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excised with a superficial keratectomy and no recurrence was observed for 12 months of follow-up (Bauer et al. 2015). In our case report, chronic keratitis with lymphocytes,


plasma cells and eosinophils was diagnosed in addition to the corneal neoplasia, and multifocal pinpoint areas of pigmentation were seen on clinical examination. The marked presence of these inflammatory cells could be a response to the neoplasia or could represent a pre-existing underlying disease process such as immune-mediated keratitis (IMMK). Immune-mediated keratitis is a group of diseases characterised as primary, nonulcerative, noninfectious, chronic corneal inflammation (Matthews and Gilger 2009). In the United States, five types of IMMK have been described in horses based on the depth of the corneal lesion and the type of infiltrate present (epithelial, superficial stromal, midstromal, endothelial, and eosinophilic) (Matthews and Gilger 2009). Clinical signs of IMMK can be unilateral or bilateral and include corneal vascularisation, cellular infiltrate and corneal oedema, with only mild signs of ocular discomfort. In all types except for eosinophilic keratitis, the cellular infiltrate consists primarily of lymphocytes and plasma cells, with variable amounts of macrophages and neutrophils (Gilger et al. 2005; Pate et al. 2012). With eosinophilic keratitis, cellular infiltrate also contains eosinophils (Yamagata et al. 1996; Lassaline-Utter et al. 2014), and corneal lesions often appear as white plaques (Brooks 2004). In our case, the presence of eosinophils on histopathology is suggestive of underlying eosinophilic keratitis. Immune-mediated keratitis can be treated with topical anti- inflammatories, although superficial keratectomy to remove the lesion often yields the best response (Yamagata et al. 1996; Brooks 2004; Gilger et al. 2005). This could help explain why inflammatory lesions did not recur in our case following superficial keratectomy to remove the neoplastic lesions. If there was an underlying chronic inflammatory disease


present, it is possible this led to migration of melanocytes into the superficial cornea as the original source of neoplastic melanocytes. In human patients, chronic inflammation has been shown to predispose an individual to neoplasia, as inflammatory mediators can induce proneoplastic mutations, resistance to apoptosis, and other changes (Shacter and Weitzman 2002). In veterinary medicine, chronic inflammatory conditions affecting the cornea and topical immunosuppressive therapy have been suggested as risk factors for corneal SCC in dogs (Dreyfus et al. 2011), and a recent case report discussed a horse that developed suspected neoplastic transformation of immune-mediated keratitis to primary corneal lymphoma (Vallone et al. 2016). This case was treated effectively with a multimodal


approach, although the necessity of using all treatment modalities is unknown. Surgical resection was performed to obtain a definitive diagnosis, and surgical clearance appeared to be complete along the outer and deep margins. Beta irradiation using strontium-90 was performed at the surgical sites intraoperatively after resection. This is a noninvasive treatment using a handheld applicator that can apply radiation safely to the ocular surface with minimal tissue penetration (Kirwan et al. 2003). This modality was chosen because at the time of surgery, corneal SCC was suspected and beta irradiation has shown to be effective at reducing recurrence of ocular SCC in horses after keratectomy (Walker et al. 1986; Plummer et al. 2007). This modality has also shown some benefit with melanocytic tumours, so may have been beneficial in our case. A study of


canine limbal melanocytic neoplasms treated with surgical resection and adjunctive strontium-90 beta radiotherapy showed good efficacy with a recurrence rate of only one in thirty cases (Donaldson, Sansom and Adams 2006). Strontium- 90 beta radiotherapy has also shown good efficacy as an adjunctive therapy for conjunctival melanocytic tumours in humans (Cohen et al. 2013). Topical MMC therapy was also used to help prevent


recurrence of neoplastic tissue growth. Mitomycin C is an antineoplastic antibiotic that is used as a chemotherapeutic agent in both human and veterinary medicine. In equine ophthalmology, topical MMC therapy has been reported most commonly for treatment of ocular SCC, and it has shown favourable clinical results when used alone, or as an adjunctive therapy to surgical excision either intraoperatively or post-operatively (Rayner and Van Zyl 2006; Malalana et al. 2010; Clode et al. 2012). Mitomycin C has also been shown as an effective therapy in people with extensive conjunctival- corneal squamous cell carcinoma (Shields et al. 2002), and is reported in people as adjunctive therapy for conjunctival and corneal melanocytic tumours (Kurli and Finger 2005; Russell et al. 2010). There are a variety of protocols reported in human and veterinary medicine for administration of MMC. The week-on/week-off regimen has been used relatively safely in horses for up to four cycles, which was the protocol used in our case (Malalana et al. 2010; Clode et al. 2012). It is thought that this regimen helps reduce ocular toxicity, as it allows time for the slowly dividing epithelial cells and limbal stem cells to repair DNA (Chen et al. 2004). Mitomycin C also has antifibrotic effects, as it has been shown to inhibit cell migration and extracellular matrix production (Abraham et al. 2006). It is used in human patients to decrease corneal haze following refractive laser eye surgeries (Teus et al. 2009), and has shown promise at decreasing corneal scarring in horses and dogs in vitro (Buss et al. 2010; Gupta et al. 2011). It may have helped decrease scarring in our case post- keratectomy. Minimal side effects were seen from the ocular treatments


in this case. The keratectomy site healed uneventfully within 19 days of surgery and radiation therapy. Raised lesions on the corneal surface were observed after corneal epithelialisation; however, these lesions were presumed to be granulation tissue rather than neoplastic masses based on appearance and the resolution with topical steroid/antibiotic solution. Within a few days of finishing the MMC cycles, the horse developed mild blepharitis and periocular depigmentation, which was presumed to be associated with the MMC therapy. Side effects such as transient conjunctivitis and periocular reactions including ulcerative and nonulcerative blepharitis have been reported in horses secondary to MMC treatment (Malalana et al. 2010; Clode et al. 2012). More significant MMC complications related to corneal epithelial and stromal defects (e.g. stromal ulcer, descemetocele, bullous keratopathy), which have previously been documented with MMC therapy in horses, were not observed in this case (Clode et al. 2012). In this case, MMC therapy was not started until after the keratectomy site was epithelialised, which has been shown to reduce the occurrence of major complications (Clode et al. 2012). The timing of complications in our case was unusual, as it did not peak until after the completion of therapy. However, persistent side effects from MMC have been reported in people despite discontinuation of therapy (Kurli and Finger


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