AUTOPHAGY IN THE EYE: FROM PHYSIOLOGY TO PATHOPHYSOLOGY.

Autophagy is a catabolic self-degradative pathway that promotes the degradation and recycling of intracellular material through the lysosomal compartment. Although first believed to function in conditions of nutritional stress, autophagy is emerging as a critical cellular pathway, involved in a variety of physiological and pathophysiological processes. Autophagy dysregulation is associated with an increasing number of diseases, including ocular diseases. On one hand, mutations in autophagy-related genes have been linked to cataracts, glaucoma, and corneal dystrophy; on the other hand, alterations in autophagy and lysosomal pathways are a common finding in essentially all diseases of the eye. Moreover, LC3-associated phagocytosis, a form of non-canonical autophagy, is critical in promoting visual cycle function. This review collects the latest understanding of autophagy in the context of the eye. We will review and discuss the respective roles of autophagy in the physiology and/or pathophysiology of each of the ocular tissues, its diurnal/circadian variation, as well as its involvement in diseases of the eye.

Near-Infrared Reflectance Imaging for Quantification of Atrophy Associated with Age-Related Macular Degeneration.

PURPOSE: To compare measurements of area of geographic atrophy (GA) in dry age-related macular degeneration (AMD) obtained by fundus autofluorescence (FAF) to those obtained by near-infrared reflectance (NIR). DESIGN: Interrater reliability analysis. METHODS: Ninety-seven confocal NIR images (Heidelberg HRA + Spectralis) and FAF images from 97 patients/eyes with GA with dry AMD were collected retrospectively from existing anonymized Doheny Image Reading Center datasets. Two masked reading center graders (N.S., J.S.) independently and blindly performed manual segmentation of the GA lesions on each NIR and FAF image using GNU Image Manipulation Program software (version 2.8.22). GA on NIR/FAF images was defined in accordance to recently published Classification of Atrophy Meeting criteria as sharply demarcated hyperreflective regions ≥250 µm in diameter. The difference and point-to-point correspondence between gradings in GA area measurements between NIR and FAF were assessed by mean difference, overlap ratio, and Dice similarity coefficient. RESULTS: Among the 97 eyes with dry AMD, the mean GA area was 7.62 ± 7.77 mm2 from FAF images and 7.65 ± 7.83 mm2 from NIR, with a mean nonsignificant difference of 0.31 ± 0.55 mm2 (2-tailed t test, P = .65). The overlap ratio in the segmented GA lesion between modalities was 0.84 ± 0.28 with a Dice similarity coefficient of 0.87 ± 0.27. Intermodal reliability was high (intraclass correlation coefficient = 0.998, P < .01). Of note, in 5 cases (5.2%), the GA lesion could be identified on the FAF image but not on the NIR image, translating into a sensitivity of 94.8%. CONCLUSIONS: GA lesions in dry AMD can be identified and quantified reliably using NIR images in many cases, though eyes with a thin choroid resulting in isoreflective GA lesions may be challenging. NIR imaging is comfortable for patients and is commonly obtained along with OCT, and therefore NIR-based GA assessment may be a useful surrogate in clinical settings.