Feline corneal sequestrum: diagnosis and treatment

Feline corneal sequestrum (FCS) is a common condition that is easily missed by owners in its early stages. It can also be clinically confused with other entities, such as a corneal foreign body. There are also situations where certain procedures, such as repeated debridement or grid keratotomy, can initiate the development of a corneal sequestrum.

A corneal sequestrum is a devitalised portion of the corneal stroma that has become necrotic. As it subsequently gets rejected by surrounding healthy corneal tissue, it can act like a foreign body and induce varying degrees of inflammation.

This condition was first described in the 1960s, and although rare case reports of a similar disease in dogs and horses exist (Bouhanna et al., 2008; Dubin et al., 2013; McLellan and Archer, 2000), it is a type of corneal pathology that appears to be unique to cats. It is seen with relative frequency in daily practice; in a recent study, FCS made up 25 percent of cases presenting with corneal disease at one centre over an eight-year period (Gómez et al., 2023).

As it subsequently gets rejected by surrounding healthy corneal tissue, [ a corneal sequestrum] can act like a foreign body and induce varying degrees of inflammation

The origin of the brown discoloration typifying FCS has yet to be elucidated. Electron microscopy studies have demonstrated coccoid bodies or granules within affected stroma (Souri, 1975). Melanin and porphyrins have been postulated but are not unequivocally found in all sequestrum specimens (Cullen et al., 2005; Featherstone et al., 2004; Newkirk et al., 2011). 

Recognising corneal sequestrum

Clinically, a corneal sequestrum appears as an oval to circular area of corneal discoloration, usually central or paracentral. It ranges from a faint, translucent, ill-defined amber or “tea”-coloured stain (usually in the early stages of disease) to a darker brown/bronze, which, with chronicity, can progress to a dense, opaque, jet-black, well-circumscribed plaque (Figures 1, 2 and 3). 

The location of a sequestrum may be indicative of the source of chronic corneal irritation; for example, lateral lower lid entropion may result in a temporally located sequestrum (Figure 4). Interestingly, Gómez et al. (2023) documented that corneal sequestra were more likely to be axially located in brachycephalic breeds and dorso-temporal in non-brachycephalic breeds. Corneal sequestra usually occur unilaterally; however, bilateral lesions can arise simultaneously or sequentially, particularly in Persians and similar purebred cats (Featherstone and Sansom, 2004).

Lesions may vary significantly in:

• Size/extent (from 1 to 10mm in diameter (Andrew et al., 2001))
• Depth (more commonly affects the anterior to mid stroma, but full-thickness involvement with corneal perforation can occur (Figure 5))
• Whether there is concurrent ulceration

Clinical signs include varying degrees of blepharospasm, epiphora and conjunctival hyperaemia – all manifestations of ocular discomfort. Differential diagnoses are listed in Box 1.

Pathogenesis

The aetiopathogenesis of FCS is still not fully understood; however, causal associations between several different types of chronic corneal insult and sequestrum formation have been demonstrated. These include: 

• Eyelid abnormalities like distichiasis or entropion (with resultant trichiasis) 
• Brachycephalic breed-related adnexal abnormalities, such as exophthalmos, lagophthalmos, entropion and medial canthal trichiasis
• Poor central corneal sensitivity and poor precorneal tear film (which are also strongly associated with brachycephaly)
• Feline herpesvirus (FHV-1) infection
• Iatrogenic causes

Feline herpesvirus

Typically, FHV-1 involvement should be suspected in cats with previous recurrent corneal ulceration, geographic corneal ulcers (the so-called “non-healing ulcers”), recurrent conjunctivitis or blepharospasm. 

FHV-1 may be an important predisposing cause of sequestrum formation in domestic shorthaired cats, with 55.1 percent of cats affected with FCS being FHV-1 positive in one study (Nasisse et al., 1998). However, it is less so in the brachycephalics (eg Persians, Exotic Shorthairs, Himalayans and Burmese) and potentially other purebred cats (eg Sphynx and Siamese), where other factors such as eyelid conformation and/or a possible hereditary basis may predominate. In a recent retrospective study, Persians were the most represented breed at 71.5 percent of sequestrum cases, followed by the Exotic Shorthair at 12.2 percent (Multari et al., 2021).

FHV-1 involvement should be suspected in cats with previous recurrent corneal ulceration, geographic corneal ulcers, recurrent conjunctivitis or blepharospasm

Iatrogenic causes

Iatrogenic corneal insult has also been associated with this condition. La Croix et al. (2001) found that treating non-healing superficial corneal ulcers in cats by debridement and grid keratotomy resulted in sequestrum development in 10 and 31 percent of eyes, respectively.

Thus far, cats have not been shown to develop spontaneous chronic corneal epithelial defects (SCCEDs) as seen in dogs. Therefore, debridement of the ulcer bed, such as via grid keratotomy, is an inappropriate form of treatment in these cases. 

Diagnostic tests

• Schirmer tear test (STT-1) and tear film break-up time (TFBUT) – to assess for underlying tear film dysfunction in non-ulcerated eyes
• Fluorescein staining – fluorescein uptake may often be appreciated at the edges of the lesion and in adjacent cornea if there is secondary corneal ulceration
• Corneal cytology – when corneal ulceration is noted, and especially in cases where a creamy-yellow corneal infiltrate is seen, as findings can guide topical antibiotic treatment choice
• FHV-1 testing – less useful as viral shedding is short-lived. Furthermore, it has been shown that a large percentage of the cat population are herpesvirus carriers; hence, direct association is difficult to prove. Clinical signs and history (eg initial viral infection with reported respiratory signs, recurrent conjunctivitis, non-healing corneal ulceration, originating from a multi-cat household, experiencing a recent stressor) are often sufficient to raise clinical suspicion of FHV-1

Treatment options

As with most conditions, medical management versus surgery are the two broad approaches to dealing with an FCS. Deciding which approach to adopt may be based on several factors, including the degree, extent and/or depth of corneal involvement, the presence or absence of ocular discomfort and the finances available. 

Accurate depth assessment of a sequestrum can be difficult and becomes increasingly so as the lesion progresses. This is because the dense, dark, necrotic stroma obscures deeper layers of the cornea, so examination may not be conclusive, even with slit-lamp biomicroscopy and higher magnification. Decisions about conservative versus surgical management cannot therefore be made based on presumed sequestrum depth; any surgeon operating on a sequestrum must be prepared to perform a grafting procedure if indicated. 

Medical management

Medical management has been advocated in cases where the sequestrum is very superficial and the patient is asymptomatic or appears comfortable (Figure 6). However, extrusion of the sequestrum towards the superficial corneal layers can take weeks to months (during which the cat may be in discomfort) or simply never occur. Additionally, if there is near full-thickness stromal involvement, sloughing of the sequestrum bears the risk of corneal perforation. Therefore, medical management should only be considered in select cases (such as those in which owners are reluctant to pursue surgical treatment due to financial constraints or patients with higher anaesthetic risk) and with ample warning of possible risks.

Key points to note when formulating a treatment plan are:

1. Pain is invariably present in the face of corneal ulceration
2. Secondary bacterial infiltration can occur and lead to keratomalacia if not addressed

A typical regime would include a topical antibiotic drop or ointment, a lacrimomimetic (ideally hyaluronate-based), potentially a systemic NSAID if there are no contraindications and, if there is clinical suspicion of FHV-1 involvement, a topical and/or systemic antiviral (eg topical ganciclovir q6 to 8h or oral famciclovir at 90mg/kg PO q8 to 12h).

Surgical treatment

Because disease progression is unpredictable, surgical management in the form of a keratectomy, with or without the placement of a graft to repair the ensuing corneal defect, is the treatment of choice. Surgery more reliably shortens the course of disease – recovery times of one to three months versus one month to a year with medical treatment (Dalla et al., 2007) – and is indicated if there is ocular pain, evidence of secondary bacterial infection and/or the lesion involves deep layers of the corneal stroma. 

An early surgical approach will reduce procedure complexity and costs and increase the likelihood of complete and safe excision of the sequestrum with reduced scarring.

What surgical technique should be used to treat corneal sequestrum?

A lamellar keratectomy forms the basis of all surgical techniques to address FCS. For anterior- to mid-stromal sequestra, a superficial keratectomy alone (Figure 7) may be appropriate and sufficient and has not been shown to lead to significantly higher recurrence rates. Placement of a soft bandage contact lens post-operatively aids ocular comfort and confers protection to the keratectomy site. 

If the sequestrum is found to extend during keratectomy and excision of half the corneal thickness/width or deeper is required to fully remove the lesion, a graft is indicated to provide tectonic support

In contrast, if the sequestrum is found to extend during keratectomy and excision of half the corneal thickness/width or deeper is required to fully remove the lesion, a graft is indicated to provide tectonic support (Figures 8 to 11). Adjunctive surgery to address the potential underlying cause (eg entropion or trichiasis) may be advised at the same time. (The various surgical techniques used to address FCS and their recurrence rates are summarised in Table 1.)

Subsequent development of FCS in the contralateral eye can occur in about 27 percent of cats (Gómez et al., 2023). Some studies suggest that brachycephalic cats are more prone to this, while others have not found this to be the case, suggesting that chronic ocular surface disease is a greater contributing factor than skull conformation. Therefore, having a conscious awareness of ocular health and implementing measures to improve or safeguard it may make a significant difference to patients.

	Surgical procedure		Images			Reported FCS recurrence rates
Non-grafting procedures	Superficial lamellar keratectomy alone		FIGURE (7A) Three-year-eight-month-old male neutered Exotic Shorthair with a corneal sequestrum in the right eye and bilateral medioventral entropion FIGURE (7B) The same eye at two weeks post-keratectomy and bilateral lower entropion correction			11 to 13 percent    (Multari et al., 2021; Pumphrey et al., 2019)
Grafting procedures	Conjunctival pedicle graft		FIGURE (8) Conjunctival pedicle graft, one month post-operatively, in the right eye of a three-year-old female Persian cat			5 percent (1/20 eyes) to 11.5 percent (6/52 eyes)   (Gómez et al., 2023; Multari et al., 2021)
	Corneo-conjunctival transposition (CCT) graft		FIGURE (9) Corneo-conjunctival transposition graft, one month post-operatively, in the left eye of a three-year-old female Persian cat			0 percent 8.3 percent 14.3 percent (1/7 eyes)   (Andrew et al., 2001; Graham et al., 2017; Multari et al., 2021; Yang et al. 2019)
	Others: fresh/frozen corneal transplants (ie homologous or heterologous keratoplasty)					0 percent (0/6 eyes)  2.9 percent  5 percent   (Laguna et al., 2015; Michel et al., 2021; Peña Gimenez and Fariña, 2002)
	Commercially available non-corneal biomaterial grafts	Amniotic membrane (equine or human based)	FIGURE (10) Post-keratectomy and Omnigen amnion graft in the right eye of a 10-year-old male neutered Persian cat. This patient also underwent bilateral medial canthoplasty			0 percent (0/7 eyes); however, graft necrosis and corneal perforation in 28 percent   (Barachetti et al., 2010)
		Porcine urinary bladder acellular matrix (ACell Vet graft)				0 (0/7 cats) to 3 percent (1/32 cats) (Balland et al., 2016)   23 percent graft dehiscence (both cats and dogs) (Chow and Westermeyer, 2016)
		Porcine small intestinal submucosa (Vetrix BioSISsingle-layer or multi-layer)	FIGURE (11A) BioSIS combined with a CCT 14 days post-surgery, in the left eye of a 12-year-old female spayed domestic shorthair FIGURE (11B) The same eye 50 days post-surgery			14 percent (5/34 eyes)    20 percent (1/5 cats)   22 percent (2/9 eyes) that received BioSIS alone   0 percent (0/6 eyes) that had BioSIS and conjunctival pedicle graft   (Featherstone et al., 2001; Goulle, 2012; Multari et al., 2021)
		Bovine pericardium (Tutopatch graft)				0/3 cats (followed up to 6 months post-op)   (Dulaurent et al., 2014)

Possible future treatment options

At present, no known treatment reliably prevents sequestrum formation; however, the use of ocular lubricants/mucinomimetics may provide additional corneal protection and possibly reduce the risk of recurrence. Additionally, pre-emptive treatment of conditions that may precipitate the formation of FCS (eg surgery to correct suboptimal eyelid conformation and entropion) may benefit some individuals. 

Take-home messages

• When dealing with FCS, consider if any form of chronic corneal insult that could be addressed is present (eg entropion)
• In cats with “non-healing” ulcers or other recurrent ocular signs, FHV-1 involvement should be suspected and treatment initiated. Repeated debridement and grid keratotomy should be avoided
• Surgical management of FCS is the gold standard. Medical treatment may be considered in select cases, and owners should be well informed about associated risks (prolonged disease course/non-resolution and concomitant discomfort, etc)
• Recurrence of sequestrum in the same eye (even if surgery has been performed) is possible, and about a quarter of cats go on to develop another sequestrum in their contralateral eye. Owner expectations should thus be managed appropriately