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    Research update: 528

    The latest research highlights for 21 February 2022.

    FEATURED ARTICLE

    Longer treatment intervals are associated with reduced treatment persistence in neovascular age related macular degeneration.

    Eye (London). 2022 Feb 9

    Teo KYC, Nguyen V, O’Toole L, Daien V, Sanchez-Monroy, Ricci F, Ponsioen TL, Morros HB, Cheung CMG, Arnold JJ, Barthelmes D, Gillies MC(4).

    AIMS: To test the hypothesis that patients treated for neovascular age related macular degeneration (nAMD) with longer treatment intervals are more likely to persist with treatment.

    Methods: Data were obtained from the prospectively-defined Fight Retinal Blindness! registry. Treatment interval at 2 years was stratified based on the mean treatment interval over the three visits prior to and including the 2-year visit. Rates of non-persistence to follow-up were assessed from 2 to 5 years.

    Results: Data from 1538 eyes were included. The overall rate of non-persistence was 51% at 5 years. Patients on longer treatment intervals (12-weeks) at 2 years were found to be less persistent to long-term follow-up. These eyes were found to have fewer active disease visits in the first 2 years (40%) than eyes treated at 4-weekly intervals (66%, p < 0.001). In the multivariable analysis, better vision at 2 years was associated with a lower risk of non-persistence (hazards ratio [HR] [95% CI]: 0.95 [0.93, 0.97], P < 0.001), while longer treatment intervals (HR [95% CI]: 1.31 [0.95, 1.8] and 1.54 [1.15, 2.06] for 12-week and > 12-week intervals vs. 4-week intervals, respectively, P = 0.002) and older patients (HR [95% CI]: 1.03 [1.02, 1.04], p < 0.001) were at higher risk of non-persistence. Conclusions: We found that patients on longer treatment intervals at 2 years were more likely to be non-persistent with treatment in later years. Reinforcing the need for ongoing treatment is important for patients on longer intervals who may feel complacent or that treatment is no longer effective, particularly if newer, longer lasting agents become widely available.

    DOI: 10.1038/s41433-022-01957-z

    PATHOPHYSIOLOGY

    Cuticular Drusen in Age-Related Macular Degeneration: Association with Progression and Impact on Visual Sensitivity.

    Ophthalmology. 2022 Feb 1

    Goh KL(1), Chen FK, Balaratnasingam C, Abbott CJ, Hodgson LAB, Guymer RH, Wu Z.

    Purpose: To determine the prognostic significance and impact on visual function of the cuticular drusen phenotype in a cohort with intermediate age-related macular degeneration (AMD). DESIGN: Longitudinal observational study.

    Participants: Participants aged 50 years or older, with bilateral large conventional drusen, without late AMD.

    Methods: Multimodal imaging (MMI) and microperimetry were performed at baseline, and then every 6 months for up to 3 years. Eyes were graded for the MMI-presence of cuticular drusen at baseline. Color fundus photographs were used to grade for the presence of pigmentary abnormalities. Optical coherence tomography (OCT) scans were used to calculate drusen volume. The association between cuticular drusen and progression to MMI-defined late AMD (including OCT signs of atrophy), as well as the impact on visual sensitivity were examined, with and without adjustment for the confounders of baseline age, pigmentary abnormalities and drusen volume.

    Main outcome measures: Time to develop MMI-defined late AMD and change in mean visual sensitivity. RESULTS: 280 eyes from 140 participants were included, with 70 eyes from 35 (25%) individuals having cuticular drusen at baseline. Cuticular drusen were not significantly associated with an increased rate of progression to late AMD, with and without adjustment for confounders (P ≥ 0.784 for both). In an adjusted model, cuticular drusen were not associated with lower baseline visual sensitivity (P = 0.758) or with a faster rate of visual sensitivity decline (P = 0.196).

    Conclusions: In a cohort with bilateral large conventional drusen, individuals with the cuticular drusen phenotype neither had a higher, nor lower, risk of developing late AMD over 3 years, and were not associated with a difference in rate of visual sensitivity decline compared to those without this phenotype. As such, individuals with this phenotype currently warrant similar monitoring strategies to those with conventional drusen.

    DOI: 10.1016/j.ophtha.2022.01.028

    REVIEW

    Neovascular age-related macular degeneration: advancement in retinal imaging builds a bridge between histopathology and clinical findings.

    Graefe’s Archive for Clinical and Experimental Ophthalmology 2022 Feb 5.

    Borrelli E, Bandello F, Souied EH, Barresi C, Miere A, Querques L, Sacconi R, Querques G.

    Purpose: To provide a review of the salient histological and imaging features in neovascular age-related macular degeneration (AMD) that will be integrated in order to have a better comprehension of the pathogenesis and clinical aspects of this disease.

    Methods: A literature review of histology and imaging features in neovascular AMD was conducted. Results: Histology has granted a detailed characterization of neovascular AMD ex vivo. In details, histological features in these eyes have offered important insights into the pathogenesis of neovascular AMD. In addition, histology donated a detailed characterization of the different types of macular neovascularization (MNV) that may complicate AMD. The introduction of optical coherence tomography angiography (OCTA) has enormously amplified our knowledge of neovascular AMD through in vivo assessment of the anatomical and pathological characteristics of this disease. New insights elucidating the morphological features of the choriocapillaris confirmed that this vascular structure plays a crucial role in the pathogenesis of neovascular AMD. OCTA also offered a detailed visualization of MNV complicating neovascular AMD.

    Conclusions: New imaging technologies offer a remarkable chance to build a bridge between histology and clinical findings in neovascular AMD.

    DOI: 10.1007/s00417-022-05577-x

    Fluocinolone acetonide implant in diabetic macular edema: International experts’ panel consensus guidelines and treatment algorithm.

    Eur J Ophthalmol. 2022 Feb 10.

    Kodjikian L, Bandello F, de Smet M, Dot C, Zarranz-Ventura J, Loewenstein A, Sudhalkar A, Bilgic A, Cunha-Vaz J, Dirven W(14), Behar-Cohen F, Mathis T.

    Center-involving diabetic macular edema (DME) is a leading cause of vision impairment in working-age adults. While its management is particularly challenging in a poorly compliant population, continuous innovation and the advent of new molecules have improved its outcome. The control of glycemia and of systemic aggravating factors remain essential to slow down progression of disease complications including DME. The indications for macular laser photocoagulation has progressively been phased out as a standard of care and replaced by local intraocular anti-VEGFs biologics and glucocorticoids (GCs). Intravitreal GCs in controlled-release drug delivery systems have allowed to reduce injection frequency and treatment burden. The non biodegradable Fluocinolone Acetonide (FAc) implant allows a long-lasting stabilization of both functional and anatomic improvements. However, adequate patient selection and monitoring through regular follow-up are essential for optimal results. Based on their experience and the latest literature, the aim of the present review is to provide international expert panel consensus on the place of the FAc implant in the treatment algorithm of DME, as well as its safety profile and how to manage it.

    DOI: 10.1177/11206721221080288

    DRUG TREATMENT

    Long term results of patients with neovascular age-related macular degeneration switched from other anti-VEGF agents to intravitreal Aflibercept.

    International Journal of Retina and Vitreous. 2022 Feb 10

    Adrean SD, Knight D, Chaili S, Ramkumar HL, Pirouz A, Grant S.

    Background: This study explores the long term anatomic and functional results of patients who were switched to intravitreal aflibercept injections (IAI) after being initially managed with other anti-VEGF agents for neovascular age-related macular degeneration (nAMD).

    Methods: Patients with nAMD were included if they started with another anti-VEGF agent and were switched to IAI. Subjects had at least 3 years of consistent therapy with IAI and at least 1 injection quarterly.

    Results: Eighty-eight patients had at least 3 years of treatment while 58 of those patients, had at least 4 years of IAI. Average treatment time with other anti-VEGF agents was 32 months prior to switching. Baseline best corrected vision (VA) was 59.4 letters (20/70 + 2). At time of switch, VA increased significantly to 66.7 letters (20/50 + 2). At 3 months after switch, VA increased significantly to 69.0 (20/40-) letters. After 3 years of consistent IAI, vision was 67.5 letters (20/40-2), and for those patients that completed 4 years of therapy, the average VA was 66.0 letters (20/50 + 2), with a gain of 6.6 letters over baseline vision. 32.1% of patients gained 3 or more lines of vision. Initial central macular thickness (CMT) was 369 µm, which improved to 347 µm at time of switch, and further improved at 3 months to 301 µm and was maintained over time.

    Conclusion: Patients switched to IAI can maintain vision over the long term. Patients treated on average for 5.7 years, had a visual gain of 8.1 letters after 3 years and 6.6 letters after 4 years of IAI therapy. CMT significantly improved following the switch and was maintained.

    DOI: 10.1186/s40942-022-00361-9

    Prophylactic Ranibizumab to Prevent Neovascular Age-Related Macular Degeneration in Vulnerable Fellow Eyes: A Randomized Clinical Trial.

    Ophthalmology Retina. 2022 Feb 1

    Chan CK, Lalezary M, Abraham P, Elman M, Beaulieu WT, Lin SG, Khurana RN, Bansal AS, Wieland MR, Palmer JD, Chang LK, Lujan BJ, Yiu G; PREVENT Study Group.

    Purpose: To determine whether prophylactic ranibizumab prevents the development of neovascular age-related macular degeneration (nAMD) in eyes with intermediate AMD for patients with pre-existing nAMD in their contralateral eye. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Adults aged 50 and older with intermediate AMD (multiple intermediate drusen [≥ 63 μm and <125 μm] or ≥1 large drusen [≥125 μm] and pigmentary changes) in the study eye and nAMD in the contralateral eye.

    Intervention: Intravitreal ranibizumab injection (0.5 mg) every 3 months for 24 months or sham injection.

    Main outcome measures: Conversion to nAMD over 24 months (primary). Change in best-corrected visual acuity from baseline to 24 months (secondary).

    Results: Among 108 enrolled participants (54 [50%] in each group), all except two were non-Hispanic Whites, 61 participants (56%) were female, and the mean age was 78 years. The mean baseline visual acuity was 77.7 letters (Snellen equivalent 20/32). The rate of conversion to nAMD over 24 months was 7 of 54 eyes (13%) in both groups (ranibizumab vs. sham hazard ratio=0.91 [95% CI, 0.32-2.59], P=.86). At 24 months, the cumulative incidence of nAMD adjusted for loss to follow-up was 14% (95% CI, 4%-23%) in the ranibizumab group and 15% (95% CI, 4%-25%) in the sham group. At 24 months, the mean change in visual acuity from baseline was -2.1 letters (standard deviation, 5.4) with ranibizumab and -1.4 letters (standard deviation, 7.7) with sham (adjusted difference=-0.8 [95% CI, -3.7 to 2.2], P=.63). The proportion of eyes that lost at least 10 letters of visual acuity from baseline at 24 months was 2 of 39 (5%) with ranibizumab and 4 of 40 (10%) with sham. There were no serious ocular adverse events in either group.

    Conclusions: Quarterly dosing of 0.5 mg ranibizumab in eyes with intermediate AMD did not reduce the incidence of nAMD as compared to sham injections; however, the study was likely underpowered given the 95% confidence interval, and a clinically meaningful effect cannot be excluded. There also was no effect on visual acuity at 24 months. Other strategies to reduce neovascular conversion in these vulnerable eyes are needed.

    DOI: 10.1016/j.oret.2022.01.019

    GENETICS

    Genetic and environmental risk factors for reticular pseudodrusen in the EUGENDA study.

    Molecular Vision. 2021 Dec 31

    Altay L, Liakopoulos S, Berghold A, Rosenberger KD, Ernst A, de Breuk A, den Hollander AI, Fauser S, Schick T.

    Purpose: The purpose of this study was to analyze genetic and nongenetic associations with reticular pseudodrusen (RPD) in patients with and without age-related macular degeneration (AMD). Methods: This case-control study included 2,719 consecutive subjects from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography (OCT) scans were evaluated for the presence of AMD and RPD. Association of RPD with 39 known AMD polymorphisms and various nongenetic risk factors was evaluated. Stepwise backward variable selection via generalized linear models (GLMs) was performed based on models including the following: a) age, sex, and genetic factors and b) all predictors. Receiver operating characteristic (ROC) curves and the areas under the curve (AUCs) were determined. Results: RPD were present in 262 cases (no AMD, n = 9 [0.7%; early/intermediate AMD, n = 75 [12.4%]; late AMD, n = 178 [23.8%]). ROC analysis of the genetic model including age, APOE rs2075650, ARMS2 rs10490924, CFH rs800292, CFH rs12144939, CFI rs10033900, COL8A1 rs13081855, COL10A1 rs3812111, GLI3 rs2049622, and SKIV2L rs4296082 revealed an AUC of 0.871. Considering all possible predictors, backward selection revealed a slightly different set of genetic factors, as well as the following nongenetic risk factors: smoking, rheumatoid arthritis, steroids, antiglaucomatous drugs, and past sunlight exposure; the results showed an AUC of 0.886. Conclusions: RPD share a variety of genetic and nongenetic risk factors with AMD. Future AMD grading systems should integrate RPD as an important risk phenotype.

    PMCID: PMC8763662

    CASE REPORT

    Simultaneous development of full-thickness macular hole and neovascular age-related macular degeneration.

    American Journal of Ophthalmology Case Rep. 2022 Jan 22, eCollection 2022 Mar.

    Aoki S, Imaizumi H.

    Purpose: To present a case of full-thickness macular hole (MH) with treatment-naïve neovascular age-related macular degeneration (nAMD).

    Observations: A 74-year-old woman presented with sudden visual impairment and floaters in her left eye. Fundus examination revealed retinal hemorrhages and hemorrhagic pigment epithelial detachment at the fovea. Optical coherence tomography angiography revealed both type 1 nAMD and stage 4 MH obscured by blood. After the first intravitreal aflibercept injection, early pars plana vitrectomy in addition to the inverted internal limiting membrane flap technique was performed to close MH without complications. This improved the patient’s visual acuity. Throughout the postoperative follow-up period of 18 months, recurrent exudates from nAMD required repetitive aflibercept injections; MH relapse was not observed.

    Conclusions: MH can be complicated by acute, treatment-naïve nAMD. Early surgical closure of secondary MH combined with anti-vascular endothelial growth factor therapy for nAMD may yield a satisfactory visual outcome.

    DOI: 10.1016/j.ajoc.2022.101325

    ADVANCES IN HOME BASED MONITORING

    A Smartphone-Based Near-Vision Testing System: Design, Accuracy, and Reproducibility Compared With Standard Clinical Measures.

    Ophthalmic Surgery Lasers and Imaging Retina. 2022 Feb, Epub 2022 Feb 1.

    Kim DG, Webel AD, Blumenkranz MS, Kim Y, Yang JH, Yu SY, Kwak HW, Palanker D, Toy B, Myung D.

    Background and objective: Ophthalmologic telemedicine has emerged during the COVID-19 pandemic. The objective of this study is to assess the accuracy and reproducibility of a smartphone-based home vision monitoring system (Sightbook) and to compare it with existing clinical standards. Patients and methods: Near Snellen visual acuity (VA) was measured with Sightbook and compared with conventional measurements for distance and near VA at an academic medical center ophthalmology clinic in 200 patients with a variety of different specified preexisting ocular conditions. Measurements of contrast sensitivity were also compared by using an existing commercially available chart system in 15 normal patients and 15 patients with age-related macular degeneration.

    Results: Sightbook VA tests were reproducible (SD = ±0.054 logMAR), and correlation with standard VA methods was significant (R > 0.87 and P < .001). Sightbook contrast sensitivity measurements were reproducible (SD/mean ratio, 0.02 to 0.04), yielding results similar to those of standard tests (R2 > 0.87 and P < .001).

    Conclusions: Smartphone-based VA and contrast sensitivity are highly correlated with standard charts and may be useful in augmenting limited inoffice care. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:79-84.].

    DOI: 10.3928/23258160-20220121-05