Faculty Bibliography

OBJECTIVE: To demonstrate a new diagnostic technique, optical coherence tomography, for high-resolution cross-sectional imaging of structures in the anterior segment of the human eye in vivo. Optical coherence tomography is a new, noninvasive, noncontact optical imaging modality that has spatial resolution superior to that of conventional clinical ultrasonography (< 20 microns) and high sensitivity (dynamic range, > 90 dB). DESIGN: Survey of intraocular structure and dimension measurements. SETTING: Laboratory. PATIENTS: Convenience sample. MAIN OUTCOME MEASURES: Correlation with range of accepted normal intraocular structure profiles and dimensions. RESULTS: Direct in vivo measurements with micrometer-scale resolution were performed of corneal thickness and surface profile (including visualization of the corneal epithelium), anterior chamber depth and angle, and iris thickness and surface profile. Dense nuclear cataracts were successfully imaged through their full thickness in a cold cataract model in calf eyes in vitro. CONCLUSIONS: Optical coherence tomography has potential as a diagnostic tool for applications in noncontact biometry, anterior chamber angle assessment, identification and monitoring of intraocular masses and tumors, and elucidation of abnormalities of the cornea, iris, and crystalline lens.

Hypotony maculopathy, a clinical syndrome consisting of choroidal folds, retinal folds, and optic disc edema, results from severe, chronically decreased intraocular pressure (IOP). Conventional therapy consists of procedures designed to normalize the IOP. We treated a patient who developed hypotony maculopathy following trabeculectomy with mitomycin C. Despite normalization of the IOP with bleb revision, neither the posterior segment architecture nor visual acuity improved. Vitrectomy with mechanical flattening of the posterior segment via intraoperative instillation of perfluorocarbon liquid was performed. The choroidal folds resolved and visual acuity improved from 20/200 to 20/20. In eyes with hypotony maculopathy in which the posterior segment anatomy and visual acuity do not improve after IOP normalization, vitrectomy with heavier-than-water liquids may improve vision.

Tenon's fibroblast (TF) bleb encapsulation is a common cause of filtering surgery failure. Various pharmacologic agents have been used in an attempt to inhibit this response. The effects of three angiogenesis inhibitors were studied. AGM-1470, a fumagillin analog and hydrocortisone 21-phosphate (HC21P) complexed with heparin or with the heparin analog beta-cyclodextrin tetradecasulfate (BCD-TDS) in modulating human tenon's fibroblasts in cell culture. It has been clinically demonstrated that well vascularized blebs are associated with a poorer prognosis. In addition to reducing bleb neovascularization, angiogenesis inhibitors may have an additional therapeutic role in decreasing fibroblast activity. Drug effects were assessed by studying cell growth rates by cell Coulter counting and rate of wound closure. TF's were grown in DMEM with 10% FBS and 1% PCN-strep with fungizone. Angiogenesis inhibitors were added to growth medium in varying concentrations: AGM-1470 alone, HC21P complexed with heparin and HC21P complexed with BCD-TDS. Controls were grown in control medium alone, medium with added ethanol, or with added BCD-TDS, heparin or HC21P. We found a dose related inhibition of cell growth with all of the angiogenesis inhibitor combinations, which was not seen in the control groups. Tenon's fibroblast proliferation was significantly inhibited by AGM-1470 as seen in the four higher concentrations (P < 0.05) with insignificant inhibition at the lowest concentration of AGM-1470 (P = 0.38). The heparin:HC21P and heparin:BCD-TDS combinations demonstrated significant inhibition at all concentrations (P < 0.05). Wound closure was significantly inhibited by all the added agents, except AGM-1470 and the controls. The rate of wound closure was significantly reduced by the highest concentrations of the heparin:HC21P and heparin:BCD-TDS combinations (P < 0.05), although it was not significantly affected by lower concentrations (P > 0.05). Rank order of potencies of these agents for inhibition of TF proliferation was AGM-1470, BCD-TDS:HC21P, heparin:HC21P, HC21P, while the rank order of potencies for these agents for inhibition of wound closure was HC21P, heparin:HC21P, BCD-TDS:HC21P, AGM-1470. These selected angiogenesis inhibitors appear to have marked inhibitory effects on TF proliferation and migration, which may have a potential clinical role in modulating wound healing associated with glaucoma filtering surgery.

The nitrovasodilators nitroglycerin (NTG) and hydralazine (HZN) were investigated for their effects on intraocular pressure (IOP) and outflow facility in the cynomolgus monkey eye in vivo. Fifty microliters of 0.1% HZN were administered topically in masked, randomized, crossover, placebo controlled trials, and by intracameral perfusion. Both NTG and HZN decreased IOP (mean IOP decrease with NTG 4.40 +/- 2.11 (S.E.M.) (+/- 4.7, S.D.) mmHg, P < 0.01, n = 5, with HZN 3.15 +/- 0.85 (S.E.M.) (+/- 2.3, S.D.) mmHg, P = 0.01, n = 7). Outflow facility increased by 92% (P < 0.05) after intracameral bolus injection of 10(-3) mol l-1 NTG, but not at lower doses. Intracameral HZN caused a significant increase in facility of outflow of 28% (P < 0.05) when perfused at a constant concentration of 10(-5) mol l-1, but not at certain other concentrations. These results demonstrate the capacity for topically applied NTG and HZN to reduce IOP in the living primate eye. They further suggest that, at certain drug doses, but not others, the IOP reduction may be mediated, in part, by an action on the outflow apparatus.