| | March 15, 1999 Despite the long-held belief that supplemental vitamin A can have a positive impact on severe cases of dry eye syndrome or instances of a keratinized ocular surface, interest in vitamin A and its various compounds such as retinol, retinaldehyde and retinoic acid, appears to be almost entirely confined to the research lab. ![[bar]](OSN%20Retinoid%20may_files/gradient.gif)
History of prior research
Review of the literature and interviews with ophthalmologists and microbiologists indicate that a retinoid product was made available a decade ago for topical application in cases of severe dry eye and corneal keratinization. When further study of the product indicated that its outcomes could not be duplicated, the product’s manufacturer’s stock plunged, the National Institute of Health reportedly suspended research funding, and the product essentially disappeared.
Inconsistent outcomes
 ---This patient suffered from irritation with a keratinized plaque in his left eye before treatment.
Photograph courtesy of Scheffer G. Tseng, MD, PhD.
Ophthalmologist Scheffer G. Tseng, MD, PhD, now of the Bascom Palmer Eye Institute in Miami, was a member of the Boston-based group that published the now infamous retinoid studies. He still prescribes a once-a-day 0.01% topical application of a retinoic acid ointment to patients who have keratinized corneal surface or lid margins. “I think that topical vitamin A is useful for the eye that has become keratinized, particularly in the very focal area, lid margin or on the surface of the eye,” Dr. Tseng told Ocular Surgery News. “However, dry eye is a very broad term, and in the general sense, dry eye patients do not have the type of pathological keratinization [that benefits from the retinoic acid compound]. What we showed in our early studies was improvements in very extreme cases, but when others looked at it in a controlled manner — particularly in milder cases — they did not come up with any therapeutic effect. So I don’t think it is right to say retinoic acid is useful for dry eye patients, because then people tend to think that it is useful in milder cases.” Dr. Tseng is hoping to do a large-scale study of retinoic acid’s relationship to corneal function in the near future. He said that he was approached at the annual American Academy of Ophthalmology meeting by a representative of a pharmaceutical company interested in working with him on clinical trials. “I have been using this compound for more than 12 years at Bascom Palmer,” Dr. Tseng said. “My own personal observation continues to support its use in some patients with severe dry eye problems.”
Meanwhile, back at the lab
 ---After 3 months of 0.01% retinoic acid ointment treatment once a day, the lesion disappeared.
Photograph courtesy of Scheffer G. Tseng, MD, PhD.
Meanwhile, animal and human studies continue to firm up the symbiotic relationship between vitamin A and a healthy corneal surface. Biochemist Sally Twining, PhD, of the Medical College of Wisconsin, suspects that the reason Dr. Tseng’s retinoic acid compound was unsuccessful in the milder dry eye cases was because he was using a form that was not water soluble, so it was at toxic levels when it was delivered to the corneal surface. “If it could be delivered in a non-toxic form such as a glucuronide, such as that used in research presented by John Ubels, PhD,” she said, “then it probably would work.” Some of the work by physiologist Dr. Ubels of Calvin College in Grand Rapids, Mich., has shown that the lacrimal gland makes a protein called retinol binding protein that binds retinol and secretes it out into the tear film, and that that is the most probable source of retinol to the epithelial surface. Dr. Twining has been studying vitamin A deficiency and proteinase in the cornea for two decades. Her studies have been published in the Journal of Nutrition, Current Eye Research and Investigative Ophthalmology, among other sources. “The work of others has shown that many dry eye syndromes are caused by a malfunction of the lacrimal gland, which makes many of the proteins in tears. If a person is not getting the retinol-binding protein from the lacrimal gland, then that person will not have adequate delivery of retinol to the ocular surface. Retinol must be bound to a protein because if it’s free, it can be toxic,” she explained. “Vitamin A is extremely important. You have to have vitamin A in order for the goblet cells of the conjunctiva to live and to produce mucus.”
Vitamin A in the cornea
In one of her studies looking at the effects of vitamin A on levels of proteinase in the cornea, what was found was that if a vitamin A-deficient animal was purposefully infected with a Pseudomonas aeruginosa, the area of infection was not as great as in cases where a normal animal was infected with the same amount of Pseudomonas aeruginosa. “We followed that up and found that one of the reasons was that the number of neutrophils that came into the cornea was different,” Dr. Twining said. “In looking at the difference in neutrophil function between a vitamin A-deficient animal and a normal animal, we found that there was a decrease in phagocytosis and killing of the organisms and that the neutrophils looked different as a result of the deficiency.” Can supplemental application of vitamin A guard against alteration of the cornea that comes about with the normal aging process? “Possibly,” Dr. Twining said, “but it hasn’t been proven yet.”
Diet and tear function
Regarding the influence of diet on tear function, B.E. Caffery, PhD, reported in Optometric Vision Science that the effect of diet on tear function is illustrated clearly by malnutrition-induced xerophthalmia. “Dietary habits in the well nourished North American society have been implicated as a cause of some tear dysfunction. A review of the ocular literature suggests that sufficient dietary protein, vitamins A, B6 and C, potassium and zinc may be necessary for normal tear function. Excesses of fat, salt, cholesterol, alcohol, protein and sucrose have been associated with or suggested as causes of tear dysfunction. No unequivocal link has been established between diet and remission of dry eye states in a well nourished population,” Dr. Caffery reported. For Your Information: - Scheffer G. Tseng, MD, PhD, can be reached at the Bascom Palmer Eye Institute, P.O. Box 016880, Miami, FL 33101; (305) 326-6046; fax: (305) 326-6306; e-mail: stseng@mednet.med.miami.edu. Dr. Tseng has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.
- Sally Twining, PhD, can be reached at the Medical College of Wisconsin, Department of Biochemistry, 8701 Watertown Plank Road, Milwaukee, WI 53226; (414) 456-8431; fax: (414) 456-6510; e-mail: stwining@mcw.edu. Dr. Twining has no direct financial interest in any of the products mentioned in this article, nor is she a paid consultant for any companies mentioned.
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