Topical fosaprepitant for the treatment of ocular pain and inflammation

Abstract

Purpose: To assess whether topical administration of fosaprepitant improves intractable chronic ocular pain and inflammation.

Methods: We report three clinical cases of female patients with drug-resistant ocular pain associated with inflammatory diseases of the ocular surface. The patients were treated for 3 (case 1) and 4 (cases 2-3) weeks with fosaprepitant eyedrops (0.1 mg/mL for case 1; 10 mg/mL for case 2-3). Patients were then followed up for at least 3 weeks. We measured ocular pain with the Visual Analogue Scale (VAS), the Ocular Surface Disease Index (OSDI), and corneal sensitivity with the Cochet-Bonnet esthesiometry. Slit-lamp photography and corneal confocal imaging were used to assess ocular surface integrity/conjunctival hyperemia and corneal nerve morphology, respectively.

Results: All three patients had severe ocular pain (score higher than 6/10 VAS scale). All patients reported a significant improvement in ocular pain after 1 week of treatment. We also observed reduced corneal epitheliopathy (case 1) and conjunctival hyperemia (cases 1-2). In two patients (cases 2-3) the treatment was repeated after 1 year and 9 weeks, respectively, and pain reduction was similar in magnitude to what we observed after the first administration.

Conclusions: Topical administration of fosaprepitant ameliorates ocular pain and clinical symptoms in three patients with intractable ocular pain associated with inflammatory diseases of the ocular surface, without adverse effects.

Importance: Fosaprepitant instillation holds promise as a treatment of chronic ocular pain, an area of unmet medical need.

Keywords: Corneal inflammation; Fosaprepitant; Ocular pain; Substance P.

Fig. 1

Clinical outcomes and biomicroscopy result in case #1. Corneal fluorescein staining demonstrates that topical fosaprepitant is not toxic for the ocular surface and improves punctate keratopathy (A–B). Topical administration of fosaprepitant effectively reduces corneal inflammation and redness after 3 weeks of treatment (C–D). The hatched area and arrows in figures C–D highlight a focus on inflammation and hyperemia in the cornea before (C) and after (D) treatment. The patient reports a reduction in ocular pain (E–F) during treatment, measured by VAS and OSDI questionnaires. Topical instillation of fosaprepitant does not affect corneal sensitivity (G), assessed using Cochet-Bonnet esthensiometer. The data are referred to the left eye.

Fig. 2

Clinical outcomes and biomicroscopy result in case #2. Biomicroscopy pictures reveal that fosaprepitant does not exert side effects after 4 weeks of treatment (B) and improves clinical outcomes to the day of enrollment (A). Topical fosaprepitant effectively reduces corneal inflammation (D) and conjunctival hyperemia (F) compared to baseline (C–E). The hatched area in figures C–D highlight a focus on corneal hyperemia before (C) and after (D) treatment. VAS questionnaire shows that fosaprepitant is effective in reducing ocular pain in both two administrations (G). Corneal sensitivity measurement revealed that NK1R antagonism does not significantly affect corneal sensitivity during the first treatment, despite the second administration (H). The data were analyzed by nonparametric Spearman's rank correlation.

Fig. 3

Clinical outcomes and biomicroscopy result in case #3. Confocal microscopy images showing the presence of numerous neuromas in patient 3 (A–B). Slit-lamp biomicroscopy pictures reveal no ocular surface defects before (C) and after (D) topical instillation with fosaprepitant. Figure B shows a high magnification detail of neuromas (arrow) detected in case 3. VAS and OSDI questionnaires demonstrate the beneficial effect of both drugs during administrations, which is reverted after suspension and placebo (P) application (E–F). Graph G shows that artificial tear eye drops application decreases during the fosaprepitant treatments, remaining stable during drug suspension and reverting during the use of placebo (P). Cochet-Bonnet measurements exhibit stable corneal sensitivity throughout fosaprepitant instillation. Statistical analysis was performed using the Mann–Whitney test (# = placebo vs. pre-treatment; $ = placebo vs. fosaprepitant), and the Kruskal-Wallis test followed Dunn's method (* = time point vs. pre-treatment). ^##P < 0.01; ^$$P < 0.01; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.