Accutane (Isotretinoin) and MGD

[Rebecca Petris]

Isotretinoin is well know to cause MGD (which is a common dry eye factor). In fact, it's used in lab and animal testing to model how MGD works.

TFOS DEWS II Pathophysiology Report

(from 7.3) A second model is induced by treatment with isotretinoin [642], a known and significant risk factor for the development of human MGD [643–652]. Treatment of rats for 3 months with isotretinoin led to keratinization and thickening of the meibomian gland ductal epithelium, a decrease in the quantity and size of acini, and many degenerated acini and acinar cell casts in the meibomian gland ducts. These isotretinoin-elicited effects could be inhibited by treatment with dehydroepiadrosterone, presumably, according to the investigators, through conversion to androgens [642]. Topical androgens, in turn, have been reported to be effective in the therapy of human MGD [653] (see TFOS DEWS II Sex, Gender, and Hormones report [1222]).

(from 7.5) A fourth DED model uses immortalized human meibomian gland epithelial cells [50]. This model involves exposure of these cells in vitro to isotretinoin [45], a well-known risk factor for the development of human MGD in vivo [643–652]. Exposure of human meibomian gland epithelial cells to isotretinoin: [a] alters the expression of thousands of genes, including an upregulation of genes for some inflammatory mediators (e.g. IL-8 and IL-1β), proteases (e.g. MMP-9), MAPK signaling, lytic vesicles, apoptosis and cell death, and suppresses genes linked to DNA replication, cell cycle, RNA transport and mitochondria; [b] increases the levels of pro-IL-1β, IL-1β and MMP-9 proteins; [c] decreases the signaling of the cell growth and survival mediator, phosphoinositide 3-kinase-protein kinase B; and [d] inhibits cell proliferation and induces cellular atrophy and death (e.g. by apoptosis, necrosis and/or autophagy) [45]. It is possible that these effects may be responsible for the acinar epithelial cell degeneration and atrophy, and reduced and abnormal secretions, that occur following isotretinoin induction of human MGD in vivo [643–652].

References in the pathophysiology report to isotretinoin

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[644] Fraunfelder FT, LaBraico JM, Meyer SM. Adverse ocular reactions possibly associated with isotretinoin. Am J Ophthalmol 1985;100:534–537.
[645] Fraunfelder FT, Fraunfelder FW, Edwards R. Ocular side effects possibly associated with isotretinoin usage. Am J Ophthalmol 2001;132:299–305.
[646] Caffery BE, Josephson JE. Ocular side effects of isotretinoin therapy. J Am Optom Assoc 1988;59:221–224.
[647] Denis P, Nordmann JP, Saiag P, Liotet S, Laroche L, Saraux H. Chronic blepharoconjunctivitis during a treatment with acitretin (Soriatane). J Fr Ophtalmol 1993;16:191–194.
[648] Mathers WD, Shields WJ, Sachdev MS, Petroll WM, Jester JV. Meibomian gland morphology and tear osmolarity: changes with Accutane therapy. Cornea 1991;10:286–290.
[649] Bozkurt B, Irke M, Atakan N, Orhan M, Geyik P. Lacrimal function and ocular complications in patients treated with systemic isotretinoin. Eur J Ophthalmol 2002;12:173–176.
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[651] Jaanus SD. Ocular side effects of selected systemic drugs. Optom Clin 1992;2:73–96.