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Laranjo, M. Ocular Melanocytic Neoplasms in Dogs and Cats. Encyclopedia. Available online: https://encyclopedia.pub/entry/18447 (accessed on 16 November 2024).
Laranjo M. Ocular Melanocytic Neoplasms in Dogs and Cats. Encyclopedia. Available at: https://encyclopedia.pub/entry/18447. Accessed November 16, 2024.
Laranjo, Mafalda. "Ocular Melanocytic Neoplasms in Dogs and Cats" Encyclopedia, https://encyclopedia.pub/entry/18447 (accessed November 16, 2024).
Laranjo, M. (2022, January 18). Ocular Melanocytic Neoplasms in Dogs and Cats. In Encyclopedia. https://encyclopedia.pub/entry/18447
Laranjo, Mafalda. "Ocular Melanocytic Neoplasms in Dogs and Cats." Encyclopedia. Web. 18 January, 2022.
Ocular Melanocytic Neoplasms in Dogs and Cats
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This entry is adapted from the peer-reviewed paper 10.3390/bioengineering8120225

Melanocytic neoplasms are the most common form of primary intraocular neoplasia, and, among those, melanomas are highly prevalent, with different incidences regarding species and anatomical location. Melanomas are histologically confirmed tumours with malignant characteristics, and melanocytomas are benign tumours with no metastatic potential. Melanomas originate from melanocytes or other neoplastic cells that develop from melanocytes or melanoblasts.

melanocytic neoplasms melanoma therapeutics

1. Treatments

The knowledge of melanocytic neoplasms biological behaviour and characteristics, the affected area’s progression, the affected structures and the patient’s species are essential in therapeutic planning [1][2][3].

2. Local Surgical Removal

Local surgical excision can be performed when there is no invasion or compromise of adjacent structures, and the neoplasm site and extent allow total removal, with generous free margins, but with eye globe preservation [1][2]. Co-adjuvant treatments may be employed after surgical excision [1][4][5][6][7]. Patients should be closely monitored in follow-up consultations, with clinical evaluation of the ocular structures [8]. Particular attention must be given to complications related to glandular portion removal [9][10][11].
Wide excision may be required when the eyelid region is affected [2]; although, the species characteristics must be considered. For example, most lid neoplasms in cats are malignant and wider excision is necessary, often requiring blepharoplasty, sliding, and eyelid grafting of adjacent or facial tissue [12][13].
Small isolated conjunctival melanomas which not compromise the adjacent structures may undergo complete surgical resection [2]; however, sometimes conjunctival transposition may be required [1][13]. In addition, the third eyelid may undergo partial excision or total removal [1][13].
In the iris, small, isolated neoplasms with well-defined borders can be submitted to local excision with iridectomy (a section of total iris thickness is extirpated) or iridociclectomy (a portion of the iris and adjacent ciliary body is excised), which may include removal of the adjacent sclera. In cats, minor complications have been reported as mild intra-operative haemorrhage, fibrin clot, corneal ulcer, postoperative ocular hypertension, dyscoria, and pseudopolycoria [14]. Sclerectomy, with or without lamellar keratectomy, may be used as a treatment for canine and feline limbal melanomas that exhibit benign biological behaviour [15][16].
The sectoral exeresis techniques of isolated neoplasms may be successful. However, if the neoplasm invades the sclera or ciliary body, the success may be limited, with the risk of postoperative complications resulting in the need for ocular bulb excision or phthisis bulbi [13]. Still, as a form of repair and to preserve the anatomy and visual function, different grafts can be applied after the surgical removal of ocular melanoma [17][18][19][7][20][21].

3. Laser

Different lasers are used to treat various conditions and ophthalmic diseases [22][23][24] such as iris cyst, capsular opacification, glaucoma, retinal detachments, and pigmented ocular neoplasms [22][25]. Depending on the wavelength, intensity, and duration of exposure, tissues can absorb energy, so the laser can be adjusted to perform photocoagulation, thermotherapy, and photodynamic therapy or undergo ionisation with photodisruption action [26]. The most commonly used lasers in veterinary ophthalmology are neodymium:yttrium-aluminium-garnet (Nd:YAG), diode and CO2 [23]. The laser’s effect depends on the absorption by eye pigments, so the grade and type of eye pigment (melanin, haemoglobin and xanthophyll) and its absorption play important roles in phototherapy [27]. Diode lasers are especially attractive to veterinary ophthalmologists because of their high melanin absorption, which is particularly useful in veterinary patients’ typically heavily pigmented eyes [23].
Nd:YAG laser is used to treat limbal melanoma in dogs and cats, reducing pigmented tissues after treatment [18][21][28]. Diode laser photocoagulation has demonstrated excellent long-term results, is technically easy to perform, minimally invasive, and well-tolerated [29], in addition to its preferential absorption in tissues containing melanin, such as melanomas [22][30]. Other advantages of laser are avoiding intraocular complications, requiring only a short duration of general anaesthesia, and not requiring donor graft tissues. However, its main limitation is the higher recurrence rate [2].
Neoplasms with flat and small dimensions, such as isolated iris melanoma, can be considered for laser photocoagulation if successful laser penetration is predicted [22][30]. Dogs with isolated iris melanomas were treated using a laser diode through an operative microscopic adapter or an indirect ophthalmoscope. An immediate decrease in masses was observed. In neoplasms with a mean thickness greater than 2 mm, additional laser therapy may be required [22][30]. The energy adjustment should be made carefully to avoid dispersion of pigmented tissue and iatrogenic damages [22][30]. Secondary alterations after treatment have been reported, as focal corneal oedema, dyscoria [24], uveitis, hyphema, and cataract [21]. However, as previously stated, it is considered a minimally invasive and well-tolerated technique compared with other therapeutic modalities [21].
In cats, it is possible to ablate small, isolated, and hyperpigmented foci of the iris [31] through a diode laser photocoagulation, which induces lesion contraction [32]. However, due to the multifocal nature of these neoplasms, new lesions may arise [33]. Moreover, without previous histological examination, there is the risk of spreading cells and, consequently, metastases [1][32]. Therefore, although the use of laser on felines pigmented lesions has been suggested, it remains controversial [2]. In contrast to cats, anterior uveal melanomas in dogs metastasise late and less frequently. Therefore, laser photocoagulation is a more attractive approach to eliminating the lesion while preserving eye structure and vision [2].
For anterior uveal neoplasms, newer endoscopic diode lasers may prove to be even more beneficial. This technique uses a 20 g endoprobe that provides light, video, and diode laser. This technique allows accessing the posterior iris and ciliary body to precise visualisation and delivery of laser energy while maintaining the anterior chamber structure and avoiding eye collapse [2].
Isolated neoplasms on the third eyelid can benefit from CO2 laser excision, which proved efficient and effective, with excellent postoperative comfort and minimal complications [11]. However, when neoplasms are extracted using heat-generating devices, caution should be taken due to the samples impairment, which can be difficult for the histological analysis [34].
Additionally, due to their highly coherent monochromatic light emission, lasers are used as light delivery devices in photodynamic therapy, as described below.

4. Photodynamic Therapy

Photodynamic therapy is an evolving modality for treating various diseases, including ocular neoplasms. Its therapeutic effect involves photochemical reactions mediated by the interaction of photosensitising agents, light, and oxygen [35][36][37], which culminates in the oxidation of cancer cells and leads to apoptosis, necrosis, antiangiogenic effects, and immune stimulation [36][37]. PDT is minimally invasive, relatively non-toxic and has no carcinogenic or mutagenic effects [35]. Side effects of photodynamic therapy in veterinary medicine are rarely observed [38][39]. However, pruritus, photosensitisation [38], and increased body temperature [35] were occasionally reported [40].
Although several reports exist on PDT use in veterinary medicine, this treatment is not part of the standard treatments for ocular neoplasms [41][42][43][44][45][46][47]. However, in human medicine, PDT is indicated in treating several eye conditions, which justifies its interest in treating veterinary eye diseases [42].
A dog with scleral melanoma was submitted to photodynamic therapy with the photosensitiser 5-ethylamino-9-diethylaminobenzo[a]phenothiazine chloride (EtNBS), administered intravenously (2.0 mg/kg), and irradiated with a diode laser until 200 J/cm2. Although a visible part of the neoplasms became paler, the neoplasm diameter remained stable two months after PDT. Corneal and local conjunctival reaction (mild) was observed consisting of chemosis and hyperaemia (grade 1) [35].
PDT was also performed in a cat with a history of four surgical resections with recurrences of eyelid melanoma. After new lesion excision, free margins were not obtained, and intraoperative PDT was performed with Acridine orange (OA-PDT) to control residual tumour cells. A xenon light of 400–700 nm wavelength and 20.7 mW/cm2 was applied for 10 min at 10 cm from the field. No postoperative complications were observed after treatment. After 9 months, local recurrence was detected, and new surgical resection with PDT was performed. The animal died 16 months after treatment, and at this time point, no tumour recurrence was detected on the original site. Notably, during the follow-ups, no adverse effect from PDT was detected on the surgical site [5].
However, these are the only studies where PDT usefulness was accessed in veterinary ocular melanoma. Although the limited reports in dogs and cats, PDT successfully treated intraocular melanomas induced in rabbits [48][49][50][51][52], with neoplasm growth arrest [49], irreversible regression [51], and neoplasm destruction [48][50]. In a recent systematic review comparing the available treatments for induced ocular melanomas in rabbits, all options were effective in treating ocular melanoma, with more conservative options such as photodynamic therapy presenting great potential and fewer side effects [53].

5. Cryotherapy

Cryotherapy consists of a rapid freezing phase followed by a slow thaw phase, allowing temperatures that originate the formation of intracellular crystals, which will cause cellular disruption [7]. Two cycles are generally considered sufficient to achieve cell disruption [7]. Cryogenic therapy is often used as adjunctive therapy for various ocular pathologies, including surface and benign and malignant intraocular lesions [54].
Several cryogenic agents are used in veterinary medicine [20][55], with different minimum temperature ranges (liquid nitrogen up to −196 °C; nitrous oxide up to −80 °C; fluoroethane up to −70 °C) [4].
Tetrafluoroethane was used in dogs with limbal melanoma [7]. The treatment consisted of lamellar resection, cryotherapy, and adjuvant graft [7]. Clinical follow-up ranged from 6 months to 8.5 years, without recurrences detection. However, some post-procedure complications have been reported as uveitis, corneal ulceration, corneal oedema, granulation tissue, dyscoria, and corneal lipidosis [7]. In addition, post-procedure inflammation may be substantial and acute. Thus, careful follow-up evaluations of all eye structures should be performed when using cryotherapy, mainly when intraocular tissues are targeted [4].
Eyelids with flat pigmented lesions or after partial surgical removal may be submitted to cryotherapy procedures [1]. However, cryotherapy is not typically curative when used to treat palpebral melanoma [12], and cutaneous depigmentation may occur after cryotherapy due to the dermal melanocytes sensitivity [56].

6. Radiotherapy

Radiotherapy involves the use of ionising radiation in the form of particles or electromagnetic waves for disease treatment, mainly of neoplastic nature [57]. Radiation therapy is the main conservative therapy for ocular melanoma in ophthalmology [58]. In veterinary medicine, radiotherapy can be performed on patients as a curative or palliative approach [59].
A retrospective study evaluated the ocular side effects of cancer-bearing dogs and cats treated with Cobalt-60 (60Co) external beam radiation in which one or both orbit(s) were included in the radiation field. Eyelid lesions, conjunctivitis, keratoconjunctivitis sicca, keratitis, ulcerative keratitis, cataract, uveitis, and retinal lesions as ocular side effects were reported [59].
Thirty dogs with limbal melanoma were treated with lamellar resection and adjunct radiotherapy using strontium-90 (90Sr) plesiotherapy [6]. With this modality of brachytherapy, a low recurrence rate was reported. Post-procedure complications included corneal scarring, corneal neovascularisation, conjunctivitis, lipid keratopathy and focal bullous keratopathy, deep scleral tapering, focal scleromalacia, globular perforation, focal bullous keratopathy, and sectoral cortical cataract [15].
This treatment method is technically simple to perform, minimally invasive, well tolerated, and highly effective but is associated with a reasonably high rate of complications [7], requiring regular ophthalmologic follow-ups [59]. Moreover, radiotherapy treatment tends to be limited due to safety precautions, licensing, and expenses related to this therapeutic modality [4].

7. Enucleation

The enucleation comprises removing the globe eye, nictitating membrane, conjunctival sac, and lid margins [2]. This surgical technique is necessary when there is no possibility of local therapy [13], by the presence of inherent and intractable secondary intraocular alterations [31], particularly in those eyes that develop secondary glaucoma [60]. Other indications for enucleations are blind and painful eyes and the assumption of species-related neoplasm aggressiveness [61][62]. Visual and comfortable eyes may be preserved, mainly when the decision is based on assessing neoplasm malignancy by incisional biopsies or cytology of intraocular aspirates [63].
In dogs, neoplasm extension, neoplasm size, and mitotic index were not reliable predictors of survival after enucleation [64]. However, in cats, the extent of diffuse iris melanoma at the time of enucleation was correlated with survival, with larger neoplasm being associated with lower survival rates [65]. In addition, extrascleral extension, necrosis within the neoplasm, a mitotic index, choroidal invasion, and increased immunostaining intensity were associated with increased metastasis in the cat after enucleation [66].
Diffuse iris melanoma cannot be clinically differentiated from benign pigmentation. Therefore, these conditions remain a dilemma for the veterinary ophthalmologist when deciding whether to excise an eye that may not be affected by a malignant process or continue monitoring an affected eye, risking metastization if it is a malignant lesion [65][67]. In addition, the enucleation procedure is associated with complications such as oedema, haemorrhage and infections [13].

8. Exenteration

Exenteration removes all orbital tissue, including the eye bulb, conjunctiva, nictitating membrane, lacrimal gland, zygomatic salivary gland, extraocular muscles, palpebral margins, and even a part of the orbital periosteum, when necessary [13]. Therefore, exenteration is a more radical therapeutic option, aiming to remove the lesion with extensive surgical margins, restricting neoplasm development and eventual recurrences [68].
This way, orbital exenteration is indicated to treat advanced stages of invasive conjunctival [69], orbital [70] melanomas and when it shows evidence of crossing the sclera [71][72]. When orbital neoplasms invade the surrounding structures, they may also require orbitectomy [13], plus adjuvant therapies [70]. Additionally, neoplasms that affect and develop in the sclera may have a poor prognosis due to the possibility of haematogenous dissemination [73].
Both enucleation and exenteration are treatments with good results in patients with ocular melanoma [4]. The complications associated with exenteration are similar to those associated with enucleation. The postoperative swelling and the long-term wound contracture are usually higher because of the more significant amounts of orbital tissues excised [13]

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Subjects: Veterinary Sciences
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Mafalda Laranjo
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