Abstract
Objective—To determine the prevalence of uveal cysts and pigmentary uveitis (PU) in Golden Retrievers in 3 Midwestern states.
Design—Prospective cross-sectional study.
Animals—164 American Kennel Club-registered Golden Retrievers in the states of Illinois, Indiana, and Michigan.
Procedures—For all dogs, biomicroscopic and binocular indirect ophthalmoscopic examinations of both eyes were performed after pupillary dilation. A finding of pigment deposition in a radial pattern or in zones on the anterior aspect of the lens capsule of 1 or both eyes was required for a diagnosis of PU.
Results—Eighty of the 328 (24.4%) eyes and 57 of the 164 (34.8%) dogs had visible uveal cysts. Of those 80 eyes with cysts, 41 (51.3%) had a single cyst located nasally and posterior to the iris, 33 (41.3%) had multiple uveal cysts, and 6 (75%) had a single, free-floating cyst. A diagnosis of PU was made for 9 (5.5%) dogs.
Conclusions and Clinical Relevance—Prevalences of uveal cysts (34.3%) and PU (5.5%) in the examined Golden Retrievers were both higher than prevalences reported previously (5.4% for uveal cysts and 1.5% for PU) in the Canine Eye Registry Foundation's 2009 All-Breeds Report. Study findings have indicated that PU is not a rare condition and should be considered as a differential diagnosis for Golden Retrievers with ocular disease.
Pigmentary uveitis is a condition unique to Golden Retrievers that was first described in 1996.1 Only 3 peer-reviewed articles2–4 documenting the clinical findings or histologic features of PU have been published to date, to our knowledge. Given the dearth of information regarding PU, there are many unanswered questions. The disease was first identified in Golden Retrievers in the Northeastern United States.4 However, now there is evidence that PU is established in Golden Retrievers across the United States. The disease affects Golden Retrievers only, has unique clinical signs, does not appear to be associated with any underlying systemic disorder, and has familial associations. Therefore, PU is highly suspected to be a heritable condition with no sex predilection in Golden Retrievers.4,a
Clinically, the hallmark of PU is pigment deposition on the anterior aspect of the lens capsule; the deposition often occurs in a radial pattern or in multifocal zones.4 The pigment on the anterior aspect of the lens capsule is considered the earliest clinical sign of PU.4 Additional clinical findings may include pigment on the corneal endothelium,3 increased pigmentation on the iridal surface,3 posterior synechiae,4 visible iridociliary cysts (in 13.3% to 42% of affected eyes4,a), accumulation of fibrinous material throughout the anterior chamber (in 18.1% to 36.6% of affected eyes4,a), glaucoma (in 30% to 46% of affected eyes3,4), and cataract development (in 36.6% to 43% of affected eyes3,4). The reported mean age of Golden Retrievers at the time that clinical signs are detected ranges from 8.12 to 8.6 years.4,a Typically, the condition affects both eyes.
Histologically, PU is characterized by cysts within the posterior chamber, many of which are often not observed during a clinical examination.3 The immunohistochemical staining pattern of the cysts suggests their origination from the ciliary body epithelium.3 In stained preparations, the cysts contain an Alcian blue–positive material, indicating that these cysts contain hyaluronic acid.2 Additional histologic findings in affected eyes may include the presence of free pigment within the trabecular meshwork, cysts extending across the anterior face of the vitreous humor, cysts attached to the lens capsule, posterior synechiae, peripheral anterior synechiae, a preiridal fibrovascular membrane, and mild lymphoplasmacytic uveitis.3,4
Uveal cysts are fluid-filled structures arising from the posterior aspect of the iris or ciliary body.5 Single or multiple cysts may be present. The cysts may be variably sized, spherical or oval, and light brown, brown, or black in color.5 Uveal cysts are usually considered to be benign.5 However, in Golden Retrievers,2 Great Danes,6 and American Bulldogs,7 uveal cysts have been associated with the development of glaucoma. In enucleated eyes of Golden Retrievers with PU, cysts are typically detected during histologic examination.3 It is not currently known whether the uveal cysts result in PU, whether PU causes uveal cyst formation, or whether cysts are merely an incidental finding.5
At the present time, the only available prevalence data regarding uveal cysts and PU is provided by the genetics committee of the American College of Veterinary Ophthalmologists or in the CERF 2009 All-Breeds Report. From 2000 through 2008, uveal cysts were detected in 2,757 of 56,123 (4.9%) Golden Retrievers that underwent eye certification examinations performed by veterinary ophthalmologists.8 In 2009, 182 of 3,373 (5.4%) Golden Retrievers similarly examined had uveal cysts.b During the same time periods, a diagnosis of PU was made for 0.2% (2000 through 2008)8 and 1.5% (2009)b of Golden Retrievers. However, these data have several likely limitations. First, dogs not used for breeding purposes are generally infrequently examined by veterinary ophthalmologists. This means that most pet Golden Retrievers are not routinely screened for the presence of this disease. In addition, most dogs used for breeding but that are past breeding age are not examined by veterinary ophthalmologists. Owing to the late age of onset of PU, the disease may be grossly underestimated in the Golden Retriever population.
Given the potential limitations of the data obtained by the American College of Veterinary Ophthalmologists or contained in the CERF 2009 All-Breeds Report and the lack of alternate PU prevalence data, the study reported here was performed to determine the prevalence of uveal cysts and PU in Golden Retrievers in 3 Midwestern states.
Materials and Methods
Examinations of both breeding and pet Golden Retrievers were conducted between November 2010 and May 2011 in Indiana, Illinois, and Michigan. The examination clinics were organized by local Golden Retriever clubs and owners. The examinations were being performed to identify Golden Retrievers with normal ocular examination findings that could serve as controls in ongoing genetic studies of PU. The participation of older animals (> 8 years of age) was encouraged. Only American Kennel Club–registered Golden Retrievers were examined. All examinations were conducted by the same board-certified veterinary ophthalmologist (WMT). The age, sex, history of PU, and pedigree data were recorded for each dog. The study conformed to the Association for Research in Vision and Ophthalmology Statement for the Use of Animals in Ophthalmic and Vision Research. Owner consent was obtained for all examinations.
For each eye of each dog, the menace response was assessed; if a menace response was present, the dog was deemed to have vision in that eye. After instillation of 1% tropicamide ophthalmic solutionc and achievement of maximal pupillary dilation, biomicroscopic and binocular indirect ophthalmoscopic examinations of both eyes were performed. For either eye, a diagnosis of PU required the presence of pigment on the anterior aspect of the lens capsule in either a radial pattern or as multifocal zones4 (Figure 1). When unilateral or bilateral PU was diagnosed, 1% proparacaine ophthalmic solutionc was applied topically to each of the dog's eyes and the IOP in both eyes was measured via applanation tonometry.d
Photograph of the left eye of a Golden Retriever with PU. Notice the characteristic radial pigment deposition and multifocal zones of pigmentation along the anterior aspect of the lens capsule.
Citation: Journal of the American Veterinary Medical Association 243, 9; 10.2460/javma.243.9.1298
Statistical analysis—Descriptive data are reported as mean ± SD and range. A χ2 test performed by use of commercial softwaree was used to compare the percentage of dogs with uveal cysts with that stated in the CERF 2009 All-Breeds Reportb (5.4%). A χ2 test was also used to compare the percentage of dogs with PU with that stated in the CERF 2009 All-Breeds Reportb (1.5%). In dogs with unilateral PU, the IOPs in the affected and unaffected eyes were compared with a paired Student t test. Significance was set at a value of P < 0.05.
Results
One hundred sixty-four Golden Retrievers (73 males and 91 females) were examined. Among all dogs, the mean ± SD age was 7.9 ± 3.8 years (range, 0.5 to 15.2 years). Eighty-one Golden Retrievers were 8 years of age or older.
Neither uveal cysts nor PU was detected in 98 of the 164 (59.8%) dogs. The mean age of dogs without uveal cysts or PU was 7.7 ± 4.3 years (range, 0.5 to 15.2 years). Uveal cysts were evident in 80 of 328 (24.4%) eyes and in 57 of 164 (34.8%) of dogs. The prevalence of uveal cysts was significantly (P < 0.001) higher than that stated in the CERF 2009 All-Breeds Report. The mean age of dogs with uveal cysts was 6.6 ± 2.0 years (range, 1.4 to 13.4 years). In the 80 eyes with uveal cysts, 41 (51.3%) had a single cyst located nasally within the iridociliary sulcus; these cysts typically did not extend past the pupillary margin. In 33 (41.3%) of the eyes with uveal cysts, multiple cysts were detected, often with at least 1 cyst extending beyond the pupillary margin. In eyes with multiple cysts, the main focus of cysts was located nasally with cysts then extending dorsally or ventrally; rarely did the cysts completely encircle the pupillary margin. In 6 (7.5%) of the eyes with uveal cysts, a single, free-floating cyst within the anterior chamber was observed.
Among the 164 dogs examined, the prevalence of PU was 5.5%. Nine Golden Retrievers had PU; the diagnosis of PU had been made previously for 3 dogs. The prevalence of PU was significantly (P < 0.001) higher than that stated in the CERF 2009 All-Breeds Report.b The mean age of dogs with PU was 10.8 ± 2.3 years (range, 6.6 to 13.9 years). The prevalence of PU in dogs ≥ 8 years old was 9.9% (8/81). Of the affected dogs, 6 were male and 3 were female. Of the 9 dogs with PU, 7 were unilaterally affected (3 right eyes and 4 left eyes) and 2 were bilaterally affected. Two dogs had been previously diagnosed as unilaterally affected with PU and remained unilaterally affected in the same eye previously diagnosed with PU. One dog had previously been diagnosed as bilaterally affected and remained bilaterally affected.
All 9 dogs with PU had vision in both eyes. Aqueous flare was not detected in any of the 11 affected and 7 unaffected eyes. Nine of the 18 eyes had multiple visible uveal cysts. Three affected eyes had cysts free floating within the anterior chamber. Of the 7 unilaterally affected dogs, 3 had multiple visible cysts in the contralateral eye and 4 did not. None of the eyes with PU in the 9 dogs were concurrently affected with glaucoma. The mean IOP in eyes with PU was 8.3 ± 1.7 mm Hg (range, 6 to 10 mm Hg; reference range, 10 to 20 mm Hg). There was no significant difference in IOP between the affected eye and the contralateral unaffected eye (P = 0.07) in the 7 unilaterally affected dogs. None of the 11 affected eyes had advanced (late immature, mature, or hypermature) cataracts; 4 affected eyes had posterior synechia. All 3 dogs for which a diagnosis of PU had been made previously were currently receiving topical corticosteroid therapy in the affected eyes. The 2 dogs that were previously known to be unilaterally affected were treated with 1% prednisolone acetate ophthalmic suspension in the affected eye only, and the dog that was previously known to be bilaterally affected was treated with neomycin-polymyxin-dexamethasone ophthalmic solution in both eyes.
Additional findings among the 164 dogs were as follows: cataracts (n = 25 dogs [15.2%]), dense nuclear sclerosis (13 [7.9%]), focal intraretinal hemorrhage (7 [4.3%]), eyelid mass (2 [1.2%]), asteroid hyalosis (2 [1.2%]), entropion (1 [0.6%]), conjunctival mass (1 [0.6%]), calcific corneal degeneration (1 [0.6%]), pigment deposition on the corneal endothelium (1 [0.6%]), iris-to-iris persistent pupillary membrane (1 [0.6%]), chorioretinal scar (1 [0.6%]), retinal dysplasia (1 [0.6%]), and central visual deficit (1 [0.6%]). The mean age of dogs with retinal hemorrhages was 11.9 ± 1.3 years (range, 9.3 to 13.4 years). The prevalence of retinal hemorrhages in Golden Retrievers ≥ 8 years old was 8.6% (7/81).
Discussion
In the present study involving Golden Retrievers in 3 Midwestern states, the prevalence of PU was 5.5%, which was significantly higher than the prevalence of 1.5% stated in the CERF 2009 All-Breeds Report,b and the prevalence of PU in dogs ≥ 8 years old was 9.9%. The higher prevalence in the older dogs was not unexpected because of the late age of PU onset.4,a The mean age of the dogs examined in the present study was 7.9 years, and 81 of the 164 dogs were ≥ 8 years old. The median age category of dogs for which data were collected and included in the CERF 2009 All-Breeds Reportb was 2 to 3 years. Therefore, the dogs included in the present study represented an older population of dogs than that used in the CERF 2009 All-Breeds Report.b In the past, eye certification examinations after dogs reached 8 years of age were not recommended.c Because of the late onset of PU, the Golden Retriever Club of America now recommends annual eye examinations for all Golden Retrievers throughout their lifetimes.f
The prevalence of uveal cysts among Golden Retrievers in the present study was 34.8%, which also was significantly higher than the prevalence of 5.4% stated in the CERF 2009 All-Breeds Report.b The reasons for the dramatic difference in prevalence between the 2 data sets are not clear. The different values may represent genetic variation within geographical regions or differences in age of the dogs at the time of the eye examination. Variation in the degree of pupillary dilation at the time of examination may also alter the rate of cyst detection because a widely dilated pupil improves the chances of observation of cysts located within the iridociliary sulcus. The degree of dilation can be affected by the interval between application of the mydriatic agent and commencement of the examination as well as the number of drops of the mydriatic agent applied to the eye. In the present study, uveal cysts were most frequently found singly and located posterior to the nasal aspect of the iris. Often the cyst was not large enough to extend beyond the pupillary margin and could only be seen when light was directed nasally and posterior to the iris leaflet. In Golden Retrievers with multiple uveal cysts, cysts were always located nasally with additional cysts extending either dorsally or ventrally. In previous reports2,6,9 describing uveal cysts in dogs, no predilection for cyst development in a particular quadrant of the eye was noted. In studies10,11 of humans with cysts in the iridociliary sulcus or pars plicata, the cysts were predominantly in the inferior, temporal, and inferotemporal quadrants; few individuals had nasally or superiorly located cysts.
A relationship between uveal cysts and the development of glaucoma in Golden Retrievers has been described.2 For most Golden Retrievers with PU, uveal cysts are detected during histologic examination of enucleated eyes, despite the fact that ophthalmic examinations do not reveal any evidence of cysts.3,4 For most Golden Retrievers with PU in the present study, ophthalmic examination revealed the presence of multiple uveal cysts. One Golden Retriever was diagnosed with unilateral PU during this study and noted to have multiple uveal cysts in both eyes at that time; within 10 months of his initial diagnosis, the dog developed PU in the contralateral eye. Longitudinal studies of dogs with uveal cysts are needed to determine whether the number and position of cysts are important risk factors for the development of PU.
None of the dogs in the present study had vision loss due to PU. According to Sapienza et al,4 75 of 142 (53%) dogs with PU developed glaucoma or vision-impairing cataracts. The owners of those dogs brought them to a veterinary ophthalmologist for evaluation because of an ocular complaint. In the present study, except for the 3 dogs known to be affected, all dogs were thought to be normal by their owners and were brought to participate in the screening examinations intended to identify dogs unaffected with PU to serve as controls for ongoing genetic studies. Their owners had noticed no visual deficits or ocular discomfort in their pets. Further research is needed to determine the benefit of early detection on long-term prognosis for dogs with PU.
All 3 dogs that were known to have PU prior to the present study were receiving topical ocular treatment with corticosteroids. All 3 dogs continued to be affected with PU, which was expected because PU is not known to spontaneously regress or resolve with treatment. None of those dogs had developed notable cataracts or glaucoma at the time of the study examination. In the study by Esson et al,3 histologic examination of globes affected with PU revealed evidence of minimal inflammation. However, all dogs from which those globes were obtained had been treated with topical or systemic anti-inflammatory drugs prior to enucleation. For dogs, the benefit of topical ocular or systemic anti-inflammatory treatment for PU has not been documented, to our knowledge. Longitudinal studies involving large numbers of dogs with PU will be required to address whether any treatments are of benefit. These studies could also determine whether slower disease progression is related to early detection and administration of therapeutic agents or merely reflects individual variation in the disease phenotype.
Results of the present study have indicated that the prevalence of PU in Golden Retrievers in these 3 Midwestern states was higher than that expected on the basis of published data. The prevalence of uveal cysts in these Golden Retrievers was also significantly higher than that reported previously for other dogs. Future studies are warranted to determine whether these differences reflect regional differences in the genetic background of Golden Retrievers or whether the prevalence of PU in Golden Retrievers throughout the United States is higher than previously described. Routine ocular examinations of Golden Retrievers ≥ 8 years old appear prudent, as many dogs may be affected without development of overt clinical signs.
ABBREVIATIONS
| CERF | Canine Eye Registry Foundation |
| IOP | Intraocular pressure |
| PU | Pigmentary uveitis |
Townsend WM, Mankey A, Gerlach JA. Association between dog leukocyte antigen haplotype and golden retriever pigmentary uveitis (abstr), in Proceedings. 40th Annu Meet Am Coll Vet Ophthalmol 2009;84.
CERF 2009 All-Breeds Report, Veterinary Medical Databases, Urbana, Ill. Available at: web.vmdb.org/home/CERF/AvailableServices/StatisticsReport.aspx. Accessed Dec 6, 2012.
Akorn, Lake Forest, Ill.
TonoPen, Reichert Ophthalmic Instruments, Depew, NY.
Quick Calcs, GraphPad Inc. Available at: graphpad.com/quickcalcs/chisquared2/. Accessed Dec 6, 2012.
Golden Retriever Club of America website. Eye exams and CERF-ing; a lifelong responsibility. Available at: www.grca.org/health/eyes.html. Accessed Dec 6, 2012.
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