Bilateral anterior segment dysgenesis in a 7-week-old domestic shorthaired cat

Abstract

A 7-week-old, intact, female domestic shorthaired cat was presented to the Atlantic Veterinary College (AVC) Ophthalmology service for a 1-week history of buphthalmia in the left eye and bilateral elevated intraocular pressures. Ocular examination revealed bilateral non-visual glaucomatous eyes. Bilateral enucleations were performed without complications and histopathology revealed anterior segment dysgenesis of varying degrees in both eyes.

Key clinical message:

Anterior segment dysgenesis is a developmental condition that can result in primary congenital glaucoma for which the best course of treatment is enucleation.

A 7-week-old intact, female, domestic shorthair cat, was admitted to the Atlantic Veterinary College (AVC) Emergency Service with a 1-week history of unilateral buphthalmia in the left eye and abnormal gray corneal appearance bilaterally. A cursory ocular examination confirmed these clinical signs. Intraocular pressures were determined to be elevated at 40 mmHg in the right eye and 32 mmHg in the left eye. No other abnormal findings were seen on physical examination. A diagnosis of bilateral glaucoma was made, and the patient was referred to the AVC Ophthalmology Service for further diagnostic testing and treatment.

The AVC Ophthalmology service determined the cat to be, bright, alert, and responsive. The cat was slightly underconditioned (body condition score = 4/9; body weight = 0.68 kg). The vital parameters were within normal limits (heart rate 160 beats/min, respiratory rate 32 breaths/min, and temperature 38.3°C). No abnormalities were noted on thoracic auscultation, abdominal palpation, or lymph node palpation.

Neuro-ophthalmic examination revealed a negative menace response in both eyes. The dazzle reflex was present in the right eye and absent in the left; blepharospasm was present in the right eye, which could have accounted for the positive reflex. The direct and consensual pupillary light reflexes could not be assessed as the pupils could not be visualized. The palpebral reflex was present in both eyes. The results of a Schirmer tear test (Schirmer tear test; JorVet, Loveland, Colorado, USA) were 3 mm/30 s and 2 mm/30 s in the right and left eyes, respectively. There was positive fluorescein (Fluorescein Sodium Ophthalmic strips; Dioptic Pharmaceuticals, Toronto, Ontario) uptake in the right eye characterized as stippling. No fluorescein uptake was noted in the left eye. The Jones test was negative for both eyes. Proparacaine ophthalmic topical drops (Procaine; Alcan Novartis, Mississauga, Ontario) were applied prior to assessing intraocular pressures (IOP) via the Tono-pen (Tono-Pen VET Veterinary Tonometer; Reichert, Buffalo, New York, USA). The IOP were 37 mmHg and 34 mmHg in the right and left eyes, respectively.

Ocular examination of the right eye revealed severe blepharospasm, microphthalmia, an erosion in the dorsomedial cornea, a diffusely gray cornea deemed to be severe central corneal edema, and iris tissue apposed the corneal endothelium with a limited anterior chamber (Figure 1). The pupil and other intraocular structures could not be visualized. Ocular examination of the left eye revealed the following: severe buphthalmos, iris tissue apposed corneal endothelium, and central white/gray corneal opacity deemed to be diffuse corneal edema. The pupil, anterior chamber, and other intraocular structures could not be visualized.

Figure 1.

Image of the patient upon ophthalmologic evaluation.

The cat was diagnosed with bilateral congenital glaucoma. As these were sightless, painful eyes, bilateral enucleations were recommended for patient welfare. Prior to surgery, the cat was administered gabapentin (Gabapentin; Chorion, Montreal, Quebec) 10 mg/kg body weight (BW), PO, q8h, and ocular lubricant (Tear-gel; Bausch and Lomb, Laval, Quebec) was instilled in both eyes, q8h. The cat also had a complete blood (cell) count (CBC), serum biochemistry, and feline leukemia virus antigen/feline immunodeficiency virus antibody test kit (FeLV/FIV SNAP test; IDEXX, Westbrook, Maine, USA) performed to assess anesthetic risk and overall well-being. The CBC revealed a normal leukocyte count [9.2 × 10⁹/L; reference interval (RI): 4.7 to 17 × 10⁹/L] with a differential characterized by a moderate neutropenia (1.012 × 10⁹/L; RI: 2.6 to 12.6 × 10⁹/L) and mild lymphocytosis (7.36 × 10⁹/L; RI: 1.5 to 7 × 10⁹/L), which was interpreted as a combined excitement and acute inflammatory leukogram. Most serum biochemistry values were within normal values for a feline patient of that age group (1). Values that were outside of normal consisted of mild hypochloremia (110 mmol/L; RI: 112 to 122 mmol/L), mild hypoglobulinemia (26 g/L; RI: 35 to 54 g/L), and elevation in A:G ratio (1.19; RI: 0.50 to 0.90), which are consistent with cats < 3 mo of age (2). The values that were outside of the reference interval for cats 8 wk of age included mild decrease in amylase (351 U/L; RI: 407 to 856 U/L) and mild hyperalbuminemia (31 g/L; RI: 24 to 30 g/L), which were attributed to individual variation. The FeLV/FIV SNAP test was negative.

The cat was positioned in right lateral recumbency, clipped, then surgically prepped using povidone-iodine (Proviodine Solution 10% Rougier Teva; Toronto, Ontario) diluted 1:50 with sterile saline (0.9% NaCl; Baxter Deerfield, Illinois, USA), and draped routinely for enucleation surgery. The trans-conjunctival enucleation approach was performed on the left eye. An eyelid speculum (Teleflex; Germany) was placed. Hemostats (Teleflex; Germany) were applied to the lateral canthus, crushing the tissue to provide hemostasis. The hemostats were removed, and an approximate 1-cm incision was made along the crushed tissue in the left eye using curved tenotomy scissors (Teleflex; Germany) to enlarge the palpebral fissure. The bulbar conjunctiva was incised 360° around the globe using tenotomy scissors to expose the underlying sclera. The extraocular muscles were transected at their insertion sites, and the optic nerve was transected blindly with tenotomy scissors, allowing the ocular globe to be removed from the orbit. Mild hemorrhage was controlled by applying a cotton roll into the orbit. A splash block was performed in the orbit using 0.5% bupivacaine (Bupivacaine; Sterimax, Oakville, Ontario) at 0.3 mg/kg BW. The third eyelid was removed using tenotomy scissors. Two allis hemostats (Teleflex; Germany) were placed; one on the upper and one on the lower eyelid to allow access to the underlying deep layers. Starting at the lateral canthus, approximately 3 mm of palpebral margin of both upper and lower eyelids were removed using curved tenotomy scissors. Any remaining conjunctiva was excised. The caruncle and all the pigmented tissues at the medial canthus were also removed. The orbit fascia and the holding layer were closed in 1 layer using 5-0 polydioxanone (PDS) (PDS; Ethicon, Markham, Ontario) on a taper needle in a simple continuous pattern to minimize dead space in the orbit. The subcutaneous layer was closed using 5-0 PDS on a taper needle in a simple continuous pattern. The skin was closed using 5-0 Ethilon (Ethilon; Ethicon, Markham, Ontario) on a cutting needle in a cruciate suture pattern. The cat was positioned in left lateral recumbency and the right eye was enucleated following the same procedure as the left eye. No intraoperative complications were noted.

This cat received cefazolin (Cefazolin; Fresenius Kabi, Toronto, Ontario), 22 mg/kg, IV q90min peri- and intra-operatively to aid in minimizing the risk of surgical site infection. Due to the cat’s age and weight, non-steroidal medications were contraindicated; therefore, a fentanyl (Fentanyl; McKesson, Saint-Laurent, Quebec) constant rate infusion was administered at a rate of 3 μg/kg per hour for 24 h after surgery to cover the immediate post-operative pain. Gabapentin at 10 mg/kg, PO, q8h was prescribed for 5 d following discharge. The kitten was discharged 24 h after surgery with an Elizabethan collar to prevent trauma to the incision sites. The skin sutures were removed 14 d after surgery. Follow-up 3 mo after discharge revealed no postoperative complications, the cat had been adopted and had reportedly adjusted well.

Following removal of extra-ocular soft tissues, both eyes were placed in 10% neutral buffered formalin and submitted for histopathology. The histopathological report revealed bilateral anterior segment dysgenesis which consisted of numerous developmental abnormalities. The anterior chambers were absent. In both eyes, the iris was severely hypoplastic and reduced to a thin fibrous band that was diffusely incorporated into the posterior corneal stroma (Figure 2). Descemet’s membrane was generally unapparent except in the in the left eye where it was visualized sporadically in a few small areas. There was no discernable trabecular meshwork and non-apparent filtration angles. Small, blunted ciliary processes extended from the posterior surface of the iris and the ciliary body was thin and small. Severe corneal edema was noted in the right eye in the deep 2/3 of the stroma, along with subtle vascularization (Figure 2). Mild, corneal edema with superficial vascularization was noted in the left eye. No obvious lens tissue was found in either eye. The posterior segment in both eyes revealed diffuse retinal detachment, with diffusely plump cuboidal retinal pigmented epithelium (RPE) accompanied by substantial shortening or loss of retinal photoreceptors. The detached retina was extensively folded in both eyes. Small foci of discontinuity in the inner and outer nuclear layers and the formation of a small rosette were noted in the right eye (possible focus of retinal dysplasia). The latter changes were more prominent and numerous in the left eye (Figure 2, inset). No significant microscopic abnormalities were noted in the choroid or tapetum.

Figure 2.

Right eye, cornea, and attached hypoplastic iris. H&E, 4×. The inner 2/3 of the cornea are markedly thickened and edematous (C). The iris is reduced to a thin fibrous band (I) and is diffusely incorporated into the posterior cornea, obliterating the anterior chamber. Inset: Left eye, retina. H&E, 10×. In areas, the inner and outer nuclear layers exhibit mildly decreased cellularity and coalesce to form a single layer. Scattered rosette-like structures are also present (R).

Discussion

Primary glaucoma is rare in cats and is subcategorized as congenital, open angle glaucoma, and closed angle glaucoma (3–5). Congenital glaucoma can be the result of ocular abnormalities, including lens abnormalities, such as microphakia, macrophakia, ectopia lentis, or anterior uveal abnormalities, such as iridoschisis, pectinate ligament dysplasia, multiple iridociliary cysts, and persistent pupillary membranes (4). Young cats with glaucoma commonly present with marked buphthalmos, corneal edema, and exposure keratitis or ulceration (3,5,6). A research study on a colony of Siamese cats with congenital glaucoma identified a simple autosomal-recessive inheritance within the breed that may indicate a genetic component to the development of congenital glaucoma (7). Kittens with this form of congenital glaucoma often present at < 6 mo of age with bilaterally symmetric, progressive glaucoma characterized by elongated ciliary processes, globe enlargement, and spherophakia (4,7). This form of congenital glaucoma results from an arrest in early postnatal development of the aqueous outflow pathways, thereby significantly elevating intraocular pressures in 8-week-old kittens compared with unaffected kittens (4,7). This cat was not Siamese; however, a genetic component is suspected as another littermate had a unilateral enucleation performed that had similar but less severe histologic lesions.

This kitten had bilaterally elevated intraocular pressures at 7 wk of age and was diagnosed with bilateral glaucoma. The age of cats can influence the intraocular pressures (3). Kittens within the first weeks of life have lower intraocular pressures than those of adult cats (3,4). When a kitten’s eyelids first open, the aqueous humor production and outflow have not reached adult levels, and therefore the intraocular pressure is low (4,8). In patients with normal development, normal adult intraocular pressures are reached by approximately 12 wk of age (4,8). Between eyelid opening and 12 wk of age, the anterior chamber matures from a shallow anterior chamber with near apposition between the iris and cornea to an adult conformation (4). Therefore, during this period of development, an elevation in IOP, as seen in this kitten, compared with adult levels is severe, as the expected value should be even lower than reported adult values.

This case cat was diagnosed with Anterior Segment Dysgenesis (ASD). This disease encompasses developmental malformations of the cornea, iris, or lens (9). Abnormalities during embryogenesis and neural crest cell differentiation can result in ASD (10). Surface ectoderm will develop into the cornea and the lens, whereas the mesenchyme from the neural crest between the surface ectoderm will develop into most of the anterior segment structures including the corneal epithelium, corneal keratocytes, stroma, trabecular meshwork, and the iris (10). The period of lens vesicle separation from surface ectoderm is critical for the development of ASD (10). It is interesting to note that in this cat, no obvious lens was located through histopathology, which could have contributed to the lack of signalling pathways leading to ASD. Beckwith-Cohen et al (6) studied the histopathology results of 22 ocular globes from 22 glaucomatous cats. The histopathological examination revealed that all had markedly affected anterior segments with a wide range of malformations, and 21 of 22 cases were identified as ASD (6). The ASD histological features mimicked those seen in this case and included ill-formed iridocorneal angle, absence of ciliary clefts, absent trabecular meshwork, termination of Descemet’s membrane, and anterior synechiae (6).

The most recommended treatment for irreversibly blind and painful eyes in glaucomatous patients is enucleation (4,5). In cats with anterior segment dysgenesis, medical treatment can be attempted for glaucoma; however, the cat will remain blind as the anomalies cannot be surgically corrected. Cats generally tolerate bilateral enucleation very well (4). It is always recommended to submit eyes after enucleation for histopathological examination, especially if intraocular neoplasia cannot be ruled out (4). The risks of intra-operative enucleation consist of hemorrhage, which was minimal in this cat (11). Post-operative complications can include orbital infection, incision dehiscence, hemorrhage, or failure to remove all conjunctiva which can encyst if incompletely excised (11). These complications were not noted in this cat upon follow-up, and it was reported that the kitten adjusted well after the bilateral enucleation was performed.

In summary, primary congenital glaucoma is rare in cats, and it often attributed to developmental abnormalities such as ASD, which is the result of a congenital condition that causes abnormal ocular development. Kittens with severe ASD, such as this case, have non-visual and painful glaucomatous eyes. In addition to severe anterior segment dysgenesis, this cat had numerous unique developmental abnormalities, such as bilateral aphakia, diffuse retinal dysplasia, and retinal detachment. Bilateral enucleations are generally tolerated well in cats and this is the recommended treatment for blind and painful eyes.