Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy
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Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy : Results from a Randomized Clinical Trial. / Schaub, Friederike; Schiller, Petra; Hoerster, Robert; Kraus, Daria; Holz, Frank G; Guthoff, Rainer; Agostini, Hansjürgen; Spitzer, Martin S; Wiedemann, Peter; Lommatzsch, Albrecht; Boden, Karl T; Dimopoulos, Spyridon; Bemme, Sebastian; Tamm, Svenja; Maier, Mathias; Roider, Johann; Enders, Philip; Altay, Lebriz; Fauser, Sascha; Kirchhof, Bernd; PRIVENT Study Group.
In: OPHTHALMOLOGY, Vol. 129, No. 10, 10.2022, p. 1129-1141.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy
T2 - Results from a Randomized Clinical Trial
AU - Schaub, Friederike
AU - Schiller, Petra
AU - Hoerster, Robert
AU - Kraus, Daria
AU - Holz, Frank G
AU - Guthoff, Rainer
AU - Agostini, Hansjürgen
AU - Spitzer, Martin S
AU - Wiedemann, Peter
AU - Lommatzsch, Albrecht
AU - Boden, Karl T
AU - Dimopoulos, Spyridon
AU - Bemme, Sebastian
AU - Tamm, Svenja
AU - Maier, Mathias
AU - Roider, Johann
AU - Enders, Philip
AU - Altay, Lebriz
AU - Fauser, Sascha
AU - Kirchhof, Bernd
AU - PRIVENT Study Group
N1 - Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.
PY - 2022/10
Y1 - 2022/10
N2 - PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD.DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis.PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry.METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy.MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.
AB - PURPOSE: Proliferative vitreoretinopathy (PVR) is the major cause for surgical failure after primary rhegmatogenous retinal detachment (RRD). So far, no therapy has been proven to prevent PVR. Promising results for 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) in high-risk eyes have been reported previously. The objective of this trial was to examine the effect of adjuvant intravitreal therapy with 5-FU and LMWH compared with placebo on incidence of PVR in high-risk patients with primary RRD.DESIGN: Randomized, double-blind, controlled, multicenter, interventional trial with 1 interim analysis.PARTICIPANTS: Patients with RRD who were considered to be at high risk for PVR were included. Risk of PVR was assessed by noninvasive aqueous flare measurement using laser flare photometry.METHODS: Patients were randomized 1:1 to verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) and placebo (balanced salt solution) intravitreally applied during routine pars plana vitrectomy.MAIN OUTCOME MEASURES: Primary end point was the development of PVR grade CP (full-thickness retinal folds or subretinal strands in clock hours located posterior to equator) 1 or higher within 12 weeks after surgery. For grading, an end point committee assessed fundus photographs. Secondary end points included best-corrected visual acuity and redetachment rate. A group sequential design with 1 interim analysis was applied using the O'Brien and Fleming boundaries. Proliferative vitreoretinopathy grade CP incidence was compared using a Mantel-Haenszel test stratified by surgeon.RESULTS: A total of 325 patients in 13 German trial sites had been randomized (verum, n = 163; placebo, n = 162). In study eyes, mean laser flare was 31 ± 26 pc/ms. No significant difference was found in PVR rate. Primary analysis in the modified intention-to-treat population results were: verum 28% vs. placebo 23% (including not assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77. Those in the per-protocol population were: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47. None of the secondary end points showed any significant difference between treatment groups. During the study period, no relevant safety risks were identified.CONCLUSIONS: Rate of PVR did not differ between adjuvant therapy with 5-FU and LMWH and placebo treatment in eyes with RRD.
KW - Dalteparin/therapeutic use
KW - Double-Blind Method
KW - Fluorouracil
KW - Heparin/therapeutic use
KW - Heparin, Low-Molecular-Weight/therapeutic use
KW - Humans
KW - Retinal Detachment/surgery
KW - Vitrectomy/adverse effects
KW - Vitreoretinopathy, Proliferative/drug therapy
U2 - 10.1016/j.ophtha.2022.05.024
DO - 10.1016/j.ophtha.2022.05.024
M3 - SCORING: Journal article
C2 - 35680097
VL - 129
SP - 1129
EP - 1141
JO - OPHTHALMOLOGY
JF - OPHTHALMOLOGY
SN - 0161-6420
IS - 10
ER -