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Purpose: To introduce and examine the utility of a retinal imaging technique using high-speed optical coherence tomography (OCT) for creating a more complete retinal structural map to aid in the evaluation of patients with macular pathology.Design: Prospective observational case series. Participants: Five patients with a variety of macular pathologies. Methods: Patients were imaged with a Fourier-domain high-speed high-resolution OCT system built at our institution. A sweeping serial OCT B-scan of the macula was acquired to create a detailed retinal structural map. The data were then used to make individual clinical observations.Results: Rapid serial OCT B-scans produced detailed macular maps for all 5 patients. Diagnoses of imaged patients included macular hole, lamellar macular hole, regressed macular hole or macular microhole, choroidal neovascular membrane (CNV) from age-related macular degeneration, and CNV from presumed ocular histoplasmosis syndrome. Reconstructed B-scans and C-scans are shown for selected patients to illustrate the additional perspectives gained by obtaining a detailed retinal map.Conclusions: Rapid serial Fourier-domain OCT B-scanning can be used to create a detailed retinal structural map. This technique provides additional information that can be missed on single OCT images and provides an accurate way to image large or complex lesions, and allows B-scan and C-scan reconstructions to be made that provide additional perspectives into retinal structures that may be missed using traditional imaging methods.

To evaluate the progression of change in the cone-driven multifocal electroretinogram (mfERG) responses in patients previously identified as having highrisk, soft drusen 63 µm or greater. Methods: Seventeen eyes of 14 patients were reevaluated after 28 to 41 months. Fundus changes were graded depending on drusen size and extent. Each of the 103 mfERG responses was analyzed and compared with agematched normal controls and with the baseline measurement. Results: Stable visual acuity was found in 12 of the 17 eyes. Drusen size or extent was increased, decreased, and unchanged in 6, 3, and 8 eyes, respectively. The mfERG responses demonstrated a significant progression in the response density loss and in N1 and P1 implicit time delay compared with the baseline evaluation regardless of drusen change. The extent of response deterioration occurred over the entire retinal area tested. Eyes having decreased drusen at follow-up were typically associated with higher response delays at baseline and follow-up than eyes with stable or increased drusen. Conclusions: Early age-related macular degeneration is associated with a progressive loss in the cone-driven mfERG response despite stable visual acuity. The response deterioration extended beyond the visible drusen area. Implicit times seem to be an important predictor of drusen regression.

Monogenetic diseases provide unique opportunity for studying complex, clinical states that underlie neurological severity. Loss of glycine decarboxylase (GLDC) can severely impact neurological development as seen in non-ketotic hyperglycinemia (NKH). NKH is a neurometabolic disorder lacking quantitative predictors of disease states. It is characterized by elevation of glycine, seizures and failure to thrive, but glycine reduction often fails to confer neurological benefit, suggesting need for alternate tools to distinguish severe from attenuated disease. A major challenge has been that there are 255 unique disease-causing missense mutations in GLDC, of which 206 remain entirely uncharacterized. Here we report a Multiparametric Mutation Score (MMS) developed by combining in silico predictions of stability, evolutionary conservation and protein interaction models and suitable to assess 251 of 255 mutations. In addition, we created a quantitative scale of clinical disease severity comprising of four major disease domains (seizure, cognitive failure, muscular and motor control and brain-malformation) to comprehensively score patient symptoms identified in 131 clinical reports published over the last 15 years. The resulting patient Clinical Outcomes Scores (COS) were used to optimize the MMS for biological and clinical relevance and yield a patient Weighted Multiparametric Mutation Score (WMMS) that separates severe from attenuated neurological disease (p = 1.2 e-5). Our study provides understanding for developing quantitative tools to predict clinical severity of neurological disease and a clinical scale that advances monitoring disease progression needed to evaluate new treatments for NKH.

Fd-OCT provides unprecedented in vivo detail of the anatomy of RAP lesions that nearly resembles histologic specimens. This study suggests that the initial neovascular process in RAP can originate either within the retina or in the sub-RPE space.