Efficacity and Safety of the Fluocinolone Acetonide Implant in Uveitic Macular Edema: A Real-Life Study from the French Uveitis Network.

PURPOSE: To evaluate the safety and efficacy of the fluocinolone acetonide implant (FAi, Iluvien® Horus pharma, Nice, France) in non-infectious uveitic macular edema (UME) and to approach the predictive factors of treatment response. METHODS: This retrospective, multicenter real-life study included patients with chronic non-infectious UME who received intravitreal FAi after at least two dexamethasone implants (DEXi). RESULTS: Twenty-six eyes from 22 patients (73.1% of females) were included. The mean age was 60.4 ± 16 years. The mean follow-up was 11.4 ± 2 months. The mean baseline best-corrected visual acuity (BCVA) was 0.43 ± 0.36 LogMAR, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). The mean baseline central macular thickness (CMT) was 429 ± 110 µm, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). Five eyes (19.2%) developed ocular hypertension during the follow-up, requiring initiation or strengthening of intraocular pressure lowering medication. The majority of eyes (77%) did not require any rescue DEXi during the available 12-month follow-up. The resolution of UME after DEXi seemed to predict the anatomical response after FAi. The baseline presence of a disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HRF) were both associated with a higher likelihood of requiring rescue DEXi injections. CONCLUSION: FAi implantation led to a significant BCVA and CMT improvement with a good safety profile over the 12-month follow-up. Predictive factors of treatment outcomes seem to include the anatomical response to DEXi and the presence of DRIL and HRF at baseline.

Study of nycthemeral variations in blood pressure in patients with non-arteritic anterior ischemic optic neuropathy.

PURPOSE: The objective of this study was to analyze the nycthemeral variations in blood pressure (BP) in individuals who presented with non-arteritic anterior ischemic optic neuropathy (NAION). METHODS: BP was recorded for 24 h (ambulatory blood pressure monitoring, ABPM) in 65 patients with acute NAION. Three definitions of nighttime periods were used: definition 1, 1 a.m.-6 a.m.; definition 2, 10 p.m.-7 a.m.; and definition 3, 10 p.m.-8 a.m. For each of these definitions, patients were classified according to the value of nocturnal reduction in BP into dippers (10-20%), mild dippers (0-10%), reverse dippers (< 0%), and extreme dippers (> 20%). RESULTS: The proportions of dippers, mild dippers, reverse dippers, and extreme dippers varied significantly depending on the definition chosen. We found the highest number of patients with extreme dipping (23%) when using the strictest definition of nighttime period (definition 1, 1 a.m.-6 a.m.), as compared with 6.2% and 1.5% for the other definitions, respectively. Overall, 13 of 33 patients without known systemic hypertension (39%) were diagnosed with hypertension after ABPM. No risk factor for NAION was associated with the extreme-dipping profile. Finally, the prevalence of systemic hypertension was high (69%). CONCLUSION: In our population of patients who had an episode of NAION, the proportion of extreme dippers was higher than that usually found in the literature. However, extreme dipping is not a frequent feature of patients with NAION as compared to patients with systemic hypertension. ABPM is recommended for all patients with NAION and unknown history of systemic hypertension.

DeepAlienorNet: A deep learning model to extract clinical features from colour fundus photography in age-related macular degeneration.

OBJECTIVE: This study aimed to develop a deep learning (DL) model, named 'DeepAlienorNet', to automatically extract clinical signs of age-related macular degeneration (AMD) from colour fundus photography (CFP). METHODS AND ANALYSIS: The ALIENOR Study is a cohort of French individuals 77 years of age or older. A multi-label DL model was developed to grade the presence of 7 clinical signs: large soft drusen (>125 µm), intermediate soft (63-125 µm), large area of soft drusen (total area >500 µm), presence of central soft drusen (large or intermediate), hyperpigmentation, hypopigmentation, and advanced AMD (defined as neovascular or atrophic AMD). Prediction performances were evaluated using cross-validation and the expert human interpretation of the clinical signs as the ground truth. RESULTS: A total of 1178 images were included in the study. Averaging the 7 clinical signs' detection performances, DeepAlienorNet achieved an overall sensitivity, specificity, and AUROC of 0.77, 0.83, and 0.87, respectively. The model demonstrated particularly strong performance in predicting advanced AMD and large areas of soft drusen. It can also generate heatmaps, highlighting the relevant image areas for interpretation. CONCLUSION: DeepAlienorNet demonstrates promising performance in automatically identifying clinical signs of AMD from CFP, offering several notable advantages. Its high interpretability reduces the black box effect, addressing ethical concerns. Additionally, the model can be easily integrated to automate well-established and validated AMD progression scores, and the user-friendly interface further enhances its usability. The main value of DeepAlienorNet lies in its ability to assist in precise severity scoring for further adapted AMD management, all while preserving interpretability.

Associations of drusen location with risk factors and incidence of late age-related macular degeneration in the Alienor study.

PURPOSE: To test the hypothesis that central drusen location is strongly linked with known Age-related Macular Degeneration (AMD) risk factors and risk of incident late AMD. METHODS: The Alienor study is a prospective population-based cohort study of residents of Bordeaux, France, followed from 2009 to 2017. On retinal photographs, we defined central drusen as at least one soft drusen (>63 µm) within 500 µm from fovea and pericentral drusen as at least one drusen 500-3000 µm from fovea, in the absence of any central drusen. Late AMD (atrophic and/or neovascular) was diagnosed using multimodal imaging. In total, 481 eyes were included in the analysis: 160 central and 321 pericentral. We investigated associations with systemic (age, sex, smoking, medical prescriptions, plasma concentrations of lipids and nutrients, UV exposure, blood pressure), ocular (retinal thickness, cataract extraction) and genetic risk scores (GRS). RESULTS: In multivariate logistic regression central drusen were associated with smoking (OR, 2.95 for smoking more than 20 pack-years, p = 0.02), HDL-cholesterol (OR, 1.57 for 1 standard deviation (SD) increase, p = 0.0048), pulse pressure (OR, 0.77 for 1 SD increase, p = 0.04), Age-Related Maculopathy Susceptibility 2 (ARMS2) GRS (OR, 1.42; 95% CI, 1.11-1.83) and complement GRS (OR, 1.55; 95% CI, 1.15-2.10). In Cox modelling, the central location of drusen (at baseline or during the follow-up) was associated with a 4.41-fold increased risk (95% CI,1.98-9.81) for an incident late AMD. CONCLUSION: Central drusen were strongly associated with AMD risk factors and incident late AMD, suggesting that it represents a key marker for AMD progression.

Ophthalmologic Phenotype-Genotype Correlations in Patients With Oculocutaneous Albinism Followed in a Reference Center.

Purpose: Albinism is a group of genetic disorders that includes several conditions related to a defect in melanin production. There is a broad phenotypic and genotypic variability between the different forms. The aim of this study was to assess the ophthalmologic characteristics according to patients' genotypes in a cohort followed in the Reference Center for oculocutaneous albinism (OCA) of Bordeaux University Hospital, France. Methods: A retrospective observational study was conducted in a cohort of patients with OCA seen in consultation in the ophthalmology department between 2017 and 2021 in whom a genetic analysis was performed. Results: In total, 127 patients with OCA were included in this study and matched with the results of the genetic analysis. In the population aged over 6 years, there was no statistical difference in binocular visual acuity between the OCA1, OCA2, and OCA4 forms (P = 0.27). There was difference in ametropia between the three forms (P = 0.003). A two-by-two comparison using the Bonferroni correction showed a significant difference in ametropia between the OCA2 and OCA4 forms (P = 0.007) and between the OCA1 and OCA2 forms (P = 0.0075). Regardless of the form, most patients (75.4%) had grade 4 foveal hypoplasia. There was no association between the grade of foveal hypoplasia and the gene involved (P = 0.87). Conclusions: We described a genotype-phenotype correlation for the three most represented forms of albinism in our cohort. This study allowed assessing the degree of visual deficiency in young children with OCA.

Association of long-term exposure to ambient air pollution with retinal neurodegeneration: the prospective Alienor study.

Chronic exposure to air pollution may have adverse effects on neurodegenerative diseases. Glaucoma, the second leading cause of blindness worldwide, is a neurodegenerative disease of the optic nerve, characterized by progressive thinning of the retinal nerve fiber layer (RNFL). We investigated the relationship of air pollution exposure with longitudinal changes of RNFL thickness in the Alienor study, a population-based cohort of residents of Bordeaux, France, aged 75 years or more. Peripapillary RNFL thickness was measured using optical coherence tomography imaging every 2 years from 2009 to 2020. Measurements were acquired and reviewed by specially trained technicians to control quality. Air pollution exposure (particulate matter ≤2.5 µm (PM2.5), black carbon (BC), nitrogen dioxide (NO2)) was estimated at the participants' geocoded residential address using land-use regression models. For each pollutant, the 10-year average of past exposure at first RNFL thickness measurement was estimated. Associations of air pollution exposure with RNFL thickness longitudinal changes were assessed using linear mixed models adjusted for potential confounders, allowing for intra-eye and intra-individual correlation (repeated measurements). The study included 683 participants with at least one RNFL thickness measurement (62% female, mean age 82 years). The average RNFL was 90 µm (SD:14.4) at baseline. Exposure to higher levels of PM2.5 and BC in the previous 10 years was significantly associated with a faster RNFL thinning during the 11-year follow-up (-0.28 µm/year (95% confidence interval (CI) [-0.44;-0.13]) and -0.26 µm/year (95% CI [-0.40;-0.12]) per interquartile range increment; p < 0.001 for both). The size of the effect was similar to one year of age in the fitted model (-0.36 µm/year). No statistically significant associations were found with NO2 in the main models. This study evidenced a strong association of chronic exposure to fine particulate matter with retinal neurodegeneration, at air pollution levels below the current recommended thresholds in Europe.

Treatment of nonarteritic anterior ischemic optic neuropathy with an endothelin antagonist: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy)-a multicentre randomised controlled trial protocol.

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients. METHODS: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process. DISCUSSION: An endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT02377271 . Registered on March 3, 2015.

B Vitamins and Incidence of Advanced Age-Related Macular Degeneration: The Alienor Study.

B vitamins may protect against age-related macular degeneration (AMD). We evaluated the associations of dietary intake and serum vitamins with the incidence of advanced AMD in the Alienor study. The Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006-2008). Examinations were performed every two years over an eight-year period. The incidence of AMD is based on retinal fundus photographs and spectral-domain optical coherence tomography examinations. Among the 861 included participants, 93 developed incident AMD during a median follow-up time of 9.8 years. Participants with normal serum folate (≥10 nmol/L) significantly had a 51% reduced risk for AMD in the fully adjusted Cox model (HR, 0.49 [95% CI, 0.25-0.95], p = 0.036). Participants with a higher dietary intake of B5 and B6 vitamins had a lower risk for developing AMD of up to 28% (HR, 0.72 for 1-SD increase [0.53-0.99], p = 0.049; HR, 0.90 [0.81-0.99], p = 0.049, respectively). This cohort study of older adults suggests a strong association between a normal serum folate status, a high dietary intake of B5 and B6 and a lower risk for developing advanced AMD. Adopting a healthy diet rich in B vitamins may help to reduce vision loss due to AMD.

Analysis of Microvascular Abnormalities in Obesity: A Comparative Study with Healthy Subjects Using Swept Source Optical Coherence Tomography Angiography and Adaptive Optics.

PURPOSE: The aim of this study was to analyze retinal microvasculature in obese subjects as compared to a normal-weight population. METHODS: In this case-control observational study, swept-source optical coherence tomography angiography (SS-OCTA) and adaptive optics (AO) were performed in eyes of nondiabetic, nonhypertensive, obese patients and in healthy controls. AO was used to calculate the wall-to-lumen ratio (WLR). The foveal avascular zone (FAZ), the macular vessel density, and the macular perfusion density of the superficial and deep capillary plexuses were analyzed in 6 × 6 mm macular OCTA cubes. SS-OCTA was also used to measure the choroidal thickness, the retinal nerve fiber layer (RNFL), and the vascular density of the retinal peripapillary capillary plexus. RESULTS: The obese group included 45 eyes (24 patients), and the control group included 46 eyes (23 subjects). The central macular density and perfusion density were significantly lower in obese patients compared to controls, in the deep retinal layer (0.28 [0.01-0.69] vs. 1.24 [0.82-1.66], p = 0.006 and 0.006 [0.001-0.015] vs. 0.025 [0.016-0.034], p = 0.01), respectively, after adjustment for systolic blood pressure. No differences were found in macular vascular density in other areas, FAZ (circularity, area, perimeter), choroidal thickness, RNFL. WLR was increased in obese patients (0.252 [0.246-0.259] vs. 0.239 [0.231-0.245] in controls, p = 0.016). CONCLUSION: Obesity was associated with retinal microvascular changes regardless of the presence of diabetes and hypertension. Our findings suggest the presence of infraclinical microvascular changes directly associated with obesity, which can be identified noninvasively through retinal imaging.

LIFELONG PROGRESSIVE RETINAL ATROPHIC LESIONS IN A PATIENT WITH PARTIAL ACQUIRED LIPODYSTROPHY (BARRAQUER-SIMONS SYNDROME).

PURPOSE: To report a case of lifelong progressive retinal atrophic lesions in a patient with partial acquired lipodystrophy, that is, Barraquer-Simons syndrome. METHODS: Case report. RESULTS: A 67-year-old female patient with Barraquer-Simons syndrome was referred for progressive visual loss. Barraquer-Simons syndrome is a rare acquired partial lipodystrophy characterized by a loss of subcutaneous fat in the upper half of the body. Fundus examination disclosed posterior atrophic lesions, particularly evident on autofluorescence images, and their progression as compared to a previous examination performed nine years earlier. Multimodal imaging confirmed the posterior atrophic lesions without any associated exudative signs and highlighted the extension of atrophic areas in the periphery. CONCLUSION: We here report for the first time a documented progressive retinal atrophy associated with Barraquer-Simons syndrome. Drusen and neovascular complications have already been described in previous reports, but no long-term follow-up was available until the present case to observe such dramatic evolution of the retinal lesions.

Quantitative Analysis of Radial Peripapillary Capillary Network in Patients With Papilledema Compared with Healthy Subjects Using Optical Coherence Tomography Angiography.

BACKGROUND: To quantitatively compare the peripapillary microvascular network between patients with papilledema and healthy subjects using swept source optical coherence tomography angiography. METHODS: In this retrospective observational study, patients with papilledema secondary to idiopathic intracranial hypertension and healthy controls were imaged with swept source optical coherence tomography angiography (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, CA) using a 6 × 6 mm scan pattern centered on the optic disc. The capillary perfusion density (CPD) and capillary flux index (CFI) of the radial peripapillary capillaries in the retinal nerve fiber layer (RNFL) were calculated using Zeiss algorithm. RESULTS: Thirty-nine eyes of 20 patients with papilledema and 66 eyes of 33 healthy subjects were imaged. The mean (P < 0.01), superior (P < 0.01), inferior (P < 0.01), and temporal (P = 0.02) CPD significantly differed between both groups. No significant difference was found between both groups for the CFI. The mean (P < 0.01), superior (P < 0.01), inferior (P = 0.01), temporal (P < 0.01), and nasal (P < 0.01) quadrants of the RNFL were positively associated with the CFI. The mean (P < 0.01), superior (P = 0.01), inferior (P = 0.01), temporal (P < 0.01), and nasal (P = 0.01) quadrants of the RNFL were negatively associated with the CPD. CONCLUSION: Our study showed a decreased peripapillary capillary density without changes in flux intensity in eyes with papilledema. There were a positive association between the CFI and the RNFL and a negative association between the CPD and the RNFL. It confirmed the discriminatory ability of OCTA in differentiating a papilledema secondary to IIH from a normal optic disc, while providing complementary information for understanding papilledema pathophysiology.

Plasma Lutein, a Nutritional Biomarker for Development of Advanced Age-Related Macular Degeneration: The Alienor Study.

Lutein and zeaxanthin may lower the risk of age-related macular degeneration (AMD). We evaluated the associations of plasma lutein and zeaxanthin with the incidence of advanced AMD in the Alienor study (Antioxydants Lipides Essentiels Nutrition et Maladies Oculaires). Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006-2008). The present study included 609 participants with complete ophthalmologic and plasma carotenoids data. Examinations were performed every two years over an eight-year period (2006 to 2017). Plasma lutein and zeaxanthin were determined at baseline from fasting blood samples using high-performance liquid chromatography. Cox proportional hazard models were used to assess associations between plasma lutein, zeaxanthin, and their (total cholesterol (TC) + triglycerides (TG)) ratios with AMD. Among the 609 included participants, 54 developed advanced incident AMD during a median follow-up time of 7.6 years (range 0.7 to 10.4). Participants with higher plasma lutein had a reduced risk for incident advanced AMD in the fully adjusted model (HR = 0.63 per 1-SD increase (95% CI, 0.41-0.97), p = 0.03). A similar association was observed using the lutein/(TC + TG) ratio (HR = 0.59 (95% CI, 0.39-0.90), p = 0.01). No associations were evidenced for other carotenoids. Higher plasma lutein was associated with a 37% reduced risk of incident advanced AMD.

INCIDENCE, PROGRESSION, AND RISK FACTORS OF EPIRETINAL MEMBRANES IN THE ELDERLY.

PURPOSE: To determine the incidence, progression rate, and risk factors for epiretinal membranes (ERMs) in a population of French elderly subjects. METHODS: Seven hundred and thirty-five eyes of 413 participants of the population-based ALIENOR study were included between 2009 and 2010. Participants were re-evaluated every 2 years between 2011 and 2017 (i.e., three follow-up visits). The mean duration of follow-up was 5.09 years (SD, 1.8; range, 0.99-7.85). Epiretinal membranes were graded from spectral-domain optical coherence tomography images according to a standardized classification. RESULTS: The incidence rate of ERMs was 9.42 per 100 eye-years (95% confidence interval, 7.36-12.05), corresponding to a 5-year cumulative incidence of 37.6%. In the final multivariable model, ERM incidence was significantly associated with vitreomacular or vitreopapillary adhesion at baseline (hazard ratio, 2.15; P = 0.02), choroidal thinning (hazard ratio, 1.04 per 10 µm decrease; P = 0.02), ERM in the contralateral eye (P = 0.02), and smoking after 85 years (hazard ratio, 6.01; P = 0.003). The 5-year cumulative progression rate was 6.9%. CONCLUSION: Incidence of ERMs was higher in our population than that previously reported, most probably because of the use of spectral-domain optical coherence tomography images. Incident ERMs were found to be associated with vitreous adhesion at baseline, choroidal thinning, ERM in the contralateral eye, and smoking after 85 years.

OCT angiography analysis in acute non-arteritic anterior ischemic optic neuropathy: The importance of segmentation.

BACKGROUND: In non-arteritic anterior ischemic optic neuropathy (NAION), optical coherence tomography angiography (OCTA) shows changes in peripapillary vascularization. However, the presence of an optic disc edema may induce artifacts that prevent visualizing the peripapillary network. The aim of this study was to evaluate the peripapillary vascularization in acute NAION using swept-source OCTA algorithms allowing segmenting only the retinal nerve fiber layer (RNFL). METHODS: Retrospective analysis of 15 eyes with acute NAION of 15 patients. The optic nerve head was imaged using swept-source OCTA. Morphological and quantitative analyzes were performed. The capillary flux index (CFI), defined as the total weighted area of perfused vasculature per unit area, and the capillary perfusion density (CPD), defined as the total area of perfused microvasculature per unit area, were quantified. Each NAION eye was compared to the unaffected fellow eye using a Wilcoxon test for matched samples. RESULTS: After segmentation at the RNFL, the morphological analysis showed less vascular dropout and more vascular tortuosity than the analysis of a larger segmentation. The quantitative analysis showed that the mean CFI and the CFI in the four quadrants were significantly higher in NAION eyes compared to healthy eyes (p = 0.0002 and p < 0.01). The mean CPD and the CFD in the inferior quadrant were lower in NAION eyes (p = 0.03 and p = 0.0054, respectively). DISCUSSION: The RNFL segmentation allowed better visualizing the peripapillary network because the edema related darkening was reduced. The increased CFI suggests an autoregulatory phenomenon to compensate the ischemic process at the ciliary vasculature.

Prevalence of epiretinal membranes in the ageing population using retinal colour images and SD-OCT: the Alienor Study.

PURPOSE: To analyse and compare the prevalence of epiretinal membranes (ERMs) obtained using either standard retinal colour images or spectral-domain optical coherence tomography (SD-OCT) in a population-based setting of French elderly subjects. METHODS: Six hundred twenty-four subjects of the Alienor cohort aged 75 years or older underwent both colour fundus imaging and SD-OCT examinations. The ERMs were graded from retinal images and SD-OCT macular scans in a masked fashion. On SD-OCT images, the early ERMs, mature contractile ERMs without foveal modifications and mature contractile ERMs with foveal alterations were distinguished. RESULTS: 610 (97.8%) subjects had gradable SD-OCT examinations, and 511 (81.9%) had gradable fundus images in at least one eye. According to colour photographs, 11.6% of participants had definite ERMs. From SD-OCT images, 52.8% of the subjects had early ERMs, 7.4% had mature ERMs without foveal involvement, and 9.7% had mature ERMs with foveal alterations. Regardless of the imaging method used, the ERMs were more often observed in pseudophakic eyes than in phakic eyes. Comparison of ERM assessment using fundus photographs versus SD-OCT images demonstrated that the specificity of retinal colour images was good (>89.3%), whereas the sensitivity remained low even though it increased with ERM severity on SD-OCT images. CONCLUSIONS: Spectral-domain optical coherence tomography (SD-OCT) examinations have high feasibility in this elderly population and are much more sensitive than standard colour images for ERM assessments, especially in the early stages of the disease. Our results further highlight the need to use SD-OCT instead of colour retinal photographs for the classification of ERMs in epidemiological studies.

Artificial Intelligence to Detect Papilledema from Ocular Fundus Photographs.

BACKGROUND: Nonophthalmologist physicians do not confidently perform direct ophthalmoscopy. The use of artificial intelligence to detect papilledema and other optic-disk abnormalities from fundus photographs has not been well studied. METHODS: We trained, validated, and externally tested a deep-learning system to classify optic disks as being normal or having papilledema or other abnormalities from 15,846 retrospectively collected ocular fundus photographs that had been obtained with pharmacologic pupillary dilation and various digital cameras in persons from multiple ethnic populations. Of these photographs, 14,341 from 19 sites in 11 countries were used for training and validation, and 1505 photographs from 5 other sites were used for external testing. Performance at classifying the optic-disk appearance was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity, as compared with a reference standard of clinical diagnoses by neuro-ophthalmologists. RESULTS: The training and validation data sets from 6779 patients included 14,341 photographs: 9156 of normal disks, 2148 of disks with papilledema, and 3037 of disks with other abnormalities. The percentage classified as being normal ranged across sites from 9.8 to 100%; the percentage classified as having papilledema ranged across sites from zero to 59.5%. In the validation set, the system discriminated disks with papilledema from normal disks and disks with nonpapilledema abnormalities with an AUC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) and normal from abnormal disks with an AUC of 0.99 (95% CI, 0.99 to 0.99). In the external-testing data set of 1505 photographs, the system had an AUC for the detection of papilledema of 0.96 (95% CI, 0.95 to 0.97), a sensitivity of 96.4% (95% CI, 93.9 to 98.3), and a specificity of 84.7% (95% CI, 82.3 to 87.1). CONCLUSIONS: A deep-learning system using fundus photographs with pharmacologically dilated pupils differentiated among optic disks with papilledema, normal disks, and disks with nonpapilledema abnormalities. (Funded by the Singapore National Medical Research Council and the SingHealth Duke-NUS Ophthalmology and Visual Sciences Academic Clinical Program.).

Incidence and Risk Factors of Reticular Pseudodrusen Using Multimodal Imaging.

Importance: Although retinal multimodal imaging is needed for diagnosing reticular pseudodrusen (RPD), the incidence of RPD in the general population typically has been assessed only using fundus photographs, which may underestimate their incidence. Objectives: To describe the incidence of RPD using retinal color photographs, spectral-domain optical coherence tomography scans, fundus autofluorescence, and near-infrared reflectance images among individuals 77 years of age or older and to analyze the associated risk factors of RPD. Design, Setting, and Participants: The ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires) Study is a cohort of French individuals 77 years of age or older. Data for this study were collected between February 22, 2011, and February 15, 2017, with a mean (SD) follow-up of 3.7 (1.0) years (range, 1.2-5.6 years). At baseline, 501 individuals were eligible to participate. Of 1002 eyes, 197 had prevalent RPD, advanced age-related macular degeneration, or ungradable images. Of the remaining 805 eyes, 333 were missing follow-up data; therefore, the statistical analyses included data from 472 eyes. Data management and statistical analyses were performed between March 15, 2017, and April 5, 2019. Main Outcomes and Measures: Reticular pseudodrusen were considered as present if detected by at least 2 of the following imaging methods: color fundus photographs, fundus autofluorescence, near-infrared reflectance, and spectral-domain optical coherence tomography images. Results: Of the 472 eyes analyzed, 263 (55.7%) were from female participants, and the mean (SD) age was 81.9 (3.2) years. Forty-three eyes developed RPD, corresponding to an annual incidence rate of 2.9% (95% CI, 1.9%-4.4%) per participant and an estimated 5-year risk of 13.5%. In multivariable analysis, 4 risk factors of incident RPD were identified: subfoveal choroidal thinning (hazard ratio [HR], 0.99; 95% CI, 0.99-1.00 per 10-µm decrease in thickness; P = .02) and the presence of the minor allelic variants rs10490924 for ARMS2 (HR, 3.57; 95% CI, 1.80-7.10; P < .001), rs1061170 for CFH (HR, 2.12; 95% CI, 1.02-4.41; P = .04), and rs10468017 for LIPC (HR, 2.57; 95% CI, 1.37-4.82; P = .003). Lipophilic statin therapy was associated with a lower incidence of RPD (HR, 0.13; 95% CI, 0.02-0.74; P = .02). Conclusions and Relevance: With the use of multimodal imaging, the RPD incidence rate was higher than previously reported in other population-based studies using fundus color images. Individuals with subfoveal choroidal thinning or carrying minor allelic variants for ARMS2, CFH, or LIPC had an increased risk for RPD, whereas lipophilic statin therapy was associated with a lower incidence.

CHOROIDAL THICKNESS, VASCULAR FACTORS, AND AGE-RELATED MACULAR DEGENERATION: The ALIENOR Study.

PURPOSE: To study the associations of subfoveal choroidal thickness with vascular risk factors and age-related macular degeneration. METHODS: Two hundred sixty-one participants of the Alienor study had gradable enhanced-depth imaging optical coherence tomography scans of the macula and available data on vascular and genetic risk factors (assessed through face-to-face interview and fasting blood samples) and age-related macular degeneration status (assessed from retinal photographs and optical coherence tomography). Subfoveal choroidal thickness was measured manually on one horizontal scan passing through the fovea. RESULTS: In a multivariate mixed linear model, subfoveal choroidal thickness was independently associated with age greater than 80 years (-21.77 µm, P = 0.02), axial length (-21.77 µm, P < 0.0001), heavy smoking (≥20 pack-years: -24.89 µm, P = 0.05), fasting blood glucose higher than 7 mmol/L (-53.17 µm, P = 0.02), and lipid-lowering treatment (+18.23, P = 0.047). After multivariate adjustment for age, sex, axial length, and vascular and genetic risk factors, subfoveal choroidal thickness was thinner in eyes with central hyperpigmentation (-45.39 µm, P = 0.006), central hypopigmentation (-44.99 µm, P = 0.001), and central pigmentary abnormalities (-44.50 µm, P = 0.001), but not in eyes with late age-related macular degeneration (-18.05 µm, P = 0.33) or soft drusen. CONCLUSION: These findings indicate a relationship between vascular risk factors and choroidal thinning and suggest an early involvement of the choroid in the pathogenesis of age-related macular degeneration.

Optical coherence tomography angiography at the acute phase of optic disc edema.

BACKGROUND: The differential diagnosis of optic disc edema at the acute phase can be challenging. OCT angiography (OCTA) is a new technology allowing the visualization of the peripapillary vascular network and optic disc capillaries. The peripapillary network alterations of glaucoma and chronic non-arteritic anterior ischemic optic neuropathy (NAION) were reported. However, no OCTA studies on acute optic disc edema from various causes. The aim of this project was to use OCTA to demonstrate the vascular changes the optic nerve head of various types of optic disc edema at the acute phase. METHODS: In this retrospective study, patients with non-arteritic anterior ischemic optic neuropathy (NAION), papillitis or papilledema were recruited. Each patient was imaged using the AngioPlex™ CIRRUS™ HD-OCT device(model 5000, Carl Zeiss Meditec, Inc., Dublin, USA) with a scanning area of 6 × 6 mm2 centered on the optic disc. A morphological analysis of the peripapillary network was performed. For some patients with unilateral optic disc edema, a quantitative analysis was performed using a swept-source OCT-A system (PLEX® Elite 9000, Carl Zeiss Meditec, Inc., Dublin, USA). Vessel perfusion density and flux index of the peripapillary area were calculated. RESULTS: Eight eyes with NAION (4 patients), 12 eyes with papillitis (6 patients) and 25 eyes with papilledema (13 patients) were imaged. The apparent disappearance or moderate pattern alteration of the peripapillary capillary vessels were observed in patients with NAION or papillitis, respectively. For papilledema, the capillaries at the surface of the optic disc were dilated and tortuous, but no peripapillary network pattern changes were observed. The quantitative analysis did not show any difference of peripapillary network between NAION and healthy eyes. For papillitis, the flux index was higher in inflammatory eyes compared to the healthy eyes in average (p = 0.03). CONCLUSION: At the acute phase, the morphological analysis of OCT-A appeared to be more useful than the quantification analysis, facilitating the differentiation between the three kinds of ONH edema: ischemic, inflammatory and papilledema.

Plasma Concentrations of Lutein and Zeaxanthin, Macular Pigment Optical Density, and Their Associations With Cognitive Performances Among Older Adults.

Purpose: We investigated the cross-sectional associations between macular pigment optical density (MPOD), plasma lutein (L), and zeaxanthin (Z) concentrations and cognitive function in 184 older adults of the 3-City-Bordeaux cohort. Methods: MPOD was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma L and Z (L+Z) concentrations were determined by high-performance liquid chromatography and were considered either crude or expressed as a ratio of the concentration of plasma lipids (total cholesterol [TC] + triglycerides [TG]). Cognitive performances were assessed using the following four separate neuropsychological tests: the Mini-Mental State Examination (MMSE), the Isaacs Set Test (IST), the Benton Visual Retention Test (BVRT), and the sum of the three free recalls of the Free and Cued Selective Reminding Test (FCSRT). These test results were summarized by a composite global cognitive z-score. Results: Higher MPOD at 0.5° was significantly associated with a higher composite z-score (ß = 0.15, 95% confidence interval [CI] 0.04-0.26), higher BVRT (ß = 0.39, 95%CI 0.08-0.70), and higher IST (ß = 1.16, 95%CI 0.11-2.22) performances. Higher plasma L+Z concentrations were significantly associated with higher IST scores (ß = 0.97, 95%CI 0.01-1.94). Furthermore, a higher L+Z/TC+TG ratio was associated with a higher composite z-score (ß = 0.12, 95%CI 0.01-0.23), along with higher IST (ß = 1.02, 95%CI 0.002-2.04) and FCSRT (ß = 1.55, 95%CI 0.41-2.69) performances. Conclusions: This analysis suggested that both higher MPOD and L+Z concentrations were significantly associated with higher cognitive performances. However, MPOD measurements have the advantage of being a fast and representative measure of long-term carotenoid intake.