Risk and Dose–Response Relationship for Pentosan Polysulfate Sodium Maculopathy
Bibliographic record
Abstract
TOPIC: To determine the pooled relative risk (RR) of pentosan polysulfate sodium maculopathy (PPSM) in patients using pentosan polysulfate sodium (PPS) and model the dose-response relationship of this association from existing literature. CLINICAL RELEVANCE: Pentosan polysulfate sodium maculopathy is an acquired, progressive retinal pigmentary disease associated with oral PPS use. Although several observational studies suggest a dose-response relationship of this association, to date, there remains no literature-pooled synthesis on the risk of PPSM across strata of cumulative dose. METHODS: Systematic review and meta-analysis (CRD42024623179). Medline, Embase, and Cochrane Central Register of Controlled Trials were searched from inception to September 15, 2024. We included studies reporting the incidence of PPS-associated maculopathy and including cumulative PPS dose information. Two independent reviewers completed study screening, data extraction, and risk of bias (ROB) assessment using the ROB in nonrandomized studies of exposures tool, and a third reviewer was consulted to resolve conflicts. The primary outcome was the RR of PPSM among patients exposed to PPS compared with nonexposed individuals, stratified by cumulative PPS dose. RESULTS: = 63.7%). CONCLUSION: Moderate certainty evidence supports a dose-dependent relationship between PPS exposure and PPSM risk, whereas higher cumulative doses significantly increase maculopathy risk. This result supports that patients should be tapered to an effective minimal dose and that they should be subject to interval maculopathy screening, especially for patients with greater cumulative dose. Future research should incorporate patient-level data to better control for potential confounding. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".