Advertisement

Expanded Clinical Spectrum of Pentosan Polysulfate Maculopathy: A Macula Society Collaborative Study

      Purpose

      Explore the spectrum of clinical manifestations of pentosan polysulfate sodium (PPS) maculopathy observed across a range of practice settings.

      Design

      Multi-institutional retrospective study.

      Participants

      Patients exhibiting findings suggestive of PPS maculopathy identified from April 30, 2019, to December 4, 2020.

      Methods

      Members of the Macula Society submitted cases of presumed PPS maculopathy for consideration in this series. Diagnosis was confirmed by masked review of fundus imaging. Clinical characteristics of confirmed cases were summarized with descriptive statistics.

      Main Outcome Measures

      Pentosan polysulfate exposure characteristics and fundus imaging features.

      Results

      There were 74 patients with PPS maculopathy included in the current study. Median (interquartile range) age at diagnosis was 62.0 years (56.0–65.8). The median duration of exposure to PPS was 14.0 years (10.2–18.9), with a median cumulative exposure of 1.5 kg (0.9–2.4). The most common presenting symptom was decreased or blurry vision (66.2%), followed by prolonged dark adaption or nyctalopia (32.4%). The most common referral diagnosis was age-related macular degeneration (54.1%); 16.2% of patients were referred for suspected PPS maculopathy. Novel imaging findings emerged, including highly asymmetric disease in 2 patients and a prominent vitelliform maculopathy in 2 patients.

      Conclusions

      Most patients with PPS maculopathy exhibit characteristic findings on multimodal fundus imaging in the setting of high cumulative exposure to the oral drug. Some patients in the current study manifested novel imaging findings, expanding our understanding of the phenotypic spectrum of this condition. We recommend considering standardized ophthalmic screening of patients treated with PPS.

      Keywords

      Abbreviations and Acronyms:

      AMD (age-related macular degeneration), CME (cystoid macular edema), FAF (fundus autofluorescence), IQR (interquartile range), logMAR (logarithm of the minimum angle of resolution), MNV (macular neovascularization), NIR (near-infrared reflectance), PPS (pentosan polysulfate sodium), RPE (retinal pigment epithelium), VA (visual acuity)
      To read this article in full you will need to make a payment
      Subscribe to Ophthalmology Retina
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hanno P.M.
        • Erickson D.
        • Moldwin R.
        • Faraday M.M.
        • American Urological Association
        Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment.
        J Urol. 2015; 193: 1545-1553
        • Anderson V.R.
        • Perry C.M.
        Pentosan polysulfate: a review of its use in the relief of bladder pain or discomfort in interstitial cystitis.
        Drugs. 2006; 66: 821-835
        • Pearce W.A.
        • Chen R.
        • Jain N.
        Pigmentary maculopathy associated with chronic exposure to pentosan polysulfate sodium.
        Ophthalmology. 2018; 125: 1793-1802
        • Hanif A.M.
        • Armenti S.T.
        • Taylor S.C.
        • et al.
        Phenotypic spectrum of pentosan polysulfate sodium-associated maculopathy: a multicenter study.
        JAMA Ophthalmol. 2019; 137: 1275-1282
        • Hanif A.M.
        • Shah R.
        • Yan J.
        • et al.
        Strength of association between pentosan polysulfate and a novel maculopathy.
        Ophthalmology. 2019; 126: 1464-1466
        • Vora R.A.
        • Patel A.P.
        • Melles R.
        Prevalence of maculopathy associated with long-term pentosan polysulfate therapy.
        Ophthalmology. 2020; 127: 835-836
        • Van Bergen T.
        • Etienne I.
        • Jia J.
        • et al.
        Heparanase deficiency is associated with disruption, detachment, and folding of the retinal pigment epithelium.
        Curr Eye Res. 2020; : 1-5
        • Greenlee T.
        • Hom G.
        • Conti T.
        • et al.
        Re: Pearce et al.: Pigmentary maculopathy associated with chronic exposure to pentosan polysulfate sodium (Ophthalmology. 2018;125:1793-1802.
        Ophthalmology. 2019; 126: e51
        • Lindeke-Myers A.
        • Hanif A.M.
        • Jain N.
        Pentosan polysulfate maculopathy.
        Surv Ophthalmol. 2021; S0039-6257: 00123-00125
      1. Elmiron (pentosan polysulfate sodium) [package insert]. Janssen Pharmaceuticals, Inc., Titusville, NJ2020
        • Jones C.A.
        • Nyberg L.
        Epidemiology of interstitial cystitis.
        Urology. 1997; 49: 2-9
        • Al-Zahrani A.A.
        • Gajewski J.B.
        Long-term efficacy and tolerability of pentosan polysulphate sodium in the treatment of bladder pain syndrome.
        Can Urol Assoc J. 2011; 5: 113-118
      2. About Adult BMI.
        (2020)
        • Oravisto K.J.
        Epidemiology of interstitial cystitis.
        Ann Chir Gynaecol Fenn. 1975; 64: 75-77
        • Jain N.
        • Li A.L.
        • Yu Y.
        • VanderBeek B.L.
        Association of macular disease with long-term use of pentosan polysulfate sodium: findings from a US cohort.
        Br J Ophthalmol. 2020; 104: 1093-1097
        • 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: 116-125
        • Hadad A.
        • Helmy O.
        • Leeman S.
        • Schaal S.
        A novel multimethod image analysis to quantify pentosan polysulfate sodium retinal toxicity.
        Ophthalmology. 2020; 127: 429-431
        • Christiansen J.S.
        • Barnes A.C.
        • Berry D.E.
        • Jain N.
        Pentosan polysulfate maculopathy versus age-related macular degeneration: comparative assessment with multimodal imaging.
        Can J Ophthalmol. 2021 Mar 12; ([Epub ahead of print])
        • Wannamaker K.W.
        • Sisk R.A.
        Large subfoveal vitelliform lesions in a case of pentosan polysulfate maculopathy.
        Ophthalmology. 2020; 127: 1641
        • Shah R.
        • Simonett J.M.
        • Lyons R.J.
        • et al.
        Disease course in patients with pentosan polysulfate sodium-associated maculopathy after drug cessation.
        JAMA Ophthalmol. 2020; 138: 894-900
        • Huckfeldt R.M.
        • Vavvas D.G.
        Progressive maculopathy after discontinuation of pentosan polysulfate sodium.
        Ophthalmic Surg Lasers Imaging Retina. 2019; 50: 656-659