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.

AIMS: To improve the diagnostic power for glaucoma by combining measurements of peripapillary nerve fibre layer (NFL), macular ganglion cell complex (GCC) and disc variables obtained with Fourier-domain optical coherence tomography (FD-OCT) into the glaucoma structural diagnostic index (GSDI). METHODS: In this observational, cross-sectional study of subjects from the Advanced Imaging of Glaucoma Study, GCC and NFL of healthy and perimetrical glaucoma subjects from four major academic referral centres of the Advanced Imaging of Glaucoma Study were mapped with the RTVue FD-OCT. Global loss volume and focal loss volume parameters were defined using NFL and GCC normative reference maps. Optimal weights for NFL, GCC and disc variables were combined using multivariate logistic regression to build the GSDI. Glaucoma severity was classified using the Enhanced Glaucoma Staging System (GSS2). Diagnostic accuracy was assessed by sensitivity, specificity and the area under the receiver operator characteristic curve (AUC). RESULTS: We analysed 118 normal eyes of 60 subjects, 236 matched eyes of 166 subjects with perimetrical glaucoma, and 105 eyes from a healthy reference group of 61 subjects. The GSDI included composite overall thickness and focal loss volume with weighted NFL and GCC components, as well as the vertical cup-to-disc ratio. The AUC of 0.922 from leave-one-out cross validation was better than the best component variable alone (p=0.047). The partial AUC in the high specificity region was also better (p=0.01), with a sensitivity of 69% at 99% specificity, and a sensitivity of 80.3% at 95% specificity. For GSS2 stages 3-5 the sensitivity was 98% at 99% specificity, and 100% at 95% specificity. CONCLUSIONS: Combining structural measurements of GCC, NFL and disc variables from FD-OCT created a GSDI that improved the accuracy for glaucoma diagnosis. TRIAL REGISTRATION NUMBER: NCT01314326.

Current knowledge indicates that the adult mammalian retina lacks regenerative capacity. Here, we show that the adult stem cell marker, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5), is expressed in the retina of adult mice. Lgr5(+) cells are generated at late stages of retinal development and exhibit properties of differentiated amacrine interneurons (amacrine cells). Nevertheless, Lgr5(+) amacrine cells contribute to regeneration of new retinal cells in the adult stage. The generation of new retinal cells, including retinal neurons and Muller glia from Lgr5(+) amacrine cells, begins in early adulthood and continues as the animal ages. Together, these findings suggest that the mammalian retina is not devoid of regeneration as previously thought. It is rather dynamic, and Lgr5(+) amacrine cells function as an endogenous regenerative source. The identification of such cells in the mammalian retina may provide new insights into neuronal regeneration and point to therapeutic opportunities for age-related retinal degenerative diseases.

AIM: To analyse ab interno trabeculectomy (AIT) with the trabectome and combined phacoemulsification with AIT (phaco-AIT) by Shaffer angle grade (SG). METHODS: Prospective study of AIT and phaco-AIT with narrow angles of SG/=3. Outcomes included intraocular pressure (IOP), medications, complications, secondary surgery and success (IOP <21 mm Hg and >20% reduction without further surgery). Exclusion criteria were missing preoperative data and <1 year follow-up. RESULTS: Of 671 included cases, at 1 year AIT SG/=3 (n=271) with an IOP reduction of 37% from 26.1+/-7.8 to 16.4+/-3.9 mm Hg (p<0.01). In phaco-AIT with SG/=3 (n=309) with an IOP reduction of 25% from 22.6+/-6.4 to 17.0+/-3.4 mm Hg (p<0.01). There was no difference between SG/=3 in reduction of IOP or medications, complications, secondary surgery and success rates (p>0.05). CONCLUSIONS: SG