Incidence and Risk Factors of Second Eye Involvement in Myopic Macular Neovascularization

Purpose: To report the cumulative incidence and risk factors of second eye involvement after diagnosis of myopic macular neovascularization (MNV) in the first eye. Design: Retrospective analysis of longitudinal data from a tertiary hospital in the Netherlands. Participants:Patients with high myopia (spherical equivalent [SE] ≤ − 6 diopters [D]), of European ethnicity, who were diagnosed with active MNV lesion in 1 eye between 2005 and 2018. Fellow eyes were free of MNV or macular atrophy at baseline, and data were collected on the SE, axial length, and presence of diffuse or patchy chorioretinal atrophy and lacquer cracks.Methods:Incidence rate and 2-, 5-, and 10-year cumulative incidences were calculated; hazard ratios (HRs) of second eye involvement were analyzed for potential risk factors using Cox proportional hazard models. Main outcomes measures: Incidence of second eye involvement after onset of myopic MNV in the first eye. Results: We included 88 patients over a period of 13 years with a mean age of 58 ± 15 years, mean axial length of 30 ± 1.7 mm and SE −14 ± 4 D at baseline. Twenty-four fellow eyes (27%) developed a myopic MNV during follow-up. This resulted in an incidence rate of 4.6 (95% confidence interval [CI], 2.9–6.7) per 100 person-years and a cumulative incidence of 8%, 21%, and 38% at 2, 5, and 10 years, respectively. Mean time until MNV development in the fellow eye was 48 ± 37 months. Patients aged &lt; 40 years at the initial presentation had a 3.8 times higher risk of bilateral myopic MNV (HR, 3.8; 95% CI, 1.65–8.69; P = 0.002). The presence of lacquer cracks in the second eye seemed to increase risk, but this did not reach statistical significance (HR, 2.25; 95% CI, 0.94–5.39; P = 0.07). Conclusions: Our study of high myopes of European descent shows very similar incidence rates for second eye myopic MNV compared with Asian studies. Our findings substantiate the importance for clinicians to monitor closely and create awareness, especially in younger patients. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article.</p

Uncertainty-aware multiple-instance learning for reliable classification:Application to optical coherence tomography

Deep learning classification models for medical image analysis often perform well on data from scanners that were used to acquire the training data. However, when these models are applied to data from different vendors, their performance tends to drop substantially. Artifacts that only occur within scans from specific scanners are major causes of this poor generalizability. We aimed to enhance the reliability of deep learning classification models using a novel method called Uncertainty-Based Instance eXclusion (UBIX). UBIX is an inference-time module that can be employed in multiple-instance learning (MIL) settings. MIL is a paradigm in which instances (generally crops or slices) of a bag (generally an image) contribute towards a bag-level output. Instead of assuming equal contribution of all instances to the bag-level output, UBIX detects instances corrupted due to local artifacts on-the-fly using uncertainty estimation, reducing or fully ignoring their contributions before MIL pooling. In our experiments, instances are 2D slices and bags are volumetric images, but alternative definitions are also possible. Although UBIX is generally applicable to diverse classification tasks, we focused on the staging of age-related macular degeneration in optical coherence tomography. Our models were trained on data from a single scanner and tested on external datasets from different vendors, which included vendor-specific artifacts. UBIX showed reliable behavior, with a slight decrease in performance (a decrease of the quadratic weighted kappa (κw) from 0.861 to 0.708), when applied to images from different vendors containing artifacts; while a state-of-the-art 3D neural network without UBIX suffered from a significant detriment of performance (κw from 0.852 to 0.084) on the same test set. We showed that instances with unseen artifacts can be identified with OOD detection. UBIX can reduce their contribution to the bag-level predictions, improving reliability without retraining on new data. This potentially increases the applicability of artificial intelligence models to data from other scanners than the ones for which they were developed. The source code for UBIX, including trained model weights, is publicly available through https://github.com/qurAI-amsterdam/ubix-for-reliable-classification.</p

Genetic Risk in Families with Age-Related Macular Degeneration

PURPOSE: To determine the contribution of common and rare genetic risk variants in families with age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS: A family cohort (355 affected and 342 unaffected family members from 144 families with AMD) and an unrelated case-control cohort (1078 patients, 952 controls), recruited from the European Genetic Database. METHODS: Genetic data of both cohorts were filtered for carriership of rare genetic variants in the coding and splice-site regions of the complement factor H (CFH) and complement factor I (CFI) genes, and 52 AMD-associated variants were extracted for calculation of genetic risk scores (GRS). To compare GRSs between familial and nonfamilial rare CFH and CFI variant carriers and noncarriers and between AMD disease stages, we performed a 2-way analysis of variance, with Bonferroni correction for multiple testing. Within families with AMD carrying rare CFH and CFI variants, we analyzed segregation patterns by calculating the proportion of affected among carriers. MAIN OUTCOME MEASURES: GRSs and segregation of rare CFH and CFI variants. RESULTS: We observed higher GRSs in familial versus nonfamilial individuals without rare CFH and CFI variants: mean GRS, 1.76 (standard error [SE], 0.08) versus 0.83 (SE, 0.03; P < 0.001). In 51 of 144 families (35.4%), rare CFH and CFI variants were identified. Within the AMD family cohort, carriers of rare CFH and CFI variants showed lower GRSs compared with noncarriers (mean GRS, 1.05 [SE, 0.23] vs. 1.76 [SE, 0.08]; P = 0.02). The proportion of affected family members with a high GRS was 57.3% (176/307). Of the affected family members with a low or intermediate GRS, 40.0% carried rare CFH or CFI variants. Among carriers of 11 rare CFH or CFI variants, the proportion affected by AMD was more than 75%. CONCLUSIONS: Genetic risk in families with AMD often is attributed to high GRSs based on common variants. However, in part of the families with a low or intermediate GRS, rare CFH and CFI variants contributed to disease development. We recommend computing GRSs and sequencing the CFH and CFI genes in families with AMD, in particular in the light of ongoing gene-specific clinical trials

Eye Size and Shape in Relation to Refractive Error in Children:A Magnetic Resonance Imaging Study

Purpose: The purpose of this study was to determine the association between eye shape and volume measured with magnetic resonance imaging (MRI) and optical biometry and with spherical equivalent (SE) in children. Methods: For this study, there were 3637 10-year-old children from a population-based birth-cohort study that underwent optical biometry (IOL-master 500) and T2-weighted MRI scanning (height, width, and volume). Cycloplegic refractive error was determined by automated refraction. The MRI images of the eyes were segmented using an automated algorithm combining atlas registration with voxel classification. Associations among optical biometry, anthropometry, MRI measurements, and RE were tested using Pearson correlation. Differences between refractive error groups were tested using ANOVA. Results: The mean volume of the posterior segment was 6350 (±680) mm3. Myopic eyes (SE ≤ -0.5 diopters [D]) had 470 mm3 (P &lt; 0.001) and 970 mm3 (P &lt; 0.001) larger posterior segment volume than emmetropic and hyperopic eyes (SE ≥ +2.0D), respectively. The majority of eyes (77.1%) had an oblate shape, but 47.4% of myopic eyes had a prolate shape versus 3.9% of hyperopic eyes. The correlation between SE and MRI-derived posterior segment length (r -0.51, P &lt; 0.001) was stronger than the correlation with height (r -0.30, P &lt; 0.001) or width of the eye (r -0.10, P &lt; 0.001). Conclusions: In this study, eye shape at 10 years of age was predominantly oblate, even in eyes with myopia. Of all MRI measurements, posterior segment length was most prominently associated with SE. Whether eye shape predicts future myopia development or progression should be investigated in longitudinal studies.</p

Eye Size and Shape in Relation to Refractive Error in Children:A Magnetic Resonance Imaging Study

Purpose: The purpose of this study was to determine the association between eye shape and volume measured with magnetic resonance imaging (MRI) and optical biometry and with spherical equivalent (SE) in children. Methods: For this study, there were 3637 10-year-old children from a population-based birth-cohort study that underwent optical biometry (IOL-master 500) and T2-weighted MRI scanning (height, width, and volume). Cycloplegic refractive error was determined by automated refraction. The MRI images of the eyes were segmented using an automated algorithm combining atlas registration with voxel classification. Associations among optical biometry, anthropometry, MRI measurements, and RE were tested using Pearson correlation. Differences between refractive error groups were tested using ANOVA. Results: The mean volume of the posterior segment was 6350 (±680) mm3. Myopic eyes (SE ≤ -0.5 diopters [D]) had 470 mm3 (P &lt; 0.001) and 970 mm3 (P &lt; 0.001) larger posterior segment volume than emmetropic and hyperopic eyes (SE ≥ +2.0D), respectively. The majority of eyes (77.1%) had an oblate shape, but 47.4% of myopic eyes had a prolate shape versus 3.9% of hyperopic eyes. The correlation between SE and MRI-derived posterior segment length (r -0.51, P &lt; 0.001) was stronger than the correlation with height (r -0.30, P &lt; 0.001) or width of the eye (r -0.10, P &lt; 0.001). Conclusions: In this study, eye shape at 10 years of age was predominantly oblate, even in eyes with myopia. Of all MRI measurements, posterior segment length was most prominently associated with SE. Whether eye shape predicts future myopia development or progression should be investigated in longitudinal studies.</p

A view from the clinic – Perspectives from Dutch patients and professionals on high myopia care

Purpose: To understand and compare perspectives of patients and professionals on current ophthalmologic care for high myopia, and to identify challenges and future opportunities. Methods: Self-reported data were collected through two online questionnaires. Patient perspective was obtained from highly myopic members of a patient organisation based in the Netherlands using a 17-item questionnaire consisting of open and multiple-choice questions regarding personal experience with myopia care. The ophthalmologist perspective was obtained from practising Dutch ophthalmologists with a 12-item questionnaire of multiple-choice questions on work-related demographics, myopia care in daily practice and need for improvement. The response rate for patients was 27% (n = 136/500) and for ophthalmologists, 24% (n = 169/716). Results: Patients were highly concerned about personal progressive loss of vision (69%) and feared their psychological well-being (82%) in case this would happen. The quality of performance of care provided by ophthalmologists was rated as excellent or satisfactory by 64% of the patients. These ratings for multidisciplinary care and insurance reimbursement were as low as 28% and 18% respectively. The mean concern among ophthalmologists about the rise in high myopia was 6.9 (SEM 0.1) on a 10-point scale. Sixty-nine per cent of the ophthalmologists reported that asymptomatic myopic patients should not be examined regularly at outpatient clinics. Ophthalmologists urged the development of clinical guidelines (74%), but did report (95%) that they informed patients about risk factors and complications. This contrasted with the view of patients, of whom 42% were discontent with information provided by ophthalmologists. Conclusions: These questionnaires demonstrated that the current clinical care delivered to highly myopic patients is in need of improvement. The expected higher demand for myopia care in the near future requires preferred practice patterns, professionals specifically trained to manage myopic pathology, accurate and comprehensive information exchange and collaboration of in- and out-of-hospital professionals across the full eye care chain.</p

The inflammatory potential of diet is associated with the risk of age-related eye diseases

Background &amp; aims: Inflammation is involved in the pathogenesis of cataract, age-related macular degeneration (AMD), and possibly open-angle glaucoma (OAG). We assessed whether the inflammatory potential of diet (quantified using the dietary inflammatory index; DII) affects the incidence of these common blinding age-related eye diseases. Serum inflammation markers were investigated as possible mediators.Methods: Participants aged &gt;45 years were selected from the prospective, population-based Rotterdam Study. From 1991 onwards, every 4–5 years, participants underwent extensive eye examinations. At baseline, blood samples and dietary data (using food frequency questionnaires) were collected. The DII was adapted based on the data available. Of the 7436 participants free of eye diseases at baseline, 4036 developed incident eye diseases during follow-up (cataract = 2895, early-intermediate AMD = 891, late AMD = 81, OAG = 169). Results: The adapted DII (aDII) ranged from −4.26 (i.e., anti-inflammatory) to 4.53 (i.e., pro-inflammatory). A higher aDII was significantly associated with increased inflammation. A higher neutrophil-lymphocyte ratio (NLR) was associated with an increased risk of cataract and AMD. Additionally, complement component 3c (C3c) and systemic immune-inflammation index (SII) were associated with increased risks of cataract and late AMD, respectively. Every point increase in the aDII was associated with a 9% increased risk of cataract (Odds ratio [95% confidence interval]: 1.09 [1.04–1.14]). The NLR and C3c partly mediated this association. We also identified associations of the aDII with risk of AMD (early-intermediate AMD, OR [95% CI]: 1.11 [1.03–1.19]; late AMD, OR [95% CI]: 1.24 [1.02–1.53]). The NLR partly mediated these associations. The aDII was not associated with OAG. Conclusions: A pro-inflammatory diet was associated with increased risks of cataract and AMD. Particularly the NLR, a marker of subclinical inflammation, appears to be implicated. These findings are relevant for patients with AMD and substantiate the current recommendations to strive for a healthy lifestyle to prevent blindness.</p