tretinoin and Xerophthalmia

Thirty patients with treatment-resistant cystic and conglobulate acne entered a randomized double-blind protocol, testing the efficacy of isotretinoin versus tetracycline. After 16 weeks of isotretinoin treatment, the mean number of cysts decreased by 64% and the mean sum of the longest diameters was reduced by 68%. After 16 weeks of tetracycline therapy, the total number of cysts showed a mean decrease of 52%, and the mean sum of the longest diameters decreased by 60%. The reduction in the number of cysts and the sum of their longest diameters that occurred after 16 weeks of treatment was statistically significant for each of the treatment groups, but there was no statistically significant difference between the treatment groups at the end of therapy. Eight weeks after the discontinuation of treatment in the isotretinoin group, there was an overall reduction from baseline of 82% in the cyst count and 88% in the sum of the longest diameters. In the tetracycline treatment group, the overall reduction from baseline in the cyst count was 54% and in the sum of the longest diameters, 60%. This led to a statistically significant difference in the two treatment groups at 24 weeks. All patients on isotretinoin experienced side effects that were primarily related to the integumentary system but necessitated discontinuation of the drug for a short period of time in only one patient. Long-term follow-up, 8 months after discontinuation of the study, showed a prolonged significant remission of acne in the isotretinoin group but not in the tetracycline group.

Topics: Acne Vulgaris; Adolescent; Adult; Cataract; Cheilitis; Clinical Trials as Topic; Double-Blind Method; Epistaxis; Female; Follow-Up Studies; Humans; Isomerism; Isotretinoin; Male; Random Allocation; Tetracycline; Tretinoin; Xerophthalmia; Xerostomia

We report the ocular and systemic manifestations of vitamin A deficiency in a child with a complicated medical history including autism and a restricted diet, living in a developed country. This child had significant vitamin A deficiency despite being under long-term medical care, yet the diagnosis was not considered until he had an ophthalmology review for visual deterioration.

Topics: Autistic Disorder; Child; Child Nutritional Physiological Phenomena; Diet; Feeding and Eating Disorders of Childhood; Feeding Behavior; Humans; Keratolytic Agents; Male; Malnutrition; Treatment Outcome; Tretinoin; Vision Disorders; Vitamin A; Vitamin A Deficiency; Xerophthalmia

Topical tretinoin has been used for a number of years to treat patients with acne vulgaris. This paper reviews some of the newer uses of tretinoin, including treatment of patients with photoaging of the skin, premalignant lesions, dry-eye disorders, and its use after dermabrasion.

Topics: Acne Vulgaris; Administration, Topical; Dermabrasion; Humans; Photosensitivity Disorders; Precancerous Conditions; Skin Neoplasms; Tretinoin; Wound Healing; Xerophthalmia

Several reports have appeared on the efficacy of topically applied 0.01% or 0.1% all-trans retinoic acid (0.04-0.4 millimolar) for treatment of xerophthalmia, conjunctival squamous metaplasia, and corneal epithelial erosions in humans and animals. An observation common to many of these studies is the occurrence of an adverse reaction to retinoic acid in the form of lid margin hyperemia and blepharoconjunctivitis. Since retinoic acid is biologically active at micromolar to nanomolar concentrations, it may be possible to reduce side effects while maintaining therapeutic effectiveness by reducing the retinoic acid concentration in ophthalmic formulations. In the present study, topical 0.005% retinoic acid in petrolatum ointment reversed corneal keratinization in xerophthalmic, vitamin A-deficient rabbits in 3-4 days while 0.0005% (2 micromolar) retinoic acid ointment was effective in 4-6 days. Further clinical trials of topical retinoic acid for treatment of ocular surface disease should be conducted using micromolar concentrations of retinoic acid which are expected to maintain a therapeutic effect while reducing adverse reactions.

Topics: Administration, Topical; Animals; Corneal Diseases; Osmolar Concentration; Rabbits; Time Factors; Tretinoin; Wound Healing; Xerophthalmia

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.

Topics: Administration, Topical; Adult; Aged; Conjunctiva; Cornea; Female; Humans; Keratoconjunctivitis; Male; Metaplasia; Pemphigoid, Bullous; Stevens-Johnson Syndrome; Tretinoin; Xerophthalmia

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.

Topics: Administration, Topical; Adolescent; Adult; Aged; Child; Child, Preschool; Eye; Female; Humans; Keratoconjunctivitis; Lacrimal Apparatus Diseases; Male; Metaplasia; Middle Aged; Ointments; Pemphigoid, Benign Mucous Membrane; Postoperative Complications; Radiotherapy; Stevens-Johnson Syndrome; Tretinoin; Visual Acuity; Xerophthalmia

Corneas of normal and vitamin A-deficient rabbits were treated topically with [11, 12-3H] retinol or [11, 12-3H] all-trans retinoic acid. Methanol extracts of these corneas were analyzed by high pressure liquid chromatography. Radiolabeled compounds were extracted from the corneas which co-migrated chromatographically with known retinoid standards. In agreement with studies on other tissues and organs, retinol was metabolized to retinoic acid and more polar compounds by corneas of normal and vitamin A-deficient rabbits. All-trans retinoic acid was isomerized to 13-cis retinoic acid in normal rabbit corneas; however, this trans-cis isomerization did not occur in vitamin A-deficient, xerophthalmic corneas.

Topics: Animals; Chromatography, High Pressure Liquid; Cornea; Isomerism; Rabbits; Tretinoin; Vitamin A; Vitamin A Deficiency; Xerophthalmia

In previous studies of topical application of retinoic acid to the eye, retinoic acid in an oil vehicle has been used. An all-trans-retinoic acid (Tretinoin, USP) formulation in a petrolatum-based ophthalmic ointment vehicle has now been developed which is chemically stable for at least one year. The ointment is effective at retinoic acid concentrations of 0.01-0.1% in reversing corneal keratinization in vitamin A-deficient, xerophthalmic rabbits. At 0.1% it also stimulates the healing rate of corneal epithelial wounds in rabbits and monkeys. Retinoic acid ointment may prove to be valuable clinically in the treatment of xerophthalmia, corneal epithelial erosions, and related ocular surface abnormalities.

Topics: Animals; Corneal Injuries; Drug Stability; Epithelium; Macaca fascicularis; Ointments; Rabbits; Tretinoin; Wound Healing; Wounds, Penetrating; Xerophthalmia

Topical retinol, tretinoin (all-trans-retinoic acid) and etretinate (a synthetic retinoid) were used in rabbits to treat experimental xerophthalmia due to vitamin A deficiency. Both 0.2% retinol and 0.1% and 0.2% tretinoin effectively reversed abnormal corneal epithelial keratinization within one to two days and restored corneal clarity within two to four days following topical application three times per day. Etretinate was ineffective in the concentration used (0.2%). In addition, application of tretinoin to one eye effectively reversed xerophthalmic changes in the other eye. Retinol did not have an effect on the other eye.

Topics: Administration, Topical; Animals; Drug Evaluation, Preclinical; Etretinate; Rabbits; Retinoids; Tretinoin; Vitamin A; Xerophthalmia

Topics: Animals; Avitaminosis; Female; Humans; Neoplasms; Neoplasms, Experimental; Nutritional Physiological Phenomena; Papilloma; Safety; Skin Neoplasms; Tretinoin; Vitamin A; Vitamins; World Health Organization; Xerophthalmia

Retinoic acid 0.1% in arachis oil was applied to one eye and arachis oil alone to the other eye, of each of 19 patients with equivalent degrees of corneal xerophthalmia in the fellow eyes. Even with concomitant systemic vitamin A therapy, topical retinoic acid was associated with more rapid healing of corneal lesions in a substantial proportion of cases. Application of retinoic acid three times a day produced no significant side effects; application five times a day, however, resulted in moderate to severe conjunctival injection and increased corneal vascularization and scarring.

Topics: Administration, Topical; Corneal Diseases; Humans; Tretinoin; Vitamin A; Xerophthalmia

In vitro perfusion of corneas of normal and vitamin A-deficient rabbits provided a model in which to study the pharmacokinetics of corneal permeability and uptake of retinoic acid and retinol. The permeability coefficients of retinoic acid and retinol were 1.49 x 10(-5) and 0.61 x 10(-5) cm/s, respectively. Removal of the corneal epithelium did not affect the permeability of these lipid-soluble retinoids; however, diffusion through xerophthalmic, vitamin A-deficient corneas was significantly reduced. The corneal uptake of retinoic acid and retinol was reduced by 50% on removal of the epithelium, was nonspecific, and was not affected by xerophthalmia. High-performance liquid chromatography indicated that these retinoids were not metabolized during diffusion through the cornea. These results show that topical application of retinoids is a rational approach to the treatment of such corneal diseases as xerophthalmia and epithelial defects.

Topics: Animals; Cornea; Epithelium; In Vitro Techniques; Permeability; Rabbits; Tretinoin; Vitamin A; Vitamin A Deficiency; Xerophthalmia

The purpose of this study was to evaluate the efficacy of topical retinoic acid (tretinoin) in the treatment of various stages of xerophthalmia caused by vitamin A deficiency. At the beginning of treatment, rabbits with similar disease in both eyes were given a normal diet and therapeutic doses (25,000 IU) of systemic vitamin A. One eye of each was treated with 0.1% retinoic acid in sesame oil one time per day. The other eye received sesame oil alone. Eyes with moderate disease (advanced keratinization and plaque formation) responded more quickly to topical retinoic acid (clear within three days) than did eyes treated with sesame oil (clear within seven days). No difference in time of response could be observed in corneas with milder or more severe disease (stromal infiltration and corneal vascularization).

Topics: Administration, Oral; Administration, Topical; Animals; Cornea; Microscopy, Electron; Rabbits; Tretinoin; Vitamin A; Xerophthalmia

The biosynthesis of corneal epithelial proteins and glycoconjugates and their response to vitamin A were measured in vitamin A-deficient and normal rats. The synthesis of specific high-molecular-weight epithelial glycoconjugates was directly related to the levels of vitamin A administered. Protein synthesis, however, remained unaltered. Since vitamin A is known to reverse the keratinization process, the vitamin A-regulated high-molecular-weight glycoconjugates may play a role in modulating the expression of the keratinizing phenotype.

Topics: Animals; Autoradiography; Cornea; Electrophoresis, Polyacrylamide Gel; Epithelium; Glycoproteins; Molecular Weight; Rats; Scintillation Counting; Tretinoin; Vitamin A Deficiency; Xerophthalmia

Eight children with corneal xerophthalmia (x2 or x3A) received standard high-protein diets and massive systemic vitamin A therapy. Retinoic acid, 0.1% in oil, was applied daily to one eye, and oil alone to the other. Topical retinoic acid proved safe and effective in speeding corneal healing, especially during the first critical days.

Topics: Administration, Topical; Animals; Child; Child, Preschool; Dietary Proteins; Female; Humans; Male; Rats; Tretinoin; Vitamin A; Vitamin A Deficiency; Xerophthalmia

Topics: Animals; Cornea; Edema; Organ Size; Rats; Tretinoin; Vitamin A; Xerophthalmia

Topics: Animals; Body Weight; Liver; Male; Organ Size; Rats; Testis; Tretinoin; Vitamin A; Vitamin A Deficiency; Xerophthalmia