Pneumatic Vitreolysis with C3F8 for Vitreomacular Traction with and without Macular Hole: DRCR Retina Network Protocols AG and AH

Written by: Joshua D. Levinson, MD

August 2021

Chan CK, Mein CE, Glassman AR, et al. Pneumatic Vitreolysis with C3F8 for Vitreomacular Traction with and without Macular Hole: DRCR Retina Network Protocols AG and AH. Ophthalmol. 2021

Treatment options for symptomatic vitreomacular traction (VMT) and macular hole (MH) include observation, pars plana vitrectomy and vitreolysis. Chemical vitreolysis with ocriplasmin has fallen out of favor due to medication-related complications and the high cost of the drug. In recent years, pneumatic vitreolysis (PVL), in which a gas bubble is used to release VMT, has garnered increased attention and support.

Chan and colleagues report the results of two multi-centered prospective trials to evaluate the safety and efficacy of PVL for symptomatic VMT with (protocol AG) and without (protocol AH) macular hole as part of the DRCR Retina Network. Both studies were terminated early by the safety committee due to risk of retinal tear and detachment associated with PVL.

Protocol AG: Randomized Clinical Trial Assessing the Effects of Pneumatic Vitreolysis on Vitreomacular Traction

Protocol AG evaluated PVL in patients with central VMT (adhesion < 3000 microns) without macular or lamellar hole. Study eyes were randomly assigned 1:1 to either PVL (0.3mL C3F8 gas) or sham injection. The investigators planned to enroll 124 patients, but due to early termination of the study, only 46 participants were included.

Twenty-three participants in the PVL group (96%) and 22 in the sham group (100%) completed the 24-week visit. At 24 weeks, the incidence of central VMT release without rescue vitrectomy was 78% (18 of 23) in the treatment group and 9% (2 of 22) in the sham group (P<0.001). Two eyes in the PVL group required vitrectomy to treat retinal detachment after the VMT release.

Protocol AH: Single-arm Study Assessing the Effects of Pneumatic Vitreolysis on Macular Hole

Protocol AH evaluated PVL (0.3mL C3F8) for full-thickness MH < 250 microns in which the central vitreomacular adhesion was 3000 microns or less. Patients were asked to perform face-down positioning for four days, at least 50% of the time.

MH closure without rescue vitrectomy was achieved in 10 of 35 eyes (29%). Among the 34 patients that completed the 24-week visit, rescue vitrectomy was performed in 23 of 34 eyes (68%). Reasons for vitrectomy included macular hole (20 eyes) and retinal detachment (4 eyes).

Combined Safety Outcomes from Both Protocols

Of 59 eyes undergoing PVL, 7 of 59 (12%) experienced a rhegmatogenous retinal detachment (n=6) or retinal tear (n=1). The incidence of retinal tear or detachment was 8% in the VMT group and 14% in the MH group.


These studies demonstrated that PVL is effective for releasing VMT but less effective for treating MH. The MH closure rate of 29% compares poorly to success rates of 80-100% reported for vitrectomy with ILM peeling and gas.

Most concerning, the studies were terminated early due to retinal tear or detachment occurring in 12% of patients receiving PVL. While PVL remains a treatment option in appropriately-selected patients with symptomatic VMT, it is important to counsel patients on the risk of retinal tear or detachment and monitor them appropriately.