BRIEF REPORT

Isotretinoin and night blindness

Ken Teo1 and Anousha Yazdabadi2

1Department of Medicine, and 2Department of Dermatology, St Vincent’s Hospital Melbourne, Melbourne,Victoria, Australia

ABSTRACT

Isotretinoin is an effective and increasingly populartreatment for acne vulgaris. There have been reportsof night blindness as a side-effect of treatmentalthough the evidence does not demonstrate a clearcausal relationship between isotretinoin therapy andthe risk of night blindness. Nevertheless, consideringthe lack of evidence in this area, it is important toeducate patients about this potential consequence,which may become longstanding and even irrevers-ible, and encourage them to promptly report changesin their night vision.

Key words: isotretinoin, synthetic retinoids, nightblindness, night vision, acne.

INTRODUCTION

Isotretinoin (13-cis-retinoic acid) is a retinoid syntheticvitamin A analogue that is an effective modality in the man-agement of acne vulgaris. It is used in the treatment ofsevere nodular acne, treatment failures, scarring or fre-quent relapses, or in cases of severe psychological distress.1

Since the 1980 there have been reports of night blindnessas a side-effect of treatment with isotretinoin.2–4 Persistentscotopic, electroretinographic changes and reduction ofdark adaptation have been described.5 Animal studies havedemonstrated persistent delays in rhodopsin regenerationand a slow recovery of rod sensitivity following light expo-sure after the administration of isotretinoin.6

The prescription of isotretinoin for acne vulgaris isincreasing. It is thus important to evaluate the literature onthis topic, especially for patients whose occupations rely onoptimal night vision.

METHODS

The current article comprises a review of Medline andPubMed databases as a means of including the full range ofarticles on isotretinoin and night blindness. The key words‘isotretinoin’, ‘retinoids’, ‘night blindness’, ‘night vision’,‘visual toxicity’, ‘dark adaptation’, ‘rod function’, ‘eye’, ‘acne’were used as search strings, and secondary referencesfound via bibliographical links were also retrieved. Non-English language articles were excluded from the review.All reports, including case reports, were included.

RESULTS

Seven articles were found – three prospective cohortstudies, one case series and three case reports. Their con-clusions are summarised in Table 1.

Incidence and risk factors

There is little information regarding the incidence of clini-cally significant night blindness following isotretinointherapy. However, from the information available, the inci-dence is estimated to be between 4 to 6%.2,7 Mollan andcolleagues7 performed a retrospective, observational, con-secutive case series of 47 military aviator applicants with aconfirmed history of oral isotretinoin use and found that twohad clinically significant abnormal vision, while 11 furtherparticipants had laboratory evidence of night blindness.

Weleber and colleagues2 conducted a prospective study ofmusculoskeletal changes associated with isotretinoin andreported a secondary finding of three patients spontane-ously developing decreased night vision especially whiledriving. Two of these three patients showed abnormalitiesin electroretinograms (ERG), while 1 of 3 patients had sub-normal electrooculograms (EOG). Dark adaptometryrevealed elevation of the cone and some instances rodthresholds in all patients tested.

Correspondence: Dr Ken Teo, 6/92 Wells Street, Southbank, Vic3006 Australia. Email: kenteogw@gmail.com

Ken Teo, MBBS (Hons). Anousha Yazdabadi, MBBS.Submitted 3 April 2013; accepted 14 August 2013.

Abbreviations:

CF cystic fibrosisDA dark adaptationEOG electrooculogramERG electroretinogramRPE retinal pigment epithelial

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Australasian Journal of Dermatology (2014) 55, 222–224 doi: 10.1111/ajd.12107

© 2013 The Australasian College of Dermatologists

Grattan and colleagues prospectively investigated altera-tions in retinal function, as assessed by ERG, in patientsbefore, during and after treatment with isotretinoin. Of thesix patients who completed the assessments, two showed adefinite deterioration in scotopic ERG (an ERG that is per-formed with low illumination stimuli) during treatmentcompared with baseline examinations and one patienthad borderline changes. None of these patients weresymptomatic.8

The only described risk factor for development of nightblindness with isotretinoin therapy is hypovitaminosis A.Welsh and colleagues9 reported on a 16-year old boy withcystic fibrosis (CF) who developed night blindness afterusing isotretinoin to treat cystic acne. They believed thatpatients with CF are at risk of suffering from this complica-tion due to a predisposition to asymptomatic vitamin Adeficiency.

Pathophysiology

At the start of the visual process, light is detected by photo-receptor cells (rods and cones) in the retina. Rods detectlight at low intensity but have poor image discrimination.They contain a photosensitive purple-red chromoproteincalled rhodopsin. Light bleaches rhodopsin to visual yellow(all trans-retinal) – producing stimulation for retinalsensory endings. This cis-to trans-isomerisation reaction isreversible to allow the regeneration of rhodopsin, a reactionthat is part of the classic visual cycle. 11-cis retinal, aretinoid, is the chromophore residing in rhodopsin and incone opsins that is responsible for vision.

11-cis-retinol dehydrogenase is a microsomal enzymethat is abundant in the retinal pigment epithelial (RPE) cellsand is essential for recycling 11-cis retinal. Isotretinoin hasbeen shown in rodents to slow the synthesis of 11-cis-retinaldehyde and the regeneration of rhodopsin by inhib-

iting 11-cisretinol dehydrogenase in the visual cycle.11,12

This is thought to be the mechanism by which isotretinoinmay interfere with dark adaptation (DA).

Clinical presentation

Common complaints include blurred vision, photophobia,excessive glare problems and decreased night vision,usually noted during driving or when lights are switched offsuddenly.

Diagnostic evaluation

Night blindness can be evaluated with ERG, EOG, darkadaptometry, visual fields, colour vision and fundoscopicexaminations.2 ERG is a test of retinal function that sumsthe flash-evoked action potential of photoreceptors andmiddle and inner retinal neurons into one action potentialmeasured at the cornea. A significant portion of retinalfunction must be disturbed before there is a significantdecrease in ERG. EOG measures the resting potential of theeye and is a sensitive measure of the functional integrity ofthe RPE. Dark adaptation is a process consisting of thebiochemical regeneration of bleached to unbleachedrhodopsin, with synchronously increasing sensitivity tolight during the course of approximately 30 minutes. Thisrecovery of sensitivity in darkness can be recorded by meas-uring the brightness of light necessary for achieving thethreshold of perception. The brightness of the flashing testlight at threshold can be recorded as a function of time inthe dark by dark adaptometry. A full ophthalmic examina-tion including visual fields, colour vision and fundoscopycan reveal signs of pre-existing ocular disease and wouldroutinely be performed prior to electrodiagnostic testing.

Table 1 Summary of literature on isotretinoin and night blindness

Author Year published Category Conclusion

Weleber et al.2 1985 Prospective cohort study Three of 50 patients developed decreased night vision.Improvement occurred with drug cessation in all patients.

Maclean et al.3 2006 Case report 19-year old pilot’s night vision was still poor 9 months afterisotretinoin withdrawal.

Brown & Grattan.5 1989 Prospective cohort study All 7 patients who fully completed the study had reductions inscotopic ERG compared to baseline. Symptoms were notcommented on.

Grattan et al.7 1987 Prospective cohort study Two of 6 patients had decreased in scotopic ERG compared tobaseline. None were symptomatic.

Welsh et al.8 1999 Case report CF patient with hypovitaminosis A developed night blindness withisotretinoin treatment. Oral vitamin A replacement resolved hisvisual symptoms in 6 months.

Mollan et al.9 2006 Case series Of 47 aviator applicants, 2 had clinically significant abnormalvision and 11 further participants had laboratory evidence ofnight blindness. Two patients had persistent ERG and DAabnormalities – 25 months and 8 years respectively aftercessation of isotretinoin therapy.

Halpagi et al.10 2008 Case report 21-year old’s night vision recovered clinically 4 months afterisotretinoin withdrawal.

CF, cyctic fibrosis; DA, dark adaptation; ERG, electroretinogram.

Isotretinoin and night blindness 223

© 2013 The Australasian College of Dermatologists

Treatment, prognosis and prevention

Cessation of isotretinoin is the cornerstone of management.Welsh and colleagues9 reported that vitamin A replacement(with the dose increased to 150 000 IU daily) led to animprovement in their patient’s night vision within a week.However, this was in the setting of the patient suffering fromhypovitaminosis A.

Fortunately, most patients’ night vision recovers clinicallyon stopping isotretinoin therapy. The time frame for this tooccur is not well documented. However, Halpagi and col-leagues12 reported that 4 months after cessation of therapy,their patient regained her night vision and ERG returned tonormal limits.

There were two reports of patients suffering poor nightvision despite ceasing isotretinoin. Maclean and colleagues3

reported that their patient subjectively felt his night visionwas still poor 9 months after isotretinoin withdrawal.In Mollan and colleagues’7 retrospective case series,two patients had persistent ERG and DA abnormalities25 months and 8 years, respectively, after cessation ofisotretinoin therapy. However, considering the lack of base-line ERG and DA information for these two patients it isdifficult to validate these findings.

For prevention, Danby13 advocated encouragingisotretinoin candidates to eat vitamin A-rich food andconsume supplements to avoid the development of nightblindness, although the efficacy of this has not been inves-tigated and the risk of hypervitaminosis A cannot beignored.

CONCLUSION

Although night blindness is an uncommon and usuallyreversible side-effect of isotretinoin treatment it is impor-tant to educate patients about this potential consequenceand encourage them to promptly report changes in theirnight vision. Measurement of serum vitamin A levels can behelpful in assessing patients with impaired night vision andsupplementary vitamin A may be beneficial in acceleratingrecovery.

This review highlights the significant paucity of informa-tion in this area to guide informed consent. The evidencedoes not demonstrate a clear causal relationship betweenisotretinoin therapy and the risk of night blindness.

REFERENCES

1. Haider A, Shaw JC. Treatment of acne vulgaris. JAMA 2004;292: 726–35.

2. Weleber RG, Denman ST, Hanifin FM et al. Abnormal retinalfunction associated with isotretinoin therapy for acne. Arch.Ophthalmol. 1986; 104: 831–7.

3. Maclean H, Wright M, Choi D et al. Abnormal night vision withisotretinoin therapy for acne. Clin. Exp. Dermatol. 1995; 20: 86.

4. Fraunfelder FT, LaBraico JM, Meyer SM. Adverse ocular reac-tions possibly associated with isotretinoin. Am. J. Ophthalmol.1985; 100: 534–7.

5. Brown RD, Grattan CEH. Visual toxicity of synthetic retinoids.Br. J. Ophthalmol. 1989; 73: 286–8.

6. Sieving PA, Chaudhry P, Kondo M et al. Inhibition of the visualcycle in vivo by 13-cis retinoic acid protects from light damageand provides a mechanism for night blindness in isotretinointherapy. Proc. Natl Acad. Sci. USA 2001; 98: 1835–40.

7. Mollan SP, Woodcock M, Siddiqi R et al. Does use ofisotretinoin rule out a career in flying? Br. J. Ophthalmol. 2006;90: 957–9.

8. Grattan CEH, Brown RD, Cowan MA et al. Retinoids and theeye – reduced rod function with isotretinoin. Br. J. Dermatol.1987; 117: 23.

9. Welsh BM, Smith AL, Elder JE et al. Night blindness precipi-tated by isotretinoin in the setting of hypovitaminosis A.Australas. J. Dermatol. 1999; 40: 208–10.

10. Marmor MF, Holder GE, Seeliger MW et al. Standard for clini-cal electroretinography 2004. Doc. Ophthalmol. 2004; 108: 107–14.

11. Law WC, Rando RR. The molecular basis of retinoic acidinduced night blindness. Biochem. Biophys. Res. Comm. 1989;161: 825–9.

12. Halpagi P, Grigg J, Klistorner A et al. Night blindness followinglow-dose isotretinoin. J. Eur. Acad. Dermatol. Venereol. 2008; 7:893–4.

13. Danby FW. Night blindness, vitamin A deficiency, andisotretinoin psychotoxicity. Dermatol. Online J. 2003; 9: 30.

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© 2013 The Australasian College of Dermatologists