Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022575 (keratoconjunctivitis sicca)
 772 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the effects of CBS-211 A, a synthetic retinoic acid analog, on a previously described experimental model of keratoconjunctivitis sicca (KCS) in the rabbit. A 9-week topical treatment with 0.02% CBS-211 A in aqueous vehicle significantly increased the conjunctival goblet cell density (P less than 0.01, impression cytology counting), stopped the evolution of the corneo-conjunctival surface alteration (P less than 0.05, rose bengal test), and restored a basically normal mucosecretory product quality in goblet cells (lectin histochemistry) compared to vehicle treatment. The results assess the efficacy of this compound in reversing KCS pathology in a relevant model different from general vitamin A deficiency models, and strongly support the rationale for using such a well-tolerated retinoid in dry eye treatment.
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PMID:Beneficial effects of a retinoic acid analog, CBS-211 A, on an experimental model of keratoconjunctivitis sicca. 173 May 41

The authors evaluated the efficacy of all-trans retinoic acid (vitamin A) ointment as a treatment for keratoconjunctivitis sicca (KCS) in a group of 11 patients selected on the basis of clinical history, slit-lamp examination results, rose Bengal staining, and tear film osmolarity. In this open-label crossover study, vitamin A ointment was no more effective than placebo in increasing tear secretion, as indicated by Schirmer test with proparacaine or tear film osmolarity, or in decreasing ocular surface disease, as indicated by rose Bengal staining. Seven patients stated some preference for the placebo ointment, two patients for the vitamin A ointment, and two patients had no preference.
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PMID:Open-label crossover study of vitamin A ointment as a treatment for keratoconjunctivitis sicca. 270 43

Despite the diverse causes of dry-eye disorders, the ocular surface epithelia in these diseases all undergo squamous metaplasia, manifested by loss of goblet cells, mucin deficiency, and keratinization. These changes account for tearfilm instability, which leads to various ocular symptoms and corneal complications. This article reviews research in the use of topical tretinoin to treat severe dry-eye disorders. To classify squamous metaplasia into stages, a modified impression cytology technique was used to monitor the therapeutic effect of topical tretinoin ointment (0.01% or 0.1%, w/w) in 22 patients. This population had severe dry-eye disorders, including keratoconjunctivitis sicca, Stevens-Johnson syndrome, inactive ocular pemphigoid, drug-induced pseudopemphigoid, and surgery- or radiation-induced dry eyes. After treatment, clinical improvements were correlated with the reversal of squamous metaplasia as evidenced by the impression cytology technique. Tretinoin may also be effective in treating conjunctival keratinization without dry eyes, as illustrated by a case study. This may represent the first reported attempt to treat ocular surface disorders by reversing diseased epithelium.
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PMID:Topical tretinoin treatment for severe dry-eye disorders. 353 23

We have demonstrated the clinical efficacy of topical all-trans retinoic acid ointment in the treatment of four severe cases of the following dry eye disorders: Keratoconjunctivitis sicca, Stevens-Johnson syndrome, drug-induced pseudopemphigoid, surgery-induced dry eye. In all four cases, impression cytology confirmed that improvements in symptoms, visual acuity, keratopathy, and Schirmer test resulted from reversal of the process of squamous metaplasia. This treatment represents the first nonsurgical approach with action directed specifically at the diseased ocular surface epithelia.
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PMID:Topical retinoid treatment for dry eye disorders. 386 77

We evaluated the clinical efficacy of treating various dry-eye disorders using 0.01% and 0.1% (weight/weight) topical all-trans retinoic acid ointment. Twenty-two patients were selected and classified into four major groups: keratoconjunctivitis sicca (6 patients; 11 eyes), Stevens-Johnson syndrome (9 patients; 17 eyes), ocular pemphigoid or drug-induced pseudopemphigoid (3 patients; 6 eyes), and surgery or radiation-induced dry eye (4 patients; 4 eyes), based on the criterion that they remained symptomatic even under maximum tolerable conventional medical and/or surgical therapies. The results indicated that squamous metaplasia with mucin deficiency secondary to goblet cell loss and keratinization may be the basis for the development of clinical symptoms and morbidities, as these epithelial abnormalities were invariably present before treatment. After treatment, all patients demonstrated clinical improvements in symptoms, visual acuity, rose Bengal staining, or Schirmer test. Most importantly, this topical vitamin A treatment caused the reversal of squamous metaplasia as evidenced by impression cytology. Therefore, this treatment may represent the first nonsurgical attempt to treat these disorders by reversing diseased ocular surface epithelium.
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PMID:Topical retinoid treatment for various dry-eye disorders. 388 May 12

Previous studies of topical retinoic acid for treatment of ocular surface disease met with limited success due to instability and irritancy of the retinoid and lack of efficacy in keratoconjunctivitis sicca. There has, however, been continued interest in the treatment of mucin deficiency and cicatrizing conjunctival diseases, such as ocular cicatricial pemphigoid (OCP), topically with retinoids. In this study the biological activity of stable, water-soluble, synthetic retinoid, N-(4-hydroxyphenyl) retinamide-O-glucuronide (4-HPROG) was investigated in vivo and in vitro using conjunctival and corneal epithelium and fibroblasts. Vitamin A-deficient rabbits with stage 3-4 corneal xerosis and squamous metaplasia confirmed by conjunctival impression cytology were treated with topical 0.1% 4-HPROG in an artificial tear vehicle for 3 weeks. Impression cytology was repeated at 2 and 3 weeks and at 3 weeks conjunctival biopsies were fixed for histology. Growth curves were generated using conjunctival fibroblasts of rabbits and humans (normals and patients with cicatrizing conjunctival disease including OCP and Stevens-Johnson syndrome) cultured in the 10(-8)-10(-6) M 4-HPROG. In vivo, corneal xerosis cleared in three days. A normal conjunctival epithelium was restored by 2 weeks and goblet cells were present by 3 wk, with no change in vehicle-treated controls. No ocular irritation occurred. In vitro, 10(-6) M 4-HPROG inhibits growth of rabbit conjunctival fibroblasts. The retinoid had no effect on proliferation of conjunctival fibroblasts from normal humans but the doubling time of cells from patients with OCP increased significantly, from 50.9 +/- 10.01 h (control) to 61.5 +/- 8.95 h (retinoid). Proliferation of conjunctival fibroblasts from a patient with Stevens-Johnson syndrome was also inhibited. N-(4-hydroxyphenyl) retinamide-O-glucuronide is biologically active and merits further study to determine its efficacy in controlling conjunctival fibrosis and treating ocular surface squamous metaplasia.
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PMID:Biological activity of N-(4-hydroxyphenyl) retinamide-O-glucuronide in corneal and conjunctival cells of rabbits and humans. 897 41