Extensive intraocular melanoma with secondary glaucoma in a 15‐month‐old Thoroughbred filly

Abstract

A 15‐month‐old, grey, Thoroughbred filly presented for investigation of a 6‐week history of corneal oedema and blepharospasm on the right eye (OD). The filly was otherwise healthy. Following ophthalmic examination, glaucoma on the OD was diagnosed. A space occupying mass within the anterior chamber was documented on transpalpebral ultrasonographic examination. This mass obliterated most of the anterior intraocular structures on the peripheral nasal side (corneal endothelium and drainage angle), leading to secondary glaucoma. After systemic and topical treatment addressing secondary glaucoma, the corneal oedema reduced. The mass was visualised as an irregularly rounded brown structure associated with the iris on the peripheral nasal side of the anterior chamber. Given the filly's signalment, location and appearance of the mass, a tentative diagnosis of intraocular melanoma was made and enucleation was performed. Histopathological evaluation of the globe revealed solid sheets of heavily pigmented melanocytic cells, disrupting the normal ciliary body architecture and extending into the iris and subretinal. The cells were pleomorphic, polyhedral to round with occasional spindle‐shaped cells, and contained moderate to large amounts of granular black‐brown pigment (melanin). The iridal component expanded into the anterior chamber, with cells directly opposed to Descemet's membrane, with loss of the endothelium and expanding and occluding the filtration angle in this area. The lesion infiltrated locally into the edge of the sclera, but did not extend through the sclera, though occasional perivascular clusters of melanophages were observed within the scleral stroma adjacent to the optic nerve. Diagnosis of a uveal melanocytic neoplasm was confirmed, with characteristics similar to only one reported case . This is a unique case of a rapidly growing, invasive, uveal melanoma in a young horse. Intraocular melanoma should be considered as a differential diagnoses for glaucoma in grey horses, regardless of the age and absence of melanocytic skin lesions.

This case report outlines a case of rapidly growing, locally invasive, uveal melanoma in a yearling, without cutaneous lesions, and highlights the need for further research into globe‐sparing treatment of intraocular neoplasms. Intraocular melanoma should be considered as one of the differential diagnoses for glaucoma in grey horses, regardless of the age and absence of melanocytic skin lesions.

1. INTRODUCTION

Melanocytic tumours originate from melanocytes and can be benign or malignant, and are most frequently diagnosed in older grey horses (Strauss et al., 2019). Equine ocular melanocytic tumours are rare but have been described in adnexal, orbital, epibulbar and intraocular tissues (Strauss et al., 2019). Anterior uveal melanocytic tumours are the most common and affect mostly grey horses, between 5 and 10 years of age (Gilger et al., 2022; Scotty et al., 2008). While melanocytic tumours are often considered benign, they can progress quickly and be locally invasive (Scotty et al., 2008). Clinical signs may be mild with no evidence of ocular pain, but the presentation depends on the location and size of the mass (Gilger et al., 2022). More progressive and invasive masses can change normal architecture of the eye and present with more severe signs of ocular disease (Gilger et al., 2022) including distortion of the pupil (dyscoria), corneal oedema and anterior uveitis (Montgomery, 2014). In some cases, glaucoma may also develop if the iridocorneal angle becomes obstructed (Myrna & Sheridan, 2019; Westermeyer et al., 2022). Glaucoma is characterised by an increased intraocular pressure (IOP) and can occur as a congenital, primary or secondary disorder. In horses, secondary glaucoma is the most common form (Westermeyer et al., 2022). The disturbance of the balance between aqueous humour production, circulation, drainage and resistance to outflow results in an abnormal intraocular pressure (IOP; Westermeyer et al., 2022). This report describes an unusual presentation of glaucoma secondary to a uveal melanoma in a 15‐month‐old Thoroughbred filly.

1.1. Case history

A 15‐month‐old, grey, Thoroughbred filly presented for investigation of a 6‐week history of corneal oedema and blepharospasm on the right eye (OD). Prior to referral, the filly had been treated with topical antimicrobials (chloramphenicol eye drops 0.5% TID) and oral phenylbutazone (2.2 mg/kg SID) for approximately 2 weeks. However, the clinical signs deteriorated rapidly, which prompted referral to the referral hospital.

1.2. Examination

The filly was bright and all vital parameters were within normal limits. There was no evidence of melanocytic disease of the skin. Ophthalmic examination of the left eye (OS) was unremarkable. Mild blepharospasm, ptosis and epiphora were present in the OD, as was marked conjunctivitis. Menace response was reduced, but direct and consensual pupillary light responses were normal. Ophthalmic examination was performed under sedation with intravenous detomidine (0.05 mg/kg) and butorphanol (0.05 mg/kg). Subsequently palpebral and supraorbital nerve blocks were performed with perineural administration of 2 mL of 2% mepivacaine solution at each site. A comprehensive ophthalmic examination was performed utilising direct ophthalmoscopy, slit‐lamp biomicroscopy, applanation tonometry (TonoPen) and B‐mode ocular ultrasonography. Intraocular pressure (IOP) was measured in each eye after application of topical anaesthesia (tetracaine hydrochloride 1%) with the head resting on a headstand at shoulder height. The mean of three measurements revealed an IOP of 36 mmHg (OD) and 19 mmHg (OS).

Increased scleral vascularity was noted dorsally and ventrally. Marked corneal oedema extended ventrally from the dorsal limbus, covering approximately three quarters of the corneal surface and preventing a complete examination of anterior chamber and posterior segments (Figure 1).

FIGURE 1.

OD with marked corneal oedema extending ventrally from the dorsal limbus was extending for approximately three quarters of the corneal surface.

Transpalpebral ultrasonographic examination was performed using a linear 12 MHz transducer (LOGICTMe) and revealed a 17.3 × 8.3 mm uniformly echogenic mass occupying the peripheral nasal anterior chamber of OD (Figure 2). The anterior border of the mass was distinguishable from the hypoechoic corneal stroma, but its posterior portion was indistinguishable from the echogenicity of the iris. Distension of the anterior chamber in the OD (8.4 mm) was evident compared to the OS (5.5 mm). Moreover, there was increased, variable echogenicity within the posterior segment. The differential diagnosis for the mass included intraocular neoplasia and intraocular haemorrhage. Therefore, it was decided not to enucleate but to treat the eye until it was possible to visualise the mass and/or to evaluate response to treatment.

FIGURE 2.

Transverse transpalpebral ultrasonography of the OD showing an uniformly echogenic mass occupying the peripheral nasal anterior chamber. Lateral is to the left of the image.

1.3. Case progression

A subpalpebral lavage system (SPL; Mila International Inc., Florence, KY) was placed in the OD in the lower eyelid and treatment was initiated with topical glaucoma treatment (dorzolamide hydrochloride 20 mg/mL and timolol 5 mg/mL TID), topical corticosteroids (prednisolone acetate 1% QID) and mydriatics (atropine sulphate 1% and phenylephrine 2.5% QID). Systemic anti‐inflammatories were administered (flunixin meglumine 1.1 mg/kg IV BID; paracetamol, 20 mg/kg PO BID).

Within 24 h of beginning therapy, an equatorial band‐shaped superficial corneal defect extending in a nasal‐temporal direction was observed and was positive to fluorescein. Topical corticosteroid therapy was discontinued, and topical antimicrobial therapy was started (chloramphenicol eye drops 0.5%, q2h), alongside with autologous serum (q2h) and topical nonsteroidal anti‐inflammatory (bromfenac 0.9 mg/mL, q2h), and continued for 7 days.

Corneal ulceration resolved by day 7 of treatment. IOP remained increased (30–35 mmHg) in the OD throughout the treatment period, and by day 13, the corneal oedema improved allowing better visualisation of the anterior chamber.

Slit‐lamp biomicroscopy revealed part of an irregularly rounded brown mass associated with the iris on the peripheral nasal side of the anterior chamber (Figure 3). The anterior surface of the mass was flattened against the posterior surface of the cornea, contacting with the corneal endothelium and the nasal portion of the drainage angle. The mass was presumptively diagnosed as a uveal melanocytic neoplasm based on its morphology, location, the animal's coat colour and clinical progression.

FIGURE 3.

Slit‐lamp biomicroscopy of the OD showing part of an irregularly rounded brown mass associated with iris on the peripheral nasal anterior chamber.

The secondary uveitis and glaucoma failed to respond to medical management so the eye was routinely removed under standing sedation and local anaesthesia using a transpalpebral exenteration technique (Pierce & Townsend, 2019) to minimise the risk of neoplastic cells being left in the orbit. Particular care was taken to grossly examine the orbital structures, as well as the cut end of the optic disc, for any evidence of abnormal tissue, but none was seen. Preoperative anti‐inflammatory and antibiotic therapy was initiated with oxytetracycline (6.6 mg/kg IV BID) and flunixin meglumine (1.1 mg/kg IV SID) and continued until discharged from the hospital 3 days postsurgery. Normal exercise resumed after 14 days. Twelve months following surgery, the filly was normal and showed no evidence of any ocular or central nervous system problems.

1.4. Histopathology

Histologic evaluation of the mass confirmed a uvealmelanoma, with charcateristics similar to one reported case (Ramadan, 1975). Grossly, the mass expanded from the iris and below the ciliary body and retina around one edge (Figures 4 and 5).

FIGURE 4.

Image of macroscopic appearance of the eye postsurgery looking into the anterior. The mass was expanding from the iris into the ciliary body and retina.

FIGURE 5.

Image of the sectioned OD showing extension of the mass into the ciliary body and retina.

Microscopically, solid sheets of heavily pigmented cells had formed, disrupting most of the normal ciliary body architecture and extending into the iris and retina. The cells were pleomorphic, polyhedral to round with the occasional spindle‐shaped cell. The cells were subdivided into packets and all contained moderate to large amounts of granular black‐brown pigment (melanin), obscuring nuclear detail in some cells. Melanomacrophages were also observed. The nuclei visible were oval with coarsely stippled chromatin, mild‐to‐moderate anisokaryosis and infrequent mitoses (<1 per 10 high‐powered fields). The iridal component expanded into the anterior chamber, with cells directly opposed to Descemet's membrane, with loss of the endothelium and expanding and occluding the filtration angle in this area. The lesion infiltrated locally into the edge of the sclera and did not extend through the sclera; occasional perivascular clusters of melanophages were observed within the scleral stroma adjacent to the optic nerve (Figure 6).

FIGURE 6.

(a, b) Subgross images of selected areas of the melanoma demonstrating extensive uveal melanocytic proliferation, entirely effacing the iris, filtration angle and ciliary body in B and extending subretinal into the choroid. In A, the mass is more localised, but still expanding the base of the iris, filtration angle and adjacent to the corneal endothelium. Arrows indicate the corneal surface epithelium. (c) Low magnification photomicrograph of the area of the melanoma indicated by the yellow dashed area in B, demonstrating localised infiltration into the scleral stroma close to the limbus (white arrow in c and d), and mild cellular atypia within the melanocytic population is evident after removal of the melanin pigment (d and e). H&E staining without bleaching (a, b) and after bleaching with potassium permanganate (c, d). Scale bars: A, B = 5 mm; C = 1 mm; D = 200 μm; E = 50 μm.

2. DISCUSSION

This is the first reported case of a yearling presenting with severe glaucoma secondary to an intraocular melanocytic neoplasm, with no concurrent cutaneous melanomas.

Ocular melanocytic neoplasms are uncommon and most frequently involve the periocular skin (Myrna & Sheridan, 2019). Intraocular masses are rare and generally occur concurrently with cutaneous melanomas in older grey horses (Myrna & Sheridan, 2019). Usually benign in nature, these tumours can lead to more severe ocular pathology such as corneal oedema and glaucoma (Myrna & Sheridan, 2019; Montgomery, 2014; Westermeyer et al., 2022). In this report, the filly presented with severe ocular disease that was unresponsive to medical treatment. Although segmental, the mass was obliterating most of the anterior intraocular structures, including the corneal endothelium and drainage angle. This may have contributed to the acute and severe presentation.

Differential diagnoses for intraocular masses include haematoma, uveal cyst or nevus, medulloepithelioma, or lymphosarcoma. Intraocular haematomas are commonly seen in horses following trauma, but these tend to decrease in size with time and appropriate treatment and have even been described to resolve spontaneously (Barnett et al., 2004). Uveal cysts and cysts of the granula iridica can be differentiated from melanomas by their appearance, and ultrasonography can also be used in this differentiation as the latter appear as a hollow hypoechoic structure (Gilger et al., 2022). Medulloepitheliomas occur in young horses as nonpigmented lesions filling the pupil or anterior chamber (Montgomery, 2014). Lymphosarcoma is the most common ocular metastatic tumour in the horse, and signs are generally consistent with anterior uveitis. Systemic signs such as weight loss or fever may also be seen in these cases (Montgomery, 2014). In the case presented, ante‐mortem diagnosis of intraocular melanoma was achieved based on the colour of the filly's coat, appearance of the mass, lack of response to treatment and absence of systemic signs.

Diagnosis of intraocular masses can be challenging; fine needle aspirates can be unrewarding due to the limited ability to extract cells from the lesions. Complications of this procedure include needle tract seeding, haemorrhage, anterior uveitis, endophthalmitis and choroidal oedema (Gilger et al., 2022) Sector iridectomy can be performed to obtain a biopsy sample if attempting to preserve the eye, but this is expensive, technically advanced and carries significant risks. Therefore, enucleation is generally the most practical way of obtaining diagnostic samples and is often the recommended treatment for intraocular neoplasia, especially when involving the ciliary body (Wang & Kern, 2015). Computed tomography (CT) of the head may have further aided diagnosis and surgical planning when determining the extent of the lesion and identifying any infiltration into the adnexal tissues. Ocular ultrasonography can be used to differentiate solid masses from cystic structures, but also to evaluate adnexal tissues (Hallowell & Bowen, 2007). This may be less valuable for the latter purpose than CT, but it is a practical and readily available diagnostic tool in equine practice (Hallowell & Bowen, 2007) and proved to be a crucial diagnostically in this case.

Definitive diagnosis of melanocytic neoplasia is often made on gross appearance due to melanin pigment. Histopathological appearance of melanomas can be very diverse; spindle is often the most common cell phenotype but may also present as mixed, epithelioid, polygonal or pleomorphic (Ramos‐Vara et al., 2014). Particularly when poorly pigmented, it may be difficult to be wholly definitive in a diagnosis of melanoma on microscopic appearance alone. Immunohistochemistry can increase the confidence in the diagnosis with a number of markers being described for this purpose in both human and animal species (Ramos‐Vara et al., 2014). In this case, the clinical features presented, alongside with the signalment of the filly, and gross and histopathological appearances of the neoplasm were supportive of melanoma as the diagnosis, and so no immunohistochemistry was performed.

Immunotherapy has been described for treatment of cutaneous and intraocular melanomas. A xenogenic DNA vaccine encoding human tyrosinase is licensed for treatment of oral melanomas in dogs and its use has been extrapolated into equines in recent years (Echelmeyer et al., 2019; Halliwell et al., 2023). However, this vaccine is not licensed in horses and is expensive. One clinical trial reports suppression of tumour growth in vaccinated compared with unvaccinated horses in a single population with cutaneous melanoma (Echelmeyer et al., 2019). But a more recent case series failed to show supporting evidence for its use in cases of intraocular melanoma (Halliwell et al., 2023), like the mass described in this report. Evidence for autologous vaccines efficacy in equine patients with melanomas (Greenberg et al., 2022) and sarcoids (Rothacker et al., 2015) has also been demonstrated. Autologous vaccines are created from excised tumours. The specific methodology may vary, but the general process involves ex vivo manipulation of tumour tissue and creation of an autologous vaccine (Greenberg et al., 2022). These vaccines stimulate humoral and cell‐mediated immune responses against tumour antigens (Greenberg et al., 2022). The use of H2 antagonist, cimetidine, has been trialled for treatment of melanomas in horses with varying results (Goetz et al., 1990; Laus et al., 2010), and its cost may be prohibitive for use in horses.

As a yet unproven racehorse, some financial constraints were in place for the treatment of this filly. Moreover, once the mass was visualised, treatment options with guaranteed success were reduced to enucleation. However, in cases for which salvaging the eye was the priority, there may be options to consider although success is variable. There have been reports of success following sector iridectomy (Knott, 2023; Scotty et al., 2008).

This report outlines a case of rapidly growing, locally invasive, uveal melanoma in a young horse and highlights the need for further research into globe‐sparing treatment of intraocular neoplasms. Therefore, intraocular melanoma should be considered as one of the differential diagnoses for glaucoma in grey horses, regardless of the age and absence of melanocytic skin lesions.

AUTHOR CONTRIBUTIONS

Regina Pereira: Conceptualisation; data curation; funding acquisition; resources; writing – original draft. Giulia Rapezzano: Conceptualisation; resources. Jonathan Withers: Supervision; writing – review and editing. Marco Duz: Supervision; writing – review and editing.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

FUNDING INFORMATION

IVC Evidensia UK – publication support.

PEER REVIEW

The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1002/vms3.1471.

Pereira, R. , Gillespie, S. , Rapezzano, G. , Withers, J. , Duz, M. , & Foote, A. (2024). Extensive intraocular melanoma with secondary glaucoma in a 15‐month‐old Thoroughbred filly. Veterinary Medicine and Science, 10, e1471. 10.1002/vms3.1471

DATA AVAILABILITY STATEMENT

The data that support the findings of this case are available from the corresponding author upon reasonable request.