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Basics ⬇

Outline

BASICS

Overview!!navigator!!

  • IMMK is a diagnosis utilized to identify a group of corneoconjunctival diseases characterized by chronic (>3 months) corneal opacities associated with variable degrees of cellular infiltrate (mild, moderate, or severe) and corneal vascularization. In general, secondary uveitis and ocular discomfort are mild to moderate, if present. Associated infectious agents are rarely identified, generally only as a result of secondary corneal ulceration and subsequent infection
  • Systems affected—ophthalmic

Signalment!!navigator!!

All ages and breeds of horses can be affected.

Signs!!navigator!!

  • Corneal opacification with mild to moderate cellular infiltrate and variable degrees of vascularization
  • Cellular infiltrate may appear yellow to white and may be associated with diffuse corneal discoloration and bullous corneal edema during phases of active, uncontrolled inflammation
  • There are five currently recognized forms of IMMK, four of which are categorized based on their location within the cornea—epithelial, superficial stroma, midstromal, and endothelial
  • Eosinophilic keratoconjunctivitis represents the fifth type. It demonstrates similarities to epithelial or anterior stromal forms of IMMK, but eosinophils are the predominant cells present
  • Epithelial and subepithelial, anterior stromal keratopathies have also been suggested as being early manifestations of IMMK
  • Endothelial IMMK is characterized by endothelial cellular infiltrates and focal or diffuse corneal edema without signs of anterior uveitis
  • Equine IMMK is commonly a unilateral disease, but both eyes can be affected

Causes and Risk Factors!!navigator!!

Immune mediated.

Diagnosis ⬆ ⬇

Outline

DIAGNOSIS

Differential Diagnosis!!navigator!!

  • Other nonulcerative keratopathies such as onchocerciasis, bacterial or fungal stromal infections (stromal abscesses), viral keratitis, infiltrative neoplasia, corneal degeneration or dystrophy, calcific band keratopathy, and bullous keratopathy
  • Chronic recurrent or persistent ulcerative keratitis or indolent ulcers
  • Specific manifestations of anterior uveitis (e.g. equine recurrent uveitis)
  • Acute or chronic glaucoma, and Descemet's membrane detachment (all of which present with variable degrees of corneal edema and ocular discomfort)
  • Infectious keratitis, especially keratomycosis, is usually more acute in onset and associated with secondary anterior uveitis and more severe ocular discomfort. However, subtle and chronic forms of epithelial, subepithelial keratomycosis associated with minimal discomfort may be a challenge to differentiate based on clinical appearances only. Cytology is necessary to rule out an infectious process

CBC/Biochemistry/Urinalysis!!navigator!!

N/A

Other Laboratory Tests!!navigator!!

  • Rule out infectious causes (bacterial or fungal) by corneal scrapings of superficial lesions for cytology, culture, and possibly histopathology
  • Deeper lesions can only be sampled during surgical intervention (e.g. lamellar or penetrating keratoplasty)

Imaging!!navigator!!

Digital infrared photography can help to differentiate corneal fibrosis from cellular infiltration and may help to identify the presence of subtle corneal (ghost) vessels.

Other Diagnostic Procedures!!navigator!!

N/A

Pathologic Findings!!navigator!!

  • Histopathology, in cases of non-eosinophilic keratoconjunctivitis, reveals stromal fibrosis, vascularization, and cellular infiltrates consisting mainly of lymphocytes and plasma cells
  • In corneal biopsies obtained during keratectomy of anterior or midstromal IMMK, lymphoplasmacytic inflammation predominates. Concomitant histiocytic and polymorphonuclear cell inflammation may be present in variable degrees. Additionally, stromal necrosis, hyperplastic corneal epithelium, stromal edema, and hyalinization, as well as neovascularization, may be identified during histologic evaluation
  • Recent immunohistochemical and immunopathologic evaluation of superficial stromal biopsy samples from horses with IMMK suggest that the pathogenesis is driven predominantly by T cells, with both helper and cytotoxic T cells being involved

Treatment ⬆ ⬇

TREATMENT

  • While many cases of IMMK respond well to topical medication, they often require chronic, low-grade continuous treatment to prevent relapses. Horses that have frequent relapses or that do not respond favorably to topical medical therapy may require surgical intervention to remove cellular infiltrates with or without a concomitant grafting procedure (e.g. amniotic membrane or conjunctival graft). Although once thought to be curative, relapses after surgical intervention in the form of a lamellar keratectomy ± conjunctival graft are being, anecdotally, more frequently identified. Thus, the search for an alternative intervention with long-term control of IMMK is a timely and important research topic
  • Two promising interventions demonstrating the potential for long-term disease control with minimal risk of complication and without the need for chronic immune-suppressive medical therapy have recently been described:
    • Bulbar subconjunctival injections of autologous bone marrow-derived mesenchymal stem cells showed promising results as it resulted in a notable reduction of corneal opacification and degeneration
    • Photodynamic therapy utilizing intrastromal indocyanine green as the photosensitive agent activated by diffuse 810 nm infrared diode laser energy has been shown to suppress active inflammation and eliminate the need for long-term topical medical therapy for up to 1.5 years in the preliminary report
    • Both treatments resulted in long-term corneal clearing and vascular regression over periods of up to 1.5 years without continual topical immune-suppressive therapy. While much research remains to be carried out before definitive answers become available, both treatment modalities have the potential to change the way that IMMK is managed in the future
  • Additionally, the use of episcleral silicone matrix cyclosporine (ciclosporin) drug delivery devices have recently been shown to effectively control anterior and midstromal IMMK
  • Of all types of IMMK, endothelial IMMK is the least amenable to medical treatment

Medications ⬆ ⬇

Outline

MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Topical corticosteroids (1% prednisolone acetate or 0.1% dexamethasone every 24 h to effect) is generally utilized initially, in combination with topical cyclosporine A every 12 h to achieve a state of quiescence. Once the clinical signs have been controlled, topical medications can be slowly tapered off (corticosteroids) or tapered down (cyclosporine A) to the lowest possible maintenance dosage (generally, this will be achieved with every 48–72 h dosage frequencies)
  • Complete or incomplete clinical improvement with topical anti-inflammatory medication helps to confirm the diagnosis and to decide when surgical or alternative intervention is indicated and/or warranted

Contraindications/Possible Interactions!!navigator!!

N/A

Follow-up ⬆ ⬇

FOLLOW-UP

Expected Course and Prognosis

  • Unless implemented surgical or alternative options achieve the desired results, long-term topical treatment every 12–72 h may be required to control the disease and prevent recurrences
  • Routine follow-up examinations are essential in recognizing recurrence of inflammation or secondary ulcerative complications

Miscellaneous ⬆ ⬇

Outline

MISCELLANEOUS

Associated Conditions!!navigator!!

  • Superficial corneal ulcers may develop concurrently with any type of IMMK that is poorly controlled. These ulcers may become secondarily infected, especially if corticosteroids are concomitantly being utilized
  • Superficial corneal ulcers may also develop secondary to chronic corneal edema associated with endothelial IMMK

Abbreviations!!navigator!!

  • IMMK = immune-mediated keratitis
  • NSAID = nonsteroidal anti-inflammatory drug

Suggested Reading ⬆ ⬇

Braus BK, Miller I, Kummer S, et al. Investigation of corneal autoantibodies in horses with immune mediated keratitis (IMMK). Vet Immunol Immunopathol 2017;187:48–54.

Brooks DE. Ophthalmology for the Equine Practitioner, 2e. Jackson, WY: Teton NewMedia, 2008.

Clode AB, Matthews AG. Diseases and surgery of the cornea. In: Gilger BC, ed. Equine Ophthalmology. Maryland Heights, MO: WB Saunders, 2011:183–266.

Gilger BC, Michau TM, Salmon JH. Immune-mediated keratitis in horses: 19 cases (1998–2004). Vet Ophthalmol 2005;8:233–239.

Gilger BC, Stoppini R, Wilkie DA, et al. Treatment of immune-mediated keratitis in horses with episcleral silicone matrix cyclosporine delivery devices. Vet Ophthalmol 2014;17(Suppl. 1):23–30.

Matthews AG, Gilger BC. Equine immune-mediated keratopathies. Vet Ophthalmol 2009;12(Suppl. 1):10–16.

McMullen Jr RJ, Clode AB, Gilger BC. Infrared digital imaging of the equine anterior segment. Vet Ophthalmol 2009;12:125–131.

Pate DO, Clode AB, Olivry T, et al. Immunohistochemical and immunopathological characterization of superficial stromal immune-mediated keratitis in horses. Am J Vet Res 2012;73:1067–1073.

Author(s) ⬆

Author: Richard J. McMullen Jr.

Consulting Editor: Caryn E. Plummer

Acknowledgment: The author and editor acknowledge the prior contribution of Andras M. Komaromy.