Indirect Traumatic Optic Neuropathy in Mild Chronic Traumatic Brain Injury

PURPOSE. To analyze the clinical presentation and optical coherence tomography (OCT) findings in indirect traumatic optic neuropathy (ITON) in veterans with chronic mild traumatic brain injury (mTBI). METHODS. This retrospective study is the first to describe the OCT pattern of subclinical to mild ITON in veterans with chronic mTBI. The thicknesses of the macular ganglion cell layer (mGCL), peripapillary retinal nerve fiber layer (pRNFL), and subfoveal choroidal layer were analyzed in young veterans who had mTBI of >6 months' duration and either blunt head injury or improvised explosive device (IED) concussions. RESULTS. Three major OCT findings were demonstrated: (1) temporal pRNFL thinning was associated with subclinical TON in the eyes of chronic mTBI patients compared with controls; within mTBI subjects, nasal mGCL thinning at the 3-mm modified Early Treatment Diabetic Retinopathy Study circle diameter distance from the fovea correlated with the corresponding temporal retinal nerve fiber layer thinning; (2) inner (1 mm) superior thinning was greater than that of the temporal mGCL in blunt head injury and could potentially distinguish it from IED concussive head trauma; and (3) subfoveal choroidal thinning was significantly worse in eyes of mTBI patients compared with those of controls. CONCLUSIONS. These OCT findings may contribute to the understanding of the spectrum of visual injuries resulting from head trauma.Clinical and Translational Sciences Institute grant at University of California, San Francisco; Kuen Lau Research FoundationOpen access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Analysis of the Gene and Protein Causing Best Macular Dystrophy

Best macular dystrophy (BMD) is an autosomal dominant inherited eye disease with a juvenile onset. Accumulation of the pigment lipofuscin in the retinal pigment epithelium can later cause macular degeneration and loss of vision. BMD have histopathologic similarities with age-related macular degeneration, the most common cause of blindness among elderly. BMD diagnosis is made with fundus examination and electrophysiology. The VMD2 gene, causing BMD, has previously been localized to 11q13 using linkage and recombination of a 12 generation family with BMD. In this study the genetic region has been further narrowed using polymorphic markers in the BMD family. A human homolog for a C. elegans protein family, expressed in retina, was identified as the VMD2 gene. It has a 1755 bp open reading frame with 11 exons and encodes a 585 amino acid protein called bestrophin. Mutation analysis of the VMD2 gene in BMD families from Sweden, Denmark and Netherlands revealed 15 missense mutations, altering single amino acids in bestrophin, accumulating in the N-terminal half of the protein. VMD2 expression analysis with in situ hybridization revealed specific localization in the retinal pigment epithelium and Northern blot showed expression in retina and brain. Clinical and genetic analysis of a BMD family with generally late onset revealed a novel bestrophin mutation. Analysis of mouse Vmd2 and bestrophin during development showed presence of mouse bestrophin in retinal pigment epithelium at postnatal day 10 and in photoreceptor outer segments during the entire postnatal period. Vmd2 expression levels were highest around birth

Retinal Vessel Width Measurement at Branchings Using an Improved Electric Field Theory-Based Graph Approach

The retinal vessel width relationship at vessel branch points in fundus images is an important biomarker of retinal and systemic disease. We propose a fully automatic method to measure the vessel widths at branch points in fundus images. The method is a graph-based method, in which a graph construction method based on electric field theory is applied which specifically deals with complex branching patterns. The vessel centerline image is used as the initial segmentation of the graph. Branching points are detected on the vessel centerline image using a set of detection kernels. Crossing points are distinguished from branch points and excluded. The electric field based graph method is applied to construct the graph. This method is inspired by the non-intersecting force lines in an electric field. At last, the method is further improved to give a consistent vessel width measurement for the whole vessel tree. The algorithm was validated on 100 artery branchings and 100 vein branchings selected from 50 fundus images by comparing with vessel width measurements from two human experts

Classification and growth rate of chorioretinal atrophy after voretigene neparvovec-rzyl for RPE65-mediated retinal degeneration

PURPOSEClassify the appearance and quantify the growth rate of chorioretinal atrophy in patients who received voretigene neparvovec-rzyl (VN) for RPE65-mediated retinal degeneration. DESIGNMulticenter retrospective analysis SUBJECTS: Patients who underwent subretinal VN injection at 5 institutions and demonstrated posterior pole chorioretinal atrophy. METHODSUltra-widefield scanning laser ophthalmoscopy or color fundus photos were assessed before and after subretinal VN. Atrophy was defined as regions with at least two of the following: (1) partial or complete retinal pigment epithelial (RPE) depigmentation, (2) round shape, (3) sharp margins, (4) increased visibility of choroidal vessels. Atrophy was qualitatively classified into different subtypes. All atrophy was manually segmented. Linear mixed effects models with random slopes and intercepts were fit using atrophy area and square root of atrophy area. MAIN OUTCOME MEASURESNumber of eyes with each atrophy pattern, and slopes of linear mixed effects models. RESULTSTwenty-seven eyes from 14 patients across 5 centers developed chorioretinal atrophy after subretinal VN. A mean of 5.8 ± 2.7 images per eye obtained over 2.2 ± 0.8 years were reviewed, and atrophy was categorized into touchdown (14 eyes), nummular (15 eyes), and perifoveal (12 eyes) subtypes. Fifteen eyes demonstrated more than one type of atrophy. Thirteen of 14 patients demonstrated bilateral atrophy. The slopes of the mixed effects models of atrophy area and square root of atrophy area (estimate ± standard error) were 1.7 ± 1.3mm2/year and 0.6 ± 0.2 mm/year for touchdown atrophy, 5.5 ± 1.3 mm2/year and 1.2 ± 0.2 mm/year for nummular atrophy, and 16.7 ± 1.8 mm2/year and 2.3 ± 0.2 mm/year for perifoveal atrophy. The slopes for each type of atrophy were significantly different in the square root of atrophy model, which best fit the data (p < 0.05). CONCLUSIONSChorioretinal atrophy following subretinal VN for RPE65-mediated retinal degeneration developed according to a touchdown, nummular, and/or perifoveal pattern. Perifoveal atrophy grew the most rapidly whereas touchdown atrophy grew the least rapidly. Understanding the causes of these findings, which are present in a minority of patients, merits further investigation

An illustration of the human expert annotation.

<p>Blue dots denote the region where the measurement should be given. Black text were superimposed by the author for the sake of illustration. Vessel width for branch 1 is calculated as the average of the three width profiles. The branch center for branch 1 is calculated as the average of the three width profile center.</p