Isotretinoin (13-CIS-RETINOIC ACID) is a synthetic counterpart of Vitamin A, approved by the

United States and prescribed to patients when diagnosed with treatment-resistant nodular and

cystic acne vulgaris (1). It functions by altering DNA transcription, affecting different stages of

the cycle such as differentiation and apoptosis, resulting in decreased size and production of

sebaceous glands and becoming an effective inhibitor of sebum secretion. (2, 3) This medication

is beneficial in treating and preventing the recurrence of resistant nodular and cystic acne, with a

success rate of approximately 90% (3). However, there is a widespread recognition that many

medicines have effects, some favorable and some of which are critical. According to a recent

review, 3.4% of patients taking Isotretinoin experienced ophthalmologic side effects. (4)

One of its reported side effects is myopia, an eye disorder that enables visual images to focus in

front of the retina, affecting the vision of distant objects. Early research did not clearly describe

the association of myopia in patients treated with Isoretinoin. However, a study highlighted that

13-cis-retinoic acid, an active constituents in Isotretinoin, activates metalloproteinase 9 resulting

in the degeneration of the cornea, making it a primary factor contributing to the development of

myopia. (3) According to a clinical trial on male acne patients given retinoids, such as

Isoretinoin, the development of the sclera and the differentiation of fibroblast into myofibroblast

are both impacted by a decrease in Transforming growth factor-beta (TGF-B), which occurs as

myopia develops. Myopia is brought on by an increase in collagen and a decrease in the

production of scleral collagen as a result of low TGF-B levels. (5)

Interestingly, the Food and Drug Administration (FDA) and the World Health Organization

(WHO) received 1741 out of approximately 2300 events with Ocular Adverse Events sporadic

reports of possible ocular adverse events associated with Isotretinoin. Out of approximately 2300

events with Ocular Adverse Events, 3.57% reported refractive change(1). Notably, short-

sightedness is the most common type of refractive error. (1) Furthermore, in a 2020 pilot study,

patients with acne vulgaris were treated with Isotretinoin, while the rest were healthy controls.

The results concluded that Isotretinoin consumption for six months resulted in increased myopia

and axial length (2) Moreover, a female patient in her late 20s underwent laser-assisted in situ

keratomileusis (LASIK) to correct her myopia but only experienced a recurrence of

nearsightedness and blurred vision after being prescribed oral Isotretinoin therapy daily to treat

her chronic inflammatory acne vulgaris. (3). Similarly, while on oral Isotretinoin therapy for

acne , a 28-year-old woman also presented with a rare case of elevated intraocular pressure (IOP)

with transient bilateral angle closure and the myopic shift. However, IOP returned to normal two

weeks after ceasing oral Isotretinoin. (4) Lastly, a patient in his early 20’s was presented with

nodulocystic acne with a history of 10 years of stable myopia. He was prescribed 0.3 mg/kg oral

Isotretinoin for his acne. After two weeks, the patient began to notice blurred vision, which

worsened over time, and his myopia increased in both eyes (6).

Surprisingly, despite complications of myopia, the technical brochure of Isotretinoin does not

mention the ocular side effect of this drug which makes it difficult for an early diagnosis (3). Due

to this, the ophthalmologists and the dermatologists are unaware of this side effect and fail to

take a comprehensive history of previous eye complaints before prescribing this drug.

Considering this, it is important to prevent patients from developing extreme myopia. To cater to

this problem, public policies and therapies must be developed. For instance, dermatologists
should only prescribe oral therapy of Isotretinoin when required and confirm any past surgical

history of LASIK treatment. Additionally, a follow-up should be practiced throughout

Isotretinoin oral therapy. If a patient experiences ocular issues following oral Isotretinoin

treatment, a consultation should be considered necessary as it would help with an early diagnosis

and treatment of Isotretinoin ocular adverse effects.

References

1. Fraunfelder FT, Fraunfelder FW, Edwards R. Ocular side effects possibly associated with

isotretinoin usage. Am J Ophthalmol. 2001;132(3):299-305.

2. Yasar E, Gurlevik U, Kemeriz F, Atalay E. Effect of isotretinoin on myopia and axial

length: a pilot study. Cutan Ocul Toxicol. 2020;39(4):385-8.

3. Qureshi K, Tariq J, Chaudhry MS, Pasha F. Oral Isotretinoin Resulting in Recurrence of

LASIK-Treated Myopia: A Rare Side Effect. Cureus. 2021;13(8):e16884.

4. Park YM, Lee TE. Isotretinoin-induced Angle Closure and Myopic Shift. J Glaucoma.

2017;26(11):e252-e4.

5. Zhu X, Xu B, Dai L, Wang Z, Feng L, Zhao J. Association between TGF-β gene

polymorphism and myopia: A systematic review and meta-analysis. Medicine (Baltimore).

2022;101(30):e29961.

6. Saraswat A. Sudden irreversible worsening of myopia with isotretinoin treatment. Indian

J Dermatol Venereol Leprol. 2011;77(5):611-2.

7. Pan CW, Ramamurthy D, Saw SM. Worldwide prevalence and risk factors for myopia.

Ophthalmic Physiol Opt. 2012 Jan;32(1):3-16. doi: 10.1111/j.1475-1313.2011.00884.x. PMID:

22150586.