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Biomedical subjects

E R Crouch

Publications and source records attributed to E R Crouch.

At least 19 recordsLinked to original sources

The birth of ocular pharmacology in the 20th century.

Nineteenth century ophthalmology, characterized by significant gains in diagnostic techniques, provided the basis for great advancements in treatment during the 20th century. Drug therapy at the turn of the century was empiric, palliative, and often toxic. The development of ocular pharmacology during the 20th century provided the basis for a rational therapeutic approach to ocular disease. Foremost among the therapeutic developments were antibiotics, due to their potential to cure conditions that frequently resulted in blindness. Second, other therapeutic classes provided palliative therapy for chronic diseases, and thus decreased morbidity. For example, drugs specifically targeting many different aspects of glaucoma have had remarkable success controlling intraocular pressure and forestalling development of blindness. In addition, other new approaches provided palliative therapy for nonblinding conditions and effective adjuncts to surgical procedures. Antiallergy and anti-inflammatory drugs greatly increased patient comfort and facilitated treatment of allergic and inflammatory reactions. Local anesthetics and analgesia reduced patient discomfort during surgery. Other adjunct drugs improved surgical outcomes by reducing inflammation and infectious complications. The 21st century will undoubtedly provide novel approaches to address many of today's therapeutic dilemmas. Photodynamic therapy, growth factors, antisense technology, and genetic-based therapies all show great promise. Many of the conditions that are only treated palliatively today will be curable in the next century using many of these pharmacological advances.

Anti-Allergic Agents↗

Topical aminocaproic acid facilitates reepithelialization of persistent epithelial defects.

PURPOSE: After corneal injury, persistent epithelial defects (PED's) may occur due to the chronic failure of the regenerating epithelium to adhere to the underlying stroma. The aim of this study was to examine the potential of epsilonaminocaproic acid (EACA) as a topical treatment for PED's. EACA inhibits the activation of plasmin, which metabolizes fibronectin. Fibronectin, a glycoprotein, anchors corneal epithelium to the basement membrane and the underlying stroma. METHODS: In anesthetized rabbits, PED's were induced with sodium hydroxide (1 N). Seven days later, during the late healing phase, treatment began with administration of EACA (30%) to the right eye and administration of vehicle alone to the left eye three times daily. A control group received neither EACA nor vehicle. Rabbits were treated for 19 days. PED's were visualized by fluorescein staining. Their size was mapped using digital planimetry. RESULTS: After 11 days of treatment with EACA, treated PED's were 50% smaller than in corneas treated with vehicle alone. Following treatment for 15 days, corneas treated with EACA had significantly greater re-epithelialization than vehicle-treated or control corneas. Frozen sections stained immunofluorescently for fibronectin appeared to qualitatively contain more adherent fibronectin in treated corneas. Transmission and scanning electron microscopy indicated that the epithelium was more polymorphic, thinner and vacuolated in untreated controls compared to EACA treated eyes. Light microscopy demonstrated more continuous adherent epithelium after EACA treatment. CONCLUSIONS: Topically administered EACA decreases both the severity and incidence of persistent epithelial defects produced by alkali bums to the cornea. EACA appears to promote adherence of the regenerating epithelium to the underlying stroma. Thus, topically administered EACA may be an effective treatment for this chronic condition.

Administration, Topical↗

Aminocaproic acid and tranexamic acid increase the rate of acute corneal reepithelialization in Sprague Dawley rats.

Antifibrinolytic agents, epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), have been reported to be efficacious in the treatment of chronic persistent epithelial defects. Within the regulatory mechanism of corneal reepithelialization, fibronectin serves as a primary adhesive component in the healing process and anchors regenerating epithelial cells to underlying stroma. EACA and TXA inhibit the activation of plasmin thereby decreasing plasmin-induced catabolism of fibronectin. In this study, acute reepithelialization following treatment with EACA and TXA was evaluated in the cultured rat cornea model. Sprague Dawley rat corneal explants with 3 mm corneal defects, induced with 1 N NaOH, were cultured with either EACA or TXA. After 12 or 24 hr incubation periods, corneal explants were stained with bromodeoxyuridine stain for measuring cellular division and migration or Trypan Blue for measuring the extent of dead cells. Both EACA and TXA increased the rate of reepithelialization in comparison to an untreated control. EACA was up to 35% more efficacious than TXA. Thus, this study demonstrated an acute effect for EACA and TXA versus the previously reported efficacy of chronic therapy required for persistent epithelial defects. Broad applications may prove beneficial in the clinical treatment of corneal abrasions, persistent corneal epithelial defects, or alkali burns.

Aminocaproic Acid↗

Topical versus intravenous administration of tranexamic acid: a comparison of intraocular and serum concentrations in the rabbit.

BACKGROUND: Tranexamic acid has been shown to greatly reduce the incidence of secondary hemorrhage when administered orally or intravenously. Topical administration of the drug should result in much lower serum concentrations, with fewer adverse effects. We performed a study to determine whether topical application of tranexamic acid would yield higher intraocular concentrations and lower serum concentrations of drug than intravenous administration. METHODS: Ten New Zealand white rabbits received 25 mg/kg of tranexamic acid intravenously every 8 hours for 3 days. Another group of 10 rabbits received one drop (0.05 mL) of commercially available tranexamic acid solution (100 mg/mL) every 8 hours for 3 days to one eye. Tranexamic acid levels in the aqueous humour, vitreous humour and serum 1 hour after administration of the last dose of drug were determined. RESULTS: Analysis of variance showed that aqueous concentrations of tranexamic acid were significantly higher with topical delivery than with intravenous administration (15 vs. 9 micrograms/mL)(p < 0.05). Serum concentrations were significantly lower following topical administration (9 vs. 19 micrograms/mL)(p < 0.01). The drug was not detected in the vitreous humour in either group. INTERPRETATION: Topical delivery of tranexamic acid may prove to be valuable in yielding therapeutic intraocular concentrations of drug in patients with hyphema while minimizing systemic toxicity.

Administration, Topical↗

Topical aminocaproic acid in the treatment of traumatic hyphema.

OBJECTIVES: To determine whether topically applied aminocaproic acid, like systemic aminocaproic acid, effectively reduces secondary hemorrhage after hyphemas and to compare the safety and effectiveness of topical application with those of systemic use and a control group. DESIGN: A prospective, randomized, double-masked, multicenter study. PATIENTS: Sixty-four patients with traumatic hyphema treated with topical or systemic aminocaproic acid and compared with 54 control patients with hyphema. Daily slitlamp examinations for hyphema grading and corneal clarity, initial and final visual acuity, applanation tonometry, and fundus indirect ophthalmoscopy were studied. Follow-up was 6 months to 5 1/2 years (mean, 2.96 years). RESULTS: Compared with the control group, topical and systemic aminocaproic acid was statistically significant in preventing secondary hemorrhage. Only 3% (2/64) of the patients who received topical or systemic aminocaproic acid had secondary hemorrhage compared with 22% (12/54) of the control group (P = .002). Final visual acuity was 20/40 or better in 30 patients (86%) in the topical group compared with 23 patients (43%) in the control group (P < .001). Final visual acuity was 20/40 or better in 20 patients (69%) in the systemic aminocaproic acid group compared with 23 patients (43%) in the control group (P = .04). The topical aminocaproic acid group had a final visual acuity of 20/40 or better in 86% of patients, compared with 69% of patients in the systemic group. CONCLUSIONS: Topical aminocaproic acid appears to be a safe, effective treatment to prevent secondary hemorrhage in traumatic hyphema. It is as effective as systemic aminocaproic acid in reducing secondary hemorrhage. No systemic side effects were observed with topical use. Topical aminocaproic acid provides an effective out-patient treatment for traumatic hyphemas.

Administration, Topical↗

Factors affecting therapeutic concentration of topical aminocaproic acid in traumatic hyphema.

Epsilon-aminocaproic acid (EACA) decreases rebleeding in traumatic hyphema through antifibrinolytic activity. Therapeutic levels were achieved in aqueous humor of rabbits after topical application. Aqueous humor EACA levels were significantly higher after pretreatment with 0.5% proparacaine. Use of EACA (60%) in a carboxypolymethylene (CPM) vehicle (0.5%, 1%, 2%, 3%, and 4%) was examined. Aqueous humors levels at 4 hours ranged from 6.18-20.42 micrograms/ml. The 2% and 3% formulas achieved the highest concentrations in aqueous. Use of EACA (15%, 30%, 40%, and 60%) in 4% CPM was also studied. At 2 and 4 hours after treatment, the 30% EACA solution most effectively achieved therapeutic levels. Velcro closure devices were attached to the rabbit's eyelids, and 200 microliters of 30% EACA in 2% CPM was administered. After 3 hours the patched eyes had a mean aqueous EACA level of 60.09 micrograms/ml compared with 8.97 micrograms/ml in unpatched eyes. When dose size was studied in patched eyes, 200-microliters doses achieved aqueous levels of 60.09 micrograms/ml, and 100-microliters doses resulted in levels of 10.40 micrograms/ml. Since epithelial toxicity was observed in eyes that had been patched, the optimum topical regimen appeared to be 200 microliters of 30% EACA in 2% CPM every 6 hours in unpatched eyes.

Acrylic Resins↗

Topical aminocaproic acid significantly reduces the incidence of secondary hemorrhage in traumatic hyphema in the rabbit model.

Systemically administered aminocaproic acid has been shown to reduce the incidence of secondary hemorrhage after traumatic hyphema. To date, no topical treatment has been shown to be effective in reducing the incidence of rebleeding in a double-masked study. Experimentally induced traumatic hyphemas in the rabbit model were treated with topical placebo gel (4% carboxypolymethylene gel only) or carboxypolymethylene gel with amino-caproic acid (treated group) in a double-masked fashion and were compared with untreated controls (control group). In both the control and placebo groups, there was a 33% rebleed rate. The treated eyes had a 10% rebleed rate that is statistically significant. The topically applied aminocaproic acid gel appears to be well tolerated locally without evidence of systemic toxicity. This study indicates that topical aminocaproic acid may be an effective alternative to systemic treatment to reduce the incidence of secondary hemorrhage in traumatic hyphema.

Acrylic Resins↗

Systemic aminocaproic acid reduces fibrinolysis in aqueous humor.

Systemically administered aminocaproic acid has been demonstrated to reduce the incidence of secondary hemorrhage in traumatic hyphema. To directly determine the concentration of aminocaproic acid in the aqueous humor, four groups of rabbits were studied following administration of four different regimens of intravenously administered aminocaproic acid. Plasma and aqueous humor samples were assayed for drug content and antifibrinolytic activity. Peak aqueous humor concentrations of aminocaproic acid ranged from 2.5 to 33 mg/dL and varied according to the systemic dose administered. The antifibrinolytic activity paralleled the aminocaproic acid content, with a peak range from 310 to 683 s. These findings indicate a direct relationship between antifibrinolytic activity and the concentration of aminocaproic acid in aqueous humor.

Aminocaproates↗

Topically applied aminocaproic acid concentrates in the aqueous humor of the rabbit in therapeutic levels.

Systemically administered aminocaproic acid, used to reduce the incidence of secondary hemorrhage in traumatic hyphema, has been shown to accumulate in the aqueous humor of rabbits in a dose-dependent manner. Eight topical preparations of aminocaproic acid were studied to determine aqueous humor concentrations. The vehicles studied included the following: sodium chloride, 0.85 g/dL; polyvinyl alcohol, 1.4 g/dL; hydroxypropyl methylcellulose, 0.4 g/dL; benzalkonium chloride, 0.01 g/dL; ethylenediamine tetraacetic acid disodium, 0.01 g/dL; dimethyl sulfoxide, 11 and 39.6 g/dL; and carboxypolymethylene, 4 g/dL. All contained 735 g/L of aminocaproic acid except for dimethyl sulfoxide (39.6 g/dL) and carboxypolymethylene (4 g/dL), which contained 238 and 600 g/L of aminocaproic acid, respectively. Aqueous humor and plasma samples were assayed for aminocaproic acid content following topical administration. Aqueous humor concentrations of aminocaproic acid ranged from undetectable (less than 0.01 mg/dL) to 5.75 mg/dL. Plasma concentrations ranged from undetectable (less than 0.01 mg/dL) to 9.85 mg/dL. Polyvinyl alcohol (1.4 g/dL) and carboxy polymethylene (4 g/dL) provided the highest aqueous humor aminocaproic acid concentrations. The aqueous humor levels with topical aminocaproic acid administration were comparable with those achieved by systemic administration. Plasma drug levels with topical aminocaproic acid were between 5% and 33% of levels achieved by systemic aminocaproic acid. This study demonstrates that aminocaproic acid can be effectively delivered into the anterior chamber of rabbits by topical application.

Acrylic Resins↗

Pediatric aphakic glaucoma.

Three cases of pediatric open-angle aphakic glaucoma are presented. These patients had congenital cataracts extracted by the extracapsular techniques of phacofragmentation or irrigation and aspiration. Each required a secondary membranectomy and had development of glaucoma six to 25 months after cataract extraction. Surgical therapy was required in each case of glaucoma, and multiple procedures were necessary. Visual outcome in the involved eye was less than 20/400. The cause of the open-angle aphakic glaucoma is most likely secondary to damage to the trabecular meshwork initiated by uveitis and lens remnants. We urge ophthalmologists who perform pediatric cataract surgery to use phacofragmentation of the cataract and posterior capsule and anterior vitrectomy with vitrectomy instrumentation. This should reduce the incidence of secondary membranes and glaucoma. Ophthalmologists should be aware of this complication and the necessity of prolonged patient follow-up.

Cataract Extraction↗

Management of posterior lenticonus complicated by unilateral cataract.

We studied 21 patients with 23 eyes with posterior lenticonus. Twenty-one of the eyes developed progressive cataractous changes that required lens aspiration in 19 eyes when vision reduction was 6/30 (20/100) or less. The inherent weakness of the diaphanous portion of the posterior lens capsule contributed to disruption of the normal lamellar arrangement of the lens fibers resulting in cataractous changes. Amblyopia was the most significant visual problem associated with posterior lenticonus. Fifteen of the 19 operated eyes in this study were amblyopic and nine of the 15 were improved to 6/15 (20/50) or better vision with occlusion therapy, after surgical aspiration of the cataractous lens and contact lens therapy.

Adolescent↗

Elephantiasis of eyelids following repeated craniotomy. Case report.

A case is reported in which craniectomy for removal of right frontal meningioma was complicated by porencephaly. A peculiar granulomatous area was found over the brain at reoperation for cranioplasty. Iodine solution was used to paint the reactive material under the scalp flap. Giant swelling of the isilateral eyelids gradually developed, ascribed to interference with lymphatic drainage from the eyelids. There was no communication between eyelids and cerebrospinal fluid spaces. The enlarged eyelids were removed by ophthalmic plastic surgery.

Brain Neoplasms↗

Aminocaproic acid in the treatment of traumatic hyphema.

Of 59 patients with traumatic hyphema studied prospectively, 32 received aminocaproic acid, an antifibrinolytic agent, to prevent secondary hemorrhage. The remaining 27 patients received placebo in an identical manner. Of the aminocaproic acid-treated patients, only one (3%) rebled, while nine patients (33%) receiving placebo suffered secondary hemorrhage. The results of this study indicate a statistically significant reduction (P less than .01) in the incidence of rebleeding in patients treated with this drug.

Adolescent↗

Retinal periarteritis secondary to syphilis.

A 43-year-old black woman showed ophthalmoscopic evidence of retinal arteriolitis two weeks after being treated for uniocular panuveitis. Angiographic examination suggested that these deposits were not intraluminal or endothelial atherosclerotic emboli or plaques, but were deposits in the outer walls of retinal arterioles. Sequential ophthalmoscopic and angiographic examinations at one-month intervals for 12 months showed no progression or change in location of these deposits. Results of clinical and laboratory investigations suggested the diagnosis of syphilis. We believe it is rare for syphilitic infection to be implicated in the diagnosis of isolated retinal arteriolitis without periphlebitis.

Adult↗