Although many ocular diseases in reality affect most portions of the globe, in this section we will deal primarily with conditions that have severe consequences to multiple anatomical structures of the eye. The most important condition is glaucoma. The developmental abnormalities discussed below are relatively uncommon, especially when compared to the incidence of glaucoma, which is a complex, common, and important condition, and one that you should know thoroughly.
Glaucoma
Glaucoma is a clinical diagnosis and is by defined by a sustained and damaging increase in intraocular pressure (IOP). Glaucoma has many etiologies, and the effects of increased IOP manifest in just about every structure in the globe. With that in mind, the impact to the retina and optic nerve are the most important, as damage to these structures leads to loss of vision and pain.
Glaucoma is most common in dogs, followed by cats and horses. It is the leading cause of enucleation in both dogs and cats.
Intraocular pressure is a balance between the production and drainage of aqueous humour. Aqueous humour is produced by the epithelial lining of the ciliary body and flows into the posterior chamber, where it provides the lens with nutrients and oxygen while removing waste products. From the posterior chamber the aqueous humour flows through the pupil into the anterior chamber, where it provides the same services to the corneal endothelium and stroma. Having served its purpose, the aqueous humour then drains through the trabecular meshwork at the iridocorneal angle, located in the anterior chamber at the junction of the cornea and iris. From there, the aqueous humour enters a venous plexus and is returned to systemic circulation.
Although in theory, an increase in intraocular pressure could be due to an increase in production or a decrease in outflow, glaucoma is never due to increased production, and is always the result of decreased outflow.
The pathological changes to the eye caused by glaucoma can be related to four basic pathophysiologic processes:
- Direct or indirect physical effects on cells caused by increased IOP.
- Compression of vasculature from increased IOP leading to hypoxia.
- Stagnation of the flow aqueous humour.
- Autotoxicity.
Let’s consider each of the structures of the globe and how they may be affected by each process, and what the consequences would be. Remember, though, that it is the damage to the retina and optic nerve that leads to blindness in these patients.
Globe:
- Increased IOP may lead to an enlarged globe that protrudes slightly from the orbit (buphthalmos). This change is dependent to a degree on the age and species of the animal; younger animals with more elastic collagen are more likely to experience a stretch in the sclera.
Cornea:
- A buphthalmic globe is susceptible to corneal desiccation and lack of proper protection from the eyelids. This can result in exposure keratitis leading to ulceration or epidermalization.
- The corneal endothelium may be damaged by a) direct pressure; b) lack of proper aqueous flow (remember, the endothelium obtains nutrients, etc, from aqueous); and c) a stretched globe that results in a stretched and permeable endothelial barrier. These changes result in corneal edema.
Uvea:
- Pressure-induced hypoxia to the uvea can lead to atrophy of the uveal tissues, a change more commonly seen in chronic cases.
- The damaged retina may release cytokines leading to a pre-iridial fibrovascular membrane.
- Pressure-induced hypoxia to the vascular endothelium can lead to the leakage of proteins into the aqueous.
Lens:
- The decreased flow of aqueous humour can lead to cataract formation.
- Buphthalmos may cause stretching and tearing of the zonular ligaments and luxation of the lens.
Retina:
- Damage to the retina is most profound on its inner most aspect, affecting the ganglion cells and the nerve fibers that carry sensory information from the retina to the optic nerve. In severe cases, atrophy can affect the entire retina (most often seen in dogs, see the section on retina for more information).
- Although an exact understanding of the pathophysiology of glaucomatous retinal atrophy is incomplete, certain elements are known: a) increased pressure on axons of ganglion cells interferes with axonal transport and contributes to ganglion cell degeneration; and b) severely increased IOP interferes with retinal blood supply, leading to ischemic injury.
Optic nerve:
- Cupping or bowing of the optic disc is characteristic and caused by increased IOP and/or decreased numbers of axons following ganglion cell death.
- Cupping of the optic disc is a pathognomonic lesion: in other words, it is a lesion found uniquely in glaucomatous globes.
Unfortunately, the lesions of glaucoma rarely give us insight into the underlying cause of increased IOP. The etiologies of glaucoma are many and varied, and broadly can be divided into two categories: primary and secondary glaucoma.
Primary glaucoma
Primary glaucomas arise without significant acquired alteration or disease to other structures of the globe. Primary glaucomas can be subdivided further into those which show maldevelopment of the trabecular meshwork at the iridocorneal angle, a phenomenon known as goniodysgenesis, and those which do not, typically referred to as ‘open-angle glaucoma’.
Most dogs with primary glaucoma have goniodysgenesis. Goniodysgenesis is present at birth and is thought to be inherited, yet glaucoma typically only manifests in older dogs (5-12 years old). This finding, combined with the fact that not all dogs with goniodysgenesis will develop glaucoma, suggests that it is not the absence of the trabecular meshwork itself that is the cause of glaucoma, but some other (less well appreciated) alteration – either physical, or, more likely, functional – that leads to increased IOP. Thus, goniodysgenesis should be regarded as a risk factor, but not a cause, for glaucoma. A dog that develops primary glaucoma and is observed to have goniodysgenesis is at high risk for developing glaucoma in the other eye.
Primary open-angle glaucoma is uncommon, and is caused by dysfunctional drainage at the iridocorneal angle, rather than abnormal iridocorneal anatomy. It occurs in dogs, horses, and cats.
Secondary glaucoma
Secondary glaucoma, as it’s name would suggest, is diagnosed when acquired changes to structures of the globe interfere with the drainage of the aqueous humour. If you know and understand the path of aqueous outflow, then it is possible, to some degree, to intuit some of the changes that might impede the flow of the aqueous humor. Some examples include, but are not limited to:
- Infiltration of the drainage angle by inflammatory cells or metastatic neoplastic disease
- The development of a fibrous membrane that spans the iridocorneal angle
- Adhesion between the pupil and the iris (posterior synechia)
Pre-iridial fibrovascular membranes (PIFM)
Fibrovascular membranes develop when the concentration of angiogenic factors in the vitreous and aqueous of the eye exceed normal levels. A pre-iridal fibrovascular membrane (PIFM, pronounced “piff-em”) is one such membrane that develops on the anterior surface of the iris. Excess angiogenic factors like VEGF are produced in a variety of conditions, including corneal neovascularization (e.g. from an ulcer), inflammation (e.g. chronic uveitis), neoplasia, and retinal hypoxia following retinal detachment.
If a PIFM extends down the iris and across the pectinate ligament and blocks the trabecular meshwork, thus obstructing the passage of aqueous humor, secondary glaucoma is the result. Alternatively, PIFMs can grow towards the lens, and can lead to an adhesion of the iris of the lens (posterior synechia). If the adhesions spans the full 360 degrees of the lens, it can obstruct the flow of aqueous from the posterior chamber, resulting in pupillary block and forward bowing of the iris, known as iris bombe (“bomb-ay”), and glaucoma.
PIFMs are the most common cause of secondary glaucoma in the dog.
Cellular infiltration
As is the case with the drain in a sink, small holes can be easily plugged by debris, preventing adequate drainage. In the case of the eye, the trabecular meshwork is particularly susceptible to becoming clogged by cells, typically from neoplasia. Just like the sink, a clogged trabecular meshwork does not drain properly, leading to accumulation of aqueous humour and increased IOP.
In dogs, obstruction of the trabecular meshwork is most commonly obstructed by neoplastic infiltrates, usually [Canine anterior uvea melanocytoma].
In cats, Diffuse iris melanoma can directly obstruct the trabecular meshwork and lead to glaucoma, and, along with Feline lymphonodular uveitis, is the main cause of secondary glaucoma in this species.
Developmental abnormalities
True developmental abnormalities of the globe are rare. They include anophthalmia, or complete absence of the eye (extremely rare and usually bilateral); microphthalmia (a small, disorganized globe present within a normal eye socket); and cyclopia (a single eye that failed to divide) or synophthalmia (a single structure that contains duplicates of multiple portions of the eye).
A coloboma is a hole in one of the structures of the eye. They can occur in the iris, retina, choroid, or optic disc.