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Biomedical subjects

C S Foster

Publications and source records attributed to C S Foster.

At least 289 records · Page 16Linked to original sources

Serious complications of topical mitomycin-C after pterygium surgery.

BACKGROUND: The use of topical mitomycin (mitomycin-C) as a medical adjunct to pterygium and glaucoma surgery is increasing. METHODS: The authors report on a series of 10 patients who experienced serious, vision-threatening complications associated with the use of this drug after pterygium surgery. RESULTS: Complications included severe secondary glaucoma (4 patients), corneal edema (3 patients), corneal perforation (1 patient), corectopia (2 patients), iritis (8 patients), sudden onset mature cataract (2 patients), scleral calcification (1 patient) and incapacitating photophobia and pain (8 patients). Two patients required penetrating keratoplasties and a third required three lamellar keratoplasties. Another patient underwent four additional surgeries including a conjunctival Z-plasty, scleral patch grafting, and conjunctival autografting before his intractable pain and photophobia resolved 15 months after the original surgery. Because of these complications, 6 patients required a total of 20 return visits to the operating room after their original pterygium surgery. In 5 eyes, visual acuity remained at 20/200 or less. Three of the six patients with the most severe complications had concomitant chronic external diseases (rosacea [3 patients], ichthyosis [1 patient], keratitis sicca [1 patient]). CONCLUSION: The authors urge extreme caution in the use of mitomycin. If mitomycin is used, the lowest possible concentration should be applied for the shortest time period in an effort to avoid these complications. A prospective multicenter study of the ophthalmic use of this medication is needed.

Adult↗

Intercellular adhesion molecule-1 (ICAM-1) and HLA-DR antigens in herpes keratitis.

PURPOSE: Intercellular adhesion molecule-1 (ICAM-1) is a cell surface glycoprotein that binds leukocyte function antigen-1 receptor on leukocytes, thereby regulating leukocyte trafficking and function at sites of inflammation. Recently, the authors demonstrated ICAM-1 in human corneas exposed to proinflammatory cytokines, but ICAM-1 has not been reported in corneal disease. In this study, the presence of ICAM-1 in human disciform herpes simplex virus (HSV) keratitis is investigated. METHODS: Immunohistochemistry was performed for ICAM-1 on 4 keratoplasty specimens from patients with corneal scarring due to disciform HSV keratitis and 1 corneoscleral biopsy of a patient with active HSV keratoscleritis using specific, characterized monoclonal antibody to ICAM-1. Negative immunohistochemical controls included monoclonal antibodies to other vascular endothelial adhesion molecules or mouse serum. RESULTS: All 5 specimens demonstrated intense ICAM-1 immunoreactivity of keratinocytes, stromal keratocytes, and endothelial cells, predominantly in regions of leukocytic infiltration. Diffuse, intense HLA-DR positivity was detected throughout the corneas. The specimens failed to react with control antibodies. CONCLUSION: These results are the first to demonstrate ICAM-1 in human corneal disease and suggest important roles for ICAM-1 and HLA-DR co-expression in generating immune responses in HSV keratitis. Increased ICAM-1 expression in regions of leukocytic infiltration may regulate leukocyte-corneal cell binding, thereby promoting immune responses and damage by activated leukocytes.

Adult↗

Results of buccal mucosal grafting for patients with medically controlled ocular cicatricial pemphigoid.

Eyelid surgery for patients with ocular cicatricial pemphigoid is risky when there is unchecked perioperative inflammation. The authors performed buccal mucosal grafts on 42 eyelids (23 eyes) of 17 patients with ocular cicatricial pemphigoid whose disease was controlled by systemic immunosuppression. Results were graded as: improved (12 cases, 16 eyes); satisfactory (2 cases, 2 eyes); or poor (5 patients, 5 eyes). Complications included breakthrough trichiasis, surface keratinization of the graft, blepharoptosis, phimosis, depressed eyelid blink, incomplete eyelid closure, submucosal abscess formation, and persistent nonhealing epithelial defects of the cornea. Technical errors at surgery accounted for two complications. Secondary corneal ulceration developed in two patients. The immunologic aspect of the disease flared or progressed in five patients in the postoperative period and necessitated an increase or change in systemic medication for immunosuppression. Buccal mucosal grafting shows promise in temporarily rehabilitating eyelids of some ocular cicatricial pemphigoid patients whose disease is controlled by immunosuppressive therapy.

Eyelid Diseases↗

Diagnostic value of anti-neutrophil cytoplasmic antibodies in scleritis associated with Wegener's granulomatosis.

Serum antineutrophil cytoplasmic antibodies (ANCAs) are a sensitive and specific marker for generalized Wegener's granulomatosis. However, ANCA sensitivity and specificity in identifying patients in whom ophthalmic signs constitute the presenting or only definitive manifestation of Wegener's granulomatosis have not been tested. The authors report on 7 patients in whom scleritis was the initial manifestation leading to the diagnosis of Wegener's granulomatosis. Six had the limited form of Wegener's granulomatosis. Results of serum ANCA tests were positive in all these patients. In contrast, the serum ANCA was negative in 54 patients with ocular inflammation due to other disorders; 16 of these patients had scleritis. Serial ANCA titers reverted to normal in only two of the four patients with Wegener's granulomatosis who attained clinical remission. One of the patients who did not revert to normal experienced relapse 2 months after discontinuation of therapy. Antineutrophil cytoplasmic antibodies appear to be both sensitive and specific for Wegener's granulomatosis-associated scleritis, and testing is useful in the evaluation of patients with scleritis.

Adolescent↗

Management of corneal complications in xeroderma pigmentosum.

Xeroderma pigmentosum is an uncommon, recessively inherited disorder characterized by hypersensitivity to ultraviolet (UV) radiation, with defective repair of DNA damage caused by short-wavelength radiation. Patients with this disease experience progressive and precancerous changes in sun-exposed areas of the skin and mucous membranes. Some patients develop progressive neurologic degeneration. Eye involvement includes lid, conjunctiva, and corneal disorders. We report clinical, histopathologic findings, and complex management strategies used for a 33-year-old woman with xeroderma pigmentosum and recurrent corneal ulcerations that required corneal transplantation, topical cyclosporin, perilimbic conjunctival resection followed by topical mitomycin C, and corneal dye-laser photocoagulation of neovascularization in the left eye.

Adult↗

Intraocular penetration of ketoconazole in rabbits.

We studied penetration of the antifungal agent ketoconazole into the cornea, aqueous humor, and vitreous of rabbits after topical, subconjunctival, and oral administration. The effect of debridement of corneal epithelium on penetration was also investigated. Ketoconazole levels in the cornea and aqueous humor were high after topical or subconjunctival administration, and increased markedly (especially in the cornea) if the corneal epithelium had been debrided before administration of the drug. For example, concentration of ketoconazole in the cornea 1 h after topical drug administration with or without complete corneal epithelial debridement was 44.0 +/- 10.1 and 1,391.5 +/- 130.0 micrograms/g, respectively. Drug levels in the vitreous were not detectable after topical or subconjunctival drug administration, but were improved slightly by prior epithelial debridement (8.3 and 0.12 micrograms/mL after 1 h, respectively). Orally administered ketoconazole resulted in high corneal concentrations (45.0 +/- 7.6 micrograms/g after 1 h) that were still substantial 24 h later (55.0 +/- 7.0 micrograms/g); levels in the aqueous were low.

Administration, Oral↗

Improved detection of disease progression in ocular cicatricial pemphigoid.

Cicatricial pemphigoid is an autoimmune systemic disease characterized by chronic conjunctival cicatrization. The natural history is one of variable degrees of progressive scarring of the ocular surface and visual loss. Previous reports have shown systemic chemotherapy to be efficacious in halting cicatrization in progressive cases. This observation makes it of critical importance to be able to detect progression of the disease as early as possible so as to allow for earlier institution of treatment. Our experience in previous studies has led us to believe that disease staging systems currently in use are relatively insensitive in detecting disease progression. We present a revised staging system that combines the strengths of the staging systems in use today and extends their sensitivity.

Humans↗

Topical cyclosporine A and corneal wound healing.

The effect of 2% topical cyclosporine A (CsA) ointment on corneal epithelial and stromal wound healing was evaluated in a masked, placebo-controlled study in rabbits. The difference in epithelial would healing rate in the treatment and placebo group was not statistically significant. There was also no difference in the values of bursting strength of 2-mm central penetrating wounds and in the measurement of hydroxyproline content in the central corneal buttons from the wounded area in both the groups. Clinical evaluation of the quality of regenerating epithelium, stromal edema, haze, and iritis did not reveal a difference between the two groups. There was a significantly higher incidence of conjunctival injection in the CsA-treated group. We conclude that topical cyclosporine A 2% does not significantly inhibit epithelial or stromal corneal wound healing.

Animals↗

Report on the sequence of DQB1*0301 gene in ocular cicatricial pemphigoid patients.

Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affects the conjunctiva and other mucous membranes. Major histocompatibility complex (MHC) class II genes are important in autoimmunity because the antigen is presented to the T cell receptor in association with these molecules. A highly statistically significant association has been observed between patients with OCP and DQw7 (DQB1*0301) gene. DNA sequences of the second and third exons of the DQB1*0301 gene were determined in three OCP patients and compared with a control homozygous cell line for DQw7 from the Tenth International Histocompatibility Workshop. The sequences were identical in the patients studied and reference cell line. This data indicates that DQB1*0301 may only partly provide the enhanced susceptibility to get OCP and that another gene(s) in linkage disequilibrium with it and other factors may play an important role in the pathogenesis.

Amino Acid Sequence↗

Immunohistopathologic findings in herpes simplex virus chorioretinitis in the von Szily model.

After anterior chamber inoculation of herpes simplex virus type 1 (HSV-1), some mice have a characteristic pattern of ocular disease, including ipsilateral anterior uveitis, relative sparing of the ipsilateral retina, and necrotizing contralateral chorioretinitis. It was reported previously that susceptibility to the contralateral chorioretinitis is associated with the Igh-1 locus; congenic mice differing at this locus have different rates of contralateral disease. The immunohistopathologic findings of this model in Igh-1 disparate congenic mice are reported after examining immune cell populations (CD4, CD8, Thy 1.2, Ia, Mac, and immunoglobulin G cells) in both ipsilateral and contralateral eyes and the recruitment kinetics of these cell types in various ocular tissues. In both HSV-susceptible BALB/c and HSV-resistant C.B-17 mice, the ipsilateral eye undergoes early cellular infiltration, and the contralateral retina is devoid of cells until day 10 postinoculation. In BALB/c mice, a late dramatic rise develops in Mac and Ia cells in the ipsilateral and contralateral choroid (P less than 0.005) compared with C.B-17 mice. The C.B-17 mice have an earlier, mild cellular infiltration of the uveal tract in the ipsilateral eye, abrogation of the late Mac and Ia cellular recruitment in the ipsilateral choroid, and an absent contralateral response. These strain-specific immunohistopathologic differences help to explain Igh-1-linked HSV retinitis patterns in this model.

Animals↗

Depletion of T-lymphocyte subsets in murine herpes-simplex-virus retinitis.

Uniocular injection of herpes-simplex virus type 1 into the anterior chamber of BALB/c mice induced contralateral retinitis with relative preservation of the ipsilateral retina. Overall 95% of T-cell deficient nude mice developed ipsi- and contralateral retinitis, suggesting the importance of T-cells in this model. We then depleted lymphocyte subsets in susceptible BALB/c and resistant CB-17 and C57BL/6J mice using anti-CD4 (helper/inducer cells) or anti-CD8 (suppressor/cytotoxic cells) monoclonal antibody. 85% of CD8-depleted, 58% of CD4-depleted and 50% of untreated BALB/c mice developed contralateral retinitis. All CD4- and CD8-depleted animals developed severe ipsilateral retinitis. These results suggest that CD8 cells (but not CD4 cells) are protective for the contralateral retina in BALB/c mice and that both subsets are important for the ipsilateral protection. In CB-17 and C57BL/6J mice, depletion produced no change in the contralateral retina but resulted in ipsilateral retinitis, suggesting different mechanisms for ipsi- and contralateral protection. The possible role of the anterior-chamber-associated immune deviation is discussed.

Animals↗

Fungal keratitis.

As Jones has emphasized, the successful management of microbial keratitis, fungal or otherwise, necessitates five steps: (1) clinical suspicion and clinical diagnosis; (2) performing the proper laboratory procedures; (3) initiating antimicrobial therapy based on the results of laboratory studies; (4) modifying the initial therapy based on the clinical response; and (5) deciding correctly when and how to terminate therapy. Keratomycosis poses special diagnostic and therapeutic challenges for ophthalmologists because of its low incidence, and its resistance to treatment, because of the lack of antifungal agents with good penetration into the eye, and because of the difficulties in obtaining meaningful in vitro drug susceptibility results for fungal isolates. We believe, however, that ophthalmologists are now diagnosing keratomycosis earlier and treating it more effectively.

Antifungal Agents↗

The T cell receptor in normal and inflamed human conjunctiva.

The majority of human peripheral blood and lymphoid tissue T cells express the TCR alpha/beta heterodimer, while the TCR gamma/delta is expressed on only a small subset of T lymphocytes. However, the majority of murine intraepithelial lymphocytes and most Thy-1+ murine dendritic epidermal cells express the TCR gamma/delta. Selective homing of avian TCR gamma/delta bearing lymphocytes to the intestinal epithelium also has been shown. These findings have suggested that these cells play a role against transformation and infection. More recently, a role in autoimmunity also has been proposed. We examined normal human conjunctiva and inflamed conjunctiva from patients with ocular cicatricial pemphigoid (OCP), an autoimmune disorder, and atopic keratoconjunctivitis (AKC). The majority of T cells in the epithelium and substantia propria of normal conjunctiva expressed the TCR alpha/beta. Tropism of TCR gamma/delta-expressing lymphocytes to normal human conjunctiva was not present. However, in OCP, there was a statistically significant increase in the absolute number of TCR gamma/delta cells/mm2 (epithelium, 33.9 +/- 10.5 [mean +/- standard error of the mean] vs. 159.9 +/- 51.5, P = less than 0.0008; substantia propria, 4.1 +/- 0.9 vs. 240.1 +/- 191.3, P less than 0.002) and TCR gamma/delta cells as a percentage of CD3+ cells (epithelium, 0.18 +/- 0.06 vs. 0.39 +/- 0.07, P = less than 0.02; substantia propria, 0.10 +/- 0.05 vs 0.33 +/- 0.08, P = less than 0.03). This was not the case for AKC. These findings suggest that TCR gamma/delta lymphocytes play a specific but undefined role in certain conjunctival inflammatory conditions and may be important in autoimmunity.

Antibodies, Monoclonal↗