Faculty Bibliography

To describe the ocurrence of Bartonella-associated neuroretinitis secondary to non-feline pet exposure, we retrospectively reviewed medical records and imaging from patients with a clinical and serologic diagnosis of Bartonella henselae (BH). Retinal imaging included color fundus photography, optical coherence tomography (OCT) and fluorescein angiography (FA). Four eyes of two patients with cat-scratch disease were included in this study, with a mean age of 35 years. The mean follow-up was 13 months, after presentation of infectious neuroretinitis. Both patients suffered from bilateral neuroretinitis after direct contact with family pets (ferret and guinea pig). All patients were treated with a long-term systemic antimicrobial therapy. Visual acuity in all improved to 20/30 or better at six months. In conclusion, humans may develop cat-scratch disease when they are exposed to Bartonella henselae (BH) in the saliva of infected cats or BH-containing flea feces reaching the systemic circulation through scratches or mucous membranes. As the cat flea (Ctenocephalides felis) may reside on non-feline mammals, Bartonella-associated neuroretinitis may result from contact with other furred family pets.

PURPOSE/OBJECTIVE:Most studies of fundus autofluorescence (FAF) in geographic atrophy (GA) have been nonquantitative, with inadequate registration of image modalities. Furthermore, as pointed out in the recent Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT, it is unclear whether decreased FAF would be correlated exclusively with a single category of OCT-defined atrophy. We sought to determine how FAF intensity in eyes with GA correlates with structural changes of the outer retina and choroid as seen on co-registered spectral domain OCT (SD-OCT) images. DESIGN/METHODS:Retrospective cross-sectional. PARTICIPANTS/METHODS:Twenty eyes of 11 patients with GA secondary to non-neovascular age-related macular degeneration (AMD). METHODS:Spectral domain OCT and FAF images for each eye were co-registered using MATLAB (MathWorks Inc, Natick, MA). On B-scans, the choroid, retinal pigment epithelium (RPE), photoreceptor (PR) layer, and outer nuclear layer (ONL) were segmented. Regions of interest (ROIs) including all atrophic and border regions were selected manually on the FAF scans. Regions of interest were subdivided into quartiles of FAF level to correlate with retinal thickness measurements taken along the B-scans. Mean choroid, RPE, PR, and ONL thicknesses were compared across quartiles using an analysis of variance factorial design testing for interaction effects, adjusted for repeated measures (on both eyes) with a within-subjects factor. RESULTS:Seventeen eyes of 10 patients were selected for analysis. The mean choroidal thicknesses were not significantly different across FAF quartiles, but the overall differences in mean RPE, PR layer, and ONL thicknesses across quartiles were statistically significant (analysis of variance, P < 0.001, P < 0.001, and P = 0.015, respectively). Post hoc analysis demonstrated significant differences in thickness among quartiles 1, 2, and 3 for the RPE and PR layers (Tukey, P < 0.01 in each case). The FAF quartiles within GA did not correlate exclusively with single categories of Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration-defined atrophy. CONCLUSIONS:Not only RPE but also PR layer thickness on SD-OCT varies significantly with FAF levels in GA. This suggests that although the RPE cells are losing thickness and function, evidenced by decreased FAF from fluorophores, delicate PR cells also succumb early in the disease process. These relationships should be pursued as a possibly better-detailed mechanism in GA.

Autofluorescence is the emission of light by naturally occurring tissue components on the absorption of incident light. Autofluorescence within the eye is associated with several disorders, such as Age-related Macular Degeneration (AMD) which is a leading cause of central vision loss. Its pathogenesis is incompletely understood, but endogenous fluorophores in retinal tissue might play a role. Hyperspectral fluorescence microscopy of ex-vivo retinal tissue can be used to determine the fluorescence emission spectra of these fluorophores. Comparisons of spectra in healthy and diseased tissues can provide important insights into the pathogenesis of AMD. However, the spectrum from each pixel of the hyperspectral image is a superposition of spectra from multiple overlapping tissue components. As spectra cannot be negative, there is a need for a non-negative blind source separation model to isolate individual spectra. We propose a tensor formulation by leveraging multiple excitation wavelengths to excite the tissue sample. Arranging images from different excitation wavelengths as a tensor, a non-negative tensor decomposition can be performed to recover a provably unique low-rank model with factors representing emission and excitation spectra of these materials and corresponding abundance maps of autofluorescent substances in the tissue sample. We iteratively impute missing values common in fluorescence measurements using Expectation-Maximization and use L₂ regularization to reduce ill-posedness. Further, we present a framework for performing group hypothesis testing on hyperspectral images, finding significant differences in spectra between AMD and control groups in the peripheral macula. In the absence of ground truth, i.e. molecular identification of fluorophores, we provide a rigorous validation of chosen methods on both synthetic and real images where fluorescence spectra are known. These methodologies can be applied to the study of other pathologies presenting autofluorescence that can be captured by hyperspectral imaging.