Feline Corneal Sequestrum

By Martin Coster, DVM, MS, DACVO
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ophthalmology@angell.org
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Corneal Sequestrum¹

Corneal sequestration is thought to occur under conditions of chronic irritation, or dryness of the corneal surface. The sequestrum is devitalized, acellular corneal stroma (Figure 1) that can range in color from very light brunescence (Figure 2) to dark black (Figure 3). The color has been ascribed to high iron content, melanin pigment, or porphyrin pigments from the tearfilm, and no single hypothesis has been definitively proven nor disproven.^2-4

Figure 1: Histopathology of a feline corneal sequestrum sample. Normal deep corneal stroma, depicted at the bottom of the image, is composed of pale to medium pink-staining collagen with evenly dispersed stromal cells and artifactual white clefts. In contrast, the necrotic anterior stroma forming the sequestrum at the top of the image is deeply purple to almost brown-tinged, devoid of cells, and more compact. The epithelium which normally forms the anterior surface of the cornea is absent.

Figure 2: Light brown corneal sequestrum in a cat. The sequestrum has been fluorescein stained, with the superior aspect highlighted in green.

Figure 3: Dark corneal sequestrum in a cat. Note the tips of the vertical pupil visible behind the dark corneal lesion; the author has sometimes seen sequestrum cases mistaken and referred for a mis-shapen pupil on a cursory examination. There is an epithelial lip around the edge of the sequestrum; to the right of the lesion is an incidental hair on the cornea.

The inciting cause of sequestrum can be irritation from entropion⁵ (congenital, developmental, traumatic, or secondary to aging orbital fat loss) (Figure 4), corneal ulceration (most commonly chronic herpesvirus infection), or breed-related exposure keratitis (Persians, Burmese, Himalayans, or other brachycephalic cats with lagophthalmia; Figure 5).⁶

Figure 4: Corneal sequestrum secondary to inferior entropion in a cat.

Figure 5: Corneal sequestrum in a brachycephalic cat.

When a sequestrum is noted, careful evaluation of the globe and orbit should be made to ensure that the eyelids are able to blink to cover the cornea – ruling out orbital space-occupying lesions (abscess, neoplasia, or feline restrictive myofibrosarcoma [orbital pseudotumor]),^7,8 buphthalmia from glaucoma, or eyelid abnormalities such as agenesis. Sequestra can also form after grid keratotomy procedures in the cat, and as such grids are generally contraindicated for non-complicated superficial indolent corneal ulceration.⁹ Tear film insufficiency (“dry eye”) may¹⁰ or may not¹¹ play a role.

Figure 6 – Large corneal sequestrum in a cat, sitting on the surface of the cornea like a “scab”. Although superficial sequestra can spontaneously slough, it is impossible to determine the depth of the lesion with an eye exam; high resolution ultrasound can help.

Corneal sequestra are typically extremely painful due to epithelial erosion. The corneal epithelium is generally unable to heal across the sequestrum, presumably due to an inability to form tight junctions over the devitalized tissue, and this leads to loose epithelial edges that are a constant source of pain as each blink disrupts the tissue. Rarely, epithelialization can occur over the sequestrum, leading to a more comfortable state, although further ulceration can later occur. Sometimes, the sequestrum can slough from the cornea, allowing for spontaneous resolution. Figure 6 shows a superficial corneal sequestrum that might slough. Unfortunately, the timeframe for sloughing can be weeks, months, or years – and with chronicity, the risks increase for infection or thickening of the sequestrum to full-thickness involvement, with resultant corneal perforation. This means that referral for microsurgical management is the general treatment of choice for any corneal sequestrum.

In those cases where medical management is elected with informed consent (for reasons of finances, unacceptable anesthetic risk, etc.), the principles of treatment encompass ocular lubrication, broad spectrum antibiosis, pain control, and management of any underlying conditions. Erythromycin ointment is a good first choice topical medication, avoiding the potential for anaphylaxis with triple antibiotic ointment, and is recommended q 2-6h depending on the amount of corneal coverage available from the eyelids. Suspected or presumed herpesvirus involvement or secondary bacterial keratitis require specific treatment. Prophylactic therapy of the contralateral eye should be considered in predisposed breeds or bilateral conditions, with an artificial tears ointment q 8-12h.

Surgical management of corneal sequestra will depend on the depth of the lesion, which can be determined with high-resolution ultrasound¹² and even spectral domain optical coherence tomography,¹³ but is more often an intraoperative decision as the layers of sequestered tissue are excised. Generally, superficial sequestra respond to superficial keratectomy with or without contact lens placement and a third eyelid flap, and this is the author’s preferred approach.^14-16 For mid-stromal lesions, cyanoacrylate adhesive (tissue glue) with contact lens placement may be used to aid post-healing following keratectomy.¹⁷

For deeper stromal lesions, corneoconjunctival transposition (Figure 7) can be performed (up to 2/3 stromal depth),^18-20 but conjunctival grafting (Figure 8) will likely be performed for very deep, perforated, or infected lesions. Conjunctival grafting may be considered for any lesion, to provide better tectonic support and vascularization to the affected area, but will result in the least satisfactory visual outcome. Other less-commonly used materials available for providing tectonic support to a cornea following excision of a sequestrum include porcine urinary bladder, bovine pericardium, amniotic membrane, corneal transplantation, and synthetic ACell Vet™.^21-25

Figure 7 – One-day post-operative corneo-conjunctival transposition graft following keratectomy for corneal sequestrum, in a cat. In this procedure, the axial sequestrum is excised by keratectomy, and normal clear cornea is transposed by sliding into the central defect, with conjunctiva following. Once healed, the central cornea regains almost complete clarity.

Figure 8 – Conjunctival graft for corneal reconstruction following keratectomy for an axial deep corneal sequestrum.

If general anesthesia is contraindicated or not possible, the author has had moderate success with corneal debridement procedures such as diamond burring and thermal cautery (a.k.a. thermokeratoplasty Figure 9), and even grid keratotomy, performed over the surface of light sequestra. These procedures are considered contraindicated with superficial ulcers due to the formation of sequestrum, but once there is a sequestrum present there is little to lose except potentially hastening the time to surgery. In highly compliant patients or with deep sedation, sequestra that are already starting to slough may be partially excised by an ophthalmologist using a Beaver scalpel blade and/or corneal scissors.

Figure 9 – Post-operative thermal cautery (a.k.a. thermokeratoplasty) for light brunescent corneal sequestrum (visible in the axial cornea with faint green fluorescein stain present). Note the opaque spots where thermal cautery was applied, and the epithelial ridge surrounding the lesion following cotton swab debridement. This cornea epithelialized and regained long-term comfort.

Acknowledgement

The author wishes to thank Dr. Pamela Mouser, DACVP for providing the histopathology image.

References

1. Maggs DJ. Cornea and sclera In: Maggs DJ, Miller PE,Ofri R, eds. Slatter’s Fundamentals of Veterinary Ophthalmology. 4th ed. St. Louis, MO: Saunders Elsevier, 2008;175-202.
2. Cullen CL, Wadowska DW, Singh A, et al. Ultrastructural findings in feline corneal sequestra. Vet Ophthalmol 2005;8:295-303.
3. Featherstone HJ, Sansom J. Feline corneal sequestra: a review of 64 cases (80 eyes) from 1993 to 2000. Vet Ophthalmol 2004;7:213-227.
4. Featherstone HJ, Franklin VJ, Sansom J. Feline corneal sequestrum: laboratory analysis of ocular samples from 12 cats. Vet Ophthalmol 2004;7:229-238.
5. Williams DL, Kim J-Y. Feline entropion: a case series of 50 affected animals (2003–2008). Vet Ophthalmol 2009;12:221-226.
6. Nasisse MP, Glover TL, Moore CP, et al. Detection of feline herpesvirus 1 DNA in corneas of cats with eosinophilic keratitis or corneal sequestration. Am J Vet Res 1998;59:856-858.
7. van der Woerdt A. Orbital Inflammatory Disease and Pseudotumor in Dogs and Cats. Vet Clin North Am Small Anim Pract 2008;38:389-401.
8. Billson FM, Miller-Michau T, Mould JRB, et al. Idiopathic sclerosing orbital pseudotumor in seven cats. Vet Ophthalmol 2006;9:45-51.
9. La Croix NC, van der Woerdt A, Olivero DK. Nonhealing corneal ulcers in cats: 29 cases (1991-1999). J Am Vet Med Assoc 2001;218:733-735.
10. Uhl LK, Saito A, Iwashita H, et al. Clinical features of cats with aqueous tear deficiency: a retrospective case series of 10 patients (17 eyes). J Feline Med Surg 2019;21:944-950.
11. Grahn BH, Sisler S, Storey E. Qualitative tear film and conjunctival goblet cell assessment of cats with corneal sequestra. Vet Ophthalmol 2005;8:167-170.
12. Bentley E, Miller PE, Diehl KA. Use of high-resolution ultrasound as a diagnostic tool in veterinary ophthalmology. J Am Vet Med Assoc 2003;223:1617-1622.
13. Famose F. Assessment of the use of spectral domain optical coherence tomography (SD-OCT) for evaluation of the healthy and pathological cornea in dogs and cats. Vet Ophthalmol 2014;17:12-22.
14. Peiffer RL, Jr., Gelatt KN. Superficial keratectomy for the treatment of chronic ulcerative keratitis and sequestrum in the domestic cat. Feline Pract 1976;6:37-40.
15. Gelatt KN, Peiffer RL, Stevens J. Chronic ulcerative keratitis and sequestrum in the domestic cat. J Am Anim Hosp Assoc 1973;9:204-213.
16. Gaiddon J, Kaswan RL, Hirsh SG. Radial keratotomy and third eyelid flap: results of a novel approach to treatment of nonprogressive stromal ulcers and defects among dogs and cats. Vet Comp Ophthalmol 1996;6:218-219.
17. Pumphrey SA, Desai SJ, Pizzirani S. Use of cyanoacrylate adhesive in the surgical management of feline corneal sequestrum: 16 cases (2011-2018). Vet Ophthalmol 2019;22:859-863.
18. Andrew SE, Tou S, Brooks DE. Corneoconjunctival transposition for the treatment of feline corneal sequestra: a retrospective study of 17 cases (1990-1998). Vet Ophthalmol 2001;4:107-111.
19. Graham KL, White JD, Billson FM. Feline corneal sequestra: outcome of corneoconjunctival transposition in 97 cats (109 eyes). J Feline Med Surg 2017;19:710-716.
20. Yang VY, Labelle AL, Breaux CB. A bidirectional corneoconjunctival transposition for the treatment of feline corneal sequestrum. Vet Ophthalmol 2019;22:192-195.
21. Balland O, Poinsard AS, Famose F, et al. Use of a porcine urinary bladder acellular matrix for corneal reconstruction in dogs and cats. Vet Ophthalmol 2016;19:454-463.
22. Dulaurent T, Azoulay T, Goulle F, et al. Use of bovine pericardium (Tutopatch(R)) graft for surgical repair of deep melting corneal ulcers in dogs and corneal sequestra in cats. Vet Ophthalmol 2014;17:91-99.
23. Barachetti L, Giudice C, Mortellaro CM. Amniotic membrane transplantation for the treatment of feline corneal sequestrum: pilot study. Vet Ophthalmol 2010;13:326-330.
24. Laguna F, Leiva M, Costa D, et al. Corneal grafting for the treatment of feline corneal sequestrum: a retrospective study of 18 eyes (13 cats). Vet Ophthalmol 2015;18:291-296.
25. Chow DW, Westermeyer HD. Retrospective evaluation of corneal reconstruction using ACell Vet^TM alone in dogs and cats: 82 cases. Vet Ophthalmol 2016;19:357-366.