Primary angle-closure glaucoma (PACG) is an important cause of bilateral blindness, in particular when resulting from acute primary angle closure (APAC). Thus, it would be important to develop novel therapies to protect retinal ganglion cells (RGCs) after APAC.
Copolymer-1 (Cop-1) is a synthetic antigenic co-polymer that acts by augmenting the body's physiological immune response and repair mechanism, and is used clinically to reduce new brain lesions in patients with multiple sclerosis.1,2 In previous murine studies, prophylaxis with Cop-1 protected the optic nerve from injury and prevented RGC death.3
In this randomized, placebo-controlled, double-masked trial, patients with APAC were randomized to receive either Cop-1 or placebo, in addition to standard medical therapy. Placebo or Cop-1 was administered through subcutaneous injections, one 24h and another one week after APAC presentation. The primary outcome measure was the number of locations progressing on visual fields (SITA Standard algorithm with a 24-2 test pattern) based on pointwise linear regression analysis; as a secondary outcome measure, they investigated the change in RNFL thickness (Cirrus SD-OCT) from baseline to week 16.
A total of 38 patients completed the study, 50% in each randomization group. The authors found a mean of 0.32 progressing visual field locations in the Cop-1 compared to 2.74 in the placebo group (p = 0.09). In addition, the change in MD between week 16 and baseline was significantly more positive in the Cop-1 group (p = 0.01). Nonetheless, they found no significant difference in mean RNFL change between groups. No significant adverse events were noted, except for injection site pain in Cop-1 (47.4%) and placebo (26.3%) groups.
This is a first randomized clinical trial reporting a potential new neuroprotective drug to prevent irreversible vision loss following APAC. The results showed less visual field progression after APAC among those receiving the new drug. However, the lack of evidence of concurrent RNFL change warrants further investigation and could potentially argue in favor the using visual fields as primary endpoints in neuroprotection clinical trials. Further research with larger sample size, longer, follow-up time and investigation of different drug doses may help confirm these initial findings.
The lack of evidence of concurrent RNFL change warrants further investigation and could potentially argue in favor the using visual fields as primary endpoints in neuroprotection clinical trials