An uncommon case of anterior segment dysgenesis in a domestic shorthair cat

P. LAZARD1* DVM, R.L. PEIFFER2 DVM, PHD, ACVO

1 2

Clinique vtrinaire, 80 rue Preire, 78100 Saint-Germain-en-Laye, FRANCE. Merck Research Laboratories, Merck and Co. WP45-226, PO Box 4, West Point, PA 19486, USA.

*Corresponding author: patrick.lazard@ladelou.com

SUMMARY A case of anterior segment dysgenesis in an 18-month-old, one-eyed, domestic shorthair cat is reported. This congenital anomaly presented with a central corneal coloboma, a microspheric lens with a partial cataract, pupillary membrane remnants and goniodysgenesis. Treatment consisted of lens removal by phacoemulsification and a corneal graft using a porcine small intestinal submucosa biomaterial (Vet BioSISt) to repair the cornea and preserve the vision. Intraocular pressure remained within the normal range. Features of this case warrant classification as Peters anomaly, first in humans in 1887 and which consists of defective development of the posterior cornea caused by abnormal migration and differentiation of neural crest cells impeded by the late separation of the lens vesicle from the surface ectoderm.

RSUM Un cas rare de dysgnsie du segment antrieur chez un chat europen Lauteur dcrit un cas de dysgnsie du segment antrieur chez un chat europen monophtalme, g de 18 mois. Cette anomalie congnitale associait un colobome cornen central accol une microsphrophakie partiellement cataracte, des rsidus de membrane pupillaire et une goniodysplasie. Lexrse du cristallin par phacomulsification suivie de la reconstruction de la corne par greffe multilamellaire dun biomatriau (Vet BioSiSt) a permis de conserver la vision. La pression intraoculaire est reste normale. Cette dysgnsie fline est rapprocher de lanomalie congnitale de Peters dcrite, pour la premire fois, chez lHomme en 1887 et caractrise par la prsence dopacits cornennes dues labsence des plans stromal et endothliodescemtique. Elle est associe un dfaut de migration et de diffrentiation des cellules embryonnaires issues de la crte neurale. Labsence de sparation du cristallin de lectoderme cphalique superficiel nest pas de rgle mais est considre par les diffrents auteurs comme un facteur aggravant le pronostic visuel, de mme que la survenue plus ou moins tardive dun glaucome primaire.

Keywords: Anterior segment dysgenesis, cat, coloboma, Peters anomaly, biomaterial graft.

Mots cls : Dysgnsie du segment antrieur, chat, colobome, anomalie de Peters, greffe de biomatriau.

Introduction
Anterior segment dysgeneses have been described in different species of animals (cattle, horses, mice, dogs and cats). They commonly present as corneal opacities which can be associated with the presence of a residual pupillary membrane and cause varying degrees of visual disturbances. [3,5,7,8,12,13,15-19,21,22]. In human ophthalmology, a spectrum of congenital anomalies of the anterior segment has been described, including Peters anomaly, congenital or infantile glaucoma, iris hypoplasia, Axenfeld-Rieger syndrome, endothelial dysplasia, sclerocornea, megalocornea, keratoconus and posterior embryotoxon. [2,5,9,10,20] . Glaucoma is a frequent association. These malformations arising during embryogenesis involve the ocular tissues derived from the migration and differentiation of the cells of the cephalic neural crest and, in the most complex cases are associated with the adhesion of the lens to the corneal endothelium. [2,5,9,10]. This paper describes the case of an anterior segment dysgenesis of the left eye in an 18-month-old, one-eyed, domestic shorthair cat with a complex clinical presentation similar to Peters anomaly.
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Clinical history
The 5 kg castrated male domestic shorthair cat was referred by a colleague, as an emergency, for a suspected anterior luxation of the left lens associated with a corneal ulcer. The cat had undergone an enucleation of the right eye at 8 months of age for an unknown reason; the condition was described by the owners as similar to the one now affecting the left eye. The cat was in good general condition and had no previous history of ocular trauma. Vision appeared normal. No sign of ocular pain could be detected and there was no periorbital inflammation. Pupillary light reflex was present. The globe was of normal size. Intraocular pressure, measured using a rebound tonometer (Tonovet, Icare Finland Oy, Espoo, Finland), was 19 mmHg. Examination of the cornea and anterior chamber using a biomicroscope (SL15, Kowa Europe GmbH, Dsseldorf, Germany), revealed no signs of inflammation or neovascularisation. The cornea was of normal size and convexity. The peripheral cornea was normal. The intermediate zone was translucent. A full thickness grey opacity 6 mm in diameter was present in the paracentral region surrounding a small central ectatic opalescent zone, with the epithelium covering the cortex of the lens. Punctuate

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fluorescein staining in the most central zone without extension into the adjacent tissues was observed. The anterior chamber was of normal depth. The spherical lens, identified in the anterior chamber, was of small size. Multifocal opacities were observed in the anterior cortex and nucleus. The lens was centred on the optic axis with corneal adhesions at the zones of modified transparency, but did not contact the iris. Strands of residual pupillary membrane were present on its surface. The pupil was normal in shape and very mobile without any detectable synechia (Fig. 1).

its transparency and conserving vision. The pre-anaesthetic blood test (complete blood count, serum biochemistry and serum protein electrophoresis) showed no abnormalities. Serological and antiviral assays (Speed-Tests FELV-FIVPIF, BVT-Virbac, La Seyne sur Mer, France) for feline immunodeficiency virus (FIV), feline infectious peritonitis (FIP) and feline leukaemia virus (FeLV) were negative, as was the bacteriological examination performed on a sample from the central zone of the cornea. Following a 4-day-course of local antibioprophylaxis (ofloxacin ointment, Exocine, Laboratoire Allergan France SAS), surgery was performed under isoflourane gaseous anaesthetic using an operating microscope (Zeiss OPMI 6, Carl Zeiss S.A.S, Le Pecq, France). Immediately prior to surgery, the anterior segment had a significantly different appearance from that of the initial examination 4 days previously. The lens had lost its spherical appearance and appeared crumpled. There was an axial corneal defect with the base comprised of the anterior capsule of the adherent lens The depth of the anterior chamber remained unchanged, with the lens remaining adhered to the posterior corneal surface in the intermediate and paracentral zones (Fig. 2). A lateral canthotomy was performed. The lens fragments were extracted by phacoemulsification (Universal II; Laboratoires Alcon S.A, Rueil- Malmaison, France) following a keratotomy 1 cm from the central zone of the cornea directed in such a way as to penetrate directly into the lens. An ocutome probe (Atiop, Alcon France S.A) was used to aspirate and remove any part of the lens capsule which was not adhered to the cornea. The anterior lens capsule was left in place with the exception of the perforated area. A high-density viscoelastic product (Healon GV, Amo, Mougins, France) was used to fill the anterior chamber. The corneal epithelium was then removed beyond the limit of the 6 mm diameter paracentral zone. To prepare the site for the biomaterial graft used to reconstruct the cornea, the underlying tissue and the exposed superficial layer of normal stroma of the intermediate zone were excised by lamellar keratectomy Two corneal grafts derived from porcine small intestinal submucosa (Vet BioSISt, Cook Inc., Hertfordshire, UK) were then superimposed using simple interrupted absorbable sutures (Vicryl 10/0, Ethicon, Janssen, Noisy-le-Grand, France). The first graft, of 6 mm diameter, was sutured directly to the borders of the paracentral zone, and the second, of 8 mm diameter, to healthy corneal stroma and epithelium. The viscous product was then aspirated and the entry point for the phacoemulsification was closed using the same suture material (Fig. 4). Reconstruction of the lateral canthus of the eyelid was performed and the nictitating membrane was sutured to the lateral aspect of the upper lid. Finally, a blepharorrhaphy was performed for additional protection. Ten mg of marbofloxacin (Marbocyl, Vetoquinol, Lures, France) and 1.5 mg of meloxicam (Metacam, Boehringer Ingelheim, Paris, France) were injected intravenously and subcutaneously respectively. An Elizabethan collar was fitted and the antibiotic was continued as a 10-day oral course (marbofloxacin at 2
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FIGURE 1 : Photo of the left eye of a cat affected by anterior segment dysgenesis (Peters anomaly). The cornea displays 4 distinct zones indicated by coloured dots: green dot = peripheral cornea, of normal appearance; white dot = equatorial zone of the lens; blue dot = zone of adhesion between the microspheric lens and the posterior cornea; black dot = the most fragile, central region, with the lens embedded in the defective cornea and covered by epithelium ; red dot = the paracentral zone, which is partially opaque. (Peters anomaly).

Following pharmacologically induced mydriasis (Mydriaticum 0.5%, Tha, Clermont Ferrand, France), the vitreous and the retina had a normal appearance on direct and indirect ophthalmologic examination. Under sedation, examination of the iridocorneal angle using a Barkan lens revealed goniodysgenesis characterised by an open iridocorneal angle and absence of the pectinate ligament fibers in many regions. Ocular ultrasound (Philips HD 11XE, Philips Ultrasound, Bothell, WA, USA) confirmed the small size spherical lens and the absence of retinal detachment. The young age of the subject, the absence of signs of prior inflammation or trauma, and the microspherophakia supported the diagnosis of a cleavage anomaly arising during embryogenesis.

Treatment
Because of the increased risk of corneal perforation in its central zone, a corneal graft using a porcine small intestinal submucosa biomaterial (Vet BioSISt, Cook Inc., Hertfordshire, UK) combined with partial lens removal was performed. The aim was to reconstruct the cornea whilst preserving

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FIGURE 2 : Photo taken during the operation. The enlarged image of the eye appears inverted due to the positioning of the animal. The most central zone of the cornea had not been impermeable for 2 days. The lens has become crumpled. The coloured marker dots refer to the same areas as described in the caption to Fig. 1.

FIGURE 3 : Photo taken during the operation at the end of phacoemulsification and after removal of the posterior lens capsule. The most central zone of the cornea has been freed of all lens tissue and communicates directly with the anterior chamber, filled with a visco-elastic product. The surgical keratotomy is visible at the zone of adhesion of the lens at the 3 oclock position. The coloured marker dots refer to the same areas as described in the caption to Fig. 1. The white dot is no longer present because of the posterior capsulectomy.

FIGURE 4 : Photo taken during the operation: view of the eye at the end of surgery after suturing the 2 superimposed grafts of porcine small intestinal submucosa (Vet BioSISt) and closure of the phacoemulsification keratotomy.

FIGURE 5 : View of the eye 1 month after surgery. The anterior chamber has a normal depth. The cornea is reconstructed and of satisfactory transparency. Visual function has been conserved.

mg/kg/day). After 20 days' isolation at the owners home, the sutures were removed from the eyelids and nictitating membrane. The anterior chamber was formed, and the biomaterial corneal grafts were incorporated in a zone of corneal granulation. No anterior synechia were present. An indometacinbased anti-inflammatory treatment (Indocollyre 0.1%; Bausch & Lomb, Lab. Chauvin, Montpellier, France), and a vitamin A ointment to promote healing (Faure, Laboratoires Europhta, Monaco) were prescribed for 1 month. At the end of this period, the eye was visually functional. The cornea presented with a small central opacity, which was relatively transparent and only slightly vascularised (Fig. 5).
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Discussion
The congenital abnormalities of this eye present similarities with anterior segment dysgeneses described in both animals and humans (corneal opacity, remnants of persistent pupillary membrane, malformation of the iridocorneal angle, ectopic microspherophakia). [2,3,5,7-10,13,15-19,21,22] The corneal coloboma and anterior chamber lesions were non-inflammatory. [2,3,9,16,17] The central corneal perforation was not of traumatic or infectious origin. [2,9,16,] The presence of microspherophakia adherent to the defective cornea could not be confused with the well-documented lens luxation of

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familial and congenital origin in the Siamese cat, [3,12,14] which is most commonly inflammatory in adult cats, and degenerative in elderly cats. [4,11-13,15,19,24] This case is similar to keratolenticular dysgenesis described by PEIFFER in 1983. In that case, a Persian kitten presented with a lens, containing a dumbbell-shaped partial cataract, embedded in a central keratoconus. Histology showed that the Descemets membrane and anterior capsule of the lens were absent, causing the corneal stroma and the lens cortex to be in close contact.[16] A similar corneal coloboma was described in a newborn infant affected by a Peters anomaly, heart malformation and hydrocephalus in 1996. [9] In many species of animal, a persistent pupillary membrane is the most common manifestation of anterior segment dysgenesis. [4,13,17,21] More rarely, clinical signs associate, in varying degrees, anatomical defects affecting the optic axis. These can be found at the level of the corneal stroma and endothelium, the iris, and the anterior aspect of the lens In all probability, this is the result of a defect in the separation between the surface ectoderm and the lens vesicle. [3,8,9,16,18] This anterior segment dysgenesis presents many similarities with Peters anomaly in humans. It is an irido-corneo-trabecular dysgenesis, which is normally bilateral, but can be unilateral and asymmetric. [2,5,10,14] It presents as a central corneal opacity caused by the absence of the endothelium and Descemets membrane. Iridocorneal adhesions arise from the iris collarette attaching to the periphery of the endothelial deficit. Lesions of the iris can also be associated with this, as well as defects of the iridocorneal angle occasionally associated with a primary glaucoma of more or less early onset. [2,9,10,20] Malformations of the face, heart, genito-urinary tract, central nervous system spinal cord, and retarded growth can equally coexist and have a hereditary nature often. [2,5,9,10,20] The association of a palpebral agenesis and an ocular anterior segment dysgenesis has been described in a domestic cat. The genetic origin of these disorders has not been proven in this species. [13,19] In human ophthalmology, dysgeneses of the ocular anterior segment are classified into either ocular anomalies caused by defective migration or differentiation of cells of the cephalic neural crest, or more complex forms of dysgenesis, in which the induction mechanisms of the lens, of ectodermal origin, are paramount. [10] In the case under discussion, the abnormal conformation of the 2 central zones of the cornea may have resulted from an anomaly of embryogenesis of the corneal stroma, the origin of which cannot be determined. The same applies to the defective migration of the lens. Only histological examination of the anterior segment would allow this hypophysis to be tested, but this would have been incompatible with our aim of preserving a functioning eyeball. In the cat, glaucoma is known to be principally secondary to uveitis, lens luxation or neoplasms of the anterior segment. [11,19,24] Primary glaucoma is rare. [7,11-13,15,17,19,22] In a histological study of 131 cases, WILCOX et al. [24] found only 3 cases of goniodysgenesis responsible for ocular hypertension. A breed disposition to primary glaucoma has

been described in the Siamese and the Persian (pectinate ligament dysplasia) and the Burmese (closed angle). [19] No publications have mentioned the angle anomalies described in this clinical case. Today, the cat is 3 years older and has shown no signs of increase in ocular pressure to date. Phacoemulsification was chosen to excise the lens due to the adhesions between the lens and the cornea. The keratotomy was performed on healthy cornea whilst taking the lens position into account so as to allow easy extraction of the lens fragments. The evacuation of the irrigation fluid was performed at the same time by means of a hand piece, via the perforation in the cornea, thus sparing the anterior chamber from ultrasound waves and debris from the lens. The preservation of the contact zone between the anterior lens capsule and the cornea supported the application of the biomaterial corneal graft, using a previously published technique. [1,6,23] The superimposition of layers allowed a good quality seal to be obtained. Due to the cats lively nature, the operated zone was protected by suturing the nictitating membrane to the upper eyelid, followed by a supplementary blepharorrhaphy. The central scar opacity had an undeniable transparency, unlike the leucomas observed by BUSSIERES and colleagues [1] in 2 cats with perforated corneal ulcers treated by excision of necrotic tissue and the application of a porcine small intestinal submucosa graft. A pedunculated conjunctival graft had been used to protect the operation site and could explain the appearance of a very opaque central leucoma. In the case under discussion, the biomaterial graft was replaced by tissue which re-covered the area with a functioning transparency, and was sufficient to preserve the vision of this one-eyed cat.

Conclusion
Anterior segment dysgeneses are well known in humans. Their pathology is well understood and their origin has been explained using animal models. Their mode of transmission and the genetic mutations responsible for these conditions have been the subject of much research. In more than 70% of cases, they are associated with congenital glaucoma, which carries a poor prognosis for vision. This clinical case closely resembles Peters anomaly, first described in 1887. As far as the author is aware, this is the first case describing an anterior segment dysgenesis with corneal perforation that was successfully treated with a biomaterial graft in the cat.

References
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