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Retinal Cases & Brief Reports Nov 2023The purpose of this study was to describe the characteristic pattern of progression of pentosan polysulfate (PPS) maculopathy with multimodal retinal imaging in two...
BACKGROUND/PURPOSE
The purpose of this study was to describe the characteristic pattern of progression of pentosan polysulfate (PPS) maculopathy with multimodal retinal imaging in two patients, including one with over 9 years of follow-up.
METHODS
Two patients with PPS maculopathy were sequentially evaluated with near-infrared reflectance (NIR) and optical coherence tomography.
RESULTS
Near-infrared reflectance showed characteristic centrifugal progression of the parafoveal hyperreflective lesions toward the vascular arcades with the development of hyporeflective areas in both cases. Optical coherence tomography demonstrated focal retinal pigment epithelium (RPE) thickening that corresponded to the hyperreflective lesions on NIR. On subsequent optical coherence tomography scans, the hyperreflective areas resolved with the development of ellipsoid zone attenuation, RPE disruption, and atrophy, which colocalized with hyporeflectivity on NIR.
CONCLUSION
This report describes the progression of pentosan polysulfate maculopathy over almost 10 years of PPS treatment and highlights the importance of NIR as a tool for the diagnosis and monitoring of PPS maculopathy. Pentosan polysulfate lesions present as areas of focal RPE thickening with ensuing development of ellipsoid zone loss and RPE drop-out. The pathophysiology of PPS toxicity is unknown and may either result from primary RPE or choroidal toxicity.
Topics: Humans; Pentosan Sulfuric Polyester; Retina; Retinal Diseases; Macular Degeneration; Retinal Pigment Epithelium; Tomography, Optical Coherence; Fluorescein Angiography
PubMed: 35344532
DOI: 10.1097/ICB.0000000000001276 -
Mayo Clinic Proceedings Jun 2021
Topics: Adult; Cystitis, Interstitial; Humans; Macular Degeneration; Middle Aged; Pentosan Sulfuric Polyester
PubMed: 34088428
DOI: 10.1016/j.mayocp.2021.04.002 -
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 -
International Urogynecology Journal May 2021Oral pentosan polysulphate (PPS) has been used in the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) for almost 35 years. However, in some recent... (Review)
Review
INTRODUCTION AND HYPOTHESIS
Oral pentosan polysulphate (PPS) has been used in the treatment of bladder pain syndrome/interstitial cystitis (BPS/IC) for almost 35 years. However, in some recent studies, questions have been raised about its efficacy in treating this condition. We aimed to evaluate the published medical literature and discuss the clinical utility of oral PPS in the treatment of BPS/IC.
METHODS
PUBMED was searched for BPS/IC, treatment and PPS. Of the initial 398 articles screened, 7 randomized controlled trials, 3 systematic reviews and 3 meta-analyses were finally included in this study (Fig. 1). Other relevant literature such as observational studies and various clinical guidelines was also reviewed. The inclusion criteria, intervention methodology and end points of the studies were examined.
RESULTS
Of the seven RCTs, five found a clear beneficial role of oral PPS in IC/BPS. The only study which did not have cystoscopy as a diagnostic and inclusion criterion failed to show any benefit of oral PPS compared to placebo. Two out of three meta-analyses clearly concluded that oral PPS had a positive role to play in the treatment of BPS/IC. Various open-label studies did conclude in favour of oral PPS as a treatment modality for these patients.
CONCLUSION
Oral PPS remains a useful pharmacological agent for treatment of BPS/IC, even though it may be effective only in a subgroup of patients.
Topics: Cystitis, Interstitial; Cystoscopy; Humans; Pentosan Sulfuric Polyester; Randomized Controlled Trials as Topic
PubMed: 32894327
DOI: 10.1007/s00192-020-04517-9 -
Biochemical Pharmacology May 2020Hepcidin peptide is crucial in the regulation of systemic iron availability controlling its uptake from the diet and its release from the body storage tissues. Hepcidin...
Hepcidin peptide is crucial in the regulation of systemic iron availability controlling its uptake from the diet and its release from the body storage tissues. Hepcidin dysregulation causes different human disorders ranging from iron overload (e.g. hemochromatosis) to iron deficiency (e.g. anemia). Hepcidin excess is common in the Anemia of Chronic Diseases or Anemia of Inflammation and in the genetic form of anemia named IRIDA; the pharmacological downregulation of hepcidin in these disorders could improve the anemia. Commercial heparins were shown to be strong inhibitors of hepcidin expression, by interfering with BMP6/SMAD pathway. The non-anti-coagulant heparins, modified to abolish the anti-thrombin binding site, were equally potent and could be used to improve iron status. To perform its anti-hepcidin activity heparin needs 2O- and 6O-sulfation and an average molecular weight (MW) up to 4000-8000 Dalton, depending on the sulfation level. The pentosane polysulfate (PPS), which shares with heparin a high degree of sulfation, is a compound with low anti-coagulant activity that is already in use for pharmaceutical treatment. In the present work we analyzed the anti-hepcidin activity of PPS in vitro and in vivo. We found that it acts as a strong inhibitor of hepcidin expression in HepG2 cells with an effect already visible after 2-3 h of treatment. It also suppressed hepcidin in mice in a dose dependent manner after 3 h and with a significant redistribution of systemic iron without evident side effects. PPS is also able to abolish the LPS dependent hepcidin upregulation similarly to that showed for heparin derivatives. These results suggest PPS as an interesting compound to control hepcidin in vivo.
Topics: Administration, Oral; Animals; Gene Expression; Hep G2 Cells; Hepcidins; Humans; Injections, Subcutaneous; Liver; Male; Mice; Mice, Inbred C57BL; Pentosan Sulfuric Polyester
PubMed: 32088260
DOI: 10.1016/j.bcp.2020.113867 -
Canadian Journal of Ophthalmology.... Apr 2024Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis....
OBJECTIVE
Pentosan polysulfate (PPS; ELMIRON, Janssen Pharmaceuticals, Titusville, NJ) is a U.S. Food and Drug Administration-approved oral medication for interstitial cystitis. Numerous reports have been published detailing retinal toxicity with the use of PPS. Studies characterizing this condition are primarily retrospective, and consequently, alert and screening systems need to be developed to actively screen for this disease. The goal of this study was to characterize ophthalmic monitoring trends of a PPS-using patient sample to construct an alert and screening system for monitoring this condition.
METHODS
A single-institution retrospective chart review was conducted between January 2005 and November 2020 to characterize PPS use. An electronic medical record (EMR) alert was constructed to trigger based on new PPS prescriptions and renewals offering ophthalmology referral.
RESULTS
A total of 1407 PPS users over 15 years was available for characterization, with 1220 (86.7%) being female, the average duration of exposure being 71.2 ± 62.6 months, and the average medication cumulative exposure being 669.7 ± 569.2 g. A total of 151 patients (10.7%) had a recorded visit with an ophthalmologist, with 71 patients (5.0%) having optical coherence tomography imaging. The EMR alert fired for 88 patients over 1 year, with 34 patients (38.6%) either already being screened by an ophthalmologist or having been referred for screening.
CONCLUSIONS
An EMR support tool can improve referral rates of PPS maculopathy screening with an ophthalmologist and may serve as an efficient method for longitudinal screening of this condition with the added benefit of informing pentosan polysulfate prescribers about this condition. Effective screening and detection may help determine which patients are at high risk for this condition.
Topics: Humans; Female; Male; Pentosan Sulfuric Polyester; Retrospective Studies; Eye; Retinal Diseases; Face
PubMed: 36878265
DOI: 10.1016/j.jcjo.2023.01.019 -
International Immunopharmacology May 2022Ulcerative colitis (UC) primarily affects the mucosa of the distal colon. Dysregulated immune response in genetically-prone persons is claimed to be responsible for...
Ulcerative colitis (UC) primarily affects the mucosa of the distal colon. Dysregulated immune response in genetically-prone persons is claimed to be responsible for chronic intestinal inflammation. This study aimed to explore the efficacy and the hematological effects of pentosan polysulfate sodium (PPS) in a dextran sulfate sodium (DSS)-induced colitis model. Forty C57BL/6 female mice were equally divided into five groups: control group, DSS-colitis group, DSS-colitis treated with 5-aminosalicylic acid, DSS-colitis treated with PPS, and DSS-colitis treated with both drugs. Disease activity index (DAI) and colon length were calculated. Colonic IL-6 and IL-35 levels were assayed by ELISA. IL-35 gene expression was evaluated by qRT-PCR. Colon tissue samples were examined by H&E stain and immunohistochemistry (IHC) of Ki67. The colitis group subjected to combined treatment showed the best outcome with significant improvement of DAI and increased colon length. Colonic IL-6 was significantly lower in both PPS- and combination-treated groups accompanied by a significantly higher IL-35 level and its EBI3 subunit mRNA expression. However, the PPS-treated colitis group showed higher gene expression of IL-35 EBI3 subunit by 1.5-fold compared with the combined group. The colon mucosa and crypts were significantly preserved in mice treated with both drugs with the best Ki67 positive cell density. PPS is a safe and promising drug in the treatment of UC as it exerted the best positive effect on the anti-inflammatory IL-35 level and gene expression. However, superior improvement of DAI was seen when PPS was added to ASA with a greater mucosal proliferation and repair.
Topics: Animals; Colitis; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Female; Interleukins; Mesalamine; Mice; Mice, Inbred C57BL; Pentosan Sulfuric Polyester; Signal Transduction
PubMed: 35247859
DOI: 10.1016/j.intimp.2022.108620 -
Ophthalmology. Retina Mar 2022Explore the spectrum of clinical manifestations of pentosan polysulfate sodium (PPS) maculopathy observed across a range of practice settings.
PURPOSE
Explore the spectrum of clinical manifestations of pentosan polysulfate sodium (PPS) maculopathy observed across a range of practice settings.
DESIGN
Multi-institutional retrospective study.
PARTICIPANTS
Patients exhibiting findings suggestive of PPS maculopathy identified from April 30, 2019, to December 4, 2020.
METHODS
Members of the Macula Society submitted cases of presumed PPS maculopathy for consideration in this series. Diagnosis was confirmed by masked review of fundus imaging. Clinical characteristics of confirmed cases were summarized with descriptive statistics.
MAIN OUTCOME MEASURES
Pentosan polysulfate exposure characteristics and fundus imaging features.
RESULTS
There were 74 patients with PPS maculopathy included in the current study. Median (interquartile range) age at diagnosis was 62.0 years (56.0-65.8). The median duration of exposure to PPS was 14.0 years (10.2-18.9), with a median cumulative exposure of 1.5 kg (0.9-2.4). The most common presenting symptom was decreased or blurry vision (66.2%), followed by prolonged dark adaption or nyctalopia (32.4%). The most common referral diagnosis was age-related macular degeneration (54.1%); 16.2% of patients were referred for suspected PPS maculopathy. Novel imaging findings emerged, including highly asymmetric disease in 2 patients and a prominent vitelliform maculopathy in 2 patients.
CONCLUSIONS
Most patients with PPS maculopathy exhibit characteristic findings on multimodal fundus imaging in the setting of high cumulative exposure to the oral drug. Some patients in the current study manifested novel imaging findings, expanding our understanding of the phenotypic spectrum of this condition. We recommend considering standardized ophthalmic screening of patients treated with PPS.
Topics: Anticoagulants; Humans; Macula Lutea; Macular Degeneration; Pentosan Sulfuric Polyester; Retinal Diseases; Retrospective Studies
PubMed: 34298229
DOI: 10.1016/j.oret.2021.07.004 -
BMC Musculoskeletal Disorders Mar 2021Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Alphaviruses, such as Ross River (RRV) and chikungunya virus (CHIKV), cause significant global morbidity, with outbreaks of crippling joint inflammation and pain, leaving patients incapacitated for months to years. With no available vaccine or specific therapeutic for any alphaviral disease, and a growing economic and public health burden, there is a serious need for the development of specific therapies.
METHODS
This study evaluated the safety and efficacy of pentosan polysulfate sodium (PPS) in subjects with RRV-induced arthralgia in a double-blind, placebo-controlled trial. Twenty subjects were randomized 2:1 to subcutaneous PPS (2 mg/kg) or placebo (sodium chloride 0.9%) twice weekly for 6 weeks. Safety evaluation included physical examination, concomitant medications, and laboratory findings. Efficacy assessments included change from baseline in joint function (hand grip strength and RAPID3) and quality of life (SF-36) at Days 15, 29, 39 and 81 after treatment initiation. Inflammatory and cartilage degradation biomarkers were exploratory endpoints.
RESULTS
PPS was well tolerated, with a similar proportion of subjects reporting at least one treatment-emergent adverse event (TEAE) in the treatment and placebo groups. Injection site reactions were the most common TEAE and occurred more frequently in the PPS group. Dominant hand grip strength and SF-36 scores improved with PPS at all time points assessed, with hand grip strength improvement of 6.99 kg (p = 0.0189) higher than placebo at Day 15. PPS showed significant improvements versus placebo in adjusted mean relative change from baseline for RAPID3 Pain (p = 0.0197) and Total (p = 0.0101) scores at Day 15. At the conclusion of the study overall joint symptoms, assessed by RAPID3, showed near remission in 61.5% of PPS subjects versus 14.3% of placebo subjects. Additionally, PPS treatment improved COMP, CTX-II, CCL1, CXCL12, CXCL16 and CCL17 biomarker levels versus placebo.
CONCLUSIONS
Overall, the improvements in strength and joint symptoms warrant further evaluation of PPS as a specific treatment for RRV-induced and other forms of arthritis.
TRIAL REGISTRATION
This trial is registered at the Australian New Zealand Clinical Trials Registry # ACTRN12617000893303 .
Topics: Arthralgia; Australia; Double-Blind Method; Hand Strength; Humans; Pentosan Sulfuric Polyester; Quality of Life; Ross River virus; Treatment Outcome
PubMed: 33711991
DOI: 10.1186/s12891-021-04123-w -
European Journal of Ophthalmology Dec 2021Pentosan polysulfate-related maculopathy is a recently described clinical entity, related to dose and long term use of this medication, and may progress despite drug...
BACKGROUND
Pentosan polysulfate-related maculopathy is a recently described clinical entity, related to dose and long term use of this medication, and may progress despite drug cessation. Cystoid macular oedema (CMO) has been reported in some cases, but there are few reports of treatment outcomes in the literature.
AIMS
We present the case of a 55 year old female, with CMO secondary to pentosan polysulfate maculopathy, that was responsive to treatment with both intravitreal anti-VEGF and steroid injections, stabilising vision over a four year follow up period.
CONCLUSIONS
This is the first report, to our knowledge, of CMO related to pentosan polysulfate maculopathy responding to intravitreal steroid injections, broadening the therapeutic options for preserving vision in these patients.
PubMed: 34866437
DOI: 10.1177/11206721211066387