In most previous canine reports, only the corneas were examined microscopically, but in one study, evaluation of the entire globe found vacuolation of cells in the bulbar conjunctiva, iris, choroid and sclera; this vacuolation was attributed to GAG accumulation.
11 In the present study, GAG accumulation was not identified in these tissues. In humans with MPS I, ocular GAG accumulation occurs in anterior chamber structures and within the uveoscleral outflow tract, resulting in narrowing of the iridocorneal angle, obstruction to aqueous drainage, and subsequent glaucoma.
1,23 –25 Additionally, GAG accumulation in the dura mater or sclera can cause compression and atrophy of the optic nerve.
1 GAGs have also been shown to accumulate in retinal ganglion cells
26 or retinal pigment epithelial cells,
1 which may further contribute to optic nerve atrophy and electroretinogram abnormalities. These additional GAG accumulations were not noted in any of the canine globes examined in this study, nor was there any evidence of glaucoma or optic nerve degeneration. This may represent a difference in the manifestations of MPS I in our dogs, which generally exhibited a somewhat milder form of disease than Hurler patients, or, less likely, an age-related sampling bias. In one human ERT study, ages ranged from 7 to 44 years.
15 In the present study, the oldest affected dogs were 40 and 50 months old, and in both cases only the cornea was available for examination. The only other associated ocular abnormality in the dogs in the present study was the presence of a preiridial fibrovascular membrane (PIFM). Formation of PIFMs is attributed to the effects of soluble vasogenic proteins like VEGF from inflammatory cells, neoplastic cells, or retinal neurons. In dogs, PIFMs most commonly occur in globes with chronic retinal detachment, retinal ischemia, chronic uveitis and intraocular tumors. In severe cases, PIFMs can obscure the iridocorneal angle, impede aqueous outflow, and result in secondary glaucoma.
27 A recent publication describes anterior chamber flare (increased protein in the aqueous) in some untreated dogs with MPS I
18 ; this may have contributed to PIFM formation in affected dogs. The PIFMs seen in the dogs in the present study were thin (mild) and did not involve the iridocorneal angle. The presence of a PIFM tended to decrease with increasing treatment dose, but given the small number of affected dogs, statistics were not performed. The underlying cause of PIFM development in these dogs is unclear but may be secondary to corneal pathology; to the best of our knowledge, similar lesions are not reported in humans.