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CUAJ %u2022 APRIL 2025 %u2022 VOLUME 19, ISSUE 4 95Guideline: IC/BPSstrates a distinctive clinical phenotype with the retinal pigment epithelium (RPE) and RPE-photoreceptor interface. In some cases, progressive RPE atrophy encroaches on the foveal center and may pose a long-term threat to central vision.55 Visual acuity is not a sensitive measure of visual dysfunction, as it remained relatively preserved even in patients with signs of toxicity, except in advanced cases with center-involved atrophy, macular edema, or choroidal neovascularization.51,58The mainstay of management is advising drug cessation. Importantly, patients should be warned that PPSinduced maculopathy can continue to progress despite PPS cessation. In a retrospective case series involving 11 patients with PPS-associated maculopathy and median cumulative PPS exposure of 1970 g, there was no evidence of disease regression in any eye following drug cessation. Rather, prospective retinal imaging demonstrated expansion of the area of involvement, suggesting PPS-associated maculopathy continues to evolve after drug cessation for at least 10 years.55 Caution is advised, as the true prevalence of PPSassociated maculopathy in the generalized population taking PPS is difficult to ascertain. PPS was widely prescribed as a mainstay of IC/BPS therapy for many years, and pre-symptomatic disease may not be easily detectable without implementation of formal retinal screening protocols. On the other hand, the current literature base may be subject to selection and screening biases, potentially overestimating reported prevalence rates. All studies to date have been retrospective, and a causative relationship has not been established. Further research is required to refine ideal screening protocols.On December 15, 2020, Health Canada issued a safety alert warning to healthcare professionals regarding long-term use of PPS and risk of pigmentary maculopathy. (https://recalls-rappels.canada.ca/en/alert-recall/elmiron-pentosan-polysulfate-sodium-andrisk-pigmentary-maculopathy). PPS is now contraindicated in patients with a personal history of any macular pathology. Prescribers are advised to assess the risk and benefits before initiating PPS and to obtain baseline ophthalmologic history and retinal exams before starting treatment. Regular retinal exams are advised thereafter for early detection of macular pathology. Patients should be counseled to report changes in vision, such as difficulty reading, slow adjustment to low or reduced light, and blurred vision, including blurry or wavy vision near or in the centre of the field of vision. Many practitioners have already been approached by legacy PPS patients seeking advice and many more are likely to come forward as concerns regarding PPS use continue to disseminate. There is no evidence to support a weaning protocol for legacy patients; however, the guideline panel suggests the following steps for weaning legacy patients off oral PPS:1. Inform the patient of the perceived risk based on observational data (Table 2). 2. Engage in shared decision-making regarding the choice to continue therapy or not. Patients opting to remain on oral PPS should seek referral for consideration of baseline ophthalmologic assessment.3. If a patient opts to discontinue the medication, use a weaning schedule that would be considered reasonable (e.g., a patient on 100 mg orally three times daily might follow twice daily x four weeks, then daily x four weeks, then discontinuing altogether).4. Follow the patient closely for worsening of symptoms or symptom flares during wean and be prepared to offer alternative treatment options using a symptom phenotype-directed approach. Table 2. Suggestions for informed consent regarding use of oral PPS Patients counseled on the risks and benefits of PPS, and informed that PPS therapy involves a potential risk of permanent vision loss. A causative link has not been established, but the observational data highlighting an association is concerning. PPS is contraindicated in patients with a history of any macular pathology.The safe dosage, duration of therapy, and cumulative dosage limits remain unknown with respect to risk of maculopathy.Presymptomatic disease may not be detectable in the absence of formal retinal screening procedures.Vision-threatening maculopathy is likely to progress even after the drug is stopped.PPS prescribing physicians should be aware of the high risk of retinal toxicity and maculopathy as cumulative dosages approach %u2265 1000 g.59Patients opting for oral PPS should seek a referral for consideration of baseline ophthalmological assessment. Any patient with vision changes and any degree of exposure to PPS should be evaluated by an ophthalmologist promptly.60PPS: pentosan polysulfate.