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. 2019 Nov 1;137(11):1275-1282.
doi: 10.1001/jamaophthalmol.2019.3392.

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

Adam M Hanif  1 , Stephen T Armenti  2 , Stanford C Taylor  3 , Rachel A Shah  4 , Austin D Igelman  3 , K Thiran Jayasundera  2 , Mark E Pennesi  3 , Rahul N Khurana  5 , Jenelle E Foote  6 , Ghazala A O'Keefe  4 , Paul Yang  3 , G Baker Hubbard 3rd  4 , Thomas S Hwang  3 , Christina J Flaxel  3 , Joshua D Stein  2 , Jiong Yan  4 , Nieraj Jain  4
Affiliations

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

Adam M Hanif et al. JAMA Ophthalmol. .

Abstract

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Hanif has received grants from the VitreoRetinal Surgery Foundation. Dr Jayasundera has received grant K23 EY026985-01from the National Institutes of Health. Dr Pennesi has consulted for Editas Medicine, ProQR Therapeutics, Nacuity Pharmaceuticals, Astellas Pharma, Gensight Biologics, Horama, Spark Therapeutics, Wave Life Sciences, Eyevensys, Nayan Pharmaceuticals, AGTC, Sanofi, and Nightstar Therapeutics. Dr Khurana has received grants from Clearside Biomedical, Roche, and Santen Pharmaceutical and has consulted for Alkahest, Allergan, Clearside Biomedical, Genentech, and Regeneron Pharmaceuticals. Dr Yang has received grants from the Foundation Fighting Blindness and National Institutes of Health; personal fees for consulting for Astellas Pharma; and clinical trial support from Sanofi, Nightstar Therapeutics, Foundation Fighting Blindness, and AGTC. Dr Hwang has received grants from the National Institutes of Health. Dr Stein has received grants from the National Institutes of Health. Dr Jain has received grants from the Foundation Fighting Blindness. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Representative Color Fundus Photography
Representative color fundus photography demonstrating a variety of disease presentations, depicting pigment clumps and pale-yellow or orange deposits.
Figure 2.
Figure 2.. Representative Fundus Autofluorescence Imaging
Representative fundus autofluorescence imaging demonstrating a variety of disease presentations. Retinal pathology was subjectively more apparent on fundus autofluorescence imaging.
Figure 3.
Figure 3.. Multimodal Imaging of Macular Pigment Alterations
Representative images from patient 17. Some macular pigment clumps on color fundus photography (A) colocalize with increased signal on fundus autofluorescence imaging (B) and near-infrared reflectance imaging (C) and often appear to reside at the level of the retinal pigment epithelium on optical coherence tomography (D). The dotted lines in panel C correspond to the cross sections in panel D in descending order.
Figure 4.
Figure 4.. Progression of Disease by Fundus Autofluorescence Imaging
Representative images from patient 29. Fundus autofluorescence imaging revealed progression of disease extent across 4 years, with particularly rapid evolution of changes over a 10-month period (panel A to panel B).
See this image and copyright information in PMC

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