A case of pentosan polysulfate maculopathy originally diagnosed as stargardt disease.

PURPOSE: To describe a patient with a past diagnosis of Stargardt disease that was later determined to be pentosan polysulfate (PPS) maculopathy. OBSERVATIONS: The patient had clinical and imaging findings uncharacteristic of Stargardt disease. Rather, her fundus resembled the recently described maculopathy ascribed to PPS. After genetic testing was found to be negative for pathologic variants, the patient was asked to cease usage of PPS. CONCLUSIONS AND IMPORTANCE: This case emphasizes the importance of reviewing patient medication profiles prior to rendering a diagnosis of a retinal dystrophy. It is essential that ophthalmologists catch drug toxicities as early as possible, to minimize risk of further irreversible vision loss due to continued medication exposure.

Introduction

Recent studies have linked chronic exposure to pentosan polysulfate (PPS; Elmiron [Janssen Pharmaceuticals, Titusville, NJ]) with the development of a pigmentary maculopathy., PPS is the only Food and Drug Administration (FDA) - approved oral medicine for the treatment of interstitial cystitis (IC)., This case highlights the importance of careful review of past medical histories and medication profiles of all patients, particularly those with retinal and imaging findings suggestive of a dystrophic process. Failure to diagnose a medication toxicity in a timely fashion may lead to preventable irreversible vision loss. Furthermore, inappropriate diagnosis of a retinal dystrophy may lead to unwarranted genetic counseling and ill-informed life and family planning.

Case report

A 41-year-old white female presented for a second opinion regarding a recent diagnosis of Stargardt disease. She complained of darkening of her vision, and progressive difficulty with reading and night vision. Her past medical history was positive for Crohn's disease, hypothyroidism, chronic interstitial cystitis, irritable bowel syndrome, and bipolar disorder. Relevant medications included adalimumab, methotrexate, gabapentin, quetiapine, naratriptan, oxcarbazepine, topiramate, and pentosan polysulfate (PPS).

Her best corrected visual acuity was 20/25 OD and 20/20 OS. Anterior segments were normal. Her dilated fundus exam demonstrated severe retinal pigment epithelial abnormalities (RPE) in both eyes, with clumps of hyper-pigmentation within larger areas of hypo-pigmentation that spanned the entire macula and circumferential peri-papillary area (Fig. 1). Near infrared reflectance and optical coherence tomography (OCT) revealed scattered hyper-reflectance and RPE deposits that localized to the hyper-pigmented deposits on fundus exam. Dark choroid was absent by fluorescein angiography (FA). Full field electroretinogram demonstrated normal amplitude rod and cone mediated responses, but with delayed timing. Electro-oculogram was normal in both eyes. Genetic testing was conducted on peripheral blood lymphocytes with retinitis pigmentosa multigene panel by massively parallel sequencing of coding regions and exon-intron boundaries including deletion/duplication analysis. There were no pathogenic variants or variants of unknown significance identified. Genes included in the testing: ABCA4, AIPL1, BEST1, C8orf37, CA4, CDHR1, CEP290, CERKL, CHM, CLRN1, CNGA1, CNGB1, CRB1, CRX, DHDDS, EYS, FAM161A, FSCN2, GUCY2D, IDH3B, IMPDH1, IMPG2, IQCB1, KIZ, KLHL7, LCA5, LRAT, MAK, MERTK, NMNAT1, NR2E3, NRL, PCARE, PDE6A, PDE6B, PRCD, PROM1, PRPF3, PRPF31, PRPF8, PRPH2, RDH12, RGR, RHO, RLBP1, ROM1, RP1, RP2, RPE65, RPGR, RPGRIP1, SAG, SEMA4A, SNRNP200, SPATA7, TOPORS, TTC8, TULP1, USH1C, USH2A (ARUP Laboratories, Salt Lake City Utah USA).

Fig. 1

Fundus photography of the right (1a) and left (1b) eye demonstrated hyper-pigmented deposits within larger areas of hypo-pigmentary changes at the level of the retinal pigment epithelium. Fluorescein angiography of the right (2a) and left (2b) eye revealed patchy hyper-fluoresence and no dark choroid. Near infrared reflectance and corresponding OCT B-scan imaging of the right (3a) and left (3b) eye demonstrated hyper-reflectance and RPE deposits that localize to the hyper-pigmented deposits seen on fundus photography (white arrowheads).

Discussion

It was felt that negative genetic testing, along with atypical clinical and imaging characteristics, rendered Stargardt disease an unlikely diagnosis. Her fundus was suggestive of a pattern dystrophy. However, the broad extent and symmetry of abnormalities were uncharacteristic. Pharmacy records were reviewed and indicated that she had been dispensed 11,500 capsules of PPS (Elmiron [Janssen Pharmaceuticals, Titusville, NJ]) over 18 years. Her prescription was for 400mg daily, which resulted in a possible cumulative exposure of 1150 g. Two recent publications detailed the clinical and imaging characteristics of patients with long term exposure to PPS., As our patient fit the reported toxicity profile, we made the diagnosis of maculopathy due to long term PPS exposure. We asked her to contact her urologist to discontinue the drug, as this maculopathy may be progressive and/or may evolve into vision-threatening geographic atrophy.,

Patient consent

Written consent to publish this case has not been obtained. This report does not contain any personal identifying information.

Funding

No funding was received for this work.

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Authorship

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Declaration of competing interest

No conflict of interest exists.