We appreciate the interest expressed in our article by Udaondo and associates. We also believe that an intravitreal injection of autologous plasmin enzyme (APE) for some retinal disorders has been shown to be safe and effective.

Udaondo and associates used a simplified and modified technique to obtain the plasmin 45 minutes before the injection. We also used the kit for the purification of APE that put the original principle to use (Sakuma T, et al. IOVS, 2006;47:ARVO E-Abstract 4684). The preparatory time for purification of APE is 120 minutes. But we can prepare the safe and highly purified APE, compared to the technique use by Udaondo and associates. The kit can purify about 1 IU of APE in 0.1 mL from 30 mL of autologous blood; samples are incubated for 48 hours to check for contamination before injection. In all vitreoretinal surgery, APE is not used immediately after diagnosing some retinal disorders. It is important to confirm whether surgeons can use APE for some retinal disorders with safety.

We attempted to evaluate the benefit of APE-assisted vitrectomy in macular hole, diabetic macular edema, and vitreomacular traction syndrome. Almost all vitreous detachment is considered to be induced by APE (0.2 IU/0.1 mL). But APE (0.2 IU/0.1 mL) did not always work at strong adhesion between vitreous and retina and therefore we needed highly purified APE (1 IU/0.1 mL).

As a result, posterior vitreous detachment (PVD) was confirmed in 88.5% of patients on an intravitreal injection of APE for branch retinal vein occlusion (BRVO). Visual acuity improved by 2 lines or more in 23 eyes (88.5%) and the retinal thickness was reduced in all eyes.

Our observations also showed that 3 eyes without a PVD after the APE injection had good visual and retinal thickness recovery. Thus, we can conclude that the induction of a PVD was not the only cause of improved best-corrected decimal visual acuity in these eyes and APE had other effects on the eyes.

It has taken long and difficult preparation time to isolate APE from autologous blood. A commercially available recombinant microplasmin or disposable kit for smooth preparation of APE may be a desirable alternative in the future. Further studies with a large sample size and longer follow-up are needed to confirm its efficacy, actions, and safety. The adhesion of vitreoretinal surface is different with respect to age, sex, and some vitreoretinal diseases. The effect of APE has to be investigated in several conditions individually.