Person:

Husain, Deeba

Background: Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. Methods: The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. Results: We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p)15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. Conclusions: The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease.

Purpose The purpose of this study was to develop an algorithm to automatically standardize the brightness, contrast, and color balance of digital color fundus photographs used to grade AMD and to validate this algorithm by determining the effects of the standardization on image quality and disease grading. Methods: Seven-field color photographs of patients (>50 years) with any stage of AMD and a control group were acquired at two study sites, with either the Topcon TRC-50DX or Zeiss FF-450 Plus cameras. Field 2 photographs were analyzed. Pixel brightness values in the red, green, and blue (RGB) color channels were adjusted in custom-built software to make the mean brightness and contrast of the images equal to optimal values determined by the Age-Related Eye Disease Study (AREDS) 2 group. Results: Color photographs of 370 eyes were analyzed. We found a wide range of brightness and contrast values in the images at baseline, even for those taken with the same camera. After processing, image brightness variability (brightest image–dimmest image in a color channel) was reduced 69-fold, 62-fold, and 96-fold for the RGB channels. Contrast variability was reduced 6-fold, 8-fold, and 13-fold, respectively, after adjustment. Of the 23% images considered nongradable before adjustment, only 5.7% remained nongradable. Conclusions: This automated software enables rapid and accurate standardization of color photographs for AMD grading. Translational Relevance This work offers the potential to be the future of assessing and grading AMD from photos for clinical research and teleimaging.

Purpose To differentiate the plasma metabolomic profile of patients with age related macular degeneration (AMD) from that of controls, by Nuclear Magnetic Resonance (NMR) spectroscopy. Methods: Two cohorts (total of 396 subjects) representative of central Portugal and Boston, USA phenotypes were studied. For each cohort, subjects were grouped according to AMD stage (early, intermediate and late). Multivariate analysis of plasma NMR spectra was performed, followed by signal integration and univariate analysis. Results: Small changes were detected in the levels of some amino acids, organic acids, dimethyl sulfone and specific lipid moieties, thus providing some biochemical information on the disease. The possible confounding effects of gender, smoking history and age were assessed in each cohort and found to be minimal when compared to that of the disease. A similar observation was noted in relation to age-related comorbidities. Furthermore, partially distinct putative AMD metabolite fingerprints were noted for the two cohorts studied, reflecting the importance of nutritional and other lifestyle habits in determining AMD metabolic response and potential biomarker fingerprints. Notably, some of the metabolite changes detected were noted as potentially differentiating controls from patients diagnosed with early AMD. Conclusion: For the first time, this study showed metabolite changes in the plasma of patients with AMD as compared to controls, using NMR. Geographical origins were seen to affect AMD patients´ metabolic profile and some metabolites were found to be valuable in potentially differentiating controls from early stage AMD patients. Metabolomics has the potential of identifying biomarkers for AMD, and further work in this area is warranted.

The complement system is a key component of innate immunity comprised of soluble components that form a proteolytic cascade leading to the generation of effector molecules involved in cellular clearance. This system is highly activated not only under general inflammatory conditions such as infections, collagen diseases, nephritis, and liver diseases, but also in focal ocular diseases. However, little is known about the role of the complement system in retinal homeostasis during aging. Using young (6-week-old) and adult (6-month-old) mice in wild type (C57BL/6) and complement knockout strains (C1q−/−, Mbl a/c−/−, Fb−/−, C3−/−, and C5−/−), we compared amplitudes of electroretinograms (ERG) and thicknesses of retinal layers in spectral domain optical coherence tomography between young and adult mice. The ERG amplitudes in adult mice were significantly decreased (p < 0.001, p < 0.0001) compared to that of young mice in all complement knockout strains, and there were significant decreases in the inner nuclear layer (INL) thickness in adult mice compared to young mice in all complement knockout strains (p < 0.0001). There were no significant differences in ERG amplitude or thickness of the INL between young and adult control mice. These data suggest that the complement system plays an important role in maintaining normal retinal integrity over time.

Purpose Eyes with age-related macular degeneration (AMD) often harbor pathological changes in the retinal periphery and perimacular region. These extramacular changes have not been well classified, but may be phenotypically and functionally relevant. The purpose of this study was to demonstrate a novel grid to systematically study peripheral retinal abnormalities in AMD using geometric distortion-corrected ultra-widefield (UWF) imaging. Methods: This is a cross-sectional observational case series. Consecutive patients with AMD without any other coexisting vitreoretinal disease and control patients over age 50 without AMD or any other vitreoretinal disease were imaged using Optos 200 Tx. Captured 200° UWF images were corrected for peripheral geometric distortion using Optos transformation software. A newly developed grid to study perimacular and peripheral abnormalities in AMD was then projected onto the images. Results: Peripheral and perimacular changes such as drusen, retinal pigment epithelium changes and atrophy were found in patients with AMD. The presented grid in conjunction with geometric distortion-corrected UWF images allowed for systematic study of these peripheral changes in AMD. Conclusion: We present a novel grid to study peripheral and posterior pole changes in AMD. The grid is unique in that it adds a perimacular zone, which may be important in characterizing certain phenotypes in AMD. Our UWF images were corrected for geometric peripheral distortion to accurately reflect the anatomical dimensions of the retina. This grid offers a reliable and reproducible foundation for the exploration of peripheral retinal pathology associated with AMD.

Purpose To describe an unusual case of intravenous drug abuse associated endogenous endophthalmitis presenting with an iris abscess. Observations A 30-year old female with history of intravenous drug use presented with a two-week history of redness and blurry vision in the right eye. An initial diagnosis of anterior uveitis was made. However, she worsened on topical steroids and mydriatics. She was found to have a hypopyon and an iris abscess. She received broad spectrum antibiotic and antifungal treatment with voriconazole, this lead to significant clinical improvement. She was discharged on oral fluconazole and lost to follow up. The patient was noncompliant with the antifungal treatment. The hypopyon and iris abscess recurred, and she required a vitrectomy with iridectomy, along with intravitreal and systemic antifungal treatment. The vitreous cultures and surgical specimen of iris issue were positive for Candida albicans, and she received voriconazole. This led to resolution of the condition with a final visual acuity of 20/20 at six month follow up. Conclusions and importance An iris abscess is a rare clinical presentation of intravenous drug use-associated endogenous endophthalmitis and as a result may present a diagnostic challenge as it requires a high level of clinical suspicion and a detailed social history to elicit the drug abuse. Early diagnosis and aggressive therapy is the key to better visual outcomes in these patients.