Severe epithelial keratopathy refractory to conventional dry eye treatment in the absence of discomfort symptoms should raise suspicion for neurotrophic corneal changes. This study aimed to evaluate the effect of topical recombinant human nerve growth factor (rhNGF) eye drops in managing refractory epithelial keratopathy with neurotrophic features. This was a retrospective case series study on patients treated with topical rhNGF for refractory epithelial keratopathy due to stage I neurotrophic keratitis (NK) at a single institution. Data regarding demographics and ocular/systemic medical history was extracted from patient charts. Visual acuity and corneal staining scores were recorded at baseline and follow-up visits, along with treatment side effects. We included 26 eyes of 14 patients with refractory epithelial keratopathy. After an 8-week treatment course, the median corneal staining score in the worse eye decreased from 4 to 1 (p=0.001). All patients showed at least one-grade improvement in corneal staining with complete or near-complete resolution in at least one eye at 8 weeks, sustained in 7 patients at three months. A better response was observed in eyes with post-radiation epithelial keratopathy, LASIK, and Sjogren's syndrome. Those with chronic use of other topical treatments and uncontrolled diabetes mellitus demonstrated incomplete responses. Eight patients reported mild to moderate ocular discomfort from drop application that fully resolved after completion of treatment. Topical rhNGF application was effective and safe in treating refractory epithelial keratopathy due to stage I NK in our cohort, although the effect was sustained only in some patients at three months. Further studies are needed to determine the optimum treatment regimen based on underlying etiology.