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Keywords:

  • horse;
  • ophthalmology;
  • neoplasia;
  • cancer;
  • therapy

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Orbit
  5. Adnexa
  6. Nictitating membrane
  7. Cornea/sclera/bulbar conjunctiva
  8. Intraocular
  9. Author's declaration of interests
  10. References

The following article discusses the clinical appearance, diagnosis and therapeutic options for ocular neoplasia in the horse based on anatomic location.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Orbit
  5. Adnexa
  6. Nictitating membrane
  7. Cornea/sclera/bulbar conjunctiva
  8. Intraocular
  9. Author's declaration of interests
  10. References

The most common tumours in the horse are sarcoids, squamous cell carcinomas (SCCs) and melanomas (Scott and Miller 2003; Valentine 2006; Schaffer et al. 2013). Ocular tumours account for approximately 10% of all equine neoplasms, and SCC is the most common tumour-type of the equine eye (Baker and Leyland 1975; Strafuss 1976; Lavach and Severin 1977; Sundberg et al. 1977; Giuliano 2011). Equine ocular tumours provide both diagnostic and therapeutic challenges. Acquisition of tissue samples for cytology and histopathology prior to surgery can prove difficult; fortunately, tumour location and appearance can assist in tumour identification. Therapeutic challenges arise from the fact that the majority of equine ocular neoplasms are malignant (locally invasive with a risk of recurrence), and complete excision with adequate margins is often impossible. As such, adjunctive therapy following surgical intervention is required in most cases. General anaesthesia for equine ocular surgery provides an additional challenge, as horses undergoing ocular surgery are at greater risk for an unsatisfactory recovery from anaesthesia (Parviainen and Trim 2000). Nevertheless, standing surgical procedures can be safely performed in horses with the appropriate temperament, utilising appropriate sedation and local anaesthesia techniques. Techniques for standing ocular procedures in horses are described in detail elsewhere and are beyond the scope of this article (Dwyer 2011; Labelle and Clark-Price 2013).

Equine ocular tumours can be categorised based on anatomic location into orbit, adnexa/palpebral conjunctiva, nictitating membrane, cornea/sclera/bulbar conjunctiva and intraocular. Each anatomic location possesses unique differentials for tumour-type, prognostic factors and therapeutic considerations. Irrespective of tumour-type, biopsy and histopathology are recommended for definitive diagnosis in all horses. Consideration should also be given to the fact that the prognosis for ocular tumours reported in the literature predominantly reflects horses treated at secondary or tertiary referral hospitals without accounting for the population of horses responding to therapy initiated by equine primary care. As a result, this review may overestimate rates of metastasis and tumour recurrence for horses presenting to equine primary practitioners. Nevertheless, successful therapy for equine ocular tumours requires early diagnosis and aggressive, appropriate intervention.

Orbit

  1. Top of page
  2. Summary
  3. Introduction
  4. Orbit
  5. Adnexa
  6. Nictitating membrane
  7. Cornea/sclera/bulbar conjunctiva
  8. Intraocular
  9. Author's declaration of interests
  10. References

Orbital neoplasia is rare in the horse compared to other species; the most common orbital tumours are neuroendocrine tumours and extra-adrenal paragangliomas, followed by anaplastic sarcoma and SCC (originating from ocular tissue) (Gilger 2011). Approximately 5% of all ocular SCCs progress to orbital invasion and/or extension to nasal and sinus cavities (Mosunic et al. 2004). Other orbital tumours reported include malignant rhabdoid tumour, fibroma, melanoma, lipoma, adenocarcinoma, metastatic lymphosarcoma, chondroma rodens and neuroepithelial tumours (Lavach and Severin 1977; Bistner et al. 1983; Richardson and Acland 1983; Sweeney and Beech 1983; Freestone et al. 1989; Hong et al. 1999; Colitz et al. 2000; Miesner et al. 2009). Orbital tumours can arise from primary orbital tissue, involve direct extension from adjacent structures (sinuses or nasal cavity), or metastasise from distant sites (e.g. lymphosarcoma). Clinical signs of retrobulbar neoplasia include exophthalmos, strabismus, elevation of the nictitating membrane and periorbital swelling (Fig1). Abnormalities detected with digital palpation can include decreased retropulsion of the globe as well as periosteal reaction/distortion of the orbital rim. Ocular abnormalities include chemosis, anisocoria (mydriasis with absent pupillary light reflex) and vision loss. Ocular ultrasound can assist in evaluating the retrobulbar space for evidence of neoplasia (mass lesion with or without indentation of the globe) but is difficult to interpret. Advanced imaging (computed tomography scan) is most appropriate for obtaining a diagnosis, evaluating the extent of tumour involvement, and facilitating surgical planning. Computed tomography can also provide anatomic landmarks for obtaining presurgical cytology and histopathology samples.

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Figure 1. (a and b) Exophthalmos, elevation of the nictitating membrane, and periorbital swelling consistent with a retrobulbar tumour.

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Unfortunately, the potential space of the equine orbit and sinuses allows for significant progression of orbital tumours before clinical abnormalities are detected. In many cases, equine orbital tumours progress beyond the scope of surgical resection by the time of diagnosis. Orbital tumours with concurrent neurological abnormalities or sinus/nasal cavity involvement (e.g. epistaxis) carry a poor prognosis (Dugan et al. 1991; Basher et al. 1997). Regional lymph nodes should be palpated to evaluate for evidence of metastases; lymph node aspirates, thoracic radiographs and abdominal ultrasound should be considered for all orbital tumours. Negative findings do not, however, rule out the possibility of metastasis.

In horses with resectable orbital tumours without evidence of metastasis, surgery typically involves exenteration with or without adjunctive therapy (Gilger 2013). Neuroendocrine tumours of the orbit grow slowly and rarely metastasise, making horses with this tumour type ideal for exenteration (Miesner et al. 2009). Recurrence following exenteration of extra-adrenal paragangliomas is rare; however, severe bleeding and decreased arterial pressure are reported intraoperatively (Miesner et al. 2009). Tumour excision with retention of globe has been attempted unsuccessfully for neuroendocrine tumours in several horses (Koch et al. 1980; Freestone et al. 1989; Goodhead et al. 1997). Exenteration for horses with orbital SCC and anaplastic sarcomas were unsuccessful in extending the survival time compared to horses receiving no treatment, indicating a worse prognosis for these tumour types (Baptiste and Grahn 2000). Regardless of tumour type, the prognosis for retention of the globe is poor; early diagnosis and surgical intervention may improve the survival time for a subset of horses diagnosed with orbital tumours.

Adnexa

  1. Top of page
  2. Summary
  3. Introduction
  4. Orbit
  5. Adnexa
  6. Nictitating membrane
  7. Cornea/sclera/bulbar conjunctiva
  8. Intraocular
  9. Author's declaration of interests
  10. References

Common eyelid tumours in the horse include SCC and sarcoid; infrequently diagnosed adnexal tumours include papilloma, melanoma and lymphosarcoma (Giuliano 2011). Ocular SCC should be considered a differential for any sessile, ulcerative, erythematous lesion with an irregular surface (Fig2) The most commonly reported location for ocular SCC in horses is the eyelid followed by the nictitating membrane (Mosunic et al. 2004). Presumptive diagnosis of ocular SCC may be reached based on lesion location and appearance, but histological confirmation is required. The underlying pathogenesis for ocular SCC is not well understood; ultraviolet light (UV) exposure, p53 mutations, viral infections, genetics, hormones and immune factors are all potential contributors to this disease (Clode 2011). Horses with hypopigmentation of ocular and periocular tissues, such as Appaloosas, Quarter Horses and Paints, appear to be predisposed to developing SCC (Lavach and Severin 1977; Walker et al. 1986; Dugan et al. 1991; King et al. 1991; Mosunic et al. 2004). Thoroughbreds, Haflingers and draught horses are also overrepresented despite normal pigmentation (Walker et al. 1986; Schwink 1987; Dugan et al. 1991; King et al. 1991).

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Figure 2. Lower eyelid squamous cell carcinoma; squamous cell carcinoma should be considered a differential for any sessile, ulcerative, erythematous lesion with an irregular surface.

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Ocular SCC in horses is locally invasive with a potentially high recurrence rate following treatment. Horses with SCC involving the eyelid or orbit are reported to have the poorest prognosis (Dugan et al. 1991). Unilateral disease is typical, although bilateral involvement can be as high as 20% in affected horses (Mosunic et al. 2004). As a result, the contralateral, ‘unaffected’ eye should be closely evaluated for evidence of neoplasia. Serosanguinous ocular discharge is easily detected and should raise the index of suspicion for SCC in the contralateral eye. Ocular SCC has a low rate of metastasis (0.3–18.6% depending on the study) that occurs late in the disease process (Mosunic et al. 2004). However, regional palpation should be performed as metastasis to local lymph nodes, salivary glands and lungs have been reported (Gelatt et al. 1974; Ellis 2006).

Treatment options include immunotherapy, intralesional chemotherapy (cisplatin), surgical excision and surgical excision with adjunctive therapy in the form of cryotherapy, radiofrequency hyperthermy, chemotherapy, radiation therapy (brachytherapy or strontium-90), CO2 laser ablation and photodynamic therapy (PDT) (Mosunic et al. 2004; Giuliano 2011). Surgical excision alone can be curative with tumour-free margins of 2 cm (Giuliano 2011), however equine periocular skin is firmly attached to underlying fascia with poor superficial blood supply, making reconstructive blepharoplasties at high risk for dehiscence or necrosis (Gelatt 1967; Lavach 1990). Thin, elastic equine eyelids are fragile and maintenance of eyelid function is paramount. As a result, surgical intervention for periocular SCC is often restricted to tumour-debulking procedures. Recurrence rates for the various therapies range widely from 0–67% depending on the treatment modality and study (Giuliano 2011). Adjunctive radiation therapy for ocular and adnexal SCC across all anatomic locations resulted in recurrence rates of 11–25% depending on the study (Mosunic et al. 2004). Surgical excision alone for periocular SCC originating from the eyelid resulted in a recurrence rate of 54% compared to 0% recurrence for surgical excision with adjunctive radiation therapy (Mosunic et al. 2004). As a result, horses undergoing surgical excision of periocular SCC should receive the benefit of adjunctive therapy. In horses where SCC invasion is significant, enucleation or exenteration is necessary to achieve complete resection (Clode 2011).

Adjunctive therapies most commonly reported for ocular SCC (with percent recurrence) include interstitial radiation/brachytherapy (16%), strontium-90 radiation (15%), cryosurgery (36%), and PDT (11%) (Giuliano 2011). Photodynamic therapy is the most recently developed adjunctive therapy for adnexal SCC, involving infiltration of the tumour with a photoactive agent that induces cellular destruction in response to local application of laser energy (Giuliano et al. 2008). An initial pilot study evaluating the effectiveness of PDT for adnexal SCC was favourable with recurrence in only 1/9 horses (repeat PDT was performed) and overall disease free intervals of 25–68 months were reported (Giuliano et al. 2008). Regardless of the treatment modality employed, horses diagnosed with ocular or adnexal SCC should be monitored routinely for recurrence or the presence of de novo tumours. Horses with hypopigmentation of ocular and periocular tissues or a history of ocular SCC may also benefit from reduced ultraviolet light exposure.

Sarcoids are cutaneous tumours of fibroblastic origin and varied clinical appearance that frequently involve the eyelids and periocular region (Ragland et al. 1970; Cotchin 1977; Genetzky et al. 1983). A surgical biopsy is required to differentiate sarcoids, which are locally invasive and nonmetastatic, from other tumours or granulation tissue (Hendrick et al. 1998). Sarcoids are classified as occult, verrucose, nodular, fibroblastic or mixed, with most periocular sarcoids being of the nodular, fibroblastic or mixed types (Giuliano 2011). Nodular sarcoids are raised, well-demarcated, ovoid tumours either restricted to subcutaneous tissues (type A) or invading the epidermis (type B; Fig3). Fibroblastic sarcoids are pedunculated (type A) or sessile (type B) and appear fleshy and ulcerated. Mixed sarcoids possess features of one or more types of sarcoid (Fig4). The pathogenesis of sarcoids is not completely understood; however, a viral aetiology is suggested with bovine papilloma virus specifically being implicated (Carr et al. 2001a,b; Chambers et al. 2003; Bogaert et al. 2007; Haralambus et al. 2010). Any breed can develop sarcoids, although Quarter Horses, Appaloosas and Arabians appear to be overrepresented (Angelos et al. 1988; Mohammed et al. 1992).

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Figure 3. a) A nodular sarcoid (type A) involving the lateral canthus. b) A nodular type B sarcoid involving the medial canthus. Type A sarcoids are completely subcutaneous and type B invade the epidermis.

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Figure 4. An extensive, mixed sarcoid involving the upper eyelid and medial canthus.

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Treatment for sarcoids includes topical medical therapy, immunotherapy, chemotherapy, surgical excision, cryotherapy, hyperthermia and brachytherapy. Local recurrence is a potential complication of any type of therapy for sarcoids. Topical medications cause significant irritation of the sarcoid allowing the immune system to mount a response to tumour tissue. Bloodroot (XXTERRA) is one such topical therapy; these substances are very irritating and should not be used on or near the eye due to the potential for severe keratitis (Giuliano 2011). Imiquimod (Aldara), an immune-response modifier with an unknown mechanism of action, has been utilised to effectively treat periocular sarcoids in one pilot study (Nogueira et al. 2006). Alopecia, erythema, and exudation are common side effects following topical application of 5% imiquimod cream, and contact with the cornea will presumably result in keratitis. As a result, periocular administration of imiquimod should be recommended with caution.

Immunotherapy and chemotherapy are administered via intralesional injection. Whole-cell bacillus Calmette-Guérin (BCG) vaccine is the most common immunotherapy agent used to treat equine ocular sarcoids. An attenuated form of Mycobacterium bovis, BCG vaccine stimulates the immune system and initiates antibody response to tumour antigens (Lavach et al. 1984; Vanselow et al. 1988; Marti et al. 1993). Protocols for BCG administration vary but typically include saturation with a dose of 1.0 ml/cm2 of surface area with reinjection every 2–4 weeks for a total of 3–9 treatments (Lavach et al. 1984; Dugan 1992; Fadok 1995). Swelling, ulceration and necrosis of the sarcoid typically occur 2–14 days post injection. Rare and potentially fatal, anaphylactic reactions can develop starting with the second injection (one horse in a case series of 309 horses developed clinical signs of anaphylactic shock); pretreatment with systemic flunixin meglumine, antihistamines or corticosteroids are indicated (Knottenbelt and Kelly 2000). An emulsion of BCG cell wall fractions can be utilised to minimise the risk of anaphylaxis while maintaining antitumour activity (Yarkoni and Rapp 1979; Dugan 1992). Recurrence rates of 0–31% are reported for sarcoids responsive to this treatment modality (Lavach et al. 1985; Knottenbelt and Kelly 2000). Fibroblastic and nodular sarcoids have an overall good response to immunotherapy; however, superficial (verrucose, occult or mixed) sarcoids typically respond poorly to BCG injections (Knottenbelt and Kelly 2000).

Intralesional cisplatin utilising an oily emulsion or biodegradable beads has resulted in recurrence of 13–67% and 15% respectively for periocular sarcoids (Théon et al. 1993; Knottenbelt and Kelly 2000; Hewes and Sullins 2006). Cisplatin can be administered alone or in conjunction with surgery. Variation in recurrence among studies may depend on differences in treatment protocols and whether surgical excision was performed. An oily emulsion has been used most commonly: 1 mg of cisplatin/cm3 of tumour tissue is injected at 2-week intervals for a total of 4 treatments (Théon et al. 2007). Side effects include tissue oedema, erythema and crusting; increased severity accompanies subsequent injections (Théon et al. 2007). Electrochemotherapy can also be performed and involves 4 cisplatin treatments followed by electrical field pulses to induce improved drug absorption via increased cell membrane permeability. General anaesthesia is required, however, as sedation does not provide sufficient immobilisation for application of electrical pulses (Tamzali et al. 2012).

Use of cryotherapy or hyperthermia should be restricted to sarcoids that have first undergone surgical debulking. Cryotherapy is administered in a double freeze/thaw cycle with a rapid freeze and slow thaw necessary for appropriate tissue freezing, using a tissue temperature probe to ensure tissue temperatures of -25°C encompassing 0.5 cm margins around the tumour (Giuliano 2011). Cryotherapy as a monotherapy resulted in a recurrence rate of 91% with a significant number of horses developing severe cicatrisation of the upper eyelid as a result of tissue necrosis (Knottenbelt and Kelly 2000). Hyperthermia therapy utilises a radiofrequency hyperthermia device to elevate tissue temperatures to 41–45°C to treat superficial lesions. Hyperthermia produced similar results as cryosurgery as a monotherapy for periocular sarcoids, and was only successful in preventing tumour regrowth when combined with surgical debulking (Knottenbelt and Kelly 2000; Ford et al. 2002).

Brachytherapy utilises interstitial administration of gamma radiation (via sealed radioactive sources) to treat periocular tumours. Due to special licensure requirements, isolation facilities and cost, brachytherapy is restricted to secondary and tertiary referral centres. Interstitial brachytherapy with iridium-192 resulted in 1-year and 5-year progression-free survival rates of 87% and 74% respectively (Théon and Pascoe 1995). Resolution rates for periocular sarcoids as high as 98–100% have also been reported for iridium-192 brachytherapy (Knottenbelt and Kelly 2000; Byam-Cook et al. 2006). Brachytherapy can also be performed with or without surgical debulking; reported side effects included alopecia, depigmentation, mild cicatrisation, orbital bone sequestrum and keratitis/corneal ulcers (Théon and Pascoe 1995; Knottenbelt and Kelly 2000; Byam-Cook et al. 2006).

Surgical therapy without adjunctive therapy is not recommended as a high recurrence rate (82% in one study) and transformation to an aggressive fibroblastic lesion have been reported (Roberts 1970; Knottenbelt and Kelly 2000). As discussed previously, reconstructive eyelid surgery also has the potential for high morbidity, so surgical intervention should be restricted to debulking procedures in conjunction with adjunctive therapy. Carbon dioxide laser ablation of sarcoids results in lower recurrence rates than surgery alone, but is at risk for exuberant granulation tissue (Palmer 1989; Marti et al. 1993). Benign neglect should also be avoided for sarcoids: as few as 6% of horses that were ‘treated’ with benign neglect avoided future therapy, and euthanasia was required for over half (65%) of this population of horses due to extensive tissue involvement (Knottenbelt and Kelly 2000). Even though metastasis is not a concern for sarcoids, early therapeutic intervention provides more treatment options and an improved prognosis as long duration and large tumour size increase the risk for recurrence (Broström 1995).

Extraocular lymphosarcoma is uncommon in horses and can be classified as diffuse or nodular (Fig5). Adnexal lymphosarcoma manifests as eyelid inflammation or diffuse, periocular swelling. Horses diagnosed with extraocular lymphosarcoma with eyelid or cutaneous involvement had a poor outcome (tumour persistence or eventual euthanasia) in the majority of cases whereas other extraocular locations (cornea, sclera, third eyelid, conjunctiva) had a good outcome in 62% of horses (Schnoke et al. 2013). Presence of bilateral extraocular lymphoma and involvement of multiple sites did not affect prognosis. Therapy for lymphosarcoma includes surgical resection, intralesional steroids, systemic corticosteroids, systemic chemotherapy or some combination thereof. Surgical resection of extraocular lesions as part of the treatment regimen, including lesions restricted to the palpebral conjunctiva, improves the chance of a positive outcome compared to horses not undergoing surgery (Schnoke et al. 2013).

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Figure 5. Extraocular lymphosarcoma involving the palpebral conjunctiva of the lower eyelid; ulceration of the conjunctival surface due to exposure has resulted in fluorescein stain uptake.

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Melanomas involving the eyelid are also relatively uncommon in horses; however, adnexal melanomas were present in 24% of horses diagnosed with melanomas in one study (Fleury et al. 2000). Melanoma is the primary differential for slowly progressive, pigmented eyelid masses and are typically hemispheric in shape (Fig6). Older horses and horses of grey coat colour have a higher incidence of cutaneous melanoma with initial onset at age 5–10 years (Fleury et al. 2000). Few reports of adnexal melanoma exist in the literature, so information regarding prognosis and response to treatment are unknown. Surgical excision, CO2 laser ablation and cryotherapy have all been recommended (Giuliano 2011). Excision of eyelid melanoma is typically curative as most tumours are benign. Surgical resection combined with photodynamic therapy has also been reported as a successful treatment option; however, thorough physical examination of affected horses is necessary to evaluate for metastatic disease (Giuliano et al. 2005).

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Figure 6. An ovoid, cutaneous melanoma involving the lower eyelid of a grey horse.

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Other neoplastic lesions affecting equine adnexa include papillomas, benign and malignant vascular tumours (e.g. haemangiosarcoma), fibroma, fibrosarcoma, adenoma, adenocarcinoma, basal cell carcinoma and mast cell tumours (Giuliano 2011). Conjunctival pseudotumours are inflammatory lesions that appear as nodular or smooth, raised pink conjunctival masses, and must be differentiated from neoplastic lesions (Moore et al. 2000b). Histopathology is required for definitive diagnosis of all adnexal tumours. Factors to consider for therapy besides tumour-type include tumour size and invasiveness, malignancy, potential for metastatic disease, and tumour location. Surgical excision with or without adjunctive therapy, as described, is warranted for most adnexal tumours.

Nictitating membrane

  1. Top of page
  2. Summary
  3. Introduction
  4. Orbit
  5. Adnexa
  6. Nictitating membrane
  7. Cornea/sclera/bulbar conjunctiva
  8. Intraocular
  9. Author's declaration of interests
  10. References

Ocular tumours restricted to the nictitating membrane include SCC and lymphosarcoma; rare reports of mast cell tumour, haemangiosarcoma, lymphangiosarcoma, adenocarcinoma and basal cell carcinoma also exist (Sansom et al. 2006; Gearhart et al. 2007; Puff et al. 2008; Payne et al. 2009; Labelle et al. 2011; Mathes et al. 2011). Squamous cell carcinoma is by far the most common tumour affecting the nictitating membrane and accounts for approximately 77% of horses undergoing excision of the nictitating membrane (Fig7). Surgical excision of the nictitating membrane for SCC has a good prognosis with a nonrecurrence rate of 90–100% depending on the study (Payne et al. 2009; Labelle et al. 2011). Performing excision of the nictitating membrane in horses with standing sedation was not associated with an increased risk of tumour recurrence compared to horses undergoing general anaesthesia (Labelle et al. 2011).

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Figure 7. A squamous cell carcinoma located on the palpebral surface of the third eyelid.

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Extraocular lymphosarcoma involving the third eyelid can appear as a discrete nodule with minimal effect on surrounding conjunctiva (Fig8) or as diffuse swelling of periocular tissues. The nodular form probably has a better prognosis because of the possibility of complete surgical resection. All horses with resectable nodular lymphosarcoma involving the nictitating membrane or conjunctiva underwent surgery in one study; 80% of these horses had a favourable outcome (complete remission and absence of systemic involvement for greater than one year) (Schnoke et al. 2013). Administration of intralesional corticosteroids was also reported by Schnoke et al. (2013) and had a favourable outcome in a limited number of horses. The anatomy of the nictitating membrane lends itself well to excision with the goal of achieving complete tumour resection. Potential complications of nictitating membrane include mild ocular discharge, orbital fat prolapse and incomplete tumour excision (Giuliano 2011; Labelle et al. 2011).

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Figure 8. (a and b) Nodular lymphosarcoma originating from the bulbar surface of the third eyelid.

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Cornea/sclera/bulbar conjunctiva

  1. Top of page
  2. Summary
  3. Introduction
  4. Orbit
  5. Adnexa
  6. Nictitating membrane
  7. Cornea/sclera/bulbar conjunctiva
  8. Intraocular
  9. Author's declaration of interests
  10. References

Squamous cell carcinoma is also the most common corneal tumour in horses, and the corneosclera and bulbar conjunctiva account for 34–37% of all ocular SCC (King et al. 1991; Mosunic et al. 2004). Corneal SCCs appear as sessile, raised pink-white masses with a cobblestone appearance (Fig9). Other differentials for corneal SCCs include eosinophilic or immune-mediated keratitis, granulation tissue, or other neoplastic lesions (vascular tumours, mastocytomas, melanoma, and lymposarcoma) (Clode 2011). Diagnosis of corneal SCC predominantly relies upon its characteristic clinical appearance and histopathological confirmation following excision. However, if eosinophilic or immune-mediated keratitis is suspected, cytology or symptomatic therapy using topical corticosteroids or cyclosporine A may be indicated.

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Figure 9. A sessile, raised pink-white mass consistent with a corneal squamous cell carcinoma originating from the ventromedial limbus.

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Treatment options for corneal SCC include surgical excision (keratectomy) alone or surgical excision with adjunctive therapy in the form of cryotherapy, radiofrequency hyperthermia, chemotherapy, B-irradiation or CO2 laser ablation. Recurrence rates for the various therapies range widely from 0 to 51% depending on the treatment modality and study (Mosunic et al. 2004; Clode 2011). Surgical excision alone and surgical excision combined with cryotherapy resulted in recurrence rates of 51% and 32%, respectively (Mosunic et al. 2004). The most recent studies evaluating surgery with adjunctive strontium-90 irradiation, CO2 laser ablation or mitomycin-C therapy had recurrence rates of 17%, 13.3% and 16.6% respectively (Plummer et al. 2007; Clode et al. 2012; Michau et al. 2012). In horses where ocular surface SCC invasion is significant, enucleation or exenteration is necessary to achieve complete resection (Clode 2011).

Other tumours involving the ocular surface include vascular tumours (e.g. haemangioma, haemangiosarcoma), mast cell tumours, epibulbar or conjunctival melanoma, nerve sheath tumours and lymphosarcoma (McMullen et al. 2008; Kappe et al. 2009; Pinn et al. 2011; Halse et al. 2013; Schnoke et al. 2013). All of these tumour types are rarely diagnosed on the equine cornea and sclera. Benign vascular tumours and mast cell tumours have a favourable prognosis following surgical excision with adjunctive therapy. Few reports of epibulbar melanoma exist and range from benign to low-grade malignancy that responds to mass removal and/or enucleation (Hirst et al. 1983; Hamor et al. 1997; McMullen et al. 2008). A single report of primary malignant melanoma responded well to exenteration following failed attempts at local excision combined with cryosurgery (Moore et al. 2000a).

The prognosis for malignant vascular tumours is poor and lymphatic metastasis frequently occurs (Hacker et al. 1986; Bolton et al. 1990). At least one horse diagnosed with corneal haemangiosarcoma responded well to keratectomy alone; however, this appears to be the exception (Pinn et al. 2011). A single report of peripheral nerve sheath tumour affecting the cornea has been reported, which necessitated enucleation; follow-up information for this horse was not available (Kappe et al. 2009). Corneoscleral lymphosarcoma may be a manifestation of systemic lymphosarcoma and associated with a grave prognosis; 95% (20/21) of horses with ocular lymphosarcoma died or were subjected to euthanasia within 6 months of diagnosis due to associated systemic disease in one study (Rebhun and Del Piero 1998). However, in a more recent report, 4 of 5 horses diagnosed with corneoscleral lymphosarcoma experienced a favourable outcome (no evidence of recurrence or systemic involvement) following surgical resection or enucleation (Schnoke et al. 2013).

Intraocular

  1. Top of page
  2. Summary
  3. Introduction
  4. Orbit
  5. Adnexa
  6. Nictitating membrane
  7. Cornea/sclera/bulbar conjunctiva
  8. Intraocular
  9. Author's declaration of interests
  10. References

Primary intraocular tumours are rare in horses; uveal melanoma is the most common intraocular tumour reported and typically affects the iris and ciliary body (Matthews and Barry 1987). Other neoplastic lesions arising from the anterior uvea include medulloepitheliomas (primary) and lymphosarcoma (metastatic). Medulloepitheliomas (teratoid and nonteratoid) can also originate from the posterior segment. Other primary tumours affecting the posterior segment include retinoblastoma, choroidal melanoma, astrocytoma, glioma and oligodendrocytoma (Gelatt et al. 1971; Lavach and Severin 1977; Knottenbelt et al. 2007; Wilkie 2011). Metastatic neoplasia can also affect the posterior segment with lymphosarcoma being most common (Wilkie 2011). Metastatic intraocular tumours are typically associated with significant uveitis and haemorrhage compared to primary tumours.

Like cutaneous melanoma, horses with grey coat colour are predisposed to uveal melanomas (Barnett and Platt 1990). However, the age of onset for intraocular melanomas is different as young adult horses (age 6–10 years of age) are most frequently affected (Barnett and Platt 1990). Clinical signs include an enlarging, pigmented mass within the anterior chamber with distortion of the pupil (dyscoria) (Fig10). If the tumour contacts the corneal endothelium, corneal oedema will also be present. Signs of anterior uveitis (aqueous flare, fibrin etc.) are typically absent; however, secondary glaucoma is a potential complication, possibly due to obstruction of aqueous outflow. Ocular signs of blepharospasm, epiphora and buphthalmia are unlikely to be present until late in the course of tumour progression. Differentials for intraocular melanomas include iris and corpora nigra cysts and iris hypoplasia (Hollingsworth 2011). The only reports of choroidal melanoma in the horse predate 1950; however, it should be considered a differential for any pigmented, raised lesions involving the fundus (McFadyean 1933). Amelanotic melanoma is also a differential for any lightly or nonpigmented intraocular mass.

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Figure 10. An intraocular melanoma arising from the lateral iris and occupying the anterior chamber with contact to the corneal endothelium.

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Most iridociliary melanomas remain static or progress slowly after initial diagnosis; however, rapid enlargement and seeding of the posterior segment with neoplastic cells are possible (Matthews and Barry 1987; Scotty et al. 2008). This tumour type does not exhibit cytological evidence of malignancy, and metastasis has not been reported (Matthews and Barry 1987). Treatment for intraocular melanomas is typically enucleation due to intraocular complications such as glaucoma. Sector iridectomy has been successfully performed in at least 2 horses with iris melanoma prior to extensive intraocular invasion or secondary complications (Latimer and Wyman 1983; Scotty et al. 2008). However, the potential for intraoperative complications (intraocular haemorrhage, incomplete excision etc.) associated with iridociliary tumour resection is high.

Medulloepitheliomas are primary intraocular tumours that occur in young horses and are derived from primitive neuroectodermal tissue (Wilcock et al. 2002). These tumours can be benign or malignant and are classified as teratoid or nonteratoid. Intraocular medulloepitheliomas typically arise form the ciliary body or optic nerve. Clinical appearance of intraocular medulloepitheliomas consists of nonpigmented, fleshy mass lesions filling the pupil or anterior chamber (Bistner 1974; Riis et al. 1990; Leiva et al. 2013). More severe ocular signs are associated with disease progression and disruption of intraocular anatomy (e.g. corneal oedema, neovascularisation, glaucoma, buphthalmia). Intraocular medulloepithliomas are locally aggressive and slow growing with rare metastasis, although orbital extension, with or without intracranial invasion, has been reported (Blodi and Ramsey 1967; Eagle et al. 1978). Enucleation is recommended for medulloepitheliomas with no evidence of extraocular extension. Astrocytomas, gliomas and oligodendrocytomas all arise from the optic nerve, are typically benign, and must be differentiated from proliferative optic neuropathy and traumatic optic neuropathy (Wilkie 2011).

Lymphosarcoma is the most common metastatic tumour of the equine eye. In horses diagnosed with systemic lymphoma, approximately 25% exhibit nonspecific ocular signs including eyelid inflammation and anterior uveitis (aqueous flare, hypopyon, iridal infiltration etc.) (Rebhun and Del Piero 1998). Posterior segment abnormalities such as retinal detachment can also be present. Systemic abnormalities are often present including fever, weight loss, lethargy and peripheral lymphadenopathy. Physical examination as well as complete blood count and serum biochemistry should be performed as part of the diagnostic evaluation of uveitis. Early recognition of ocular lesions consistent with lymphosarcoma may allow for more rapid diagnosis (Rebhun and Del Piero 1998). Ocular therapy should include topical corticosteroids and atropine as well as systemic corticosteroids. Enucleation for intraocular lymphoma is typically not indicated except for palliative reasons (e.g. secondary glaucoma) as the prognosis for systemic lymphosarcoma in horses is grave.

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Orbit
  5. Adnexa
  6. Nictitating membrane
  7. Cornea/sclera/bulbar conjunctiva
  8. Intraocular
  9. Author's declaration of interests
  10. References
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