Acta Ophthalmologica最新文献

The development of effective therapeutics for dry eye disease (DED) is challenging due to its complex pathophysiology, heterogeneous patient presentation and the significant failure rate of previous clinical development programs. This underlines the importance of the selection of appropriate endpoints for clinical trials. The presented systematic review retrospectively analyzes the endpoints used in controlled clinical trials in studies of DED. Published clinical trials in the field of DED were reviewed from 2000 to 2023 and the used clinical endpoints were recorded by type and frequency of use. All studies that met the primary keyword search across various databases (PubMed, Embase, The Cochrane Library, Web of Science and Medline) were imported into Rayyan which was used to facilitate the screening process and support the collaboration between the reviewers. 93 876 studies were found of which 33 908 remained after duplicates were removed. All abstracts were screened for eligibility independently by two reviewers. 355 articles remained for full-text review, of which 194 were included in the present systematic review. The most frequently investigated product was topical medicinal products (88 studies), followed by topical lubricants (57 studies) and nutritional supplements (22 studies). Corneal fluorescein staining (45 studies) and the ocular surface disease index (OSDI; 96 studies) were the most frequently used primary objective and subjective outcome parameters. However, a sustainable number of studies failed to show statistically significant differences between treatment and control groups, despite improvements from baseline. Our findings show that corneal fluorescein staining and OSDI are the most frequently used endpoints in clinical studies, although they frequently are not able to detect differences between the treatment and control groups. Therefore, to enhance the efficiency and reliability of DED clinical trials, a consensus on optimal outcome measures is crucial, and the exploration of novel endpoints should be prioritized. PROSPERO Registration Number: CRD42022350817.

Purpose: To compare the inflammatory response in the eye after trabeculectomy to after phacoemulsification, focusing on anterior chamber flare (AC flare) and central macular thickness (CMT).

Methods: Data from 436 participants in two randomized controlled trials were analysed. Anterior chamber flare was measured in 69 participants undergoing trabeculectomy and 367 participants undergoing phacoemulsification preoperatively. Postoperative assessments were made on day 7 in trabeculectomy participants and on day 3 in phacoemulsification participants. CMT was assessed at baseline and 3 months postoperatively in both groups and 4 weeks postoperatively for trabeculectomy participants and 3 weeks postoperatively for phacoemulsification participants.

Results: At baseline, AC flare and CMT were comparable between the groups. Early postoperatively, AC flare was 22.1 ph/ms [95% CI 19.1, 25.7] for trabeculectomy and 18.9 ph/ms [95% CI 17.8, 20.2] for phacoemulsification. Both groups significantly increased in AC flare from their baseline values, but the difference in increase between them was not significant (p = 0.46). In the trabeculectomy group, CMT showed no significant increase at 4 weeks but a significant rise of 2.3 microns from baseline to 3 months from 241 microns [95% CI 235.9, 246.1] to 243.3 microns [95% CI 237.6, 249.1] (p = 0.038). In the phacoemulsification group, CMT was significantly increased at 3 weeks and remained significantly elevated at 3 months from 242.6 microns [95% CI 240.4, 244.8] to 249.8 microns [95% CI 247.3, 252.4], increased by 7.2 microns (p < 0.0001). CMT increased significantly more after phacoemulsification compared to trabeculectomy at 3 to 4 weeks (p = 0.014) and 3 months (p < 0.0001) with respect to baseline values.

Conclusion: No significant difference in AC flare was found between trabeculectomy and phacoemulsification participants at baseline and early postoperatively. CMT did not increase at 4 weeks but increased significantly at 3 months after trabeculectomy. Phacoemulsification led to a significantly higher CMT increase at both 3 weeks and 3 months with respect to baseline compared to trabeculectomy.

Purpose: To compare bleb morphology after trabeculectomy using a visual grading system, the Indiana Bleb Appearance Grading Scale (IBAGS) and anterior segment optical coherence tomography (AS-OCT).

Methods: Fifty-seven patients who underwent trabeculectomy were included in this study. Clinical evaluations of the bleb and imaging with anterior segment OCT were conducted 12 months postoperatively. Bleb assessments were performed using a slit-lamp microscope with the IBAGS and a 3D AS-OCT CASIA2.

Results: Bleb height evaluations from IBAGS and AS-OCT measurements showed a moderate positive correlation (p = 0.03), indicating alignment between the two systems. IBAGS variables explained about 16% of the variance in IOP, with a significant negative relationship between bleb height and IOP (for each unit increase in bleb height, IOP decreased by 1.9 mmHg; p = 0.03). The overall model fit was significant for IBAGS (p = 0.03) but not for AS-OCT (p = 0.2), suggesting that IBAGS may be more relevant for predicting IOP.

Conclusion: IBAGS demonstrated a stronger association with IOP, suggesting its greater relevance in assessing trabeculectomy bleb morphology for predicting surgical success. Additionally, we found a significant correlation between bleb height measurements obtained from IBAGS and the AS-OCT system. By integrating both systems, a more comprehensive approach to monitoring bleb function can be achieved, ultimately improving the accuracy of postoperative glaucoma management.

Purpose: We lack knowledge on the potentially progressive nature of and the prevalence of complications to myopia as a characteristic trait of Stickler syndrome.

Methods: This cross-sectional study combines ophthalmic examination and medical record data on Danish patients with genetically confirmed Stickler syndrome type 1 (COL2A1) and type 2 (COL11A1). The main outcomes are axial length, spherical equivalent refraction (SER), SER over time, and myopic maculopathy category by fundus photography.

Results: The study includes 71 patients with type 1 (age: median = 29 years, IQR = 15-49 years; 44% male) and 13 with type 2 Stickler syndrome (age: median = 27 years, IQR = 9-33 years; 69% male). For type 1, the median SER was -6.00 dioptres (D) (IQR = -8.88 to -2.19 D) and -6.75. (IQR = -10.88 to -1.94) for type 2, (p = 0.52). Mean axial length was 25.99 ± 1.99 and 26.55 ± 3.45 mm, respectively (p = 0.57). SER was nonprogressive in childhood in both subtypes. Myopic maculopathy was present in 28 (43%) type 1 and five (42%) type 2 patients. The odds for higher category myopic maculopathy increased by a factor of 2.15 with each mm of axial elongation (95% CI = 1.14 to 4.04, p = 0.02) but not with age (odds ratio = 1.02 per year, 95% CI = 0.97 to 1.09, p = 0.39) in type 1.

Conclusion: We find myopia in our cohort is nonprogressive. We find no difference in axial length or refractive error between subtypes. Myopic maculopathy is common, its severity depending on axial length, not age. These findings are relevant for risk stratification of vision-threatening myopia.

Purpose: It is important for clinicians to identify patients with glaucoma at higher risk of poor adherence to topical therapy at an early stage to prescribe alternative treatments. An expert-based set of statements was developed to assist clinicians in the early identification of patients at high risk of low adherence and subsequent poorer clinical outcomes.

Methods: A two-step strategy was used. First, statements were developed by a panel of experts using data from a literature search as a starting point. Second, we measured agreement with the statements in a representative group of ophthalmologists managing patients affected by glaucoma.

Results: A total of 18 statements and consensus was reached for all. The available evidence and clinical experience have identified some subpopulations at high risk of poor adherence. These include young individuals with competing interests, being frequently away from home, multiple comorbidities and particularly when they affect joint function of the hands or cognitive abilities, being asymptomatic, and being poorly informed about the severity of the disease. The unavailability of caregivers and living alone seems to be relevant factors, particularly in older and more frail patients.

Conclusion: Taken together our results allow us to profile patients with glaucoma who will be more likely to show poor adherence to topical treatments. Moreover, the consensus statements can be used to identify patients who are unsuitable for topical drops and who would benefit more from alternative treatments.

Purpose: To evaluate long-term outcomes of anti-VEGF therapy for nAMD using the Polish Retinal Therapeutic Program Monitoring Registry.

Methods: The cohort consisted of 63 840 eyes with nAMD qualified for treatment from 2016 to 2022, with follow-up through 31 October 2023. Long-term follow-up (>5 years) was conducted for 7631 eyes. Statistical comparisons and multivariate logistic regression analysed differences between treatment failure and long-term treatment, treatment effectiveness, drug efficacy and predictive factors.

Results: The relative risk of nAMD in females was 1.45. By the last follow-up, 17 518 (48.6%) patients discontinued treatment due to patient-related factors, 7202 (20.0%) due to treatment failure, 6285 (17.4%) for other reasons and 5065 (14.0%) due to death or clinical complications. Long-term patients were significantly younger, more of them were previously treated, received fewer injections per year and had better baseline BCVA and lower CRT than the failure group. Females and previously treated patients had a higher likelihood of long-term therapy, while older age and initial ranibizumab treatment increased the risk of failure. Patients with an initial BCVA >0.4 logMAR had significantly worse BCVA outcomes, while CRT and treatment strategy showed no significant differences. Introduction of programme exclusion if treatment gap >4 months reduced long breaks, increased injection numbers, slightly lowered BCVA and had no significant effect on CRT.

Conclusion: Early visual acuity response, drug choice (aflibercept), and healthcare system modifications influence long-term success and adherence in nAMD management. While systemic changes improved continuity and injection frequency, they did not enhance visual outcomes, highlighting the need for individualized treatment strategies.

Purpose: To investigate whether primary open-angle glaucoma (POAG) is associated with an increased long-term risk of developing Alzheimer's disease, given its shared neurodegenerative features.

Methods: A 20-year longitudinal, registry-based matched cohort study was conducted using Danish national health registries from 1998 to 2018. Individuals aged 65 years or older with POAG identified by registration with the diagnostic code (ICD-10 = H40.1*) or at least four redeemed glaucoma prescriptions (ATC = S01E*) within 1 year entered the cohort. Each individual with POAG was randomly matched with five controls of the same sex and birth year. The outcome of Alzheimer's disease was defined by registration with the diagnostic code (ICD-10 = G30*, F00*). A Cox regression model adjusting for age, sex and systemic comorbidities estimated the hazard ratio (HR) for Alzheimer's disease and a Fine-Grey competing-risk model accounted for death as a competing event.

Results: The study included 61 829 individuals with POAG and 306 794 matched controls (42.63% males, 57.37% females; median age 75.22 years, IQR: 70.35-80.63). Alzheimer's disease developed in 1.61% of individuals with POAG and 1.59% of controls. POAG did not appear to increase the risk of Alzheimer's disease (adjusted HR 0.98, 95% CI: 0.93-1.03). Competing risk analyses found a slightly increased risk of Alzheimer's disease observed among men with POAG (sHR 1.12, 95% CI: 1.03-1.21), whereas no association was found among women (sHR 1.00, 95% CI: 0.94-1.07).

Conclusion: In this nationwide matched cohort study, POAG was not clearly associated with an overall increased risk of developing Alzheimer's disease over 20 years.

The Consortium for Refractive Error and Myopia (CREAM) was established in 2011, bringing together an international team of researchers studying more than 30 cohorts. Since its establishment, CREAM has played a pivotal role in research investigating the genetics of myopia and other refractive errors, serving as a key driver of progress in the field. The aim of this review is to highlight the latest advances and insights from CREAM, with a focus on research carried out in the past 5 years. We performed a literature review of journal articles authored by the CREAM consortium since the year 2020, when the last review of CREAM consortium findings was published. Key discoveries from recent CREAM studies were the identification of SIX6, CRX, PER3, PDCD6IP, MAPT, CHST6, GRHL2, USH2A, P4HTM, COL4A4 and ATM as high-confidence candidate genes associated with myopia development. Variants in enhancers and lncRNA regions were shown to have potential regulatory effects on refractive error; the DDIT4 gene was highlighted as a potential hotspot for future analyses. A polygenic risk score for predicting high myopia with an area under the curve (AUC) accuracy of 0.78 was made openly available; prediction accuracy was close to that required for clinical use. A shared genetic architecture for refractive error and axial length was confirmed. Novel findings were the identification of rare, large-effect gene variants through targeted and whole exome sequencing and the development of a polygenic risk score for predicting children at risk of developing high myopia. Large-scale multi-ancestry genome-wide association studies of the myopia endophenotypes axial length and corneal curvature doubled the number of common genetic variants known to be associated with these traits. Nevertheless, much remains to be done to fulfil the promise of myopia genetics research for improving the detection of children at above-average risk of high myopia, and the prevention and treatment of myopia.

Purpose: To assess whether atrial fibrillation (AF) is associated with an increased risk of age-related macular degeneration (AMD).

Methods: This multinational retrospective cohort study included individuals aged 50 years or older, with or without AF at baseline, from healthcare organisations across 21 countries during 2015-2020 in the TriNetX database. Participants were classified into those with and without AF, and followed for up to 5 years to observe the occurrence of AMD, including both dry and wet forms, and other cerebrovascular outcomes. The AF and non-AF groups were 1:1 propensity score-matched to balance baseline characteristics and comorbidities. Outcomes were assessed using Cox regression models and Kaplan-Meier analysis.

Results: A total of 113 974 individuals were included in the final analysis. The mean follow-up (standard deviation [SD]) is 4.09 (1.30) years in the AF group and 4.53 (0.95) years in the non-AF group. During follow-up, 1169 individuals developed AMD, 527 developed dry AMD, and 242 developed wet AMD. Compared to individuals without AF, those with AF have a significantly higher risk of developing AMD (hazard ratio [HR], 2.72; 95% confidence interval [CI], 2.42-3.11), dry AMD (HR, 2.55; 95% CI, 2.12-3.07), wet AMD (HR, 2.50; 95% CI, 1.90-3.28), and ischemic stroke (HR, 1.67; 95% CI, 1.60-1.73). Across most subpopulations, AF is consistently linked to higher risks of both dry and wet AMD.

Conclusion: Individuals with AF experience a higher risk of developing both dry and wet forms of AMD compared to individuals without AF.

Purpose: To analyse pain sensation after phototherapeutic keratectomy (PTK) using chilled eye drops or drops at room temperature during the early postoperative period.

Methods: Our randomised controlled, parallel-group study conducted in the Department of Ophthalmology, Goethe-University, Frankfurt (Main), Germany, with blinded participants and outcome assessors included patients undergoing PTK. Postoperatively, eye drops in one group were chilled and in the other group at room temperature (warm). Patients completed pain questionnaires six times on the first 3 postoperative days. Pain intensity was primarily assessed by means of the numerical rating scale (NRS) at 8 a.m. on Day 1. Secondary outcomes included pain on the visual analogue scale (VAS), sensory qualities of pain, overall pain intensity, epiphora, foreign body sensation and additional need for analgesics.

Results: Fifty-one patients were analysed in the chilled group and 49 in the warm group. Median NRS and VAS on Day 1 were 2 (range: 0-8) and 13 (0-76) in the chilled group and 1 (0-8) and 4 (0-79) in the warm group, respectively (p = 0.11 and 0.10). On Day 2, values were 2 (0-7) and 14 (0-52) in the chilled group and 2 (0-10) and 19 (0-99) in the warm group (p = 0.34 and 0.82). There was no significant difference in secondary outcomes. Additional painkillers on Day 1 were required by 29% and 18%, respectively (p = 0.23).

Conclusion: Using chilled eye drops following PTK does not reduce pain compared with eye drops at room temperature in the early postoperative period.