Mechanisms of Inflammation in Proliferative Vitreoretinopathy: From Bench to Bedside

Table 2

Outcomes of randomized, controlled, clinical trials in humans with and without proliferative vitreoretinopathy (PVR).

Agent(s)	Dose and target	Patients	Treatment groups	Outcomes	Ref.
5-FU and LMWH	200 μg/mL 5-FU and 5 IU/mL LMWH,; 5-FU inhibits DNA synthesis and fibroblast proliferation; LMWH binds fibronectin, bFGF, PDGF, and other growth factors	174 patients at; High risk for PVR	Intravitreal inf.: placebo versus 5-FU and LMWH	Placebo: 23/87 (26.4%) postoperative PVR, 22/87 (25.3%) reoperation with 16/22 (72.7%) due to PVR 5-FU and LMWH: 11/87 (12.6%, 𝑃=0.02*) postoperative PVR, 17/87 (19.5%) reoperation with 9/17 (52.9%) due to PVR; No difference in visual acuity outcomes, nor complication rates	[68]
5-FU and LMWH	200 μg/mL 5-FU and 5 IU/mL LMWH,; For target, see Row 1 above	157 patients with established grade C PVR	Intravitreal inf.: placebo versus 5-FU and LMWH	Placebo: 51% (𝑛=84) retinal reattachment (RRA); at 6 months with no reoperation; 5-FU and LMWH: 56% (𝑛=73) RRA at 6 months with no reoperation (𝜒^2=2.9, 𝑃=0.59)	[69]
5-FU and LMWH	200 μg/mL 5-FU and 5 IU/mL LMWH,; For target, see Row 1 above	615 patients with unselected primary RRD	Intravitreal inf.: placebo versus 5-FU and LMWH	Placebo: 86.8% RRA, 4.9% development of PVR, (𝑛=288); 5-FU and LMWH: 82.3% RRA (𝑃=0.12),; 7% development of PVR (𝑃=0.072), (𝑛=327); No difference in final mean visual acuity	[70]
Dauno-rubicin	7.5 μg/mL,; inhibits cell proliferation; and migration	286 patients; with advanced preoperative PVR after RRD	Surgery only versus surgery with intravitreal inf. of daunorubicin	Surgery only: 73/135 (54.1%) RRA with no reoperation at 6 months; Surgery and daunorubicin: 89/142 (62.7%) RRA; with no reoperation a 6-month post-op (𝑃=0.07); Daunorubicin: less reoperation 1st year postop (46.1% versus 34.5%, 𝑃=0.005*)	[75]
13-cis-retinoic acid (13cRA)	10 mg orally, 2x daily, for 8 weeks,; inhibits proliferation; of RPE cells	35 patients with primary retinal detachment and PVR	Surgery only versus surgery and oral 13cRA	Surgery only: 12/19 (63.2%) RRA at one-year follow-up; Surgery and 13cRA: 15/16 (93.8%) RRA at one-year followup (𝑃=0.047*)	[80]

5-FU: 5-fluorouracil. LMWH: low-molecular-weight heparin. bFGF: basic fibroblast growth factor. PDGF: platelet-derived growth factor. inf.: infusion. RRD: rhegmatogenous retinal detachment. post-op: postoperative. *statistically significant difference compared to control. RRA: retinal reattachment. RPE: retinal pigment epithelium. 13cRA: 13-cis-retinoic acid. Ref: Reference number.