Exophthalmos and corneal edema in a young ferret

WHAT’S YOUR DIAGNOSIS Thomas M. Donnelly, DVM, Column Editor

Exophthalmos and corneal edema in a young ferret Amy J. Funk, DVM, Tiffani D. Rogers, DVM, DACLAM, Rose Marie Dobbins, & Kelli Boyd, DVM, PhD A technician discovered a 6-week-old male ferret with an eye abnormality during a morning health check. The ferret had been born in the research facility as part of a breeding colony maintained for influenza research and, prior to this observation, had had no ocular problems or developmental delays. Upon physical examination, a corneal opacity was noted in the left eye, as well as a diminished menace response. Other objective physical examination findings included a body temperature of 102.4 °F, body weight of 255 g, a heart rate of 160 beats/min, and a respiratory rate of 36 breaths/min. The animal was adequately hydrated, its mucous membranes were pink, and its capillary refill time was less than 3 s. Activity and appetite were unaffected and all other physical parameters were within normal limits. The ferret shared a modified rabbit cage (Allentown, Allentown, NJ) with two littermates, both of which appeared healthy with no ophthalmic abnormalities. Neither parent of the 6-week-old male ferret had a history of ocular disease. The initial clinical assessment was idiopathic corneal edema, possibly from an immature cataract. No treatment

was initiated at that time and the animal was monitored closely for any changes. Two weeks later, the attending husbandry technician reported acute changes to the left eye. Upon reexamination, the left eye was markedly larger and the ferret lacked a menace response. The acute progression of clinical signs necessitated that the animal be euthanized and submitted for necropsy. On gross examination, unilateral exophthalmos and corneal opacity in the left eye were the only abnormalities found in the ferret (Fig. 1). Both eyes were collected and fixed in 10% neutral buffered formalin, processed routinely, embedded in paraffin, and sectioned at 4 µm. Histologic findings included thin sclera, corneal edema, anterior synechia (Fig. 2), and inner retinal atrophy (Fig. 3). The anterior synechia were broad and precluded a detailed examination of the filtration angle. Retinal atrophy consisted of the loss of the ganglion cells, the inner plexiform layer, and a thin inner nuclear layer. Figure 1 shows an obvious size difference between the right and left eye. What condition is consistent with these histological results? Is this ocular condition

FIGURE 2 | Photomicrograph of the left eye of the ferret in Figure 1 showing the anterior chamber of the eye. (H&E stain, ×100 magnification.)

FIGURE 3 | Photomicrograph of the left eye of the ferret in Figure 1 showing the retina. There is marked depletion of the inner layers in the affected retina (a) compared with the retina of the unaffected right eye (b). (H&E stain, ×200 magnification.)

FIGURE 1 | Unilateral exophthalmos and corneal edema in the left eye of an 8-week-old male ferret.

commonly seen in ferrets? What are other possible ocular maladies? Are any of these conditions related?

What’s your diagnosis?

Department of Animal Resources, St. Jude Children’s Research Hospital, 332 N. Lauderdale St., Memphis, TN 38105. Correspondence should be addressed to A.J.F. ([email protected]).

LAB ANIMAL

Volume 35, No. 9 | OCTOBER 2006

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WHAT’S YOUR DIAGNOSIS

Diagnosis | Glaucoma The microscopic findings supported a clinical diagnosis of glaucoma with corneal edema Glaucoma is defined as “a series of pathological conditions with clinical manifestations varying with the elevation in intraocular pressure and its consequences1.” Although glaucoma is a common disease in companion animals, it is rarely reported in ferrets2. To understand the pathophysiology of glaucoma, it is helpful to review the flow of aqueous humor. Aqueous humor is produced via active secretion by the ciliary body, which is part of the uveal tract between the iris and the choroids. The ciliary body consists of ciliary processes and the ciliary muscle. Aqueous humor composition is controlled by the filtering angle of blood vessel walls within the ciliary body and by junctions of cells in the ciliary epithelium, where ultrafiltration of the aqueous humor occurs. The drainage of aqueous humor first passes into the posterior chamber, through the pupil, and then into the anterior chamber, later traveling between the pectinate ligaments and entering the ciliary cleft that contains the trabecular meshwork. Finally, aqueous humor filters through the meshwork to enter the scleral venous plexus and reenters the venous system. Glaucoma is clinically diagnosed by showing there is increased intraocular pressure (IOP) using an applanation tonometer (Tono-Pen). We did not obtain IOP values in this ferret, but made the diagnosis by ocular histopathology. A recent paper by MontianiFerreira et al.3 reported normal intraocular pressure as 14.50 ± 3.27 mmHg in 15 ferrets using a Tono-Pen (Bio-Rad, San Jose, CA). Mean values for IOP were 14.28 ± 3.24 mmHg for hobs and 14.68±3.40 mmHg for jills (P=0.74). There was no significant difference in IOP between left and right eyes (P < 0.98). For IOP measurements, this investigation used unsedated ferrets. Previously, Sapienza et al.4 found that ferrets had an average IOP of 22.8 ± 5.5 mmHg. In another report, Murcia and Guerra5 found an average IOP of 21 ± 4 mmHg. However, the results of Montiani-Ferreira et al.3 indicated a lower average IOP of 14.5 ± 3.2 mmHg. This might be explained by the fact that fer2


rets in the study by Montiani-Ferreira et al.3 were not anesthetized nor given any potentially IOP-altering drug (e.g., medetomidine, which lowers IOP in some animal species or ketamine, which increases IOP in other animal species; Murcia and Guerra5 used both of these drugs in their research). Sapienza et al.4 did not use sedation or any anesthetic procedure (except for topical anesthesia) and still obtained higher results than MontianiFerreira et al.3. This might be explained by fluctuation of the IOP at the different times of the day in which the ferrets were evaluated, differences in physical restraint used on the ferrets, or the use of differently calibrated Tono-Pens (Tono-Pen II, Bio-Rad). There are three classes of glaucoma in small animals: primary, secondary, and congenital. Primary glaucoma is idiopathic and unrelated to ocular disease1; secondary glaucoma results from pre-existing or concomitant diseases; and congenital glaucoma is present at birth or shortly after and is the rarest type of glaucoma1. In this case, the advanced disease process made examination of the filtration angle impossible; therefore, the underlying defect was not characterized. In New Zealand white rabbits, congenital glaucoma or buphthalmia is inherited as an autosomal recessive trait6. The condition is secondary to goniodysgenesis (abnormal formation of the anterior chamber angle). The increased size of the globe or buphthalmia (which literally means “cattle eye”) is secondary to glaucoma. Buphthalmia can be detected at as early as three months of age in rabbits7 and may affect one or both eyes; most cases that present unilaterally become bilateral with time6,7. Associated corneal changes may include increased diameter, increased vascularity, bluish tint, chemosis, and sometimes a flattening of the cornea6,7. Acquired glaucoma in rabbits can be secondary to uveitis or intraocular neoplasia. It is thought that primary glaucoma and glaucoma secondary to lens-induced uveitis do occur in ferrets, but there is no scientific data supporting the efficacy of agents such as topical β-blockers, carbonic anhydrase inhibitors, parasympathomimetic agents, and pros-

taglandin analogues in ferrets2. In one case of bilateral glaucoma in a 7-year-old neutered male ferret, a diode laser was used to perform unilateral transscleral cyclophotocoagulation to control the pressure in one of the two affected eyes that had been unresponsive to medical therapy. After three months of followup, the pressure was controlled with alternateday application of a topical steroid2. Two ocular conditions described in ferrets and resembling glaucoma (the primary clinical sign is exophthalmos) are lymphosarcoma 8 and zygomatic salivary gland mucocele9. Orbital lymphosarcoma has only been reported in two ferrets; signs include exophthalmos, increased retropulsion of the globe, and protrusion of the third eyelid8. A soft fluctuant swelling dorsotemporal to the eye with serosanguineous fluid is found in ferrets with exophthalmos due to a zygomatic salivary gland mucocele9. It is interesting to speculate if congenital cataracts could give rise to glaucoma. Cataracts are not uncommon in ferrets10–13, as suggested by the incidence of cataracts in a reaserch colong of ferrets in the UK. Ryland first reported cataracts in juvenile ferrets12. A case of juvenile cataracts in a nine-monthold ferret, described by Utroska and Austin, was thought to be a heritable condition13. Miller et al. evaluated three groups of ferrets for the presence of cataracts by use of a slit-lamp biomicroscopy11. The authors demonstrated that in certain populations of ferrets, slowly progressive cataracts can spontaneously form with high frequency, citing a 47% incidence of cataracts in young ferrets11. The mechanism of cataractogenesis in ferrets is unknown and may be multifactorial11; causes for cataracts in ferrets may have genetic or nutritional components14. The wide appreciation of the ferret as a laboratory animal and exotic pet has meant clinicians must develop an increasing awareness of normal ocular physiological parameters, relevant ocular clinical signs, and diagnostic methods to treat ocular diseases in this species. The clinical and ocular histopathological findings described in this report should help clinicians recognize diswww.labanimal.com

WHAT’S YOUR DIAGNOSIS

tinct pathological changes associated with glaucoma of the ferret eye. If identified early, glaucoma may be managed successfully. 1. 2.

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Slatter, D.H. Fundamentals of Veterinary Ophthalmology (Saunders, Philadelphia, 1990). Good, K.L. Ocular disorders of pet ferrets. Vet. Clin. North Am. Exotic Anim. Pract. 5(2), 325–339 (2002). Montiani-Ferreira, F., Mattos, B.C. & Russ, H.H. Reference values for selected ophthalmic diagnostic tests of the ferret (Mustela putorius furo). Vet. Ophthalmol. 9(4), 209–213 (2006). Sapienza, J.S., Porcher, D., Collins, B.R., Gum, G.G. & Brooks, D.E. Tonometry in clinically normal ferrets (Mustela putorius furo). Prog. Vet. Comp. Ophthalmol. 1(4), 291–294 (1991).

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Murcia, M.M.L. & Guerra, A.H. Ocular findings in 22 adult ferrets (Mustela putorius furo). In International Veterinary Ophthalmology Meeting: European College of Veterinary Ophthalmologist— European Society of Veterinary Ophthalmologists—Dortmunder Kreis (German Eye Panel). Munich, Germany, 10–13 June 2004. Hanna, B.L., Sawin, P.B. & Sheppard, L.B. Recessive buphthalmos in the rabbit. Genetics 47(5), 519–529 (1962). Burrows, A.M. et al. Development of ocular hypertension in congenitally buphthalmic rabbits. Lab. Anim. Sci. 45(4), 443–449 (1995). McCalla, T.L. et al. Lymphoma with orbital involvement in two ferrets. Vet. Comp. Ophthalmol. 7(1), 36–38 (1997). Miller, P.E. & Pickett, J.P. Zygomatic salivary gland mucocele in a ferret. J. Am. Vet. Med.

Assoc. 194(10), 1437–1438 (1989). 10. Andrews, P.L.R., Illman, O. & Mellersh, A. Some observations of anatomical abnormalities and disease states in a population of 350 ferrets (Mustela furo L.). Z. Versuchstierkd. 21(6), 346–353 (1979). 11. Miller, P.E., Marlar, A.B. & Dubielzig, R.R. Cataracts in a laboratory colony of ferrets. Lab. Anim. Sci. 43(6), 562–568 (1993). 12. Ryland, L.M. & Gorham, J.R. The ferret and its diseases. J. Am. Vet. Med. Assoc. 173(9), 1154–1158 (1978). 13. Utroska, B. & Austin, W.L. Bilateral cataracts in a ferret. Vet. Med. Small Anim. Clin. 74(8), 1176–1177 (1979). 14. Fox, J.G. in Biology and Diseases of the Ferret (ed. Fox, J.G.) 307–320 (Williams & Wilkins, Baltimore, 1998).

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