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Original Investigation
September 5, 2019

Phenotypic Spectrum of Pentosan Polysulfate Sodium–Associated Maculopathy: A Multicenter Study

Author Affiliations
  • 1Emory University School of Medicine, Atlanta, Georgia
  • 2Department of Ophthalmology and Visual Sciences, University of Michigan Kellogg Eye Center, Ann Arbor
  • 3Casey Eye Institute, Department of Ophthalmology, Oregon Health and Science University, Portland
  • 4Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia
  • 5Northern California Retina Vitreous Associates, Mountain View
  • 6Midtown Urology, Atlanta, Georgia
JAMA Ophthalmol. Published online September 5, 2019. doi:10.1001/jamaophthalmol.2019.3392
Key Points

Question  What are the exposure characteristics and clinical manifestations of pentosan polysulfate sodium–associated maculopathy?

Findings  In this case series, 35 affected patients reporting long-term pentosan polysulfate sodium exposure were identified. Fundus examination revealed macular pigment clumps amidst yellow subretinal deposits in mild disease with atrophy in more extensive disease, and fundus autofluorescence imaging demonstrated a pattern of abnormality centered on and involving the fovea, occasionally extending to the retinal periphery.

Meaning  These findings suggest pentosan polysulfate sodium–associated maculopathy is a vision-threatening condition that can manifest in the setting of long-term exposure to the drug, and multimodal imaging posits a distinctive clinical phenotype.


Importance  A unique pigmentary maculopathy was recently described in 6 patients with long-term exposure to pentosan polysulfate sodium (PPS), a long-standing oral therapy for interstitial cystitis.

Objective  To characterize the exposure characteristics and clinical manifestations of PPS–associated maculopathy.

Design, Setting, and Participants  In this multi-institutional case series, medical records of patients who exhibited the characteristic maculopathy in the setting of prior PPS exposure were retrospectively reviewed. Data were collected from August 1, 2012, to October 1, 2018, and data were analyzed from October 2018 to January 2019.

Main Outcomes and Measures  Drug exposure, visual acuity, and retinal imaging characteristics.

Results  Of the 35 included patients (70 eyes), 34 (97%) were female, and the median (range) age was 60 (37-79) years. The median (range) duration of PPS intake was 15 (3-22) years, and the median (range) cumulative exposure was 1.61 (0.44-4.31) kg. The leading visual symptoms were metamorphopsia, blurred vision, and prolonged dark adaptation. Median (range) logMAR visual acuity of all eyes was 0.10 (−0.12 to 1.18). Fundus examination often revealed hyperpigmented macular spots (34 of 64 eyes [53%]) with interspersed pale-yellow deposits, although less commonly in eyes that exhibited retinal pigment epithelial atrophy (6 of 26 eyes [23%]; P < .001). Optical coherence tomography showed foci of retinal pigment epithelium elevation or thickening associated with hyperreflectance on near-infrared reflectance imaging. Fundus autofluorescence imaging typically revealed a symmetric, confluent pattern of hyperautofluorescent and hypoautofluorescent spots that involved the fovea in all eyes and extended to the retinal periphery in 24 eyes (36%). Longitudinal evaluation demonstrated dynamic changes in pigmentary abnormalities.

Conclusions and Relevance  These findings suggest that PPS–associated maculopathy is a vision-threatening condition that can manifest in the setting of long-term exposure to the drug. Multimodal imaging posits a distinctive clinical phenotype, characterized in this cohort by dynamic alterations within the retinal pigment epithelium and at the retinal pigment epithelium–photoreceptor interface. Ongoing work might explore causality and direct screening guidelines.

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