The neuroprotective effect of hesperidin in NMDA-induced retinal injury acts by suppressing oxidative stress and excessive calpain activation.

We found that hesperidin, a plant-derived bioflavonoid, may be a candidate agent for neuroprotective treatment in the retina, after screening 41 materials for anti-oxidative properties in a primary retinal cell culture under oxidative stress. We found that the intravitreal injection of hesperidin in mice prevented reductions in markers of the retinal ganglion cells (RGCs) and RGC death after N-methyl-D-aspartate (NMDA)-induced excitotoxicity. Hesperidin treatment also reduced calpain activation, reactive oxygen species generation and TNF-α gene expression. Finally, hesperidin treatment improved electrophysiological function, measured with visual evoked potential, and visual function, measured with optomotry. Thus, we found that hesperidin suppressed a number of cytotoxic factors associated with NMDA-induced cell death signaling, such as oxidative stress, over-activation of calpain, and inflammation, thereby protecting the RGCs in mice. Therefore, hesperidin may have potential as a therapeutic supplement for protecting the retina against the damage associated with excitotoxic injury, such as occurs in glaucoma and diabetic retinopathy.

Clinical Factors Associated with Lamina Cribrosa Thickness in Patients with Glaucoma, as Measured with Swept Source Optical Coherence Tomography.

PURPOSE: To investigate the influence of various risk factors on thinning of the lamina cribrosa (LC), as measured with swept-source optical coherence tomography (SS-OCT; Topcon). METHODS: This retrospective study comprised 150 eyes of 150 patients: 22 normal subjects, 28 preperimetric glaucoma (PPG) patients, and 100 open-angle glaucoma patients. Average LC thickness was determined in a 3 x 3 mm cube scan of the optic disc, over which a 4 x 4 grid of 16 points was superimposed (interpoint distance: 175 µm), centered on the circular Bruch's membrane opening. The borders of the LC were defined as the visible limits of the LC pores. The correlation of LC thickness with Humphrey field analyzer-measured mean deviation (MD; SITA standard 24-2), circumpapillary retinal nerve fiber layer thickness (cpRNFLT), the vertical cup-to-disc (C/D) ratio, and tissue mean blur rate (MBR) was determined with Spearman's rank correlation coefficient. The relationship of LC thickness with age, axial length, intraocular pressure (IOP), MD, the vertical C/D ratio, central corneal thickness (CCT), and tissue MBR was determined with multiple regression analysis. Average LC thickness and the correlation between LC thickness and MD were compared in patients with the glaucomatous enlargement (GE) optic disc type and those with non-GE disc types, as classified with Nicolela's method. RESULTS: We found that average LC thickness in the 16 grid points was significantly associated with overall LC thickness (r = 0.77, P < 0.001). The measurement time for this area was 12.4 ± 2.4 minutes. Average LC thickness in this area had a correlation coefficient of 0.57 with cpRNFLT (P < 0.001) and 0.46 (P < 0.001) with MD. Average LC thickness differed significantly between the groups (normal: 268 ± 23 µm, PPG: 248 ± 13 µm, OAG: 233 ± 20 µm). Multiple regression analysis showed that MD (ß = 0.29, P = 0.013), vertical C/D ratio (ß = -0.25, P = 0.020) and tissue MBR (ß = 0.20, P = 0.034) were independent variables significantly affecting LC thickness, but age, axial length, IOP, and CCT were not. LC thickness was significantly lower in the GE patients (233.9 ± 17.3 µm) than the non-GE patients (243.6 ± 19.5 µm, P = 0.040). The correlation coefficient between MD and LC thickness was 0.58 (P < 0.001) in the GE patients and 0.39 (P = 0.013) in the non-GE patients. CONCLUSION: Cupping formation and tissue blood flow were independently correlated to LC thinning. Glaucoma patients with the GE disc type, who predominantly have large cupping, had lower LC thickness even with similar glaucoma severity.

Blue light and near-infrared fundus autofluorescence in acute Vogt-Koyanagi-Harada disease.

BACKGROUND/AIMS: To investigate the characteristics of fundus autofluorescence (FAF) in acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: FAF photography with blue light (BL-FAF) and near-infrared light (NIR-FAF) was performed on 10 eyes of five patients using a confocal scanning laser ophthalmoscope before and after treatment. The FAF images were followed for 6 months and retrospectively reviewed with comparisons of the other imaging modalities. RESULTS: At presentation, four eyes of two patients who presented soon after the initial ocular symptoms showed mild and uniform hyperautofluorescence in the macula mixed with hypoautofluorescence in the areas of serous retinal detachment. After immediate treatment with an intravenous high-dose steroid, the abnormal FAF returned to normal at 6 months. The other six eyes of three patients, who presented weeks after the symptoms, initially demonstrated diffuse and mottled hyperautofluorescence over the posterior pole, mixed with hypoautofluorescence induced by serous retinal detachment in four eyes. After treatment with an intravenous high-dose steroid, all six eyes showed scattered and widespread hyperautofluorescence, which gradually became evident and concentrated in the macula, partially resulting in some hypoautofluorescent dots at 6 months. The BL-FAF and the NIR-FAF demonstrated similar FAF patterns, but more evidently in NIR-FAF. CONCLUSION: FAF photography non-invasively visualised sequential metabolic and functional changes in the retinal pigment epithelium (RPE) in acute VKH disease. The results suggest that early and sufficient treatment with a high-dose steroid might prevent persistent RPE damage. In addition, NIR-FAF can be an alternative method for the early detection of RPE abnormality.