Verteporfin without light stimulation inhibits YAP activation in trabecular meshwork cells: Implications for glaucoma treatment.

Verteporfin, a photosensitizer, is used in photodynamic therapy to treat age-related macular degeneration. In a glaucoma mouse model, Verteporfin without light stimulation has been shown to reduce intraocular pressure (IOP) but the mechanism is unknown. Recent studies have shown that Verteporfin inhibits YAP without light stimulation in cancer cells. Additionally, YAP has emerged as an important molecule in the pathogenesis of glaucoma. We hypothesize that YAP inactivation by Verteporfin in trabecular meshwork (TM) may be related to the reduced IOP observed in vivo. As contractility of TM tissues is associated with IOP, collagen gel contraction assay was used to assess the effect of Verteporfin on contractility of TM cells. Human TM cells were embedded in collagen gel and treated with Verteporfin for 48 h. Areas of collagen gel sizes were quantified by ImageJ. To assess the effect of Verteporfin on the expression of YAP, human TM cells were treated with Verteporfin for 24 h and the expression of YAP was determined by Western blotting. To determine the cytotoxic effect of Verteporfin, human TM cells were treated with Verteporfin for 24 h, and then the cell viability was assessed by WST-1. We demonstrated here that Verteporfin (i) abolishes TM cell-mediated collagen gel contraction in a dose-dependent manner, (ii) attenuates expression of YAP and CTGF (connective tissue growth factor, a direct YAP target gene) in a dose-dependent manner, and (iii) has no significant cytotoxicity below 2 µM. Taken together, Verteporfin may facilitate aqueous humor outflow through the conventional outflow system and reduce IOP by inactivating YAP.

A multicenter analysis of the ophthalmic knowledge assessment program and American Board of Ophthalmology written qualifying examination performance.

OBJECTIVE: To compare the performance on the American Board of Ophthalmology Written Qualifying Examination (WQE) with the performance on step 1 of the United States Medical Licensing Examination (USMLE) and the Ophthalmic Knowledge Assessment Program (OKAP) examination for residents in multiple residency programs. DESIGN: Comparative case series. PARTICIPANTS: Fifteen residency programs with 339 total residents participated in this study. The data were extracted from the 5-year American Board of Ophthalmology report to each participating program in 2009 and included residency graduating classes from 2003 through 2007. Residents were included if data were available for the USMLE, OKAP examination in ophthalmology years 1 through 3, and the WQE score. Residents were excluded if one or more of the test scores were not available. METHODS: Two-sample t tests, logistic regression analysis, and receiver operating characteristic (ROC) curves were used to examine the association of the various tests (USMLE, OKAP examination year 1, OKAP examination year 2, OKAP examination year 3, and maximum OKAP examination score) as a predictor for a passing or failing grade on the WQE. MAIN OUTCOME MEASURES: The primary outcome measure of this study was first time pass rate for the WQE. RESULTS: Using ROC analysis, the OKAP examination taken at the third year of ophthalmology residency best predicted performance on the WQE. For the OKAP examination taken during the third year of residency, the probability of passing the WQE was at least 80% for a score of 35 or higher and at least 95% for a score of 72 or higher. CONCLUSIONS: The OKAP examination, especially in the third year of residency, can be useful to residents to predict the likelihood of success on the high-stakes WQE examination.

Analysis of normal peripapillary choroidal thickness via spectral domain optical coherence tomography.

PURPOSE: To analyze the normal peripapillary choroidal thickness utilizing a commercial spectral domain optical coherence tomography (OCT) device and determine the intergrader reproducibility of this method. DESIGN: Retrospective, noncomparative, noninterventional case series. PARTICIPANTS: Thirty-six eyes of 36 normal patients seen at the New England Eye Center between April and September 2010. METHODS: All patients underwent high-definition scanning with the Cirrus HD-OCT. Two raster scans were obtained per eye, a horizontal and a vertical scan, both of which were centered at the optic nerve. Two independent graders individually measured the choroidal thickness. Choroidal thickness was measured from the posterior edge of the retinal pigment epithelium to the choroid-scleral junction at 500-µm intervals away from the optic nerve in the superior, inferior, nasal, and temporal quadrants. Statistical analysis was conducted to compare mean choroidal thicknesses. Intergrader reproducibility was assessed by intraclass correlation coefficient and Pearson's correlation coefficient. Average choroidal thickness in each quadrant was compared with retinal nerve fiber layer (RNFL) thickness in their respective quadrants. MAIN OUTCOME MEASURES: Peripapillary choroidal thickness, intraclass coefficient, and Pearson's correlation coefficient. RESULTS: The peripapillary choroid in the inferior quadrant was significantly thinner compared with all other quadrants (P<0.001). None of the other quadrants were significantly different from each other in terms of thickness. The inferior peripapillary choroid was significantly thinner compared with all other quadrants at all distances measured away from the optic nerve (P<0.001). Generally, the peripapillary choroid increases in thickness the farther it was away from the optic nerve and eventually approaching a plateau. The intraclass correlation coefficient ranged from 0.62 to 0.93 and Pearson's correlation coefficient ranged from 0.74 to 0.95 (P<0.001). Neither RNFL thickness nor average age was significantly correlated with average choroidal thickness. CONCLUSIONS: Manual segmentation of the peripapillary choroidal thickness is reproducible between graders, suggesting that this method is accurate. The inferior peripapillary choroid was significantly thinner than all other quadrants (P<0.001). FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Evaluation of computer-based retinopathy of prematurity (ROP) education for ophthalmology residents: a randomized, controlled, multicenter study.

PURPOSE: To evaluate the effect of a computer-based training program-Massachusetts Eye & Ear ROP Trainer-on residents' knowledge of retinopathy of prematurity (ROP) management. METHODS: In this prospective, randomized study, ophthalmology residents from nine different training programs consented to participate. Those who completed the study were randomly assigned to either the Trainer or the control group. The ROP Trainer was created using clinical cases encompassing the stages of ROP in digital pictures and videos. It includes sections on screening decisions, examination techniques, and diagnosis, and a reference section with the expert video clips and a searchable image library. Subjects in the control group were asked to study standard print material on ROP. A pre- and post-test, consisting of theoretical and practical (diagnosis) questions, and a post-intervention satisfaction test were administered. Accuracy of ROP diagnosis was assessed. RESULTS: A total of 180 residents agreed to participate, of whom 60 completed the study. Residents in the Trainer group had statistically significant improvements (P = 0.003) in ROP knowledge and diagnostic ability (P = 0.005). Residents randomized to the Trainer group were more satisfied with the training materials than were those in the control group. There was no significant difference in improving knowledge by year of training, sex, or country. Considering all training levels, a statistically significant increase was observed in sensitivity for the diagnosis of preplus or worse, zone I or II, ROP stage, category, and aggressive posterior ROP in the Trainer group. CONCLUSIONS: In this study, the Trainer was shown to significantly improve ROP knowledge and diagnostic skills of residents, regardless of sex, year, of training, or country.

Choroidal Vessel Diameters in Pseudoexfoliation and Pseudoexfoliation Glaucoma Analyzed Using Spectral-Domain Optical Coherence Tomography.

PURPOSE OF THE STUDY: The purpose of the study was to analyze choroidal vessel diameters in pseudoexfoliation (PXF) and pseudoexfoliation glaucoma (PXFG) using spectral-domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: Fifty patients (100 eyes) with PXF and PXFG who underwent high-definition 1-line raster SD-OCT imaging at New England Eye Center, Boston, were retrospectively identified and divided into unilateral PXFG (26 patients, 52 eyes), unilateral PXF (4 patients, 8 eyes), bilateral PXFG (4 patients, 8 eyes), and bilateral PXF (16 patients, 32 eyes). Eyes with concomitant chorioretinal pathology, history of shunting/filtering for glaucoma, and significant anisometropia were excluded. SD-OCT scans were divided into subfoveal, central, and peripheral zones and choroidal vessel diameters were measured. RESULTS: In patients with unilateral PXFG, mean choroidal vessel diameter was 12.9 µm smaller in the affected eyes when compared with their contralateral eyes (45.7 vs. 58.6 µm; P<0.0001) with the greatest reduction (16.6 µm) in the subfoveal zone (49.0 vs. 65.6 µm; P<0.0001). In patients with unilateral PXF, the mean choroidal vascular diameter was 13.3 µm smaller in the affected eyes when compared with their contralateral eyes (42.8 vs. 56.1 µm; P=0.02). As expected, no significant difference was observed between the 2 eyes of patients with bilateral PXFG (45.5 vs. 45.7 µm; P=0.95) and bilateral PXF (51.4 vs. 50.2 µm; P=0.52). CONCLUSIONS: Choroidal vessel diameters are smaller in the affected eyes of patients with unilateral PXF and PXFG when compared with their contralateral unaffected eyes. These changes appear to be independent of the presence or absence of glaucoma. Future studies may identify the choroidal vascular changes and their relationship with the pathogenesis of these conditions.

Clinical assessment of mirror artifacts in spectral-domain optical coherence tomography.

PURPOSE. To investigate the characteristics of a spectral-domain optical coherence tomography (SD-OCT) image phenomenon known as the mirror artifact, calculate its prevalence, analyze potential risk factors, measure severity, and correlate it to spherical equivalent and central visual acuity (VA). METHODS. OCT macular cube 512 x 128 scans taken between January 2008 and February 2009 at the New England Eye Center were analyzed for the presence of mirror artifacts. Artifact severity was determined by the degree of segmentation breakdown that it caused on the macular map. A retrospective review was conducted of the medical records of patients with artifacts and of a random control group without artifacts. RESULTS. Of 1592 patients, 9.3% (148 patients, 200 eyes) had scans that contained mirror artifacts. A significantly more myopic spherical equivalent (P < 0.001), worse VA (P < 0.001), longer axial lengths (P = 0.004), and higher proportions of moderate to high myopia (P < 0.001) were found in patients with mirror artifacts than in patients without artifacts. Worse VA was associated with increased artifact severity (P = 0.04). CONCLUSIONS. In all scans analyzed, a high prevalence of mirror artifacts was found. This image artifact was often associated with patients with moderate to high myopia. Improvements in instrumentation may be necessary to resolve this problem in moderately and highly myopic eyes. Operators should be advised to properly position the retina when scanning eyes. In cases in which peripheral abnormalities in topographic measurements of retinal thickness are found, corresponding OCT scans should be examined for the presence of mirror artifacts.