Diagnostic Ophthalmology

History and clinical signs

A 9-week-old bloodhound cross dog was examined by the ophthalmology service at the Western College of Veterinary Medicine (Saskatoon, Saskatchewan). This dog presented for evaluation of an enlarged right eye that had been present since birth. The menace response and dazzle reflex were absent in the right eye. The pupil could not be visualized in the right eye to evaluate the direct pupillary light reflex in this eye; however, the consensual pupillary light reflex was absent in the left eye. The palpebral and oculocephalic reflexes were normal bilaterally. Schirmer tear test (Schirmer Tear Test Strips; Alcon Canada, Mississauga, Ontario) values were 15 mm/min bilaterally. The intraocular pressures (IOPs) were estimated with a rebound tonometer (Tonovet; Tiolat, Helsinki, Finland) and were 17 and 12 mmHg in the right and left eyes, respectively. Fluorescein staining (Fluorets; Bausch & Lomb Canada, Markham, Ontario) of the cornea was negative bilaterally. Distant examination revealed marked buphthalmos and corneal opacity in the right eye. Following application of 0.5% tropicamide (Mydriacyl; Alcon Canada), direct examination using a transilluminator (Welch Allyn Finoff Transilluminator; Welch Allyn, Mississauga, Ontario) and handheld biomicroscope (Kowa SL-17 Portable Slit Lamp; Kowa Co, Tokyo, Japan) revealed multiple iris-to-iris and iris-to-lens persistent pupillary membranes (PPMs) and an incipient capsular cataract at the insertion site of the PPM in the dorsomedial lens of the left eye. Examination of the right eye revealed extensive superficial corneal vascularization, mild diffuse corneal edema, a central corneal facet, and central corneal fibrosis. In addition, the anterior chamber was absent, with uveal-like tissue adjacent to the corneal endothelium in this eye. Indirect ophthalmoscopic (Heine Omega 500; Heine Instruments Canada, Kitchener, Ontario) examination was not possible in the right eye but was normal in the left eye. Photographs of the right and left eyes at presentation are provided for your assessment (Figure 1).

Figure 1.

Photographs of the right (A) and left (B) eyes of a 9-week-old bloodhound cross dog.

What are your clinical diagnoses, differential etiologic diagnoses, therapeutic plan, and prognosis?

Discussion

The ophthalmic diagnoses were congenital glaucoma and nonulcerative exposure keratitis of the right eye, and iris-to-iris and iris-to-lens persistent pupillary membranes (PPMs) in the left eye.

Glaucoma is a condition characterized by elevated intraocular pressure (IOP) due to reduced outflow of aqueous humor (1). Congenital glaucoma is glaucoma that is present at birth or that develops within the first year of life (2). Congenital glaucoma may be unilateral or bilateral and usually manifests with severe globe enlargement (buphthalmos). Buphthalmos occurs rapidly and dramatically in young eyes due to greater elasticity of the immature sclera (3). Extensive buphthalmos results in corneal exposure, referred to as exposure keratitis (or keratopathy), which may include corneal ulceration, pigmentation, vascularization, and scarring. Clinically, the IOP in the buphthalmic globe may be elevated or normotensive, as seen in this dog. This phenomenon is thought to be related to compensatory globe enlargement, scleral thinning, and uveal atrophy, and reflects the chronicity of glaucoma (3). The rapid globe stretching that occurs with congenital glaucoma can be somewhat protective of the retina and optic nerve, and vison can be maintained longer than expected in some puppies (3).

Congenital glaucoma is associated with anterior segment dysgenesis (ASD). The embryological development of the anterior segment is complex and there is a wide spectrum of abnormalities that are considered manifestations of ASD (4,5). Anterior segment dysgenesis may manifest with anomalous formation of the cornea, anterior chamber, uvea, or lens (4,5). Features of ASD include hypoplastic uveal tissues; lens malformations such as microphakia, spherophakia, and cataract; and abnormalities of the iridocorneal angle, including hypoplasia or aplasia of the pectinate ligaments, ciliary cleft, and trabecular meshwork (2,4,6). Anomalies of the iridocorneal angle contribute to the pathogenesis of inadequate aqueous humor exit, and thus, glaucoma (3). The cause of ASD is usually idiopathic, related to a genetic mutation or due to in utero exposure to toxins, infectious agents, or nutritional deficiencies (7). It is not recommended to breed animals that are diagnosed with clinical features of ASD, apart from iris-to-iris PPMs.

Persistent pupillary membranes are among the most common congenital ocular anomalies in dogs and are also a manifestation of ASD (4). In the embryo, there is a solid sheet of mesenchymal tissue between the corneal endothelium and the future iris that ultimately remodels to form the anterior chamber (5). The portion of this sheet spanning the pupil is called the pupillary membrane, and the pupil is formed by regression of this membrane. Failure of complete regression of the pupillary membrane results in persistence of tissue strands (5). There are 3 possible PPM variants based on the strand attachments: iris-to-iris (extending from one location of the iris collarette to another), iris-to-lens (extending from the iris collarette to the anterior lens capsule), and iris-to-cornea (extending from the iris collarette to the posterior cornea). Iris-to-iris PPMs do not cause ocular pathology and are usually considered incidental findings. Iris-to-cornea and iris-to-lens PPMs cause opacities at the site of insertion, which can affect vision. The left eye of this dog had iris-to-lens PPMs with an incipient cataract at a strand insertion site. Fortunately, the cataract was small enough to have minimal consequences for vision. The lack of anterior chamber in the right eye was most likely a manifestation of more extreme failure of embryonic mesenchymal tissue remodeling.

Treatment of congenital glaucoma depends on the visual status of the globe. Medical therapy for visual eyes can include topically applied prostaglandin analogues in addition to carbonic anhydrase inhibitors/beta-adrenergic agonist medications. Topical lubricants and lacrimostimulants may be beneficial for reducing corneal desiccation, and topical antibiotics are necessary if corneal ulceration is present. Blind globes should be treated surgically by enucleation and the globe should be submitted for histopathology to help confirm the etiology. Permanent blindness was indicated in this puppy by the absence of a dazzle reflex in the right eye and the lack of a consensual pupillary light reflex in the left eye. Due to the buphthalmos, exposure keratitis, and blindness, this dog was returned to his referring veterinarian for enucleation of the right eye. Histopathology of the globe confirmed the diagnosis of congenital glaucoma and ASD.

Congenital glaucoma is caused by ASD; however, not all manifestations of ASD lead to glaucoma (4). Both eyes of this dog exhibited manifestations of ASD, but only the anomalies of the right eye were severe enough to cause glaucoma. Glaucoma caused by ASD is associated with hypoplasia of the uvea, including the iridocorneal angle structures (2). The primary clinical manifestation of congenital glaucoma is extensive buphthalmos in young or neonatal animals. Despite the potential for vision retention allowed by compensatory globe stretching, the prognosis for congenital glaucoma is poor, as animals eventually become blind and extensive buphthalmos often leads to exposure keratitis. As globe stretching and keratitis are painful sequelae, enucleation is indicated for blind globes.