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      Topical fosaprepitant for the treatment of ocular pain and inflammation

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          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.

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          Most cited references15

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          Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective

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            Diagnosis and management of neurotrophic keratitis

            Neurotrophic keratitis (NK) is a degenerative disease characterized by corneal sensitivity reduction, spontaneous epithelium breakdown, and impairment of corneal healing. Several causes of NK, including herpetic keratitis, diabetes, and ophthalmic and neurosurgical procedures, share the common mechanism of trigeminal damage. Diagnosis of NK requires accurate investigation of clinical ocular and systemic history, complete eye examination, and assessment of corneal sensitivity. All diagnostic procedures to achieve correct diagnosis and classification of NK, including additional examinations such as in vivo confocal microscopy, are reviewed. NK can be classified according to severity of corneal damage, ie, epithelial alterations (stage 1), persistent epithelial defect (stage 2), and corneal ulcer (stage 3). Management of NK should be based on clinical severity, and aimed at promoting corneal healing and preventing progression of the disease to stromal melting and perforation. Concomitant ocular diseases, such as exposure keratitis, dry eye, and limbal stem cell deficiency, negatively influence the outcome of NK and should be treated. Currently, no specific medical treatment exists, and surgical approaches, such as amniotic membrane transplantation and conjunctival flap, are effective in preserving eye integrity, without ameliorating corneal sensitivity or visual function. This review describes experimental and clinical reports showing several novel and potential therapies for NK, including growth factors and metalloprotease inhibitors, as well as three ongoing Phase II clinical trials.
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              Corticosteroids and glaucoma risk.

              Corticosteroids (glucocorticoids), used frequently as potent anti-inflammatory agents, increase the risk of glaucoma by raising the intraocular pressure (IOP) when administered exogenously (topically, periocularly or systemically) and in certain conditions of increased endogenous production (e.g. Cushing's syndrome). Approximately 18 to 36% of the general population are corticosteroid responders. This response is increased to 46 to 92% in patients with primary open-angle glaucoma (POAG). Patients over 40 years of age and with certain systemic diseases (e.g. diabetes mellitus, high myopia) as well as relatives of patients with POAG are more vulnerable to corticosteroid-induced glaucoma. The association of corticosteroid-induced ocular hypertension in other conditions which are considered as risk factors for glaucoma (racial origins, hypertension, migraine, vasospasm) is likely but not fully established. The proposed mechanism of corticosteroid-induced glaucoma includes morphological and functional changes in the trabecular meshwork system and is similar to the pathogenesis of POAG. Trabecular cells exposed to corticosteroids in vitro show endoreplication of nuclei, an increase in cell size and excessive production of an approximately 56kD glycoprotein, identified as myocilin and transcribed by the GLC1A gene. Induction of ocular hypertension after corticosteroid administration depends on the specific drug, the dose, the frequency of administration and the corticosteroid responsiveness of the patient. The risk of corticosteroid-induced glaucoma can be minimised with judicious use of corticosteroids, as well as education of patients and medical practitioners. New treatment modalities include modified steroids and nonsteroidal anti-inflammatory agents that will have less effect on the elevation of IOP.
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                Author and article information

                Contributors
                Journal
                Am J Ophthalmol Case Rep
                Am J Ophthalmol Case Rep
                American Journal of Ophthalmology Case Reports
                Elsevier
                2451-9936
                25 November 2023
                December 2023
                25 November 2023
                : 32
                : 101964
                Affiliations
                [1]Cornea and Ocular Surface Disease Unit, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy
                Author notes
                []Corresponding author. ferrari.giulio@ 123456hsr.it
                Article
                S2451-9936(23)00172-X 101964
                10.1016/j.ajoc.2023.101964
                10698007
                38077782
                6b629dda-ad32-4afa-a7de-44e9173f84fd
                © 2023 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 June 2023
                : 31 October 2023
                : 19 November 2023
                Categories
                Image

                ocular pain,corneal inflammation,substance p,fosaprepitant

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