David J. Maggs, BVSc (hons), DACVO
Ocular surface hyperaemia (so-called "red-eye") is one of the most common and potentially one of the most critical reasons animals are presented for ocular disease. It is essential that patients with this sign are not interpreted as "just a bout of allergic conjunctivitis" or "he must have got some dust in his eye" before more serious and potentially blinding diseases such as ulcerative keratitis, uveitis, or glaucoma are ruled out. The goal of this session is to heighten awareness of the differential diagnoses that may cause ocular hyperaemia and to define simple clinical methods to differentiate these.
"Ocular Blood Vessels are a Diagnostician's Best Friend"
In many ways, ocular blood vessels are the diagnostician's best friend since they "always" go to where the problem is. That is, if there is superficial irritation (irritation of the conjunctiva or superficial cornea) then superficial blood vessels will become hyperaemic. However, if inflammation involves deeper structures - uveitis, glaucoma, scleritis, or deep (stromal) keratitis - then deeper episcleral blood vessels become engorged. Thus, clinically differentiating superficial conjunctival vessels from deep episcleral vessels changes the diagnosis, diagnostic testing necessary, treatment, and prognosis.
Clinically Relevant Anatomy and Physiology
Although there are blood vessels spanning from the most superficial bulbar conjunctiva through to the sclera, for the purposes of this session we will categorize them into 2 distinct and clinically useful classes: deep or episcleral and superficial or conjunctival blood vessels. In the normal animal, the blood vessels in the bulbar conjunctiva are so fine that the conjunctiva appears almost transparent permitting the white sclera to be seen through it. The palpebral conjunctiva is normally a pale pink but can become more obvious with hyperthermia or excitement, and should be approximately the same colour as other mucus membranes. Bulbar conjunctival vessels extend right up to the limbus. Episcleral vessels - although larger - are usually not prominent when seen through subconjunctival tissues. The exception is some brachycephalic individuals, particularly dogs, in which one or two obvious episcleral blood vessels are sometimes seen in normal, uninflamed eyes. Episcleral blood vessels supply the intraocular structures via the uveal tract and therefore "dive" through the sclera at the iris root - a millimetre or two behind the limbus. The importance of these anatomical facts will become more obvious when we discuss some of the means to differentiate deep from superficial blood vessels.
Mechanisms of Ocular Hyperaemia
In addition to physiologic vasodilation due to hyperthermia, there are (at a mechanistic level) two common ways a blood vessel becomes hyperaemic or "injected."
1. Vasodilatation due to release of inflammatory mediators (i.e., "inflammation")
2. Hydrostatic engorgement due to decreased venous return
The release of vasoactive mediators at a specific site acts locally to cause (among other things) dilation of the blood vessels that supply that site. Therefore this mechanism for hyperaemia dictates that a reasonably "focused" vasodilatation should ensue. That is, if there is uveal inflammation, and release of vasoactive factors within the uvea, then the deep or episcleral blood vessels that supply the uveal tract should become injected. By contrast, conjunctival inflammation should incite only conjunctival vessel hyperaemia. This strict rule breaks down somewhat with more significant or major inflammation. Insults, such as uveitis that are severe enough to induce episcleral congestion, will sometimes also produce some "innocent bystander" hyperaemia of the overlying and smaller conjunctival blood vessels; however, the inverse is unlikely. Therefore, satisfying oneself that episcleral congestion is not present is the most critical decision whenever "red eye" is a presenting sign.
Blood vessels terminating (in the case of arterioles) or originating (in the case of venules) in the conjunctiva and uvea share a common pathway through the orbit to and from the major vessels of the head and neck. Therefore, orbital disease can cause enlargement ("injection") of deep and/or superficial ocular vessels via hydrostatic pressure (decreased venous return) and via local inflammatory effects on these vessels en route to and from the eye. Therefore, all eyes with hyperaemia should be examined for evidence of altered globe position (strabismus, enophthalmos, or exophthalmos) and, so long as there is no risk of globe rupture, should also be retropulsed.
Differentiation of Deep Episcleral and Superficial Conjunctival Hyperaemia
Conjunctival vessels are superficial, small (fine), branch frequently, and move easily with gentle pressure from a cotton-tipped applicator or by lateral motion of the upper eyelid, extend to the limbus, and blanch within seconds after application of 1 drop of a topical vasoconstrictor such as dilute (1%) phenylephrine. By contrast, episcleral vessels are larger, branch less, appear to "stop short" of the limbus, and blanch more slowly, if at all, with topical vasoconstrictors (Figure 1).
Potential Clinical Diagnoses in Reddened Eyes
Since superficial vessels indicate superficial disease and deep vessels indicate deeper disease, it is possible to compile a list of potential likely causes of red eye in association with deep or superficial vascular injection (Figure 2). This list guides diagnostic testing and ensures that painful, vision-threatening or potentially life-threatening diseases are not written off simply as conjunctivitis. The only confusion in this list is brought about by the principle of "innocent bystander" inflammation discussed earlier. Subtle (early) glaucoma, orbital disease, and uveitis can cause only mild conjunctival hyperaemia before they progress to a stage where they cause episcleral hyperaemia.
Diagnostic Tests for "Every" Red Eye
The following is a brief outline of the diagnostic tests that should be considered for all cases of reddened eye.
Retroillumination is a simple but extremely useful technique for assessment of reddened eyes. A focal light source held close to the examiner's eye and directed over the patient's nose from at least arm's length is used to elicit the fundic reflection. Each eye is illuminated equally and the fundic reflex is used to assess and compare pupil size, shape, and equality. Some general rules help interpret retroillumination findings:
Conjunctivitis - never associated with anisocoria
Uveitis - often associated with miosis
Glaucoma - often associated with mydriasis
The Schirmer tear test (STT) should be performed on all reddened eyes but especially those in which there is mucoid discharge. The only exception is those with an obvious deep ulcer in which this test may be unsafe. Normal STT values for dogs are > 15 mm in 60 seconds. However STT values in normal cats range widely (3–32 mm; mean = 17 mm in 60 seconds) and are more difficult to interpret than in dogs.
Tonometry or measurement of intraocular pressure (IOP) is essential in every reddened eye since it permits differentiation of the two major, vision-threatening conditions in which red eye is the hallmark feature - uveitis (in which IOP tends to be low) and glaucoma (which is defined by elevated IOP). Across large populations, normal canine and feline IOP is reported as 10–25 mm Hg. However, some variation occurs. Comparison of IOP between right and left eyes permits application of a reasonable rule of thumb that IOP should not vary between eyes of the same patient by more than ~20%. Perhaps the most important role for tonometry is the monitoring of progress of these diseases and the titration of medications needed.
Aqueous flare occurs as a result of breakdown of the blood-ocular barrier with subsequent leakage of proteins into the anterior chamber. Therefore, it is a pathognomonic sign of uveitis and a test must be performed in every reddened eye. It is best detected using a very focal, intense light source (the small circular aperture on the direct ophthalmoscope works well) in a totally darkened room. The passage taken by the beam of light is viewed from an angle. In the normal eye, a focal reflection is seen where the light strikes the cornea. The beam is then invisible as it traverses the almost protein- and cell-free aqueous humor in the anterior chamber but becomes visible again as a focal reflection on the anterior lens capsule and then as a diffuse beam through the body of the normal lens. If uveitis has allowed leakage of serum proteins into the aqueous humour, then these cause a scattering of the light as it passes through the anterior chamber. Aqueous flare is therefore detected when the beam of light is visible traversing the anterior chamber.
Application of fluorescein dye to the cornea should be routinely used in all reddened eyes to diagnose corneal ulcers. It should be performed after all other parts of the exam are completed so as not to alter the STT result or affect visualization of other structures.
Retropulsion of the globe is a simple but useful method for investigating orbital disease. This is performed by applying gentle digital pressure to both globes through closed eyelids. The resistance to retropulsion and the resilience with which the globes "spring" back against the retropulsive force are subjectively assessed. Retropulsion of the globe in a variety of directions may further localize orbital masses or outline smaller masses that would be missed by direct caudal retropulsion only. This should not be done in eyes at risk of rupture.