The Most Common Cause of Blindness in Horses: Equine Recurrent Uveitis (ERU)
Equine recurrent uveitis (ERU) is an immune-mediated inflammation of one or both eyes that is relapsing and remitting in nature. Prevalence rates have been estimated to be between 8-25% in a number of studies. The first episode of uveitis typically occurs between 4-8years of age, although not exclusively. Subsequent flare ups of inflammation follow an unpredictable course, recurrences can be seen weeks or months after quiescence from the first attack. Initially, recurrences were thought to follow the moon cycles and hence the condition was originally known as ‘moon blindness’.
Horses or ponies that suffer a single episode of uveitis are not considered to have ERU until a relapse is seen, i.e. they suffer two or more episodes of uveitis. A relapse may be seen up to two years after the first attack, the risk of developing ERU is very much less if more than two years passes without a second episode. The same is true for unilateral cases; these may become bilateral with time, but that risk is much reduced if two or more years passes without the fellow eye being affected.
Genetic studies have identified a genetic susceptibility associated with equine leucocyte antigen 9 (ELA-9) similar to the association of certain human leucocyte antigen haplotypes and some autoimmune uveitides in humans. The Appaloosa breed is particularly prone to ERU, and when it occurs, appears to be particularly aggressive in this breed.
Clinical signs
Clinical signs may vary with the location of the ocular inflammation: inflammation of the posterior segment may be less grossly evident than anterior uveitis. A horse with classic acute anterior uveitis presents with tearing, blepharospasm and miosis. The blepharospasm can be variable from mild to severe accompanied by marked eyelid swelling.
Note blepharospasm of right eye.
Tip: Where this is more subtle, the angle of the eyelashes is a good indicator of ocular pain - they are directed more vertically rather than at 45’
Examination of the affected eye often initiates profuse lacrimation and discomfort, necessitating sedation with or without local nerve blocks (auriculopalpebral block – motor block allowing the eye to be opened; supraorbital block – sensory block – particularly useful if a lavage system is to be placed in the upper eyelid).
The conjunctiva may be hyperaemic, and deeper layers such as the episcleral vessels similarly affected. Corneal oedema may or may not be present, secondary to endothelial cell dysfunction caused by the intraocular inflammation. Aqueous flare, due to increased protein leakage into the aqueous humour, can be seen with a focal bright light, particularly if held at a tangent whilst examining the eye (seen rather like smoke across a pub room lit by a torch – although not these days) is pathognomonic for uveitis. This is usually accompanied by miosis, often best appreciated by looking at both eyes from a distance using the direct ophthalmoscope to retroilluminate the pupils.
Posterior uveitis may appear relatively benign externally and is frequently missed by owners. A more insidious form of ERU may be present with persistent low grade intraocular inflammation that leads to vision loss in the absence of outwardly painful episodes. This insidious ERU has been reported to be more common in Appaloosas and draft breeds. Evidence of chorioretinitis (either active inflammation, seen as grey-white changes within the retina, or inactive scarring seen as either areas of tapetal hyperreflectivity in the tapetal fundus, or depigmentation in the non-tapetal fundus) may be apparent, often accompanied by vitreal degeneration. Clumps and strands of inflammatory material are frequently seen in the anterior vitreous, near the ciliary body.
Cob pony with bilateral severe acute uveitis following foaling.
Note: blepharospasm, lacrimation and epiphora, conjunctival & episcleral hyperaemia, mild corneal oedema and a severe fibrinous flare in the anterior chamber obscuring further intraocular examination
Below: close up view demonstrating deep corneal vascularisation of perilimbal cornea and yellow fibrinous flare
More chronic signs include keratic precipitates (accumulations of inflammatory cells on the posterior corneal surface), synechiae (attachments of the iris margin to either the lens – posterior - or cornea – anterior), atrophy of the granula iridica, cataracts, pigment dispersal onto the lens surface or cornea, vitreal degeneration (floaters and debris), and retinal detachments.
Horse with ERU of the left eye. This horse had been on treatment for two weeks. The pupil had been dilated with atropine.
Note: atrophy of granula iridica, fine spicules of cataract at 9 o’clock and vitreal degeneration behind the lens (most obvious at 4 o’clock).
Pony with chronic uveitis of the right eye.
Note: diffuse corneal oedema, hazy anterior chamber (due to corneal oedema and aqueous flare), multiple posterior synechiae to anterior lens capsule and anterior lens capsule cataract (the remainder of lens and posterior segment could not be assessed due to the extensive synechiae)
Calcific band keratopathy is also seen as a chronic lesion of ERU, presenting as an area of corneal lipid/calcium deposition in the anterior stroma of the cornea. The interpalpebral portion of the cornea is most commonly affected – hence forming a band shaped lesion. This area may ulcerate causing ocular pain and complicating treatment of the ERU with topical steroids. It is best treated with a superficial keratectomy to remove the affected stroma, which once healed, will allow continued treatment of the uveitis with topical steroids (see later).
The inflammation of ERU has been demonstrated by immunohistochemistry to be largely CD4+ T cell driven. The ciliary body epithelium has also been shown to produce cytokines that stimulate equine lymphocytes. High concentrations of interferon-γ (IFN-γ) and interleukin-2 (IL-2) have been demonstrated in the aqueous and vitreous of ERU cases. Identifying triggering factors for relapses is a major area of research.
There has been a huge amount of speculation as to the cause of ERU. Leptospirosis has been implicated as a cause of ERU, with some evidence supporting this hypothesis. Experimental infection of ponies with Leptospira interrogans serovar pomonaresulted in uveitis in all cases, nearly a year following exposure with some ponies developing repeated episodes of ocular inflammation. Leptospiral DNA has been identified in aqueous humour and vitreous in ERU cases. In Germany this has been documented more substantially than similar studies in the USA. So far, similar studies in the UK have not been published. A serological survey of ERU cases in the UK was reported but did not show a significant association between serum titres and uveitis. Subsequent studies have, however, shown that serological titres are poorly correlated with disease and that the presence of Leptospiral organisms, DNA or antibodies can be demonstrated in the absence of serological conversion.
More recent work from the USA and Germany suggests that Leptospiral molecular mimicry of ocular antigens exists and may be responsible for the development of repeated episodes of uveitis. Elegant research, again in Germany and USA, has demonstrated a number of self antigens to be implicated in recurrent inflammation, most notably retinal S-antigen and interphotoreceptor binding protein.
Medical therapy
Preservation of vision and relief of pain are the goals of therapy for ERU. Control of ocular inflammation is therefore the mainstay of treatment. Where high titres, or better still rising titres, are demonstrated to L. Interrogans serovars antibacterial therapy should be considered. Vaccination against Leptospira using bovine vaccines in horses has not been demonstrated to be beneficial.
Treatment to control ocular inflammation should be aggressive. Often apparent failures of treatment are due to inadequacy of treatment. Topical corticosteroids are the most commonly employed anti-inflammatory drugs. Prednisolone acetate (Pred Forte™) or dexamethasone hydrochloride (Maxidex™, or in combination with neomycin and polymixin B, Maxitrol™) have good ocular penetration. Minimum treatment should be six times daily application and as this is frequently difficult for horse owners, a subpalpebral lavage system should be considered to facilitate treatment. Infusion pumps can be connected to this system allowing hourly medication and avoiding a head shy horse.
The subpalpebral lavage system can be placed in the upper or lower eyelid and opinions vary as to the most suitable location. It is important that the footplate of the lavage system is placed well into the conjunctival fornix so that it cannot impinge on the cornea and cause an ulcer. Such complications are difficult to deal with, given that topical corticosteroids must be discontinued and one arm of inflammatory control is lost.
Atropine application will help to dilate the pupil and relieve ciliary spasm, thereby alleviating a great deal of ocular pain. Atropine is also reported to assist in stabilising the blood aqueous barrier. It should only be applied sufficient to keep the pupil maximally dilated; some atropine will be absorbed systemically and can cause ileus. Monitoring for signs of colic is important in horses receiving atropine, and all owners should be made of aware of the risks. If a pupil fails to dilate with two applications of atropine it is unlikely to do so with atropine alone. Aggressive control of ocular inflammation may enhance the mydriatic effect of atropine by removing the miotic stimulus. The addition of phenylephrine to the topical medications may assist in mydriasis, however, topical 10% phenylephrine has been associated with hypertension in man and therefore should be used with caution in animals with cardiovascular disease.
Systemic non-steroidal anti-inflammatory drugs are an important facet of treatment. The most severe cases usually require flunixin, often in excess of the licensed five day course. Again, owners must be appraised of this, as well as the risks of gastric and renal side effects. Once inflammation is better controlled, weaning onto phenylbutazone may be appropriate, although risks of gastric and renal side effects do remain. The use of corticosteroids systemically can be considered but the attendant laminitis risks should be thoroughly discussed with the owner, and the dose should be tapered, not abruptly ceased.
Identifying triggering factors for relapses is a major area of research. Treating inflammatory episodes fails to tackle the underlying disease, each episode causing increasing permanent damage and a closer step toward blindness. This has lead to the development of surgical treatments for ERU that aim to reduce the frequency and severity of future attacks.
Surgical treatments
Pars Plana Vitrectomy
Vitrectomy is a highly specialised procedure where the core of the vitreous gel is removed and replaced with saline. The idea is to remove inflammatory cells and cytokines that are sequestered in the vitreous. Leptospiral organisms have also been identified within this material, leading many surgeons to include a low dose of gentamicin in the replacement fluid. It is important to note that higher doses will chemically ablate the ciliary body and cause phthisis of the globe. This surgical approach has been used successfully in Germany (by specialist equine surgeons: Professor Hartmut Gerhards, Dr. Bettina Wollanke, Dr. Uwe Heidbrink, Dr.Birgit Fruhauf, Dr. Bernhard Ohnesorge, Dr Eckehard Deegan; and specialist ophthalmologist: Professor Michael Boeve) for a number of years, where it has dramatically reduced the number of attacks compared with untreated horses. It is not to be undertaken lightly, as it requires a general anaesthetic and specialised surgical knowledge and equipment.
The vitrectome is introduced into the posterior segment via an incision at the pars plana region of the ciliary body. Visualisation of the cutting end of the vitrectome and its direction can be transpupillary or via an endoscopic probe depending on surgeon preference/experience, as well as the presence of cataract which would preclude transpupillary visibility. Cataract progression without further inflammatory episodes may continue, thus some surgeons believe the best surgical candidates for this procedure are those without observable evidence of cataract formation. Other surgeons argue that using endoscopic vitrectomy allows horses with early cataract formation to benefit from a reduction in painful inflammatory episodes even if preservation of vision cannot be guaranteed. The procedure is undertaken during quiescence and only where there is evidence of ERU (two or more documented episodes of uveitis). Retinal detachment is a risk of the procedure, as well as with ERU itself, and post-operative endophthalmitis, notwithstanding the general anaesthetic risks.
Pars plana vitrectomy on equine patient. Photo courtesy of AcriVet
Professor Bernhard Spiess (specialist ophthalmologist at Zurich University, Switzerland) reports that vitrectomy is best employed in cases with a positive vitreal Leptospiral PCR or culture result. Unfortunately this sample is best achieved by vitrectomy, and certainly under general anaesthetic, so is somewhat after the event. Those with negative PCR or culture are better treated with a suprachoroidal cyclosporine implant.
Recurrence rates following vitrectomy vary with authors between 2 and 28% over the first year following vitrectomy
Suprachoroidal Sustained Release Cyclosporine Implant
This modality was developed by Professor Brian Gilger and his colleagues at North Carolina State University in USA. Initially an intravitreal device was developed as cyclosporine poorly penetrates the intact eye. However post operative vitreal detachment and vitreal haemorrhage were significant complications associated with implantation. A suprachoroidal implant was developed that avoided penetrating the eye with its incumbent risks, whilst preserving the intraocular penetration.
Again, these are best implanted in the quiescent phase of the disease. They take between 30-45 days to reach therapeutic concentrations and therefore traditional medical treatments are best applied if relapses occur within this post-operative period. All cases should receive systemic flunixin, topical antibiotic cover and atropine post-operatively. Some cases will also require topical anti-inflammatory drugs.
Recurrence rates following cyclosporine implant placement are reported as 25%, with recurrences generally being less severe and of shorter duration. The slow-release implant has a delivery duration of 3.2 years.
ERU is the most common cause of blindness in horses
Each episode should be treated with intensive anti-inflammatory therapy both systemically and topically
A subpalpebral lavage system should be considered early
For long-term management consider surgical therapy – either pars plana vitrectomy or suprachoroidal cyclosporine implant.
First published in Veterinary Times 25th May 2009