Comparison of Digital Widefield Retinal Imaging With Indirect Ophthalmoscopy in Pediatric Patients.

BACKGROUND AND OBJECTIVE: Approximately 16,000 children in the United States lose vision each year because of retinal disease. The authors compare digital ultra-widefield (UWF) photography to indirect ophthalmoscopy in children. PATIENTS AND METHODS: Prospective, single-center study of patients ages 3 to 17 years. Retinal area during indirect ophthalmoscopy was compared with retinal area in digital UWF fundus photographs. Image quality was graded. A survey to assess the usefulness of the retinal image was obtained. RESULTS: The retinal area (mean ± standard deviation, mm2) evaluated with indirect ophthalmoscopy was 413 ± 194 mm2, compared with 652 ± 117 mm2 with widefield photography (P < .001). The difference was largest in children younger than 14. Image quality was significantly associated with patient cooperation. CONCLUSIONS: High-quality UWF photographs evaluate more peripheral retina than the in-office dilated funduscopic exam in children under 14. Photography assisted with family counseling in 17% of patients and the avoidance of examination under anesthesia in 2% of patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:580-585.].

Prostaglandin E2 promotes features of replicative senescence in chronically activated human CD8+ T cells.

Prostaglandin E2 (PGE2), a pleiotropic immunomodulatory molecule, and its free radical catalyzed isoform, iso-PGE2, are frequently elevated in the context of cancer and chronic infection. Previous studies have documented the effects of PGE2 on the various CD4+ T cell functions, but little is known about its impact on cytotoxic CD8+ T lymphocytes, the immune cells responsible for eliminating virally infected and tumor cells. Here we provide the first demonstration of the dramatic effects of PGE2 on the progression of human CD8+ T cells toward replicative senescence, a terminal dysfunctional state associated multiple pathologies during aging and chronic HIV-1 infection. Our data show that exposure of chronically activated CD8+ T cells to physiological levels of PGE2 and iso-PGE2 promotes accelerated acquisition of markers of senescence, including loss of CD28 expression, increased expression of p16 cell cycle inhibitor, reduced telomerase activity, telomere shortening and diminished production of key cytotoxic and survival cytokines. Moreover, the CD8+ T cells also produced higher levels of reactive oxygen species, suggesting that the resultant oxidative stress may have further enhanced telomere loss. Interestingly, we observed that even chronic activation per se resulted in increased CD8+ T cell production of PGE2, mediated by higher COX-2 activity, thus inducing a negative feedback loop that further inhibits effector function. Collectively, our data suggest that the elevated levels of PGE2 and iso-PGE2, seen in various cancers and HIV-1 infection, may accelerate progression of CD8+ T cells towards replicative senescence in vivo. Inhibition of COX-2 activity may, therefore, provide a strategy to counteract this effect.