March 9, 2018 Conference
Dr. Tommy Stryjewski, MEEI/Harvard Medical School
Dr. Leo Kim, Massachusetts Eye and Ear Infirmary
PURPOSE: Methotrexate is an antiproliferative and anti-inflammatory agent with minimal ocular and systemic toxicity, and it is a good candidate to study for the prevention of proliferative vitreoretinopathy (PVR). The purpose of this study was to attempt to prevent recurrent retinal detachment (RD) due to PVR in a series of high risk eyes.
METHODS: We conducted a prospective study of 10 eyes with RD due to PVR. Eight of these eyes had undergone multiple procedures for recurrent RD and two eyes had RD after primary repair of severe open globe injury. All 10 eyes underwent surgery which included retinectomy and silicone oil. A total of 10 intravitreal injections of methotrexate (400 mcg/0.1 ml) were administered per patient: one at the conclusion of surgery, eight weekly injections from postoperative week 1 through week 8, and one additional injection at postoperative week 12. Outcomes included recurrent RD and PVR. We then treated an additional 16 eyes with 13 injections each.
In addition, fibrous proliferations excised at the time of PVR surgery were grown in culture. The cells were exposed to varying concentrations of methotrexate.
RESULTS: There was 99% compliance, as 99 out of a possible 100 total injections were given. All patients had 3-4 years of follow-up except for one patient who had only 4 months. One trauma patient developed severe PVR at month 4 (one month after the last injection), which is much later than expected. Three eyes developed RD without any observable evidence of PVR. Only one eye developed an observable epiretinal membrane and it was clinically insignificant. For the additional 16 eyes, only 1 eye developed recurrent RD due to PVR.
Cultured human PVR cells exhibited uncontrolled proliferation and extracellular band formation. Methotrexate exposure resulted in decreased cell proliferation and decreased band formation in a dose response manner.
CONCLUSIONS: The use of multiple intravitreal methotrexate injections is a reasonable approach for the prevention of PVR. This small prospective study with long term follow-up demonstrates safety and tolerability, and there is a suggestion of efficacy in this cohort and in the additional 16 eyes. In addition, there is some confirmatory laboratory evidence using cultured human PVR cells. There is enough favorable evidence that this approach warrants further study.