Faculty Bibliography

BACKGROUND: Limited data are available to guide optimal positioning of glaucoma drainage devices (GDD) in relation to the limbus and optic nerve. The authors aim to provide guidelines for appropriate and safe GDD implantation. METHOD: The optimal positioning of five different GDD were evaluated using necropsy eyes of varying axial lengths. The dependent variable that was measured was the maximum distance that a GDD could be placed posterior to the limbus while remaining 2 mm away from the optic nerve. RESULTS: The average maximum distance posterior to the limbus of the anterior plate edge ranged between 9.0-15.0 mm in the superotemporal quadrant for the GDD tested. The distances for superonasal, inferonasal, and inferotemporal quadrants ranged between 8.0-14.0 mm, 9.0-14.0 mm, and 11.0-17.0 mm, respectively. The Molteno device could be placed most posteriorly while remaining 2 mm away from the nerve. The Ahmed FP7 and S2 were the least amenable to posterior placement before encroaching on the 2 mm limit. CONCLUSION: The maximum distance that a GDD can be placed posterior to the limbus, before encroachment around the optic nerve, varies between different devices and quadrants of placement. Taking a measurement of the exact distance of the plate from the limbus during GDD surgery is recommended.

Overfiltering blebs can lead to postoperative problems including hypotony maculopathy, decreased vision, and increased ocular discomfort. Many methods have been used in the past with varying results. Various lasers have been used in an attempt to cause localized scarring and fibrosis. We report a treatment technique to noninvasively treat a patient with an overfiltering bleb using trypan blue and a frequency-doubled continuous-wave neodymium:YAG laser emitting green light.

OBJECTIVE: To compare the detection of clinically significant diabetic macular edema (DME) by an optical coherence tomography (OCT) grid scanning protocol and biomicroscopic examination. DESIGN: Retrospective case series. PARTICIPANTS: Outpatients at the Doheny Eye Institute. METHODS: The clinical and imaging records of a consecutive series of 71 eyes of 40 patients referred for DME who underwent OCT using the both the Macular Grid 5 (MG5) scanning protocol (to allow a more evenly distributed sampling of points in the macula) and the standard Fast Macular Thickness Map (FMTM) pattern were reviewed. An automated algorithm was developed to generate a retinal thickness map using the MG5 data, which was then compared with a normative database to identify presumed areas of retinal edema. Clinically significant macular edema (CSME) was also identified by clinical examination and stereoscopic fundus photographs for comparison with the results of the OCT protocols. MAIN OUTCOME MEASURES: Sensitivity and specificity of scanning protocols. RESULTS: Optical coherence tomograms were inspected visually, and automatically detected retinal boundaries were found to be correct in 69 of 71 MG5 scans and in 65 of 71 FMTM scans. Macular Grid 5 scanning was performed twice in each eye, and the repeatability (pooled standard deviation) of the total area of edema was 0.48 mm2 (coefficient of variation, 6.8%). Sensitivity and specificity of the MG5 for detection of CSME relative to the clinical examination were 89% and 86%, respectively, with kappa being 0.74. Macular Grid 5 and FMTM assessment of foveal CSME also showed good agreement, with kappa being 0.68. CONCLUSIONS: The analysis algorithm for the OCT MG5 grid scan seems to be accurate and repeatable. Automated detection of CSME by the MG5 analysis correlated well with the clinical grading and standard OCT analysis (FMTM). Macular Grid 5 provides more information regarding the perifoveal macula than FMTM and may be of value to clinicians in planning treatment and in future studies of macular edema.

OBJECTIVE: To demonstrate the ability to segment and analyze individual intraretinal layers, including the outer retinal complex (ORC; outer nuclear layer and inner and outer segments of the photoreceptor cells), in healthy eyes using images acquired from the latest commercially available optical coherence tomography (OCT) system (StratusOCT; Carl Zeiss Meditec, Inc., Dublin, CA) and from the ultrahigh resolution OCT (UHR-OCT) prototype. METHODS: Thirty-seven eyes from 37 healthy subjects underwent complete ophthalmologic examination using StratusOCT and UHR-OCT. ORC was identified and measured using a segmentation algorithm. RESULTS: For StratusOCT, mean weighted ORC thickness +/- SD was 91.1 +/- 7.9 microm, and mean weighted total retinal thickness +/- SD was determined to be 258.9 +/- 10.1 microm. For UHR-OCT, mean weighted ORC thickness +/- SD was 96.4 +/- 6.3 microm, and mean weighted total retinal thickness +/- SD was determined to be 263.4 +/- 9.2 mum. There was a higher rate of algorithm failure with UHR-OCT images. CONCLUSIONS: Photoreceptor layer thickness can be calculated by measuring ORC on OCT images using a macular segmentation algorithm. ORC values may serve as a useful objective parameter in determining the efficacy of various therapeutic modalities that target the photoreceptor layer in various diseases.

OBJECTIVE: To evaluate retinal anatomy using ultrahigh-resolution optical coherence tomography (OCT) in eyes after successful surgical repair of full-thickness macular hole. METHODS: Twenty-two eyes of 22 patients were diagnosed as having macular hole, underwent pars plana vitrectomy, and had flat/closed macular anatomy after surgery, as confirmed with biomicroscopic and OCT examination findings. An ultrahigh-resolution-OCT system developed for retinal imaging, with the capability to achieve approximately 3-microm axial resolution, was used to evaluate retinal anatomy after hole repair. RESULTS: Despite successful closure of the macular hole, all 22 eyes had macular abnormalities on ultrahigh-resolution-OCT images after surgery. These abnormalities were separated into the following 5 categories: (1) outer foveal defects in 14 eyes (64%), (2) persistent foveal detachment in 4 (18%), (3) moderately reflective foveal lesions in 12 (55%), (4) epiretinal membranes in 14 (64%), and (5) nerve fiber layer defects in 3 (14%). CONCLUSIONS: With improved visualization of fine retinal architectural features, ultrahigh-resolution OCT can visualize persistent retinal abnormalities despite anatomically successful macular hole surgery. Outer foveal hyporeflective disruptions of the junction between the inner and outer segments of the photoreceptors likely represent areas of foveal photoreceptor degeneration. Moderately reflective lesions likely represent glial cell proliferation at the site of hole reapproximation. Thin epiretinal membranes do not seem to decrease visual acuity and may play a role in reestablishing foveal anatomy after surgery.

We recently described an IL-1-regulated stress response specific to the eye's aqueous outflow pathways that is diagnostic of glaucomas of diverse etiology. The goal of this study was to further identify IL-1-regulated signalling pathways in normal TM cells and determine whether their activity is altered in glaucomatous TM cells. Activity of the MAPK, p38, and JNK signalling pathways, represented by protein kinases ERK1/2, p38, and JNK-1, was followed by western blotting using antibodies specific for the active phosphorylated forms, after treatment of normal (N=5) or glaucomatous (N=5) cell lines by IL-1. Active forms of each of these kinases could be detected in normal and glaucomatous cells prior to treatment. When normal cells were stimulated with exogenous IL-1, an increase in activity of each of the kinases was observed. In contrast, treatment of glaucomatous cells with IL-1 resulted in little or no change in kinase activity. This difference was shown to be statistically significant by use of the paired two-tailed Student's t-test. Interference with IL-1 autocrine signalling in glaucomatous cell lines by treatment with IL-1 receptor antagonist (IL-1ra) had no effect on constitutive p38 or JNK activity (ERK was not examined). The results suggest that the MAPK, p38 and JNK signal transduction pathways are relatively unresponsive in glaucomatous cells as compared to normal cells. These results provide new information about the behaviour of glaucomatous TM cells, which may be important for understanding the pathophysiology of high-tension glaucoma.

PURPOSE: To determine the effect of corneal drying on the outcome of optical coherence tomography (OCT). DESIGN: Cohort study. PARTICIPANTS: Seventeen normal participants (mean age, 39+/-12 years). METHODS: Subjects underwent a series of peripapillary circular StratusOCT scans (version 3.0; Carl Zeiss Meditec, Inc., Dublin, CA) in a randomly selected eye. Baseline scan sets were acquired, and thereafter, blinking was prevented by taping the eyelid. Eyelid taping was immediately followed by 6 to 8 serial scan sets, each separated by 20 seconds. After removing the eyelid tape, 3 additional scans were acquired at 1, 2, and 4 minutes of blinking freely. MAIN OUTCOME MEASURES: The analyzed outcome measures were scan quality as defined by signal-to-noise ratio (SNR) and signal strength (SS) provided by the built-in OCT software and mean nerve fiber layer (NFL) thickness. RESULTS: Significant reductions in SNR, SS, and NFL were noted at each scanning point in the drying phase (for each, P<0.015, paired t test) except for NFL thickness measurements acquired at 140 and 160 seconds. The reduction in NFL thickness exceeded the 95% confidence limit of the reported reproducibility error of StratusOCT after 15 seconds of corneal drying. After 1 and 2 minutes of blinking freely, there was still a significant reduction in NFL thickness compared with the baseline value, which was no longer evident at the 4-minute scan. CONCLUSIONS: Corneal dryness affects OCT scan quality and measured NFL thickness after a short exposure time. It is recommended to instruct those who are scanned to blink frequently or to instill artificial tears.

PURPOSE: To identify differentially expressed glycogenes in trabecular meshwork (TM) of eyes with primary open-angle glaucoma (POAG). METHODS: Total RNA was isolated from TM of cadaveric eyes derived from donors with diagnosed glaucomas of different etiologies and from normal control subjects. RNA was amplified and hybridized to the GLYCOv2 oligonucleotide microarray that contains probes for carbohydrate-binding proteins, glycosyltransferases, and other genes involved in the regulation of glycosylation. Statistical analysis was used to identify differentially expressed genes between normal and POAG samples. RESULTS: This study revealed that POAG TM and normal TM have distinct gene expression profiles. Of the 2001 genes on the array, 19 genes showed differential expression of greater than 1.4-fold in POAG. Mimecan and activinA, which have been shown to be upregulated in models of glaucoma, were both found to be elevated in POAG TM. Many genes were identified for the first time to be differentially regulated in POAG. Among the upregulated genes were: (1) cell adhesion molecules including platelet endothelial cell adhesion molecule-1 and P-selectin, both of which are targets of NFkappaB, which has been shown to be activated in glaucomatous TM; (2) lumican, a core protein of keratan sulfate proteoglycans; and (3) the receptor for IL6, a cytokine that has been shown to be upregulated in TM in response to elevated intraocular pressure. Among the downregulated genes were chondroitin-4-O-sulfotransferase involved in the synthesis of chondroitin sulfate chains and the receptor for PDGFbeta, a growth factor that has been shown to stimulate both TM cell proliferation and phagocytic activity. Results for several genes were confirmed by RTq-PCR. CONCLUSIONS: Microarray technology was used to show, for the first time, that POAG TM has a distinct glycogene expression profile. Differentially expressed glycogenes identified in this study have not been previously investigated for their role in the pathogenesis of POAG and thus are novel factors for further study of the mechanism of the disease and for their possible use as diagnostic markers.