Collie Eye Anomaly

not just a problem for collies. CEA is more technically known as Choroidal Hypoplasia (CH). It is a recessively inherited eye disorder that
causes abnormal development of the choroid - an important layer of tissue under the retina of the eye. This disease is seen most frequently in U.S. collies, but also worldwide in Rough and Smooth Collies, Border Collies, Australian Shepherds, Lancashire Heelers, and Shetland
Sheepdogs. Since the choroid layer does not develop normally from the start, the primary abnormality can be diagnosed at a very young age.
Regrettably, there is no treatment or cure for CEA.

The symptoms and signs – the clinical phenotype – can vary greatly among affected dogs within one breed, between parent and offspring
and even within a litter. This creates a difficult situation for the breeder. Learning about the genetic cause and the course of the disease will help you understand how to manage it better and eventually avoid it altogether with genetic testing.

The primary problem is choroidal hypoplasia (CH). There is under-development (hypoplasia) of the eye tissue layer called the choroid. The
choroid appears pale and thin, almost transparent, and the blood vessels of the choroid can easily be recognized in those “thin” areas.
The ophthalmologist, looking at the back of the eye (the fundus) with an ophthalmoscope, typically will see an area of choroidal thinning that
appears like a “window” to the underlying vessels and sclera.

MILD disease: Mild disease is very common in U.S. collies and is present in the other breeds named above. It is easily recognizable on careful
ophthalmologic examination as early as 5 to 8 weeks of age. The lesion appears as an area lateral (temporal) to the optic disc with reduction or absence of pigment so that the underlying vessels of the choroid are seen. The choroidal vessels may be reduced in number and of abnormal shape. The underlying white sclera might also be visible. Once the retina changes to its adult color around 3 months of age, the normal pigment sometimes masks the changes in the choroid (so-called “go normal” – read more below). In mildly affected dogs, choroidal thinning is the only detectable abnormality and the dog retains normal vision throughout life. However, dogs with mild disease can produce severely affected offspring.

(The eye anomaly “merle” can be confused with choroidal hypoplasia, primarily in dogs from merle to merle breeding and whose coat color is whiter than their littermates. Although both conditions are inherited, can occur in the same breed and exhibit a range of fundus anomalies, there are sufficient dissimilarities for the ophthalmologist to make the distinction.)

SEVERE disease: In severely affected dogs, approximately 25% of dogs with CEA/CH, there are related problems with the health of the eye that can result in serious vision loss in some cases. Colobomas are seen at and near the optic nerve head as outpouchings or “pits” in the eye
tissue layers. Colobomas can lead to secondary complications such as partial or complete retinal detachments and/or growth of new but
abnormal blood vessels with hemorrhage – bleeding inside the eye. This happens in 5-10% of dogs with CEA/CH, generally by 2 years of age, and can affect either one or both eyes. Complications of severe disease can lead to vision loss, although this disorder only rarely threatens total blindness.

CEA/CH is not progressive in the usual sense. The essential features, choroidal hypoplasia and coloboma, are congenital – the abnormalities
develop as the eye develops. These features are also stationary once ocular development is complete around 8-12 weeks of life. Retinal
detachments and/or aberrant vessel formation can be congenital or develop later, in general only in eyes with colobomas.

Based on research done jointly by scientists at Cornell University and at The Fred Hutchinson Cancer Research Center, BOTH the mild and
severe forms of CEA/CH disease now are proven to result from the exact same gene and mutation in ALL of the affected breeds named above. This disease gene is located on canine chromosome number 37 and the disease-causing mutation has been identified. The mutation acts like a RECESSIVE mutation. That means, both parents of an affected dog must have at least one copy of the mutation and both parents must have passed a copy of the mutation to the offspring. The affected dog is HOMOZYGOUS RECESSIVE – that is, both copies of the gene are
mutant. ALL dogs that are homozygous recessive affected will show at least the mild form of the disease. ALL affected dogs, regardless of the actual severity of the lesions, are homozygous for the same mutant gene.

(A dog with one mutant copy and one normal copy of the CEA/CH gene is a carrier – is heterozygous. A dog with two copies of the normal
CEA/CH gene is homozygous normal.)

The frequency of CEA/CH disease varies among breeds and by country of origin. The U.S. registration organization, CERF, reported the
incidence in the U.S. of choroidal hypoplasia, optic disc/nerve coloboma and retinal detachment among several affected breeds over the period of 1991 to 1999. (Comparable data from other countries isn’t available to us yet.)

The frequency of the CEA/CH gene mutation in U.S. Rough and Smooth Collies appears to be extremely high. In general, the frequency of
affecteds in Rough and Smooth Collies is well over 50%, and in some populations has been observed to be as high as 85-90% of dogs
examined. Of the remaining, most are carriers. The frequency of the CEA/CH gene mutation in European Shetland Sheepdogs appears to be
significantly higher than in the U.S.

You might ask: if the mild form and the severe form of CEA/CH disease are caused by the exact same genetic mutation, why do some dogs have only mild disease while others have severe disease? Is the severity due to diet, activity, or other insults like infections or trauma? So far, there are no clues that non-genetic factors are responsible. Instead, there are probably other independently acting “modifier” genes that influence CEA/CH gene expression. If that is so, eventually these modifier genes will be detected, although the chore will be difficult. Possibly, by choosing mildly affected dogs and avoiding severely affecteds in a breeding program, breeders have concentrated positive influencing
independent modifier genes in their line. The CEA/CH gene frequency may not have changed, but the disease may be partially suppressed as
long as the modifying genes are carried along. This is a risky approach, since the identity of those influencing genes – indeed even their number and action – is a complete unknown.

You might also ask: is it true that early choroidal hypoplasia can “go normal,” that is, reverse to a normal appearance? There are occasional
reports of puppies, found to be affected as early as 5 weeks of age, that appear to “go normal” when re-examined some months later. The
abnormal features seem to disappear or lessen due to pigment changes and masking of the thin choroid areas. (However, if a dog had a
coloboma, this will remain – it is a permanent lesion.) The majority of dogs that “go normal” are homozygous for the CEA/CH mutation,
especially if they “go normal” slowly or incompletely. A small minority, however, are heterozygous carriers that tend to “go normal” at a very
young age. Regardless, the genetic status of such dogs was and remains constant during their lifetime, so these dogs can pass the mutant disease gene to their offspring. Testing will help you identify the genetic status of dogs that have an ambiguous clinical diagnosis.