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Biomedical subjects

D L Epstein

Publications and source records attributed to D L Epstein.

At least 91 records · Page 5Linked to original sources

A case-control study of risk factors in open angle glaucoma.

In a case-control study using an exploratory health questionnaire, we examined the relationship between primary open angle glaucoma (POAG) and a variety of personal characteristics and potential toxic exposures in patients in a general eye service. There were 83 patients with definite POAG, 121 POAG suspects, and 237 controls. Using multiple logistic regression analysis for simultaneous evaluation of potential risk factors, we found that black race (rate ratio = 6.8; 95% confidence interval [CI] = 2.8 to 16.0) and untreated systolic hypertension (rate ratio = 5.8; 95% CI = 2.2 to 15) were the most important risk factors. Current cigarette smoking was also associated with glaucoma (rate ratio = 2.9; 95% CI = 1.3 to 6.6). Suggestive associations were found with family history of glaucoma, definite or borderline diabetes, and myopia. The effects of many of these personal characteristics and exposures as risk factors were also noted for the glaucoma suspect group, though not as strongly as for the definite glaucoma cases.

Alcohol Drinking↗

Neodymium:YAG laser trabeculopuncture in juvenile open-angle glaucoma.

The authors performed neodymium:YAG (Nd:YAG) laser trabeculopuncture (YLT) in eight eyes of six patients with uncontrolled juvenile open-angle glaucoma. Two methods of treatment were evaluated: either two confluent trabeculotomies, each 1 clock hour in extent; or focal treatment in four quadrants. In six eyes (75%), the intraocular pressure (IOP) was controlled (less than or equal to 19 mmHg) after a mean follow-up period of 6 +/- 2 months. All successful treatments were associated with blood reflux from the site of trabeculopuncture into the anterior chamber at the time of the procedure. Energy levels required for a single trabeculotomy (1 clock hour in extent) and for one focal trabeculopuncture, were 156 +/- 59 mJ and 42 +/- 24 mJ, respectively. The clinical results suggested that confluent trabeculotomy may be superior to focal treatment. No major complications were encountered with either treatment. The authors propose the use of YLT in uncontrolled juvenile glaucoma before surgically invasive goniotomy or filtration operations.

Adolescent↗

Alterations of aqueous humour outflow following argon laser trabeculoplasty in monkeys.

We performed argon laser trabeculoplasty in one eye in each of three cynomolgus monkeys, leaving the contralateral eyes as controls. Four weeks later in both eyes of each monkey we infused cationized ferritin as a tracer of the aqueous outflow pathways for 30-40 minutes before fixation. In the control eyes cationized ferritin was found throughout the conventional aqueous outflow tract, labelling trabecular endothelial cells, both inner and outer walls of Schlemm's canal, and the collecting channels. No permeation of cationized ferritin through continuous cellular layers such as the corneal endothelium was detected. In the lasered spots of the treated eyes cationized ferritin was found to label the cellular sheet covering the trabecular scar at the lasered site, but no tracer was detected within the scar or in Schlemm's canal immediately beneath. In contrast in adjacent non-lasered regions the trabecular cells, the observed juxta-canalicular herniations, and the vacuoles of the inner wall as well as Schlemm's canal itself were extensively labelled. Our findings suggest impermeability to aqueous humour flow through the actual lasered lesion, with shift of flow to adjacent, non-lasered regions. In the normal monkey these regions compensate structurally and functionally in ways that may help to deal with this diverted flow.

Animals↗

Morphometric analysis of the craniofacial development of the CD-1 mouse fetus exposed to alcohol on gestational day eight.

Fetal alcohol syndrome (FAS) describes a pattern of dysmorphogenesis observed in some offspring of women who consumed alcohol during pregnancy; partial expression of this pattern are fetal alcohol effects (FAE). The purpose of this investigation was to measure selected craniofacial parameters in the CD-1 mouse fetus following exposure to alcohol on gestational day (D) 8. CD-1 mice were mated for 1 hr; D0.0 designated by the presence of a vaginal plug. On D8, 0 hr, and D8, 4 hr, 33 dams were injected intraperitoneally (IP) with 25% (v/v) alcohol in physiological saline solution (0.015 ml/gm maternal body weight). Appropriate controls were maintained. The animals were sacrificed every 12 hr from D12.0 through D17.0. Implantation sites were examined and recorded as live, dead, or resorbed fetuses. All live fetuses were weighed, examined for gross defects, and fixed in Bouin's solution. Twenty-three bilateral parameters were recorded for linear dimensions defining face and cranium. The fetal weights were statistically lower in treated as compared to control fetuses only on D16.0 through D17.0. Statistical analysis of the morphometrics identified five distinct growth patterns in treated mice as compared to controls. The anomalies induced in the CD-1 mouse fetus following exposure to alcohol on D8.0 resembled FAE rather than FAS. Morphometric analysis of the craniofacial region may be an important clinical tool for the quantitative identification of alcohol-related effects in the offspring of women who consumed alcohol while pregnant.

Animals↗

Influence of ethacrynic acid on outflow facility in the monkey and calf eye.

Living monkeys were perfused via the anterior chamber by the two step constant pressure technique with the sulfhydryl (SH)-reactive diuretic, ethacrynic acid (ECA) at dosages from 0.1 to 1.0 mM. Above 0.37 mM a reproducible increase in outflow facility (C) was observed. At 0.5 mM C increased 115% with ECA compared to a 22% increase in control eyes (n = 9; P less than 0.01). In three monkeys simultaneous perfusion of ECA with cysteine in 10% excess prevented this effect. In enucleated calf eyes at dosages ranging from 0.1 to 0.5 mM ECA a similar increase in outflow facility was demonstrated. Simultaneous perfusion of 0.1 mM ECA with 0.5 mM cysteine blocked this increase in facility. At high dosages (6 mM) of ECA a decrease in C of 35% was observed (P less than 0.01, n = 8). Electron microscopic studies of the perfused monkey eyes did not readily explain the observed facility effects of ECA, except for the occurrence of a small number of breaks in the inner wall endothelium of Schlemm's canal. The juxtacanalicular meshwork appeared normal. Moderate to profound trabecular endothelial cell swelling was observed with ECA alone and with simultaneous cysteine. Morphologic studies performed 4 and 11 weeks after repetitive acute exposure to ECA indicated that the tissues of the outflow pathway appeared normal. The importance of this work is that it points to a new class of drugs that may be used someday to treat glaucoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A double-masked comparison of betaxolol vs timolol in the treatment of open-angle glaucoma.

We conducted a six-month prospective, double-masked randomized trial comparing betaxolol with timolol at 0.25% and 0.5% concentrations in the treatment of primary open-angle glaucoma in 38 patients. To qualify, patients had to demonstrate an average intraocular pressure in at least one eye of greater than or equal to 26 mm Hg without treatment. The median intraocular pressure was consistently lower in the timolol group than in the betaxolol group (after four weeks of therapy, it was 20.2 mm Hg for timolol vs 22.5 mm Hg for betaxolol; P less than .04). Adjunctive therapy was required in eight patients in the betaxolol group compared to one in the timolol group (P less than .05). Betaxolol appears to be a clinically effective and safe agent in the treatment of open-angle glaucoma. However, the magnitude of the decrease in intraocular pressure with it may not be as great as that with timolol and there may be a greater need for adjunctive therapy with it than with timolol.

Adult↗

Corneal changes during pilocarpine gel therapy.

Fifteen of 53 patients (28%) receiving long-term pilocarpine gel therapy were noted to have a subtle, diffuse superficial corneal haze. Results of a masked examination of patients using pilocarpine gel vs pilocarpine eyedrops and the finding of the haze unilaterally in patients using the gel unilaterally suggested that the haze is related to the pilocarpine gel. In most patients the haze persisted for two years after gel treatment was discontinued; the haze disappeared in two patients. Although patients remain asymptomatic with unaltered visual acuities, the long-term effect of this corneal change is unknown.

Conjunctiva↗

Delayed response to argon laser trabeculoplasty in monkeys. Morphological and morphometric analysis.

In eight cynomolgus monkeys we performed argon laser trabeculoplasty and evaluated morphological changes in the trabecular meshwork (TM). Four weeks after laser treatment, the treated spots were detected as regions of flattened and collapsed beams covered by a cellular sheet extending from the corneal endothelium. The inner wall of Schlemm's canal beneath these regions was flat, with no vacuoles despite fixation with intraocular pressure maintained at 15 mm Hg. Adjacent nonlasered spots had wide open intertrabecular spaces with herniations of juxtacanalicular TM and of inner wall endothelium into and across the lumen of Schlemm's canal. The herniations contained chronic inflammatory cells and large vacuoles. Statistical morphometric analysis in three monkeys established that these herniations were significantly wider, more numerous, and contained more vacuoles than did control eyes. Our findings suggest that a biologic process is involved in these reactions to argon laser trabeculoplasty. Scarring is seen to obliterate TM in spots treated by the laser, and this apparently causes the flow of the aqueous humor to be diverted through adjacent nonlasered regions that become structurally altered to compensate for this overload of flow.

Animals↗

Additive effect of betaxolol and epinephrine in primary open angle glaucoma.

Betaxolol hydrochloride is a topical beta 1-blocking agent that has been found to be safe and effective in lowering intraocular pressure (IOP) in patients with glaucoma. We administered open-label epinephrine for four weeks to 19 patients who were already being treated with masked 0.5% timolol maleate or 0.5% betaxolol. In patients receiving betaxolol, epinephrine produced a significant additional lowering of mean IOP from 24.5 +/- 0.7 to 19.4 +/- 0.6 mm Hg at one week (P less than .0001) and to 20.7 +/- 0.5 mm Hg at four weeks (P less than .0001). This was accompanied by a statistically significant increase in mean outflow facility from 0.12 +/- 0.1 to 0.17 +/- 0.03 microL/min/mm Hg at one week (P less than or equal to .05) and to 0.18 +/- 0.02 microliter/min/mm Hg at four weeks (P less than or equal to .004). Consistent with previous reports, patients receiving timolol exhibited no significant changes in IOP or outflow facility after the addition of epinephrine to their treatment regimen. These results suggest that epinephrine's agonist effect on the outflow channels is mediated through beta 2-adrenergic receptors and that combined therapy with betaxolol and epinephrine may be clinically useful.

Adrenergic beta-Antagonists↗

The use of glaucoma shell tamponade in leaking filtration blebs.

Our experience with the use of glaucoma shell tamponade for bleb leaks in six patients is described. All patients had posterior lip sclerectomies, with leaking blebs diagnosed intraoperatively (2 patients), early (2 patients) and late (2 patients) following surgery. The glaucoma shell works by applying a high resistance to excessive aqueous humor run-off through the leaking wound, and promotes conjunctival epithelial closure by approximating the wound edges. In all six cases the use of the glaucoma shell tamponade was fully effective. The leaks were sealed off and diffuse functioning filtering blebs were maintained, with very low intraocular pressure. We recommend the use of the glaucoma shell tamponade as the treatment of choice for bleb leaks prior to considering surgical repair.

Aged↗

Optic disc cupping in arteritic anterior ischemic optic neuropathy resembles glaucomatous cupping.

Five cases of anterior ischemic optic neuropathy secondary to biopsy-proven giant cell arteritis are presented. In each case, cupping of the optic disc, which closely resembled glaucomatous cupping, was observed in the affected eye. The presence of glaucoma was ruled out on the basis of normal intraocular pressures and normal tonographic measurements of facility of outflow. These cases indicate that arteritic ischemic optic neuropathy can result in optic disc cupping, which closely resembles glaucomatous cupping. The similarities in the appearance of cupping of these discs with that seen in eyes with glaucoma suggest that the pathogenesis of cupping in glaucoma and in arteritic ischemic optic neuropathy may share some common mechanisms.

Aged↗

Neodymium:YAG laser iridotomy as a possible contribution to lens dislocation.

We report on a patient with angle-closure glaucoma in the right eye that was apparently triggered by lens subluxation and tilting forward after trauma to the eye. Further inferior dislocation of the lens was detected after neodymium:yttrium aluminum garnet (Nd:YAG) laser iridotomy was performed superotemporally. We suspect that the Nd:YAG laser iridotomy, which was performed peripherally, might have induced further zonular rupture and lens dislocation due to a shock-wave effect, especially when the lens was already tilted forward. We suggest that the use of the Nd:YAG laser in cases in which subluxation of the lens is suspected should be considered as potentially hazardous.

Aged↗

Glucose 6-phosphate dehydrogenase of calf trabecular meshwork.

Activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of calf trabecular meshwork were measured and found to be 0.23 and 0.47 mumole/min/g tissue, respectively. Glucose 6-phosphate dehydrogenase was purified 450-fold with a yield of 91% by anion exchange chromatography and 2',5'-ADP agarose affinity chromatography. It was activated by Ca2+, Mg2+, and Mn2+. It was deactivated by p-chloromecuribenzoate, p-chloromercuribenzene sulfonate, and iodoacetamide, but this deactivation could be prevented by pretreatment with cysteine or glutathione. Its rate was regulated by the NADPH/NADP+ ratio, being maximal at a ratio of 0, and negligible at a ratio of 10. At the physiological ratio of 5, its rate was approximately half maximal. On disc gel electrophoresis of both the crude and purified enzyme, seven bands of glucose 6-phosphate dehydrogenase activity could be seen. The isozyme pattern was similar to that of calf retina, but different from that of calf liver. These data suggest that trabecular meshwork is well supplied with the capacity to generate NADPH. Typical demands for NADPH may be to detoxify H2O2 and/or organic peroxides through the glutathione peroxidase/glutathione reductase system, and both generating and removing products of the "killing reaction" during phagocytosis.

Animals↗

The Slate turkey: a model for secondary angle closure glaucoma.

An inherited eye disease leading to a secondary angle closure glaucoma has been observed in turkeys (Meleagris gallapavo) of the Slate variety. The initial indications of the disease involve a low grade aqueous cell and flare reaction, associated with progressive posterior synechiae formation resulting in pupillary block and iris bombé. A midperipheral iridocorneal adhesion follows, accompanied by corneal edema, breaks in Descemet's membrane, and buphthalmos. IOP is not elevated substantially until a complete iris bombé occurs. Expression of the defect is sex-influenced, with females exhibiting the most severe pathological changes.

Animals↗