The syndrome Multiple Congenital Ocular Anomalies (MCOA) is a congenital eye disorder in horses. It was first described in Rocky Mountain Horses in 1999 [1]. Previous studies have shown that both the Silver coat colour and the MCOA syndrome in horses are caused by the same missense mutation in the premelanosome protein (PMEL) gene [2, 3]. The mutation, a change from cytosine (C) to thymine (T), causes a dilution of the eumelanin pigment especially in the mane and tail [2]. PMEL encodes the transmembrane glycoprotein PMEL also known as PMEL17, which is essential for the biogenesis of eumelanin in the melanosomes. PMEL forms fibrillary structures where melanin is deposited during melanogenesis [4, 5]. Post translational and proteolytic processing of PMEL are required for a correct formation of the fibrillar matrix. It is not clear how these processes are regulated [6, 7]. In a study from 2011 a knock-out mouse line where PMEL had been inactivated was created [8]. It was shown that PMEL was important for eumelanin production in skin, choroid and retinal pigment epithelium. However, full-field electroretinogram did not show any impaired function of the retina [8].

Clinically, Silver coloured horses can be subdivided into two different groups, the Cyst phenotype and the MCOA phenotype, according to the severity of the ocular defects. Horses with the Cyst phenotype are known to be heterozygous for the Silver mutation (CT). They have less severe ocular signs predominantly iridociliary cysts, usually in the temporal quadrant of the eye. The cysts are translucent and can be up to a centimetre in size. Horses with the MCOA phenotype are known to be homozygous for the Silver mutation (TT). They have more severe clinical signs including iridal stromal hypoplasia, miotic pupils, retinal dysplasia, cataract, cornea globosa and iridociliary cysts occasionally extending subretinally [1, 9–11]. An incomplete dominant mode of inheritance has been suggested [10, 12, 13].

The ocular defects that are present in horses homozygous for the Silver mutation cause visual impairment or blindness [1, 9–11]. It is still unknown if vision is impaired in horses heterozygous for the Silver mutation. Hence, more information is needed to investigate how the MCOA syndrome affects the vision in horses heterozygous for the Silver mutation. A recent study in Comtois and Rocky Mountain horses reported that horses with the Silver mutation, both heterozygotes and homozygotes, had deeper anterior chambers of the eye compared to wild-type horses. A significant difference in the depth of the chamber was also detected between heterozygous and homozygous horses [11]. An abnormal distance between the refractive surfaces of the eye is likely to cause refractive errors. The purpose of the present study was to investigate if Icelandic horses with the Silver mutation have refractive errors compared to wild-type horses of the same breed.

This study was performed to provide additional insight into how the MCOA syndrome affects the vision in horses heterozygous for the Silver mutation. Our results indicate that horses older than 16 years carrying the Silver mutation are more likely to be myopic than wild-type horses of the same age. In the present study CT horses older than 16 years on average were more myopic than wild-type horses of the same age. No difference in the refractive state could be observed between genotypes (CT and CC) in horses younger than 16 years.

A myopic shift in elderly individuals has also been observed in human beings and dogs [15–17]. Although humans experience a hyperopic shift with age as they develop presbyopia, a long-term study has shown that this trend reverses in the direction of myopia in the oldest group (70 years and older) [15]. To our knowledge, there are few studies on how the refractive state changes with age in horses. A degree project at the Swedish University of Agricultural Sciences by Löf from 2007, where 116 Standardbred trotters were included in a cross-sectional study, showed that elderly horses had a progression towards myopia. In the current study we observed a significant difference in the refractive state between CT and CC horses in ages 16–21 years. Horses older than 21 years could not be further analysed because of small sample size. Seven of the CT horses had moderate or severe myopia (−1.5 D or more) and five of these were 16 years or older. These horses were not closely related and they came from different stables.

The observed shift towards myopia in elderly CT horses may also suggest that the Silver mutation exerts a slowly progressive effect on the optics of the eye. However, one important limitation is that this was a cross-sectional study and we did not have the possibility to follow these horses from when they were foals up to old age. The MCOA syndrome is generally thought to be non-progressive [1], although there are indications that at least some clinical signs may progress [11]. The study by Ségard et al. from 2013, where 59 Comtois and 16 Rocky Mountain horses ranging from 10 days to 18 years of age were included, reported no differences in presence of ocular abnormalities between young, adult and old horses for the majority of the defects detected [11]. However, a possible increase in the number of cystic lesions with age was suggested. Foals with the Silver mutation, both homozygotes and heterozygotes, had significantly fewer cysts compared to adult and old horses of the same genotype [11]. The study by Plummer and Ramsey from 2011 [18], where 53 American Miniature horses were included, showed no correlation between age and presence of ocular abnormalities. The median age of the horses in that study was 5.3 years with a range from 1.5 to 219 months (18.25 years). Hence, the median age of the horses was lower in the previous studies [11, 18] compared to our study. In our study, 23 (32%) of the CT horses of different ages had visible cysts in one or both eyes. No correlation between age and presence of cysts or other ocular abnormalities could be observed. Cysts were hard to detect in TT horses because of miotic pupils. Most likely both CT and TT horses had cysts that could not be detected because we neither dilated the pupil, nor used more sensitive methods such as ultrasonography to evaluate the presence of cysts. However, that was beyond the scope of this study.

We found no difference in the refractive state between genotypes (CT and CC) in horses younger than 16 years. One possible reason could be that the refractive errors were minimized by other, compensatory mechanisms. Therefore it would have been interesting to measure other parameters, including anterior chamber depth and axial length that could shed light on the underlying causes of the refractive results of the horses in our study. Unfortunately, the ophthalmic examinations were performed in stables and no equipment for precise measuring of additional ocular biometric parameters was available.

Only five TT horses were included in our study. These horses were difficult to find, probably because of a low frequency of the TT genotype, as horse owners are recommended not to mate two Silver coloured horses. TT horses had more severe ocular signs than CT horses, which is in accordance with previous studies [1, 9–11]. These horses also represented a special challenge to refract because of their miotic pupils. Skiascopy could not be performed in one of the TT horses because of cataractous lenses in combination with very miotic pupils, two clinical signs already described as being part of the MCOA phenotype [1, 9–11]. TT horses were myopic (−2 D or more) in one or both eyes regardless of age. Only one CT horse in the study had an immature cataract visible to the naked eye. This horse was also myopic (−3 D in the right eye and −2 D in the left eye). Some individuals, both CT and TT, seem to have more severe clinical signs of the MCOA syndrome. Hence, additional genetic factors may be involved. None of the wild-type horses in the study were myopic (−1.5 D or more). The Icelandic horse as a breed seems to be slightly hyperopic on average. This is in accordance with the results from a degree project at the Swedish University of Agricultural Sciences by Östberg in 2007, where 26 Icelandic horses with a median age of 11.5 years were included.

Eye (left or right) did not have a significant impact on the refractive state. This was as expected since the MCOA syndrome is reported to affect the eyes bilaterally [1]. The previous study by Ségard et al. from 2013 reported no significant difference in depth of the anterior chamber between right and left eye [11]. Sex was also not found to affect the refractive state in the present study. This was in accordance with previous studies [19, 20].

The horses in the present study were examined without dilation of the pupils. Previous studies have shown that cycloplegia has no impact on streak retinoscopic evaluation of refraction [19, 21]. Two degree projects at the Swedish University of Agricultural Sciences from 2007 by Östberg and Löf also showed that cycloplegia is not needed before retinoscopy in horses older than 9 months.

We considered the horizontal refractive values most convenient to obtain because of the ellipsoid shape of the pupil in horses and therefore most accurate to assess. Hence, only the horizontal values were used in the statistical analyses. However, the differences between the horizontal and vertical values were less than 0.5 D in all horses and therefore none of the horses were considered to be astigmatic.

One of the major strengths of our study is that we have a large dataset that represents a wide range of ages in a homogenous population with only one breed. Each CT and TT horse was well matched by a wild-type horse of the same breed and age ± 1 year.

This study provides valuable information about the refractive state in Icelandic horses with the Silver mutation which can be used in future breeding recommendations. Horse owners should be aware that Silver colored horses older than about 16 years may have an increased risk to become myopic compared with wild-type horses.

Our results indicate that horses older than 16 years carrying the Silver mutation are more likely to be myopic than wild-type horses of the same age.