Challenges in diagnosing canine spindle cell tumours using immunohistochemistry, illustrated by three nonpigmented malignant cases from the nictitating membrane.

BACKGROUND: Nonpigmented malignant spindle cell tumours of the membrana nictitans are rare in dogs. In twenty-three years only three cases have been diagnosed in Scandinavia. This study describes the three cases of malignant tumours of the membrana nictitans recorded by the Eye Pathology Section, University of Copenhagen, Denmark, with reference to the clinical appearance and work-up, the treatment and prognosis, and the histopathological description including immunohistochemistry. The three cases are compared to previous publications on canine tumours of the nictitating membrane. We emphasize the importance of using protocols that are adapted to the specific species such as dogs. Opposite the human tissue responses, we even need more than one marker when diagnosing melanomas in dogs. RESULTS: The dogs presented were an 8-year-old Dachshund, a 12-year-old Akita and a 14-year-old Shetland Sheepdog. All three dogs were entire females. All three nictitating membrane tumours developed on the right nictitating membrane as firm or multilobulated hyperaemic masses. Two of the tumours were macroscopically nonpigmented, the third being partly pigmented on the surface and ulcerated. According to the histopathology and for two of the cases immunohistochemistry with dog-adapted protocols the diagnoses included one hemangiosarcoma and two amelanotic melanomas. Tumour regrowth developed in all three cases and repeated resections were completed 1, 2 and 3 times, respectively, with recurrence experienced within 1.5 months - 3 years. CONCLUSIONS: Nonpigmented malignant spindle cell tumours of the canine membrana nictitans are rare. Treatment of choice should be complete excision with a minimal histologic tumour-free distance and in case of a recurrence a full resection of the nictitating membrane. We strongly recommend a dog-adapted protocol for immunohistochemistry.

Association of FGF4L1 Retrogene Insertion with Prolapsed Gland of the Nictitans (Cherry Eye) in Dogs.

Cherry eye is the common name for prolapse of the nictitans gland, a tear-producing gland situated under the third eyelid of dogs. Cherry eye is characterized by a red fleshy protuberance in the corner of the eye, resembling a cherry. This protrusion is a displacement of the normal gland of the third eyelid, thought to be caused by a defect in the connective tissue that secures the gland in place. Options for treatment may include anti-inflammatory medications in mild cases, but surgical replacement of the gland is usually indicated. Cherry eye is most often seen in dogs under the age of two years, with certain breeds having a higher incidence, suggesting a potential genetic association. Integration of panel genetic testing into routine clinical practice allows for the generation of large numbers of genotyped individuals paired with clinical records and enables the investigation of common disorders using a genome-wide association study (GWAS) approach at scale. In this investigation, several thousand cases and controls for cherry eye in both purebred dogs and mixed breeds are used for a large-scale GWAS, revealing a single peak of genome-wide significance on canine chromosome 18, directly at the location of the previously identified FGF4 insertion known to cause chondrodysplasia in several breeds.

Tumor-like lymphoplasmacytic conjunctivitis in the third eyelid in a dog.

This report aims to describe a case of tumor-like lymphoplasmacytic conjunctivitis in a 7-year-old spayed-female Pomeranian. On complete ophthalmic examination, a mass with papillary projections was noted on the bulbar surface of the right third eyelid. Debulking of the mass was performed while preserving as much of the third eyelid as possible. On the histopathological examination, the mass was diagnosed as lymphoplasmacytic conjunctivitis with mild epithelial hyperplasia. Although a slight regrowth of the mass was noted 3 weeks after surgery, intralesional injection of triamcinolone acetonide led to its disappearance. There was no further recurrence after 5 months.

Changes in tear production in a dog with keratoconjunctivitis sicca for a year after inevitable nictitating membrane gland resection due to suspicion of a malignant tumour.

Since the removal of the NM causes KCS in dogs, it was contraindicated to remove the NM unless unavoidable such as in a malignant tumour. However, to the best of author's knowledge, there are no reports of conjunctivitis and keratitis owing to decreased tear production following removal of the NM gland. This case study demonstrates the tear production changes in a dog for a year after removal of the nictitating membrane (NM) due to suspicion of a malignant tumour. A 13-year-old spayed female English Cocker Spaniel who had suffered from severe ocular discharge, discomfort, keratoconjunctivitis sicca (KCS), and NM enlargement in the right eye was brought to our hospital. The dog could not tolerate treatment with topical 0.2% cyclosporine or corticosteroids. The dog's right eye had NM gland prolapse, severe follicular conjunctivitis and a very low Schirmer tear test-1 (STT-1) value of 3 mm/min. Furthermore, the result of fine needle aspiration of the enlarged NM gland suggested a risk of malignancy. Despite the risk of KCS, complete NM resection was performed to diagnose the tumour. Fortunately, the final histopathological evaluation revealed chronic inflammation without any evidence of malignancy. Contrary to concerns that the STT-1 value would further decrease after the removal of the NM gland, the STT-1 value remained elevated compared to that before surgery, and the clinical symptoms improved for a year. It is generally known that NM gland resection is not recommended due to the risk of developing iatrogenic KCS unless a malignant tumour is suspected. In this case, surgical removal of the inflammatory NM gland that was not responsive to medications had a positive effect on KCS. Since the inflammatory and structural disease of the NM was strengthening KCS, the outcome was thought to be different from that when the normal third eyelid was removed.

Marsupialization for the treatment of nictitating membrane cyst in a dog: case report / Marsupialização para o tratamento de cisto em membrana nictitante de cão: relato de caso

This study aims to describe the first Brazilian report of a nictitating membrane cyst's surgical treatment in a dog. A 6-month-old female French Bulldog presented at HOSVET-UNIME with a reddish mass-like structure in the medial canthus of both eyes, with a history of recurrent third eyelid gland prolapse previously treated with two surgeries performed at another clinic. Physical examination revealed a third eyelid gland prolapse in the right eye and a cyst in the left eye's third eyelid. The animal was submitted to surgical correction of the right eye's third eyelid prolapse using pocket technique and of the left eye's third eyelid using marsupialization technique for the cyst's treatment. 180 days after th1e surgical procedure no recurrence was observed. The marsupialization technique for the treatment of a third eyelid's lacrimal cyst in a dog allowed the maintenance of its gland and prevented the formation of a new cystic cavity.(AU)

O objetivo do presente trabalho é descrever o primeiro relato no Brasil de tratamento cirúrgico de um cisto da membrana nictitante em um cão. Um Buldogue Francês, fêmea, seis meses, foi atendido no Hosvet-Unime, com queixa de aumento de volume avermelhado no canto medial de ambos os olhos, com histórico de recidiva de prolapso de glândula da terceira pálpebra, onde haviam sido realizadas duas cirurgias anteriormente em outro local. Ao exame físico, foi observado prolapso de glândula da terceira pálpebra no olho direito e a presença de um cisto na terceira pálpebra do olho esquerdo. O animal foi submetido ao procedimento cirúrgico de sepultamento de glândula da terceira pálpebra no olho direito e uma marsupialização na terceira pálpebra do olho esquerdo para o tratamento do cisto. Cento e oitenta dias após o procedimento cirúrgico, não foi observada recidiva. A técnica de marsupialização para tratamento de cisto lacrimal na terceira pálpebra em um cão possibilitou a manutenção da sua glândula e impediu a formação de nova cavidade cística.(AU)

Surgical treatment of nictitans gland prolapse and cartilage eversion accompanying the nictitating membrane (third eyelid) rotation in cats.

The third eyelid rotation associated with the nictitans gland prolapse and third eyelid cartilage eversion is a rarely encountered ocular disorder. The present retrospective study includes the distribution of the relevant deformations in the cartilage and nictitans gland accompanying the third eyelid rotation in the cat according to breed, age, and gender-based differences, as well as the clinical manifestations, surgical therapeutic approach (partial resection of the scrolled car- tilage portion combined with the Morgan pocket technique), and the outcome of the procedure, concurrently monitoring whether or not the functions of the nictitating membrane were preserved after the procedure, the likelihood of relapse and the potential complications. A total of sixteen eyes surgically treated with the above-mentioned surgical method that belonged to thirteen cats diagnosed with the nictitans gland prolapse and cartilage eversion accompanying the third eyelid rotation were included in the study. The most common breeds were Persian (38.4%) and British shorthair (38.4%), with five cases from each. Three cats (20%) were bilaterally affected, while there was a unilateral involvement in ten of the cases (80%). Out of the ten cases with a unilateral lesion, the right eye was affected in 6 (60%) individuals, while the left eye was involved in four (40%). Nine cats were male, and four were female. The study was conducted in an attempt to surgically correct the third eyelid cartilage eversion and prolapsed nictitans gland responsible for the nictitating membrane rotation in cats by the partial removal of the everted cartilage com- bined with the Morgan pocket technique. Follow-ups were performed twice every other week in the postoperative period, followed by a one-time clinical inspection at the end of the first, third, and sixth months.

Treatment of prolapsed gland and cartilage deformity of the nictitating membrane with pocket technique and chondrectomy alone, or combined with a wedge conjunctivectomy: 132 dogs (1998-2018).

OBJECTIVE: To evaluate the results obtained using Morgan pocket technique and chondrectomy (MPTC) alone, or combined with a wedge conjunctivectomy (MPTC + WC) for the treatment of prolapsed gland associated with cartilage deformity of the nictitating membrane (PGCD) in dogs. PROCEDURE: Medical records of dogs diagnosed with PGCD that received a MPTC or MPTC + WC were reviewed between 1998 and 2018. Success rate was defined by lack of recurrence of the prolapsed gland with a minimum of 6 months follow-up. Histological examination of the excised cartilage was performed in 13 eyes. RESULTS: A total of 132 dogs (181 eyes) met the inclusion criteria. Median follow-up time was 25 months (range, 6-166 months). MPTC was used in 131 eyes with 91.6% success rate. MPTC + WC was used in 50 eyes with 100% success rate. Postoperative complications occurred in 6.9% and 4%, respectively, for MPTC and MPTC + WC, including lacrimal cysts (8 eyes) or corneal erosion (3 eyes). Recurrence and complications rates were significantly lower using MPTC + WC compared with MPTC in the giant breed dogs (P = .019 and P = .002, respectively), but not in the overall study population (P = .328 and P = .290, respectively). Histological cartilage anomalies were noted in 2/13 specimens from chronic PGCD. CONCLUSIONS: MPTC + WC offers a good therapeutic option for giant breed dogs with PGCD. The combined technique provides a good apposition and mobility of the nictitating membrane onto the ocular surface and potentially reduces the risk of recurrence in these giant canine breeds.

Nictitating membrane fixation improves stability of the contact lens on the animal corneal surface.

We evaluated the feasibility and safety of nictitating membrane fixation to address reduced contact lens stability by the nictitating membrane in a rabbit model. Under general anesthesia, twelve animals received a horizontal mattress suture between the nictitating membrane and the upper eyelid of one eye. To assess the effects of this technique and secondary side effects, contact lens stability test, Schirmer tear test, tear break-up time measurement, eye tissue pathology and morphology were evaluated. Contact lens stability was increased after nictitating membrane fixation. The percentage of contact lens retention in the nictitating membrane fixed rabbit after 4 hours was 90% whereas that in the untreated rabbit was 42.5%. In addition, there were no significant differences in tear quantity and quality between the fixed and untreated eyes. Furthermore, no remarkable pathological lesions were found in gross observation during the 1-month time period or the following pathological examination. In this study, we demonstrated that nictitating membrane fixation increases contact lens stability without specific side effects using a rabbit model. This minimally invasive procedure could be useful when designing animal models for testing new contact lenses and has potential to apply to other biomaterial research on the ocular surface.

Persistent unilateral nictitating membrane in a 9-year-old girl: A rare case report.

We report a case of persisting nictitating membrane in a 9-year-old girl presenting to us with the complaints of fleshy mass in the medial part of the left eye since birth, which was nonprogressive. On examination, her left eye was amblyopic with a vision of 20/500. The membrane was continuous with the medial canthus and was spread in a horizontal fashion, covering the underlying bulbar conjunctiva and one-third of the cornea. The globe however moved freely underneath the membrane, indicating no attachment between the globe and overlying membrane. The patient underwent simple excision of the nictitating membrane with good outcome.

Marsupialization of a cyst of the nictitating membrane in three dogs.

BACKGROUND: Development of cysts has been reported as a potential complication after surgical repositioning of nictitating membrane gland protrusion using the conjunctival pocket technique. To the authors' knowledge, no treatment for these cysts has ever been published. OBJECTIVES: This short case series describes a surgical technique of marsupialization as a treatment option for these cysts and proposes a pathogenesis for cyst formation. CASES DESCRIPTION: Three dogs were each referred for a unilateral subconjunctival mass-like lesion involving the bulbar side of the nictitating membrane. Complete ophthalmologic examination revealed a pink, translucent, soft, and nonpainful mass protruding from the bulbar surface of the nictitating membrane in all cases. Treatment consisted in marsupialization of the cyst on the palpebral surface of the nictitating membrane and was curative with no short-term postoperative complication and favorable long-term outcome for the three dogs. Histopathological findings were consistent with a lacrimal cyst. CONCLUSION: Marsupialization appears to be a safe, simple, and effective treatment for nictitating membrane cyst secondary to surgical correction of gland prolapse using conjunctival pocket technique in dogs. Further studies on a larger number of cases are necessary to determine whether marsupialization is the technique of choice and to further investigate the pathophysiology of cyst formation after conjunctival pocket repositioning of prolapsed glands.

Use of a nictitating membrane flap for treatment of feline acute corneal hydrops-21 eyes.

OBJECTIVE: To evaluate the effectiveness of the use of a nictitating membrane flap (NMF) as therapy in 19 cats (21 eyes) affected with feline acute corneal hydrops (FACH). METHODS: Medical records from 19 cats diagnosed with FACH and treated with a NMF were retrospectively evaluated. Information was collected from multiple veterinary hospitals and included signalment, medical history, therapy, and ocular outcome. RESULTS: Breeds included 13 Domestic Shorthairs, 2 Exotic Shorthairs, 2 Maine Coons, 1 Persian, and 1 Domestic Medium Hair. Two cats were bilaterally affected. Median age of cats was 3.2 years (range 0.26-15 years). Eleven patients were spayed females, 6 were neutered males, and 2 were intact males. Topical steroids were previously administered in 5 (23.8%) eyes; oral steroids were previously administered in 7 cats (36.8% of patients); three patients received both oral and topical steroids. Thirteen of 21 (61.9%) eyes had a history of ocular disease including ulcerative and nonulcerative keratitis, anterior uveitis, corneal sequestrum, conjunctivitis, and glaucoma. Median duration of NMF was 15 days (range 6-30 days). Follow-up ranged from 12 to 1601 days (median 169 days). Corneal perforation occurred in 1 (4.7%) eye and was successfully repaired. One lesion (4.7%) in a diabetic patient did not resolve. Nineteen of the treated eyes (90.5%) resolved with no complications. CONCLUSIONS: A nictitating membrane flap successfully treated 90.5% of FACH eyes (89.5% of patients).

Pocket technique or pocket technique combined with modified orbital rim anchorage for the replacement of a prolapsed gland of the third eyelid in dogs: 353 dogs.

The aim of this retrospective study was to evaluate the results obtained in 353 dogs (420 eyes) using two different surgical techniques for correction of a prolapsed gland of the third eyelid: the Morgan's pocket technique and a technique combining Morgan's approach with a slightly modified periosteal anchoring technique of Stanley and Kaswan. The pocket technique was used in 234 eyes and the combined technique in 186 eyes. Successful repositioning was obtained in 95% of all cases, with recurrence occurring in 5%. The recurrence rate in large breed dogs such as the English Bulldog and Boxer was lower with the combined technique than with the pocket technique.

Unilateral choristoma of the nictitating membrane in a horse.

CASE DESCRIPTION: A 2-year-old Morgan mare was evaluated because of a corneal ulceration. CLINICAL FINDINGS: An irregular, deep stromal corneal ulcer in an area of malacia was noted in the left eye. Hypopyon was present in the ventral portion of the anterior chamber with moderate aqueous flare. The nictitating membrane of the left eye had hairs originating from its leading edge that contacted the corneal surface. TREATMENT AND OUTCOME: General anesthesia was induced, and a bulbar pedicle conjunctival graft was performed. The conjunctiva at the leading edge of the nictitating membrane, including the aberrant hair follicles, was excised. Microscopically, a nonkeratinized stratified squamous epithelium, sebaceous glands, and hair shafts were present, confirming a choristoma of pilosebaceous origin at the leading edge of the nictitating membrane. Six weeks after surgery, the horse had no signs of discomfort, with no regrowth of the hairs; no loss of vision was evident. CLINICAL RELEVANCE: Ocular choristomas develop secondary to defective fetal cellular differentiation and are rarely reported in the equine literature. The choristoma in this horse contained ectopic hair follicles with hair growth as well as sebaceous glands. This finding emphasizes the importance of a thorough adnexal examination in horses with corneal disease.

Carbon dioxide (CO2) laser third eyelid excision: surgical description and report of 7 cases.

PURPOSE: To describe a novel technique for third eyelid (TEL) excision using a carbon dioxide (CO2) laser. STUDY DESIGN: Prospective. ANIMALS STUDIED: The procedure was performed on six canine patients and one feline patient. METHODS: The laser was set to 6 Watts (W) of power and a linear continuous setting. Forceps were used to elevate the TEL and, with a protective shield covering the cornea, the base was cut and cauterized simultaneously. Minimal to no hemorrhage was observed, and the conjunctiva was left to heal by second intention. RESULTS: Seven patients underwent unilateral surgical TEL excision. All patients had suspected neoplasms affecting either the glandular tissues or conjunctival surfaces of the TEL. Clean surgical margins were achieved in all but one patient. All surgical sites were considered healed by 14 days showing mild-to-moderate conjunctival hyperemia and accumulation of mucoid discharge at the ventronasal fornix. One patient experienced postoperative keratoconjunctivitis sicca. Prolapse of orbital fat was not observed in any patient. CONCLUSION: Use of CO2 laser appears to be an efficient and effective means for surgical third eyelid removal with excellent postoperative comfort and minimal complications.

Characterization and outcome following excision of masses in the nictitating membranes of horses: 50 cases (1998-2012).

OBJECTIVE: To determine the histologic findings associated with masses in the nictitating membranes (third eyelids) of horses and to identify prognostic factors associated with recurrence and the outcome. DESIGN: Retrospective case series. ANIMALS: 50 horses with masses in a third eyelid. PROCEDURES: Medical records of horses with partial or complete excision of a third eyelid and submission for histologic evaluation between September 1998 and November 2012 were reviewed. Horses were included if follow-up information for at least 1 year after surgery was available. Information regarding signalment and treatment was obtained from the medical records. Histopathology reports were examined to determine surgical margins and vascular invasion. Data were analyzed by means of a χ(2) test to determine the association between recurrence and type of excision (partial or complete), surgical margins, vascular invasion, and use of chemotherapy as well as the association between partial excision of a third eyelid prior to referral and outcome. RESULTS: Squamous cell carcinoma was the predominant tumor type of the third eyelid. There was recurrence in 10 of 50 (20%) horses; recurrence was at a mean of 2.25 years and median of 1.5 years after excision. Partial excision prior to referral was associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with masses in a third eyelid, recurrence and mortality rates were high, which suggested that long-term monitoring is important for all patients in which partial or complete third eyelid excision is performed.

Suture anchor placement technique around the insertion of the ventral rectus muscle for the replacement of the prolapsed gland of the third eyelid in dogs: 100 dogs.

OBJECTIVE: To evaluate a rapid and efficacious procedure to anchor the prolapsed gland of the third eyelid in dogs. METHODS: This is a retrospective study of 100 affected dogs (122 eyes) with third eyelid gland prolapse that were surgically anchored with a nonabsorbable suture around the insertion of the ventral rectus muscle. RESULTS: Hundred dogs (122 eyes) were included in this study. Twenty-three pure-bred and several mixed-breed dogs were represented with the right eye affected in 60 cases and the left eye in 62 cases. Thirty-four eyes (27.9%) were previously operated on at another facility prior to referral. The average age of the patients was 2.2 years (57 days to 11 years). No recurrences of gland prolapse were observed over the course of study. Minor intraoperative conjunctival perforations were observed and easily repaired at the time of the surgery in 21 cases (17.2%). Five cases demonstrated preexistent keratoconjunctivitis sicca (KCS), and all had improved Schirmer tear test following surgical correction and medical therapy. CONCLUSIONS: The suture anchor placement technique provides a cosmetic, rapid, and successful replacement of the prolapsed gland of the third eyelid in dogs. No recurrences were noted. Complications were easily addressed.

Thermal cautery of the canine third eyelid for treatment of cartilage eversion.

OBJECTIVE: To present a novel, minimally invasive technique for everted third eyelid cartilage correction in dogs that employs the use of low-energy cautery to remodel the cartilage. PROCEDURES: Twelve eyes of ten dogs had cautery performed under general anesthesia to correct everted third eyelid cartilage. The tip of a handheld cautery unit or an electrocautery handpiece was applied to the bulbar conjunctival surface of the third eyelid at the central location of cartilage convexity and treated to effect. This resulted in gradual conjunctival contraction and cartilage softening that remodeled the third eyelid to return to a more normal, physiologic position. When the tips of the cartilage bar were also curled, cautery was briefly applied to the convex surface to straighten the cartilage in a similar manner. RESULTS: Blanching of the conjunctiva at the site of treatment occurred. Char was sometimes present and was gently removed with a scalpel blade to improve postoperative patient comfort. Mild conjunctival hyperemia was noted in a few patients for 1-2 days after surgery, but there were no signs of discomfort or eyelid swelling. All dogs had good results in terms of cartilage correction with no recurrence; however, one of the Great Danes that had concurrent third eyelid gland prolapse required gland replacement surgery. CONCLUSIONS: Thermal cautery is a simple, inexpensive means of correcting third eyelid cartilage eversion in dogs with a high rate of success that preserves normal tissue while restoring function.

Perilimbal pocket technique for surgical repositioning of prolapsed nictitans gland in dogs.

The objective of this prospective study was to investigate the success rate, practicality and complications of a new perilimbal pocket technique for the replacement of prolapsed nictitans gland in 30 dogs (44 eyes). A first incision was made in the bulbar conjunctiva, 2-3 mm from and parallel to the infero-nasal limbus, a second incision on the bulbar aspect of the nictitating membrane (NM), 2-3 mm parallel to the free edge. The gland was returned to its normal position by suturing the subconjunctival tissues of the NM to the episcleral tissues, using four to six interrupted horizontal mattress sutures. The English bulldog, Neapolitan mastiff, great dane and American cocker spaniel were commonly presented. Nictitans gland prolapse occurred prior to one year of age in 83.3 per cent of dogs, and unilaterally in 15 patients. The procedure was easy to perform, and had a 90.9 per cent success rate, with minimal complications. The median duration of follow-up, conducted by ophthalmic examination or telephone contact with the owners, was 21.5 months. Tear production and ocular health were not affected in 17 eyes with at least six months follow-up. There was a statistically significant increase between preoperative and postoperative Schirmer tear test-1 measurements.