Faculty Bibliography

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.

OBJECTIVE: To assess microstructural changes in the retina that may explain incomplete visual recovery after anatomically successful repair of rhegmatogenous retinal detachments (RD) using ultrahigh-resolution optical coherence tomography (UHR OCT). DESIGN: Retrospective observational case series. PARTICIPANTS: Seventeen patients with decreased visual acuity after RD repair. Twelve patients had macula-involving and 5 had macula-sparing RDs. METHODS: The UHR OCT prototype capable of approximately 3 mum axial resolution was developed for clinical use. The UHR OCT images through the center of the fovea in 17 patients with visual complaints after RD surgery were obtained. Patients were either postoperative patients from the New England Eye Center or tertiary referrals. Baseline visual acuity, preoperative lens status, location of retinal detachment, macular involvement, and postoperative visual acuity were recorded. MAIN OUTCOME MEASURES: The UHR OCT images after RD repair. RESULTS: The UHR OCT images were obtained 1 to 84 months (median, 5 months) postoperatively. The mean preoperative logarithm of the minimum angle of resolution (logMAR) visual acuity was 1.37 (Snellen equivalent, 20/390). The mean postoperative logMAR visual acuity was 0.48 (Snellen equivalent, 20/60). Anatomical abnormalities that were detected included distortion of the photoreceptor inner/outer segments (IS/OS) junction in 14 of 17 patients (82%), epiretinal membranes in 10 of 17 patients (59%), residual subretinal fluid in 3 of 17 patients (18%), and cystoid macular edema in 2 of 17 patients (12%). Of the 5 patients with preoperative macula-on detachments, 4 had distortion of the outer retina after RD repair. CONCLUSIONS: The higher resolution of UHR OCT facilitates imaging of the IS/OS junction. Therefore, UHR OCT is able to confirm prior histopathologic findings that damage to photoreceptor outer segments may occur as a consequence of retinal detachment. This may explain poor postoperative visual acuity in eyes with anatomically successful repair.

PURPOSE: To develop an eye-motion-tracking optical coherence tomographic (OCT) method and assess its effect on image registration and nerve fiber layer (NFL) thickness measurement reproducibility. METHODS: A system capable of tracking common fundus features based on reflectance changes was integrated into a commercial OCT unit (OCT II; Carl Zeiss Meditec, Inc., Dublin, CA) and tested on healthy subjects and patients with glaucoma. Twenty successive peripapillary NFL scans were obtained with tracking and 20 without tracking, for 40 images in each session for each eye. Subjects participated in one session on three different days. Composite OCT scans and composite fundus images were generated for assessment of eye tracking. NFL thickness measurement reproducibility was also assessed. RESULTS: Seven healthy and nine glaucomatous eyes of 16 subjects were recruited. A qualitative assessment of composite OCT scans and composite fundus images showed little motion artifact or blurring along edges and blood vessels during tracking; however, those structures were less clearly defined when tracking was disengaged. There was no significant reproducibility difference with and without tracking in both intra- and intersession NFL measurement SD calculations in any location. The mean retinal pixel SD was significantly smaller with tracking than without (490.9 +/- 19.3 microm vs. 506.4 +/- 31.8 microm, P = 0.005, paired t-test). CONCLUSIONS: A retinal-tracking system was successfully developed and integrated into a commercial OCT unit. Tracking OCT improved the consistency of scan registration, but did not influence NFL thickness measurement reproducibility in this small sample study.

The utility of needle bleb revision with bevacizumab in a patient with a failing bleb following trabeculectomy is explored. The patient had previously failed needle bleb revision with mitomycin C. After needling and injection of 1 mg of bevacizumab, the bleb was noted to be more diffuse with a decrease in surface neovascularization. Bevacizumab may be an effective medication for rescuing failing filtering blebs that exhibit neovascularization.

The utility of intravitreal bevacizumab injection in a patient with neovascular glaucoma following central retinal vein occlusion is explored. Bevacizumab (1 mg in 0.04 mL) was used after failed intraocular pressure (IOP) control with transscleral cyclophotocoagulation and panretinal photocoagulation. IOP improved within 2 days and the patient experienced marked improvement in comfort. Bevacizumab may be an effective medication for the treatment of neovascular glaucoma.

OBJECTIVES: To define optical coherence tomographic (OCT) criteria for the diagnosis of a lamellar macular hole, and to increase understanding of lamellar hole pathogenesis by examining fine anatomic features using ultrahigh-resolution optical coherence tomography (UHR OCT). DESIGN: Retrospective observational case series. PARTICIPANTS: Nineteen eyes of 18 patients with lamellar holes were imaged with UHR OCT between 2002 and 2004. METHODS: A UHR OCT system was developed for use in the ophthalmology clinic. All 6 UHR OCT images for each eye imaged were examined. Lamellar holes were diagnosed based on a characteristic OCT appearance. Criteria for the OCT diagnosis of a lamellar hole were as follows: (1) irregular foveal contour; (2) break in the inner fovea; (3) intraretinal split; and (4) intact foveal photoreceptors. From 1205 eyes of 664 patients imaged with UHR OCT, and retrospectively reviewed, 19 eyes of 18 patients were diagnosed with a lamellar hole based on these criteria. All 19 eyes were also imaged with standard resolution OCT. Their charts were retrospectively reviewed. MAIN OUTCOME MEASURES: Standard and ultrahigh-resolution OCT images. RESULTS: On chart review, clinical diagnosis of a lamellar hole was made in only 7 of 19 eyes (37%). Twelve of 19 eyes (63%) had an epiretinal membrane (ERM) on clinical examination. Ten of 19 eyes (53%) had a posterior vitreous detachment. On UHR OCT, 17 of 19 eyes (89%) had ERMs. Eleven ERMs had an unusual thick appearance on UHR OCT. Due to poor visual acuity, 4 eyes underwent vitrectomy. Only 1 of 4 surgeries (25%) was visually and anatomically successful. Another eye improved visually, but a lamellar hole persisted. One eye progressed to a full-thickness macular hole preoperatively, which reopened after surgery. One eye developed a full-thickness hole postoperatively. CONCLUSIONS: The diagnosis of a lamellar hole can be made based on OCT criteria, which could be applied to both standard and ultrahigh-resolution OCT. The increased resolution of UHR OCT sheds light on the pathogenesis of the lamellar hole. Epiretinal membranes were visualized on UHR OCT in the majority of eyes. Many ERMs had an unusual thick appearance on UHR OCT, which may represent either trapped vitreous or posterior hyaloid, and may help stabilize retinal anatomy. Conversely, ERM contraction may play a role in lamellar hole formation. Vitrectomy surgery was anatomically and visually successful in only 1 of 4 patients, suggesting caution when performing vitrectomy on lamellar holes.