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Biomedical subjects

D L Epstein

Publications and source records attributed to D L Epstein.

At least 145 records · Page 8Linked to original sources

Exfoliation syndrome.

We reviewed the records of 74 patients with exfoliation syndrome. Patients with exfoliation syndrome represented 12% of the current Glaucoma Clinic population. There were 40 unilateral and 34 bilateral cases. Thirteen percent of the patients who originally had unilateral exfoliation later developed exfoliation in the fellow eye. Forty percent of the affected eyes with exfoliation had appreciable cataracts. Evidence for bilateral glaucoma was present in only 22% of the patients with unilateral exfoliation (and ipsilateral glaucoma). The evidence suggests that the exfoliation syndrome is, in most cases, the cause of the glaucoma, and that this is generally a true secondary open-angle glaucoma. Trabecular pigmentation may be a prognostic factor relating to the occurrence of glaucoma.

Aged↗

Influence of intraocular pressure on aqueous outflow facility in enucleated eyes of different mammals.

Freshly enucleated monkey, calf, and human eyes were quantitatively perfused with mock aqueous humor through the anterior chamber by a constant pressure technique. After baseline perfusion at 15 mm Hg, intraocular pressure was raised to 45 mm Hg and later reduced back to 15 mm Hg. Calf and human (both adult and infant) eyes had lower outflow facilities at 45 than at 15 mm Hg. However, four types of monkey eyes did not show decreased facility of outflow at elevated perfusion pressure, and after return of pressure to 15 mm Hg, facility of outflow actually increased compared to baseline, unlike both calf and human eyes. The results indicate that there are significant differences in the response of enucleated mammalian eyes to an elevation in perfusion pressure. Factors other than, or in addition to, collapse of Schlemm's canal may be important in the pathogenesis of the pressure-induced decrease in outflow facility found in human eyes.

Adult↗

Metabolism of calf trabecular (reticular) meshwork.

It has been found that calf eyes are an excellent source of trabecular meshwork tissue for biochemical studies. Homogenates of pooled meshwork were centrifuged at 27K X g and 1.5K X g. The high-speed supernatants produced lactate at 0.35 mumole/min/gm tissue in the presence of hexokinase-saturating concentrations of glucose (10 mM) at pH 7. The optimum pH was 7.6. In the absence of ammonia, lactate could be produced from fructose 1,6-diphosphate but not from glucose or glucose 6-phosphate. The optimum ammonia concentration was 1 to 2 mM. Lactate was produced at an even greater rate from fructose, but only poorly from sorbitol or galactose (all at 10 mM). The activity of hexokinase, glucose 6-phosphate dehydrogenase and UDPG dehydrogenase was measured. Fructokinase could not be detected. The low-speed supernatant readily oxidized succinate, malate, and glutamate at about 0.012 muAtO/min/gm tissue. The oxidative rate in vivo is estimated to be about one third of this. These results demonstrate that knowledge of the normal metabolism of calf trabecular meshwork may be obtained with relative ease, with possible important implications for understanding the disease of glaucoma.

Animals↗

Choroidal effusion during glaucoma surgery in patients with prominent episcleral vessels.

Rapid intraoperative choroidal effusion and flattening of the anterior chamber occurred during glaucoma filtering surgery in four young patients with prominent episcleral vessels, elevated episcleral venous pressure, and advanced open-angle glaucoma. Two of these four patients had Sturge-Weber syndrome. Intraoperative release of suprachoroidal fluid (SCF) through a posterior sclerotomy facilitated reformation of the anterior chamber and repositioning of the iris and ciliary body. Posterior sclerostomy performed prior to opening the anterior chamber minimized the above-mentioned untoward series of events. Analysis of SCF and serum demonstrated considerable differences in total protein and individual immunoglobulin levels; this appears to be a manifestation of molecular sieving at the level of the choriocapillaris. Choroidal detachment and postoperative serous retinal detachment are manifestation of this phenomenon.

Adult↗

Experimental perfusions through the anterior and vitreous chambers with possible relationships to malignant glaucoma.

Enucleated eyes were perfused alternately via the anterior and vitreous chambers. At low intraocular pressure (IOP), vitreous humor presented considerable resistance to forward flow of perfusion fluid in calf eyes, but not in human eyes. In human eyes when the perfusion pressure was increased to 60 mm Hg, the resistance to flow forward from the vitreous body increased, but became practically nil again when the IOP was decreased. At high pressure the volume of the vitreous body apparently increases and the anterior hyaloid membrane probably presses against the ciliary body, reducing the area of hyaloid membrane through which fluid can flow. Whether increased perfusion pressure can in some other manner change the permeability of human vitreous to resemble that of the calf remains unanswered. Our results suggest that factors other than, or in addition to, simple diversion of aqeous humor must be important in malignant glaucoma.

Animals↗

Identification of isoenzyme C as the principal carbonic anhydrase in human ciliary processes.

Carbonic anhydrase was extracted from the excised processes of the ciliary bodies of 10 pairs of enucleated human eyes, and the isoenzyme composition was assayed by measuring the degree of inhibition produced by acetazolamide at two standard concentrations. Also, the effect of incubating with iodoacetate was determined in two pairs of these eyes. Only isoenzyme C was detected. Accordingly, it seems that differences in reduction of intraocular pressure that are common among patients treated for glaucoma with systemic carbonic anhydrase inhibitors, despite uniform serum concentrations, are not attributable to interindividual variation of carbonic anhydrase isoenzymes in the ciliary processes.

Acetazolamide↗

Decreased libido--a side effect of carbonic anhydrase inhibitor.

Thirty-nine cases of decreased libido in glaucoma patients on carbonic anhydrase inhibitors are reported. This symptom completely reversed or markedly improved after discontinuation of the drug in all cases. Twelve of these patients restarted their carbonic anhydrase inhibitor medication which resulted in a recurrence of decreased libido symptoms. There were 3 cases of impotency which reversed after discontinuation of the drug. Most likely, these symptoms are a result of the malaise and depression occurring in some patients on carbonic anhydrase inhibitor therapy.

Adult↗

A repeated dose-response study of methazolamide in glaucoma.

Twenty-two patients with open-angle glaucoma were given weekly courses of methazolamide at different dosages. Mean intraocular pressure reductions of 3.3, 4.3, and 5.6 mm Hg were achieved at dosages of 25 mg, 50 mg, and 100 mg of methazolamide every eight hours, respectively. Maximal intraocular pressure lowering was still present nine to ten hours after administration. The mean reduction in outflow pressure for all eyes receiving a daily dosage of 300 mg was only 31%, but this included eyes (17% of the total) that demonstrated less than 13% reduction in outflow pressure, despite similar methazolamide serum levels. Eight patients subsequently received acetazolamide, 250 mg four times a day for a week. The effect of this dosage of acetazolamide on pressure was between the effects of 50 and 100 mg of methazolamide three times daily.

Aged↗

Serum obstruction of aqueous outflow in enucleated eyes.

We perfused enucleated human eyes via the anterior chamber by the constant pressure technique. Infusion of human serum into the anterior chamber of enucleated human eyes for 30 minutes at 23 mm Hg pressure induced a 42% decrease in facility of outflow, which was not relieved by irrigation of the anterior chamber with balanced salt solution or alpha-chymotrypsin. Diluted serum also reduced the facility of outflow. Measured in a glass viscometer, diluted serum had less viscosity than undiluted, but interfered with outflow from the eye more than anticipated on the basis of viscosity alone. When we used lens depression to induce tension on the iridocorneal angle to simulate the effects of contraction of the ciliary muscle, outflow facility increased in control eyes that had not been exposed to serum and in serum-perfused eyes. However, the partial obstruction to outflow that had been induced by serum persisted. Normal serum components may become adsorbed or entrapped in the aqueous outflow system so as to obstruct outflow, and this may result in secondary glaucoma in eyes with chronic uveitis.

Anterior Chamber↗

Phenylephrine provocative testing in the pigmentary dispersion syndrome.

Forty-nine patients with bilateral pigmentary dispersion syndrome (abnormal accumulation of pigment in the anterior chamber, principally from the posterior layers of the iris), including 31 patients with pigmentary glaucoma, underwent 10% phenylephrine testing in one eye for evaluation of liberation of pigment floaters into the anterior chamber and the influence of phenylephrine on the intraocular pressure. Ten patients with pigmentary glaucoma developed a 3+ to 4+ pigment response, but only two demonstrated a pressure rise greater than 2 mm Hg. The highest pressure rise observed was 7 mm Hg. Nine patients with pigmentary dispersion syndrome but without glaucoma also developed a 3+ to 4+ pigment response, but none of these had a pressure rise. The incidence of pigment liberation was higher in older patients and in pigmentary glaucoma patients receiving topical antiglaucoma therapy at the time of testing. The extent of iris transillumination did not correlate with the grade of phenylephrine-induced pigment liberation. Two pigmentary glaucoma patients, who did not liberate pigment or have a pressure rise when tested with phenylephrine, did exhibit spontaneous or exercise-induced liberations of pigment into the anterior chamber, with marked rises of intraocular pressure and obstruction of aqueous outflow.

Adult↗

Obstruction of aqueous outflow by lens particles and by heavy-molecular-weight soluble lens proteins.

Enucleated human eyes were perfused via the anterior chamber at 25 mm Hg pressure with lens particles (whole lens homogenates) in one series of experiments and with soluble lens proteins from human cataractous lenses in another series. Adding 1% of a homogenate of a single cataractous lens to the anterior chamber induced a 68% decrease in outflow. Perfusion with HMW soluble lens proteins (1 mg/ml; MW more than 150 million) caused a 60% decrease in outflow in 1 hr. In neither series was the obstruction to outflow relieved by subsequent irrigation of the anterior chamber with balanced salt solution or alpha-chymotrypsin. The results show that both lens particles and soluble lens proteins can directly obstruct the aqueous outflow pathways of human eyes. Such obstruction may be a significant factor in certain lens-induced glaucomas.

Aqueous Humor↗

Identification of heavy-molecular-weight soluble protein in aqueous humor in human phacolytic glaucoma.

Aqueous humor was obtained by paracentesis at the time of cataract surgery from six patients with phacolytic glaucoma, diagnosed on the basis of acute unilateral open-angle glaucoma associated with an apparently leaking hypermature or mature cataract, and from six control patients with immature cataracts. Three of the latter had primary open-angle glaucoma. Quantities of heavy-molecular-weight (HMW) protein (MW greater than 150 X 10(6)) sufficient to obstruct aqueous outflow were identified in all six phacolytic aqueous humor specimens but in none of the controls. Three of the hypermature cataractous lenses from the cases of phacolytic glaucoma were also examined and were found to have 14-fold greater quantities of HMW protein in their liquefying cortex than were present in the cortex of immature cataractous lenses. These findings, correlated with experimental HMW protein perfusion studies in excised human eyes that we have already reported, strongly suggest that direct obstruction of the aqueous outflow channels by liberated HMW soluble lens protein may be a significant and previously unappreciated factor in the pathogenesis of phacolytic glaucoma.

Aqueous Humor↗

Carbonic anhydrase inhibitor side effects. Serum chemical analysis.

Multiple serum chemical values were examined in 92 patients with chronic glaucoma who were treated with the carbonic anhydrase inhibitors (CAIs) acetazolamide or methazolamide, seeking relationships between serum composition and symptomatic side effects. Of the 92 patients, 44 complained of a symptom-complex of malaise, fatigue, weight loss, depression, anorexia, and loss of libido, which we have found most commonly to threaten continuation of therapy. Patients who had this symptom complex were significantly more acidotic than those without it. Ten of 24 patients who had chemical evidence of excessive acidosis reported a dramatic alleviation of symptoms when sodium bicarbonate was administered, although their serum CO2-combining power changed little. There was no correlation of the symptom complex with serum potassium concentration, except in a few patients who were simultaneously receiving chlorothiazide diuretics for systemic hypertension and who became frankly hypokalemic.

Acetazolamide↗

Cystoid macular edema occurring 13 years after cataract extraction.

Thirteen years after cataract extraction, a patient complained of diminished visual acuity. In the interim visual acuity was 6/6 (20/20), or 6/7.5 (20/25+2). Fluorescein angiography demonstrated cystoid macular edema. Except for vitreous adherence to the inner surface of the cataract wound, no ocular cause for the macular edema was apparent.

Cataract Extraction↗

Secondary open-angle glaucoma in histiocytosis X.

A 9 month-old boy developed secondary open-angle glaucoma associated with fever and multiple lytic bone lesions 2 1/2 months after cataract aspiration. An open bone biopsy provided a diagnosis of histiocytosis X. Hisiocytes similar to those in the bone were identified in a specimen of aqueous humor from the affected eye. No other cells were found. The abnormal histiocytes may have caused the glaucoma by infiltrating the trabecular angle structures and mechanically obstructing aqueous outflow from the eye.

Bone Diseases↗

Cataractogenic effects of a boron hydride disulfide compound.

The disulfide form but not the sulfhydryl form of a boron hydride compound was found to be cataractogenic. Apparently this compound attaches to the sulfhydryl group of Na-K ATPase in the lens epithelium inactivating this crucial enzyme. The consequence is that a defect in the cation pump activity arises, leading to a rapid influx of Na ions and loss of K ions and marked increase in hydration. These changes are thought to lead to opacification.

Acute Disease↗

Reversible unilateral lens opacities in a diabetic patient.

Following one month of poor diabetic control, a 54-year-old patient presented with a unilateral posterior subcapsular cataract, consisting of numerous fine, feathery, streak-like opacities radiating from a dense, round, central, posterior, subcapsular plaque. Except for extensive pseudoexfoliation, the fellow lens was clear. After a subsequent week of strict diabetic control, the feathery streak-like opacities had almost disappeared. The findings are discussed in relation to the experimentally induced sugar cataract in which sugar alcohol accumulation and subsequent lens swelling result in a potentially reversible lens opacification.

Blood Glucose↗

Evaluation of possible microwave-induced lens changes in the United States Air Force.

An Air Force examination team performed ophthalmologic examinations on 817 subjects in a double blind fashion. The subjects included 477 workers in the microwave radiation field and 340 control subjects with no known history of occupational exposure to microwave radiation. The intent of the study was to determine if a significant difference existed between the two groups for the presence of three lenticular findings equated with early cataract formation. No significant difference was found. Thus, this study does not support the contention that microwave exposure in the military environment is causing human cataracts at levels permitted by U.S. Safety Standards.

Adult↗