Richard P. Juster

Trabecular Meshwork Cellularity in Primary Open-angle Glaucoma and Nonglaucomatous Normals

The trabecular meshwork cellularity (cells/unit tissue area) was compared in patients with primary open-angle glaucoma (POAG) with that of nonglaucomatous (NG) individuals. The NG specimens (n = 69) include specimens from the prenatal period (n = 14) as well as the postnatal period to age 98 years (n = 55). The glaucoma specimens (n = 49) covered a wide-range of ages (23-80 years) and were obtained at trabeculectomy (n = 31) or at autopsy (n = 18). Our results show that the trabecular cellularity in NG specimens decreases most rapidly and in a nonlinear manner in the late fetal period and for the first few years of postnatal life. This rapid decline in cellularity then slows down to proceed in a nearly linear manner for the remainder of the 98 years of life studied. The meshworks from patients with POAG have a lower cellularity than normals over the wide range of ages examined, but both types of specimens undergo similar declines in cellularity with age. Thus, the age-cellularity curves for both the NG and POAG specimens are parallel to each other. The loss of cells occurs in a gradient-like manner with the inner tissues being most affected and the outermost tissues least affected. A variety of statistical tests show that these changes in cellularity are highly significant and specific. These findings are compared to the loss of endothelial cells in the cornea and they are discussed in relation to the important clinical characteristics of POAG.

Two-dimensional echocardiographic determination of aortic and pulmonary artery sizes from infancy to adulthood in normal subjects.

The aorta, right pulmonary artery and pulmonary trunk were measured from the 2-dimensional echocardiogram (2-D echo) of 110 normal subjects aged 1 day to 18 years. The vessel diameters were measured from the parasternal short-axis view, the suprasternal long-axis view and the suprasternal short-axis view. Measurements were made at end-systole and at end-diastole and in both an axial and lateral direction where possible. When analyzed with respect to body surface area (BSA), the echocardiographic measurements were linearly related to the square root of the BSA, and there was inequality of variance around the relation. To establish a range of normal values for each vessel dimension, a weighted regression analysis was used to produce estimates of the regression line and a set of tolerance intervals. The systolic vessel dimension was larger than the diastolic vessel dimension and the measurement of a vessel in an axial direction was larger than the measurement of the same vessel in a lateral direction. In general, when a vessel was measured in several views, the largest diameter was obtained using the view that imaged the vessel in cross section. These data on normal values for the echocardiographic measurement of the aorta and pulmonary arteries at different BSAs should be useful for identifying patients with abnormalities in arterial size and for the serial assessment of arterial size in children who have undergone surgical or medical therapy.

Ahmed Valve Implantation with Adjunctive Mitomycin C and 5-Fluorouracil: Long-term Outcomes

PURPOSE To evaluate long-term outcomes after Ahmed valve implantation in patients with glaucoma when using adjunctive intraoperative mitomycin C (MMC) and postoperative 5-fluorouracil (5-FU). DESIGN Retrospective, interventional, consecutive case series. METHODS A consecutive series of eyes undergoing Ahmed valve implantation, either alone (AHMED eyes) or in combination with cataract surgery (AHMED+PHACO), using both intraoperative MMC and postoperative 5-FU were evaluated. Failure was defined as the first occurrence of any of the following: 1) the first of three consecutive visits where intraocular pressure (IOP) was >18 mm Hg or <20% IOP reduction from baseline and the final number of topical medications was not reduced by at least two from baseline, 2) the need for additional surgery, or 3) the development of serious complications. RESULTS A total of 130 eyes underwent Ahmed valve implantation with intraoperative exposure to 0.5 mg/ml MMC (median time: eight minutes; range, four to 10) and postoperative subconjunctival injections of 5 mg of 5-FU (median: five injections; range, zero to nine). Kaplan-Meier estimates of the cumulative probability of valve success and confidence interval (CI) at the sixth follow-up year were 0.72 (95% CI, 0.59 to 0.82) for AHMED eyes (n = 88), 0.84 (95% CI, 0.65 to 0.93) for AHMED+PHACO eyes (n = 42). A median of two fewer medications were required relative to baseline for both AHMED and AHMED+PHACO eyes. CONCLUSIONS The adjunctive use of both intraoperative MMC and postoperative 5-FU with Ahmed valve implantation results in high success rates. IOP was well controlled in the majority of patients within the six-year postoperative period.

Long-term follow-up of initially successful trabeculectomy with 5-fluorouracil injections

PURPOSE To study the long-term results (1-14 years) of trabeculectomies with 5-fluorouracil injections that were successful at 1 year. DESIGN A retrospective noncomparative case series. INTERVENTION/PARTICIPANTS: We identified 87 patients (87 eyes) who had trabeculectomies with 5-fluorouracil injections from 1984 to 1989 that were successful at 1 year and had a follow-up range of 1.0 to 14.7 years (mean, 8.1, standard deviation of 4.4 years). All patients had previously failed glaucoma surgery (66.7%), cataract surgery (47.1%), or other diagnoses making them at high risk for failure. MAIN OUTCOME MEASURES Successful control of intraocular pressure (IOP) was defined as IOP less than 21 mmHg or a reduction of 33% if preoperative pressure was less than 21 mmHg. Statistical analysis was performed using Kaplan-Meier life table analysis. RESULTS If an eye is considered successful by IOP at 1 year, the probability of successful control is 61% at 5 years, 44% at 10 years, and 41% at 14 years. CONCLUSIONS Despite successful IOP control at 1 year, trabeculectomies with 5-fluorouracil injections show a continual loss of IOP control over time.

Correlation of Visual Field, Treatment Fields, and Dose in Helium Ion Irradiation of Uveal Melanoma

We correlated predicted radiation distributions in 29 patients with uveal melanoma (treated with 5,000 to 8,000 rads of helium ion therapy) with fundus photography and visual field deficits. The tumor was entirely within the treatment region in all patients. The fraction of the predicted high-dose and low-dose regions corresponding with an absolute scotoma was fitted by a linear regression model (r2 = .721) with three independent variables: dose region, initial condition, and time since therapy. The defect in the maximum-dose region increased at an average rate of 0.270/year. This differed (P = .002) from the rate in the penumbra region: (0.104/year). The rate in the penumbra differed (P = .01) from that in the predicted low-dose region, where scotoma did not increase with time. The pattern and time course of visual field loss in the different radiation dose regions tended to support the conclusion that isodose calculations are accurate. The data were consistent with the hypothesis that visual loss secondary to irradiation results primarily from radiation vasculopathy and not from direct damage to photoreceptors or ganglion cells. Development of an absolute scotoma may require a dose in excess of 5,000 rads.

Profiling of Cytokines Secreted by Conventional Aqueous Outflow Pathway Endothelial Cells Activated In Vitro and Ex Vivo With Laser Irradiation

PURPOSE To profile which cytokine genes are differentially expressed (DE) as up- or downregulated by cultured human trabecular meshwork (TMEs) and Schlemms canal endothelial cells (SCEs) after three experimental treatments consisting of selective laser trabeculoplasty (SLT) irradiation, exposure to media conditioned either by SLT-irradiated TMEs (TME-cm) or by SCEs (SCE-cm). Also, to profile which cytokines are upregulated ex vivo in SLT-irradiated human conventional aqueous outflow pathway (CAOP) tissues. METHODS After each treatment, Affymetrix microarray assays were used to detect upregulated and downregulated genes for cytokines and their receptors in TMEs and SCEs. ELISA and protein antibody arrays were used to detect upregulated cytokines secreted in SLT-irradiated CAOP tissues ex vivo. RESULTS The SLT irradiation upregulated numerous cytokine genes in TMEs, but only a few in SCEs. Exposure to TME- and SCE-cm induced SCEs to upregulate many more cytokine genes than TMEs. Selective laser trabeculoplasty irradiation and exposure to TME-cm downregulated several cytokine genes in TMEs but none in SCEs. Selective laser trabeculoplasty irradiation induced one upregulated and three downregulated cytokine-receptor genes in TMEs but none in SCEs. Exposure to TME-cm induced upregulation of one and downregulation of another receptor gene in TMEs, whereas two unique cytokine-receptor genes were upregulated in SCEs. Cytokine protein expression analysis showed that at least eight cytokines were upregulated in SLT-irradiated human CAOP tissues in situ/ex vivo. CONCLUSIONS This study has helped us identify a cytokine signaling pathway and to consider newly identified mechanisms regulating aqueous outflow that may lay the foundation for the future development of cytokine-based glaucoma therapies.

Flow Cytometry Measurement of Nuclear RNA Content in Uveal Melanoma

We retrospectively studied the nuclear RNA content in uveal melanomas with known, long-term follow-up. Thirty patients had spindle cell melanomas, 25 had mixed cell tumors, and 9 had epithelioid cell neoplasms. Epithelioid cell types had a higher nuclear RNA content compared to mixed or spindle cell types (p less than 0.05). Using the Cox proportional hazards model, the nuclear RNA content appeared to be an independent prognostic indicator in uveal melanomas, and an increased nuclear RNA content was associated with a worse prognosis (p = 0.001).