolution; none progressed to advanced stage namely neovascular glaucoma or phthisis bulbi, respectively. No ocular or systemic side effects related to intravitreal injections were observed during follow-up. In terms of 42 affected eyes that could cooperate with visual examination, best corrected visual acuity improved in 14 (14/42, 33.3%) eyes, stabled in 25 (25/42, 59.5%) eyes, and worsened in 3 (3/42, 7.1%) eyes. In the field of complications, 22 (22/62, 35.5%) eyes developed cataracts; 33 (33/62, 53.2%) eyes developed vitreoretinal fibrosis, of whom 14 (14/33, 42.4%) eyes in the subgroup of stage 3B developed progressive TRD; 40 (40/62, 64.5%) eyes developed subretinal fibrosis. Multivariate regression analysis showed increased clinical stage may be associated with the development of vitreo- and subretinal fibrosis (adjusted odds ratio:16.77,17.59; 95% CI:4.50-62.53, 3.98-77.86, respectively, all P < 0.001).

    Conclusion: Adjuvant intravitreal ranibizumab or conbercept combined with ablative therapies may be a long-term safe and effective treatment for juvenile Coats disease.

    DOI: 10.1007/s00417-023-06162-6

    Lesion area progression in eyes with neovascular age-related macular degeneration treated using a proactive or a reactive regimen.

    Eye (London, England) 2023 Jul 1.

    Cozzi M, Monteduro D, Esposito RA, Spooner KL, Fraser-Bell S, Staurenghi G, Romano F, Airaldi M, Chang AA, Invernizzi A.

    Background: To compare the change in lesion area over 4 years of follow-up in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a proactive or a reactive regimen in routine clinical practice.

    Methods: This was a multicentre, retrospective comparative study. Totally, 202 treatment-naïve nAMD eyes (183 patients) received anti-VEGF therapy according to a proactive (n = 105) or reactive (n = 97) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had baseline fluorescein angiography and annual optical coherence tomography (OCT) imaging. Two masked graders independently delineated the lesion’s margins from serial OCT images and growth rates were calculated.

    Results: At baseline, the mean [SD] lesion area was 7.24 [5.6] mm2 in the proactive group and 6.33 [4.8] mm2 in the reactive group respectively (p = 0.22). After four years of treatment, the mean [SD] lesion area in the proactive group was 5.16 [4.5] mm2 showing a significant reduction compared to the baseline (p < 0.001). By contrast, the mean [SD] lesion area kept expanding in the reactive group during the follow-up and was 9.24 [6.0] mm2 at four years (p < 0.001). The lesion area at 4 years was significantly influenced by treatment regimen, baseline lesion area, and proportion of visits with active lesions.

    Conclusions: Eyes treated using a reactive strategy had an increased lesion area and worse visual outcomes at 4 years. By contrast, the proactive regimen was associated with fewer recurrences of active disease, shrinkage of the lesion area, and better vision at four years.

    DOI: 10.1038/s41433-023-02652-3

    Second eyes to develop neovascular age-related macular degeneration have fewer symptoms and better one-year visual outcomes.

    BMC Ophthalmology. 2023 Jul 7;

    Akkan Aydoğmuş FS, Onwuka O, Saddemi J, Lasalle CC, Ramsey DJ.

    Background: This study compares the visual and anatomical outcomes for the eyes of patients who developed sequential neovascular age-related macular degeneration (nAMD), both at the time of diagnosis and at one year after treatment.

    Methods: The study comprised a retrospective case series of 52 patients whose eyes were diagnosed sequentially with nAMD. All eyes were treated with three monthly loading doses of anti-vascular endothelial growth factor agents, followed by further intravitreal injections, as required. Baseline characteristics and outcomes at one year after diagnosis and initial treatment were compared between first and second eyes and included visual acuity (VA), central macular thickness (CMT), and pigment epithelial detachment (PED) height on optical coherence tomography (OCT) imaging.

    Results: VA at diagnosis was better for second eyes compared with first eyes to develop nAMD (logMAR 0.68 ± 0.51 versus logMAR 0.41 ± 0.34, P = 0.002) and remained so at one year (logMAR 0.61 ± 0.60 versus logMAR 0.42 ± 0.37, P = 0.041). Similarly, PED height at diagnosis was higher in first eyes (225 ± 176 μm versus 155 ± 144 μm, P = 0.003) and also at one year (188 ± 137 μm versus 140 ± 112 μm, P = 0.019). Whereas most patients reported symptoms at first eye diagnosis (71.2%), half as many second eyes were symptomatic (28.8%, P < 0.001). Significantly more symptomatic first eyes experienced visual distortions (32.4% versus 13.3%) or scotomas (29.4% versus 6.7%), compared with a less specific visual complaint of blurry vision (38.2% versus 80.0%, P = 0.006).

    Conclusions: Compared with first eyes to develop nAMD, second eyes tended to have better vision, smaller PED heights, and fewer symptoms likely because monitoring permitted earlier diagnosis.

    DOI: 10.1186/s12886-023-03021-0


    Histology, dimensions, and fluorescein staining characteristics of nodular and cuticular drusen in age-related macular degeneration.

    Retina (Philadelphia, Pa.) 2023 Jun 29.

    Evers CD, Chen L, Messinger JD, Killingsworth M, Freund KB, Curcio CA.

    Purpose: To enable in vivo analysis of drusen composition and lifecycle, we assessed macular nodular and cuticular drusen using histology.

    Methods: Median and interquartile range (IQR) of base widths of single (non-confluent) nodular drusen in 3 sources were determined histologically: 43 eyes of 43 clinically undocumented donors, in an online resource; one eye with punctate hyperfluorescence in fluorescein angiography (FA); and two eyes of one patient with bilateral “starry sky” cuticular drusen. All tissues were processed for high-resolution epoxy-resin histology and for cuticular drusen, transmission electron microscopy.

    Results: All drusen localized between the retinal pigment epithelium basal lamina and inner collagenous layer of Bruch’s membrane. They were solid, globular, homogeneously stained with toluidine blue, and uncovered by basal laminar deposit and basal mounds. Median base widths were 13.0 µm (Source 1, N=128 drusen, IQR 7.7, 20.0 µm), 15.3 µm (Source 2, N=87, IQR 10.6, 20.5 µm), and 7.3 µm (Source 3, N=78, IQR 3.9, 14.1 µm).

    Conclusions: In three samples, >90% of solitary nodular drusen were <30 µm, the visibility threshold in color fundus photography; these drusen are hyperfluorescent in FA. Whether these progress to soft drusen, known as high-risk from epidemiology studies and hypofluorescent, may be determinable from multimodal imaging datasets that include FA.

    DOI: 10.1097/IAE.0000000000003871


    Red Wine Extract Prevents Oxidative Stress and Inflammation in ARPE-19 Retinal Cells.

    Cells. 2023 May 17;

    Cornebise C, Perus M, Hermetet F, Valls-Fonayet J, Richard TAires V, Delmas D

    Age-related macular degeneration (AMD) is one of the most commonly occurring ocular diseases worldwide. This degenerative condition affects the retina and leads to the loss of central vision. The current treatments are focused on the late stage of the disease, but recent studies have highlighted the importance and benefits of preventive treatments and how good dietary habits can reduce the risk of progression to an advanced form of the disease. In this context, we studied whether resveratrol (RSV) or a polyphenolic cocktail, red wine extract (RWE), are able to prevent the initiating events of AMD (i.e., oxidative stress and inflammation) in human ARPE-19 retinal pigment epithelial (RPE) cells and macrophages. This study highlights that RWE and RSV can prevent hydrogen peroxide (H2O2) or 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced oxidative stress and can subsequently prevent DNA damage via the inhibition of the ATM (ataxia telangiectasia-mutated)/Chk2 (checkpoint kinase 2) or Chk1 signaling pathways, respectively. Moreover, ELISA assays show that RWE and RSV can prevent the secretion of proinflammatory cytokines in RPE cells and in human macrophages. Interestingly, RWE exhibits a greater protective impact compared to RSV alone, even though RSV was more concentrated when used alone than in the red wine extract. Our results suggest that RWE and RSV may have potential interest as preventive nutritional supplementations against AMD.

    DOI: 10.3390/cells12101408


    Rapid Improvement in Lipid Maculopathy Following Faricimab Therapy in Recalcitrant Familial Exudative Vitreoretinopathy.

    Ophthalmic Surgery, lasers & imaging retina. 2023 Jun 1:

    Ghoraba HH, DeBoer C, Moshfeghi DM.

    A monocular 22-year-old man with recalcitrant familial exudative vitreoretinopathy presented with progressive subretinal lipid exudation and lipid maculopathy that responded poorly to repeated aflibercept injections. The subretinal exudation started temporally and gradually progressed, involving the macula and the retinal periphery in all 4 quadrants. At the 22-month follow-up visit, macular and peripheral subretinal exudation persisted despite a total of 29 injections. Faricimab was then injected once every 2 weeks for a total of 3 injections, which resulted in rapid dramatic resolution of the macular and most of the peripheral subretinal exudation. No ocular or systemic adverse events were noted. [Ophthalmic Surg Lasers Imaging Retina 2023;54:xxx-xxx.].

    DOI: 10.3928/23258160-20230609-01