Table 1.
Major Studies of IVT MTX for PVR.
| Study a | Study Type | Groups | Outcome Measures | Results/Conclusions |
|---|---|---|---|---|
| Sunalp et al
13
PMID 6245019 |
Preclinical; rabbit dermal fibroblast injection in rabbit eyes | • BSS • Triamcinolone • Adriamycin (doxorubicin) • 5-FU • MTX • Trifluridine |
• Percentage of animals with RD after treatment | • Significantly fewer RDs in adriamycin, triamcinolone, and 5-FU
treated eyes • No benefit to MTX or trifluridine treatment |
| Eliott and Stryjewski
14
US Patent 10,272,089 |
Preclinical; in vitro assays of cells derived from PVR extracted during human retina surgery | • Control (growth medium) • 400 µg MTX • 200 µg MTX • 100 µg MTX |
• Growth and cellular morphology after 72 h, 1 wk, and 2 wk | • 72 h: Similar growth of PVR cells in all groups with typical
epithelioid morphology • 1 week: All cells exposed to MTX showed growth inhibition, lack of confluency, and less epithelioid-appearing; continued growth in control plate • 2 wk: Similar findings to week 1 with continued growth in the control plates |
| Amarnani et al
15
PMID 28777835 |
Preclinical; in vitro assays of 6 PVR specimens extracted during human retina surgery | • Vehicle control vs MTX (100 µM, 200 µM, or 400 µM) treatment of PVR-derived cell cultures in vitro | • Cell density • Ki-67 immunofluorescence (proliferation marker) • Caspase-3/7 immunofluorescence (apoptosis marker) |
• Reduced cell density 6 wk after MTX treatment (not dose
dependent) • Reduced cell proliferation 24 h after MTX treatment (dose dependent) • Increased apoptosis 6 wk after MTX treatment (dose dependent) |
| Eliott and Stryjewski
14
US Patent 10,272,089 |
Prospective nonrandomized single-arm pilot study | • 10 patients requiring PPV for RD repair with serial postop IVT MTX injections | • Development of PVR • Rate of redetachment • Final visual acuity |
• 0/10 eyes developed PVR during injection period • 2/10 eyes had redetachment • Median postop visual acuity 20/200 • Mild corneal toxicity in 1/10 eyes |
| Benner et al
5
PMID 31179399 |
Retrospective chart review of series of patients with PVR | • Serial low-dose MTX IVT injection after RD surgery (5 patients) | • 6-month visual acuity • Re-detachment rate |
• Final VA range from 20/60 to HM • Redetachment in 0/5 patients • Mild corneal toxicity in 1/5 patients |
| Nourinia et al
16
PMID 28777835 [15] |
Prospective single-arm interventional pilot study | • 11 patients with RD and PVR, with 250 µg MTX injected into silicone oil after RD surgery, then repeat injections @ 3 wk + 6 wk | • Postop redetachment rate • Postop VA |
• 0/11 redetachment rate posteriorly; 2/11 peripheral retina
re-detachment rate • Improved mean postop logMAR VA: 1.02 ± 0.51 (postop) vs 2.62 ± 0.04 (preop) (P = .003) |
| Ghasemi Falavarjani et al
17
PMID 31136255 |
Prospective randomized comparative interventional | • Intra-silicone-oil injection of 250 µg MTX after RD surgery
(n, 22) • No MTX after RD surgery (n, 22) |
• Postop redetachment rate • Final postop VA |
• 1/22 (MTX) vs 5/22 (control) eyes had redetachment
(P = .18) • Final mean logMAR VA: 1.51 ± 0.63 (MTX) vs 1.57 ± 0.44 (control) (P = .77) |
| Roca et al
18
PMID 33900444 |
Retrospective case-control study of eyes with RD and PVR | • Eyes with weekly MTX injections • 9 control eyes |
• Postop reattachment rate • Final postop VA |
• 86% of MTX eyes completely reattached vs. 22% of control eyes
completely reattached (P = .0406) • Final VA (logMAR mean) 1.92 (MTX) vs 2.05 (control, P, NS) |
| Sadaka et al
19
PMID 27698550 |
Retrospective chart review of patients with RD having PPV; judged to be at risk for PVR | • 29 patients requiring PPV for RD repair with 40 mg MTX added to 500 mL BSS during PPV | • Improved or stable VA at 6 months • VA ≥ 20/200 • Recurrent PVR without RD • Redetachment requiring reoperation |
• 24/29 eyes with improved or stable VA • 19/29 eyes with VA ≥ 20/200 • 3/29 eyes with recurrent PVR without RD • 3/29 eyes with redetachment requiring reoperation |
| Jahangir et al
20
PMID 34462712 |
Prospective nonrandomized single-arm study | • 30 patients with or at risk for PVR requiring PPV for RD repair with MTX added to BSS bottle intraop | • Reattachment rate • Final VA |
• Retina remained reattached at 4 mo in 24/30 eyes • Postop logMAR BCVA 1.01 vs. 1.35 preoperative (P < .05) |
| El Baha et al
2
PMID 34336257 |
Prospective nonrandomized case series of MTX added to intraop BSS vs retrospective chart review of controls | • I: RD with PVR +MTX (n = 42) • II: Recent RD, high risk for PVR, +MTX (n = 35) • III: Recent RD, no risk for PVR, +MTX (n = 24) • Ia: Retrospective with established PVR (n = 30) • IIa: Retrospective with high risk for PVR (n = 30) • IIIa: Retrospective with no risk for PVR (n = 29) |
• Anatomic outcome of retinal reattachment • Final VA |
• Group I (31/42 reattachment rate) vs. Group Ia (26/30
reattachment rate) (P = .2) • Group II (27/35 reattachment rate) vs. Group IIa (28/30 reattachment rate) (P = .07) • Group III (23/24 reattachment rate) vs. Group IIIa (23/29 reattachment rate) (P = .07) • Group I (0.11 ± 0.15 BCVA) vs. Group Ia (0.04 ± 0.04) (P = .07) • Group II (0.15 ± 0.12 BCVA) vs. Group IIa (0.08 ± 0.06) (P = .03) • Group III (0.16 ± 0.14 BCVA) vs. Group IIIa (0.08 ± 0.05) (P = .03) |
Abbreviations: 5-FU, 5-fluorouracil; BCVA, best-corrected visual acuity; BSS, balanced salt solution; HM, hand motion vision; IVT, intravitreal; MTX, methotrexate; NS, not significant; PPV, pars plana vitrectomy; PVR, proliferative vitreoretinopathy; RD, retinal detachment; VA, visual acuity.
a
First author.