Equine recurrent uveitis

What it is

Equine recurrent uveitis (ERU, also called "moon blindness" or periodic ophthalmia) is an immune-mediated inflammation of the uvea (iris, ciliary body and choroid) that runs with repeated episodes or with persistent low-grade inflammation. Each episode leaves damage, and over time cataracts, synechiae, glaucoma, retinal detachment and blindness develop.

Two main factors are involved in its origin:

• Leptospires: many eyes with ERU have a persistent intraocular infection with Leptospira; antibodies produced inside the eye, bacterial DNA and, in some cases, live leptospires are found in the vitreous. Uveitis can appear months or years after a systemic infection that went unnoticed.
• Genetics: in the Appaloosa and other breeds with the leopard complex spotting pattern, ERU has a hereditary basis and usually takes the insidious form.

Three clinical forms are described:

• Classic: acute episodes of active inflammation separated by quiet periods.
• Insidious: continuous low-grade inflammation, without obvious pain, which goes unnoticed until the damage is severe; typical of the Appaloosa.
• Posterior: mainly affects the vitreous, choroid and retina; common in European warmbloods, where it is strongly associated with intraocular leptospiral infection.

Who it affects

Horses of any breed, usually adults. Overrepresented are the Appaloosa and other breeds carrying the LP gene (such as the Knabstrupper) and, in Europe, warmbloods. Risk rises with exposure to leptospires (stagnant water, contact with wildlife and livestock).

Anatomy involved

• Eyes (Bulbus oculi): the horse's globe is among the largest of the domestic mammals, with a horizontally oval pupil and pigmented thickenings on the edge of the iris, the corpora nigra (granula iridica). The anterior uvea (iris and ciliary body) produces aqueous humour, and the posterior uvea (choroid) nourishes the outer retina; the fibrous tapetum lucidum lies in the dorsal fundus. The horse's retina is paurangiotic: its vessels only surround the optic disc. The blood-ocular barrier separates blood from the inside of the eye; in ERU it breaks down, and protein, fibrin and inflammatory cells pass into the aqueous humour and vitreous. Repeated inflammation produces synechiae, atrophy of the corpora nigra, cataracts, lens luxation, vitreous opacities and liquefaction, retinal lesions around the optic disc ("butterfly" lesions), glaucoma and, finally, small shrunken eyes (phthisis bulbi).

Clinical signs

• Acute episode: tearing, blepharospasm and photophobia, corneal oedema, miosis, aqueous flare, fibrin or hypopyon in the anterior chamber and low intraocular pressure. One or both eyes may be affected.
• Chronic forms: dark, dull iris, atrophied corpora nigra, synechiae, irregular pupil or one that does not dilate, cataracts, cloudy or yellowish vitreous, progressive loss of vision and sometimes glaucoma.
• In the insidious form the horse may show no pain, and the owner notices the problem when there are cataracts or blindness.

Diagnosis

• It is clinical: a history of repeated episodes and the findings of a full ophthalmic examination with slit lamp and ophthalmoscope. A corneal ulcer must be ruled out with fluorescein before corticosteroids are used.
• Ocular ultrasound when opacities prevent examination of the fundus: vitreous opacities, retinal detachment.
• Leptospires: serum serology (microscopic agglutination test) is of little value on its own. Most reliable is testing aqueous humour or vitreous for antibodies (compared with those in blood, the Goldmann-Witmer coefficient) and for DNA by PCR; the result guides the choice of surgical treatment.

Treatment and prevention

• Acute episode: topical corticosteroids (if there is no corneal ulcer) or subconjunctival ones, topical atropine to dilate the pupil, relieve pain and prevent synechiae, and systemic non-steroidal anti-inflammatories (such as flunixin). Treatment is continued and tapered slowly after remission. Protection from light (fly mask).
• Pars plana vitrectomy: removes the vitreous with its antigens and leptospires; it is the preferred option in eyes with proven intraocular leptospiral infection, with few recurrences, although with a risk of cataract and retinal detachment.
• Suprachoroidal cyclosporine implants: release the immunosuppressant inside the eye for years; they are reserved mainly for cases without leptospires.
• Intravitreal low-dose gentamicin injection is a more recent alternative with few data.
• Enucleation of blind, painful eyes.
• Prevention: reducing exposure to leptospires (rodent control, keeping horses from stagnant water), fly control and eye checks in horses of predisposed breeds.
• The horse is a food-producing species in many countries. In the EU its passport states whether it is excluded from the food chain, and this determines which medicines may be used and with which withdrawal periods.

Key studies

There are no randomised trials of ERU treatment: the evidence comes from observational studies, some with many cases.

• Gerding and Gilger (2016), retrospective study of 224 horses (338 eyes) with ERU at a US hospital. 24.1% were Appaloosas. At the first visit 28.4% of eyes were already blind. Leptospiral titres were positive in 40 of 88 horses tested (45.5%). The globe was lost in 12.1% of eyes; according to owners, 29.4% of horses did not return to their previous use and 14.9% were euthanised because of the disease. These are referral cases, probably more severe than average.
• Dwyer et al. (1995), study of 372 horses in the USA. 56% of horses with uveitis were seropositive to Leptospira Pomona versus 9% of horses without uveitis (OR 13.2). Seropositive horses with uveitis were more likely to go blind (59% versus 24%; OR 4.4), and Appaloosas were overrepresented (OR 8.3). Serology only shows exposure, not that leptospires are the cause.
• Wollanke et al. (2001), cross-sectional study of 242 horses (270 eyes) undergoing vitrectomy in Germany and 39 controls. Leptospires were cultured from the vitreous in 120 of 229 horses with ERU (52%) and from no control eye. Only 76% of culture-positive horses had a vitreous titre at least 4 times higher than the serum titre. These were eyes selected for surgery at a single clinic.
• Geiger et al. (2022), retrospective study of intraocular samples from 1387 eyes with ERU, 237 with other types of uveitis and 216 healthy eyes from the same clinic in Munich. In eyes with ERU, antibodies against leptospires were found in 83% (by MAT and by ELISA) and DNA by PCR in 72%; there were no antibodies in eyes with other uveitis or in healthy eyes. The eyes come from a referral centre for vitrectomy and may not represent ERU in other regions or breeds.
• Sandmeyer et al. (2020), study of 145 Appaloosas in western Canada. 14% had ERU. Age (OR 1.15 per year) and the LP/LP genotype (OR 19.4 versus lp/lp) increased the risk. The sample is small and from a single region.
• Gilger et al. (2010), cohort of 151 eyes of 133 horses from the USA and Europe with a suprachoroidal cyclosporine implant, followed for 13–85 months. At last follow-up 78.8% of eyes were visual, with a mean of 0.09 uveitis episodes per month. There was no control group.