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Objectives: To test the "vascular depression" hypothesis, the authors investigated whether smaller retinal arteriolar or larger venular calibers, which are markers of cerebral microvascular disease, were associated with incident late-life depression.Methods: The authors included 3,605 participants (age > or =55 years) from the population-based Rotterdam Study with no depression at baseline (1993-1995) and fundus photographs gradable for retinal vascular caliber measurements. The authors identified persons with incident depressive symptoms and syndromes using psychiatric interviews during follow-up visits and continuous monitoring. The follow-up was complete until October 2005.Results: After a mean follow-up of 9.0 years, 555 participants developed incident depression, including 312 with depressive syndrome. Neither smaller arteriolar (age- and sex-adjusted hazard ratio: 1.01; 95% confidence interval: 0.93-1.10), nor larger venular calibers (hazard ratio: 1.02; 95% confidence interval: 0.94-1.12) were associated with incident depressive syndromes.Conclusions: Our data showed no evidence of an association between retinal vascular calibers and incident late-life depression. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this study was to describe prevalent vascular retinal lesions among patients with type 2 diabetes enrolled in the ADVANCE Retinal Measurements (AdRem) study, a substudy of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. RESEARCH DESIGN AND METHODS: Seven-field stereoscopic photographs of both eyes were obtained at the baseline assessment of the ADVANCE trial. All photographs were graded in a central reading center. Gradable retinal images were received from 1,605 patients. RESULTS: The number of patients with any retinopathy (Early Treatment of Diabetic Retinopathy Study [ETDRS] score > or = 20) was 645 (40.2% [95% CI 37.8-42.6]); of these, 35 (2.2% [1.6-3.0]) had severe diabetic retinopathy (ETDRS score > or = 50). Focal arterial narrowing, venous beading, and arteriovenous nicking were present in 3.8, 5.1, and 9.8% of participants, respectively. Among participants included in this study, Chinese and South-Asian patients had more retinopathy than Caucasians, as defined both by ETDRS score (49.4, 46.0, and 31.3%, respectively; P < 0.001, adjusted for age, sex, A1C, systolic blood pressure, and duration of diabetes) and specific vascular lesions (e.g., arteriovenous nicking 12.3, 8.5, and 7.5%, respectively; adjusted P < 0.005). A1C, duration of diabetes, and systolic blood pressure were similarly associated with increased retinal lesions in Chinese, South-Asian, and Caucasian patients. CONCLUSIONS: Using a sensitive diagnostic procedure, more than one-third of patients with type 2 diabetes enrolled in the AdRem study had retinal lesions at baseline. Despite differences in prevalence and severity of retinopathy among Chinese, South-Asian, and Caucasian patients included in this study, the cross-sectional associations among established risk factors for retinopathy and retinal lesions were similar across ethnic groups. [ABSTRACT FROM AUTHOR]

Patient-reported outcome measures (PROMs) assess the impact of disease on quality of life from the patient's perspective. Our purpose was to provide an overview of current PROMs used for vitreomacular interface disorders: macular hole, epiretinal membrane, and vitreomacular traction. We review the content coverage of all identified PROMs, assess them against quality-of-life issues as identified from earlier qualitative studies, and assess their psychometric quality (measurement properties). We identified 86 studies that used a PROM and 2 qualitative studies on quality of life of patients with a vitreomacular interface disorder. Current PROMs used in vitreomacular interface disorders have a limited content coverage and unknown psychometric quality. The National Eye Institute Visual Functioning Questionnaire was used most. None of the condition-specific PROMs used patient consultation during content development, and there is only a small overlap between the content of PROMs and quality-of-life issues in qualitative studies. Reporting of psychometric quality was sparse, and mostly limited to concurrent validity and responsiveness. There is a need for properly developed and validated PROMs in vitreomacular interface disorders., Competing Interests: Declaration of Competing Interest NA, (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To determine the thickness of the conjunctiva, episclera and sclera in healthy individuals using anterior segment optical coherence tomography (AS-OCT)., Methods: We prospectively included 107 healthy individuals of different age groups (18-39 years, 40-54 years, 55-69 years and ≥70 years). For each eye, AS-OCT scans of four quadrants (temporal, nasal, superior and inferior) were acquired. The thickness of the conjunctiva, episclera and sclera was measured for each scan. In addition, the axial length of both eyes was measured, and general characteristics, including smoking, allergies and contact lens use, were collected., Results: The mean conjunctival thickness was significantly different between the nasal and superior quadrants (87 ± 30 μm vs. 77 ± 16 μm; p < 0.001), as well as the superior and inferior quadrants (77 ± 16 μm vs. 86 ± 19 μm; p = 0.001). The mean episcleral thickness was larger in the superior (174 ± 54 μm) and inferior (141 ± 43 μm) quadrants, compared to the nasal (83 ± 38 μm) and temporal quadrants (90 ± 44 μm). The mean scleral thickness of the inferior quadrant was the largest (596 ± 64 μm), followed by the nasal (567 ± 76 μm), temporal (516 ± 67 μm) and superior (467 ± 52 μm) quadrants (all p < 0.001). The averaged scleral thickness increased 0.96 μm per age year (0.41-1.47 μm, p < 0.001)., Conclusions: This study provides an assessment of the thickness of scleral and adjacent superficial layers in healthy individuals determined on AS-OCT, which could enable future research into the use of AS-OCT in diseases affecting the anterior eye wall., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Competing Interests: The authors have no funding or conflicts of interest to declare.

Importance: High myopia incidence and prevalence is increasing worldwide, and the visual burden caused by myopia is expected to rise accordingly. Studies investigating the occurrence of myopic complications in individuals of European ancestry with high myopia are scarce, hampering insights into the frequency of myopic retinal complications in European individuals and their visual burden., Objective: To assess the frequency of myopic macular features in individuals of European ancestry with high myopia., Design, Setting, and Participants: This cross-sectional analysis of the Dutch Myopia Study (MYST) and individuals with high myopia from the Rotterdam Study (RS) included 626 patients with high myopia (spherical equivalent of refractive error [SER] ≤-6 diopters [D] or axial length [AL] ≥26 mm) who underwent an extensive ophthalmic examination including multimodal retinal imaging. In addition to this combination of a population-based cohort study and mix-based high myopia study, a systematic literature review was also performed to compare findings with studies of individuals of Asian ancestry., Exposures: High myopia, age, and AL., Main Outcomes and Measures: Frequency of myopic macular and optic disc features: tessellated fundus, myopic macular degeneration (MMD), staphyloma, peripapillary intrachoroidal cavitation, peripapillary atrophy (PPA), and "plus" lesions (choroidal neovascularization, Fuchs spot, and lacquer cracks)., Results: The mean (SD) SER of the combined study population (MYST and RS) was -9.9 (3.2) D; the mean (SD) age was 51.4 (15.1) years, and 387 (61.8%) were women. The prevalence of MMD was 25.9% and increased with older age (P for trend <.001), lower SER (odds ratio [OR], 0.70; 95% CI, 0.65-0.76; P < .001), and higher AL (OR, 2.53; 95% CI, 2.13-3.06; P < .001). Choroidal neovascularization or Fuchs spot was present in 2.7% (n = 17), both lesions in 0.3% (n = 2), and lacquer cracks in 1.4% (n = 9). Staphyloma, PPA, and MMD were highly prevalent in visual impaired and blind eyes (frequency was 73.9% [20 of 27], 90.5% [19 of 21], and 63.0% [17 of 27] of unilateral blind eyes for MMD, staphyloma, and PPA, respectively). Seven previous studies in Asian populations reported a variable MMD frequency ranging from 8.3% to 64%, but frequencies were similar for comparable risk profiles based on age and SER., Conclusions and Relevance: In this cross-sectional study of a highly myopic Dutch population of European ancestry, myopic retinal features were frequent; were associated with age, SER, and AL; and occurred in all visually severely impaired eyes. The absence of treatment options for most of these retinal complications emphasizes the need for effective strategies to prevent high myopia.

Objective: To identify the clinical characteristics and prevalence of neoplastic and nonneoplastic inflammatory masquerade syndromes (IMSs) in a tertiary center and determine the useful diagnostic tests., Methods: A retrospective cohort study of consecutive 1906 patients diagnosed with intraocular inflammatory disease., Results: Of all patients initially diagnosed with intraocular inflammatory disease, we identified 116 (6%) patients with noninflammatory causes (neoplastic IMSs in 36/116; 31% and nonneoplastic IMSs in 52/116; 45%). In addition, 26 patients (22%, 1.4% of all) had drug-induced uveitis and 2 (2%, 0.1% of all) had paraneoplastic uveitis. The large B-cell lymphoma was the most common neoplastic IMS (78%), and the major clinical features were presence of cells and floaters in the vitreous (69%) and chorioretinal lesions (33%). The causes of nonneoplastic IMSs included retinal vascular disorders (38%), hereditary retinal diseases (31%), and degenerative ocular disorders (19%). The common clinical manifestations consisted of chorioretinal scars (27%), small white-yellow retinal lesions (17%), and leaking vessels on fluorescein angiography (14%)., Conclusion: Noninflammatory causes were determined in 6% of a large population with initial diagnosis of intraocular inflammatory disease. Although neoplastic IMS was commonly characterized by vitreous cells and opacities, most common definitive diagnoses in nonneoplastic IMS encompassed diverse retinal disorders.

Purpose: To study the prevalence and severity of diabetic retinopathy (DR) in patients with macular telangiectasia type 2 (MacTel 2)., Design: Retrospective case series., Participants: Patients with a diagnosis of MacTel 2 treated at the Rotterdam Eye Hospital or Erasmus Medical Center between 2014 and 2018 were included., Methods: The following information was retrieved from patient files: demographics, history of diabetes mellitus and hypertension, presence of DR, and severity of DR, that is, mild, moderate, severe, or proliferative. Presence of diabetic macular edema (DME) was assessed using OCT., Main Outcome Measures: Presence and severity of DR., Results: Two hundred six eyes of 103 patients were included. At the onset of MacTel 2, the mean age was 61 years (standard deviation [SD], 9.8 years) and 64 (62%) were women. Mean follow-up was 71 months (SD, 60 months). Diabetes mellitus type 2 was present in 50 patients (49%) and hypertension was present in 47 patients (46%). Mild DR was present in 22 eyes (11%), of which 14 eyes (7%) showed signs at baseline and 8 eyes (4%) showed signs at a later time during follow-up. Ten eyes (5%) demonstrated remission of mild DR during follow-up. Both eyes (1%) in 1 patient progressed to moderate DR. Severe DR, proliferative DR, and DME did not occur., Conclusions: Although diabetes mellitus was highly prevalent among MacTel 2 patients, no patients showed severe or proliferative DR or DME. These findings suggest that MacTel 2 could have a protective effect on the progression of DR. We hypothesize that our results may be explained by the role of Müller cells in the development of MacTel 2 and DR, and therefore a link between both diseases warrants additional studies., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Treatments for geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), are currently under development. Understanding the natural course is needed for optimal trial design. Although enlargement rates of GA and visual acuity (VA) in the short term are known from clinical studies, knowledge of enlargement in the long term, life expectancy, and visual course is lacking., Objective: To determine long-term enlargement of GA., Design, Setting, and Participants: In this study, participant data were collected from 4 population-based cohort studies, with up to 25 years of follow-up and eye examinations at 5-year intervals: the Rotterdam Study cohorts 1, 2, and 3 and the Blue Mountains Eye Study. Data were collected from 1990 to 2015, and data were analyzed from January 2019 to November 2020., Main Outcomes and Measures: Area of GA was measured pixel by pixel using all available imaging. Area enlargement and enlargement of the square root-transformed area, time until GA reached the central fovea, and time until death were assessed, and best-corrected VA, smoking status, macular lesions according to the Three Continent AMD Consortium classification, a modified version of the Wisconsin age-related maculopathy grading system, and AMD genetic variants were covariates in Spearman, Pearson, or Mann-Whitney analyses., Results: Of 171 included patients, 106 (62.0%) were female, and the mean (SD) age at inclusion was 82.6 (7.1) years. A total of 147 of 242 eyes with GA (60.7%) were newly diagnosed in our study. The mean area of GA at first presentation was 3.74 mm2 (95% CI, 3.11-4.67). Enlargement rate varied widely between persons (0.02 to 4.05 mm2 per year), with a mean of 1.09 mm2 per year (95% CI, 0.89-1.30). Stage of AMD in the other eye was correlated with GA enlargement (Spearman ρ = 0.34; P = .01). Foveal involvement was already present in incident GA in 55 of 147 eyes (37.4%); 23 of 42 eyes (55%) developed this after a mean (range) period of 5.6 (3-12) years, and foveal involvement did not develop before death in 11 of 42 eyes (26%). After first diagnosis, 121 of 171 patients with GA (70.8%) died after a mean (SD) period of 6.4 (5.4) years. Visual function was visually impaired (less than 20/63) in 47 of 107 patients (43.9%) at last visit before death., Conclusions and Relevance: In this study, enlargement of GA appeared to be highly variable in the general population. More than one-third of incident GA was foveal at first presentation; those with extrafoveal GA developed foveal GA after a mean of 5.6 years. Future intervention trials should focus on recruiting those patients who have a high chance of severe visual decline within their life expectancy.

Purpose: Current prediction models for advanced age-related macular degeneration (AMD) are based on a restrictive set of risk factors. The objective of this study was to develop a comprehensive prediction model applying a machine learning algorithm allowing selection of the most predictive risk factors automatically., Design: Two population-based cohort studies., Participants: The Rotterdam Study I (RS-I; training set) included 3838 participants 55 years of age or older, with a median follow-up period of 10.8 years, and 108 incident cases of advanced AMD. The Antioxydants, Lipids Essentiels, Nutrition et Maladies Oculaires (ALIENOR) study (test set) included 362 participants 73 years of age or older, with a median follow-up period of 6.5 years, and 33 incident cases of advanced AMD., Methods: The prediction model used the bootstrap least absolute shrinkage and selection operator (LASSO) method for survival analysis to select the best predictors of incident advanced AMD in the training set. Predictive performance of the model was assessed using the area under the receiver operating characteristic curve (AUC)., Main Outcome Measures: Incident advanced AMD (atrophic, neovascular, or both), based on standardized interpretation of retinal photographs., Results: The prediction model retained (1) age, (2) a combination of phenotypic predictors (based on the presence of intermediate drusen, hyperpigmentation in one or both eyes, and Age-Related Eye Disease Study simplified score), (3) a summary genetic risk score based on 49 single nucleotide polymorphisms, (4) smoking, (5) diet quality, (6) education, and (7) pulse pressure. The cross-validated AUC estimation in RS-I was 0.92 (95% confidence interval [CI], 0.88-0.97) at 5 years, 0.92 (95% CI, 0.90-0.95) at 10 years, and 0.91 (95% CI, 0.88-0.94) at 15 years. In ALIENOR, the AUC reached 0.92 at 5 years (95% CI, 0.87-0.98). In terms of calibration, the model tended to underestimate the cumulative incidence of advanced AMD for the high-risk groups, especially in ALIENOR., Conclusions: This prediction model reached high discrimination abilities, paving the way toward making precision medicine for AMD patients a reality in the near future., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Scleritis is a sight-threatening inflammation characterized by severe pain and redness of the eye. It can cause blindness by severe complications like scleral and corneal necrosis, keratitis, and uveitis. The pathogenesis of scleritis is largely unknown due to a combination of the rarity of the disease, the little available human tissue-based research material, and the lack of animal models. The immune system is assumed to play a crucial role in the pathogenesis of scleritis. Multiple clues indicate probable antigenic stimuli in scleritis, and the involvement of matrix metalloproteinases in the destruction of scleral tissue. In this article we review the current insights into the pathogenesis of scleritis, and we suggest new hypotheses by implementing knowledge of systemic autoimmune disease pathogenesis. Understanding the pathogenesis of scleritis is crucial to improve the clinical management, as well as to find novel treatment modalities., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: To generate conclusive evidence regarding the noninferiority of intravitreal bevacizumab compared with ranibizumab in patients with diabetic macular edema (DME)., Design: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial., Participants: Eligible patients were older than 18 years, diagnosed with type 1 or type 2 diabetes mellitus, with glycosylated hemoglobin of less than 12%, central area thickness of more than 325 μm, and visual impairment from DME with a best-corrected visual acuity (BCVA) between 24 letters and 78 letters., Methods: From June 2012 through February 2018, a total of 170 participants were randomized to receive 6 monthly injections of either 1.25 mg bevacizumab (n = 86) or 0.5 mg ranibizumab (n = 84)., Main Outcome Measures: Primary outcome was change in BCVA from baseline to month 6 compared between the 2 treatment arms. The noninferiority margin was 3.5 letters., Results: The difference in mean BCVA between treatment arms was 1.8 letters in favor of ranibizumab after 6 months of follow-up; BCVA improved by 4.9±6.7 letters in the bevacizumab group and 6.7±8.7 letters in the ranibizumab group. The lower bound of the 2-sided 90% confidence interval (CI) was -3.626 letters, exceeding the noninferiority margin of 3.5 letters. Central area thickness decreased more with ranibizumab (138.2±114.3 μm) compared with bevacizumab (64.2±104.2 μm). In a post hoc subgroup analysis, participants with a worse BCVA at baseline (≤69 letters) improved by 6.7±7.0 letters with bevacizumab and 10.4±10.0 letters with ranibizumab, and central area thickness decreased significantly more in the ranibizumab arm of this subgroup compared with the bevacizumab arm. Participants with an initially better BCVA at baseline (≥70 letters) did not demonstrate differences in BCVA or OCT outcomes between treatment arms., Conclusions: Based on change in BCVA from baseline to month 6, the noninferiority of 1.25 mg bevacizumab to 0.5 mg ranibizumab was not confirmed. Only the subgroup of patients with a lower BCVA at baseline showed better visual acuity and anatomic outcomes with ranibizumab. Our study confirmed the potential differential efficacy of anti-vascular endothelial growth factor agents in the treatment of DME as well as the difference in response between patient groups with different baseline visual acuities., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Comparing the efficacy of intravitreal injections of bevacizumab to ranibizumab in the treatment of macular edema (ME) resulting from retinal vein occlusion (RVO)., Design: Comparative, randomized, double-masked, multicenter, noninferiority clinical trial. The noninferiority margin was 4 letters., Participants: Patients with vision loss resulting from ME secondary to a branch or (hemi) central RVO who might benefit from anti-vascular endothelial growth factor treatment were eligible for participation., Methods: From June 2012 through February 2018, 277 participants were randomized to receive injections of 1.25 mg bevacizumab (n = 139) or 0.5 mg ranibizumab (n = 138). The follow-up was 6 months with a monthly dosing interval., Main Outcome Measures: The primary outcome was a change in visual acuity from baseline at 6 months. Changes in the central area thickness and safety were studied as secondary outcomes., Results: The mean visual acuity (±standard deviation) improved, with 15.3±13.0 letters for bevacizumab and 15.5±13.3 letters for ranibizumab after 6 months of monthly treatment. The lower limit of the 2-sided 90% confidence interval was -1.724 letters, which is within the noninferiority margin of 4 letters. Even in the branch and (hemi-)central RVO subgroups, minimal differences were found in visual acuity outcomes between treatment arms. Changes in central area thickness on OCT at 6 months did not differ significantly between treatment groups, with a decrease of 287.0±231.3 μm in the bevacizumab group and 300.8±224.8 μm in the ranibizumab group. Severe adverse events (SAEs) were also distributed equally over both treatment groups: 10 participants (7.1%) in the bevacizumab group and 13 participants (9.2%) in the ranibizumab group experienced SAEs., Conclusions: This study showed, based on the change in visual acuity, that bevacizumab is noninferior to ranibizumab for patients with ME resulting from RVO of either subtype when receiving monthly injections for a period of 6 months. In addition, anatomic and safety outcomes did not differ between treatment groups. Based on our findings, bevacizumab may be an effective alternative to ranibizumab., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Ocular biometry varies within groups of emmetropic, hyperopic or myopic children. The aim of this study was to quantify the effect of foetal and infant growth on ocular biometry in early childhood, to determine the most important period for this association, and to examine genetic overlap with height and birth weight., Methods: 5931 children (50.1% girls) from a population-based prospective birth cohort study underwent intra-uterine and infant growth measurements at second and third trimester, and from birth to 72 months. An ophthalmic examination including axial length (mm) and corneal radius of curvature (mm) was performed at 6 years of age. The associations between prenatal and postnatal growth variables and axial length and corneal radius of curvature were assessed with conditional linear regression analyses. Weighted genetic risk scores for birth weight and height were calculated and causality was tested with Mendelian randomisation., Results: Weight and length from mid-pregnancy to 2 years of age were most important prognostic factors for axial length and corneal radius of curvature at age 4.9-9 years (mean 6.2 years S.D. 0.5). For height (Standard deviation score), the association with axial length and corneal radius of curvature was highest for the measurement at 12 months (β 0.171 p < 0.001 and 0.070 p < 0.001). The genetic height and birth weight risk scores were both significantly associated with ocular biometry., Conclusions: Larger neonates had longer axial length and greater corneal radius of curvature. Growth during pregnancy and 2 years postnatally is the most important period underlying this association and may be partly genetically determined by genes associated with height., (© 2019 The Authors. Ophthalmic & Physiological Optics published by John Wiley & Sons Ltd on behalf of College of Optometrists.)

Purpose: What patients should eat to reduce their risk of age-related macular degeneration (AMD) is still unclear. We investigated the effect of a diet recommended by Health Councils on AMD., Design: Prospective population-based cohort study., Methods: Four thousand two hundred and two participants from the Rotterdam Study ≥55 years of age who were free of AMD at baseline were included and followed up for 9.1 ± 5.8 years. Incident AMD was graded on fundus photographs. Dietary data were collected using a validated 170-item food frequency questionnaire, and food intakes were categorized into food patterns based on guidelines from Health Councils. Associations with incident AMD were analyzed using Cox proportional hazards models that were adjusted for age, sex, total energy intake, smoking, body mass index, hypertension, education, and income., Results: Seven hundred fifty-four people developed incident AMD. Intake of the recommended amounts of vegetables (≥200 g/day), fruit (2×/day), and fish (2×/week) were 30.6%, 54.9%, and 12.5%, respectively. In particular, the intake of fish (2×/week) decreased the risk of incident AMD (hazard ratio 0.76 [95% confidence interval 0.60-0.97]). Intake of the recommended amounts of all 3 food groups was only 3.7%, but adherence to this pattern showed a further reduction of the risk of incident AMD (hazard ratio 0.58 [95% confidence interval 0.36-0.93]). Younger age, higher income, and not smoking were associated with this food pattern, but the risk-lowering effects remained significant after additional adjustment for these factors., Conclusion: A diet of 200 grams per day of vegetables, fruit two times per day, and fish two times per week is associated with a significantly reduced risk of AMD., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To identify risk factors for axial length (AL) elongation and incident school myopia., Design: Population-based prospective birth-cohort study., Participants: Four thousand seven hundred thirty-four children examined at 6 and 9 years of age from the Generation R Study in Rotterdam, The Netherlands., Methods: Axial length and corneal radius (CR) were measured with an IOLMaster 500 and daily life activities and demographic characteristics were obtained by questionnaire. Three thousand three hundred sixty-two children (71%) were eligible for cycloplegic refractive error measurements. Linear regression models on AL elongation were used to create a risk score based on the regression coefficients resulting from environmental and ocular factors. The predictive value of the prediction score for myopia (≤-0.5 diopter) was estimated using receiver operating characteristic curves. To test if regression coefficients differed for baseline AL-to-CR ratio, interaction terms were calculated with baseline AL-to-CR ratio and environmental factors., Main Outcome Measures: Axial length elongation and incident myopia., Results: From 6 to 9 years of age, average AL elongation was 0.21±0.009 mm/year and myopia developed in 223 of 2136 children (10.4%), leading to a myopia prevalence at 9 years of age of 12.0%. Seven parameters were associated independently (P < 0.05) with faster AL elongation: parental myopia, 1 or more books read per week, time spent reading, no participation in sports, non-European ethnicity, less time spent outdoors, and baseline AL-to-CR ratio. The discriminative accuracy for incident myopia based on these risk factors was 0.78. Axial length-to-CR ratio at baseline showed statistically significant interaction with number of books read per week (P < 0.01) and parental myopia (P < 0.01). Almost all predictors showed the highest association with AL elongation in the highest quartile of AL-to-CR ratio; incidental myopia in this group was 24% (124/513)., Conclusions: Determination of a risk score can help to identify school children at high risk of myopia. Our results suggest that behavioral changes can offer protection particularly in these children., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To analyse ophthalmological adverse events associated with mitogen-activated protein kinase kinase (MEK) inhibition with pimasertib treatment for metastatic cutaneous melanoma (CM)., Methods: In this prospective observational, cohort-based, cross-sectional study, eight patients treated with the MEK inhibitor pimasertib received a complete ophthalmic examination. This included Early Treatment of Diabetic Retinopathy Study best-corrected visual acuity, visual field testing, colour vision testing, slit-lamp examination, applanation tonometry, indirect ophthalmoscopy, digital colour fundus photography and optical coherence tomography (OCT). In selected cases, fluorescein angiography was performed., Results: Serous subretinal fluid (SRF) developed in all patients, within a time frame of 9-27 days after the start of treatment. The fovea was involved in six of eight patients (75%). None of the patients with foveal SRF [excluding a patient who developed a bilateral retinal vein occlusion (RVO)] experienced visual symptoms. Subretinal fluid (SRF) decreased or resolved in all patients, despite continuation of study medication in six of eight patients (75%). Complaints in the CM patient (13%) consisted of experiencing a dark fleck in the inferior part of the visual field of the right eye 1 week after the start of treatment, due to an RVO. Subsequent intravitreal bevacizumab treatment resulted in functional and anatomical improvement., Conclusion: Patients with metastatic CM who are treated with the MEK inhibitor pimasertib are at high risk of development of ocular adverse events including serous retinopathy and possibly RVO, stressing the need of adequate ophthalmological follow-up including OCT during administration of pimasertib, despite the fact that SRF generally does not lead to ophthalmological complaints., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Increasing evidence shows that thinner retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL), assessed on optical coherence tomography (OCT), are reflecting global brain atrophy. Yet, little is known on the relation of these layers with specific brain regions. Using voxel-based analysis, we aimed to unravel specific brain regions associated with these retinal layers. We included 2,235 persons (mean age: 67.3 years, 55% women) from the Rotterdam Study (2007-2012) who had gradable retinal OCT images and brain magnetic resonance imaging (MRI) scans, including diffusion tensor (DT) imaging. Thicknesses of peripapillary RNFL and perimacular GCL were measured using an automated segmentation algorithm. Voxel-based morphometry protocols were applied to process DT-MRI data. We investigated the association between retinal layer thickness with voxel-wise gray matter density and white matter microstructure by performing linear regression models. We found that thinner RNFL and GCL were associated with lower gray matter density in the visual cortex, and with lower fractional anisotropy and higher mean diffusivity in white matter tracts that are part of the optic radiation. Furthermore, thinner GCL was associated with lower gray matter density of the thalamus. Thinner RNFL and GCL are associated with gray and white matter changes in the visual pathway suggesting that retinal thinning on OCT may be specifically associated with changes in the visual pathway rather than with changes in the global brain. These findings may serve as a basis for understanding visual symptoms in elderly patients, patients with Alzheimer's disease, or patients with posterior cortical atrophy., (© 2018 Wiley Periodicals, Inc.)

Purpose: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population., Design: Cross-sectional meta-analysis., Participants: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9±12.3-82.1±4.2 years) of the European Eye Epidemiology (E3) consortium., Methods: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis., Main Outcome Measures: Determinants of pRNFLT., Results: Mean pRNFLT ranged from 86.8±21.4 μm in the Rotterdam Study I to 104.7±12.5 μm in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (β = -0.38 μm/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (IOP) (β = -0.36 μm/mmHg; 95% CI, -0.56 to -0.15), visual impairment (β = -5.50 μm; 95% CI, -9.37 to -1.64), and history of systemic hypertension (β = -0.54 μm; 95% CI, -1.01 to -0.07) and stroke (β = -1.94 μm; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (β = -3.11 μm; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (β = 1.39 μm/diopter; 95% CI, 1.19-1.59) and smoking (β = 1.53 μm; 95% CI, 1.00-2.06 for current smokers compared with never-smokers)., Conclusions: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: Genome-wide association studies and targeted sequencing studies of candidate genes have identified common and rare variants that are associated with age-related macular degeneration (AMD). Whole-exome sequencing (WES) studies allow a more comprehensive analysis of rare coding variants across all genes of the genome and will contribute to a better understanding of the underlying disease mechanisms. To date, the number of WES studies in AMD case-control cohorts remains scarce and sample sizes are limited. To scrutinize the role of rare protein-altering variants in AMD cause, we performed the largest WES study in AMD to date in a large European cohort consisting of 1125 AMD patients and 1361 control participants., Design: Genome-wide case-control association study of WES data., Participants: One thousand one hundred twenty-five AMD patients and 1361 control participants., Methods: A single variant association test of WES data was performed to detect variants that are associated individually with AMD. The cumulative effect of multiple rare variants with 1 gene was analyzed using a gene-based CMC burden test. Immunohistochemistry was performed to determine the localization of the Col8a1 protein in mouse eyes., Main Outcome Measures: Genetic variants associated with AMD., Results: We detected significantly more rare protein-altering variants in the COL8A1 gene in patients (22/2250 alleles [1.0%]) than in control participants (11/2722 alleles [0.4%]; P = 7.07×10 -5 ). The association of rare variants in the COL8A1 gene is independent of the common intergenic variant (rs140647181) near the COL8A1 gene previously associated with AMD. We demonstrated that the Col8a1 protein localizes at Bruch's membrane., Conclusions: This study supported a role for protein-altering variants in the COL8A1 gene in AMD pathogenesis. We demonstrated the presence of Col8a1 in Bruch's membrane, further supporting the role of COL8A1 variants in AMD pathogenesis. Protein-altering variants in COL8A1 may alter the integrity of Bruch's membrane, contributing to the accumulation of drusen and the development of AMD., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)