James A. Kimble

Comprehensive analysis of gene expression in human retina and supporting tissues

Understanding the influence of gene expression on the molecular mechanisms underpinning human phenotypic diversity is fundamental to being able to predict health outcomes and treat disease. We have carried out whole transcriptome expression analysis on a series of eight normal human postmortem eyes by RNA sequencing. Here we present data showing that ∼80% of the transcriptome is expressed in the posterior layers of the eye and that there is significant differential expression not only between the layers of the posterior part of the eye but also between locations of a tissue layer. These differences in expression also extend to alternative splicing and splicing factors. Differentially expressed genes are enriched for genes associated with psychiatric, immune and cardiovascular disorders. Enrichment categories for gene ontology included ion transport, synaptic transmission and visual and sensory perception. Lastly, allele-specific expression was found to be significant forCFH,C3 andCFB, which are known risk genes for age-related macular degeneration. These expression differences should be useful in determining the underlying biology of associations with common diseases of the human retina, retinal pigment epithelium and choroid and in guiding the analysis of the genomic regions involved in the control of normal gene expression.

Branch Retinal Artery Occlusion: Visual Prognosis

PURPOSE To evaluate the visual prognosis in eyes with branch retinal artery occlusion (BRAO). DESIGN Retrospective, observational, consecutive case series. METHODS Retrospective medical record review of 52 consecutive eyes of 52 patients with BRAO seen at two vitreoretinal practices in Birmingham, Alabama. Only eyes with decreased central macular perfusion on fluorescein angiography (FA) were included. Eyes with anterior segment or optic nerve disease, lack of retinal whitening or a delay in arterial filling on FA, central retinal artery occlusion, and cilioretinal artery occlusion were excluded. The main outcome measure was presenting best-corrected visual acuity (BCVA) and its relationship to final BCVA. RESULTS On presentation, 54% of eyes with BRAO had BCVA of 20/40 or better. At the mean 14-month visit, 60% of all eyes had visual acuity (VA) of 20/40 or better. VAs of 20/40 or better were retained by 89% of eyes with baseline BCVA of 20/40 or better. Only 14% of eyes with 20/100 or worse BCVA improved to 20/40 or better. Neither visible emboli (P > or = .244) nor the region of macular involvement (P = .142) were significant with respect to visual improvement. CONCLUSIONS Visual prognosis after BRAO seems to be correlated to presenting VA. Eyes with initial VA of 20/40 or better usually remained at 20/40 or better. Individuals with poor VA of 20/100 or worse generally did not show the significant improvement reported in previous studies.

Quantification of fluorescein-stained drusen associated with age-related macular degeneration.

Background: Previous studies of age-related macular degeneration have not quantified the number of drusen that accumulate fluorescein. Histopathologic studies have demonstrated druse subregions with different degrees of hydrophobicity, and these subregions might potentially exhibit different degrees of fluorescein uptake. Methods: We evaluated macular drusen from 35 age-related macular degeneration patients by measuring druse area in color digital images and fluorescein angiograms, using 2 morphometric methods. Results: Of 828 drusen evaluated, 405 had a corresponding fluorescein angiogram signal. About half of all drusen per eye (49.57%) stained in each participant. Among fluorescein-stained drusen, druse size measured in color images did not differ significantly from the sizes measured in corresponding fluorescein images (P = 0.8105), across the range of druse sizes. Conclusion: These findings indicate that our understanding of drusen subregion staining may not directly correlate to in vivo observations of macular drusen in age-related macular degeneration.

Imaging of Dalen-Fuchs Nodules in a Likely Case of Sympathetic Ophthalmia by Fluorescein Angiography and OCT.

Sympathetic ophthalmia (SO) is a well-known but rare autoimmune disease in which the sympathizing eye suffers granulomatous panuveitis after trauma to the fellow eye. An unusual case of SO occurring 32 years after trauma to the fellow eye, and 1 year after unsuccessful vitrectomy/scleral buckle repair of an acute retinal detachment in the inciting eye was presented. An optical coherence tomography imagery of Dalen-Fuchs nodules, not previously reported, and rare angiographic imaging of SO in its acute phase was demonstrated.