FEATURED ARTICLE
Predictors of myopic macular degeneration in a 12-year longitudinal study of Singapore adults with myopia.
British Journal of Ophthalmology. 2022 May 9.
Foo LL, Xu L, Sabanayagam C, Htoon HM, Ang HNM, Zhang J, Ohno-Matsui K, Cheng CY, Hoang QV, Tan CS, Saw SM, Wong CW).
Purpose: To investigate the predictive factors for myopic macular degeneration (MMD) and progression in adults with myopia.
Methods: We examined 828 Malay and Indian adults (1579 myopic eyes) with myopia (spherical equivalent (SE) ≤-0.5 dioptres) at baseline who participated in both baseline and 12-year follow-up visits of the Singapore Malay Eye Study and the Singapore Indian Eye Study. Eye examinations, including subjective refraction and axial length (AL) measurements, were performed. MMD was graded from fundus photographs following the Meta-Analysis for Pathologic Myopia classification. The predictive factors for MMD development and progression were assessed in adults without and with MMD at baseline, respectively as risk ratios (RR) using multivariable modified Poisson regression models. The receiver operating characteristic curve was used to visualise the performance of the predictive models for the development of MMD, with performance quantified by the area under the curve (AUC).
Results: The 12-year cumulative MMD incidence was 10.3% (95% CI 8.9% to 12.0%) among 1504 myopic eyes without MMD at baseline. Tessellated fundus was a major predictor of MMD (RR=2.50, p<0.001), among other factors including age, worse SE and longer AL (all p<0.001). The AUC for prediction of MMD development was found to be 0.78 (95% CI 0.76 to 0.80) for tessellated fundus and increased significantly to an AUC of 0.86 (95% CI 0.84 to 0.88) with the combination of tessellated fundus with age, race, gender and SE (p<0.001). Older age (p=0.02), worse SE (p<0.001) and longer AL (p<0.001) were found to be predictors of MMD progression.
Conclusions: In adults with myopia without MMD, tessellated fundus, age, SE and AL had good predictive value for incident MMD. In adults with MMD, 1 in 10 eyes experienced progression over the same period. Older age, more severe myopia and longer AL were independent risk factors for progression.
DOI: 10.1136/bjophthalmol-2021-321046
DRUG TREATMENT
Association Between Visual Acuity and Residual Retinal Fluid Following Intravitreal Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.
JAMA Ophthalmology. 2022 May 12.
Patil NS, Mihalache A, Dhoot AS, Popovic MM, Muni RH, Kertes PJ.
Importance: The association between residual subretinal fluid (SRF) and intraretinal fluid (IRF) and visual acuity following anti-vascular endothelial growth factor (VEGF) treatment is not well understood.
Objective: To examine the association of residual retinal fluid, SRF, and IRF with visual acuity following anti-VEGF treatment in patients with neovascular age-related macular degeneration (nAMD).
Data sources: A systematic literature search was performed from January 2005 to August 2021 using Ovid MEDLINE, Embase, and the Cochrane Library.
Study Selection: Peer-reviewed articles reporting on visual acuity stratified by the presence or absence of any residual SRF, IRF, or any retinal fluid at last study observation after intravitreal bevacizumab, ranibizumab, aflibercept, or brolucizumab in patients with nAMD were included. Studies that were noncomparative, included fewer than 10 eyes, or reported on other anti-VEGF agents were excluded.
Data Extraction and Synthesis: Two independent reviewers conducted data extraction and synthesis. The Cochrane risk of bias tool 2 and ROBINS-I were used to assess risk of bias and GRADE evaluation was conducted to assess certainty of evidence.
Main Outcomes and Measures: Primary outcomes were BCVA at last study observation, change in BCVA from baseline, and retinal thickness at last study observation.
Results: In this systematic review and meta-analysis, 11 studies (6 randomized clinical trials [RCTs]) comprising 3092 eyes were included in our analysis. Across all included studies, the BCVA of eyes with residual SRF was better than eyes without SRF (weighted mean difference [WMD], 3.1 letter score; 95% CI, 0.05 to 6.18; P = .05; GRADE, low certainty of evidence; 6 studies; 1931 eyes) but similar in RCTs (WMD, 2.7 letter score; 95% CI, -2.40 to 7.84; P = .30; GRADE, low certainty of evidence; 3 studies; 1406 eyes). The BCVA of eyes with residual IRF was worse than that of eyes without IRF (WMD, -8.2 letter score; 95% CI, -11.79 to -4.50; P < .001; GRADE, low; 7 studies; 2114 eyes).
Conclusions And Relevance: The findings suggest that the presence of residual SRF was associated with slightly better BCVA at last study observation; however, baseline differences in BCVA existed and this conclusion was primarily driven by 1 study. The presence of residual IRF was associated with substantially worse BCVA at last study observation and less improvement of BCVA from baseline. The conclusions are limited by the inclusion of data from observational studies, heterogeneity, and a low certainty of evidence.
DOI: 10.1001/jamaophthalmol.2022.1357
Characterisation of the vascular anterior surface of type 1 macular neovascularisation after anti-VEGF therapy.
British Journal Ophthalmol. 2022 May 10.
Corvi F, Bacci T, Corradetti G, Staurenghi G, Sarraf D, Freund KB, Sadda S.
Background: To evaluate whether the status of vasculature at the top of type 1 macular neovascularisation (MNV) could function as mediator of the observed protective effect against the development of complete retinal pigment epithelial and outer retinal atrophy (cRORA).
Methods: In consecutive treatment-naïve patients, the vasculature at the anterior surface of the MNV was isolated using a slab designed to extract the most superficial vascular portion of the MNV lesion showing a choriocapillaris (CC)-like structure which we termed the ‘neo-CC’. The ratio between the neo-CC area (isolated using this custom slab) and the MNV area (isolated using the standard outer retina-CC slab) at baseline and at last follow-up was evaluated.
Results: Forty-four eyes from 44 patients were included. 20 showed cRORA by the final follow-up (median 23 months), whereas 24 did not progress to atrophy (median 23.5 months). The proportion of MNV with neo-CC at the anterior surface was significantly lower in eyes which progressed to cRORA compared with those which did not. The multivariate regression showed that a lower proportion of neo-CC coverage over the MNV was associated with an increased odds for cRORA development.
Conclusions: More extensive coverage of neo-CC is associated with a lower likelihood of development of macular atrophy in eyes receiving antivascular endothelial growth factor therapy, suggesting the protective effect of a type 1 MNV may be mediated by the development of a neo-CC and may provide insights into the biological significance of MNV as a response mechanism in eyes with age-related macular degeneration.
DOI: 10.1136/bjophthalmol-2021-320047
MERLIN: Phase 3a, Multicenter, Randomized, Double-Masked Trial of Brolucizumab in Participants With nAMD and Persistent Retinal Fluid.
Ophthalmology. 2022 May 7.
Khanani AM, Brown DM, Jaffe GJ, Wykoff CC, Adiguzel E, Wong R, Meng X, Heier JS; MERLIN investigators.
Purpose: To assess the 52-week efficacy and safety of brolucizumab 6 mg administered every 4 weeks (q4w) compared to aflibercept 2 mg dosed q4w in eyes with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid.
Design: A multicenter, randomized, double-masked Phase 3a study.
Participants: Participants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment).
Intervention: Eyes were randomized (2:1) to intravitreal brolucizumab 6 mg or aflibercept 2 mg q4w up to and including Week 100.
Main Outcome Measures: The primary endpoint was analysis of noninferiority in mean best-corrected visual acuity (BCVA) change from baseline to Week 52 (margin: 4 letters). Other key endpoints included change in central subfield thickness (CST) from baseline to Week 52, fluid-free status (no intraretinal fluid [IRF] and no subretinal fluid [SRF]), and safety.
Results: At Week 52, brolucizumab was noninferior to aflibercept in BCVA change from baseline (least squares mean difference was -0.6 ETDRS letters [95% CI: -2.1, 0.9; P<0.001]). Visual stabilization or improvement (no worse than 5-letter loss in BCVA) occurred at comparable rates (82.5% brolucizumab; 82.0% aflibercept), as did the gain of ≥15, ≥10, and ≥5 letters (brolucizumab: 16.9%, 22.3%, and 35.8%, respectively; aflibercept: 17.4%, 20.2%, and 31.5%, respectively). A total of 4.8% and 1.7% of participants reported ≥15-BCVA letter loss from baseline at Week 52 in the brolucizumab and aflibercept groups, respectively. In eyes treated with brolucizumab compared to those treated with aflibercept, the CST was significantly reduced (P<0.001) and there was a significantly greater proportion of eyes that were fluid-free at Week 52 (40.4% brolucizumab vs 19.0% aflibercept; 95% CI: 13.9, 29.0; P<0.001). Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, were 9.3% (0.8% and 2.0%) for brolucizumab vs 4.5% (0% and 0%) for aflibercept, respectively.
Conclusions: Visual acuity outcomes in previously treated participants with nAMD and persistent retinal fluid receiving brolucizumab 6 mg dosed q4w were noninferior to aflibercept 2 mg dosed q4w, with superior anatomical outcomes. However, incidence of IOI, including retinal vasculitis and retinal vascular occlusion were also higher, leading to study termination.
DOI: 10.1016/j.ophtha.2022.04.028
PATIENT EXPERIENCE
nAMD: optimization of patient care and patient-oriented information with the help of an internet-based survey.
Graefes Archives for Clinical Experimental Ophthalmology. 2022 May 13.
Schmid A, Bucher F, Liczenczias E, Maslanka Figueroa S, Müller B, Agostini H.
Purpose: This survey was conducted to identify factors that influence how patients with neovascular age-related macular degeneration (nAMD) deal with their disease and information that are considered useful from a patient’s point of view.
Methods: A total of 5035 patients with nAMD living in Germany were interviewed via internet-based cross-sectional survey, where the following information was collected: personal data, disease awareness, and patients’ needs. In addition, a Quality of Life questionnaire (SF-12v2) could be completed.
Results: Out of the 5035 participants, more males than females participated (55% vs 45%), and most participants were in the age groups 76 to 85 years (37%) and 66 to 75 years (35%). Seventy-three percent of patients rated their understanding of the disease as at least sufficient, and more than two-thirds of the patients (68%) were aware that their disease needs to be controlled on a regular basis and treated on an “as needed” basis. Regarding potential risk factors for AMD, most participants were aware of age (89%), but only 39% of hereditary load and 33% of smoking as evidence-based risk factors, indicating a need for further information. The doctor remains the major source of information (93%), with internet (29%), brochures (14%), opticians (13%), or patient support groups (4%) with only limited contribution. Distance to the treatment center was identified as one of the factors, which had the greatest influence on patients’ compliance. A “treat as needed” regime turned out to be the preferred control and treatment schedule in contrast to a “fixed appointment” every 4 weeks.
Conclusion: This internet-based survey appears to be representative for nAMD patients. To increase patients’ compliance, proximity to the treatment center and a “treat as needed” regime turned out to be important factors as well as patients’ awareness of their disease. In this regard, the reported desire for more information indicates that patients’ knowledge still needs to be improved. Our results will help to further optimize patient care and patient-oriented information.
DOI: 10.1007/s00417-022-05678-7
Patients views on a new surveillance pathway involving allied non-medical staff for people with treated diabetic macular oedema and proliferative diabetic retinopathy.
Eye (Lond). 2022 May 6.
Prior L, Lois N; EMERALD Study Group.
Background/Objective: To explore acceptability by patients and health care professionals of a new surveillance pathway for people with previously treated and stable diabetic macular oedema (DMO) and/or proliferative diabetic retinopathy (PDR).
Subject/Methods: Structured discussions in 10 focus groups with patients; two with ophthalmic photographers/graders, and one with ophthalmologists, held across the UK as part of a large diagnostic accuracy study (EMERALD).
Results: The most prominent issues raised by patients concerned (i) expertise of the various professionals within clinic, (ii) quality of interactions with clinic professionals, especially the flow of information from professionals to patients, and (iii) wish to be treated holistically. Ophthalmologists suggested such issues could be best dealt with via a programme of patient education and tended to overlook deeper implications of patient concerns for the organisation of services.
Conclusion: For patients, the clinical service should not only include the identification and treatment of disease but also exchange of information, reassurance, and mitigation of anxiety. Alterations in the standard care pathway need to take account of such concerns and their implications, in addition to any assessments of ‘efficiency’ that may flow from changes in diagnostic technology, or the division of professional labour.
DOI: 10.1038/s41433-022-02050-1
NUTRITION AND LIFESTYLE
Development, implementation and evaluation of the online Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) program: The protocol for a pilot trial.
PLoS One. 2022 May 12.
Tang D, Macniven R, Bender N, Jones C, Gopinath B.
Introduction: People with age-related macular degeneration (AMD) are more likely to experience loneliness, have poorer diets and be less physically active than people without AMD. The online Movement, Interaction and Nutrition for Greater Lifestyles in the Elderly (MINGLE) program is a holistic evidence-based intervention aiming to support people with AMD by incorporating physical activity, social interaction and nutrition education components all delivered via a COVID-19-safe Zoom platform. This study will involve two phases: 1) a formative qualitative study with AMD patients to identify the barriers and facilitators to participating in the proposed MINGLE program; and 2) a 10-week pilot study to evaluate the feasibility, acceptability and preliminary efficacy of MINGLE.
Methods and Analysis: Phase 1 involves AMD patients who will be recruited from an eye clinic in Western Sydney, Australia to participate in audio-recorded semi-structured interviews. Verbatim interview transcripts will be coded using the Capability, Opportunity, Motivation and Behaviour (COM-B) model and themes established. These themes will be used as a guide to specifically tailor the proposed MINGLE program to people with AMD. Phase 2 involves 52 AMD patients who will then be recruited from the same clinic to participate in the MINGLE program. Pre-post questionnaires will be administered to intervention participants to collect information on the following variables: demographics, socioeconomic status, vision function, loneliness, quality of life (including depression), falls risk, physical activity (level), and dietary intake. The acceptability and feasibility of the MINGLE program will also be evaluated using descriptive statistics.
TRIAL REGISTRATION NUMBER: ACTRN12621000939897p.
DOI: 10.1371/journal.pone.0267581
Study is funded in part by Macular Disease Foundation Australia
RISK OF DISEASE
Impact of obstructive sleep apnea on the expression of inflammatory mediators in diabetic macular edema.
European Journal of Ophthalmology 2022 May 2.
Yang Y, Somani S.
Purpose: To determine differences in inflammatory markers expressed in diabetic macular edema (DME) patients with and without obstructive sleep apnea (OSA).
Methods: This was a prospective, cross-sectional study. Patients with treatment naive DME were enrolled in the study. They were stratified into 2 groups based on Apnea Hypopnea Index (AHI) from overnight polysomnography: OSA + (AHI ≥ 15) and OSA – (AHI<15). Multiplex immunoassay was performed for aqueous and serum cytokines including VEGF, placental growth factor (PGF), ICAM, IL2, IL3, IL6, IL8, IL10, IL17, vascular cell adhesion molecule-1 (VCAM1), monocyte attractant protein-1 (MCP1), epidermal growth factor (EGF) and platelet derived growth factor (PDGF). Statistical significance was defined as p < 0.004 using Bonferroni correction.
Results: 32 DME positive patients were enrolled in the study; of which 17 patients were OSA + and 15 OSA-. The OSA + cohort had significantly higher levels of serum EGF (p = 0.003), and trended towards higher levels of most serum cytokines including ICAM and IL6. OSA- cohort had significantly higher levels of aqueous IL17 compared to the OSA + cohort (2.97 ± 1.7 vs. 1.4 ± 0.46 pg/mL, p = 0.004). There were no significant differences in other aqueous cytokines.
Conclusions: OSA + group trended towards higher levels of most serum inflammatory markers, suggesting a greater pro-inflammatory state. However, they did not have significantly greater level of aqueous cytokines.
DOI: 10.1177/11206721221099247
Epiretinal Membrane in Patients with Diabetic Macular Edema.
Ophthalmologica. 2022 Apr 27. doi: 10.1159/000524742. Online ahead of print.
Rabina G, Hilely A, Barequet D, Cohen S, Lipin N, Mimouni M, Glick A, Barak A, Loewenstein A, Schwartz S.
PURPOSE: To compare anatomical and functional outcomes of pars plana vitrectomy (PPV) with epiretinal membrane (ERM) peeling in diabetes retinopathy (DR) patients with and without diabetic macular edema (DME). METHODS: A retrospective interventional case series of consecutive patients who underwent PPV with ERM peeling. Patients were divided into two groups: With and without preoperative DME. Visual acuity (VA) and optical coherence tomography (OCT) parameters were evaluated before surgery and during 12 months follow-up. RESULTS: A total of 354 patients underwent PPV with ERM peeling, of which 51 met the inclusion criteria. Twenty-three were diagnosed with DME and were younger (66.3±9.6 vs 73.1±8.2years, p=0.001), had longer diabetes mellitus (DM) duration (18.9±7.1 vs 14.3±10.9 years, p=0.04) and higher HbA1C% (7.6±1.4 vs. 7.1±1.3, p=0.04). VA improved from 20/105 to 20/60 Snellen (p=0.004) and central macular thickness (CMT) decreased from 469.3±64.9μm to 331.1±92.2μm (p<0.001) in the DME group and from 20/87 to 20/44 Snellen (p<0.001) and from 463.1±53.5μm to 341.3±49.5 μm (p=0.01) in the non DME group. Yearly intravitreal injections rate decreased from 5.9±2.5 to 2.9±3.0 (p<0.001) injections in the DME group. CONCLUSIONS: DME patients with ERM, experience significant improvement in VA, macular thickness and yearly intravitreal injections after PPV with ERM peeling. DME patients are younger, with longer duration of DM and higher HbA1C% levels at presentation in comparison to diabetic ERM patients without DME.
DOI: 10.1159/000524742
EARLY RESEARCH
Safety and therapeutic effects of orally administered AKST4290 in newly diagnosed neovascular age-related macular degeneration.
Retina. 2022 Feb 15.
Stewart MW, Garg S, McCaskill Newman E, Jeffords E, Konopinska J, Jackson S, Sikorski BL, Rawner ES.
Purpose: To evaluate the safety and therapeutic effects of orally administered AKST4290 (formerly BI 144807 and ALK4290) in treatment-naive patients with neovascular age-related macular degeneration (nAMD).
Methods: In this prospective, multicenter, open-label Phase 2a pilot clinical study, 30 patients with newly diagnosed nAMD self-administered AKST4290 (400 mg) orally twice daily for 6 weeks. Patients were examined weekly for safety, to measure best corrected visual acuity (BCVA), and to perform exploratory morphological assessments. The primary endpoint was the mean change in BCVA from baseline to end of treatment, and the secondary endpoint was safety. Exploratory endpoints investigated potential changes in macular morphology.
Results: Mean BCVA improved by +7.0 letters (95% CI, 2.2-11.7); 24 patients (82.8%) had stable or improved BCVA, with 6 (20.7%) gaining >= 15 letters. No patients experienced severe or serious adverse events (SAEs).
Conclusions: In this 6-week study, AKST4290 treatment was associated with improved BCVA scores in patients with treatment-naive nAMD. All adverse events (AEs) were mild or moderate in severity and no safety issues were identified. Treatment of nAMD with AKST4290 warrants further investigation in randomized, placebo-controlled trials.
DOI: 10.1097/IAE.0000000000003446
