Faculty Bibliography

Characterizing the collagen fiber orientation and organization in the eye is necessary for a complete understanding of ocular biomechanics. In this study, we assess the performance of polarized light microscopy to determine collagen fiber orientation of ocular tissues. Our results demonstrate that the method provides objective, accurate, repeatable and robust data on fiber orientation with microm-scale resolution over a broad, cm-scale, field of view, unaffected by formalin fixation, without requiring tissue dehydration, labeling or staining. Together, this shows that polarized light microscopy is a powerful method for studying collagen architecture in the eye, with applications ranging from normal physiology and aging, to pathology and transplantation.

BACKGROUND: The study aims to correlate Fourier-domain optical coherence tomography (FD-OCT) with Goldmann visual field (GVF) to show the photoreceptor (PR) structure and function relationship in the first described case of cancer-associated retinopathy (CAR) from Merkel cell carcinoma. FINDINGS: A case study of a patient with CAR who was imaged with serial GVF and FD-OCT over a 2-year period was carried out. En face images were created using a custom algorithm from the volumetric Fourier-domain OCT scans at the PR level. The areas of decreased PR reflectivity on the en face images were compared with GVF obtained at the same time point. Regions of reduced signal on en face scans corresponded with the position and shape of the GVF scotomas. Initially, the vision improved without PR changes. Cross-sectional OCTs showed early recovery of the outer nuclear layer and later improvement in the nerve fiber layer. Worsening vision corresponded with recurrence of the underlying cancer. Progressive global retinal atrophy was seen over time. CONCLUSIONS: Merkle cell carcinoma can cause CAR. Retinal function recovered without structural PR recovery. Transient vision improvements in treated CAR patients may be due to layers other than the PRs, but eventual vision decline results from significant progressive retinal atrophy.

PURPOSE: To evaluate longitudinal changes in circumpapillary retinal nerve fiber layer (RNFL) thickness, as measured by spectral-domain optical coherence tomography (SD OCT), in children with optic pathway gliomas. DESIGN: Longitudinal cohort study. METHODS: Global and quadrant-specific circumpapillary RNFL thickness measures were acquired using either a hand-held SD OCT during sedation or a table-top SD OCT in children old enough to cooperate. Vision loss was defined as either a 0.2 logMAR decline in visual acuity or progression of visual field. Percent change in circumpapillary RNFL thickness in eyes experiencing vision loss was compared to eyes with stable vision. RESULTS: Fifty-five eyes completed 250 study visits. Ten eyes (18%) from 7 patients experienced a new episode of vision loss during the study and 45 eyes (82%) from 39 patients demonstrated stable vision across study visits. Percent decline of RNFL thickness between the baseline visit and first event of vision loss event was greatest in the superior (-14%) and inferior (-10%) quadrants as well as global average (-13%). Using a threshold of >/=10% decline in RNFL, the positive and negative predictive value for vision loss when 2 or more anatomic sectors were affected was 100% and 94%, respectively. CONCLUSIONS: Children experiencing vision loss from their optic pathway gliomas frequently demonstrate a >/=10% decline of RNFL thickness in 1 or more anatomic sectors. Global average and the inferior quadrant demonstrated the best positive and negative predictive values. Circumpapillary RNFL is a surrogate marker of vision and could be helpful in making treatment decisions for children with optic pathway gliomas.

Idiopathic demyelinating optic neuritis (ON) most commonly presents as acute unilateral vision loss and eye pain and is frequently associated with multiple sclerosis. Although emphasis is often placed on the good recovery of high-contrast visual acuity, persistent deficits are frequently observed in other aspects of vision, including contrast sensitivity, visual field testing, color vision, motion perception, and vision-related quality of life. Persistent and profound structural and functional changes are often revealed by imaging and electrophysiologic techniques, including optical coherence tomography, visual-evoked potentials, and nonconventional MRI. These abnormalities can impair patients' abilities to perform daily activities (e.g., driving, working) so they have important implications for patients' quality of life. In this article, we review the sequelae from ON, including clinical, structural, and functional changes and their interrelationships. The unmet needs in each of these areas are considered and the progress made toward meeting those needs is examined. Finally, we provide an overview of past and present investigational approaches for disease modification in ON.

The mechanical characteristics of the trabecular meshwork (TM) are linked to outflow resistance and intraocular pressure (IOP) regulation. The rationale behind this technique is the direct observation of the mechanical response of the TM to acute IOP elevation. Prior to scanning, IOP is measured at baseline and during IOP elevation. The limbus is scanned by spectral-domain optical coherence tomography at baseline and during IOP elevation (ophthalmodynamometer (ODM) applied at 30 g force). Scans are processed to enhance visualization of the aqueous humor outflow pathway using ImageJ. Vascular landmarks are used to identify corresponding locations in baseline and IOP elevation scan volumes. Schlemm canal (SC) cross-sectional area (SC-CSA) and SC length from anterior to posterior along its long axis are measured manually at 10 locations within a 1 mm segment of SC. Mean inner to outer wall distance (short axis length) is calculated as the area of SC divided by its long axis length. To examine the contribution of adjacent tissues to the effect IOP elevations, measurements are repeated without and with smooth muscle relaxation with instillation of tropicamide. TM migration into SC is resisted by TM stiffness, but is enhanced by the support of its attachment to adjacent smooth muscle within the ciliary body. This technique is the first to measure the living human TM response to pressure elevation in situ under physiological conditions within the human eye.

PURPOSE: We minimized the influence of image quality variability, as measured by signal strength (SS), on optical coherence tomography (OCT) thickness measurements using the histogram matching (HM) method. METHODS: We scanned 12 eyes from 12 healthy subjects with the Cirrus HD-OCT device to obtain a series of OCT images with a wide range of SS (maximal range, 1-10) at the same visit. For each eye, the histogram of an image with the highest SS (best image quality) was set as the reference. We applied HM to the images with lower SS by shaping the input histogram into the reference histogram. Retinal nerve fiber layer (RNFL) thickness was automatically measured before and after HM processing (defined as original and HM measurements), and compared to the device output (device measurements). Nonlinear mixed effects models were used to analyze the relationship between RNFL thickness and SS. In addition, the lowest tolerable SSs, which gave the RNFL thickness within the variability margin of manufacturer recommended SS range (6-10), were determined for device, original, and HM measurements. RESULTS: The HM measurements showed less variability across a wide range of image quality than the original and device measurements (slope = 1.17 vs. 4.89 and 1.72 mum/SS, respectively). The lowest tolerable SS was successfully reduced to 4.5 after HM processing. CONCLUSIONS: The HM method successfully extended the acceptable SS range on OCT images. This would qualify more OCT images with low SS for clinical assessment, broadening the OCT application to a wider range of subjects.

PURPOSE: To evaluate agreement among experts of Heidelberg retina tomography's (HRT) topographic change analysis (TCA) printout interpretations of glaucoma progression and explore methods for improving agreement. METHODS: 109 eyes of glaucoma, glaucoma suspect and healthy subjects with >/=5 visits and 2 good quality HRT scans acquired at each visit were enrolled. TCA printouts were graded as progression or non-progression. Each grader was presented with 2 sets of tests: a randomly selected single test from each visit and both tests from each visit. Furthermore, the TCA printouts were classified with grader's individual criteria and with predefined criteria (reproducible changes within the optic nerve head, disregarding changes along blood vessels or at steep rim locations and signs of image distortion). Agreement among graders was modelled using common latent factor measurement error structural equation models for ordinal data. RESULTS: Assessment of two scans per visit without using the predefined criteria reduced overall agreement, as indicated by a reduction in the slope, reflecting the correlation with the common factor, for all graders with no effect on reducing the range of the intercepts between the graders. Using the predefined criteria improved grader agreement, as indicated by the narrower range of intercepts among the graders compared with assessment using individual grader's criteria. CONCLUSIONS: A simple set of predefined common criteria improves agreement between graders in assessing TCA progression. The inclusion of additional scans from each visit does not improve the agreement. We, therefore, recommend setting standardised criteria for TCA progression evaluation.