Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress.

Oxidative stress is a known contributor to the progression of dry eye disease pathophysiology, and previous studies have shown that antioxidant intervention is a promising therapeutic approach to reduce the disease burden and slow disease progression. In this study, we evaluated the pharmacological efficacy of the naturally occurring prenylated chalconoid, xanthohumol, in preclinical models for dry eye disease. Xanthohumol acts by promoting the transcription of phase II antioxidant enzymes. In this study, xanthohumol prevented tert-butyl hydroperoxide-induced loss of cell viability in human corneal epithelial (HCE-T) cells in a dose-dependent manner and resulted in a significant increase in expression of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of phase II endogenous antioxidant enzymes. Xanthohumol-encapsulating poly(lactic-co-glycolic acid) nanoparticles (PLGA NP) were cytoprotective against oxidative stress in vitro, and significantly reduced ocular surface damage and oxidative stress-associated DNA damage in corneal epithelial cells in the mouse desiccating stress/scopolamine model for dry eye disease in vivo. PLGA NP represent a safe and efficacious drug delivery vehicle for hydrophobic small molecules to the ocular surface. Optimization of NP-based antioxidant formulations with the goal to minimize instillation frequency may represent future therapeutic options for dry eye disease and related ocular surface disease.

Water-Drinking Test in Central Serous Chorioretinopathy.

PURPOSE: To evaluate choroidal changes in central serous chorioretinopathy (CSCR) patients after water-drinking test (WDT). METHODS: This prospective study included treatment-naïve acute and chronic CSCR eyes and healthy controls. Intraocular pressure and optical coherence tomography measurements with choroidal vascular index (CVI) measurements were done at baseline. Patients were asked to drink 1 L of water, and tests were repeated at 15, 30, and 45 min. RESULTS: Fifty-six eyes from 42 patients were enrolled. Choroidal area, luminal area, and stromal area were higher at baseline in eyes with acute CSCR compared to healthy controls. Chronic CSCR eyes showed an increase in choroidal area and stromal area and a decrease in the luminal area at 15 min. There was a significant decrease in CVI at 30 and 45 min in chronic CSCR and CVI at 45 min in fellow eyes of acute CSCR. Repeated-measures analysis of variance (ANOVA) showed a significant change in central macular thickness in acute CSCR, choroidal thickness in fellow eyes of acute CSCR, stromal area, and total choroidal area in chronic CSCR. Mixed model ANOVA showed that the change in various choroidal parameters seen had no interaction with the eye type. CONCLUSION: Although change in various parameters was seen in acute CSCR, chronic CSCR, and fellow eyes of acute CSCR following WDT, the change was not significantly different among the groups.

Wide-field choroidal vascular analysis in central serous chorioretinopathy.

PURPOSE: To report the wide-field choroidal vessel analysis in central serous chrorioretinopathy (CSCR) and their fellow eyes. METHODS: Wide-field optical coherence tomography (WF-OCT) images (55°) were obtained using Spectralis HRA + OCT (Heidelberg Engineering, Germany) in extremes of gazes in all quadrants and manual montages were created to obtain wide field images up to equator. Choroidal thickness (CT), large choroidal vessel layer thickness (LCVT), and choroidal vascularity index (CVI) were calculated in macular segment (twice the disc to fovea distance) and all four quadrants. Regression analysis was performed to identify the factors influencing CVI. RESULTS: Thirty-one patients of CSCR including 39 eyes of CSCR (32 chronic, 7 acute) and 23 fellow eyes were analyzed. CT and LCVT were significantly higher in submacular choroid than all extramacular segments in both CSCR and fellow eyes (all p values <0.01). CVI varied significantly in different segments in horizontal (p < 0.01 in both) and vertical meridian (p < 0.01 and p = 0.01 respectively) in CSCR and fellow eyes. Both CSCR and fellow eyes had highest CVI in nasal segment with minimum CVI in macular segment. Age (p = 0.85), gender (p = 0.39), chronicity of the disease (acute vs chronic, p = 0.57), axial length (p = 0.67), SBP (p = 0.81), and DBP (p = 0.94) were not significantly correlated to CVI. CONCLUSION: CVI shows significant regional variation with macular segment showing the lowest CVI whereas nasal segments have highest CVI in both CSCR and their fellow eyes. On the contrary, submacular segment has highest CT and LCVT with taper towards periphery in both CSCR and fellow eyes.

En-face choroidal vascularity map of the macula in healthy eyes.

PURPOSE: To report the en-face choroidal vascularity index in healthy eyes. METHODS: Thirty eyes of 30 healthy individuals were studied. Multiple high-density cross-sectional swept source optical coherence tomography scans were obtained to create a volume scan. The choroid was segmented for the whole volume scan and choroidal inner boundaries were flattened. Subsequently, multiple en-face scans separated by 25 µm were obtained and binarized. Choroidal vascularity index was calculated at level of choriocapillaris, medium, and large choroidal vessels. RESULTS: The mean age of the study cohort was 35.6 ± 8.8 years. The overall mean en-face choroidal vascularity index was 54.25 ± 0.55%. There was a statistically significant difference of choroidal vascularity index in choriocapillaris (53.16 ± 0.43%), medium choroidal vessel (51.38 ± 0.27%), and large choroidal vessel (55.69 ± 0.87%) (p < 0.01). Choroidal vascularity index analysis in three subgroups based on subfoveal choroidal thickness (low: <300 µm, medium: 300-400 µm, high: >400 µm) showed a statistically significant difference (p = 0.001). Choroidal vascularity index showed a significant correlation with subfoveal choroidal thickness (r = 0.441; p = 0.015), whereas there was no significant correlation of age (p = 0.21), refraction (p = 0.20), and gender (p = 0.67) with en-face choroidal vascularity index. CONCLUSION: En-face choroidal vascularity index shows a significant variation at the level of choriocapillaris, medium choroidal vessel, and large choroidal vessel in normal eyes. Choroidal vascularity index reaches a nadir at the level of medium choroidal vessel and reaches the maximum value at large choroidal vessel near choroidoscleral interface. En-face choroidal vascularity index shows a significant physiological variation and appears to increase with increase in subfoveal choroidal thickness.

New Insights on Choroidal Vascularity: A Comprehensive Topographic Approach.

Purpose: To obtain a choroidal vascularity index (CVI) map of macular area on an Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Methods: The study was a cross-sectional study involving 30 eyes of 30 healthy individuals. In brief, a shadow-compensated automated algorithm was used to segment and binarize the individual optical coherence tomography (OCT) B-scans. This was followed by three-dimensional reconstruction of these processed B-scans to obtain the overall thickness and vascularity maps. ETDRS grid was overlaid on both the extrapolated thickness and vascularity maps to obtain the corresponding sector-wise CVI. The main outcome measure was to evaluate the topographical variation of CVI in the macular area. Results: The mean age of the study participants was 44.33 ± 16.29 years (range, 18-70 years). CVI showed no significant difference in different rings, subfields, or quadrants of the ETDRS map. CVI had a negative correlation with age (r = -0.384, P = 0.03). There were no statistically significant differences between CVI of both eyes in either rings or the full ETDRS grid (P = 0.30) among normal subjects. Conclusions: The variation in CVI does not follow similar patterns as seen in choroidal thickness (CT) in various locations. The novel choroidal vascularity mapping in the macular area may expand understanding on regional differences of choroidal vasculature in healthy eyes.