Acta Ophthalmologica最新文献

Purpose: Ophthalmology encompasses comprehensive medical and surgical care for patients with diverse visual system disorders, significantly impacting eye health, vision, and quality of life. European ophthalmologists undergo specialized residency training to acquire necessary competencies, emphasizing theoretical knowledge, clinical and surgical skills, and professional behaviour. The European Union of Medical Specialists (UEMS) and the European Board of Ophthalmology (EBO) advocate for competency-based medical education (CBME), standardized training frameworks, and harmonized assessments across Europe.

Methods: In 2023, a survey among European ophthalmologists demonstrated broad consensus on establishing unified training requirements. Subsequently, a Core Working Group developed European Training Requirements (ETRs) for ophthalmology, detailing curricula, subspecialty rotations, and Entrustable Professional Activities (EPAs) across a structured four-year residency.

Results: These ETRs, formally approved by UEMS in October 2024, incorporate simulation-based training, workplace-based assessments (WPBA), and innovative evaluation methods such as electronic portfolios. Certification as a European Specialist in Ophthalmology involves passing rigorous summative assessments, including the European Board of Ophthalmology Diploma (EBOD) examination. Training institutions must offer substantial clinical exposure, robust infrastructure, and comprehensive educational resources. Faculty support, continuous quality assurance, regular audits, and clinical governance frameworks are essential.

Conclusion: The ETRs also highlight the importance of interprofessional collaboration and encourage subspecialty expansion in emerging areas like ophthalmic oncology and global ophthalmology. Designed as a dynamic, "living document," the ETRs will evolve with scientific and technological advancements, supporting high-quality ophthalmic education and practice while respecting national diversity and sovereignty.

Purpose: To examine the incidence of pars plana vitrectomy (PPV) for full-thickness macular hole (FTMH), epiretinal membrane (ERM) and floaters over time and across regions in Denmark.

Methods: This nationwide registry-based study included all patients undergoing PPV for FTMH, ERM, or floaters in Denmark from 2010 to 2023. Crude and age-standardized incidence rates were calculated using Poisson regression, stratified by sex, age, region and year.

Results: Among 11 693 patients undergoing PPV, the median age was 71 years (IQR, 66-76) and 83% (9744/11 693) were pseudophakic at surgery. Overall incidence rates per 100 000 person-years were 5.7 (95% CI, 5.5-5.8) for FTMH, 7.1 (6.9-7.2) for ERM, and 1.8 (1.7-1.9) for floaters. FTMH surgery was more common in females across all ages, while ERM and floater surgeries were more frequent in males aged ≥60 years. From 2010-2012 to 2021-2023, the incidence increased for FTMH and ERM, while floater surgery declined in females and remained stable in males. Regional variation was observed for all indications, most notably for ERM.

Conclusion: The incidence of PPV for both FTMH and ERM rose significantly from 2010 to 2023. The regional variation in FTMH may indicate undertreatment, while differences in ERM and floater surgeries reflect the absence of standardized guidelines for ERM and floater surgery, underscoring the need for national guidelines to ensure equitable ophthalmic care.

Purpose: This systematic review aims to evaluate and synthesize the existing literature on the interventions used for submacular haemorrhage (SMH), highlighting the controversies and differences in clinical practice.

Method: A systematic review was conducted following the PRISMA guidelines. A comprehensive search was performed across multiple databases, including MEDLINE, EMBASE and Cochrane Library, to identify studies on SMH treatment. Inclusion criteria encompassed randomized controlled trials, cohort studies and case series that focused on different therapeutic interventions. Data on functional outcomes, efficacy and safety of the interventions were extracted and analysed.

Results: The review included 150 studies, of which 38 were included in the network meta-analysis. The analysis of best corrected visual acuity (BCVA) Included 26 studies, 20 interventions and 2125 eyes. Heterogeneity was moderate (I² = 28.9%). Non-vitrectomy therapies showed better BCVA outcomes and fewer complications (e.g. retinal detachment, vitreous haemorrhage), while vitrectomy-based treatments achieved better anatomical results. According to P-score ranking, "Observation" had the highest probability of being most effective for BCVA (P-score = 0.8051), followed by anti-VEGF monotherapy and non-vitrectomy combinations. However, this result should be interpreted cautiously, as the "Observation" group was based on only two studies (26 eyes) with clinical heterogeneity. No publication bias was detected (Egger's test p = 0.582).

Conclusions: There is no consensus on a standard evidence-based treatment for SMH. Minimally invasive strategies are promising, but factors such as timing, lesion size and anti-VEGF use remain critical. Further large-scale randomised trials are needed to define optimal management.

Purpose: To estimate the risk of rhegmatogenous retinal detachment (RRD) following pars plana vitrectomy (PPV) for full-thickness macular hole (FTMH) or epiretinal membrane (ERM) in pseudophakic eyes.

Methods: We conducted a nationwide Danish registry-based cohort study from 2010 to 2023. Eyes entered the study at phacoemulsification surgery (age ≥ 50) and were followed until outcome (RRD), exposure (PPV), or censoring (death, end of study, or competing events). PPV was analysed as a time-dependent exposure occurring after phacoemulsification surgery, with eyes considered exposed from the time of PPV onwards.

Results: A total of 680 858 eyes were included. Median follow-up was 4.8 years (IQR, 2.5-7.9) after phacoemulsification and 5.0 years (2.5-7.9) after PPV, with a median interval of 76 days (39-328) between procedures. The 1-year cumulative incidence of RRD after PPV for FTMH was 0.62% (95% CI, 0.40-0.93), significantly higher in males. For ERM, it was 0.43% (0.27-0.66), with no sex difference. Compared to phacoemulsification alone, the hazard ratio (HR) for RRD was increased in males operated on for FTMH (HR 2.60; 1.62-4.17) and in females operated on for ERM (HR 1.93; 1.07-3.49). Among those who remained event-free 1 year postoperatively, no significant difference in RRD risk was observed between groups.

Conclusions: PPV in pseudophakic eyes has a low risk of RRD but higher than that of phacoemulsification surgery after the first year, with notable sex variations for FTMH. Among those who remained event-free 1 year postoperative, no difference in RRD risk was observed between PPV and phacoemulsification surgery.

Background: Intraocular lenses (IOLs) employing extending focus and multifocality technologies are becoming increasingly popular in cataract and lens surgeries. However, research on the preoperative factors affecting subjective surgical outcomes remains elusive.

Methods: 188 emmetropic bilaterally operated patients were analysed. We compared the outcomes of non-diffractive enhanced monofocal Tecnis Eyhance (N = 86) and non-diffractive extended depth-of-focus AcrySof Vivity (N = 102) IOLs in terms of visual acuities, dysphotopsia (graded from 0 to 100) and spectacle-independent visual function index (VF)-14 questionnaire scores. Next, we analysed correlations between the baseline ocular parameters and refractive outcomes with the dysphotopsia and VF-14 scores. Multivariable linear regression analyses were adjusted for patient age, sex and IOL type.

Results: Acrysof Vivity provided better uncorrected near (0.19 ± 0.12 vs. 0.27 ± 0.13 LogMAR units, p < 0.001) and uncorrected intermediate visual acuities (0.11 ± 0.10 vs. 0.15 ± 0.10 LogMAR units, p = 0.033), and better spectacle-independent VF-14 scores (93.2 ± 5.7 vs. 80.9 ± 12.2; p < 0.001), but higher glare scores (8.60 ± 17.2 vs. 2.16 ± 5.74; p = 0.035) compared to Tecnis Eyhance. Photopic (r = 0.283; B 9.39, 95% CI 4.66 to 14.1; p = 0.006) and mesopic pupil size (r = 0.263; B 6.35, 95% CI 2.91 to 9.79; p = 0.045) were associated with overall dysphotopsia scores. The axial length of the eye (r = -0.374; B -3.47, 95% CI -4.73 to -2.22; p < 0.001), total corneal irregular astigmatism (r = -0.388; B -27.3, 95% CI -39.2 to -15.5; p < 0.001), and corneal higher-order aberrations (r = -0.219; B -14.3, 95% CI -26.5 to -1.98; p = 0.023) inversely associated with VF-14 scores. Angles kappa and alpha were not associated with the levels of dysphotopsia or VF-14 scores.

Conclusions: Patient-related factors, including corneal irregularity, pupil size and axial length of the eye, may explain the high patient-reported outcome measures variability after the implantation of non-diffractive extending focus IOLs.

Purpose: To determine the repeatability of retinal blood vessel parameters (from proprietary software and the raw vessel data) measured in vivo in healthy individuals at rest, during and post flicker light (FL) provocation using a standardised protocol.

Methods: We recorded the diameters of one retinal artery and one vein in each of 33 healthy adult volunteers at rest, during and post FL provocation on two occasions using the Retinal Vessel Analyser (RVA). Repeat visits were scheduled at three different timepoints: (1) within 30 mins on the same day, (2) within a fortnight and (3) within a month (n = 11, each). All participants underwent intraocular and systemic blood pressure assessment to ensure these were comparable between visits.

Results: Retinal vessel parameters at rest, during and post FL provocation were comparable between all pairs of visits for all three groups. Repeatability between visits was assessed using Bland-Altman Analyses and Intraclass Correlation Coefficients (ICCs). Maximum dilation for arteries and veins and maximum constriction for arteries due to FL provocation computed from raw dilation data showed better repeatability than that generated by the RVA software. Time to reach maximum dilation in arteries and veins and maximum constriction in arteries was on average comparable but least repeatable between visits.

Conclusions: Retinal vessel parameters computed from the raw RVA data may be superior in quality to the output from the proprietary software because the latter uses fixed narrow time-windows to determine the parameters. Variance within healthy controls, pathology groups and repeatability parameters alongside systemic haemodynamic parameters should be considered when utilising dynamic retinal vascular parameters as study endpoints.

Purpose: Retinal Pigment Epithelial (RPE) cells perform critical functions in the visual cycle. Their melanin pigmentation, which is organized into specialized compartments - melanosomes, is highly critical for proper vision. A chemical method to induce pigmentation in a non-pigmented model of ARPE-19 cells was applied using L-DOPA as a repurposed drug from the current treatment of Parkinson's disease.

Methods: L-DOPA was optimized for its toxic effect on ARPE-19 cells along with pigmentation development. Gene expression and immunocytochemistry confirmed upregulation of melanogenesis-related genes and proteins. Melanosomes were characterized by TEM.

Results: We found 1000 μM L-DOPA to induce pigmentation of ARPE-19 cells by Day 3, and achieve full pigmentation by Day 5. By Day 5, L-DOPA at 1000 μM induced mitochondrial and nuclear DNA damage. However, the gene expression of RPE-specific markers (tyrosinase, TYRP1, CRALBP, PEDF) was significantly different in L-DOPA-treated ARPE-19 cells compared to non-treated ones. Positive expression for Tyrosinase enzyme was confirmed by ICC on both Day 3 and Day 5 of L-DOPA treatment. Transmission electron microscopy showed the de novo melanosome formation with ultrastructural features of various stages of maturity (Stage I to IV), apical-basal polarity and melanosome localization on the apical side of the L-DOPA-treated ARPE-19 cells.

Conclusion: Our study showed that L-DOPA treatment could induce de novo melanosome formation in amelanotic RPEs. We propose a newer approach of developing an ex vivo model for de novo pigmentation of RPE cells with cell-specific modification and culture condition optimization.

Purpose: Immune checkpoint inhibitors (ICI) have revolutionised the treatment of several malignancies. However, the results of ICI therapy remain unsatisfactory in metastatic uveal melanoma (UM). We analysed the expression of PD1, PD-L1, T-cell and macrophage markers in a set of matched primary and metastatic UM in an attempt to better understand the low effectiveness of ICI in metastatic UM.

Methods: Thirty-two samples (19 metastases and 13 primary UM) were stained for PD-L1, PD1, CD3, CD4, CD8, CD68, CD163, HLA class I and BAP1. T-cell markers were scored quantitatively, while PD-L1, CD68, CD163 and BAP1 were scored semiquantitatively. The immunohistochemical (IHC) scores were compared between all primary and metastatic UM samples and between matched cases.

Results: Both the general and the matched analyses revealed that the IHC scores for PD-L1 expression on tumour cells were lower in metastatic UM than in primary UM. Conversely, T-cell markers, including PD1, were significantly higher in UM metastases than primary UM, while macrophages did not show a difference. Metastases with a low HLA Class I expression lacked PD-L1 and PD1 expression. BAP-1 loss was associated with increased lymphocytic infiltration.

Conclusions: While UM metastases had higher lymphocytic infiltrates than primary UM, PD-L1 showed a lower expression in metastases. We believe that the low effectiveness of ICI in the treatment of metastatic UM may be partly explained by the low PD-L1 expression. We propose that primary tumours may be more responsive to ICI therapy than metastases and could be targeted in a (neo)adjuvant setting for patients at high risk of developing metastases.