Acta Ophthalmologica最新文献

Purpose: This study evaluates whether mesopic microperimetry (MMP) provides a more robust measure of retinal function compared to visual acuity (VA) in age-related macular degeneration (AMD) clinical trials, with a focus on optimal analysis strategies.

Method: Fellow-eyes of unilateral neovascular AMD were prospectively studied. Presenting VA was measured. The Macular Integrity Assessment Microperimeter (MAIA) was used with a 4 to 2 staircase strategy with a 10° diameter grid containing 37 loci. Three analysis strategies were calculated: the mean of 37 sensitivity thresholds (MS), the per cent reduced threshold (PRT), and the log-transformed candela mean (MS cd log). Sample size requirements were calculated for 12- and 24-month follow-ups using a paired one-sided T-test (α = 0.05, power = 0.80).

Results: N = 123 were analysed (82 (65.5%) females; mean age 74.2 (7.8) years). Ranked high to low, the required sample size at 12 months was: MS (n = 51), MS cd log (n = 52), PRT (n = 139), and VA (n = 203). Similar trends were seen at 24 months, with MS requiring the smallest sample size (n = 85) and VA the largest (n = 1673).

Conclusion: All MMP analysis strategies outperformed VA, and MS required the least number of patients to show significant changes. This trend was consistent for both 12 and 24 months. These findings provide strong statistical arguments for the use of MMP in longitudinal within-subjects clinical trials and suggest that averaging decibels is optimal.

Purpose: To define the curriculum content for two interactive learning courses on age-related macular degeneration (AMD): (1) an advanced course tailored for general ophthalmologists and (2) a basic course for non-ophthalmologist healthcare staff. This initiative aims to establish a national consensus on the educational framework for AMD management among general ophthalmologists in Denmark.

Methods: We conducted a three-round Delphi study. The Delphi panel consisted of 33 ophthalmologists (28 retinal specialists from Denmark and five internationally recognized retinal specialists), eight non-ophthalmologist healthcare staff (six optometrists, one ophthalmic nurse and one clinic assistant) with experience in managing patients with AMD. To ensure national representation, we recruited panel participants from all five Danish regions.

Results: Response rates were 85%, 73% and 71% for Delphi rounds 1, 2 and 3, respectively. In the first round, participants suggested a total of 390 potential curriculum components and learning goals: 211 components for the advanced course and 179 for the basic course. After the third round, the panel reached consensus on an AMD curriculum, which included 46 topics for the advanced course (e.g., OCT interpretation: signs of disease activity versus atrophic changes) and 15 topics for the basic course (e.g., visual requirements for driving).

Conclusion: This study reached consensus on the curricula for courses on AMD for general ophthalmologists and non-ophthalmologist healthcare staff. This forms the basis for developing instructional, virtual, interactive courses that can support the development and maintenance of competencies related to AMD, both in Denmark and abroad.

Purpose: Myopia is a growing concern in children worldwide, leading to significant visual impairments. This study investigates the efficacy of plano spectacle lenses with lenslets in preventing the onset of myopia in pre-myopic children. This study aims to contribute to the development of evidence-based strategies for myopia prevention by assessing compliance, efficacy and safety of plano spectacle lenses with lenslets.

Methods: This randomized controlled trial involves 388 pre-myopic children aged 6-9 years. Participants are randomly assigned to either the intervention group, using plano spectacle lenses with lenslets for at least 8 h daily with smart frames recording wearing time, or the control group, which receives no intervention. The primary outcome is the 1-year cumulative incidence of myopia. Secondary outcomes include changes in spherical equivalent under cycloplegia, axial length, choroidal thickness, visual acuity and accommodation function over the study period. Statistical analyses, including chi-squared tests and t-tests, will evaluate these outcomes.

Discussion: This study will offer valuable insights into the use of plano spectacle lenses with lenslets in slowing down the progression to myopia in children at risk. Findings are expected to inform clinical practices and shape guidelines for myopia prevention strategies among the paediatric population.

Trial registration: NCT06860737.

Objective: To assess the prevalence and associations of the detectability of the three-layer sign (TLS) in a general population, including individuals with age-related macular degeneration (AMD) or without any retinal disease.

Methods: Using OCT images running horizontally through the foveola of participants of the population-based Beijing Eye Study, we assessed the TLS detectability. We defined the TLS as the visibility of the ellipsoid zone (EZ), interdigitation zone and retinal pigment epithelium (RPE)/Bruch's membrane line as separate units in the foveola on optical coherence tomographic (OCT) images.

Results: The study included 1566 eyes (age: 65.3 ± 9.8 years; axial length: 23.01 ± 0.93 mm; range: 19.90 mm-28.93 mm), randomly selected within each group of normal eyes (n = 592; 37.8%), eyes with early AMD (n = 700; 44.7%), intermediate AMD (n = 267; 17.0%), and late AMD (n = 7; 0.4%). In the normal group, TLS prevalence decreased with older age (OR: 0.93; p < 0.001), declining from 217/265 (81.9%) in the 50-59 years age group to 57/126 (45.2%) in individuals aged 70+ years. In the whole study cohort, TLS prevalence decreased (p < 0.001) from 389/592 (65.7%) in the normal group to 334/700 (47.7%), 66/267 (24.7%) and 0/7 (0%) in early AMD, intermediate AMD and late AMD, respectively. In multivariable analysis, higher TLS prevalence was associated with younger age (OR: 0.92; p < 0.001), female sex (OR: 1.65; p < 0.001), lower AMD stage (OR: 0.51; p < 0.001), better best-corrected visual acuity (OR: 0.42; p = 0.03), and lower prevalence of a flat retinal pigment epithelium elevation (OR: 0.68; p = 0.04).

Conclusions: The foveal TLS may be taken as a qualitative sign of the intactness of the deep layers of the fovea, with its prevalence decreasing with older age, higher AMD stage and worse best-corrected visual acuity.

Purpose: To investigate the association between best-corrected visual acuity (BCVA) and quantitative macular fluid volumes, compared to central subfield thickness (CST) in treatment-naïve and previously treated patients with active neovascular age-related macular degeneration (nAMD).

Methods and analysis: Baseline data were collected from 290 eyes of 290 participants consecutively enrolled in a prospective, randomized phase III clinical trial. Intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED) volumes were quantified and localized using an MDR-certified AI algorithm (Fluid Monitor, RetInSight). Fluid volumes and CST were included in linear regression models for comparison.

Results: Significantly greater IRF volumes within each macular region were observed in treatment-naïve patients, whereas larger PED volumes contributed to higher CST values in pretreated patients. In both subgroups, the largest proportion of BCVA variance could be explained by measuring IRF and SRF volumes within the entire 6-mm area (adjusted R² = 0.140 and 0.225, respectively). In pre-treated eyes, CST explained only half as much BCVA variance as the 6-mm fluid model, and the model's fit was even poorer when compared to the CST model in the treatment-naïve subgroup (adjusted R² = 0.078 vs. 0.198).

Conclusion: The examination of IRF and SRF volumes significantly impacts BCVA in nAMD. The weaker association of CST highlights its limitations as a parameter of disease activity. These findings emphasize the necessity of distinct fluid volume quantification as a relevant surrogate for visual function loss or benefit in nAMD, with particular emphasis on treatment duration and fluid in regions beyond the central 1-mm.

Purpose: This report evaluates the association of three distinct leakage patterns of choroidal vascular hyperpermeability (CVH) on indocyanine green angiography (ICGA), previously correlated with disease chronicity, with retinal sensitivity measured by microperimetry in central serous chorioretinopathy (CSC): unifocal indistinct signs of hyperpermeability (uni-FISH), multifocal (multi-FISH), and diffuse (DISH).

Methods: The CERTAIN study is a retrospective analysis of consecutive CSC patients referred to a tertiary centre between 01/09/2021 and 30/11/2022. Patients underwent ultra-widefield (UWF) and 55° ICGA plus comprehensive multimodal imaging, including microperimetry. Two independent graders assessed CVH patterns on UWF and 55° ICGA. In case of disagreement, a third grader adjudicated. Eyes with CVH and mesopic microperimetry data were included.

Results: In total, 154 eyes from 91 CSC patients were included. On UWF ICGA, DISH showed lower macular sensitivity than the uni-FISH reference (-2.61 dB, p = 0.047). Sensitivity was also lower (-2.24 dB, p = 0.03) when comparing DISH to a combined uni- and multi-FISH group (FISH). On 55° ICGA, DISH again showed lower sensitivity versus uni-FISH (-3.13 dB, p = 0.01) and the FISH group (-2.82 dB, p = 0.010).

Conclusions: The CVH patterns of uni-FISH, multi-FISH, and DISH demonstrate a marked association with levels of retinal sensitivity in CSC patients, particularly macular sensitivity, which is lower in DISH compared to (uni-)FISH. Our findings highlight the potential role of ICGA patterns in assessing disease severity and functional prognostication.

Purpose: Diabetic retinopathy (DR) is a leading cause of vision loss in middle-aged adults globally. Although artificial intelligence (AI)-based screening tools like IDx-DR (classification) and Thirona RetCAD (regression) have shown high sensitivity in controlled settings, real-world screening faces challenges due to missing or low-quality images and inadequate adaptation to local healthcare needs. The objective was to compare the performance of two AI-based DR screening algorithms (IDx-DR and RetCAD) that analyse non-mydriatic images, against ophthalmologists' mydriatic fundoscopy with image analysis and the impact of customized referral threshold modification ('Greifswald modification') on screening outcomes.

Methods: This one-centre observational study included 1716 patients with diabetes mellitus (Clinical Trials Register: DRKS00035967). Sensitivity, specificity, the proportion of ungradable images and the reduction in ophthalmologic evaluations were assessed. Customized referral threshold modification was conducted using the Youden Index.

Results: In 98 patients (5.7%), no images could be acquired, and 35 patients (2.1%) had incomplete image sets for IDx-DR. IDx-DR rejected 438 patients (25.5%) due to image quality, while RetCAD flagged 134 eyes from 120 patients (6.9%) but provided output for all. Among analysable images, sensitivities ranged from 70.4% (RetCAD) to 93.6% (RetCAD with Greifswald modification). Including all patients reduced sensitivity from 52.7% (IDx-DR) to 79.9% (RetCAD with Greifswald modification). AI screening reduced ophthalmologic exam needs by 47.5% to 78.5%.

Conclusions: Real-world DR screening performance of AI algorithms, when including non-analysable patients, can be substantially lower than in controlled studies. The use of regression algorithms enabled the customization of referral thresholds, improving screening accuracy and reducing the clinical burden.

Purpose: This study aimed to investigate the prevalence, healthcare resource utilization (HCRU) and associated costs of myopia in Germany, comparing mild/moderate and high myopia across various age groups using real-world data.

Methods: A retrospective cross-sectional study was conducted using data from the WIG2 benchmark database. Patients with a diagnosis of myopia (ICD-10-GM H52.1) were categorized into mild/moderate or high myopia. The study population was stratified into preschool (0-5 years), primary school (6-9 years), secondary school (10-17 years), adult (18-59 years), elderly (60-75 years) and very old (>75 years) age groups. Prevalence trends were evaluated across paediatric and adolescent subpopulations. Propensity score matching was applied to balance group differences. HCRU and associated costs were analysed for each cohort.

Results: Between 2018 and 2022, mild/moderate myopia consistently exhibited higher prevalence across all age groups compared to high myopia. Prevalence of both myopia types increased significantly with age, particularly in females, with mild/moderate myopia reaching 19.86% (95% CI 19.08-20.66) at age 17, compared to 14.00% (95% CI 13.37-14.67) in males. In 2022, individuals with high myopia had significantly higher ophthalmic HCRU and associated costs compared to those with mild/moderate myopia. The economic burden was notably higher in older age groups, with increased hospitalizations and outpatient visits. High myopia incurred higher costs across all age groups, with the largest difference in the very old cohort (€234.20).

Conclusion: This study highlights the significant clinical and economic burden of high myopia in Germany. Targeted interventions are needed to manage myopia progression and reduce healthcare costs, particularly in ageing individuals.

Purpose: To evaluate visual, anatomical and safety outcomes of aflibercept 8 mg in previously treated patients with neovascular age-related macular degeneration (nAMD).

Methods: This retrospective study included nAMD patients switched to aflibercept 8 mg from prior anti-VEGF therapies at Sahlgrenska University Hospital between February 2024 and February 2025. Data on best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) height, fluid status, treatment intervals, time to fluid recurrence and adverse events were collected.

Results: 181 eyes (167 patients; mean age 80.4 ± 8.5 years; 67.7% female) were included, with a median follow-up of 12.9 weeks (range 4.1-48.1). A total of 415 injections were administered (mean 2.1 ± 1.5 per eye). BCVA remained stable (baseline 0.46 ± 0.31 logMAR; post-treatment 0.47 ± 0.37 logMAR; p = 0.18). CRT decreased significantly (-19.5 ± 47.2 μm; p < 0.001), as did PED height (-37.4 ± 68.4 μm; p < 0.001). Intraretinal fluid prevalence decreased from 34.3% to 19.3% (p < 0.001) and subretinal fluid from 53.0% to 33.7% (p < 0.001). The median maximal dry interval achieved was nine weeks, and analysis of interval extension showed a statistically significant mean increase of 1.27 ± 4.24 weeks overall (p = 0.0009), particularly in eyes dry at baseline. The median time to fluid recurrence among those with reactivation was ten weeks. Higher baseline CRT predicted greater CRT reduction (-44.1 μm per 100 μm increase; p < 0.001) but shorter dry intervals. Safety was favourable, with one case (0.6% per eye; 0.2% per injection) of mild anterior uveitis and no cases of intraocular pressure elevation.

Conclusions: Switching to aflibercept 8 mg led to stable vision, significant anatomical improvements, extended treatment intervals and a favourable short-term safety profile. Longer follow-up is warranted.

Congenital aniridia is a rare ocular disorder affecting the majority of eye structures and can be associated with systemic manifestations. The main visible phenotypic characteristic is the partial or complete absence of the iris; however, foveal hypoplasia is a more frequent and reliable clinical sign. Other ocular comorbidities are associated with the disease, such as cataract, keratopathy and optic nerve hypoplasia. Mutation in the PAX6 gene is the most common cause of congenital aniridia, but other causative mutations exist. The main ocular symptoms experienced by those with congenital aniridia are photophobia, glare, low visual acuity, dryness/irritation of the ocular surface and nystagmus. Management and follow-up of patients with congenital aniridia can be challenging due to the lack of effective therapeutic options and the complexity of ocular manifestations and outcomes. These guidelines for the diagnosis, management and care of congenital aniridia have been developed at the European level, thanks to ANIRIDIA-NET, based on a review of the scientific literature on clinical and molecular characterization, therapeutic options as well as non-medical approaches.