Introduction

A meta-analysis of over 3000 patients found that around 25% of patients treated with Accutane experienced dry or irritated eyes. [1] But that’s not the only ocular issue acne patients face, it’s also well understood that a course with the acne drug could also rob you of your night vision. This effect can be profound, with one 16-year-old patient essentially “becoming blind” after the onset of dark. [2]

Furthermore, the loss of night vision is one of the consequences of Accutane treatment that can persist long after the treatment has been ceased. [3] Ophthalmic damage, and in particular night blindness, might not be an obvious consequence of treatment with a Vitamin A derivative such as vitamin A as a deficiency in the vitamin is also linked to these same side effects. What explains this apparent paradox?

Well in an effort to maintain a homeostasis in the body, the enzymes typically involved in the production of retinoids become suppressed. In particular, the enzyme 11-cis retinol dehydrogenase, which synthesise the vital 11-cis retinal. In fact, on this website I present the robust scientific evidence of epigenetic suppression of the enzymes with this family Aldehyde Dehydrogenases (read more here).

The form of vitamin A within Accutane is Isotretinoin, which undergoes isomerisation into All-trans-retinoic acid within cells. This bypasses all the other retinoid metabolites that serve a number of other important functions such as maintaining eye health.

A connection to androgens

Another important function of these Retinol Dehydrogenase enzymes is in the production of androgens from various hormone precursors. Androgens are the generic name for the typically male hormones such as testosterone but includes a vast array of other vital neurosteroids.

When Isotretinoin downregulates these Retinol Dehydrogenases, it not only disrupts retinoid signalling but also hormone cascades too. For example, the repression of retinol dehydrogenase-4 by Accutane inhibits the production of the very potent androgen dihydrotestosterone (DHT), which might contribute to its anti-acne effects.[4] Suppressing these potent androgens may be beneficial in treating acne, but it can have disastrous consequences for another androgen regulated organ, the eyes!

Meibomian Glands visible below eyelashes, Rapidreflex, CC BY-SA 4.0, via Wikimedia Commons

It might not seem obvious, but eyes are highly dependent on the same hormones that grow muscles and beards, due to the presence of the sebaceous gland in the eyelids called the meibomian gland. This gland secretes protective lipids over the surface of the eye and when its action is disrupted due to deprivation of androgens, it can result in dry burning eyes – a condition called Meibomian Gland Dysfunction.

Meibomian Gland Dysfunction is frequent symptom of anti-androgen medications such as Finasteride, as well as genetic conditions such as Androgen Insensitivity Syndrome. [5][6] Incredibly, the Meibomian Gland Dysfunction caused by Accutane treatment has even been successfully treated by the topical application of the androgen precursor dehydroepiandrosterone (DHEA). [7]

The researchers in this study found a significant reduction in the activity of the Androgen receptor, an aberration that was resolved with the concomitant use of DHEA by restoring the cascade of crucial androgens.  Whilst a topical form of DHEA like the one used in the study might not be available over the counter, this study gives a profound insight into the diverse intended side effects of Accutane treatment.

Article Summary

• Accutane and Eye Health: About 25% of patients treated with Accutane (Isotretinoin) experience dry or irritated eyes, and it can also lead to night blindness, which may persist even after stopping the treatment. There are some case reports of severe night vision loss, effectively becoming blind in low-light conditions due to Accutane.
• Vitamin A Paradox: Accutane, a Vitamin A derivative, paradoxically causes vision issues similar to those caused by Vitamin A deficiency. This is due to the suppression of enzymes, particularly 11-cis retinol dehydrogenase, which is crucial for eye health and night vision.
• Hormonal Disruption: Accutane downregulates enzymes like Retinol Dehydrogenase-4, disrupting both retinoid signaling and androgen production. This suppression, particularly of the potent androgen dihydrotestosterone (DHT), contributes to its acne treatment effects.
• Impact on Eyes: Androgens play a key role in eye health due to their role in the function of the meibomian glands in the eyelids, which secrete protective lipids. Accutane-induced androgen suppression can lead to Meibomian Gland Dysfunction, causing dry and burning eyes.
• Meibomian Gland Dysfunction: This condition, common in anti-androgen treatments, can result from Accutane treatment but has been treated successfully with topical application of the androgen precursor DHEA. Animal studies have demonstrated that DHEA restores androgen activity in the eyes, offering insights into Accutane’s side effects and potential treatments for related conditions.

Related Articles

Why Accutane Causes Dry Eyes and How To Treat It

Accutane & Autoimmunity: The Link To Sjogren’s Syndrome

References

Click Arrow to Show References

[1] Adverse Events in Isotretinoin Therapy: A Single-Arm Meta-Analysis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9180136/

[2] Isotretinoin-Induced Night Blindness https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533586/

[3] Abnormal night vision with isotretinoin therapy for acne https://academic.oup.com/ced/article-abstract/20/1/86/6629649?redirectedFrom=fulltext&login=false

[4] 13-cis-Retinoic acid competitively inhibits 3α-hydroxysteroid oxidation by retinol dehydrogenase RoDH-4: a mechanism for its anti-androgenic effects in sebaceous glands? https://www.sciencedirect.com/science/article/abs/pii/S0006291X03003322

[5] The effect of finasteride on dry eye disease https://iovs.arvojournals.org/article.aspx?articleid=2778997

[6] Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface? https://pubmed.ncbi.nlm.nih.gov/12883343/

[7] Role of topical dehydroepiandrosterone in ameliorating isotretinoin-induced Meibomian gland dysfunction in adult male albino rat https://www.sciencedirect.com/science/article/abs/pii/S0940960217300092