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Retina (Philadelphia, Pa.) Jul 2023To assess genetic associations for pentosan polysufate sodium maculopathy.
PURPOSE
To assess genetic associations for pentosan polysufate sodium maculopathy.
METHODS
Genetic testing for inherited retinal dystrophy genes using exome testing and for 14 age-related macular degeneration-associated single nucleotide polymorphisms (SNPs) using panel testing were performed. In addition, full-field electroretinograms (ffERG) were obtained to identify any cone-rod dystrophy.
RESULTS
Eleven of 15 patients were women, with a mean age of 69 (range 46-85). Inherited retinal dystrophy exome testing in five patients revealed six pathogenic variants, but failed to confirm inherited retinal dystrophy in any patient genetically. FfERG performed in 12 patients demonstrated only nonspecific a- and b-wave abnormalities in 11 cases and was normal in one case. For age-related macular degeneration single nucleotide polymorphisms, CFH rs3766405 ( P = 0.003) and CETP ( P = 0.027) were found to be statistically significantly associated with pentosan polysulfate maculopathy phenotype compared with the control population.
CONCLUSION
Pentosan polysulfate maculopathy is not associated with Mendelian inherited retinal dystrophy genes. However, several age-related macular degeneration risk alleles were identified to be associated with maculopathy compared with their frequency in the normal population. This suggests a role for genes in disease pathology, particularly the alternative complement pathway. These findings would benefit from further investigation to understand the risk of developing maculopathy in taking pentosan polysulfate.
Topics: Female; Male; Humans; Pentosan Sulfuric Polyester; Cystitis, Interstitial; Macular Degeneration; Retinal Dystrophies; Cone-Rod Dystrophies
PubMed: 36996461
DOI: 10.1097/IAE.0000000000003794 -
The Journal of Veterinary Medical... Oct 2022The aim of this study was to investigate the anti-hepcidin effect of pentosan polysulfate (PPS) in Mongolian horses. Twenty-six healthy horses were randomly allocated in...
The aim of this study was to investigate the anti-hepcidin effect of pentosan polysulfate (PPS) in Mongolian horses. Twenty-six healthy horses were randomly allocated in to two-groups; one group was treated with a PPS once a week for 4-weeks while another group keeping as placebo. Blood samples at day 0 (D0), before race (BR; day 28) and after race (AR; day 28) were analyzed for serum biochemistry, hepcidin and iron concentrations. Significant reduction of hepcidin was observed at AR in PPS group when compared with BR placebo (P<0.05) and AR placebo (P<0.01). Mean hepcidin concentration difference of D0-BR and BR-AR in PPS was greater than the placebo whereas the iron concentration difference is reduced compared to placebo. Results indicate a novel therapeutic application of PPS as an anti-hepcidin compound to control hepcidin in horses while emphasizing further molecular studies.
Topics: Animals; Horses; Iron; Pentosan Sulfuric Polyester
PubMed: 36047165
DOI: 10.1292/jvms.22-0113 -
Drugs 2006Pentosan polysulfate (pentosan polysulfate sodium; ELMIRON), a heparin-like, sulfated polysaccharide, is used to manage bladder pain and discomfort in adults with... (Review)
Review
Pentosan polysulfate (pentosan polysulfate sodium; ELMIRON), a heparin-like, sulfated polysaccharide, is used to manage bladder pain and discomfort in adults with interstitial cystitis (IC). Preliminary clinical models suggest that pentosan polysulfate repairs damaged glycosaminoglycan (GAG) layers lining the urothelium and in vitro data suggest it may provide an anti-inflammatory effect in patients with IC. Pentosan polysulfate shows beneficial effects in a proportion of patients with IC in terms of the improvement of a patient's overall condition and the relief of pain, and it is a generally well tolerated therapy. It is the only US FDA-approved oral treatment for the relief of bladder pain or discomfort associated with IC, and data support its role as an important option in the treatment of patients with IC.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Cystitis, Interstitial; Drug Therapy, Combination; Humans; Pelvic Pain; Pentosan Sulfuric Polyester; Treatment Outcome
PubMed: 16706553
DOI: 10.2165/00003495-200666060-00006 -
American Journal of Hematology Mar 1994Pentosan polysulfate is a low-molecular-weight sulfated polysaccharide used as an antithrombotic drug. We present two patients who developed thrombocytopenia and venous... (Review)
Review
Pentosan polysulfate is a low-molecular-weight sulfated polysaccharide used as an antithrombotic drug. We present two patients who developed thrombocytopenia and venous thrombosis during treatment with pentosan polysulfate. The relationship between pentosan polysulfate and thrombocytopenia is supported by platelet aggregation and serotonin release tests. In the light of the literature and our two cases, it appears that pentosan polysulfate alone as standard heparin and low-molecular-weight heparin can induce thrombocytopenia and thrombosis. Platelet counts should therefore be periodically monitored during pentosan polysulfate treatment. In the case of pentosan polysulfate-induced thrombocytopenia, it seems that heparin or low-molecular-weight heparin should not be instituted during the acute phase even if platelet aggregation studies are negative, because of their low sensitivity. After remission of thrombocytopenia, whether or not glycosaminoglycans can be reinstituted, at least temporarily, after antibody had disappeared is still an open question.
Topics: Aged; Aged, 80 and over; Female; Femoral Vein; Humans; Middle Aged; Pentosan Sulfuric Polyester; Platelet Aggregation; Serotonin; Sinus Thrombosis, Intracranial; Thrombocytopenia; Thrombosis
PubMed: 7507640
DOI: 10.1002/ajh.2830450312 -
Ophthalmic Surgery, Lasers & Imaging... Jan 2021To provide new insights into toxic maculopathy secondary to pentosan polysulfate (PPS) utilizing multimodal testing.
BACKGROUND AND OBJECTIVE
To provide new insights into toxic maculopathy secondary to pentosan polysulfate (PPS) utilizing multimodal testing.
PATIENTS AND METHODS
Retrospective case-series of four patients from two academic centers evaluated with multimodal imaging, electrophysiology, dark adaptometry (DA), and genetic testing.
RESULTS
Median age was 58 years, exposure to PPS was 18.5 years, and cumulative dose of was 2,025 grams. Seven of eight eyes had visual acuity of 20/40 or better. Optical coherence tomography (OCT) angiography demonstrated increased choriocapillaris flow voids (54.25%) in cases compared to controls (13.2%). Two subjects had abnormal foveal avascular zone configurations. Two subjects demonstrated collapse of the retinal pigment epithelium nodular excrescences and progressive retinal thinning over 4 to 5 years on OCT. Electrophysiology was normal (3/3 patients), but DA was delayed (2/2 patients).
CONCLUSIONS
The authors describe novel findings of PPS maculopathy, including flow voids in the choriocapillaris. Progressive retinal thinning may suggest a secondary retinal effect. These findings may improve understanding of the pathophysiology. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:13-22.].
Topics: Humans; Macular Degeneration; Middle Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Retinal Pigment Epithelium; Retrospective Studies
PubMed: 33471910
DOI: 10.3928/23258160-20201223-04 -
Obstetrics and Gynecology May 2020Recent studies have implicated long-term pentosan polysulfate use with vision loss from a newly described macular condition. Affected patients report difficulty with...
Recent studies have implicated long-term pentosan polysulfate use with vision loss from a newly described macular condition. Affected patients report difficulty with reading and adjusting to dim lighting, and they occasionally develop severe visual disability. Macular changes resemble those seen in age-related macular degeneration, potentially leading to misdiagnosis. The objectives of this Current Commentary are to summarize studies evaluating the association between pentosan polysulfate use and macular disease, to educate pentosan polysulfate prescribers about the clinical manifestations of this condition, and to provide recommendations for screening at-risk patients.
Topics: Adult; Aged; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Middle Aged; Pentosan Sulfuric Polyester
PubMed: 32282604
DOI: 10.1097/AOG.0000000000003794 -
Ophthalmic Surgery, Lasers & Imaging... Jul 2023To compare the risk factors for the development and progression of pigmentary retinopathy in patients exposed to pentosan polysulfate sodium (PPS).
BACKGROUND AND OBJECTIVE
To compare the risk factors for the development and progression of pigmentary retinopathy in patients exposed to pentosan polysulfate sodium (PPS).
MATERIALS AND METHODS
Retrospective cohort study of patients exposed to PPS with at least two follow-up visits with multimodal imaging.
RESULTS
A total of 97 patients were included (33 with PPS-associated retinopathy and 64 without). The average follow-up was 29.4 months, overall cumulative dose was 1,220 ± 910 g (1,730 ± 870 vs 959 ± 910; < 0.0001), and total PPS duration was 12.1 ± 7.1 years (16.0.2 ± 6.1 vs 10.1 ± 6.9; < 0.0001). The best-corrected visual acuity remained stable during follow-up. At presentation, the average area of the retinopathy in the worse eye was 54.1 ± 50 mm in the PPS-retinopathy group, worsening at a rate of 6.10 ± 10 mm/year. Patients who developed choroidal neovascular membranes (CNVMs) had faster rates of retinopathy progression (11.6 ± 12 vs 3.53 ± 7.6 mm/year, = 0.036). No patient had the exact same gene mutation.
CONCLUSION
PPS-associated pigmentary retinopathy can continue to progress over time, even after discontinuing the medication. CNVM development may be associated with faster rates of retinopathy progression. .
Topics: Humans; Pentosan Sulfuric Polyester; Follow-Up Studies; Retrospective Studies; Retinal Diseases; Retinitis Pigmentosa; Sodium
PubMed: 37310751
DOI: 10.3928/23258160-20230522-02 -
JAMA Ophthalmology Aug 2020
Topics: Disease Progression; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Pharmaceutical Preparations; Retinal Diseases
PubMed: 32644128
DOI: 10.1001/jamaophthalmol.2020.2364 -
Retinal Cases & Brief Reports Nov 2023The purpose of this study was to report a unique case of pentosan polysulfate sodium (PPS) maculopathy with remarkable rapid progression over 2 years. These findings...
PURPOSE
The purpose of this study was to report a unique case of pentosan polysulfate sodium (PPS) maculopathy with remarkable rapid progression over 2 years. These findings show the importance of early detection of macular disease to limit toxic exposure and reduce the risk of progression.
METHODS
Multimodal retinal imaging including fundus autofluorescence, near-infrared reflectance with pseudocolor, and spectral domain optical coherence tomography was performed in an elderly patient with a history of PPS therapy (cumulative dose of 1,205 g) at baseline and 2 years later.
RESULTS
Baseline multimodal retinal imaging failed to show significant macular findings of PPS toxicity in either eye, but on repeat evaluation 2 years later, advanced features of PPS maculopathy were detected in both eyes with fundus autofluorescence, near-infrared reflectance, pseudocolor, and spectral domain optical coherence tomography.
CONCLUSION
This report describes a remarkable case of rapid progression of PPS maculopathy as documented with multimodal retinal imaging. The dramatic progression of macular findings over just 2 years underscores the importance of early detection and prompt withdrawal of therapy, if systemically feasible, to retard the development and rate of progression of PPS maculopathy.
Topics: Humans; Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Macular Degeneration; Retina; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 35385434
DOI: 10.1097/ICB.0000000000001273 -
JAMA Ophthalmology Jan 2022Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to...
IMPORTANCE
Case series have identified a macular condition hypothesized to be associated with the use of pentosan polysulfate sodium (PPS). Observational studies seeking to quantify this association have yielded equivocal results.
OBJECTIVE
To estimate the association between PPS exposure and maculopathy.
DESIGN, SETTING, AND PARTICIPANTS
This disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System from January 2013 through June 2020.
EXPOSURE
Adverse event reports for pentosan polysulfate were selected and compared with adverse event reports associated with drugs taken for the following indications: interstitial cystitis, cystitis, bladder disorder, or bladder pain.
MAIN OUTCOME MEASURES
Retinal adverse events were identified using the retinal disorders Standardized Medical Dictionary for Regulatory Activities (MedDRA) Query, which includes conditions associated with retinal damage attributable to blockage of its blood supply, nutritional deficiencies, toxins, and diseases affecting the retina.
RESULTS
There were 2775 reports available for analysis in the PPS group (of which 1966 were for women [70.9%]) and 6833 reports in the other drugs group (of which 4036 [59.1%] were for women). The proportion of adverse events for any macular event relative to all other events was elevated for the users of PPS compared with those using other interstitial cystitis and bladder pain drugs (proportionate reporting ratio [PRR], 1.21 [95% CI, 1.01-1.44]). With respect to specific retinal conditions, macular degeneration (20 [0.8%] vs 15 [0.2%]), maculopathy (83 [3.4%] vs 2 [0.03%]), retinal dystrophy (3 [0.1%] vs 0), retinal injury (5 [0.2%] vs 0), and retinal toxicity (3 [0.1%] vs 0) were proportionately more common among users of PPS compared with those using other interstitial cystitis and bladder pain drugs, respectively.
CONCLUSIONS AND RELEVANCE
The results of the current study add to the growing evidence that PPS use is associated with an increased risk of maculopathy. Studies that rule out prevalent retinal abnormalities prior to the initiation of PPS would strengthen the current body of literature.
Topics: Anticoagulants; Cystitis, Interstitial; Female; Humans; Macular Degeneration; Male; Pain; Pentosan Sulfuric Polyester; Retinal Dystrophies
PubMed: 34792558
DOI: 10.1001/jamaophthalmol.2021.4778