Search PubMed⌕ Search

Biomedical subjects

D L Epstein

Publications and source records attributed to D L Epstein.

At least 73 records · Page 4Linked to original sources
PubMed1991

MK-507 versus sezolamide. Comparative efficacy of two topically active carbonic anhydrase inhibitors.

Topical carbonic anhydrase inhibitors MK-507 and sezolamide hydrochloride (previously known as MK-417) were compared in a double-masked, randomized, placebo-controlled study in 82 patients with bilateral primary open-angle glaucoma or ocular hypertension. MK-507 was given every 8 or 12 hours, sezolamide every 8 hours, or placebo every 8 or 12 hours for 4 days. Both drugs lowered intraocular pressure (IOP) substantially. MK-507 was somewhat more active than sezolamide, with a peak mean IOP reduction of 26.2% for MK-507 versus 22.5% for sezolamide, although the difference between the treatments was not statistically significant. These drugs may have potential in the treatment of glaucoma.

Administration, Topical↗
PubMed1991

The pressure and volume dependence of the rate of wash-out in the bovine eye.

The rate of increase of outflow facility (the wash-out rate) was measured in bovine eyes at 6 and 15 mm Hg. The time-rate-of-change of facility was less at 6 mm Hg (0.20: delta facility/hour) than at 15 mm Hg (0.44). However, when the data was analyzed as a function of volume passing through the outflow system, the volume-rate-of-change of facility was the same at 6 (0.35: delta facility/ml) and 15 mm Hg (0.34). This was consistent with the hypothesis of macromolecules "washing-out" of the aqueous outflow system, if these macromolecules were saturable in the perfusate.

Animals↗
PubMed1991

Morphology of the trabecular meshwork and inner-wall endothelium after cationized ferritin perfusion in the monkey eye.

Nine eyes of five cynomolgus monkeys were perfused through the anterior chamber with cationized ferritin (CF) at normal and increased intraocular pressure. After perfusion with glutaraldehyde, the morphologic appearance of the endothelial lining of Schlemm's canal (SC) and of the adjacent regions was analyzed using tangential and sagittal serial sections. The CF, which binds to negatively charged surfaces, was observed to be adherent to the free surfaces of trabecular cell membranes and to accumulate in the cribriform layer underlining the endothelial lining of SC. Tangential sections of the inner-wall endothelium demonstrated that separations of the adjacent cell membranes occur between the tight junctions forming openings or lacunae and bent, tunnel-like channels that represent continuous paracellular pathways. Complete staining of these inner-wall paracellular pathways with CF were observed indicating that the adjoining membranes are negatively charged and that the perfused fluid had passed through these intercellular channels. These paracellular pathways appeared enlarged and were more easily identified at elevated perfusion pressure. In general, intracytoplasmic vacuoles demonstrated heavy staining with CF on their luminal surface but only faint staining on the adluminal (cribriform-facing) surface. Apparent giant vacuoles were observed to be often not real intracellular vacuoles but rather dilatations of the paracellular spaces. This study demonstrates that there are paracellular routes through the inner-wall endothelium by which high molecular-weight substances such as ferritin and macrophages can leave the anterior chamber. Probably there are both transcytoplasmic and paracellular mechanisms of aqueous outflow that may vary under different conditions of pressure or flow.

Animals↗
PubMed1990

Influences of glutathione and sulfhydryl containing compounds on aqueous humor outflow function.

Several sulfhydryl reactive compounds have previously been shown to influence aqueous humor outflow facility. The purpose of the current study was to investigate the effect of glutathione depletion on certain of these sulfhydryl actions. Enucleated calf, monkey, and human eyes were perfused via the anterior chamber by the constant pressure (15 mmHg) technique. In calf eyes, perfusion of 10 mM cysteamine produced a small (-23%, P = 0.03) decrease in outflow facility that was also observed after hyaluronidase pretreatment. In contrast, following pretreatment with 1 mM BCNU [1,3 bis(2 chlorethyl)-1-nitrosourea], an inhibitor of glutathione reductase, and 10 mM diamide, a glutathione oxidant, which did not by themselves significantly affect outflow facility, perfusion of cysteamine resulted in an opposite effect--a remarkably large (+90%, P less than 0.001) increase in outflow facility. Other reduced and oxidized sulfhydryl-containing compounds such as cysteine, beta-mercaptoethanol, and glutathione, itself, as well as the non-sulfhydryl reducing agent, ascorbic acid, were substituted for cysteamine in this protocol and found to produce similar effects of varying magnitudes. In general, the reduced sulfhydryl containing compounds and ascorbic acid were the most effective. Pretreatment with BCNU alone without diamide did not produce this effect. Treatment with BCNU and diamide resulted in a greater than 75% decrease in reduced glutathione levels and a concomitant tenfold increase in glutathione mixed disulfide levels (0.229 vs. 0.030 mumol g-1 wet weight) in the calf trabecular meshwork. The subsequent perfusion with cysteamine reversed this mixed disulfide formation.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Chloromercuribenzenesulfonate↗
PubMed1990

The filtration characteristics of the aqueous outflow system.

To determine the filtration characteristics of the aqueous outflow system, microspheres (0.18 micron -1.1 micron) were perfused through enucleated human and bovine eyes. The microspheres were smaller than morphologically determined flow dimensions, and yet a significant fraction of all sizes of microspheres were captured. The bovine (calf) aqueous outflow system was found to be a far more efficient filter than was the human outflow system. Combining the experimental results with morphological observations and theoretical calculations leads to the conclusion that 'sticky wall' interactions are responsible for much of the microsphere capture, and that the site of filtration may be distinct from the site of flow resistance. Consequently, the dimension of the sites generating flow resistance cannot be determined from filtration studies.

Animals↗
PubMed1990

Absence of time-dependent facility increase ("washout") in the perfused enucleated human eye.

During the course of constant-pressure anterior chamber perfusion experiments in eyes from a number of species, measured outflow facility increases progressively with perfusion time. One possible explanation for this phenomenon has been that the technique of perfusion induces a loss of extracellular material from the outflow pathway. Therefore, this general observation has been termed the "wash-out" effect. Data from the authors' laboratories demonstrate that although outflow facility increases in cynomolgus monkey eyes by 26% and 42% from baseline over 90 minutes in vivo and in vitro, respectively, this does not occur in the enucleated human eye. The absence of washout in the human eye probably cannot be explained by postmortem conditions since enucleated monkey eyes undergo a similar magnitude of washout as the monkey eye in vivo. Furthermore, since washout does not occur in the perfused human infant eye, the age of the donor cannot explain the difference in washout properties between human and other primate eyes. The monkey eye in vivo is a valuable model in the study of outflow physiology. However, the difference in washout behavior between human and other primate eyes may point to a potentially important fundamental difference in the biology of the outflow pathways in these two species.

Adolescent↗
PubMed1989

Patterns of aqueous humor outflow in glaucomatous and nonglaucomatous human eyes. A tracer study using cationized ferritin.

We used cationized ferritin, which binds to negatively charged membrane surfaces, as a tracer to delineate the aqueous humor outflow pathway by perfusing it into the anterior chamber of 14 normal human eyes and five with primary open angle glaucoma. In the normal human eyes, diffuse labeling with cationized ferritin was evident throughout the outflow pathway, while in the glaucomatous eyes distinctly different staining patterns were noted. A decorating pattern similar to that seen in normal eyes was observed, as well as apparent areas of underperfusion, suggestive of possible segmental changes in aqueous outflow. These findings may support the hypothesis that primary open angle glaucoma is a segmental disease of the outflow system due to possible regional increases in resistance to aqueous outflow.

Adult↗
PubMed1989

Analysis of the proteins of calf and cow trabecular meshwork: development of a model system to study aging effects and glaucoma.

The proteins from the trabecular meshwork (TM) of calf and cow eyes were analysed to determine if differences in composition were present and to examine whether this tissue could be used as a framework for the study of glaucoma. Differences in polypeptide composition or amount of protein could be detected with extractions using either acetic acid, neutral buffers and urea, or guanidine hydrochloride. In general, the results suggest that an aggregation of proteins may be occurring with aging. The acid-soluble fraction of both calf and cow TM resembled older human TM specimens with the most prominent protein around 68 kD. To test the utility of the bovine TM system, a mixed function oxidation system was used to determine how the proteins of the TM would react to oxidative stress. Aggregation of the proteins in calf TM as well as actin could be demonstrated, consistent with the idea that the aggregation seen in the cow TM might be the result of oxidation of this tissue. The present study lays a foundation for future work on bovine TM and is consistent with the hypothesis that aging changes in this tissue might be a result of oxidative processes.

Actins↗
PubMed1989

A long-term clinical trial of timolol therapy versus no treatment in the management of glaucoma suspects.

One hundred seven patients with intraocular pressures (IOPs) between 22 and 28 mmHg with normal visual fields on Goldmann perimetry and without evidence of optic nerve damage were randomly assigned to either a timolol treatment (TT) or a no treatment (NT) arm in a prospective clinical trial. The patients were followed for an average of 56 and 51 months, respectively. Criteria for failure were a confirmed IOP of greater than 32 mmHg, stereophotographically documented optic nerve progression, or development of glaucomatous visual field loss by Goldmann or Octopus perimetry. Nine patients failed in the TT group and 17 in the NT group (P = 0.07). Of the nine TT group failures, six had discontinued timolol before failure (4 for greater than 6 months). In a Cox proportional hazards analysis controlling for confounding variables, timolol was found to be significantly protective with an adjusted risk ratio of 0.38 (95% confidence interval = 0.16-0.89, P = 0.03). When only field and disc failure criteria were considered, timolol treatment was found to be significantly protective in an analysis considering patients who stopped timolol as being lost to follow-up (P = 0.05). A higher tonographic facility of outflow was protective in all analyses. A trend toward a substantial loss of effectiveness of timolol on IOP was not observed. Seasonal fluctuations in IOP were observed (P = 0.0007), with higher IOP occurring in the winter. The results demonstrate a favorable influence of timolol therapy on the clinical course of patients with mildly elevated IOP.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1989

Trabecular meshwork recovery after phagocytic challenge.

The short and long term response of the trabecular meshwork to a phagocytic challenge and the response of the meshwork to different types of foreign particles was studied by injecting one eye of 25 adult cats with a phagocytic agent (zymosan, blood, or latex microspheres) while the fellow eye received a control solution. Eyes were examined histologically at various intervals from one day to five months after infusion. Active trabecular cell phagocytosis and changes in cell shape were found with all agents. The extent of these changes varied with the agent used. Zymosan caused marked changes and inflammation, with numerous macrophages found throughout the meshwork. Trabecular cell migration and cell loss occurred, although it was often difficult to distinguish macrophages from rounded trabecular cells. The meshwork eventually recovered from this inflammatory insult, as trabecular lamellae became less edematous and once again acquired a lining of trabecular cells. Blood and latex microspheres caused less disruption, with microspheres often found in otherwise normal appearing cells. Trabecular cellularity was quantitated after the blood and the zymosan infusions. No cell loss was observed after the blood infusion, while zymosan-infused eyes had an initial 15% cell loss (p less than .04) when compared with fellow control eyes. This zymosan-associated trabecular cell loss may have been due to phagocytosis, inflammation, or a combination of both. The cell loss had recovered by the end of 150 days (p less than .02), as trabecular cell numbers in experimental eyes became comparable to fellow control eyes.

Animals↗
PubMed1989

Trabecular precipitates and elevated intraocular pressure following argon laser trabeculoplasty.

Two patients with pseudoexfoliation glaucoma underwent argon laser trabeculoplasty for control of intraocular pressure. Within 1 month both patients developed elevated intraocular pressure associated with many large inflammatory precipitates on the trabecular meshwork detected only by gonioscopy. Treatment with topical steroids for 7 to 10 days resolved these precipitates and lowered the intraocular pressure. We believe our patients had severe trabeculitis occurring as a late reaction to argon laser trabeculoplasty. An increase in intraocular pressure following trabeculoplasty warrants careful gonioscopic examination; in fact we recommend routine gonioscopy for all patients after laser treatment.

Aged↗
PubMed1989

Two-dimensional gel electrophoresis of calf aqueous humor, serum, and filter-bound proteins.

Recent studies have demonstrated that bovine and primate aqueous humor (AH) obstruct flow when perfused through artificial membranes with pore sizes similar to those found in the aqueous outflow pathway. Proteinaceous AH components were implicated in this phenomenon, which is not observed with serum diluted to comparable protein concentrations. In this study, we used two-dimensional gel electrophoresis to characterize the protein composition of calf AH and to identify those proteins binding to the filters and presumably causing this obstruction. Comparison of AH and serum under denaturing conditions showed quantitative and qualitative differences in their protein content. Among the most important: AH was seen to possess two protein subunit trains (approximately 28 kD and approximately 48 kD) not found in serum and two trains (approximately 28 kD and approximately 80 kD) with additionally charged components not found in serum. Serum, on the other hand, possesses one train (approximately 80-90 kD) not found in AH as well as a slightly greater relative amount of high-molecular weight protein subunits. The finding that hydrophobic filters retain more protein components than do hydrophilic filters suggests that the type and amount of protein adhering to them is determined largely by hydrophobic interactions. Whether such interactions occur in the outflow system, and if so, how they may relate to aqueous drainage remains to be determined.

Animals↗
PubMed1988

Experimental ab interno sclerotomies using a pulsed-dye laser.

We studied the use of a short-pulse, flashlamp-pumped dye laser, emitting at 666 nm, to create ab interno sclerotomies in cynomolgus monkeys using a fiberoptic delivery system. Because of the low optical absorption of the sclera in the visible portion of the spectrum, ablation of sclera by continuous wave lasers emitting in this region requires high energies and produces significant thermal damage to surrounding tissues. To enhance the optical absorption of sclera, methylene blue dye was applied iontophoretically; patent sclerotomies were obtained in all 10 eyes of six cynomolgus monkeys, with energies ranging from 15 to 50 mj/pulse. Thermal damage to the adjacent sclera was confined to 300 microns. Complications included mild intraoperative hyphema at all pulse energies and iridodialysis at higher pulse energies. Filtration blebs routinely failed within 7 days; the use of 5-fluorouracil postoperatively significantly prolonged bleb duration. The small incision technique described allows ab interno sclerotomies to be created with low pulse energies without the need for conjunctival dissection, thereby avoiding the problems associated with conjunctival wounds. An advantage of this technique is that it can be modified to create ab interno sclerotomies noninvasively by delivering pulsed visible radiation through the cornea with a gonioscopic-slitlamp system.

Animals↗
PubMed1988

Levobunolol and betaxolol. A double-masked controlled comparison of efficacy and safety in patients with elevated intraocular pressure.

In a double-masked, randomized, controlled clinical trial, the authors evaluated the ocular hypotensive efficacy of twice-daily treatment with levobunolol (0.25 and 0.5%) and betaxolol (0.5%) in 85 patients with open-angle glaucoma or ocular hypertension. During the 3-month study, intraocular pressure (IOP) reductions in the two levobunolol groups were significantly greater than in the betaxolol group. From a mean baseline IOP of approximately 25 mmHg, overall mean reductions were 6.2 and 6.0 mmHg for the 0.25 and 0.5% levobunolol groups, respectively, and 3.7 mmHg for the betaxolol group. No clinically or statistically significant among-group differences were noted in the systemic safety variables evaluated. These data suggest that although all three treatments are effective, levobunolol provides a greater reduction in IOP than betaxolol.

Betaxolol↗
PubMed1988

A clinical trial of timolol and epinephrine in the treatment of primary open-angle glaucoma.

Forty-seven patients with chronic open-angle glaucoma who required therapy but who had never been treated previously were enrolled in a prospective randomized, long-term clinical trial comparing the effectiveness of 0.5% timolol maleate and 1% epinephrine. Patients were followed for an average of 33 months. There were 20 failures, 18 of which were because of inadequate intraocular pressure (IOP) control (required 20% reduction in outflow pressure). Twelve failures were in the epinephrine group and eight were in the timolol group. During the first year of therapy, 35% compared with 0% of patients failed in the epinephrine and timolol groups, respectively (P less than 0.01). During the later years of the study, the failure rates in the two groups were similar. The results suggest that timolol is superior to epinephrine during the first year of therapy, and likely as effective as epinephrine in the long-term treatment of glaucoma.

Aged↗
PubMed1988

Anterior and posterior axial lens displacement and human aqueous outflow facility.

We studied the effect of anterior and posterior axial crystalline lens displacement (and thereby ciliary tone) on the aqueous humor outflow facility in enucleated human eyes. After attaching a reversible footplate plunger to the anterior lens capsule with cyanoacrylate, the lens was placed in one of three positions: "neutral baseline," posterior displacement (2.5 mm), or anterior displacement (2.0 mm). In seven pairs of eyes, the mean "neutral baseline" was not statistically different from the control eye, but anterior lens displacement decreased outflow facility "C" by 0.14 (36%) (P less than 0.0001), and posterior displacement increased "C" by 0.18 (50%) (P less than 0.01). Anterior or posterior lens displacement after complete ciliary body detachment produced no effect on outflow facility in two pairs. Histologic correlation studies demonstrated narrowing of the intertrabecular spaces and Schlemm's canal in the eyes fixed in anterior lens displacement, and widening of the same structures in the eyes fixed in posterior lens displacement. The lens-zonular-ciliotrabecular force vectors are responsible for the compression or decompression of the meshwork and Schlemm's canal in this model, with compression decreasing, and decompression increasing aqueous humor outflow facility.

Aqueous Humor↗
PubMed1988

Hydrogen peroxide removal by the calf aqueous outflow pathway.

Previous studies have shown that aqueous humor of calf and human eyes contains about 25 microM hydrogen peroxide. We have studied the removal of hydrogen peroxide by the outflow pathway of intact, freshly enucleated, calf eyes. Eyes were immersed under silicone oil that had a density greater than water and medium containing various agents was perfused into the anterior chamber. Medium passing through the trabecular meshwork and out the cut ends of the aqueous veins was trapped by the silicone oil and harvested. By measuring the concentration of hydrogen peroxide in the anterior chamber and in the emerging medium, we were able to study the rate of removal by the outflow structures and the effect of inhibitors on this rate. At 1 mM hydrogen peroxide, the amount emerging was undetectable by our methods. At 10 mM, the results were inconsistent, suggesting that tissue damage may have been occurring. At 5 mM, the concentration in the emerging medium was reduced 150-1000-fold, depending on time and conditions. This rate of removal could be reduced by 3-aminotriazole, reaching a maximum inhibition of about 50% at 80 mM. Addition of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) to further inhibit removal did not yield reliable results unless the concentration of H2O2 was lowered below 5 mM. Using loss of lactate dehydrogenase activity as a measure of cell damage, we found a 30% drop in activity after perfusing with BCNU, diamide, and 3-aminotriazole, followed by 3 hr with 10 mM hydrogen peroxide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitrole↗