Exploration of Potential Associations Between Sulfated Polysaccharide Exposure and Retinal Findings

Purpose: Pentosan polysulfate sodium (PPS), a widely used treatment for interstitial cystitis, has been linked to a distinctive macular toxicity. A recent case report described a similar phenotype with fondaparinux, a related sulfated polysaccharide, raising the possibility of a broader class effect. We explored potential associations between exposure to non-PPS sulfated polysaccharides and retinal imaging findings resembling PPS maculopathy. Methods: We conducted a single center retrospective study from 2018-2024. Emory Healthcare electronic health records were queried for adults with exposure to fondaparinux, enoxaparin, chondroitin containing products, alginate containing products, and/or dalteparin. Macular imaging during the study period was required for inclusion. A retina specialist reviewed macular imaging for features resembling PPS maculopathy. Given the high number of enoxaparin users with short exposure durations, imaging review for this group was limited to >1 year of documented exposure. Results: A total of 218 patients were evaluated, including patients exposed to alginate (n = 12), fondaparinux (n = 25), chondroitin sulfate (n = 111), and enoxaparin (n = 70). Mean age at first qualifying macular imaging was 67.4 years and 59.5% were women. There were no cases resembling classic PPS maculopathy. Some patients did exhibit subtle macular pigment alterations without a clear diagnosis [fondaparinux 1 (4.0%); chondroitin sulfate 3 (2.7%); alginate 1 (8.3%)]. Conclusions: This study did not identify a relationship between non-PPS sulfated polysaccharide exposure and the development of macular disease resembling classic PPS maculopathy. Larger studies with increased power may be warranted to determine whether a rare association may be present.