ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

BACKGROUND: To describe adaptive optics (AO) imaging of foveal sparing in geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: Flood-illumination AO infrared (IR) fundus images were obtained in four consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes). Adaptive optics IR images were overlaid with confocal scanning laser ophthalmoscope near-IR autofluorescence images to allow direct correlation of en face AO features with areas of foveal sparing. Adaptive optics appearance of GA and foveal sparing, preservation of functional photoreceptors, and cone densities in areas of foveal sparing were investigated. RESULTS: In 5 eyes of 4 patients (all female; mean age 74.2 ± 11.9 years), a total of 5 images, sized 4° × 4°, of foveal sparing visualized on confocal scanning laser ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face AO images revealed GA as regions of inhomogeneous hyperreflectivity with irregularly dispersed hyporeflective clumps. By direct comparison with adjacent regions of GA, foveal sparing appeared as well-demarcated areas of reduced reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of note, in these areas, en face AO IR images revealed cone photoreceptors as hyperreflective dots over the background reflectivity (mean cone density 3,271 ± 1,109 cones per square millimeter). Microperimetry demonstrated residual function in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence. CONCLUSION: Adaptive optics allows the appreciation of differences in reflectivity between regions of GA and foveal sparing. Preservation of functional cone photoreceptors was demonstrated on en face AO IR images in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence.

AMP-dependent kinase inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis by suppressing the dissociation between c-Abl and Prdx1 proteins in endothelial cells.

Caveolin-1 is the primary structural component of endothelial caveolae that is essential for transcellular trafficking of albumin and is also a critical scaffolding protein that regulates the activity of signaling molecules in caveolae. Phosphorylation of caveolin-1 plays a fundamental role in the mechanism of oxidant-induced vascular hyper permeability. However, the regulatory mechanism of caveolin-1 phosphorylation remains unclear. Here we identify a previously unexpected role for AMPK in inhibition of caveolin-1 phosphorylation under oxidative stress. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), inhibited oxidative stress-induced phosphorylation of both caveolin-1 and c-Abl, which is the major kinase of caveolin-1, and endocytosis of albumin in human umbilical vein endothelial cell. These effects were abolished by treatment with two specific inhibitors of AICAR, dipyridamole, and 5-iodotubericidin. Consistently, knockdown of the catalytic AMPKα subunit by siRNA abolished the inhibitory effect of AICAR on oxidant-induced phosphorylation of both caveolin-1 and c-Abl. Pretreatment with specific c-Abl inhibitor, imatinib mesylate, and knock down of c-Abl significantly decreased the caveolin-1 phosphorylation after H2O2 exposure and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Interestingly, knockdown of Prdx-1, an antioxidant enzyme associated with c-Abl, increased phosphorylation of both caveolin-1 and c-Abl and abolished the inhibitory effect of AICAR on the caveolin-1 phosphorylation. Furthermore, co-immunoprecipitation experiment showed that AICAR suppressed the oxidant-induced dissociation between c-Abl and Prdx1. Overall, our results suggest that activation of AMPK inhibits oxidative stress-induced caveolin-1 phosphorylation and endocytosis, and this effect is mediated in part by stabilizing the interaction between c-Abl and Prdx-1.

Sensitivity and Specificity of Ultrawide-Field Fundus Photography for the Staging of Sickle Cell Retinopathy in Real-Life Practice at Varying Expertise Level.

PURPOSE: To evaluate the sensitivity and specificity of ultrawide-field fundus photography (UWF-FP) for the detection and classification of sickle cell retinopathy (SCR) by ophthalmologists with varying degrees of expertise in retinal disease. METHODS: Patients presenting with sickle cell disease (SCD) in the Créteil University Eye Clinic, having undergone UWF-FP and ultrawide-field fluorescein angiography (UWF-FA) on the same day, were retrospectively included. Eyes with previous retinal photocoagulation were excluded. SCR was graded independently by UWF-FP and UWF-FA using Goldberg classification by two ophthalmologists with varying expertise levels. RESULTS: Sixty-six eyes of 33 patients were included in the study. The sensitivity of UWF-FP for the detection of proliferative SCR was 100%, (95% confidence interval [CI95%] 76.8-100) for the retinal specialist and 100% (CI95% 71.5-100) for the ophthalmology resident. The specificity of UWF-FP for the detection of proliferative SCR was 100% (CI95% 92.7-100) for the retinal specialist and 98.1% (CI95% 89.7-100) for the ophthalmology resident. CONCLUSIONS: UWF-FP is a valuable exam for proliferative SCR screening, with excellent sensitivity and specificity and a good inter-grader agreement for ophthalmologists with various degree of skills, and is easy to use in a real-life setting.

Laser Photocoagulation for Peripheral Retinal Capillary Hemangioblastoma in von Hippel-Lindau Disease.

PURPOSE: To study the efficacy and limits of laser photocoagulation for retinal capillary hemangioblastoma (RCH) of various sizes in von Hippel-Lindau disease. DESIGN: Retrospective study. PATIENTS: The records of 176 patients with von Hippel-Lindau were reviewed retrospectively. Seventy-four patients with 304 RCHs in 100 eyes were treated primarily with laser photocoagulation. Eyes with concomitant rhegmatogenous or tractional retinal detachment or with papillary RCH were excluded. METHODS: The treatment consisted of inactivating RCH using direct green laser photocoagulation with long-duration laser burns (0.1-0.7 seconds). MAIN OUTCOME MEASURES: The number of RCH lesions per eye, RCH size in disc diameter (DD) at diagnosis, the presence of retinal lipid exudation or subretinal fluid, and visual acuity were recorded. Final outcomes included RCH inactivation, posttreatment complications, and final visual acuity. RESULTS: Patient mean age was 28 years (range, 8-62). Mean follow-up duration after treatment was 4.5 years (range, 0.4-17.5). Median RCH size was 0.25 DD (range, 0.25-3.00). Laser alone inactivated 97% of RCHs. A mean number of 1.6 laser sessions (range, 1-8) were needed to achieve RCH inactivation. A single laser session allowed coagulating 77% of RCHs. Their median size was 0.50 DD (range, 0.25-1.50). More than 1 laser session was needed to inactivate 23% of RCHs. Their median size was 1 DD (range, 0.25-3.00). Among them, 29 (10% of all RCHs) needed additional laser session during the first 48 hours. Their median size was 1.5 DD (range, 0.5-3). Subretinal fluid transiently increased in 7 eyes after the first laser session and was controlled promptly by additional photocoagulation. Additional cryotherapy was needed only in 7 eyes with large RCH partially inactivated by laser. In all eyes, visual acuity remained stable during the follow-up. CONCLUSIONS: In the absence of tractional retinal detachment, laser photocoagulation allowed inactivating most RCHs up to 3 DD, even when they were associated with subretinal fluid. Laser photocoagulation alone inactivated 100% of RCHs up to 1 DD, and 73% of larger RCHs. In such cases, additional cryotherapy increased RCH inactivation to 94% so that 99% of all treated RCHs were finally inactivated.

Visual acuity at presentation in the second eye versus first eye in patients with exudative age-related macular degeneration.

PURPOSE: To assess the difference in best-corrected visual acuity (BCVA) at presentation between the first and second eye in patients with bilateral neovascular age-related macular degeneration (AMD). METHODS: We reviewed the charts of all patients who had a clinical examination for neovascular AMD at the University Eye Clinic of Creteil in January 2013. We retrospectively analyzed demographic and clinical data for 264 patients. RESULTS: In the fellow eye, choroidal neovascularization (CNV) developed in 75/264 patients (28.4%) with a time interval between the 2 events of 30.3 months (range 6-145). Data were available on 65 patients: 14/65 (21.5%) were asymptomatic, 24/65 (36.9%) had BCVA >20/40, whereas at the time of CNV diagnosis in the first eye, no patient was asymptomatic (p<0.0001), and 11/65 (16.9%) eyes had BCVA >20/40 (p<0.0001). The mean BCVA of the first affected eye was 0.68 (± 0.41) logarithm of minimum angle of resolution (logMAR) and the mean BCVA for the second eye was 0.36 (± 0.29) logMAR (p<0.0001). CONCLUSIONS: The BCVA at the time of diagnosis of CNV was higher in the second eye than in the first affected eye. This was possibly due to several factors including systematic bilateral examination in follow-up of unilateral exudative AMD that allowed detection of 20% of cases.

Appearance of medium-large drusen and reticular pseudodrusen on adaptive optics in age-related macular degeneration.

PURPOSE: To investigate the appearance of medium-large drusen and reticular pseudodrusen on adaptive optics (AO). METHODS: In 14 consecutive patients, AO infrared (IR) images were overlaid with confocal scanning-laser-ophthalmoscope IR reflectance images and IR-referenced spectral-domain optical coherence tomography. RESULTS: In eight eyes of six patients, a total of 19 images of medium-large drusen were investigated by AO imaging. En face AO revealed medium-large drusen as highly hyper-reflective round/oval lesions, always centred and/or surrounded by a continuous/discontinuous hyporeflectivity. Cone photoreceptors were detected overlying drusen, appearing either as continuous 'bright' hyper-reflective dots over a 'dark' hyporeflective background, or as continuous 'dark' hyporeflective dots over a 'bright' hyper-reflective background. In eight eyes from eight patients, a total of 14 images of pseudodrusen were investigated by AO imaging. En face AO revealed reticular pseudodrusen as isoreflective lesions, always surrounded by a continuous/discontinuous hyporeflectivity. Cone photoreceptors were detected overlying pseudodrusen as 'bright' hyper-reflective dots over either a hyporeflective or isoreflective background. No 'dark' hyporeflective dots were detected in eyes with reticular pseudodrusen only. Cone photoreceptors were counted on the border of the drusen and pseudodrusen, respectively, and in a visibly healthy zone in its absolute vicinity. A similar decrease in cone appearance was observed for drusen and pseudodrusen (15.7% vs 16.2%). CONCLUSIONS: AO allows differences in reflectivity between medium-large drusen and reticular pseudodrusen to be appreciated. The cone mosaics may be detected as continuous 'bright' hyper-reflective dots overlying/on the border of drusen and pseudodrusen deposits, and possibly as continuous 'dark' hyporeflective dots overlying drusen only.