AIM: To investigate the effect of adding autologous serum eye drops to the postoperative regime after amniotic membrane transplantation for severe persistent corneal ulcers. METHODS: Forty eyes of 40 patients with persistent corneal ulcers were randomly assigned to artificial tears (sodium hyaluronate 0.2%, ATs group, n=20) or autologous serum eye drops (ASEDs, n=20) following treatment with amniotic membrane transplantation. Digital slit lamp images were acquired from all patients before and 30d post treatment. The area with fibrovascular tissue was calculated using Image J. Central corneal sensitivity was assessed by Cochet-Bonnet aesthesiometry before and one month after treatment. Scar tissue transparency was assessed with a novel optical densitometry. RESULTS: Mean age of patients was 61.65±16.47y and 57.3±19.11y in the ATs group and ASEDs group, respectively. Twenty-two male and 18 female patients were included in the study. The improvement in visual acuity was significantly greater in the ASEDs group (0.14±0.04) than the ATs (0.08±0.04; P=0.00046). Cochet-Bonnet aesthesiometry improved significantly after treatment with a similar rate between groups. There were no statistically significant differences in the area of postoperative fibrovascular tissue between the two groups (P=0.082). The success rate in the two groups was similar. The difference in densitometry between the ATs and ASEDs group was statistically significant (P=0.042) with greater reduction from baseline in the ASEDS group. CONCLUSION: Autologous serum eye drops can lead to better visual acuity, more stable results and improved densitometry and should be considered in the postoperative care following amniotic membrane transplantation.