Pretest on mTOR Inhibition in PVR Prevention
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Proliferative vitreoretinopathy (PVR) remains the leading cause of surgical failure after rhegmatogenous retinal detachment (RRD) repair, affecting up to 10% of cases. Despite decades of research, no pharmacologic agent has been formally approved for PVR prevention. A recent multicenter cohort study published in JAMA Ophthalmology may signal a turning point.
🔬 Study Overview
Researchers analyzed data from 681 patients across 15 countries who underwent primary RRD repair while receiving systemic mammalian target of rapamycin (mTOR) inhibitor (MTI) therapy—such as sirolimus, everolimus, or temsirolimus—for unrelated medical conditions. These patients were matched against 47,626 controls not exposed to MTIs.
📉 Key Findings
At 1-year follow-up, MTI therapy was associated with:
| Outcome | MTI Group | Control Group | Relative Risk (RR) | P Value |
|---|---|---|---|---|
| Subsequent RD | 3.7% | 6.3% | 0.58 (95% CI: 0.36–0.94) | .03 |
| PPV for RD | 6.2% | 10.9% | 0.57 (95% CI: 0.40–0.82) | <.001 |
| Complex RD Repair | 4.8% | 8.1% | 0.60 (95% CI: 0.40–0.91) | .01 |
No significant difference was found when comparing MTI therapy to systemic methotrexate (MTX) therapy, suggesting comparable efficacy.
🧬 Mechanistic Rationale
MTIs inhibit the PI3K/AKT/mTOR pathway, implicated in glial proliferation and fibrosis—hallmarks of PVR. Prior in vitro studies and animal models support this pathway’s role in retinal scarring and inflammation.
⚠️ Safety Profile
MTI use was associated with increased rates of:
- Stomatitis (1.5% vs 0%)
- Hypertension (46% vs 31.3%)
- Hyperlipidemia (25% vs 19.5%)
- Dermatitis (10.3% vs 5.9%)
These findings underscore the need for careful patient selection and monitoring.
🧠Clinical Implications
This study suggests systemic MTIs may offer a protective effect against PVR-related complications post-RRD repair. While causality cannot be confirmed, the data support further investigation into MTIs—potentially via intravitreal delivery or combination therapy with MTX.
đź“Ś Takeaway
Modulating mTOR signaling could represent a viable strategy for PVR prophylaxis. Prospective trials are warranted to validate efficacy, optimize dosing, and assess long-term safety.
“Patients who underwent initial RD repair and were concomitantly being treated with systemic MTI therapy were less likely to develop a subsequent PVR-related RD compared with matched patients not exposed to systemic MTI therapy.”
— Alsoudi et al., JAMA Ophthalmology, 2025
Citation:
Alsoudi AF, Loya A, Wai K, et al. Mammalian Target Rapamycin Inhibition as a Therapeutic Target for Prevention of Proliferative Vitreoretinopathy. JAMA Ophthalmol. 2025;143(9):777-784. doi:10.1001/jamaophthalmol.2025.2497
