NAVLE Special Senses

Equine Immune-Mediated Keratitis Study Guide

📅 March 28, 2026 ⏱ 25 min read

Immune-mediated keratitis (IMMK) represents a group of non-infectious, non-ulcerative inflammatory disorders of the equine cornea.

Overview and Clinical Importance

Immune-mediated keratitis (IMMK) represents a group of non-infectious, non-ulcerative inflammatory disorders of the equine cornea. These conditions are characterized by chronic corneal opacity resulting from an aberrant immune response, likely triggered by foreign proteins, microbial antigens, or self-antigens. IMMK is common in both Europe and North America and represents a significant category of equine ophthalmologic disease on the NAVLE.

The hallmark of IMMK is chronic corneal opacity without corneal ulceration or significant uveitis. Classic histopathologic findings include lymphocytic-plasmacytic corneal cellular infiltrates, often accompanied by corneal neovascularization, edema, and fibrosis. Early diagnosis and appropriate immunomodulatory therapy are essential for preserving vision.

Subtype	Prevalence (USA)	Clinical Appearance	Key Features	Prognosis
Superficial Stromal	45%	Yellow-white stromal infiltrate with prominent subepithelial arborizing vasculature from limbus	Initially under upper lid; minimal pain; diffuse vascularization	Good with treatment
Midstromal (Deep)	27%	Dense midstromal infiltrate with surrounding edema; may show yellow-green coloration from plasma leakage	Episodic recurrence; subepithelial bullae may form and rupture; calcium deposition possible	Fair; may require long-term therapy
Endothelial (Endotheliitis)	23%	Diffuse full-thickness corneal edema; often vertical pattern; arborizing deep vasculature	Slowly progressive; endothelial pump failure leads to persistent blue cornea; may cause bullous keratopathy	Poor; least responsive to therapy
Epithelial	Rare	Multifocal punctate epithelial opacities; irregular coalescing islands of thickened epithelium	No corneal vascularization; weak transient fluorescein retention; no stromal edema	Good; responds well to dexamethasone

Pathogenesis and Etiology

The pathogenesis of IMMK remains incompletely understood, but an aberrant immune reaction to corneal antigens is considered highly likely given the favorable response to topical corticosteroids and cyclosporine A therapy.

Proposed Mechanisms

Molecular mimicry: The immune system may recognize corneal autoantigens that cross-react with foreign proteins or microbial epitopes
Autoantibody production: Some horses with IMMK demonstrate autoantibodies against maspin (SERPINB5), a corneal protein that inhibits neovascularization
Dendritic cell accumulation: In vivo confocal microscopy reveals dense networks of dendritic cells in the epithelial basement membrane and immediate subepithelial stroma in epithelial, superficial stromal, and midstromal forms
Loss of immune tolerance: Chronic corneal inflammation may lead to upregulated antigen-presenting cells that effectively present autoantigens to the adaptive immune system

High-YieldThe epithelial form may be associated with viral or fungal antigens residing in the superficial cornea causing chronic immune stimulation. Always rule out subepithelial keratomycosis, which can appear identical to epithelial IMMK.

Sign	Characteristics	Clinical Significance
Corneal opacity	Chronic, progressive; blue-white to yellow-white; location varies by subtype	Hallmark finding; distinguishes from acute ulcerative keratitis
Pain/Discomfort	Minimal to mild in USA cases; may be more pronounced in European cases (37% blepharospasm)	Helps differentiate from infectious keratitis which is typically very painful
Corneal vascularization	Variable; arborizing pattern in superficial forms; deeper vessels in stromal types	Indicates chronicity; depth helps classify subtype
Corneal ulceration	Absent or secondary to bullae rupture (28.6% in European study)	Secondary ulceration may occur; complicates treatment
Uveitis	Typically absent; reported in 25% of European cases	Presence increases odds of enucleation 8.9-fold

Classification of IMMK Subtypes

IMMK is classified based on the anatomic depth of the primary inflammatory lesion. The USA and UK use slightly different classification systems, but both recognize four to five distinct subtypes. Understanding these subtypes is critical for prognosis and treatment selection.

IMMK Subtypes: Prevalence and Key Features

Diagnostic Test	Findings in IMMK	Purpose
Slit-lamp biomicroscopy	Localizes depth of infiltrate and edema; identifies subtype	Essential for classification and prognosis
Fluorescein staining	Negative or weak transient retention in epithelial form	Rule out corneal ulceration
Corneal cytology	Lymphocytes, plasma cells; NO bacteria, fungi, or eosinophils (unless EK)	Rule out infectious causes and eosinophilic keratitis
Bacterial and fungal culture	Negative for pathogens	Essential to rule out stromal abscess and keratomycosis
Tonometry	Normal IOP	Rule out glaucoma as cause of corneal edema
Schirmer tear test	Normal (greater than 15 mm/min)	Rule out keratoconjunctivitis sicca

Clinical Presentation

Signalment

Age: Typically middle-aged horses (mean age 11.9 years, range 5-19 years)
Breed: No specific breed predisposition documented
Laterality: Unilateral in 85% of cases; bilateral involvement possible (especially eosinophilic keratitis)

Clinical Signs

NAVLE TipOn the NAVLE, remember that IMMK is characterized by chronic, non-ulcerative corneal opacity with MINIMAL PAIN and ABSENT UVEITIS. This is the key differentiator from infectious keratitis (stromal abscess, fungal keratitis) which is typically very painful with significant anterior uveitis.

Condition	Key Distinguishing Features	Diagnostic Approach
Stromal abscess	Severe pain, hypopyon, marked uveitis, dense stromal infiltrate	Cytology/culture positive for bacteria or fungi
Keratomycosis (fungal keratitis)	Severe pain, ulceration, melting, satellite lesions, feathery margins	Fungal elements on cytology; positive fungal culture
Equine recurrent uveitis	Miosis, aqueous flare, hypopyon, secondary corneal edema	Prominent anterior uveitis signs; history of recurrence
Glaucoma	Buphthalmos, corneal striae, elevated IOP, mydriasis	Tonometry shows elevated IOP (greater than 30 mmHg)
EHV keratitis	Punctate corneal erosions, dendritic pattern, history of respiratory disease	PCR for EHV-2, EHV-5; may overlap with epithelial IMMK

Diagnosis

The diagnosis of IMMK is based on clinical signs, exclusion of infectious causes, and response to immunomodulatory therapy. There is no definitive diagnostic test for IMMK.

Diagnostic Criteria

Progressive or chronic (greater than 3 months duration) nonulcerative corneal opacity
Mild to moderate corneal cellular infiltrate
Variable corneal vascularization and edema
Absence of microorganisms on cytology and culture
Response to immunomodulatory therapy

Recommended Diagnostic Workup

High-YieldBefore initiating immunosuppressive therapy, ALWAYS perform corneal cytology and culture to rule out infectious keratitis. Immunosuppression in the presence of bacterial or fungal infection can lead to rapid corneal deterioration and globe loss.

Differential Diagnosis

Subtype	First-Line Treatment	Adjunct Therapy	Expected Response
Epithelial	Topical dexamethasone 0.1% q6h	Topical antibiotic if epithelial defect from scraping	Rapid clearing; rarely recurs
Superficial Stromal	Topical cyclosporine A 0.2% q12h	Topical dexamethasone after re-epithelialization; consider episcleral CsA implant	Clearing in 7-10 days for short duration cases; longer for chronic
Midstromal	Topical cyclosporine A 0.2% q12h	Topical/systemic doxycycline; topical NSAIDs; episcleral CsA implant	Clearing in 10-14 days; long-term maintenance often required
Endothelial	Topical dexamethasone q6h or topical bromfenac (NSAID)	Topical 5% NaCl for bullae; cyclosporine A often ineffective	Poor response; often progressive despite therapy

Treatment

Treatment of IMMK is based on immunosuppressive and anti-inflammatory therapy. The specific approach varies by subtype, and treatment is often required long-term or lifelong. Early intervention improves prognosis.

Medical Treatment by Subtype

Surgical Treatment

Surgical intervention may be necessary for cases refractory to medical therapy:

Superficial keratectomy: Removal of affected corneal tissue; curative in 13/13 eyes with superficial IMMK in one study; can be performed in standing, sedated horse
Conjunctival graft: May be combined with keratectomy; provides vascular supply and drug delivery to cornea
Episcleral cyclosporine A implant: Silicone matrix device providing sustained drug release; placed subsclerally adjacent to suprachoroidal space; reduces need for frequent topical medication
Enucleation: Reserved for end-stage disease with chronic pain and blindness; increased risk with blepharospasm (OR 5.5) and uveitis (OR 8.9)

Exam Focus: For superficial and midstromal IMMK, cyclosporine A is the drug of choice. For epithelial IMMK, topical dexamethasone is highly effective. For endothelial IMMK, prognosis is poor regardless of treatment.

Eosinophilic Keratitis

Eosinophilic keratitis (EK) is considered a distinct subtype of immune-mediated corneal disease characterized by eosinophilic infiltration. It is believed to represent a delayed hypersensitivity reaction to parasitic or environmental allergens.

Clinical Features of Eosinophilic Keratitis

Pain level: Moderate to severe (more painful than other IMMK forms)
Appearance: White to pink raised plaques on corneal surface; caseous discharge; yellow perilimbal infiltrate
Location: Commonly under third eyelid, ventral-medial and ventral-lateral cornea
Seasonality: Increased prevalence in summer months (June-August)
Laterality: More commonly bilateral compared to other IMMK types
Associated signs: Blepharospasm, epiphora, conjunctival hyperemia, chemosis; secondary corneal ulceration common

Diagnosis of Eosinophilic Keratitis

Corneal cytology is diagnostic: Abundant eosinophils, often with mast cells, plasma cells, neutrophils, and lymphocytes. Use a cytology brush rather than swab for best sample collection.

Treatment of Eosinophilic Keratitis

Topical corticosteroids: Dexamethasone 0.1%; use with caution if ulcerated
Topical antibiotics: For secondary bacterial infection prevention
Oral cetirizine: 0.4 mg/kg PO q12h; reduces recurrence
AVOID topical NSAIDs: May increase severity of eosinophilic keratitis
Treatment duration: Mean 64 days (range 45-106 days); self-limiting over 8-12 weeks in some cases
Superficial keratectomy: Shortest time to resolution (14 days in one study)

NAVLE TipEK Memory Aid - "EOSINOPHILIC = E.O.S.": Eyes are painful, Occurs in summer, Steroids are treatment of choice. Remember that topical NSAIDs are CONTRAINDICATED in eosinophilic keratitis - they may potentiate inflammation via leukotriene B4.

Prognosis

Prognosis varies significantly by IMMK subtype:

Epithelial: Excellent; rapid response to topical dexamethasone; rarely recurs
Superficial stromal: Good; responds to medical therapy or surgical keratectomy
Midstromal: Fair; responds to cyclosporine A but may require long-term therapy; episodic recurrence common
Endothelial: Poor; least amenable to therapy; often progresses despite treatment; highest risk of enucleation
Eosinophilic keratitis: Good; self-limiting but treatment accelerates resolution; may recur seasonally

High-YieldThe more CHRONIC the duration of IMMK prior to diagnosis, the POORER the response to medical therapy. Early intervention is critical for optimal outcomes.

Memory Aids for IMMK

IMMK Subtype Mnemonic: "SEME"

S = Superficial stromal (45%, most common)
E = (midstromal, dEEp) (27%)
M = (endothelial, inner-Most) (23%)
E = Epithelial (rare)

Treatment Selection: "Deep = Doom"

The DEEPER the IMMK lesion, the WORSE the prognosis and the MORE REFRACTORY to treatment. Endothelial IMMK = poor prognosis despite therapy.

CsA vs. Dexamethasone Decision

"CsA for Stroma, Dex for Surface": Cyclosporine A is first-line for stromal forms. Dexamethasone works best for epithelial IMMK.

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