Progression Of Macular Degeneration Research Articles

Exploring the association of vitamin D levels with age-related macular degeneration progression: A systematic review

Exploring the association of vitamin D levels with age-related macular degeneration progression: A systematic review

Risk Factor of Neovascular Age­related Macular Degeneration Progression after Cataract Surgery

The prevalence of late AMD, including neovascular AMD or geographic atrophy, and cataract in the same eye after age 80 years is estimated to be 12 and 68 %, respectively. There is currently no consensus on whether cataract surgery is beneficial or harmful for people with dry AMD. Although cataract surgery has been reported to provide better visual outcomes in eyes with AMD 6 months after surgery compared with previously followed eyes, it is unclear whether the timing of surgery relative to the start of AMD treatment influences long-term outcomes. The question of risk factors predisposing to the occurrence of exudation after cataract surgery in people with nAMD remains controversial.

Descemet Stripping Only: Long-Term Outcomes.

Descemet stripping only (DSO) is a relatively novel treatment for Fuchs endothelial corneal dystrophy (FECD). In this procedure, a central area of Descemet membrane and endothelium is removed without the insertion of donor tissue. Evaluation of long-term outcomes (≥5 years) after DSO is imperative to establish the validity of this procedure and to determine its role in the management of Fuchs endothelial dystrophy. Published outcomes are limited but promising. This study evaluates the 5- and 6-year outcomes of patients who had DSO at a single institution. This is a retrospective chart review of patients with FECD who underwent DSO in 2016 and 2017. Eleven patients and 13 eyes met the criteria. Twelve of 13 eyes achieved corneal clearance. Two eyes had corneal decompensation requiring subsequent endothelial keratoplasty (EK). Of the 10 eyes that maintained clear corneas, 9 had a best-corrected visual acuity (BCVA) of at least 20/30 (mean logarithm of the minimim angle of resolution [logMAR] visual acuity [VA] 0.18 ± 0.16) at 5 years post-operatively (POY5). At 6 years, 7 of 8 eyes had a VA better than 20/40 (mean logMAR VA 0.17 ± 0.04). One patient had decreased VA due to progression of macular degeneration. Patients who required EK achieved good vision and corneal clearance. This is the largest series of patients with long-term follow-up after DSO. Ten of the 13 eyes (77%) responded and maintained clear central corneas for at least 5 years. Patients with failed DSO can achieve corneal clearance and good vision with subsequent EK. These patient outcomes support the role of DSO in the management of patients with FECD.

The role of B vitamins in the development and progression of age-related macular degeneration

In recent years, the importance of B vitamins as biologically active nutrients with potential effects preventing the development and progression of age-related macular degeneration has been analysed. This work is a review of the current literature from the last 10 years, dealing with the subject of the properties of B vitamins and research providing epidemiological data on its intake and plasma concentration and their impact on the disease in patients with macular degeneration.
 The review confirms the important beneficial role of B vitamins in limiting the development and progression of macular degeneration. Although further randomized trials are needed to evaluate diet and determine selected plasma antioxidants over a longer, at least several years’ period while taking into account pokara number of risk factors for modifiable and determine selected plasma antioxidants over a longer, at least several years’ period while taking into account a number of risk factors for modifiable and non-modifiable macular degeneration.

Identifying Imaging Predictors of Intermediate Age-Related Macular Degeneration Progression.

Intermediate age-related macular degeneration (iAMD) is a risk factor for progression to advanced stages, but rates of progression vary between individuals. Predicting individual risk is advantageous for programing timely and effective treatment and for patient stratification into future clinical trials. We conducted a prospective and noninterventional study following patients with iAMD for 24 months. Optical coherence tomography parameters related with drusen, hyper-reflective foci (HRF), presence of incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and ellipsoid zone (EZ) status were explored at the baseline. Patients were reclassified at the end of the follow-up period and divided according to their progression. A risk prediction model for progression to late AMD was developed. A total of 135 patients were enrolled in the study and 30.4% developed late disease. A multivariate logistic regression model was created using those optical coherence tomography parameters, further optimized by backward feature elimination. Parameters offering the best fit in prediction progression were presence of iRORA, EZ status, drusen area and presence of HRF. iRORA is the feature that provides a higher probability of developing late AMD (odds ratio, 12.91; P = 0.000), followed by EZ disruption status (odds ratio, 3.54; P = 0.0018). The area under the receiver operating characteristic curve calculated for the testing set was 0.77 (95% confidence interval, 0.56-0.98). The combination of iRORA and EZ disruption constitute a high risk of progression to complete RORA within 2 years. We propose a practical and useful model to help clinicians in their daily practice in predicting individual progression to advanced AMD.

The Predictive Capabilities of Artificial Intelligence-Based OCT Analysis for Age-Related Macular Degeneration Progression-A Systematic Review.

The era of artificial intelligence (AI) has revolutionized our daily lives and AI has become a powerful force that is gradually transforming the field of medicine. Ophthalmology sits at the forefront of this transformation thanks to the effortless acquisition of an abundance of imaging modalities. There has been tremendous work in the field of AI for retinal diseases, with age-related macular degeneration being at the top of the most studied conditions. The purpose of the current systematic review was to identify and evaluate, in terms of strengths and limitations, the articles that apply AI to optical coherence tomography (OCT) images in order to predict the future evolution of age-related macular degeneration (AMD) during its natural history and after treatment in terms of OCT morphological structure and visual function. After a thorough search through seven databases up to 1 January 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 1800 records were identified. After screening, 48 articles were selected for full-text retrieval and 19 articles were finally included. From these 19 articles, 4 articles concentrated on predicting the anti-VEGF requirement in neovascular AMD (nAMD), 4 articles focused on predicting anti-VEGF efficacy in nAMD patients, 3 articles predicted the conversion from early or intermediate AMD (iAMD) to nAMD, 1 article predicted the conversion from iAMD to geographic atrophy (GA), 1 article predicted the conversion from iAMD to both nAMD and GA, 3 articles predicted the future growth of GA and 3 articles predicted the future outcome for visual acuity (VA) after anti-VEGF treatment in nAMD patients. Since using AI methods to predict future changes in AMD is only in its initial phase, a systematic review provides the opportunity of setting the context of previous work in this area and can present a starting point for future research.

Peran Karotenoid Sebagai Pencegahan Degenerasi Makula

Macular degeneration or often called Age-related Macular Degeneration (AMD) is a degenerative disease that attacks the center of vision in the retina, namely the macula. In an effort to prevent the progression of AMD, consuming antioxidants has been shown to inhibit the AMD development process. Although currently there is no definite number of AMD sufferers in Indonesia, it is estimated that the number of AMD sufferers will continue to increase. Carotenoids are one of the antioxidant compounds that have been shown to inhibit the development of macular degeneration. Carotenoids are divided into several classes, one of which is the xanthophyll class. Lutein and zeaxanthin compounds belong to the xanthophyll class. The content of lutein and zeaxanthin in body plasma has been shown to reduce the risk of macular diseases such as AMD. This study aims to determine the role of carotenoids as the prevention of macular degeneration. The method used is a literature review in the form of a narrative review. Search literature in the form of journals and textbooks through Google Scholar, PubMed, Science Direct, and Research Gate, indexed by Scopus, ISSN, national journals and international journals. The journals used were published in the last 5 years and books published in the last 10 years. The results of the analysis show that carotenoid antioxidants are proven to be able to act as a prevention of AMD by reducing oxidative stress. Carotenoids will quench free radicals, thereby preventing the occurrence of lipid peroxidation, and preventing the formation of AMD. Carotenoids also prevent damage mediated by exposure to blue light. Consumption of lutein and zeaxanthin can also reduce the expression of VEGF (vascular endothelial growth factor) in the retina so that it can inhibit the increase of VEGF. It can be concluded that carotenoid antioxidants can prevent the progression of macular degeneration.

Oxidative stress in retinal pigment epithelium degeneration: from pathogenesis to therapeutic targets in dry age-related macular degeneration.

Age-related macular degeneration is a primary cause of blindness in the older adult population. Past decades of research in the pathophysiology of the disease have resulted in breakthroughs in the form of anti-vascular endothelial growth factor therapies against neovascular age-related macular degeneration; however, effective treatment is not yet available for geographical atrophy in dry age-related macular degeneration or for preventing the progression from early or mid to the late stage of age-related macular degeneration. Both clinical and experimental investigations involving human age-related macular degeneration retinas and animal models point towards the atrophic alterations in retinal pigment epithelium as a key feature in age-related macular degeneration progression. Retinal pigment epithelium cells are primarily responsible for cellular-structural maintenance and nutrition supply to keep photoreceptors healthy and functional. The retinal pigment epithelium constantly endures a highly oxidative environment that is balanced with a cascade of antioxidant enzyme systems regulated by nuclear factor erythroid-2-related factor 2 as a main redox sensing transcription factor. Aging and accumulated oxidative stress triggers retinal pigment epithelium dysfunction and eventually death. Exposure to both environmental and genetic factors aggravates oxidative stress damage in aging retinal pigment epithelium and accelerates retinal pigment epithelium degeneration in age-related macular degeneration pathophysiology. The present review summarizes the role of oxidative stress in retinal pigment epithelium degeneration, with potential impacts from both genetic and environmental factors in age-related macular degeneration development and progression. Potential strategies to counter retinal pigment epithelium damage and protect the retinal pigment epithelium through enhancing its antioxidant capacity are also discussed, focusing on existing antioxidant nutritional supplementation, and exploring nuclear factor erythroid-2-related factor 2 and its regulators including REV-ERBα as therapeutic targets to protect against age-related macular degeneration development and progression.

Lipofuscin-Mediated Photic Stress Induces a Dark Toxic Effect on ARPE-19 Cells.

Lipofuscin granules from retinal pigment epithelium (RPE) cells contain bisretinoid fluorophores, which are photosensitizers and are phototoxic to cells. In the presence of oxygen, bisretinoids are oxidized to form various products, containing aldehydes and ketones, which are also potentially cytotoxic. In a prior study, we identified that bisretinoid oxidation and degradation products have both hydrophilic and amphiphilic properties, allowing their diffusion through the lipofuscin granule membrane into the RPE cell cytoplasm, and are thiobarbituric acid (TBA)-active. The purpose of the present study was to determine if these products exhibit a toxic effect to the RPE cell also in the absence of light. The experiments were performed using the lipofuscin-fed ARPE-19 cell culture. The RPE cell viability analysis was performed with the use of flow cytofluorimetry and laser scanning confocal microscopy. The results obtained indicated that the cell viability of the lipofuscin-fed ARPE-19 sample was clearly reduced not immediately after visible light irradiation for 18 h, but after 4 days maintaining in the dark. Consequently, we could conclude that bisretinoid oxidation products have a damaging effect on the RPE cell in the dark and can be considered as an aggravating factor in age-related macular degeneration progression.

Predicting Age-Related Macular Degeneration Progression with Contrastive Attention and Time-Aware LSTM.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. Identifying patients at high risk of progression to late AMD, the sight-threatening stage, is critical for clinical actions, including medical interventions and timely monitoring. Recently, deep-learning-based models have been developed and achieved superior performance for late AMD prediction. However, most existing methods are limited to the color fundus photography (CFP) from the last ophthalmic visit and do not include the longitudinal CFP history and AMD progression during the previous years' visits. Patients in different AMD subphenotypes might have various speeds of progression in different stages of AMD disease. Capturing the progression information during the previous years' visits might be useful for the prediction of AMD progression. In this work, we propose a Contrastive-Attention-based Time-aware Long Short-Term Memory network (CAT-LSTM) to predict AMD progression. First, we adopt a convolutional neural network (CNN) model with a contrastive attention module (CA) to extract abnormal features from CFPs. Then we utilize a time-aware LSTM (T-LSTM) to model the patients' history and consider the AMD progression information. The combination of disease progression, genotype information, demographics, and CFP features are sent to T-LSTM. Moreover, we leverage an auto-encoder to represent temporal CFP sequences as fixed-size vectors and adopt k-means to cluster them into subphenotypes. We evaluate the proposed model based on real-world datasets, and the results show that the proposed model could achieve 0.925 on area under the receiver operating characteristic (AUROC) for 5-year late-AMD prediction and outperforms the state-of-the-art methods by more than 3%, which demonstrates the effectiveness of the proposed CAT-LSTM. After analyzing patient representation learned by an auto-encoder, we identify 3 novel subphenotypes of AMD patients with different characteristics and progression rates to late AMD, paving the way for improved personalization of AMD management. The code of CAT-LSTM can be found at GitHub.

Long-term Outcomes of Adding Lutein/Zeaxanthin and ω-3 Fatty Acids to the AREDS Supplements on Age-Related Macular Degeneration Progression

After the Age-Related Eye Disease Study 2 (AREDS2) study, the beta carotene component was replaced by lutein/zeaxanthin for the development of the revised AREDS supplement. However, it is unknown if the increased risk of lung cancer observed in those assigned beta carotene persists beyond the conclusion of the AREDS2 trial and if there is a benefit of adding lutein/zeaxanthin to the original AREDS supplement that can be observed with long-term follow-up. To assess 10-year risk of developing lung cancer and late age-related macular degeneration (AMD). This was a multicenter epidemiologic follow-up study of the AREDS2 clinical trial, conducted from December 1, 2012, to December 31, 2018. Included in the analysis were participants with bilateral or unilateral intermediate AMD for an additional 5 years after clinical trial. Eyes/participants were censored at the time of late AMD development, death, or loss to follow-up. Data were analyzed from November 2019 to March 2022. During the clinical trial, participants were randomly assigned primarily to lutein/zeaxanthin and/or ω-3 fatty acids or placebo and secondarily to no beta carotene vs beta carotene and low vs high doses of zinc. In the epidemiologic follow-up study, all participants received AREDS2 supplements with lutein/zeaxanthin, vitamins C and E, and zinc plus copper. Outcomes were assessed at 6-month telephone calls. Analyses of AMD progression and lung cancer development were conducted using proportional hazards regression and logistic regression, respectively. Self-reported lung cancer and late AMD validated with medical records. This study included 3882 participants (mean [SD] baseline age, 72.0 [7.7] years; 2240 women [57.7%]) and 6351 eyes. At 10 years, the odds ratio (OR) of having lung cancer was 1.82 (95% CI, 1.06-3.12; P = .02) for those randomly assigned to beta carotene and 1.15 (95% CI, 0.79-1.66; P = .46) for lutein/zeaxanthin. The hazard ratio (HR) for progression to late AMD comparing lutein/zeaxanthin with no lutein/zeaxanthin was 0.91 (95% CI, 0.84-0.99; P = .02) and comparing ω-3 fatty acids with no ω-3 fatty acids was 1.01 (95% CI, 0.93-1.09; P = .91). When the lutein/zeaxanthin main effects analysis was restricted to those randomly assigned to beta carotene, the HR was 0.80 (95% CI, 0.68-0.92; P = .002). A direct analysis of lutein/zeaxanthin vs beta carotene showed the HR for late AMD was 0.85 (95% CI, 0.73-0.98; P = .02). The HR for low vs high zinc was 1.04 (95% CI, 0.94-1.14; P = .49), and the HR for no beta carotene vs beta carotene was 1.04 (95% CI, 0.94-1.15; P = .48). Results of this long-term epidemiologic follow-up study of the AREDS2 cohort suggest that lutein/zeaxanthin was an appropriate replacement for beta carotene in AREDS2 supplements. Beta carotene usage nearly doubled the risk of lung cancer, whereas there was no statistically significant increased risk with lutein/zeaxanthin. When compared with beta carotene, lutein/zeaxanthin had a potential beneficial association with late AMD progression.

N-Glycosylation Patterns across the Age-Related Macular Degeneration Spectrum.

The pathogenesis of age-related macular degeneration (AMD) remains elusive, despite numerous research studies. Therefore, we aimed to investigate the changes of plasma and IgG-specific N-glycosylation across the disease severity spectrum. We examined 2835 subjects from the 10.001 Dalmatians project, originating from the isolated Croatian islands of Vis and Korčula. All subjects were classified into four groups, namely (i) bilateral AMD, (ii) unilateral AMD, (iii) early-onset drusen, and (iv) controls. We analysed plasma and IgG N-glycans measured by HPLC and their association with retinal fundus photographs. There were 106 (3.7%) detected cases of AMD; 66 of them were bilateral. In addition, 45 (0.9%) subjects were recorded as having early-onset retinal drusen. We detected several interesting differences across the analysed groups, suggesting that N-glycans can be used as a biomarker for AMD. Multivariate analysis suggested a significant decrease in the immunomodulatory bi-antennary glycan structures in unilateral AMD (adjusted odds ratio 0.43 (95% confidence interval 0.22–0.79)). We also detected a substantial increase in the pro-inflammatory tetra-antennary plasma glycans in bilateral AMD (7.90 (2.94–20.95)). Notably, some of these associations were not identified in the aggregated analysis, where all three disease stages were collapsed into a single category, suggesting the need for better-refined phenotypes and the use of disease severity stages in the analysis of more complex diseases. Age-related macular degeneration progression is characterised by the complex interplay of various mechanisms, some of which can be detected by measuring plasma and IgG N-glycans. As opposed to a simple case-control study, more advanced and refined study designs are needed to understand the pathogenesis of complex diseases.

Predicting Age-related Macular Degeneration Progression with Longitudinal Fundus Images Using Deep Learning.

Accurately predicting a patient's risk of progressing to late age-related macular degeneration (AMD) is difficult but crucial for personalized medicine. While existing risk prediction models for progression to late AMD are useful for triaging patients, none utilizes longitudinal color fundus photographs (CFPs) in a patient's history to estimate the risk of late AMD in a given subsequent time interval. In this work, we seek to evaluate how deep neural networks capture the sequential information in longitudinal CFPs and improve the prediction of 2-year and 5-year risk of progression to late AMD. Specifically, we proposed two deep learning models, CNN-LSTM and CNN-Transformer, which use a Long-Short Term Memory (LSTM) and a Transformer, respectively with convolutional neural networks (CNN), to capture the sequential information in longitudinal CFPs. We evaluated our models in comparison to baselines on the Age-Related Eye Disease Study, one of the largest longitudinal AMD cohorts with CFPs. The proposed models outperformed the baseline models that utilized only single-visit CFPs to predict the risk of late AMD (0.879 vs 0.868 in AUC for 2-year prediction, and 0.879 vs 0.862 for 5-year prediction). Further experiments showed that utilizing longitudinal CFPs over a longer time period was helpful for deep learning models to predict the risk of late AMD. We made the source code available at https://github.com/bionlplab/AMD_prognosis_mlmi2022 to catalyze future works that seek to develop deep learning models for late AMD prediction.

Отдаленные результаты применения комбинированного лазерного лечения друзеноидной отслойки ретинального пигментного эпителия

Drusenoid pigment epithelial detachment is a condition characterized by separation of the retinal pigment epithelium from the underlying Bruch’s membrane due to formation of drusenoid deposits. The disorder represents the intermediate stage of the age-related macular degeneration, and is a risk factor for the age-related macular degeneration progression to late stage characterized by geographic atrophy, which results in the irreversible central vision loss. Management of patients with this disorder is in most cases limited to follow-up. The feasibility of using the multimodality low power mode laser therapy for treatment of drusenoid pigment epithelial detachment is reported. The results of laser photocoagulation of the retina demonstrate the morphological and functional recovery: retinal pigment epithelial detachment sealing, improvement of visual function, and restored retinal architecture.

Gene-based analysis of bi-variate survival traits via functional regressions with applications to eye diseases.

Genetic studies of two related survival outcomes of a pleiotropic gene are commonly encountered but statistical models to analyze them are rarely developed. To analyze sequencing data, we propose mixed effect Cox proportional hazard models by functional regressions to perform gene-based joint association analysis of two survival traits motivated by our ongoing real studies. These models extend fixed effect Cox models of univariate survival traits by incorporating variations and correlation of multivariate survival traits into the models. The associations between genetic variants and two survival traits are tested by likelihood ratio test statistics. Extensive simulation studies suggest that type I error rates are well controlled and power performances are stable. The proposed models are applied to analyze bivariate survival traits of left and right eyes in the age-related macular degeneration progression.

Deep-learning-based Prediction of Late Age-Related Macular Degeneration Progression.

Both genetic and environmental factors influence the etiology of age-related macular degeneration (AMD), a leading cause of blindness. AMD severity is primarily measured by fundus images and recently developed machine learning methods can successfully predict AMD progression using image data. However, none of these methods have utilized both genetic and image data for predicting AMD progression. Here we jointly used genotypes and fundus images to predict an eye as having progressed to late AMD with a modified deep convolutional neural network (CNN). In total, we used 31,262 fundus images and 52 AMD-associated genetic variants from 1,351 subjects from the Age-Related Eye Disease Study (AREDS) with disease severity phenotypes and fundus images available at baseline and follow-up visits over a period of 12 years. Our results showed that fundus images coupled with genotypes could predict late AMD progression with an averaged area under the curve (AUC) value of 0.85 (95%CI: 0.83–0.86). The results using fundus images alone showed an averaged AUC of 0.81 (95%CI: 0.80–0.83). We implemented our model in a cloud-based application for individual risk assessment.

The Association of Aspirin Use with Age-Related Macular Degeneration Progression in the Age-Related Eye Disease Studies: Age-Related Eye Disease Study 2 Report No. 20

To analyze the potential association between aspirin use and progression of age-related macular degeneration (AMD). Two prospective cohort studies within 2 controlled clinical trials of oral supplementation for age-related eye disease. Age-Related Eye Disease Study (AREDS) participants 55 to 80 years of age and AREDS2 participants 50 to 85 years of age. Propensity scores for aspirin use were calculated for AREDS and AREDS2 participants separately by logistic regression. Of the participants without late AMD (geographic atrophy [GA] or neovascular AMD) in either eye at study baseline, aspirin users were matched 1:1 with nonusers by propensity score (separately for AREDS and AREDS2). Proportional hazards regression was performed, adjusting for age, on the matched participants to evaluate associations between aspirin propensity score and progression to late AMD (and its subtypes). Progression to late AMD on color fundus photographs, graded centrally. Of the 3734 eligible AREDS participants, 1049 (28.1%) were taking aspirin, and of the 2403 eligible AREDS2 participants, 1198 (49.9%) were taking aspirin. After matching by propensity score, the characteristics of the users and nonusers were similar in both studies. Of the 1950 matched AREDS participants and 1694 matched AREDS2 participants, over a median follow-up of 10.1 years and 5.0 years, respectively, the numbers who progressed to late AMD, GA, or neovascular AMD were 454 (23.3%), 345 (17.7%), and 278 (14.3%), respectively, in AREDS and 643 (38.0%), 402 (24.6%), and 341 (20.1%) in AREDS2. The hazard ratios of progression in quintile 5 (highest propensity for aspirin use) versus 1 (reference) were 1.17 (P = 0.35), 1.24 (0.25), and 0.95 (0.81), respectively, in AREDS and 1.26 (0.09), 1.46 (0.03), and 1.12 (0.58) in AREDS2. No significant association with progression to late AMD was observed for quintiles 2 through 5 for any of the 3 outcomes in either study. Aspirin use was not associated significantly with progression to late AMD or its subtypes in either the AREDS or AREDS2. Patients with AMD need not avoid aspirin for this reason when its use is medically indicated.

Effect of 2-year nutritional supplementation on progression of age-related macular degeneration.

To examine the effect of a long-term nutritional supplementation on age-related macular degeneration progression. In this prospective, double-blind, placebo-controlled study, 80 patients with intermediate age-related macular degeneration were randomized (2:1) to receive 1 tablet/day of a nutritional supplement containing a mixture of carotenoids, vitamins and omega-3 fatty acids or placebo. Age-related macular degeneration progression assessed by digital fundus photography (primary outcome) and best-corrected visual acuity were evaluated. Differences between arms were tested using chi-square test or Fisher's exact test. Seventy-four patients completed the follow-up at 24 months (48 in the treated arm and 26 in the placebo arm). An age-related macular degeneration progression was observed in the 2.1% of patients of the treated arm and in the 15.4% of patients in the placebo arm (p = 0.05, Fisher's exact test). Best-corrected visual acuity data alone were not statistically significant among groups. A clinically meaningful stabilization of intermediate age-related macular degeneration over a period of 2 years may be obtained by treating patients with a mixture of carotenoids, vitamins and omega-3 fatty acids.

Validated Prediction Models for Macular Degeneration Progression and Predictors of Visual Acuity Loss Identify High-Risk Individuals

To determine predictive factors and risk scores for conversion to overall advanced age-related macular degeneration (AMD), geographic atrophy (GA), neovascular disease (NV), and loss of vision, and to validate the model for AMD in an external cohort. Progression to advanced AMD was evaluated using stepwise survival analysis. Risk scores including genetic, demographic, behavioral, and ocular factors were derived for 3 AMD endpoints and were validated and calibrated in a large independent cohort. Vision loss of 15 or more letters was evaluated as a new endpoint in genetic analyses. Eight common and rare variants in genes CFH, C3, ARMS2, COL8A1, and HSPH1/B3GALTL conferred a significantly higher risk of transition to advanced AMD. Three loci (C2, CFB, RAD51B) were associated with lower rate of progression. A protective effect was suggested for CTRB1 and PELI3. The age-adjusted area under the curve (AUC) for the composite model including 13 loci model was 0.900 over 12 years (0.896 in the validation cohort). Generally, progressors had a higher risk category and nonprogressors had a lower risk category when genetic factors were considered. Furthermore, there was heterogeneity between models for GA and NV. The model was calibrated in the validation cohort. Determinants of visual loss included age, education, body mass index, smoking, and several common and rare genetic variants. Eyes with the same baseline macular grade had a wide range of estimated probability of subsequent progression and visual loss based on the validated risk score. Identifying high-risk individuals at an earlier stage using predictive modeling could lead to improved preventive and therapeutic strategies in the era of precision medicine.

Further Evidence That Cataract Surgery Is Not Associated With Macular Degeneration Progression.

Further Evidence That Cataract Surgery Is Not Associated With Macular Degeneration Progression.