Pentosan Polysulfate-Associated Macular Disease In Patients With Interstitial Cystitis

As the approved oral agent for interstitial cystitis, pentosan polysulfate sodium (PPS) has been widely used since its approval in 1996. Historically recognized adverse effects of PPS are not serious. In 2018, however, use of long-term PPS was reported to be associated with vision loss from a newly described macular condition. Six patients with a history of interstitial cystitis were identified with unique macular pigment changes in the setting of chronic exposure to PPS. Most patients with PPS maculopathy reported prominent visual symptoms of difficulty reading and difficulty adjusting to dim lighting and occasionally developed severe visual disability. Subsequently, this association was demonstrated in a retrospective cross-sectional study of a local database and corroborated in a retrospective matched cohort study using a large national claims database. The cohort study involving 1604 patients newly exposed to PPS determined that they were significantly more likely to develop a new macular disease compared with matched control subjects (odds ratio, 1.41; confidence interval, 1.09-1.83). In advanced cases, some patients have atrophy of the macula resulting in legal blindness. The aims of this commentary were to summarize studies evaluating the association between PPS use and macular disease, to educate prescribers of this agent on the clinical manifestations of this condition, and to provide recommendations for screening patients at risk. Strength of association: In small retrospective studies, other potential risk factors for this maculopathy, including other medication exposures, smoking history, body mass index, or diseases affecting the kidney, liver, and spleen, did not appear to confer additional risk for developing this disease. The association between PPS and the newly described maculopathy was confirmed while excluding any other interstitial cystitis-related exposures as potential risk factors with the odds ratio of 11.25, with a 95% confidence interval of 3.69 to 34.33. Clinical presentation and functional effects: A multi-institutional retrospective series of 35 affected patients found relatively mild changes, which may have contributed to the delayed recognition of this disease. Many of these patients were initially diagnosed withmore common conditions, such as age-related macular degeneration or pattern dystrophy. A larger study of 138 patients with longer-term exposure to PPS found that approximately 40% of patients with duration of use 10 years or more showed evidence of the PPS maculopathy. That study used modern point-of-care imaging techniques, including optical coherence tomography and fundus autofluorescence imaging, and demonstrated striking abnormalities helping distinguish this condition from other forms of macular disease. Recommendations for prescribers are as follows: _ The authors recommend that providers discuss the risks associated with PPS with their patients and prescribe the lowest necessary dose and duration of PPS for patients who require long-term treatment. _ The current screening protocol includes a baseline examination with fundus photography, optical coherence tomography, and fundus autofluorescence imaging. These should generally be performed by a retina specialist. _ Testing should be repeated within 5 years after initiation of PPS and annually thereafter. _ Potential risk factors include atypical PPS dosing regimens, history of smoking or macular disease, and decreased renal, hepatic, or splenic function._ Patients diagnosed with PPS maculopathy should stop taking the drug and discuss alternative management options for interstitial cystitis with their treating physician. _ Patients should be told that visual symptoms may persist and worsen after drug cessation. Emerging evidence demonstrates an association between long-term PPS exposure and a newly described vision-threatening macular condition. Pentosan polysulfate sodium has been widely prescribed since 1996, and its use represents a major patient safety issue. This condition has characteristic findings that can be identified by modern retinal imaging technologies available to most retina specialists. Further studies are needed in PPS-exposed patients to establish causality, quantify risk of retinal disease, assess long-term visual outcomes of affected patients, and establish formal screening guidelines.