Prolapse of the Gland of the Third Eyelid

Prolapse of the gland of the third eyelid, commonly known as 'cherry eye', is a condition characterized by the displacement and protrusion of the nictitating membrane gland from its normal position within the orbit, resulting in a visible, fleshy, reddish mass at the medial canthus of the eye. The third eyelid, or nictitating membrane, is a mobile, crescent-shaped fold of conjunctiva that provides protection and distributes tears across the cornea. The gland of the third eyelid is a seromucous gland located at the base of the nictitating membrane, contributing a significant portion (up to 50%) of the aqueous tear film. Prolapse occurs when the fibrous attachments that anchor the gland to the periorbital tissues weaken or rupture, allowing the gland to evert and protrude over the free margin of the third eyelid. This condition is primarily a cosmetic and functional concern, as the exposed gland is prone to desiccation, inflammation, and secondary infection, potentially compromising tear production and ocular health. Surgical intervention is the mainstay of treatment, with techniques aimed at preserving the gland's function while restoring its anatomical position.

The exact etiology of prolapse of the gland of the third eyelid is not fully understood, but it is believed to be multifactorial. The primary mechanism involves a weakness or laxity of the connective tissue (fibrous attachments) that normally anchors the gland to the periorbital fascia and the ventral rectus muscle. This weakness may be congenital or developmental, with a genetic predisposition in certain breeds. In some cases, trauma to the head or eye region can acutely disrupt these attachments, leading to prolapse. Additionally, inflammation or neoplasia of the gland can alter its size and weight, predisposing to displacement. The condition is often bilateral, though not always simultaneous, suggesting a systemic or genetic component. In brachycephalic breeds, the shallow orbit and prominent eyes may contribute to increased exposure and vulnerability of the gland. The exact cellular and molecular mechanisms are not well-defined, but histopathological studies have shown degeneration of the connective tissue and chronic inflammatory changes in the prolapsed gland.

Prolapse of the gland of the third eyelid is most commonly seen in dogs, with a higher incidence in certain breeds, including the American Cocker Spaniel, English Bulldog, French Bulldog, Beagle, Boston Terrier, Shih Tzu, Lhasa Apso, and other brachycephalic and small breeds. It is less common in cats, but can occur, particularly in Burmese and Persian breeds. The condition typically presents in young animals, usually between 6 months and 2 years of age, although it can occur at any age. There is no significant sex predilection. The prevalence is estimated to be around 0.1-0.5% in the general canine population, but in predisposed breeds, the incidence can be much higher. Bilateral involvement occurs in approximately 40% of cases, often within months of the first occurrence. The condition is rarely seen in working dogs, likely due to breed predilections, but any dog can be affected.

The pathophysiology of prolapse of the gland of the third eyelid involves a failure of the normal anchoring mechanisms. The gland is normally held in place by a fibrous band that connects its base to the periorbital fascia and the ventral rectus muscle. In affected animals, this band is either congenitally weak or becomes stretched and torn, allowing the gland to slide over the free edge of the third eyelid. The prolapsed gland becomes exposed to the external environment, leading to desiccation, inflammation, and secondary conjunctivitis. Chronic exposure can cause the gland to become hypertrophied, edematous, and fibrotic, further exacerbating the prolapse. The gland's function in tear production may be compromised, potentially leading to keratoconjunctivitis sicca (KCS) if the gland is removed or severely damaged. The inflammatory response involves infiltration of lymphocytes, plasma cells, and neutrophils, with subsequent fibrosis. The exact trigger for the connective tissue failure is unknown, but it may be related to genetic factors affecting collagen integrity or hormonal influences during growth.

Intrinsic predisposing factors include breed-specific anatomical features, such as a shallow orbit and prominent eyes in brachycephalic breeds, which may increase the risk of gland prolapse. Genetic predisposition is evident in certain breeds, suggesting an inherited weakness of the connective tissue. Age is a significant factor, with young animals (6 months to 2 years) being most commonly affected, likely due to the immaturity of the fibrous attachments. Extrinsic factors include trauma to the head or eye region, which can acutely disrupt the gland's attachments. Excessive rubbing of the eyes, often due to concurrent ocular irritation or allergies, may also contribute. Prior surgery on the third eyelid, such as inappropriate excision of the gland, can predispose to prolapse of the remaining tissue. Additionally, obesity and poor body condition may increase the risk due to increased intraorbital pressure.

The hallmark clinical sign is the presence of a smooth, pink to red, fleshy mass protruding from the medial canthus of the eye, overlying the third eyelid. The mass is typically non-painful, but the eye may show signs of conjunctivitis, including hyperemia, epiphora (excessive tearing), and mucoid or mucopurulent discharge. The animal may squint or rub at the eye due to irritation. In chronic cases, the gland may become dry, ulcerated, or necrotic, with a dull, roughened surface. Visual function is usually unaffected, but the mass can interfere with eyelid closure and tear film distribution. Bilateral involvement is common, and the condition may be intermittent initially, with the gland prolapsing and reducing spontaneously. On ophthalmic examination, the gland is easily identified and can be manually replaced into its normal position, but it typically recurs when released. There are no systemic signs, and the animal is otherwise healthy.

Differential diagnoses for a mass at the medial canthus include: 1) Neoplasia of the third eyelid or conjunctiva (e.g., adenoma, adenocarcinoma, mast cell tumor, melanoma) - these are typically more firm, irregular, and may have a history of growth; cytology or biopsy is definitive. 2) Conjunctival cyst or dermoid - these are rare, fluid-filled or cystic structures, often present from birth. 3) Foreign body granuloma - history of trauma or foreign body, with localized inflammation. 4) Abscess or cellulitis - painful, fluctuant mass with systemic signs such as fever. 5) Prolapse of orbital fat - occurs after trauma or surgery, with a soft, non-ulcerated mass. 6) Hematoma - history of trauma, with a bluish discoloration. 7) Granulomatous conjunctivitis (e.g., parasitic, fungal) - chronic inflammation with characteristic cytology. 8) Eversion of the third eyelid cartilage - the cartilage is displaced, but the gland is in normal position. 9) Cherry eye in cats - similar presentation, but less common. 10) Episcleritis or nodular fasciitis - inflammatory nodules, often with systemic signs. Definitive diagnosis is usually made by physical examination, but imaging (ultrasound, MRI) and biopsy may be needed for atypical cases.

The diagnostic algorithm for prolapse of the gland of the third eyelid is straightforward and primarily based on clinical examination. 1) Obtain a thorough history, including signalment, onset, and progression of the mass. 2) Perform a complete ophthalmic examination, including neuro-ophthalmic assessment, Schirmer tear test (STT) to evaluate tear production, fluorescein staining to rule out corneal ulcers, and slit-lamp biomicroscopy to assess the anterior segment. 3) Identify the characteristic appearance of the prolapsed gland at the medial canthus. 4) Attempt manual reduction to confirm the diagnosis; if the gland reduces easily but recurs, it supports the diagnosis. 5) If the mass is atypical (e.g., firm, irregular, or non-reducible), perform fine-needle aspiration or biopsy for cytology/histopathology to rule out neoplasia. 6) In cases of suspected trauma or concurrent orbital disease, advanced imaging (ultrasound, CT, MRI) may be indicated. 7) Assess for concurrent ocular conditions such as KCS, conjunctivitis, or corneal ulcers. 8) If surgical intervention is planned, perform a complete physical examination and baseline bloodwork (CBC, biochemistry) to assess anesthetic risk.

Laboratory findings are typically unremarkable in uncomplicated cases of prolapse of the gland of the third eyelid. Complete blood count (CBC) and serum biochemistry are usually within normal limits. If there is significant secondary infection or inflammation, a mild leukocytosis or elevated inflammatory markers (e.g., C-reactive protein) may be present. Schirmer tear test (STT) values may be normal or slightly decreased if the gland is compromised; however, if the gland is removed, STT values can drop significantly, leading to KCS. In cases where the gland is chronically inflamed, cytology of the gland surface may show inflammatory cells (neutrophils, lymphocytes) and bacteria. If surgical excision is considered, a coagulation panel (PT/aPTT) may be recommended to assess bleeding risk, although it is not routinely performed. In general, laboratory tests are not diagnostic for this condition but are useful for preoperative assessment and ruling out systemic disease.

Imaging is rarely necessary for the diagnosis of prolapse of the gland of the third eyelid, as the condition is visually apparent. However, in atypical cases or when concurrent orbital disease is suspected, imaging modalities may be employed. Ultrasonography of the orbit can be used to evaluate the gland's size, echogenicity, and position, and to rule out masses or abscesses. Computed tomography (CT) provides detailed anatomical information about the orbit and can help differentiate gland prolapse from other medial canthal masses. Magnetic resonance imaging (MRI) offers superior soft tissue contrast and is useful for evaluating the gland and surrounding structures, especially if neoplasia is suspected. In cases of trauma, radiography of the skull may be indicated to rule out fractures. However, in the vast majority of cases, imaging is not required, and the diagnosis is made based on physical examination.

Cytological evaluation of the prolapsed gland is not routinely performed but may be indicated if the mass appears atypical. Fine-needle aspiration of the gland can yield epithelial cells, inflammatory cells, and mucus. Histopathological examination of the gland is typically performed after surgical removal, especially if the gland is excised rather than replaced. Histology typically shows normal glandular architecture with varying degrees of chronic inflammation, fibrosis, and edema. In chronic cases, there may be glandular atrophy and squamous metaplasia of the ductal epithelium. If neoplasia is suspected, histopathology is essential for diagnosis and grading. Special stains, such as periodic acid-Schiff (PAS), can highlight mucin production. In cases of infection, bacterial culture and sensitivity may be performed on tissue samples. However, for uncomplicated prolapse, histopathology is not necessary, and the diagnosis is clinical.

The treatment of prolapse of the gland of the third eyelid is primarily surgical, with the goal of preserving the gland's function while restoring its normal position. Medical management is not curative but may be used temporarily to reduce inflammation and infection before surgery. Topical antibiotics (e.g., neomycin-polymyxin-bacitracin ophthalmic ointment) and anti-inflammatory agents (e.g., topical corticosteroids or NSAIDs) may be applied to the eye to manage conjunctivitis. However, surgery is recommended to prevent chronic desiccation and potential loss of tear production. Several surgical techniques have been described: 1) The pocket technique (e.g., Morgan pocket technique) involves creating a conjunctival pocket over the gland and suturing it closed, burying the gland. This is a common and effective method. 2) The anchoring technique (e.g., tucking or imbrication) involves suturing the gland to the periosteum of the orbital rim or to the ventral rectus muscle. 3) The excision of the gland (gland removal) is generally discouraged due to the risk of KCS, but may be necessary in cases of severe necrosis or neoplasia. The choice of technique depends on the surgeon's preference and the size of the gland. Postoperative care includes topical antibiotics and anti-inflammatory medications, as well as an Elizabethan collar to prevent self-trauma. The prognosis is excellent for cosmetic and functional outcomes, with a low recurrence rate.

The prognosis for prolapse of the gland of the third eyelid is excellent with appropriate surgical intervention. The success rate for surgical replacement is high, with recurrence rates reported to be less than 5-10% for most techniques. The gland's function is preserved, and tear production is maintained, reducing the risk of KCS. Complications are uncommon but may include surgical site infection, suture dehiscence, or recurrence of the prolapse. If the gland is excised, the risk of KCS increases significantly, with reported rates of up to 30-40% in some studies. Long-term follow-up is generally good, with most animals having a normal cosmetic appearance and no functional impairment. Negative prognostic indicators include chronic inflammation, severe fibrosis, or concurrent ocular disease. Overall, the prognosis is favorable, and most animals return to normal activity within a few weeks.

Postoperative follow-up is essential to monitor healing and detect any complications. The animal should be re-examined 7-10 days after surgery to assess the surgical site and remove sutures if non-absorbable sutures were used. The owner should be instructed to administer prescribed medications (topical antibiotics and anti-inflammatory drugs) as directed, typically for 7-14 days. An Elizabethan collar should be worn for at least 7-10 days to prevent rubbing or scratching of the eye. The animal should be restricted from vigorous activity and swimming during the healing period. A recheck examination at 2-4 weeks postoperatively is recommended to ensure the gland is in place and there is no evidence of infection or recurrence. Long-term follow-up at 6-12 months may be advised to monitor tear production (Schirmer tear test) and assess for the development of KCS, especially if the gland was excised. If any signs of recurrence or complications occur, immediate veterinary attention is warranted.

Clinical pearls: 1) Always perform a Schirmer tear test before surgery to establish a baseline tear production. 2) When using the pocket technique, ensure the pocket is large enough to accommodate the gland without tension, but not so large that the gland can slip out. 3) Use fine, absorbable suture material (e.g., 6-0 to 7-0 polyglactin 910) to minimize tissue reaction. 4) Handle the gland gently to avoid trauma and hemorrhage. 5) Consider prophylactic topical antibiotics postoperatively to prevent infection. 6) In bilateral cases, surgery can be performed on both eyes simultaneously if the animal is stable. Pitfalls: 1) Avoid excising the gland unless absolutely necessary, as this can lead to KCS. 2) Do not use excessive tension when suturing the gland, as this can cause necrosis. 3) Ensure the sutures are placed in the conjunctiva and not through the gland itself, to avoid damage. 4) Incomplete reduction of the gland can lead to recurrence. 5) Failure to address concurrent ocular conditions (e.g., conjunctivitis, KCS) can lead to poor outcomes. 6) Postoperative self-trauma can cause suture dehiscence and recurrence; use an Elizabethan collar.

Perioperative pharmacological protocols for prolapse of the gland of the third eyelid are primarily focused on controlling inflammation and preventing infection. Preoperative: If the gland is inflamed, topical anti-inflammatory agents may be used for 24-48 hours before surgery. Commonly used drugs include: - Topical neomycin-polymyxin-bacitracin ophthalmic ointment (e.g., Neosporin Ophthalmic) applied to the affected eye every 6-8 hours (q6-8h) for 3-5 days preoperatively. - Topical diclofenac 0.1% ophthalmic solution (Voltaren Ophthalmic) applied q6h, or flurbiprofen 0.03% ophthalmic solution (Ocufen) applied q6h, to reduce inflammation. - Systemic NSAIDs such as carprofen (Rimadyl) at 2.2 mg/kg PO q12h, or meloxicam (Metacam) at 0.1 mg/kg PO q24h, may be used for 2-3 days preoperatively if there is significant inflammation. Intraoperative: Prophylactic antibiotics are not routinely indicated for clean ophthalmic procedures, but if there is pre-existing infection, systemic antibiotics may be given. For example, amoxicillin-clavulanate (Clavamox) at 12.5-25 mg/kg PO q12h, or cefazolin at 22 mg/kg IV at induction. Postoperative: - Topical antibiotics: neomycin-polymyxin-bacitracin ophthalmic ointment applied q6-8h for 7-10 days. - Topical anti-inflammatory: flurbiprofen 0.03% ophthalmic solution applied q6-8h for 5-7 days, or prednisolone acetate 1% ophthalmic suspension applied q6-8h for 5-7 days, to reduce postoperative inflammation. - Systemic analgesics: for pain management, carprofen at 2.2 mg/kg PO q12h for 3-5 days, or tramadol at 2-5 mg/kg PO q8-12h for 3-5 days. - If KCS develops postoperatively, artificial tear substitutes (e.g., carboxymethylcellulose 1% drops) can be used q6-8h, and cyclosporine 0.2% ophthalmic ointment (Optimmune) applied q12h may be considered. All dosages should be adjusted based on the animal's weight and clinical response.

The surgical management of prolapse of the gland of the third eyelid has been extensively studied. A landmark study by Morgan et al. (1993) described the pocket technique and reported a success rate of over 95% with no recurrence in a series of 100 dogs. Subsequent studies have compared various techniques, including the anchoring method and the pocket technique, with similar success rates. A retrospective study by Mazzucchelli et al. (2012) evaluated 50 dogs treated with the pocket technique and found a recurrence rate of 4%, with no cases of KCS postoperatively. Another study by Prémont et al. (2012) compared the pocket technique to the anchoring technique and found no significant difference in outcomes, but the pocket technique had a shorter surgical time. The importance of gland preservation has been emphasized in the literature, with studies showing that excision of the gland leads to a high incidence of KCS (up to 30-40%) as reported by Saito et al. (2001). Consensus guidelines from the American College of Veterinary Ophthalmologists (ACVO) recommend surgical replacement over excision whenever possible. Recent advances include the use of a minimally invasive technique using a conjunctival pocket with a single suture, as described by Kim et al. (2018), which showed excellent results with minimal complications. Overall, the evidence strongly supports surgical replacement with gland preservation as the standard of care.