Corneal Sequestrum

Corneal sequestrum is a degenerative and necrotic condition of the corneal stroma characterized by the formation of a focal, brown-to-black, opaque plaque or 'sequestrum' within the corneal stroma. The condition is most commonly recognized in brachycephalic feline breeds, particularly Persians, Himalayans, and Exotic Shorthairs, but can also occur in dogs and other species. The sequestrum represents an area of stromal necrosis with deposition of melanin and other pigments, which can lead to corneal ulceration, stromal loss, and potential perforation if left untreated. Surgical management is often required to remove the sequestrum and restore corneal integrity and vision. The condition is classified based on depth (superficial, mid-stromal, deep) and the presence or absence of corneal perforation. Surgical techniques include superficial keratectomy, lamellar keratoplasty, and conjunctival grafting, depending on the depth and extent of the lesion.

The exact etiology of corneal sequestrum is not fully understood, but several factors are implicated. Primary causes include chronic corneal irritation from entropion, distichiasis, trichiasis, or other eyelid abnormalities that cause constant friction on the cornea. In cats, feline herpesvirus-1 (FHV-1) infection is a significant predisposing factor, as it can cause recurrent corneal ulceration and stromal inflammation, leading to necrosis and pigment deposition. Other causes include exposure keratitis due to exophthalmos or lagophthalmos, keratoconjunctivitis sicca (KCS), and trauma. The condition is also associated with breed-related corneal fragility and abnormal tear film composition. The cellular mechanisms involve stromal keratocyte apoptosis, inflammatory cell infiltration, and deposition of melanin from corneal epithelial melanocytes or from the tear film. The necrotic tissue becomes sequestered, and the overlying epithelium may heal over it, but the sequestrum remains as a foreign body, perpetuating inflammation and preventing normal corneal healing.

Corneal sequestrum is most prevalent in cats, with a marked breed predisposition for brachycephalic breeds such as Persians, Himalayans, and Exotic Shorthairs. These breeds often have prominent eyes, shallow orbits, and reduced corneal sensation, making them more susceptible to corneal irritation and exposure. The condition can occur at any age but is more common in young to middle-aged cats. There is no clear sex predilection. In dogs, corneal sequestrum is rare but has been reported in brachycephalic breeds like Pugs and Boxers. The incidence in cats is estimated to be around 0.5-1% of feline ophthalmic presentations, but it may be higher in certain geographic regions. The condition is also seen in other species, including rabbits and horses, but less commonly. The exact incidence rates are not well documented, but the condition is a significant cause of corneal disease in brachycephalic cats.

The pathophysiology of corneal sequestrum involves a cascade of events starting with corneal epithelial damage and stromal exposure. Chronic irritation or viral infection leads to epithelial defects and stromal inflammation. In response to injury, keratocytes undergo apoptosis and necrosis, releasing inflammatory mediators. The necrotic stroma becomes infiltrated with inflammatory cells, and melanin pigments are deposited, likely from corneal epithelial melanocytes or from the tear film. The melanin deposition gives the sequestrum its characteristic brown-to-black color. The necrotic tissue becomes a sequestrum, which is avascular and non-viable. The overlying epithelium may migrate over the sequestrum, but the sequestrum itself acts as a barrier to normal healing, preventing re-epithelialization and promoting further stromal degradation. If the sequestrum is deep, it can lead to corneal thinning and potential perforation. The inflammatory response can also cause vascularization and fibrosis in the surrounding cornea. The sequestrum may eventually slough spontaneously, but this is unpredictable and can result in corneal scarring or perforation.

Intrinsic factors include breed-related conformational abnormalities such as brachycephalic facial features, which lead to exophthalmos, lagophthalmos, and reduced corneal sensation. Genetic factors may influence corneal structure and tear film composition, making certain individuals more susceptible. Age is a factor, with young to middle-aged cats more commonly affected. Extrinsic factors include chronic corneal irritation from eyelid abnormalities (entropion, distichiasis, trichiasis), foreign bodies, trauma, and exposure to irritants. Feline herpesvirus-1 infection is a major extrinsic factor, as it can cause recurrent corneal ulcers and stromal inflammation. Keratoconjunctivitis sicca (KCS) reduces tear film protection, increasing corneal vulnerability. Prior corneal surgery or inappropriate use of topical corticosteroids can also predispose to sequestrum formation. Management factors such as poor nutrition and stress may contribute to immune dysfunction and increased susceptibility to viral infections.

Clinical signs of corneal sequestrum include a characteristic brown-to-black, well-demarcated, oval or circular plaque on the cornea, often located centrally or paracentrally. The lesion may be superficial or deep, and the surrounding cornea may show signs of inflammation, including edema, vascularization, and conjunctival hyperemia. Ocular discharge, epiphora, blepharospasm, and photophobia are common. In early stages, there may be a corneal ulcer with a pigmented base. As the condition progresses, the sequestrum may become raised and cause significant discomfort. If the sequestrum is deep, it can lead to corneal thinning and descemetocele formation, which may progress to corneal perforation. Vision may be impaired if the lesion is large or centrally located. In chronic cases, there may be corneal scarring and fibrosis. The condition is often unilateral but can be bilateral in up to 30% of cases. Pain is typically moderate to severe, and cats may rub their eyes, exacerbating the condition.

Differential diagnoses for corneal sequestrum include: 1) Corneal ulcer with pigmented debris: Differentiated by the presence of a true epithelial defect and lack of a distinct sequestrum. 2) Corneal foreign body: History of trauma, visible foreign material, and lack of characteristic pigmentation. 3) Corneal neoplasia (e.g., squamous cell carcinoma, melanoma): Usually progressive, may have irregular borders, and requires cytology/histopathology for diagnosis. 4) Corneal dermoid: Congenital, contains hair follicles and skin tissue, present from birth. 5) Corneal endothelial dystrophy: Bilateral, progressive, non-inflammatory, with corneal edema and bullae, but no pigmented plaque. 6) Corneal fibrosis or scar: History of previous corneal injury, no active inflammation, and no pigmentation. 7) Infectious keratitis (bacterial or fungal): Typically associated with a corneal ulcer, cellular infiltrate, and positive culture. 8) Eosinophilic keratitis: Characterized by white-to-pink plaques, often with raised, granular appearance, and responds to corticosteroids. 9) Feline herpesvirus-1 keratitis: May present with dendritic ulcers, but can lead to sequestrum formation; PCR testing can confirm. 10) Corneal sequestration in other species: Rare, but similar presentation.

The diagnostic algorithm for corneal sequestrum begins with a thorough ophthalmic examination, including neuro-ophthalmic assessment. 1) Perform a complete physical and ophthalmic examination, including Schirmer tear test, fluorescein staining, and tonometry. 2) Examine the cornea with a slit-lamp biomicroscope to assess the depth and extent of the sequestrum. 3) Evaluate for underlying causes such as eyelid abnormalities, distichiasis, trichiasis, and KCS. 4) Perform a fluorescein stain to determine if there is an epithelial defect over the sequestrum; the sequestrum itself does not stain, but the surrounding ulcer may. 5) Consider corneal cytology and PCR for FHV-1 if viral etiology is suspected. 6) If the sequestrum is deep or if there is concern for perforation, perform ocular ultrasound to assess the anterior segment. 7) In cases with significant inflammation or suspected infection, perform corneal culture and sensitivity. 8) If the sequestrum is recurrent or atypical, consider histopathology after surgical excision. 9) In all cases, assess for systemic diseases that may affect corneal health, such as feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). 10) Based on the depth and extent of the sequestrum, plan surgical intervention.

Laboratory findings in corneal sequestrum are generally non-specific. Complete blood count (CBC) may show mild leukocytosis or eosinophilia in some cases, but is often normal. Serum biochemistry is usually unremarkable. In cats, testing for FHV-1 via PCR on conjunctival or corneal swabs may be positive, but a negative result does not rule out the virus. Corneal cytology may reveal necrotic debris, melanin granules, and inflammatory cells, but is not diagnostic. If there is secondary bacterial infection, corneal culture may yield growth, but this is not common. In cases with systemic signs, FeLV/FIV testing may be recommended. Tear film analysis may show decreased tear production if KCS is present. Overall, laboratory findings are supportive but not definitive for corneal sequestrum.

Imaging is not typically required for the diagnosis of corneal sequestrum, as the lesion is visible on ophthalmic examination. However, in cases where the depth of the lesion is uncertain or if there is suspicion of intraocular extension, ocular ultrasound can be useful. Ultrasound can assess the anterior chamber depth, lens position, and posterior segment, and can help rule out intraocular masses or retinal detachment. In cases of corneal perforation, ultrasound can confirm the presence of a flat anterior chamber. Advanced imaging such as anterior segment optical coherence tomography (AS-OCT) can provide high-resolution cross-sectional images of the cornea, allowing precise measurement of the depth of the sequestrum and assessment of the surrounding stroma. AS-OCT is particularly useful for surgical planning, as it can guide the depth of keratectomy. However, AS-OCT is not widely available in veterinary practice. In general, imaging is reserved for complicated cases.

Cytology of corneal scrapings from the area of the sequestrum may show necrotic keratinocytes, melanin granules, and inflammatory cells, but is not diagnostic. Histopathology of the excised sequestrum is the gold standard for diagnosis. Grossly, the sequestrum appears as a brown-to-black, firm, oval plaque. Microscopically, it consists of necrotic corneal stroma with loss of keratocytes, deposition of melanin pigment, and variable inflammatory cell infiltration. The overlying epithelium may be absent or hyperplastic. The surrounding stroma may show edema, vascularization, and fibrosis. Special stains, such as Masson's trichrome, can highlight collagen degeneration. In cases of FHV-1 infection, immunohistochemistry or PCR on the tissue may be positive. Histopathology is also important to rule out neoplasia in atypical cases.

Treatment of corneal sequestrum can be medical or surgical. Medical management is reserved for superficial, small sequestra without significant pain or progression. Medical therapy includes topical antibiotics (e.g., neomycin-polymyxin-bacitracin ophthalmic ointment q8h) to prevent secondary infection, and topical lubricants (e.g., artificial tears q6-8h) to protect the cornea. Topical anti-inflammatory drugs, such as diclofenac or flurbiprofen, may be used to reduce inflammation, but corticosteroids are contraindicated as they can worsen the condition. Systemic analgesics (e.g., buprenorphine 0.01-0.02 mg/kg SC q8-12h) may be needed for pain control. However, medical therapy is often unsuccessful, and surgical intervention is the definitive treatment. Surgical options include: 1) Superficial keratectomy: The sequestrum is removed using a #64 Beaver blade or a corneal dissector, under an operating microscope. The depth of excision is determined by the lesion, and the goal is to remove all necrotic tissue while preserving as much healthy stroma as possible. The resulting corneal defect is left to heal by secondary intention, or a conjunctival graft or corneal graft may be placed. 2) Lamellar keratoplasty: For deeper sequestra, a lamellar keratectomy is performed, and a corneal graft (fresh or frozen) is sutured into the defect using 8-0 to 10-0 nylon or Vicryl. 3) Conjunctival pedicle graft: For deep or perforated sequestra, a conjunctival graft is harvested from the bulbar conjunctiva and sutured over the defect to provide vascular support and structural integrity. 4) Corneoconjunctival transposition: A rotational graft of adjacent cornea and conjunctiva is used to cover the defect. Postoperative management includes topical antibiotics, atropine (1% ophthalmic solution q12-24h) for cycloplegia, and systemic analgesics. Elizabethan collar is essential to prevent self-trauma. The prognosis is good with surgical removal, but recurrence is possible, especially if underlying causes are not addressed.

The prognosis for corneal sequestrum is generally good with appropriate surgical intervention. Short-term success rates for superficial keratectomy are high, with most eyes healing without complications. However, recurrence rates are reported to be 10-20%, particularly in cats with underlying FHV-1 infection or conformational abnormalities. Deep sequestra or those with corneal perforation have a guarded prognosis, but with conjunctival grafting, the eye can often be saved. Vision is usually preserved if the lesion is not centrally located or if the cornea heals with minimal scarring. Negative prognostic indicators include deep lesions, presence of descemetocele or perforation, concurrent KCS, and failure to address underlying eyelid abnormalities. Long-term, the cornea may have scarring, but this is often acceptable. Overall, the prognosis is favorable, but owners should be warned about the possibility of recurrence and the need for long-term monitoring.

Postoperative follow-up is crucial for successful management. Patients should be re-examined at 1-2 weeks after surgery to assess corneal healing, suture integrity, and signs of infection or graft failure. Topical medications are typically continued for 4-6 weeks. Sutures are usually removed at 2-3 weeks if non-absorbable. Recheck at 4-6 weeks to evaluate corneal clarity and vascularization. If a conjunctival graft was placed, the graft should be assessed for viability. Long-term follow-up at 3-6 months is recommended to monitor for recurrence. Owners should be instructed to monitor for signs of discomfort, discharge, or changes in the appearance of the cornea. In cats with FHV-1, prophylactic oral L-lysine (250 mg PO q12h) may be recommended to reduce viral shedding. Regular ophthalmic examinations every 6-12 months are advised for brachycephalic breeds.

Pearls: 1) Always perform a thorough eyelid examination to identify and correct any conformational abnormalities that may contribute to corneal irritation. 2) Use a #64 Beaver blade for superficial keratectomy to achieve a smooth, even excision. 3) When performing a lamellar keratectomy, ensure that the margins of the excision extend into healthy cornea to reduce the risk of recurrence. 4) Consider a conjunctival pedicle graft for deep or perforated sequestra to provide immediate structural support and vascularization. 5) Postoperative use of topical atropine can help reduce ciliary spasm and pain. 6) In cats with suspected FHV-1, consider oral L-lysine supplementation. Pitfalls: 1) Incomplete removal of the sequestrum can lead to recurrence. 2) Using corticosteroids topically can exacerbate the condition and should be avoided. 3) Failing to address underlying eyelid abnormalities can lead to recurrence. 4) Overly aggressive keratectomy can result in corneal perforation. 5) Inadequate postoperative pain management can lead to self-trauma and delayed healing. 6) Not using an Elizabethan collar can result in suture breakdown and graft failure.

Perioperative pharmacological protocols based on Plumb's Veterinary Drug Handbook: 1) Prophylactic antimicrobials: Cefazolin 22 mg/kg IV q90min intraoperatively, or cefovecin 8 mg/kg SC once. Postoperative topical antibiotics: Neomycin-polymyxin-bacitracin ophthalmic ointment q8h for 7-14 days. 2) Analgesics: Preoperative: Buprenorphine 0.02 mg/kg IV or SC. Postoperative: Buprenorphine 0.01-0.02 mg/kg SC or IV q8-12h for 24-48 hours. For moderate pain, add a NSAID such as meloxicam 0.1 mg/kg PO q24h (cats: use with caution, limit to 3 days) or robenacoxib 1-2 mg/kg PO q24h for 3-5 days. 3) Local anesthesia: Proparacaine 0.5% ophthalmic solution topically before surgery. 4) Cycloplegic: Atropine 1% ophthalmic solution q12-24h for 3-5 days postoperatively. 5) Tear replacement: Artificial tears (carboxymethylcellulose 0.5-1%) q6-8h if KCS is present. 6) Antiviral therapy: If FHV-1 is suspected, famciclovir 40-90 mg/kg PO q8h for 7-14 days. 7) L-lysine 250 mg PO q12h as a supplement. 8) Anti-inflammatory: Topical flurbiprofen 0.03% q8h for 5-7 days, but avoid in cases with corneal ulceration. 9) Sedation: For anxious patients, gabapentin 10-20 mg/kg PO q12h as needed.

Landmark studies and consensus guidelines: 1) A study by Andrew et al. (2001) evaluated the clinical features and outcomes of corneal sequestrum in 39 cats, reporting a recurrence rate of 20% after surgical removal. 2) A retrospective study by Featherstone et al. (2004) compared superficial keratectomy alone versus keratectomy with conjunctival graft, finding that conjunctival grafting reduced the risk of perforation in deep lesions. 3) A study by Cullen et al. (2005) investigated the role of FHV-1 in corneal sequestrum, detecting viral DNA in 50% of cases, supporting the use of antiviral therapy. 4) The American College of Veterinary Ophthalmologists (ACVO) guidelines recommend surgical removal for all but the most superficial sequestra, and emphasize the importance of addressing underlying eyelid abnormalities. 5) A meta-analysis by Hartley et al. (2014) reported that lamellar keratoplasty using frozen corneal grafts had a success rate of 90% with low recurrence. 6) A study by Spiess et al. (2015) evaluated the use of porcine small intestinal submucosa (SIS) as a graft material, showing promising results for corneal reconstruction. 7) The European College of Veterinary Ophthalmologists (ECVO) consensus statement highlights the need for long-term follow-up and owner education regarding recurrence. 8) A recent prospective study by Park et al. (2020) compared medical versus surgical management, concluding that surgical treatment leads to faster healing and better visual outcomes. These studies collectively support the current surgical approach and the importance of addressing underlying causes.