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    Research update: 505

    The latest research highlights for 9 August 2021


    Predictive Factors for Long-Term Outcomes of Cataract Surgery in Patients Receiving Active Treatment for Neovascular Age-Related Macular Degeneration.

    J Clin Med. 2021 Jul 15;10(14):3124.

    Choi EY, Kim TY, Lee CS.

    BACKGROUND: the safety and efficacy of cataract surgery in eyes with exudative neovascular age-related macular degeneration (nAMD), receiving active treatment, remain unclear. We evaluated the long-term outcomes and associated predictive factors of cataract surgery in eyes with exudative nAMD.

    METHODS: this retrospective cohort study included 65 eyes (61 patients) treated with anti-vascular endothelial growth factor (VEGF) injections within six months preoperatively. Changes in best-corrected visual acuity (BCVA) and anti-VEGF treatment patterns from before to up to four years after surgery were assessed. Predictive factors were identified in association with one-year surgical outcomes.

    RESULTS: the BCVA improved at six months (p < 0.001) and was maintained for three years postoperatively. The interval between anti-VEGF injections increased 3.4 times postoperatively (p = 0.001). Risk factors for poor BCVA were low preoperative BCVA (p < 0.001) and prolonged nAMD duration (p = 0.003). Prolonged nAMD duration and short exudation-free period were associated with more frequent postoperative anti-VEGF treatments (p = 0.028 and p = 0.003, respectively). AMD subtypes were not associated with both vision and injection pattern outcomes.

    CONCLUSIONS: patients with cataracts receiving nAMD treatment can safely undergo surgery with favorable long-term visual benefits. The preoperative BCVA, nAMD duration, and exudation-free period are potential predictors of surgery outcomes.

    DOI: 10.3390/jcm10143124

    Long-term analysis of clinical features and treatment outcomes of inflammatory choroidal neovascularization.

    Am J Ophthalmol. 2021 Jul 20:S0002-9394(21)00381-0.

    Kim M, Lee J, Park YG, Park YH.

    PURPOSE: To investigate the long-term clinical features and treatment outcomes of patients with inflammatory choroidal neovascularization (CNV) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF).

    DESIGN: Retrospective, interventional, consecutive case series

    METHODS: Sixty-five eyes of 65 patients with inflammatory CNV treated with anti-VEGF injections and followed up at least 12 months were included. Retrospective chart review was conducted at a single tertiary referral center.

    RESULTS: Study participants were followed up for 60.6±42.8 (range, 16-160) months. Mean age was 33.4±10.8 years, and mean refractive error was -3.94±1.35 D in spherical equivalent. Final best-corrected visual acuity (BCVA) was 0.21±0.20 logMAR after treatment. Patients were treated with bevacizumab (76.9%), ranibizumab (4.6%), aflibercept (3.1%), and drug combinations (15.4%). Systemic corticosteroid or immunosuppressant use was not correlated with visual outcome, required number of anti-VEGF injections, and recurrence. Commonly occurring optical coherence tomography (OCT) features included ellipsoid zone disruption, choroidal hypertransmission, retinal pigment epithelium atrophy or absence (RPEA), intraretinal hyperreflective foci (HRF), choroidal vessel engorgement, focal choroidal excavation, and irregular vascular loops (on OCT angiography). RPEA after treatment (β=0.238, P=.036) and BCVA (β=0.267, P=.029) showed significant correlation with final BCVA. Twenty-eight patients (43.1%) experienced recurrence; intraretinal HRF after treatment was the single risk factor for recurrence (OR 2.712, P=.031).

    CONCLUSIONS: Inflammatory CNV recurrence showed higher rates over time after anti-VEGF treatment than previously reported, even though the overall visual outcome was good. Baseline BCVA and RPEA after treatment are significant predictors for visual outcome. Intraretinal HRF after anti-VEGF treatment suggests the potential risk of recurrence.

    DOI: 10.1016/j.ajo.2021.07.014

    Randomised, Double-blind, Comparative Clinical Study of New Ranibizumab Biosimilar in Neovascular (Wet) Age-Related Macular Degeneration.

    Clin Ophthalmol. 2021 Jul 16;15:3087-3095.

    Apsangikar P, Ghadge P, Naik M, Nair S, Payghan R.

    PURPOSE: The study was undertaken for regulatory purposes to establish clinical biosimilarity and interchangeability of a ranibizumab biosimilar with reference product.

    PATIENTS AND METHODS: A total of 159 subjects with neovascular (wet) age-related macular degeneration (AMD) were dosed with ranibizumab. Initial double blind period of 16 weeks was followed by open-label phase till week 24. Efficacy assessment was performed at weeks 1, 4, 8, 12, 16, 20 and 24 based on best corrected visual acuity. Change in central macular thickness was assessed by optical coherence tomography from baseline to week 24. Immunogenicity assessment was done in both arms at baseline, week 16 and week 24. Safety evaluation included clinical and ophthalmic examination, adverse events, vital signs, laboratory parameters and immunogenicity in both treatment arms.

    RESULTS: In the biosimilar test arm, 104 (98.11%) and 105 (99.06%) patients lost fewer than 15 letters in visual acuity at week 16 and week 24, respectively, compared with 53 (100%) at both follow-ups in reference arm. In the test arm, 27 (25.47%) and 34 (32.08%) patients gained at least 15 letters in visual acuity till week 16 and week 24 respectively, compared with 17 (32.08%) and 23 (43.30%) in the reference arm. In the test arm, mean change in central macular thickness at 24 weeks was -89.93 µm against -64.42 µm in the reference arm. Difference was statistically not significant for any endpoint at 16 and 24 weeks for the primary and secondary endpoints.

    CONCLUSION: The evaluation of efficacy, safety and immunogenicity was concluded to show no meaningful clinical difference for biosimilar ranibizumab with the reference product.

    DOI: 10.2147/OPTH.S307746


    Dose Response in the Subthreshold Nanosecond Laser Trial in Early Stages of AMD: A LEAD Study Report.

    Ophthalmic Surg Lasers Imaging Retina. 2021 Jul;52(7):380-386.

    Cohn AC, Runciman J, Hodgson LAB, Caruso E, Arnold JJ, Chen FK, Chakravarthy U, Heriot WJ, Guymer RH, Wu Z; LEAD Study Group.

    BACKGROUND AND OBJECTIVE: To examine the association between treatment parameters and the progression to late age-related macular degeneration (AMD) in the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a randomized, controlled trial of a subthreshold nanosecond laser (SNL) for slowing disease progression in the early stages of AMD.

    PATIENTS AND METHODS: The association between treatment parameters early in the trial period for participants in the SNL arm of the LEAD study and time to develop late AMD during the 3-year trial duration was examined. Parameters included treatment energy at the baseline and 6-month visits and the number of laser spots visible on fundus autofluorescence (FAF) imaging taken at 6 and 12 months (taken as a proxy measure of early, adequate delivery of the laser treatment at the baseline and 6-month visits, respectively).

    RESULTS: A multivariable analysis revealed there were no significant associations between time to develop late AMD and number of FAF-visible laser spots at 6-months (adjusted P = .537) nor laser energy used at baseline (adjusted P = .910). No significant associations were also observed when evaluating FAF-visible spots at 12-months (adjusted P = .107) and the average laser energy used at baseline and 6 months (adjusted P = .558).

    CONCLUSIONS: This study did not find any evidence to suggest that there was a dose response for the effect of laser treatment using these treatment parameters on the progression of AMD.

    DOI: 10.3928/23258160-20210628-04


    Diagnostic accuracy of monitoring tests of fellow eyes in patients with unilateral neovascular age related macular degeneration (EDNA study).

    Ophthalmology. 2021 Jul 27:S0161-6420(21)00557-1.

    Sivaprasad S, Banister K, Azuara-Blanco A, Goulao B, Cook JA, Hogg R, Scotland G, Heimann H, Lotery A, Ghanchi F, Gale R, Menon G, Downey L, Hopkins N, Scanlon P, Burton B, Ramsay C, Chakravarthy U.

    OBJECTIVE: To evaluate the diagnostic accuracy of routinely used tests of visual function and retinal morphology compared to fundus fluorescein angiography (FFA) to detect onset of active macular neovascularisation in unaffected fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD).

    DESIGN: Prospective diagnostic accuracy cohort study conducted in 24 eye clinics in the UK over 3 years.

    PARTICIPANTS: Older adults (>50y) with recently diagnosed unilateral nAMD with a fellow (study) eye free of nAMD.

    INDEX TESTS: Self-reported vision, Amsler, clinic measured visual acuity, fundus assessment, and spectral domain optical coherence tomography (OCT).


    MAIN OUTCOME MEASURE: Sensitivity and specificity of the 5 index tests.

    RESULTS: Of 552 participants monitored for up to three years, 145 (26.3%) developed active nAMD in the study eye, of whom 120 had an FFA at detection and constituted the primary analysis cohort. Index test positives at nAMD detection in those confirmed by FFA were, self reported vision much worse 5, distortion on Amsler 33, 10-letter decrease in acuity from baseline 36, fundus examination 64; OCT 110. Index test sensitivities % (95% CI) were: self-reported vision 4.2 (1.6 to 9.8); Amsler 33.7 ( 25.1 to 43.5); visual acuity 30.0 ( 22.5 to 38.7); fundus examination 53.8 (44.8 to 62.5) and OCT 91.7 (85.2 to 95.6). All 5 index test specificities were high at 97.0 (94.6 to 98.5), 81.4 [76.4 to 85.5), 66.3 (61.0 to 71.1), 97.6 (95.3, 98.9), and 87.8 (83.8, 90.9), respectively. The combination of OCT with one other index test which was a secondary outcome measure increased sensitivity marginally and decreased specificity for all combinations except fundus examination.

    CONCLUSION: Tests of self-reported change in vision, unmasking of new distortion, measurements of acuity and fundus checks to diagnose active nAMD performed poorly in contrast to OCT. Our findings support a change to guidelines in clinical practice to monitor for onset of nAMD.

    DOI: 10.1016/j.ophtha.2021.07.025

    En Face Swept-source optical coherence tomography angiography Choroidal Vasculography (CVG) a tool to discriminate choroidal abnormalities in Polypoidal Choroidal Vasculopathy.

    Expert Rev Med Devices. 2021 Jul 30.

    Arias JD, Parra MM, Hoyos AT, Arango F, Viteri EJ, Arevalo JF.

    BACKGROUND: Swept source optical coherence tomography angiography (SS-OCT-A) choroidal vasculography (CVG) is an imaging method which allows the evaluation of deep choroid details, being a promising too in choroidal pathologies as polypoidal choroidal vasculopathy (PCV).

    RESEARCH DESIGN AND METHODS: Cross-sectional study performed at FOSCAL International Clinic in Colombia. CVG features in patients with PCV were evaluated using SS-OCT CVG.

    RESULTS: Twenty-two eyes of 21 patients were included. The mean age was 72.7 ± 6.5 years old (range: 48.6-95.4 years old). Twelve (57.1%) patients were male. The mean number of polyps detected by SS-OCT-A CVG before treatment with anti-VEGF therapy was 2.04 ± 1.18, which decreased after treatment to 1.18 ± 0.71. This result was statistically significant (p<0.05). All polypoidal lesions detected by B-scan were visualized using CVG. Polyp circularity and surrounding reflectivity indicated activity of disease.

    CONCLUSION: En face SS-OCT-A CVG is an alternative tool to evaluate choroidal structure at different depths without a contrast dye, providing information for the diagnosis and follow-up of patients with PCV. This imaging modality do not pretend to replace gold standard tests in PCV as ICGA, but rather provides choroidal imaging features of PCV, when ICGA is not available.

    DOI: 10.1080/17434440.2021.1963230

    Long-term retinal changes in progressive geographic atrophy.

    Eur J Ophthalmol. 2021 Jul 24:11206721211035636.

    Gallagher D, Kalra G, Rasheed MA, Vupparaboina KK, Singh SR, Chhablani J.

    BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of blindness with loss of retinal layers over long term. We aim to evaluate these changes in eyes with progressive non-exudative AMD with geographic atrophy (GA).

    METHODS: This retrospective study included patients with GA with a minimum of 4 years follow up. Retinal layers on spectral domain optical coherence tomography (SD-OCT) were segmented based on their reflectivity patterns using validated semi-automated segmentation algorithm. The thickness of the segmented retinal layers was measured. Horizontal length of GA at baseline and last follow-up were also measured. Regression analysis was performed to correlate changes in RPE layer thickness with other retinal layers and the length of GA on OCT.

    RESULTS: A total of 351-line scans including 17 foveal scans showing presence of GA at final visit that is, a total of 2457 retinal layer bands were analyzed. Outer nuclear layer (ONL) (p = 0.02), outer segment layers (OSL) (p = 0.01), and retinal pigment epithelium (RPE) (p = 0.01) showed a statistically significant variation between baseline and final visit. Regression analysis showed the change in ONL (r = 0.72; p = 0.01) and OSL (r = 0.93, p < 0.01) correlated significantly with change in RPE thickness whereas rest of the layers failed to show significant correlation.

    CONCLUSION: Outer retinal layers (ONL and OSL) show more significant and widespread changes in retinal thickness and correlated most significantly with RPE thickness changes in eyes with GA due to AMD. Assessment of various retinal layer bands can be used as surrogate quantitative parameters to study eyes with GA.

    DOI: 10.1177/11206721211035636


    Non-steroidal Anti-inflammatory Drug Use and Risk of Age-Related Macular Degeneration in the California Teachers Study.

    Drugs Aging. 2021 Jul 26.

    Xu X, Ritz B, Coleman AL, Liew Z, Deapen D, Lee E, Bernstein L, Pinder R, Marshall SF, Heck JE.

    PURPOSE: The aim of this study was to examine whether use of regular aspirin and/or other non-steroidal anti-inflammatory drugs (NSAIDs) is associated with the development of age-related macular degeneration (AMD).

    METHODS: In the California Teachers Study cohort (N = 88,481) we identified diagnoses of AMD up to December 31, 2012 by linkage to statewide hospital discharge records. Aspirin, ibuprofen, other NSAIDs, and acetaminophen use and comprehensive risk factor information were collected via self-administered questionnaires at baseline in 1995-1996 and a follow-up questionnaire in 2005-2006. We employed Cox proportional hazard regression to model AMD risk.

    RESULTS: We did not find any associations between AMD and frequency and duration of aspirin or ibuprofen use reported at baseline. In the subsample with more specific information on medication use, we observed a 20% decrease in risk of AMD among low-dose aspirin users (HR 0.81, 95% CI 0.70-0.95) and a 55% decrease among cyclooxygenase-2 (COX-2) inhibitor users (HR 0.45, 95% CI 0.26-0.78) during 6.3 years of average follow-up.

    CONCLUSION: The decrease in risk of intermediate- or late-stage AMD among women who reported regular use of low-dose aspirin or specific COX-2 inhibitors suggests a possible protective role for medications with COX-2 inhibitory properties or aspirin at doses used for cardiovascular disease prevention.

    DOI: 10.1007/s40266-021-00885-z

    Association Between Age-Related Macular Degeneration and Risk of Heart Failure: A Population-Based Nested Case-Control Study.

    J Am Heart Assoc. 2021 Aug 3;10(15):e020071.

    Chang CC, Huang CH, Chou YC, Chang JY, Sun CA.

    BACKGROUND: Heart failure (HF) is a major health problem worldwide because of its high morbidity and mortality. Recently, the role of the microvasculature in HF has gained more attention. Age-related macular degeneration (AMD) is manifested through geographic atrophy or the development of neovascularization. However, there are limited data on investigations about the association between AMD and HF. The purpose of this study was to examine the association of AMD with the risk of HF in a large population-based cohort of men and women.

    METHODS & RESULTS: A nested case-control study using Taiwan’s National Health Insurance Research Database was conducted between 2000 and 2012. Newly diagnosed heart failure cases (n=13 721) and matched controls (n=54 884) in the database were recruited. Patients who had ≥2 clinical visits with a diagnosis of AMD at least 1 year before the diagnosis of HF were identified as patients with AMD. Conditional logistic regressions were performed to calculate odds ratios and 95% CIs to assess the association between AMD and risk of HF. AMD was associated with a 1.58-fold increased risk of HF (95% CI, 1.16-1.87) (P<0.001) after adjustment for potential confounders. This significant association was evident in both nonexudative and exudative AMD subgroups.

    CONCLUSIONS: Our study provides evidence that AMD was associated with an increased risk of HF. Further molecular and pathophysiological studies are needed to clarify the underlying pathophysiological mechanisms behind the association of AMD with HF.

    DOI: 10.1161/JAHA.120.020071


    Arcuate Vitelliform detachment with morning glory disc maculopathy: OCT findings of evolution and resolution after early surgery.

    BMJ Case Rep. 2021 Jul 27;14(7):e244329.

    Singh DV, Sharma Y, Reddy RR, Sharma A.

    Morning glory disc (MGD) is known to develop secondary maculopathy and vision loss. We followed a 7-year-old girl with MGD in right eye from 2010 to 2021. Her best-corrected Snellen visual acuity (BCVA) was 20/20 in both eyes till 2017. She presented with reduced vision in right eye with BCVA of 20/80 in 2018. Optical Coherence Tomography (OCT) revealed maculopathy related to MGD in right eye and arcuate Vitelliform neurosensory detachment (V-NSD) temporal to fovea. She underwent 25G vitrectomy with internal limiting membrane peeling. Resolution of retinoschisis and V-NSD was analysed by OCT and fundus autofluorescence (FAF) postoperatively. Arcuate V-NSD was hyperfluorescent on FAF and concentric to optic disc. It resolved slowly with BCVA improving to 20/20 at 18 and 30 months postoperatively. We report excellent outcome following early vitrectomy for MGD-related maculopathy and recommend serial follow-up and considering early vitrectomy whenever traction and BCVA worsens. We also describe arcuate V-NSD with MGD.

    DOI: 10.1136/bcr-2021-244329

    Multimodal imaging of Hypotrichosis with juvenile macular dystrophy: a case report.

    BMC Ophthalmol. 2021 Jul 23;21(1):284.

    Scalzo GC, Carnevali A, Piccoli G, Ceravolo D, Bruzzichessi D, Iuliano R, Tallerico R, Gatti V, Giannaccare G, Scorcia V.

    BACKGROUND: To report the first Italian case of hypotrichosis with juvenile macular dystrophy complicated by macular neovascularization diagnosed through multimodal imaging.

    CASE PRESENTATION: An 11-year-old boy was referred to our Institution for bilateral maculopathy of unknown origin. Multimodal imaging helps the diagnosis of Juvenile Macular Dystrophy with Hypotrichosis (HJMD). Fundus examination showed several alterations of the retinal pigment epithelium and circular pigmented area of chorioretinal atrophy. Structural spectral domain optical coherence tomography (OCT) showed some backscattering phenomenon with several alterations of retinal pigment epithelium and photoreceptor layer in both eyes. Moreover, OCT showed hyperreflective lesion beneath the neuroepithelium in left eye. OCT angiography (OCT-A) revealed a pathologic neovascular network in choriocapillaris plexus, probably the result of a fibrovascular membrane. Multifocal electroretinograms (MfERGs) showed functional alterations in 12.22° of the central retina. In order to confirm the suspicion of HJMD, the child and both parents underwent genetic testing. Both parents resulted to be heterozygous healthy carriers of a single variation.

    CONCLUSION: Multimodal imaging, in particular OCT-A, is a useful aid, along to clinical findings and genetics, for the diagnosis of inherited retinal dystrophies.

    DOI: 10.1186/s12886-021-02037-8


    Pachychoroid neovasculopathy: A comparative review on pathology, clinical features, and therapy.

    Eur J Ophthalmol. 2021 Jul 29:11206721211036290.

    Sagar P, Sodhi PS, Roy S, Takkar B, Azad SV.

    There have been major changes in our understanding of choroidal diseases in the last decade owing to multiple retinal and choroidal imaging related advances. A major conceptual pivot is establishment of pachychoroid and its spectrum of clinical disorders: pachychoroid pigment epitheliopathy, central serous chorioretinopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization, peripapillary pachychoroid syndrome, and focal choroidal excavation. However, considerable overlaps in manifestations and therapeutics of these disorders make differentiation amongst them difficult. This review is focused on pathogenesis and clinical aspects of pachychoroid neovasculopathy (PNV). Since PNV was defined as a separate entity around 5 years ago, there have been numerous contrasting observations surrounding it. We review and summarize these studies, and also compare PNV with other disorders of the pachychoroid spectrum in detail. There are important differences between etiologies of neovascular age related macular degeneration and PNV. Yet the current treatment strategies for PNV have been extrapolated from the trials for the former. Future research needs to validate this assumption with long-term results.

    DOI: 10.1177/11206721211036290