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Survey of Ophthalmology 2022Pentosan polysulfate sodium (PPS), a semisynthetic sulfated polysaccharide, is the only FDA-approved oral therapy for interstitial cystitis. Recent studies have... (Review)
Review
Pentosan polysulfate sodium (PPS), a semisynthetic sulfated polysaccharide, is the only FDA-approved oral therapy for interstitial cystitis. Recent studies have described a progressive, vision-threatening macular condition associated with long-term PPS use. We reviewed all publications concerning PPS maculopathy to consolidate known clinical features and to evaluate the strength of this association. Current literature supports a strong dose-dependent association between PPS exposure and a progressive maculopathy impacting the retinal pigment epithelium (RPE) and RPE-photoreceptor interface that may worsen even after drug cessation. Initial symptoms may include prolonged dark adaptation and difficulty reading with relative visual acuity preservation. Fundus examination often shows macular pigment clumps corresponding to lesions of focal RPE thickening. Fundus autofluorescence most clearly depicts the condition, with a distinctive pattern of hypo- and hyperautofluorescent spots in the posterior pole that sometimes extends to the retinal periphery. Many cases also show a characteristic peripapillary hypoautofluorescent halo. Near infrared reflectance may aid in early detection. RPE atrophy, cystoid macular edema, and macular neovascularization may also occur, potentially resulting in loss of central acuity. This newly described association implies significant public health risk. Ophthalmologists should screen PPS users with multimodal retinal imaging, and prescribers should minimize dose and duration of PPS use.
Topics: Anticoagulants; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Retinal Diseases; Retinal Pigment Epithelium
PubMed: 34000253
DOI: 10.1016/j.survophthal.2021.05.005 -
The Canadian Journal of Urology Dec 2023Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S. Food and Drug Administration approved... (Review)
Review
INTRODUCTION
Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S. Food and Drug Administration approved oral medication for the treatment of IC pain and symptoms. Recently, articles described a pigmentary maculopathy in IC patients on long term PPS therapy. Currently, there is no definitive study directly linking PPS as the cause of the pigmentary maculopathy. The aim of this review is to evaluate if PPS is the causative factor of the pigmentary maculopathy or if PPS use is only associated with the pigmentary maculopathy.
MATERIALS AND METHODS
A comprehensive review of peer reviewed journals using the search terms IC, maculopathy, mast cells, immune inflammatory components, Tamm-Horsfall protein, cations and tight junctions was performed to examine the pathophysiology and role of chronic inflammation in IC and known retinal maculopathies.
RESULTS
Chronic inflammatory cells have been reported in age-related macular degeneration choroid blood vessels and in bladder submucosal and detrusor layers in IC patients. Studies in IC and maculopathies demonstrate a significant milieu of activated chronic inflammatory and immunologic responses that cause a more "leaky" epithelium and a subsequent cascade of inflammatory events that results in the pathological changes seen in these two conditions.
CONCLUSIONS
After an analysis of the literature describing a pigmentary maculopathy in IC patients on long term PPS, a causal relationship does not appear to be present. An alternate model is proposed postulating that the causative factor for the pigmentary maculopathy is the underlying inflammatory state associated with IC and not PPS use.
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Cystitis, Interstitial; Pain; Inflammation
PubMed: 38104330
DOI: No ID Found -
Stem Cells and Development Aug 2022This review highlights the attributes of pentosan polysulfate (PPS) in the promotion of intervertebral disc (IVD) repair processes. PPS has been classified as a... (Review)
Review
Pentosan Polysulfate, a Semisynthetic Heparinoid Disease-Modifying Osteoarthritic Drug with Roles in Intervertebral Disc Repair Biology Emulating the Stem Cell Instructive and Tissue Reparative Properties of Heparan Sulfate.
This review highlights the attributes of pentosan polysulfate (PPS) in the promotion of intervertebral disc (IVD) repair processes. PPS has been classified as a disease-modifying osteoarthritic drug (DMOAD) and many studies have demonstrated its positive attributes in the countering of degenerative changes occurring in cartilaginous tissues during the development of osteoarthritis (OA). Degenerative changes in the IVD also involve inflammatory cytokines, degradative proteases, and cell signaling pathways similar to those operative in the development of OA in articular cartilage. PPS acts as a heparan sulfate (HS) mimetic to effect its beneficial effects in cartilage. The IVD contains small cell membrane HS proteoglycans (HSPGs) such as syndecan, and glypican and a large multifunctional HS/chondroitin sulfate (CS) hybrid proteoglycan (HSPG2/perlecan), that have important matrix-stabilizing properties and sequester, control, and present growth factors from the FGF, VEGF, PDGF, and BMP families to cellular receptors to promote cell proliferation, differentiation, and matrix synthesis. HSPG2 also has chondrogenic properties and stimulates the synthesis of extracellular matrix (ECM) components and expansion of cartilaginous rudiments, and has roles in matrix stabilization and repair. Perlecan is a perinuclear and nuclear proteoglycan (PG) in IVD cells with roles in chromatin organization and control of transcription factor activity, immunolocalizes to stem cell niches in cartilage, promotes escape of stem cells from quiescent recycling, differentiation and attainment of pluripotency and migratory properties. These participate in tissue development and morphogenesis, ECM remodeling and repair. PPS also localizes in the nucleus of stromal stem cells, promotes development of chondroprogenitor cell lineages, ECM synthesis and repair and discal repair by resident disc cells. The availability of recombinant perlecan and PPS offers new opportunities in repair biology. These multifunctional agents offer welcome new developments in repair strategies for the IVD.
Topics: Cartilage, Articular; Extracellular Matrix Proteins; Heparan Sulfate Proteoglycans; Heparinoids; Heparitin Sulfate; Humans; Intervertebral Disc; Pentosan Sulfuric Polyester; Stem Cells
PubMed: 35102748
DOI: 10.1089/scd.2022.0007 -
Current Opinion in Ophthalmology May 2021The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS). (Review)
Review
PURPOSE OF REVIEW
The aim of the present review is to provide a comprehensive summary of available knowledge regarding toxic maculopathy secondary to pentosan polysulfate sodium (PPS).
RECENT FINDINGS
PPS toxicity was described in 2018, and additional studies characterize it as dysfunction of the retinal pigment epithelium centered on the posterior pole, which can progress despite drug cessation. Requisite exposure can be as little as 0.325 kg and 2.25 years but averages closer to 1-2 kg and 10-15 years. Multimodal imaging should include near-infrared reflectance, optical coherence tomography, and fundus autofluorescence. Cross-sectional studies demonstrate evidence correlating cumulative dosing and the likelihood/severity of maculopathy. Early estimates of prevalence range from 12.7 to 41.7% depending on dosing, with overall rates around 20%.
SUMMARY
Reasonable evidence associates maculopathy with extended exposure to PPS, with an average reported incidence of around 20% in patients with long-term exposures. Patients with unexplained retinal pigment epithelium changes and difficulty with dark adaptation should be questioned regarding PPS exposure, and patients with known exposure to PPS should be examined. Further research is needed to refine screening protocols. Currently, providers should consider baseline examination and examination at 5 years and/or 500 g of exposure followed by yearly screening.
Topics: Anticoagulants; Drug-Related Side Effects and Adverse Reactions; Humans; Multimodal Imaging; Pentosan Sulfuric Polyester; Retinal Diseases; Retinal Pigment Epithelium
PubMed: 33710012
DOI: 10.1097/ICU.0000000000000754 -
JAMA Ophthalmology Mar 2023
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Retinal Diseases
PubMed: 36729463
DOI: 10.1001/jamaophthalmol.2022.6158 -
Canadian Journal of Ophthalmology.... Feb 2022To evaluate whether pentosan polysulfate maculopathy manifests distinctive imaging features that can be differentiated from those found in age-related macular...
OBJECTIVE
To evaluate whether pentosan polysulfate maculopathy manifests distinctive imaging features that can be differentiated from those found in age-related macular degeneration (AMD).
METHODS
Local databases were queried to identify patients with a diagnosis of interstitial cystitis who were seen at the Emory Eye Center between May 2014 and January 2019 and who had fundus imaging available for review. Ninety patients met the eligibility criteria. Masked graders categorized patients based on imaging characteristics as follows: category 1: pentosan polysulfate maculopathy; category 2: AMD or drusen; category 3: neither; and category 4: unsure. Pentosan polysulfate exposure characteristics were compared among groups.
RESULTS
Of the 90 subjects evaluated, 79 (88%) were female and the median age was 61.5 years (range, 30-89). Seventeen patients were placed in category 1; 25 in category 2; 47 in category 3, and; 1 in category 4. Among categories 1 to 4, respectively, 17 (100%), 15 (60%), 28 (60%), and 0 patients had exposure to pentosan polysulfate (p = 0.007). Mean cumulative exposure to pentosan polysulfate across the four categories was 2.1, 0.36, 0.34, and 0 kg, respectively (p < 0.00001). Eyes with pentosan polysulfate maculopathy did not have typical drusen in the macula.
CONCLUSION
Although pentosan polysulfate maculopathy resembles some aspects of AMD, the two conditions can be differentiated with the use of multimodal fundus imaging.
Topics: Anticoagulants; Female; Humans; Macula Lutea; Macular Degeneration; Male; Middle Aged; Multimodal Imaging; Pentosan Sulfuric Polyester; Retinal Diseases
PubMed: 33722504
DOI: 10.1016/j.jcjo.2021.02.007 -
Urology Jan 2021To 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...
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.
Topics: Cystitis, Interstitial; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Prevalence; Urologists
PubMed: 33045286
DOI: 10.1016/j.urology.2020.08.072 -
Journal of Oncology Pharmacy Practice :... Oct 2022Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a...
INTRODUCTION
Hemorrhagic cystitis can commonly occur following an allogeneic hematopoietic cell transplant and treatment options are currently limited. Pentosan polysulfate, a heparin-like, sulfated polysaccharide, is used to relieve bladder pain and discomfort associated with interstitial cystitis. Initial reports in patients with hemorrhagic cystitis demonstrate that pentosan polysulfate may hasten hemorrhagic cystitis resolution and control symptoms.
METHODS AND RESULTS
This report includes a retrospective case series of six patients who received pentosan polysulfate for the treatment of hemorrhagic cystitis following an allogeneic hematopoietic cell transplant. Pentosan polysulfate was initiated at a median of 4.5 days (range: 3-18) following hemorrhagic cystitis onset and continued for a median duration of 17.5 days (range: 7-64). Four patients were tested for BK virus and all were found to have BK viremia and viruria around the time of pentosan polysulfate initiation. The median number of red blood cell transfusions seemed to decrease in the patients initiated on pentosan polysulfate. All patients received a multi-agent treatment regimen, which included pentosan polysulfate, and half the patients had symptom resolution. The median time to symptom resolution from pentosan polysulfate initiation was 9 days (range: 7-10).
CONCLUSION
Pentosan polysulfate was well-tolerated and seemed to assist with symptom resolution. Future studies are needed to confirm the impact of pentosan polysulfate on the treatment of hemorrhagic cystitis.
Topics: Cystitis; Cystitis, Interstitial; Hematopoietic Stem Cell Transplantation; Hemorrhage; Humans; Pentosan Sulfuric Polyester; Retrospective Studies
PubMed: 35642262
DOI: 10.1177/10781552221105295 -
CMAJ : Canadian Medical Association... May 2021
Topics: Anticoagulants; Cystitis, Interstitial; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Time Factors; Vision Disorders
PubMed: 33941523
DOI: 10.1503/cmaj.201900 -
Ophthalmology. Retina Nov 2023
Topics: Humans; Pentosan Sulfuric Polyester; Visual Field Tests; Macular Degeneration; Retinal Diseases
PubMed: 37619623
DOI: 10.1016/j.oret.2023.08.009