AbstractPurpose To evaluate the efficacy of a new matrix therapy agent (RGTA, Cacicol®), an analogue of heparan sulphates, for management of severe neurotrophic keratopathy.Methods We carried out a prospective, single‐centre, uncontrolled study of 11 eyes in 11 patients, presenting corneal neurotrophic ulcers, despite use of preservative‐free artificial tears for 15 days. Mean age was 58 years. All patients had corneal anaesthesia. RGTA treatment was instilled in the morning,as the fist eyedrop, on alternate days. Main outcome measures were for each patient healing of the corneal surface and best corrected visual acuity during and after treatment.Results Eight patients displayed complete healing of the ulcer, after a mean period of 8.7 weeks (range; 1 to 22 weeks). Mean ulcer area decreased significantly, from 11.12% to 6.37% (p=0.0479) in the first week, to 1.56% (p=0.0054) at one month. Treatment failure was observed in three cases, requiring amniotic membrane transplantation in two patients and penetrating keratoplasty in one patient. At the end of the study, none of the patients displayed a significant improvement in visual acuity. None of the patients reported pain or discomfort during instillation of RGTA eyedrops.Conclusion This heparin mimetic, which may stimulate extracellular matrix healing, may be a possible, non‐invasive, alternative therapy in severe neurotrophic keratopathy. However, randomized studies are necessary.