Dry eye
Isotretinoin, also known as 13-cis-retinoic acid, is a commonly used oral medication for severe acne. The primary mechanism of action is to decrease sebum production, which in turn decreases comedogenesis.
While isotretinoin is a very effective treatment option for patients with recalcitrant acne vulgaris, its clinical use can be associated with a variety of adverse events ranging in severity and implications. These range from common mucocutaneous effects to ocular complications.
The reduction in sebum production by the meibomian glands of the eye sets the stage for a range of ocular effects. These include milder manifestations such as ocular surface alterations, dry eye diseases, ocular irritation and visual field defects.
Additionally, more serious consequences including retinal toxicity, corneal opacities and optic neuritis have been reported; these could potentially lead to permanent ocular damage if unrecognised.
Despite isotretinoin’s widespread usage, there exists a gap in the literature on the incidence of ophthalmologic side effects attributed to isotretinoin use.
What was the aim of this study?
In our study, Ocular side effects of systemic isotretinoin – a systematic review and summary of case reports, we conducted a systematic review and meta-analysis to present ocular side effects and their corresponding incidences in patients using isotretinoin. This involved synthesizing data from 53 studies to establish a comprehensive foundation for the meta-analysis.
Additionally, we compiled 41 case reports and studies into a narrative piece to provide a qualitative exploration of isotretinoin use and less common ocular adverse events.
Our aim was not only to summarise the incidence of ocular adverse events of isotretinoin use, but to equip eye care professionals (ECPs) with actionable knowledge to proactively monitor and mitigate potential ocular adverse events. The results of our study may be used by ECPs to guide clinical decisions and monitoring for patients on isotretinoin both with and without ocular side effects.
Acne
What do the results of this study show?
Dry eye was the most commonly reported adverse effect with an overall reported incidence of 27% among 16 studies (19,906 total patients). Some studies measured this formally with the Schirmer test, tear breakup time (TBUT), or ocular surface disease index (OSDI) scores.
Other complaints of ocular discomfort that may serve as surrogates for dry eye included photophobia (9% incidence rate), contact lens intolerance (7%) and hyperemia of the eyes (11%). A less common side effect, with a reported incidence of 10%, was inflammation of the eyelid.
These conditions included blepharitis, meibomitis, chalazion, hordeolum, and scaling and collarettes of the eyelids. Another less common adverse effect was conjunctival inflammation (overall incidence of 4%) including conjunctivitis and conjunctival papillary hypertrophy.
Finally, with an overall incidence of 3%, were visual acuity changes, including alterations in visual acuity, refractive vision changes, nyctalopia and abnormal colour vision. There was no report of corneal alteration or change in intraocular pressure.
What are the limitations of the work?
There was high variability in the reported incidence of various ocular side effects between studies, which made it challenging to determine the exact incidence of some of the reported adverse effects. This variability suggests potential reporting bias.
Other factors that may have contributed to the high variability include differing study designs, populations and data reporting methods. Altogether, the reported incidence rates may be higher than the actual prevalence of these ocular side effects.
What further work still needs to be undertaken in this field?
Further work is still needed to better understand the implications of isotretinoin ocular adverse events. One important question that remains is if ocular side effects persist after isotretinoin is stopped. This has important implications for understanding optimal timing in monitoring adverse events, initiating timely treatments, and in considering discontinuation of isotretinoin.
Additionally, the heterogeneity in our research results suggests a need for more robust and standardised methodologies in subsequent studies. This would increase the reliability and comparability of findings, ultimately allowing for better estimates of the true incidences of ocular adverse events due to isotretinoin.
Why might this work be important to ECPs?
For ECPs, our study offers insights for managing patients undergoing isotretinoin treatment. For isotretinoin-induced dry eye, the most common adverse event, we recommend proactive measures such as lubricating eye drops, reducing contact lens use and suggesting screen time reduction.
Our findings also emphasise the importance of screening for potential ocular side effects in isotretinoin-treated patients. Notably, awareness of rare yet serious complications such as retinal toxicity is needed. In case reports for rare but serious ocular adverse events, the presenting symptoms were not always severe.
Some patients presented with persistent moderate to severe dry eye; if persistent and not responsive to treatment, dry eye symptoms may warrant an ophthalmologic referral. Additionally, ophthalmologic screening examinations may be more important to consider for patients with pre-existing ocular conditions.
Lastly, our work emphasises the importance of collaborative communication between dermatologists and ECPs. By increasing awareness of the ocular side effects of isotretinoin, we hope to increase communication between dermatologists and ECPs to provide comprehensive management for patients undergoing isotretinoin treatment.
Conclusion
Ocular side effects of systemic isotretinoin can have serious consequences if not recognised and appropriately treated. Dry eye is the most common side effect and can lead to more serious complications such as ocular inflammatory conditions and ocular infection. It is recommended that prescribers of isotretinoin monitor for dry eye.
Patients with dry eye may benefit from lubricating eye drops and ophthalmologic examination to determine the severity of ocular disease. Lastly, our work emphasises the importance of awareness about isotretinoin’s ocular side effects and effective communication between dermatologists and ECPs for comprehensive patient management during isotretinoin treatment.
Olivia Lamberg is a fourth year medical student at University of Michigan Medical School, currently applying into dermatology residency. She has a strong interest in public health and clinical research as evidenced by the following research project which aims to bridge the fields of dermatology and ophthalmology care.
- Dr Yolanda Helfrich is a clinical professor of dermatology and the residency program director of the Department of Dermatology at the University of Michigan Medical School. With a strong interest in clinical research, Dr Yolanda Helfrich brings more than 12 years of experience as the director of the Program for Clinical Research in Dermatology (PCRiD). She has served as the principal investigator for more than 25 clinical trials, advancing our understanding of conditions such as rosacea, atopic dermatitis, psoriasis, lichen planus and other dermatologic concerns.
- Full findings were published in: Lamberg O, Strome A, Jones F, Mleczek J, Jarocki A, Troost JP, Helfrich Y. Ocular side effects of systemic isotretinoin–a systematic review and summary of case reports. Journal of Dermatological Treatment. 2023. https://www.tandfonline.com/doi/full/10.1080/09546634.2023.2213364