A simple scoring system relevant to prognosis for early AMD, and practical for use in a busy clinic, can be developed using SD-OCT criteria alone.

Drusen are lipid-, mineral-, and protein-containing extracellular deposits that accumulate between the basal lamina of the retinal pigment epithelium (RPE) and Bruch’s membrane (BrM) of the human eye. They are a defining feature of age-related macular degeneration (AMD), a common sight-threatening disease of older adults. The appearance of heterogeneous internal reflectivity within drusen (HIRD) on optical coherence tomography (OCT) images has been suggested to indicate an increased risk of progression to advanced AMD. Here, in a cohort of patients with AMD and drusen, we show that HIRD indicated an increased risk of developing advanced AMD within 1 year. Using multimodal imaging in an independent cohort, we demonstrate that progression to AMD was associated with increasing degeneration of the RPE overlying HIRD. Morphological analysis of clinically imaged cadaveric human eye samples revealed that HIRD was formed by multilobular nodules. Nanoanalytical methods showed that nodules were composed of hydroxyapatite and that they differed from spherules and BrM plaques, other refractile features also found in the retinas of patients with AMD. These findings suggest that hydroxyapatite nodules may be indicators of progression to advanced AMD and that using multimodal clinical imaging to determine the composition of macular calcifications may help to direct therapeutic strategies and outcome measures in AMD.

Background: Current manual diabetic retinopathy (DR) screening using eye care experts cannot scale to screen the growing population of diabetes patients who are at risk for vision loss. EyeArt system is an automated, cloud-based artificial intelligence (AI) eye screening technology designed to easily detect referral-warranted DR immediately through automated analysis of patient's retinal images.Methods: This retrospective study assessed the diagnostic efficacy of the EyeArt system v2.0 analyzing 850,908 fundus images from 101,710 consecutive patient visits, collected from 404 primary care clinics. Presence or absence of referral-warranted DR (more than mild nonproliferative DR [NPDR]) was automatically detected by the EyeArt system for each patient encounter, and its performance was compared against a clinical reference standard of quality-assured grading by rigorously trained certified ophthalmologists and optometrists.Results: Of the 101,710 visits, 75.7% were nonreferable, 19.3% were referable to an eye care specialist, and in 5.0%, the DR level was unknown as per the clinical reference standard. EyeArt screening had 91.3% (95% confidence interval [CI]: 90.9–91.7) sensitivity and 91.1% (95% CI: 90.9–91.3) specificity. For 5446 encounters with potentially treatable DR (more than moderate NPDR and/or diabetic macular edema), the system provided a positive “refer” output to 5363 encounters achieving sensitivity of 98.5%.Conclusions: This study captures variations in real-world clinical practice and shows that an AI DR screening system can be safe and effective in the real world. This study demonstrates the value of this easy-to-use, automated tool for endocrinologists, diabetologists, and general practitioners to address the growing need for DR screening and monitoring.

for the ProgStar Study Group IMPORTANCE Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease. OBJECTIVE To describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study. DESIGN, SETTING, AND PARTICIPANTSA multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye.EXPOSURES Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. Progression rates were estimated from linear mixed models with time as the independent variable. MAIN OUTCOMES AND MEASURESYearly rate of progression using the growth of atrophic lesions measured by fundus autofluorescence.RESULTS A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm 2 . The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm 2 . Mean progression of DDAF was 0.51 mm 2 /y (95% CI, 0.42-0.61 mm 2 /y), and of total decreased fundus autofluorescence was 0.35 mm 2 /y (95% CI, 0.28-0.43 mm 2 /y). Rates of progression depended on the initial size of the lesion. CONCLUSIONS AND RELEVANCEIn Stargardt disease with DDAF lesions, fundus autofluorescence may serve as a monitoring tool for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.