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Biomedical subjects

R A Thoft

Publications and source records attributed to R A Thoft.

At least 55 records · Page 3Linked to original sources
PubMed1987

In vivo effects of 5-FU on ocular surface epithelium following corneal wounding.

We evaluated the dose relationship between the antiproliferative and toxic effects of 5-fluorouracil (5-FU) on the ocular surface epithelium following experimental corneal epithelial wounding in rabbits. Central corneal epithelial defects 8 mm in diameter were made using n-heptanol. 5-FU (0.05 mg, 0.5 mg, or 5.0 mg per day in divided doses) or saline was applied topically for up to 18 days beginning on the day of wounding. The animals were sacrificed at 1, 7 or 14 days after wound closure. The effect on the ocular surface epithelium was assessed by observation of the clinical and histological appearance, and determination of the rate of corneal epithelial defect closure, corneal epithelial mitotic rate and conjunctival goblet cell frequency. A daily dose of 0.05 mg of topical 5-FU for 18 days had no discernable clinical or histopathological effect compared to wounded, saline treated controls. Treatment with 0.5 mg daily prevented the high mitotic rate typically noted 1 day immediately following defect closure, yet had no significant effect on clinical appearance, histological appearance, or healing rate. Daily topical application of 5.0 mg of 5-FU reduced the corneal epithelial mitotic rate to approximately 1% of the wounded controls, with persistent epithelial defects occurring in 22% of the eyes in this group. In those eyes which did heal, the corneal epithelium was markedly thinner than controls 1 day after defect closure. Fourteen days after healing, epithelial thickness in this group varied from 2 to 13 cells across each cornea, with the thickest area occurring centrally and tapering gradually to the limbus.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1986

Inhibition of vascularization in rabbit corneas by heparin: cortisone pellets.

The purpose of this work was to study the effectiveness of heparin plus cortisone, and of cortisone alone in control of corneal vascularization in rabbit eyes. Corneal vascularization was induced by de-epithelialization of the cornea and limbus and part of the bulbar conjunctiva with concurrent trephination and excision of a central 2-mm diameter corneal button. Inhibition of vascularization by polymer pellets impregnated with heparin (Panheprin, Abbott Laboratories; Chicago, IL) and cortisone, or neither drug was studied by implanting the pellets into the eyes at the time of injury and following the eye clinically and histologically. Wounded corneas with empty pellets developed vascularization extending from the limbus to the central cornea within 3 wk (n = 10). In other wounded eyes, heparin:cortisone pellets prevented vascularization (n = 10) while cortisone pellets slowed, but did not totally inhibit vascularization (n = 6). In other eyes, clear autografts were transplanted into vascularized eyes; and the ability of the drug-impregnated pellets to inhibit grafts vascularization was evaluated. In eyes with heparin:cortisone pellets inserted into the donor button at the time of keratoplasty, the autografts remained clear for at least 6 wk (n = 10) but subsequently vascularized if the sutures were not removed, while cortisone pellets slowed but did not block vascularization (n = 6). If heparin:cortisone pellets were inserted into the vascularized host tissue, rather than into the donor button, vascularization of the graft occurred (n = 6). Thus, heparin (Panheprin, Abbott Laboratories; Chicago IL) plus cortisone inhibited vascularization in rabbit cornea in the models studied: The effect of other commercially available heparins remains to be studied.

Animals↗
PubMed1985

Collagen gel for ocular surface.

A replacement ocular surface requires a substrate that is easily manipulated surgically, does not cause an inflammatory reaction, and is nontoxic to epithelial cells. This work evaluates the usefulness of a collagen gel as a substrate for corneal epithelial cells by determining the ocular toxicity of the gel and the ability of the gel to support and maintain corneal epithelial cells in vitro. Collagen gels, made from Vitrogen, were easily manipulated and were well-tolerated in rabbit eyes for up to 6 wk (n = 3). Epithelial sheets placed on collagen gels and incubated at 37 degrees C for up to 13 days remained well-apposed to the gels and appeared normal, but thinned, from five to three layers. The basal cells extended cytoplasmic blebs into the gels, but only one sheet of five sheets showed basement membrane deposition by 6-13 days. Thus, the collagen gels appear to meet the criteria defined above and may be a suitable substrate in biofabricated ocular surfaces.

Animals↗
PubMed1985

5-Fluorouracil toxicity to the ocular surface epithelium.

The antimetabolite, 5-fluorouracil (5-FU), has been used to control proliferation of retinal pigment epithelial cells and fibrocytes, and is currently the subject of a multicenter clinical trial of its value in the control of scarring after glaucoma operations. To evaluate possible ocular surface toxicity, the effect of 5-FU on the mitotic rate and differentiation of the ocular surface epithelium in rabbits was measured. 5-FU was instilled into eyes with 10-mm diameter central epithelial wounds and into nonwounded eyes at a dose of 9 mg per day for 4 days. Saline treated control wounded eyes healed within 4 days (n = 5) while 40% (4 of 10) of the 5-FU treated wounded eyes had defects at 4 days. The normal mitotic rate of the corneal epithelium was 1.0 +/- 0.3 (n = 4) tritiated thymidine labeled cells per 100 basal corneal epithelial cells after 2.5 hr incubation. Saline treated control wounded eyes had an increased mitotic rate, 7.1 +/- 1.3 (n = 5) labeled cells per 100 basal corneal epithelial cells after 2.5 hr incubation. Topical 5-FU decreased both of those rates to about 1% of normal. The normal conjunctival epithelial mitotic rate was 1.8 +/- 0.4 (n = 4) labeled cells per 60 basal cells after per 2.5 hr incubation. This rate was the same in wounded eyes, but was decreased in eyes treated with 5-FU. Thus, 5-FU (9 mg/day topically) has serious toxic effects to ocular surface epithelium which must be carefully considered if this drug is to be used clinically.

Animals↗
PubMed1984

Ocular cicatricial pemphigoid associated with hyperproliferation of the conjunctival epithelium.

We determined the mitotic rate, measured by evaluating uptake of tritiated thymidine autoradiographically, and the frequency of goblet cells in conjunctival epithelial biopsy specimens from nine normal subjects and from 11 patients (seven women and four men ranging in age from 50 to 80 years) with ocular cicatricial pemphigoid. The mitotic rate of patients with the disease was significantly higher than that of normal subjects, 7.2 +/- 2.2 vs 1.6 +/- 0.2 labeled cells per 100 basal epithelial cells (P less than .01). The goblet cell frequency, however, was significantly less in patients than in normal subjects. This suggests that ocular cicatricial pemphigoid is associated with hyperproliferation of the conjunctival epithelium, with a concurrent failure of normal conjunctival differentiation.

Aged↗
PubMed1984

Keratoepithelioplasty.

Keratoepithelioplasty is a new surgical procedure for the treatment of persistent epithelial defects in patients without healthy donor tissue in their fellow eyes. After a total superficial keratectomy, lenticules of donor cornea covered by epithelium are placed at the corneoscleral limbus. The epithelium spreads from the lenticules and covers the center of the cornea. In three of four patients with persistent defects of long duration, healing was successful and vision improved. The three successful procedures were in patients who had had chemical injuries. They retained useful visual function without recurrence of epithelial healing problems. In the fourth case, it was impossible to determine whether the procedure was useful because the patient, who had atopic keratoconjunctivitis, required a penetrating keratoplasty two months after the keratoepithelioplasty.

Adult↗
PubMed1984

The role of lens implantation in cataract surgery.

Cataract surgery results in a substantial loss of the refractive power of the eye, which may be corrected by wearing cataract glasses, by using contact lenses, or by replacing the cataractous lens with an intraocular lens implant. This chapter discusses the advantages and disadvantages of each of these methods, and emphasizes the role of lens implants. The three kinds of intraocular lens implants currently available include the iris-supported lens, the anterior chamber lens, and the posterior chamber lens. Intraocular lens implants are rapidly becoming the method of choice in many patients who require cataract operations.

Cataract Extraction↗
PubMed1984

Histology of human conjunctival transplantation.

The technique of conjunctival transplantation has proven very successful in reestablishing an intact ocular surface in patients with severe ocular surface disease in whom conventional treatment has failed. We present follow-up on the histology of the transplanted conjunctival tissue in four alkali-burned patients who underwent penetrating keratoplasty 3-28 months following conjunctival transplantation. The corneal button was re-epithelialized in all patients. The fate of the transplanted tissue agreed with experimental observations made in the rabbit model, i.e., under areas of vascularization and inflammation, the transplanted tissue resembled conjunctiva with numerous goblet cells and 3-4 cell layers of nonkeratinized, stratified epithelium. In one patient, a definite "transition zone" from conjunctival to corneal appearing epithelium was seen in an area with minimal inflammation and vascularization, again confirming the animal results showing that transdifferentiation of conjunctival to corneal epithelium can occur.

Adult↗
PubMed1984

Conjunctival epithelial wound healing.

In vivo conjunctival epithelial healing in albino rabbits was investigated by light microscopy following both n-heptanol and trephined conjunctival wounding. Reepithelialization occurred faster following n-heptanol treatment (3 days) versus trephination (6-7 days). No goblet cells were present in the migrating epithelium during reepithelialization. After 1 day of wounding, goblet cells disappeared several millimeters peripheral to the wound margin in both types of wounds. Goblet cells first reappeared peripherally 1 week after wounding before they appeared in the central wound area. These observations indicate that a large area of conjunctival epithelium surrounding a wound is involved with repair of that wound. Since the goblet cell content of conjunctival epithelium appears to change as a result of the stresses of epithelial repair, the goblet cell population may reflect the presence of reparative or proliferative processes in the ocular surface.

Animals↗
PubMed1983

Idoxuridine-induced conjunctival cicatrization.

Four patients had idoxuridine-induced conjunctival cicatrization similar to ocular cicatricial pemphigoid develop, but in the treated eye only. Three of the four patients had chronic, recurrent herpes simplex epithelial and stromal keratitis. The fourth patient had Sjögren's syndrome. All received idoxuridine (0.1% drops and/or 0.5% ointment) and topical corticosteroids from one to 3 1/2 years. Substantial morbidity resulted that included visual loss, stromal ulceration, corneal scarring, and keratinization. Conjunctival biopsy specimens showed cicatrization with a mixed inflammatory cell reaction and absence of goblet cells. Results of direct immunofluorescent microscopy of the conjunctiva were either negative or nonspecific for autoantibody. No circulating autoantibody was detected in any of the four patients.

Conjunctival Diseases↗
PubMed1983

Goblet cell density in ocular surface disease. A better indicator than tear mucin.

Mucinlike glycoprotein from tears and conjunctival goblet cell densities were determined in normal subjects and in patients. The results indicated that although there was a statistically significant decrease, a substantial amount of mucinlike glycoprotein was present in tears from patients with ocular cicatricial pemphigoid (OCP), radiation keratitis, and corneal anesthesia. In the same patients, the goblet cell count was profoundly decreased in OCP and radiation keratitis, well out of proportion to the modest fall in mucinlike glycoprotein. This indicated that the tear mucin content shows minimal variation over a great variation in goblet cell density, suggesting that while moderate mucin deficiency may be associated with surface abnormalities, such mucin deficiency may not be the only cause of the ocular surface epithelial problems characteristic of these diseases. In addition, it is proposed that the goblet cell content of the conjunctiva is a sensitive indicator of primary ocular surface disease.

Cell Count↗
PubMed1983

Keratin-like proteins in corneal and conjunctival epithelium are different.

Using SDS polyacrylamide slab-gel electrophoresis, water-insoluble (keratin-like) proteins in normal and regenerated ocular surface epithelium from rabbits were studied. The results indicated that keratin-like proteins from corneal and conjunctival epithelia in vivo distinctly different. Regenerated epithelia from either source retained their original keratin characteristics for at least 10 days after healing over the cornea, but at very early stages of healing migrating and regenerated epithelia showed either an extra band or a prominent band in addition to the original keratin-like proteins. Three months after healing, however, regenerated conjunctival epithelium on the cornea had changed its keratin characteristics, and resembled, but was not identical to, corneal epithelium.

Animals↗