Abstract

Acute uveitis (inflammation of the uveal tract: iris, ciliary body, choroids) manifests as miosis, bulbar conjunctival hyperaemia, iridal swelling, photophobia and blepharospasm. Glaucoma, cataract and corneal opacity can be secondary. Systemic infections and immune-mediated diseases are the most common causes of bilateral uveitis.¹

Recurrent uveitis is the most common cause of blindness in horses. Although the inciting cause is often not determined, systemic disease is often suspected. The uveitis is perpetuated by immunological responses to persistent antigen or similarity of the antigen with ocular tissues.² This is consistent with many other species, and we propose a similar aetiology for a case of severe bilateral uveitis, glaucoma and corneal oedema in a Californian sea lion following systemic melioidosis.

Caddy, a mature female Californian sea lion (~80 kg), initially showed altered feeding behaviour for a few days, then only ate 2.5 kg fish on 23/9/02. As this occurred during the "melioidosis season", she was commenced on one of the intensive antibiotic regimes adapted at Ocean Park for treating pinnipeds with suspected septicaemic melioidosis (ceftazidime 30 mg/kg im tid). Haematology suggested a moderate leucocytosis with left shift and 4% bands. Serum Fe was also low (9.3 µmol/L). Over the next three days she became anorexic, listless and febrile (39.1°C). Cultures of blood samples taken on the 26th and 28th of September 2002 were positive for Burkholderia pseudomallei. She recommenced eating on the fourth day, her blood parameters improved marginally but she remained febrile, and the treatment was changed to meropenem (17.5 mg/kg sc tid), sulphadiazine / trimethoprim (25 mg/kg po bid) and folic acid (40 mg po bid).

Caddy continued to improve and after 3 weeks was changed to the eradication therapy (chloramphenicol 12.5 mg/kg bid + doxycycline 7.5 mg/kg bid + trimethoprim/sulphadiazine 25 mg/kg bid + folic acid 40 mg bid). She returned to the exhibit, still on therapy, on 6/11/02. Two days later her appetite decreased for three days before she became anorexic, depressed and refused to return to the off-exhibit pools or enter the water. She also had profuse epiphora and opacity of both eyes, but there were no apparent ocular surface abnormalities. Rectal temperature was normal. The trainers coaxed her into the off-exhibit area, meropenem was recommenced and she was also given ciprofloxacin (3 drops tid) and flurbiprofen (3 drops tid) eye drops. A blood sample on 23/10/03 indicated liver pathology (moderately elevated AST, ALT, and bile acids), so she was also given liver protectants (folinic acid 15 mg po sid, Essentiale 1 tab po sid, Legalon 70 1 tab po tid, vitamin E 200 IU po sid + vitamin C 500 mg po sid).

The following day she was swimming and seemed improved. There were small, bilateral central ulcers and her left eye seemed more opaque. Meropenem was ceased after 5 days and eradication therapy changed to amoxicillin-clavulanic acid (6mg/ kg combined dose po tid) supplemented with additional amoxicillin (12 mg/kg PO TID), as at that time dry eye was one of the suspected differential diagnoses and trimethoprim-sulpha drugs have been reported to cause dry eye. Three days later, the corneal oedema was worse with extensive bilateral ulcerations and irregularities. Each evening, Gentamicin eye ointment was commenced to increase contact time and she was kept away from direct sunlight. Two days later there was severe bilateral oedema with multiple small fluorescein positive ulcers. Digital images were sent to a consultant veterinary ophthalmologist.

The tentative diagnosis was uveitis secondary to systemic disease and ulcers secondary to oedema. We ceased ciprofloxacin drops and garamicin ointment, continued the flurbiprofen and commenced "Neosporin" (polymyxin B + neomycin + gramicidin) 3 drops 5x/day and carprofen 2 mg/kg bid. Ulcers were resolving within 6 days, but the oedema remained. Although the surface irregularities improved, both corneas became more opaque. On 3/12/02, flurbiprofen and Neosporin were ceased and steroidal garamycin eye drops commenced. By 14/12/02, comparing images with normal sea lions indicated both eyes were glaucomatous. Latanoprost (50 ug/ml one drop sid) was added 5 minutes before other drops. On 24/12/02, she was examined by a human ophthalmologist who confirmed the tentative diagnosis of uveitis and severe glaucoma, although tonometry to confirm this was not performed, as it would have required anaesthesia. Dorzolamide (2% 1 drop tid) and timolol (0.5% 1 drop bid) were commenced and latanoprost was increased to 1 drop bid. Both globes seemed smaller the next day.

Over the next two months, the size of the globes appeared to vary with a decreasing trend, but the degree of opacity remained unchanged. Ultrasound examination on 29/1/03 under operant conditioning detected no abnormalities in the retina, vitreous or lens. By 17/2/03, both corneas were smooth and less opaque. By 27/2/03, the corneas were clearing ventrally and the uvea was visible.

Caddy was first examined by RS on 24/3/03. She was visual in both eyes and her globes were probably normal sized, but looked larger due to the oedematous corneas. The peripheral corneas were clearing in both eyes. There was some striate pigment coning in from the limbus laterally in the right eye. The central corneas were mildly oedematous. Both anterior chambers were normal, with no visible synechia. The endothelium had degenerated in both eyes. We ceased topical treatment, continued carprofen and kept her out of sunlight as much as possible.

Despite several episodes of increased opacity and corneal pitting, generally both eyes continued to improve and appeared essentially normal by 12/11/03. Three weeks later after Caddy was allowed out into direct sunlight both eyes showed moderate opacity. When she was returned to a covered, shady area the opacity decreased again. Once her eyes return to normal, her exposure to sunlight will be closely controlled and very gradual to allow her eyes to re-adjust.

We speculate that the systemic bacterial infection (Burkholderia pseudomallei) initiated the uveitis and the resulting oedema lead to the corneal ulcerations. This case demonstrates that even severe cases of uveitis/glaucoma/corneal oedema can resolve following aggressive and continued therapy and expert advice.

Acknowledgments

The authors are grateful to Dr. Alvin Kwok and Dr. Richard Smith for their invaluable advice, Wendy Chan for technical assistance, and Gary Wong, Harriet Chiu and the rest of the Marine Mammal Dept. for their invaluable help with training Caddy for a range of medical behaviours and for treating her.

References

1.  Anonymous. 1998. Ophthalmology. In: Aiello S.E., and A. Mays (eds.). The Merck veterinary manual, 8th ed. Merck & Co., Inc., N.J., U.S.A. P. 354.

2.  Anonymous. 1998. Ophthalmology. In: Aiello S.E., and A. Mays (eds.). The Merck veterinary manual, 8th ed. Merck & Co., Inc., N.J., U.S.A. P. 360.