Golden Retriever Pigmentary Uveitis (GRPU)

GRPU is a progressive anterior uveitis, typically affects both eyes, has no gender predilection and affects the Golden Retriever only.

Steve Dugan, DVM, MS, Diplomate of the ACVO

Golden Retriever Pigmentary Uveitis (GRPU) was first described and published in 1996 within the American College of Veterinary Ophthalmologists Genetic Committee report of “Ocular Disorders Presumed to be Inherited in Purebred Dogs”.  Available information indicates this is a significant health issue in the Golden Retriever breed.  In many cases, there are no outward clinical signs of disease in its earliest and potentially most treatable stages.  According to the ACVO Genetics committee report (ref 3), the inheritance pattern in “NOT DEFINED” and the breeding advise is “NO”.  Because GRPU often develops after the prime reproductive years, it is difficult to control in a breeding program; thus, the most prudent breeding strategy is to minimize the genetic contribution of all related Golden Retrievers.

Anecdotally, GRPU is speculated to be an inherited, breed-related, immune-mediated disorder causing primary uveitis as GRPU is not associated with any underlying metabolic or endemic infectious/systemic disorders.  GRPU is a progressive anterior uveitis, typically affects both eyes, has no gender predilection, affects the Golden Retriever only, has been documented to affect the Golden Retriever across the US, the mean age of affectation has been reported to be 8.6 +/- 2.1 years, and has an ophthalmic hallmark of the appearance of pigment dispersion (exfoliation) upon the anterior capsule of the lens in a radial orientation or in multifocal zones with or without visible uveal cysts.  Pigment on the anterior capsule of the lens is considered the earliest clinical sign of GRPU.  The largest retrospective, peer-reviewed clinical report written by Sapienza et. al. (ref 1) described clinical findings in 75 Golden Retrievers (142 affected eyes).  Visible uveal cysts were noted in 19/142 (13%) of the cases.  While the presence of uveal cysts does not mean that an individual has Pigmentary Uveitis, almost all Golden Retrievers with Pigmentary Uveitis do have iris/uveal cysts.  In another clinical, but prospective study, with the goal of determining the prevalence of uveal cysts and pigmentary uveitis in Golden Retrievers in three Midwestern states (ref 2), 80/328 (24%) eyes had visible uveal cysts.

The level of aqueous flare is minimal in most cases of GRPU.  Fibrinous debris has been observed within the anterior chamber of 52/142 (37%) of affected eyes and was associated with a poor prognosis as 19/52 (37%) of those eyes with pre-existent fibrin subsequently developed glaucoma.  Posterior synechiae were identified in 71/142 (50%) of affected eyes.  Secondary obstructive glaucoma developed as a sequelae in 66/142 (46%) of the eyes based upon buphthalmos and optic disc atrophy with or without an associated elevation in IOP; 38/142 eyes (27%) were considered glaucomatous at the time of initial examination whereas 28/142 (20%) subsequently developed glaucoma from 3 weeks to 3 years later.  The mechanism of secondary glaucoma can be multifactorial and may include: mechanical angle closure by iridociliary cysts, heavy deposition of pigment within the iridocorneal filtration angle, pupillary block, release of uveal cystic contents, and/or inflammatory cellular material blocking the aqueous outflow pathway.  Post-inflammatory cataract ranging from incipient, clinically insignificant to mature/hypermature were identified in 53/142 (37%) eyes and was considered another sequelae to chronic, unrelenting uveitis.   Additional clinical findings can include uveal-based pigment adherent to the corneal endothelium and diffuse hyperpigmentation of the iris surface.

GRPU is not known to spontaneously regress or resolve with treatment.  Treatment has been largely directed against clinical uveitis and minimizing the occurrence of glaucoma.  Topical, subconjunctival, and oral corticosteroids, oral nonsteroidal immunosuppressants such as Azathioprine, Timolol 0.5% and Dorzolamide 2%, as well as intracameral tissue plasminogen activator (tPA) have all been used in various combinations.  Despite medical and surgical, transcleral diode laser cyclophotocoagulation (TSDLCPC), intervention via Sapienza et. al., 46% of all eyes examined became blind from glaucoma.  Transcleral diode laser cyclophotocoagulation was performed when preservation of vision was the primary goal but failed to do so on all 11 treated eyes; however, TSDLCPC successfully controlled the glaucoma in 10/11 (91%) eyes.  Enucleation and intrascleral prostheses (ISP) were performed on 4 and 14 permanently blind, painful, glaucomatous eyes, respectively.

Histopathology was performed on the eviscerated contents of the glaucomatous eyes that received ISP’s and all of the enucleated globes and revealed a preiridal fibrovascular membrane in 2 eyes and mild lymphocytic anterior uveitis in 2 eyes, but the extent of uveal inflammation in most cases was described as minimal and depigmentation of the uveal tract (typical of immune-mediated ocular diseases such as uveodermatologic syndrome) was not a feature on any microscopic sections.  Thus, histologic evidence of severe inflammation causing glaucoma was limited in the cases for which histopathology was obtained via Sapienza et. al.  Thin-walled iridociliary cysts were identified in 15/18 (83%) biopsy samples and it has thus been hypothesized that iridociliary cysts are associated with the development of glaucoma in the Golden Retriever breed.   However, cysts within the posterior chamber oftentimes are not observed during the clinical examination.  The immunohistochemical staining pattern of the cysts suggested their origination from the ciliary body epithelium.  Uveal cysts, fluid-filled structures arising from the posterior aspect of the iris or ciliary body, by themselves are usually considered to be benign; however, in the Golden Retriever, Great Dane, and American Bulldogs, uveal cysts have been associated with the development of glaucoma.  Thus, it is not known if uveal cysts result in GRPU, whether GRPU causes cyst formation, or whether iridociliary cysts are merely an incidental finding.  In the prospective study by Townsend et. al. (ref 2), uveal cysts alone were identified in 80/328 (24%) eyes or 57/164 (35%) dogs with the mean age of the Golden Retrievers with uveal cysts of 6.6 +/- 2.0 years.  Whereas, 9/164 (6%) dogs were diagnosed with GRPU with a mean age of 10.8 +/- 2.3 years.

Because of the late onset of GRPU, the Golden Retriever Club of America now recommends annual eye certification exams for all Golden Retrievers throughout their lifetime.  The prognosis for vision for Golden Retrievers diagnosed with PU is considered to be guarded, particularly in advanced cases with excessive posterior synechiae and fibrin clot formation.

References

  • Sapienza JS, Domenech FJS, Prades-Sapienza A. Golden Retriever uveitis: 75 cases (1994-1999).  Vet Ophthalmology 2000; 3: 241-246.
  • Townsend WM, Gornik KR. Prevalence of uveal cysts and pigmentary uveitis in Golden Retrievers in three Midwestern states.  JAVMA 2013; 243: 1298-1301.
  • Golden Retriever. In: Ocular disorders presumed to be inherited in purebred dogs. Genetics Committee of the American College of Veterinary Ophthalmologists, 2013.
  • Golden Retriever Club of America website available at: grca.org/health/uveitis2.html. Accessed March 26, 2015.