Vitamin A is a vital, fat-soluble nutrient found in various foods including dairy products, meat, and certain types of fish (National Institutes of Health, 2021). It is absorbed in the intestinal lumen and converted into natural retinoid derivatives such as retinol, retinoic acid, and retinaldehyde (Samarawickrama et al, 2014).

Vitamin A acts positively on the immune and reproductive systems and, notably, on the visual system (NIH, 2021). It aids numerous visual functions including post-traumatic corneal healing, conjunctival goblet cell renewal (Samarawickrama et al, 2014), and rhodopsin production in the photoreceptors to maintain vision (NIH, 2021). A vitamin A deficiency may lead to serious systemic and ocular complications such as respiratory infections, gastrointestinal problems, xerophthalmia, nyctalopia, and corneal ulceration (Wu, 2015).

Several retinol derivatives are used in medicine and in cosmetic applications in topical or systemic formulations. This article discusses the effects of vitamin A and its derivatives on the ocular surface, particularly with respect to the tear film and the meibomian glands.

Impact of Systemic Vitamin A on the Ocular Surface

Isotretinoin (13-cis retinoic acid [RA]) is an oral medication used to treat advanced forms of acne by acting on sebaceous glands of the skin, with the goal of decreasing inflammation and sebum production (Tanriverdi et al, 2021). In vitro studies have shown that 13-cis RA provokes cellular changes and significantly alters gene expression in the meibomian glands (P < 0.05), causing increased cellular destruction and necrosis (Ding et al, 2013). This can lead to meibomian gland atrophy and to altered secretions, which are key factors in dry eye disease (Düzgün et al, 2020).

With a structure analogous to that of the sebaceous glands of the skin, the meibomian glands can be similarly affected by oral 13-cis RA (Knop et al, 2011), resulting in a decrease in density as well as in size of the meibomian glands (Düzgün et al, 2020). This leads to lower lipid production and to increased tear film evaporation.

The meibomian glands seem to be affected uniformly when using 13-cis RA (Mathers et al, 1991). This finding can be used to differentiate its effects from other causes of meibomian gland dysfunction, which result in nonsymmetrical atrophy of the glands (Mathers et al, 1991). While the function of the lacrimal gland remains intact, systemic absorption of oral 13-cis RA may be found in the tears through its secretions (Tanriverdi et al, 2021; Mathers et al, 1991) and may affect the ocular surface. Furthermore, increased osmolarity of the tears, blepharitis, and contact lens intolerance have been reported in conjunction with oral use of 13-cis RA (Tanriverdi et al, 2021).

Impact of Topical Vitamin A on the Ocular Surface

Although the ocular side effects of systemic vitamin A derivatives are well established in the literature, there is a paucity of information on its topical use.

Because of its anti-aging effect (Kafi et al, 2007), 13-cis RA is a common ingredient in cosmetics (Ding et al, 2013). While topical creams are known to exhibit minimal absorption through the skin, a month-long facial application of a retinoid/antibiotic cream resulted in a significant (P < 0.001) increase in symptoms (measured using the Ocular Surface Disease Index questionnaire) and tear osmolarity as well as a decrease in tear stability (Bayhan et al, 2016). Limitations of the study included its short duration (one month) and the lack of meibomian gland imaging and of assessment of ocular symptoms and signs post-treatment. Longer studies are warranted to ascertain whether these effects persist.

Most artificial tears do not contain vitamin A or its derivatives, but some that do may be available in international markets. Some commercially available lubricating ointments do contain vitamin A or its derivatives (i.e., retinol palmitate), and ointments have a longer residence time on the ocular surface and are in contact with the palpebral conjunctiva where the meibomian glands reside. Typically, ointments are prescribed for overnight use, and their prolonged contact time with the conjunctiva may increase the side effects on the tear film and the meibomian glands. This may increase the risks of atrophy and loss of function similar to the findings of in vitro studies (Ding et al, 2013).

Future in vivo studies are needed to investigate the effects of topical use of vitamin A and its derivatives on the meibomian glands.

Clinical Pearls

The literature suggests that topical and systemic use of vitamin A or its derivatives may produce similar adverse effects on the tear film and the meibomian glands and, therefore, should be used with caution in and around the eyelids. With the increasing trends in cosmetic use of retinoids, as well as existing ophthalmic ointments with similar ingredients, eyecare practitioners need to be aware of the potential effects on the tear film and the meibomian glands, particularly for experienced as well as novice contact lens wearers.

Understanding the composition of ocular lubricants and asking patients about cosmetic use will be increasingly important in unraveling potential causes of dry eye disease and contact lens discomfort. Advising patients to avoid the eyelid area should be a first step in establishing application guidelines for cosmetics containing vitamin A. CLS

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