Acitretin-Associated Maculopathy

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Nasal Temporal therapy and development or exac- 380 µm erbation of CSCR. 160 µm Caroline R. Baumal, MD, FRCSC Adam Martidis, MD Steven N. Truong, MD 250 Boston, Mass µm The authors have no relevant finan- cial interest in this article. 47 dB Corresponding author: Caro- A line R. Baumal, MD. FRCSC, Depart- Log Reflection ment of Vitreoretinal Surgery, New Inferior Superior England Eye Center, 750 Washing- ton St, Box 450, Boston, MA 02111 (e-mail: [email protected]). 210 µm

1. Garg SP, Dada T, Talwar D, Biswas NR. Endog- enous cortisol profile in patients with central se- 250 rous chorioretinopathy. Br J Ophthalmol. 1997; µm 81:962-964. 2. Wakakura M, Ishikawa S. Central serous chorioretinopathy complicating systemic corticosteroid treatment. Br J Ophthalmol. 1984;68:329-331. 3. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioreti- 45 dB nopathy. Ophthalmology. 2002;109:1834-1837. B Log Reflection 4. Schalenbourg A, Leys A, De Courten C, Cout- teel C, Herbort CP. Corticosteroid-induced cen- Figure 2. A, Cross-sectional optical coherence tomography demonstrates a collection of fluid under the tral serous chorioretinopathy in patients with fovea, confirming the diagnosis of central serous chorioretinopathy after a subtenon injection of ocular inflammatory disorders. Klin Monatsbl Au- corticosteroid. B, Optical coherence tomography shows resolution of the fluid and return of the foveal genheilkd. 2002;219:264-267. depression.

the initial report detailing the on- interpreted as CME or may be over- set of CSCR following periocular shadowed by features of coexisting Acitretin-Associated corticosteroid injection with confir- CME. Visual symptoms from sec- Maculopathy mation by OCT imaging. Periocu- ondary CSCR may be attributed to lar corticosteroids may be adminis- the primary diagnosis of uveitis, and Isotretinoin and etretinate are syn- tered for the treatment of uveitis as thus the fundus examination that is thetic retinoids commonly used to well as postoperative CME. The required to detect this entity may be treat skin disorders. Ocular ad- presence of intraocular inflamma- omitted. Optical coherence tomo- verse effects have been reported af- tion secondary to uveitis may affect graphic imaging may be especially ter short- and long-term use of these the retinal pigment epithelial bar- helpful in this scenario to differenti- drugs,1-4 with keratoconjuctivitis rier and increase susceptibility to lo- ate between the features of CSCR and sicca1 being the most common one. cal periocular corticosteroid ef- CME. It is unlikely that the topical Nictalopia and decreased dark fects. A similar mechanism has been corticosteroid drops played a role in adaptation have been described in proposed in a small series that re- the development of CSCR because of patients treated with isotretinoin2 ported CSCR following systemic cor- the relatively brief time of adminis- and etretinate.3 Furthermore, ab- ticosteroid therapy for uveitis that tration and the lack of posterior- normalities in the electroretino- occurred secondary to bird-shot cho- segment penetration, especially in gram (ERG), including reduced sco- rioretinopathy, Vogt-Koyanagi- this patient with phakic eyes. In con- topic amplitudes1,3 and color vision,3 Harada disease, and scleritis.4 trast, periocular corticosteroids are in- have also been reported. A variety of contributing fac- jected directly behind the globe to in- The case of a 32-year-old man tors may account for the paucity of duce a posterior pole effect. who noted decreased visual acuity reports linking CSCR and the com- Because almost every other (VA) after long-term use of acitre- mon procedure of periocular corti- route of corticosteroid administra- tin (Neotigason), a metabolite of costeroid injection. In eyes with tion, including local intra-articular etretinate, is reported. Slitlamp bio- uveitis, clinical features such as syn- injection, has been linked with microscopy, fluorescein angiogra- echiae, pupil constriction, or media CSCR thus far, it appears logical that phy (FFA), and electrophysiology opacity severe enough to warrant the periocular depot corticosteroid findings are described. periocular corticosteroid administra- injection would be associated with tion may preclude visualization of development of this disorder.2,3 The Report of a Case. A 32-year-old distinct macular details. Subtle fluid periocular route should be in- white man was seen in the emer- from CSCR that is related to a peri- cluded in the suggested etiologic as- gency department on July 26, 2002, ocular corticosteroid injection may be sociation between corticosteroid reporting a 3-day history of blurred

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C D

Figure 1. Color fundus photographs (A and B) and fluorescein angiograms (C and D) obtained at the initial examination. Cystoid macular edema was observed on slitlamp biomicroscopy in both eyes and demonstrated in late frames of the fluorescein angiogram. In addition, diffuse hyperfluorescence at the level of the retinal pigment epithelium and involving most of the macula was also noted.

vision in both eyes. His medical his- use of acitretin, and thus, this treat- though attenuated compared with tory was remarkable for previous ment was then discontinued. baseline, were still observed on FFA. hepatitis B infection and severe pso- Therapy with slow-release oral ac- riasis for which he had been treated etazolamide (Diamox-SR), 250 mg Comment. The patient described with acitretin, 30 mg/d, for the past twice a day, was also started. herein had diffuse RPE changes at year. His ocular and family histo- Three days later, his symp- the macula and macular edema. To ries were unremarkable. toms of blurred vision had im- our knowledge, these retinal abnor- On ophthalmic examination, proved, although his VA remained malities have not been previously de- VA was measured at 6/9 OU. Ante- 6/9 OU. The cystoid macular edema scribed in patients using oral reti- rior segment and intraocular pres- had completely resolved (Figure 2). noids. The cystoid macular edema sures were normal. On fundus Only hyperfluorescence from RPE observed at the initial examination examination, retinal pigment epi- was present (Figure 2). Treatment resolved in only 3 days after discon- thelium (RPE) abnormalities at the with oral acetazolamide was discontinuation of acitretin therapy and ini- macula and cystoid macular edema tinued. tiation of oral acetazolamide treat- were present (Figure 1). Diffuse Electrophysiology, including ment. Because etretinate has a early and late hyperfluorescence at full-field ERG and pattern ERG prolonged half-life,5 it seems more the level of the RPE at the macula (PERG), was performed on Decem- likely that the resolution of the was observed on FFA (Figure 1). ber 12, 2002, and disclosed no ab- macular edema observed was the re- Late leakage of fluorescein in fo- normalities. At his last follow-up sult of the treatment with acetazol- veal cystic spaces was also noted visit, March 31, 2003, his VA was 6/6 amide rather than being related to (Figure 1). Retinal changes were sus- OU and no macular edema was pres- the discontinuation of the retinoid pected to be possibly related to the ent. The RPE abnormalities, al- therapy. It is also likely that the

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Figure 2. Fluorescein angiogram obtained 3 days after the initial examination. Although diffuse hyperfluorescence at the level of the retinal pigment epithelium was still observed, cystoid macular edema had completely resolved.

macular edema was the result of RPE only if the above anatomical and 8. Salzman J, Seiple W, Carr R, Yannuzzi L. Elec- trophysiological assessment of aphakic cystoid dysfunction, since the leakage ob- functional changes reappear follow- macular oedema. Br J Ophthalmol. 1986;70:819- served on FFA appeared to come ing reinitiation of the therapy. Be- 824. from RPE and responded well to oral cause it is not yet clear whether these acetazolamide therapy. Further- changes are totally reversible, treat- more, diffuse RPE changes were pres- ment with acitretin has not been ent on FFA and no abnormalities on reestablished. Self-induced, Bilateral the retinal vessels were seen. Retinal Detachment Evidence suggests that reti- Noemi Lois, MD, PhD in Tourette Syndrome noids are directly involved in the for- Marion White, FRCP mation and accumulation of lipo- Aberdeen, Scotland In 1885, the French neurologist fuscin in the RPE6,7 that, in its turn, Georges Gilles de la Tourette de- 7 could compromise RPE function. The authors have no relevant finan- scribed 9 patients with childhood- However, the mechanism by which cial interest in this article. onset tics accompanied in some by acitretin could have caused the RPE We thank Alison Farrow and uncontrollable noises and utter- changes observed in this patient re- Sandra McKay for their technical as- ances, as well as hyperactivity and 1 mains uncertain. Although a dys- sistance. obsessive-compulsive behavior. The function in the fluid-pumping Corresponding author: Noemi current diagnosis of Tourette syn- mechanism of the RPE appeared to Lois, MD, PhD, Retina Service, Oph- drome, according to the Diagnostic be present in this patient, the alter- thalmology Department, Aberdeen and Statistical Manual of Mental Dis- ation of the RPE was not severe Royal Infirmary, Foresterhill, Aber- orders, Fourth Edition (DSM-IV), in- enough to compromise the support- deen AB25 2ZN, Scotland (e-mail: volves multiple motor tics and at ing role of the RPE on photorecep- [email protected]). least 1 vocal tic, which occur many tor cell function and, thus, to im- times a day, nearly every day, or in- pair the PERG. This is, however, not 1. Brown RD, Grattan CE. Visual toxicity of synthetic termittently for more than 1 year. surprising. Salzman et al8 found that retinoids. Br J Ophthalmol. 1989;73:286-288. Tics must begin before age 18 years.2 47% of patients with aphakic macu- 2. Weleber RG, Denman ST, Hanifin JM, Cunning- The average age of onset is 7 years, ham WJ. Abnormal retinal function associated lar edema had a normal PERG. Fur- with isotretinoin therapy for acne. Arch Oph- and boys are more commonly af- thermore, diffuse RPE abnormali- thalmol. 1986;104:831-837. fected than girls. Motor tics are char- 3. Weber U, Melnik B, Goerz G, Michaelis L. Ab- ties on fundus autofluorescence normal retinal function associated with long- acterized by involuntary move- images have been detected in some term etretinate? Lancet. 1988;1:235-236. ments such as facial grimacing, patients with a normal PERG (N. L. 4. Fraunfelder FT, LaBraico JM, Meyer SM. Ad- frequent eye blinking, blepharo- verse ocular reactions possibly associated with and G. E. Holder, PhD, unpub- isotretinoin. Am J Ophthalmol. 1985;100:534- spasm, spitting, and arm jerking. Vo- lished data, 1998). 537. cal tics often have an aggressive or Because symptoms, VA, and 5. Rollman O, Vahlquist A. Retinoid concentra- sexual component, such as grunt- tions in skin, serum and adipose tissue of pa- macular abnormalities appeared tients treated with etretinate. Br J Dermatol. 1983; ing, barking, echolalia, and copro- months after initiating acitretin 109:439-447. lalia (uncontrolled swearing). The 6. Katz ML, Norberg M. Influence of dietary vita- therapy and have continued to im- min A on autofluorescence of leupeptin- condition often results in deleteri- prove since its discontinuation, it is induced inclusions in the retinal pigment epi- ous social consequences. We re- possible that this drug may have thelium. Exp Eye Res. 1992;54:239-246. port a case of self-induced bilateral 7. Kennedy CJ, Rakoczy E, Constable IJ. Lipofus- played a role in their occurrence. cin of the retinal pigment epithelium: a review. retinal detachment in a young man However, this could be confirmed Eye. 1995;9:763-771. with Tourette syndrome who was

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