Treatment of corneal and periocular neoplasia in horses: beyond the scalpel
Izak Venter
+27 833089237
izak@vetsfocus.co.za
Ocular neoplasia
Most common ocular tumors in the horse:
10% of all equine neoplasms
Locally invasive with a risk of recurrence
Anatomical location:
Orbit
Eyelids/palpebral conjunctiva
Third eyelid
Cornea/sclera/bulbar conjunctiva
Intraocular
Therapeutic challenges
Adnexal neoplasia
Common
Squamous cell carcinoma [SCC]
Sarcoid
Uncommon
Papilloma
Melanoma
Lymphosarcoma
Corneal neoplasia
Common
Squamous cell carcinoma [SCC]
Very Uncommon
Papilloma
Melanoma
Haemangioma
Squamous cell carcinoma [SCC]
Mucocutaneous squamous cell carcinoma (MC-SCC)
The nature of MC-SCC varies widely
Slow growing, benign tumours
Rapidly growing, highly malignant and invasive tumours
Frequency of metastasis for MC-SCC is reported to be as high as 19%
Local lymph nodes
Salivary glands
Lungs
Unilateral disease is typical
Bilateral involvement can be as high as 20%
Examine contralateral, ‘unaffected’ eye
Serosanguinous ocular discharge
Pathogenesis
Chronic irritation
UV radiation
Pathogenesis
Equine caballus papillomavirus-2 (EcPV-2)
Necessary but not sufficient
UV drives most periocular SCC, while EcPV-2 is a major oncogenic initiator
Both converge through COX-mediated tumour progression
Pathogenesis
🌞 Chronic UV Exposure (Initiation)
⬇�• UV-B DNA damage
• Reactive oxygen species (ROS)�• Local immunosuppression
⬇
🧬 Genetic Damage & Mutation
⬇�• p53 mutation → ↓ apoptosis�• DNA repair failure�• Clonal expansion of mutated keratinocytes
⬇
🔬 Pre-Neoplastic Change
⬇�Hyperplasia → Dysplasia → Carcinoma in situ
🔥 COX-2 Upregulation (Occurs early after UV exposure. )
⬇�↑ COX-2 → ↑ Prostaglandin E2 (PGE2)
Effects:
⬇
🧫 Invasive Squamous Cell Carcinoma
⬇�• Basement membrane invasion�• Local tissue destruction�• ± Regional metastasis
Clinical signs
Small superficial nodules
Covered with normal skin
Ulceration and malodorous necrosis
Hyperemic eyelid erosive plaques
Papillomatous SCC
Raised mass with a pink, cobblestone appearance
Ulceration
Necrosis
Infiltrate the orbit
Clinical signs
Small superficial nodules
Covered with normal skin
Ulceration and malodorous necrosis
Hyperemic eyelid erosive plaques
Papillomatous SCC
Raised mass with a pink, cobblestone appearance
Ulceration
Necrosis
Infiltrate the orbit
Differential diagnosis
Habronema
Calcified material
Cytology - eosinophils
Diagnosis
Local lymph nodes palpation and fine needle aspirates
Biopsy and histopathology
Metastasis
44% for G3
3% for G1
25% for G2
80 % G3 tumours
Treatment SCC
Surgical management
Cryotherapy
Hyperthermia
Radiotherapy
Chemotherapy
Photodynamic therapy
Most successful when treatment is initiated early
Surgical treatment
Visible tumour = tip of iceberg
Beyond margins:
UV-damaged epithelium
Mutated keratinocyte clones
COX-driven inflammatory microenvironment
± Viral oncogenesis contribution
⬇
Microscopic disease remains after “complete excision”
⬇
If you only remove what you can see, you leave behind what caused it
Surgical treatment
Debulk total tumor size
2‐cm tumor‐free margin
Extensive blepharoplastic procedures
Surgical treatment
Enucleation/exenteration
Cryotherapy �
Liquid nitrogen at -196°C
Lyse tumour cells - intracellular ice formation
Double or triple freeze–thaw cycle
Rapid freeze and slow thaw
Protect the underlying cornea
Early or precancerous SCC
Radiotherapy�
Ionising radiation
Damage nucleic acids and protein
Free radical formation
Brachytherapy
Gamma radioactive sources
High dose of radiation
Minimal radiation to surrounding tissues
Isotopes
Parallel rows approximately 1 cm apart
Total treatment time 7 days
High cost, limited availability, licensure issues, and human radiation exposure
Anti-neoplastic Pharmacologic Classification
Cytotoxics
Mechanism: Direct tumour cell kill or replication inhibition
Examples:
�➡ Direct DNA damage or replication interference�➡ True cytotoxic pharmacology
Immune-Mediated Anti-Neoplastic Agents (Non-Classical Cytostatics)
Mechanism: Immune activation → tumour control
Examples:
�➡ TLR-7 immune activation�➡ Indirect tumour suppression
NSAIDs with Anti-Neoplastic Activity (Adjunct Tumour Modulation)
Mechanism: COX inhibition → ↓ PGE2 → tumour microenvironment effects
Examples:
Cisplatin
Inhibits DNA synthesis by binding to DNA
Intralesional injection
10 mg/ml, followed by mixing with sesame seed oil (60%)
3.3 mg cisplatin/ml
1 mg cisplatin/cm3 of tissue
4 intra tumoral injections given at 2-week intervals
Cisplatin implants
Cisplatin-containing biodegradable pellets [1.6 mg, 3 mg]
Localized, sustained-release chemotherapy
Each bead releases cisplatin over approximately 4–5 weeks, achieving high local cytotoxic concentrations while minimizing systemic exposure and toxicity
Advantages
Cisplatin implants
Lesion Type / Location | Recommended Bead Strength | Rationale |
Periocular, eyelid, lip, nasal regions | 1.6 mg | Reliable release profile and tissue penetration without corneal irritation |
Cisplatin implants
Tumour Bed | Area (cm²) | No. of 1.6 mg Beads | Total Dose (mg) |
3 × 3 cm | 9 | 3 | 4.8 |
4 × 3 cm | 12 | 4 | 6.4 |
6 × 5 cm | 30 | 10 | 16 |
Dosage and Placement
Cisplatin implants
Tumour Type | Long-term Resolution (≥ 2 years) | Notes |
Sarcoid & spindle-cell tumours | ≈ 91 % | High remission Minimal adverse effects |
Squamous cell carcinoma (SCC) | 60–83 % | Best results with debulking + beads |
Melanoma | ≈ 93 % | Durable response, especially in grey horses |
Clinical Efficacy
Cisplatin implants
Adverse Effects
• Mild transient local inflammation or oedema
• Keratitis risk if implanted too close to cornea or upper eyelid
• Systemic absorption minimal
Post-operative Management
• NSAID: Flunixin 1.1 mg/kg PO q24 h × 3 days
• Advise handlers to avoid contact with wound exudate due to residual cisplatin risk
Imiquimod: Clinical Pharmacology�
Immune Response Enhancement
Interferon-α (IFN-α)
TNF
IL-8, 10, 12
TLR-7 / 8 → NF-κB → Cytokine burst
Drives both innate and adaptive anti-tumour immune responses
Imiquimod
Cellular Immune Effects
Innate Immune Activation
Antigen Presentation Enhancement
Adaptive Immune Activation
Skin application� ↓�Dendritic cell activation� ↓�Lymph node priming� ↓�Cytotoxic T-cell tumour targeting
Direct Tumour Microenvironment Effects
Pro-Apoptotic Effects
Anti-Angiogenic Effects
↑
↓
Imiquimod
DOSAGE AND ADMINISTRATION:
Apply three times weekly
More frequent application does not enhance therapeutic outcomes and may exacerbate local irritation.
Treatment duration typically ranges from 2 to 3 months for small lesions.
SIDE EFFECTS:
Erythema
Alopecia
Exudation
Depigmentation
Typically emerge within two weeks
Subside within 8 weeks
NB Pro inflammatory product
Mitomycin C
Antineoplastic antibiotic (Streptomyces caespitosus )
Bioreductive alkylating agent
Potent cytotoxic effect on rapidly dividing cells
Inhibits fibrosis and wound healing responses
Mechanism of Action
�MMC = DNA Damage + Anti-Fibrotic = Dual Anti-Tumour Effect
�DNA cross-linking� ↓�Inhibits DNA synthesis � ↓�Tumour cell apoptosis / necrosis
PLUS
↓ Fibroblast proliferation�↓ ECM production�↓ Post-surgical scarring
MMC basically locks tumour DNA closed — if DNA can’t open, the tumour can’t grow
Why MMC Works Well for Ocular SCC
Treats entire ocular surface → hits subclinical disease
Can reduce recurrence vs surgery alone
Can be used: Alone / Post-debulking
Indications
Primary Corneal SCC
Limbal SCC
Third eyelid SCC
Conjunctival SCC
Best use scenarios
Dosage Protocol
Typical protocol
Evidence Snapshot
Equine study outcomes
MMC alone → resolution in 6 / 8 eyes
Surgery + MMC → resolution in 7 / 9 eyes
No major complications reported
Shows favourable comparison to surgery alone recurrence rates
COX inhibition: Piroxicam�
Not a primary curative therapy
Adjunct / supportive anti-tumour therapy
SCC often has inflammatory + COX-2 driven biology
Piroxicam = COX inhibition → potential anti-tumour effect
COX-2–derived prostaglandins are linked to tumour growth, angiogenesis and metastasis
COX inhibition →
↓ Prostaglandin E2 →
↓ Tumour cell survival signals
↓ Angiogenesis
↓ Immunosuppression
�Equine Sarcoid
Locally invasive
Benign fibroblastic skin tumours
Most common equine tumour
Key Concepts
�Classification�
Aggression ↑ → Need multimodal therapy
Low aggression | High aggression |
Ocult | Fibroblastic |
Verrucous | Mixed |
Nodular | Malevolant |
�Aetiology
Core Drivers
BPV is causally associated with sarcoid development, but infection alone is not sufficient.
Flies may act as mechanical vectors
�Treatment
“Why Are There 40+ Treatments?”
Because no single treatment works for all sarcoids
There is no consistently reliable treatment for every sarcoid type, location and patient.
What desperation + internet advice produces
Burnt toast rubbed on lesion
Cigarette ash paste
Toothpaste + baking soda mixtures
Superglue “to suffocate tumour”
Battery acid
Household bleach
Vinegar soaks
�Diagnosis
Presumptive diagnosis based on
clinical appearance
Presence of more than one lesion with characteristics of sarcoid is strongly suggestive
Definitive diagnosis - histopathology
Biopsy-induced trauma or irritation may exacerbate the lesion and induce proliferation
Biopsy ONLY if treatment planned immediately
Never wake the dragon unless you are ready to kill it
Treatment
Not All Sarcoids React The Same
Options include:
�Treatment
🚫 High-Risk “Do Not Cut First” Sarcoids
Periocular Sarcoids
Fibroblastic / Ulcerated Sarcoids
Previously Interfered Sarcoids
�Treatment
🚫 High-Risk “Do Not Cut First” Sarcoids
Periocular Sarcoids
Fibroblastic / Ulcerated Sarcoids
Previously Interfered Sarcoids
Periocular oncology is unforgiving
Small decisions create permanent outcomes
Precision matters more than aggression
Think first
Cut last