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To assess the effectiveness of an active learning approach to measuring the contrast sensitivity function (CSF) in patients with various degrees of dry age-related macular degeneration (AMD) under multiple luminance conditions.Cross-sectional study.Patients with AMD (26 intermediate AMD, 19 AMD with subretinal drusenoid deposits [SDD], 20 geographic atrophy [GA]) and 23 age-matched controls were tested with the Manifold Contrast Vision Meter (Adaptive Sensory Technology) and the qCSF algorithm, which applies active learning to estimate a model of the CSF's global shape. Testing was performed under conditions of standard and low luminance. For each AMD severity, the area under log CSF (AULCSF) and contrast sensitivities at individual spatial frequencies were calculated for analysis. Low-luminance deficits (LLDs) for visual acuity (VA) and AULCSF were calculated as the difference between standard and low luminance values.Progressive decreases in AULCSF were observed as disease severity increased. For standard luminance, pairwise comparisons revealed significant differences between control/intermediate AMD (P.0005), control/SDD (P.0005), control/GA (P.0005), and intermediate AMD/GA (P.005). Similarly, for low luminance, pairwise comparisons revealed significant differences between the controls and each disease group (all P.0005), in addition to significant differences between intermediate AMD/SDD (P.005), and intermediate AMD/GA (P.005). No correlations were found between LLD VA and LLD AULCSF in any AMD groups.Contrast sensitivity measured via qCSF under both standard- and low-luminance conditions correlates with advancing stages of dry AMD. The interaction between luminance and contrast sensitivity appears to reflect a different aspect of visual function than the interaction between luminance and VA.

Background/purpose Age-related macular degeneration is the most prevalent cause of permanent vision loss in the developed world. Drusenoid pigment epithelial detachments are a biomarker of age-related macular degeneration disease progression and typically result in poor visual prognosis. Low luminance visual acuity (LLVA) has been previously been shown to correlate with the severity of age-related macular degeneration. However, the degree of spontaneous improvement of this functional outcome is still under investigation. Methods Observational clinical case report. Results A drusenoid pigment epithelial detachment that increased in size with the development of hyperreflective foci spontaneously improved with restoration of normal foveal contour over the span of 41 months without progression to geographic atrophy or choroidal neovascularization. Although best-corrected visual acuity remained stable both before and after the pigment epithelial detachment resolution, low luminance visual acuity decreased from a baseline of 59 (20/63 -1) to 39 (20/160 -1) letters over 17 months. However, over the subsequent 24 months, low luminance visual acuity improved by 35 letters to 74 letters (20/32 -2). Conclusion Drusenoid pigment epithelial detachments can resolve without treatment. Low luminance visual acuity seems to correlate with the anatomic improvement and can improve spontaneously by more than six lines of vision.

Age-related macular degeneration (AMD) is one of the major causes of vision loss in the elderly in most developed countries. Among other causes, oxidative stress in the retinal pigment epithelium (RPE) has been hypothesized to be a major driving force of AMD pathology. Oxidative stress could be treated by antioxidant administration into the RPE cells. However, to achieve high in-vivo efficacy of an antioxidant, it is imperative that the agent be able to penetrate the tissues and cells. Evidence suggests that lipophilicity governs cellular penetrance. Out of many antioxidant candidates, N-acetyl-L-cysteine (a prodrug of L-cysteine) (NAC) is a potent antioxidant as the bioavailability of the parent drug, L-cysteine, determines the production of glutathione; the universal antioxidant that regulates ROS. To increase the lipophilicity, four ester derivatives of N-acetylcysteine: N-acetylcysteine methyl ester, N-acetylcysteine ethyl ester, N-acetylcysteine propyl ester, and N-acetylcysteine butyl ester were synthesized. To mimic in vitro AMD conditions, hydroquinone, a component of cigarette smoke, was used as the oxidative insult. Cytosolic and mitochondrial protection against oxidative stress were tested using cytosolic and mitochondrial specific assays. The results provide evidence that these lipophilic cysteine prodrugs provide increased protection against oxidative stress in human RPE cells compared with NAC.

Purpose This study investigated the effects of esterification and increased lipophilicity on cellular penetration, accumulation and retention in ARPE-19-nic cells using ester functionalized rhodamine B dyes. Methods Rhodamine B was esterified to generate four dyes with increasing lipophilicity. Cellular uptake, retention and mitochondrial localization were investigated in vitro using ARPE-19-nic cells using direct intracellular and extracellular and mitochondrial fluorescence quantitation, confocal and high-resolution live cell imaging and co-localization with Mito-GFP. Results Cellular penetrance, mitochondrial accumulation, and retention of the esterified dyes were increased in ARPE-19-nic cells compared with the nonesterified parent dye by direct fluorescence quantitation. Imaging demonstrated intracellular accumulation was confined to mitochondria as confirmed by colocalization with Mito-GFP. Conclusions Esterification is an effective way to increase lipophilicity of a dye to improve cellular penetration of chemical entities. These observations may be key to improving retinal drug delivery for retinal pigment epithelium-based diseases. Translational relevance Understanding the intracellular distribution of drugs into retinal pigment epithelium cells is a critical component for identifying potential therapies for retinal pigment epithelium-based diseases.