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Pentosan Polysulfate Maculopathy: What Urologists Should Know in 2020

Published:October 09, 2020DOI:https://doi.org/10.1016/j.urology.2020.08.072

      Abstract

      Objective

      To conduct a review of current literature to assess whether an association exists between Pentosan Polysulfate Sodium and the development of macular disease, as it is the only oral medication approved by the Food and Drug Administration for the management of interstitial cystitis.

      Materials and Methods

      A systematic review was conducted by the authors separately, with review methods established prior to the conduct of the review. Databases searched included PubMed, Ovid, Medline, EBSCO, and Google Scholar. A search was conducted for the terms “Pentosan Polysulfate Maculopathy,” “Pentosan Polysulfate Retinopathy,” and “Interstitial Cystitis Maculopathy.” All papers reporting on primary data were included. There were no study sponsors.

      Results

      A total of 14 papers reporting on primary data were identified. Most papers reported on the development of macular disease in the setting of chronic pentosan polysulfate sodium exposure. No randomized controlled trials have been performed to date and data was insufficient to perform a meta-analysis. Nevertheless, patients with interstitial cystitis were more likely to receive a diagnosis of maculopathy after several years of the medication use.

      Conclusion

      Although the nature of the published studies renders them prone to confounders, currently available data suggest an increased risk for developing maculopathy after years of pentosan polysulfate sodium use. In light of this, and the marginal effectiveness of the medication for the average individual, we suggest that education be provided as to the possible association and that regular ophthalmic evaluation be recommended for patients who are continued on chronic Pentosan Polysulfate Sodium.
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      References

        • Swain SM
        • Parker B
        • Wellstein A
        • Lippman ME
        • Steakley C
        • DeLap R
        Phase I trial of pentosan polysulfate.
        Invest New Drugs. 1995; 13: 55‐62https://doi.org/10.1007/BF02614221
        • Frileux C
        Un nouvel anticoagulant de synthèse le thrombocid [Thrombocid: a new synthetic anticoagulant].
        Presse Med. 1951; 59: 159
        • Koncz J
        • Bucherl E.
        Beitrag zur Wirkungsweise des Anticoagulans Thrombocid [On the mode of action of thrombocid].
        Klin Wochenschr. 1951; 29: 650https://doi.org/10.1007/BF01490174
        • van Ophoven A
        • Vonde K
        • Koch W
        • Auerbach G
        • Maag KP
        Efficacy of pentosan polysulfate for the treatment of interstitial cystitis/bladder pain syndrome: results of a systematic review of randomized controlled trials.
        Curr Med Res Opin. 2019; 35 (9): 1495-1503https://doi.org/10.1080/03007995.2019.1586401
        • Nickel JC
        • Barkin J
        • Forrest J
        • et al.
        Randomized, double-blind, dose-ranging study of pentosan polysulfate sodium for interstitial cystitis.
        Urology. 2005; 65: 654‐658https://doi.org/10.1016/j.urology.2004.10.071
        • Lush RM
        • Figg WD
        • Pluda JM
        • et al.
        A phase I study of pentosan polysulfate sodium in patients with advanced malignancies.
        Ann Oncol. 1996; 7: 939‐944https://doi.org/10.1093/oxfordjournals.annonc.a010797
        • Jepsen JV
        • Sall M
        • Rhodes PR
        • Schmidt D
        • Messing E
        • Bruskewitz RC
        Long-term experience with pentosan polysulfate in interstitial cystitis.
        Urology. 1998; 51: 381-387https://doi.org/10.1016/s0090-4295(97)00714-0
        • Hanno PM
        Analysis of long-term Elmiron therapy for interstitial cystitis.
        Urology. 1997; 49: 93-99https://doi.org/10.1016/s0090-4295(97)00179-9
        • Pearce WA
        • Chen R
        • Jain N
        Pigmentary maculopathy associated with chronic exposure to pentosan polysulfate sodium.
        Ophthalmology. 2018; 125: 1793‐1802https://doi.org/10.1016/j.ophtha.2018.04.026
        • Hanif AM
        • Armenti ST
        • Taylor SC
        • et al.
        Phenotypic spectrum of pentosan polysulfate sodium-associated maculopathy: a multicenter study [published online ahead of print, 2019 Sep 5].
        JAMA Ophthalmol. 2019; 137: 1275‐1282https://doi.org/10.1001/jamaophthalmol.2019.3392
        • Greenlee T
        • Hom G
        • Conti T
        • Babiuch AS
        • Singh R
        Re: Pearce et al.: Pigmentary maculopathy associated with chronic exposure to pentosan polysulfate sodium (Ophthalmology. 2018;125:1793-1802).
        Ophthalmology. 2019; 126: e51https://doi.org/10.1016/j.ophtha.2018.12.037
        • Ludwig CA
        • Vail D
        • Callaway NF
        • Pasricha MV
        • Moshfeghi DM
        Pentosan polysulfate sodium exposure and drug-induced maculopathy in commercially insured patients in the United States.
        Ophthalmology. 2020; 127: 535‐543https://doi.org/10.1016/j.ophtha.2019.10.036
        • Jain N
        • Li AL
        • Yu Y
        • VanderBeek BL
        Association of macular disease with long-term use of pentosan polysulfate sodium: findings from a US cohort [published online ahead of print, 2019 Nov 6].
        Br J Ophthalmology. 2019; (bjophthalmol-2019-314765)https://doi.org/10.1136/bjophthalmol-2019-314765
        • Shea BJ
        • Reeves BC
        • Wells G
        • et al.
        AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both.
        BMJ. 2017; 358: j4008
        • Vora RA
        • Patel AP
        • Yang SS
        • Melles R
        A case of pentosan polysulfate maculopathy originally diagnosed as stargardt disease.
        Am J Ophthalmol Case Rep. 2020; 17100604https://doi.org/10.1016/j.ajoc.2020.100604
        • Mishra K
        • Patel TP
        • Singh MS
        Choroidal Neovascularization associated with pentosan polysulfate toxicity.
        Ophthalmol Retina. 2019; 4: 111-113https://doi.org/10.1016/j.oret.2019.08.006
        • Wingelaar MJ
        • Raevis JJ
        • Conlin KA
        • Stepien KE
        Retinal toxicity in a patient on pentosan polysulfate sodium [published online ahead of print, 2020 Apr 17].
        Urology. 2020; (S0090-4295(20)30384-8)https://doi.org/10.1016/j.urology.2020.04.006
        • Huckfeldt RM
        • Vavvas DG
        Progressive maculopathy after discontinuation of pentosan polysulfate sodium.
        Ophthalmic Surg Lasers Imaging Retina. 2019; 50: 656-659https://doi.org/10.3928/23258160-20191009-10
        • Hadad A
        • Helmy O
        • Leeman S
        • Schaal S
        A novel multimethod image analysis to quantify pentosan polysulfate sodium retinal toxicity.
        Ophthalmology. 2020; 127: 429-431https://doi.org/10.1016/j.ophtha.2019.10.013
        • Foote J
        • Hanif AM
        • Jain N
        MP47-03 - Chronic exposure to pentosan polysulfate sodium is associated with retinal pigmentary changes and vision loss.
        J Urol. 2019; 201 (supplement): 45
        • Vora RA
        • Patel AP
        • Melles R
        Prevalence of maculopathy associated with long-term pentosan polysulfate therapy.
        Ophthalmology. 2020; 127: 835-836https://doi.org/10.1016/j.ophtha.2020.01.017
        • Wang D
        • Au A
        • Gunnemann F
        • et al.
        Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis.
        Can J Ophthalmol. 2020; 55 (ISSN 0008-4182): 116-125https://doi.org/10.1016/j.jcjo.2019.12.001
        • Barnes AC
        • Hanif AM
        • Jain N
        Pentosan polysulfate maculopathy versus inherited macular dystrophies: comparative assessment with multimodal imaging [published online ahead of print, 2020 May 21].
        Ophthalmol Retina. 2020; (S2468-6530(20)30200-1)https://doi.org/10.1016/j.oret.2020.05.008
      1. Optum Clinformatics Data Mart Database. Available at: https://web.uri.edu/optum/ Accessed June 30, 2020

      2. IBM MarketScan Research Databases. Available at:https://www.ibm.com/products/marketscan-research-databases Accessed June 30, 2020

        • Drucker1 AM
        • Fleming P
        • Chan A-W
        Research techniques made simple: assessing risk of bias in systematic reviews.
        J Invest Dermatol. 2016; 136: e109ee114https://doi.org/10.1016/j.jid.2016.08.021
        • Sterne JAC
        • Savović J
        • Page MJ
        • et al.
        RoB 2: a revised tool for assessing risk of bias in randomised trials.
        BMJ. 2019; 366: l4898
      3. GA Wells, B Shea, D O'Connell, et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses. Ottawa Hospital Research Institute. Available at: http://www.ohri.ca/home.asp. Accessed June 6, 2020.

        • Jones CA
        • Nyberg L
        Epidemiology of interstitial cystitis.
        Urology. 1997; 49: 2-9https://doi.org/10.1016/s0090-4295(99)80327-6
        • Nickel JC
        • Herschorn S
        • Whitmore KE
        • et al.
        Pentosan polysulfate sodium for treatment of interstitial cystitis/bladder pain syndrome: insights from a randomized, double-blind, placebo-controlled study.
        J Urol. 2015; 193: 857-862
        • Shah R
        • Simonett JM
        • Lyons RJ
        • Rao RC
        • Pennesi ME
        • Jain N
        Disease course in patients with pentosan polysulfate sodium-associated maculopathy after drug cessation.
        JAMA Ophthalmol. 2020; 138: 894-900
        • Ortho−McNeil−Janssen Pharmaceuticals
        Elmiron (Pentosan Polysulfate sodium).
        U.S. Food and Drug Administration, 2020 (Available at:) (RevisedAccessed June 30, 2020)
        • Doiron RC
        • Bona M
        • Nickel JC
        Possible drug-induced, vision-threatening maculopathy secondary to chronic pentosan polysulfate sodium (Elmiron®) exposure.
        Can Urol Assoc J. 2020; 14: 10-11https://doi.org/10.5489/cuaj.6401
      4. Elmiron (Pentosan Polysulfate Sodium) [Product Monograph].
        Janssen Inc., TorontoON2019 (Updated: October 2019. Accessed June 6, 2020)

      Linked Article

      • Re: Pentosan Polysulfate Maculopathy: What Urologists Should Know in 2020
        UrologyVol. 152
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          I was pleased to see the systematic review of pentosan polysulfate (PPS) maculopathy by Paredes Mogica and De1, in which the authors provide a valuable summary of our current understanding of this condition. Although there is a growing body of literature on the topic in ophthalmic journals,2-6 it is important that urologists assimilate our findings of this drug-associated retinal disease when making treatment decisions for patients with interstitial cystitis (IC).
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