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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
JournalJAMA ophthalmology
DOIs
StateAccepted/In press - Jan 1 2019

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Pentosan Sulfuric Polyester
Multicenter Studies
Retinal Pigment Epithelium
Visual Acuity
Multimodal Imaging
Interstitial Cystitis
Dark Adaptation
Retinal Pigments
Optical Imaging
Vision Disorders
Optical Coherence Tomography
Causality
Pharmaceutical Preparations
Atrophy
Medical Records
Outcome Assessment (Health Care)
Guidelines
Phenotype

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Hanif, A. M., Armenti, S. T., Taylor, S. C., Shah, R. A., Igelman, A. D., Jayasundera, K. T., ... Jain, N. (Accepted/In press). Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study. JAMA ophthalmology. https://doi.org/10.1001/jamaophthalmol.2019.3392

Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy : A Multicenter Study. / Hanif, Adam M.; Armenti, Stephen T.; Taylor, Stanford C.; Shah, Rachel A.; Igelman, Austin D.; Jayasundera, K. Thiran; Pennesi, Mark; Khurana, Rahul N.; Foote, Jenelle E.; O'Keefe, Ghazala A.; Yang, Paul; Hubbard, G. Baker; Hwang, Thomas; Flaxel, Christina; Stein, Joshua D.; Yan, Jiong; Jain, Nieraj.

In: JAMA ophthalmology, 01.01.2019.

Research output: Contribution to journalArticle

Hanif, AM, Armenti, ST, Taylor, SC, Shah, RA, Igelman, AD, Jayasundera, KT, Pennesi, M, Khurana, RN, Foote, JE, O'Keefe, GA, Yang, P, Hubbard, GB, Hwang, T, Flaxel, C, Stein, JD, Yan, J & Jain, N 2019, 'Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study', JAMA ophthalmology. https://doi.org/10.1001/jamaophthalmol.2019.3392
Hanif, Adam M. ; Armenti, Stephen T. ; Taylor, Stanford C. ; Shah, Rachel A. ; Igelman, Austin D. ; Jayasundera, K. Thiran ; Pennesi, Mark ; Khurana, Rahul N. ; Foote, Jenelle E. ; O'Keefe, Ghazala A. ; Yang, Paul ; Hubbard, G. Baker ; Hwang, Thomas ; Flaxel, Christina ; Stein, Joshua D. ; Yan, Jiong ; Jain, Nieraj. / Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy : A Multicenter Study. In: JAMA ophthalmology. 2019.
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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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AU - Shah, Rachel A.

AU - Igelman, Austin D.

AU - Jayasundera, K. Thiran

AU - Pennesi, Mark

AU - Khurana, Rahul N.

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AU - O'Keefe, Ghazala A.

AU - Yang, Paul

AU - Hubbard, G. Baker

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N2 - 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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