The Red Eye: Keratitis, Conjunctivitis, Episcleritis, Scleritis, Pterygium/Pinguecula
David Peak
Neha Shaik
THE CLINICAL CHALLENGE
The etiology of the red eye includes the spectrum from nonemergent conditions to potentially sight-threatening true emergencies. The terminology can be challenging because some terms such as conjunctivitis and keratitis merely refer to pathology of a particular part of the eye, but the clinician must infer the cause of the pathology in order to effectively treat the patient. Inciting pathology can also affect multiple parts of the eye simultaneously and be related to infection, toxins, trauma, or inflammatory conditions. An understanding of the various conditions will help inform the urgency of ophthalmology consultation or follow-up.
PATHOPHYSIOLOGY
The conjunctiva covers the anterior portion of the eye (except the cornea) and provides eye protection, lubrication, and a degree of immune defense. The conjunctiva can be subdivided into three parts: the palpebral/tarsal conjunctiva, which lines the eyelids; the bulbar conjunctiva, lining the globe to the limbus; and the fornices, which form the junction between the bulbar and the palpebral conjunctiva. The palpebral conjunctiva is somewhat loose and flexible, allowing for movement, unlike the bulbar conjunctiva. The conjunctiva consists of a superficial epithelial layer, the substantia propria, and a deep fibrous layer. The epithelial layer is composed of nonkeratinized stratified squamous and columnar epithelial cells, goblet cells (more numerous close to the fornix), blood vessels, fibrous tissue, lymphatics, melanocytes, T- and B-cell lymphocytes, Langerhans cells, and accessory lacrimal glands. The middle substantia propria contains numerous lymphocytes, mast cells, plasm cells, and neutrophils. The deepest fibrous layer contains nerves and blood vessels.
Bulbar conjunctival vessels are normally invisible to barely visible to the naked eye. They dilate and cause redness owing to multiple stimuli, including allergens, irritants, fever, infections, and even some emotional states. The bulbar conjunctiva may also reveal other pathology such as icterus in the case of significant elevations in serum bilirubin concentrations.
The palpebral conjunctiva is normally pink and smooth. It may become pale with significant anemia or injected and swollen with inflammatory and infectious conditions. In patients with severe allergic vernal keratoconjunctivitis, there may be a cobblestoning-type pattern with giant papillae (>1 mm diameter).
The cornea is a dome-shaped transparent ocular tissue extending from the sclera at the limbus. The cornea is made up of multiple avascular layers, normally transparent and highly innervated with unmyelinated nerve endings. The cornea is considered to have the highest density of pain receptors in the entire body (roughly 300-600 times greater than skin), making it highly sensitive to touch, which results in reflexive closing.
Nutrients and oxygen diffuse through the cornea from tears on the outside and the aqueous humor on the inside surface. Because transparency is so important, the cornea is thought to have what is referred to as immunologic immunity, meaning that it will generally tolerate introduction of minor antigens with little or no inflammatory response.
The episclera is a fibrous, elastic structure consisting of two layers that both contain vessels originating from the anterior ciliary arteries that stem from the ophthalmic artery. The episclera lies between Tenon capsule and the sclera. Compared to the scleral stroma, the collagen bundles of the episclera are less dense, thinner, and more irregularly arranged.
The sclera is mostly collagenous and avascular and provides strength and some degree of flexibility to the globe, covering the posterior five-sixths of its surface with an anterior opening for the cornea and a posterior opening for the optic nerve. The sclera is continuous with the stromal layer of the cornea at the junction between them, which is called the limbus and, posteriorly, with the optic nerve’s dura and arachnoid sheaths. The sclera is composed of fibrils of Type I collagen that are arranged in irregular and interlacing bundles (which account for the opaque quality as well as strength and flexibility), elastic fibers, fibroblasts, and proteoglycans and glycoproteins. The tendons of the rectus muscles inset into the superficial scleral collagen. If one were to make a model of the eye using a tennis ball, the sclera would be akin to the rubber core of the ball, functioning to protect and maintain the shape of the eye.
A small portion of the anterior sclera (the “white of the eye”) is visible. The sclera may appear more brownish in individuals with more melanin, which deposits in the conjunctiva and sclera, and this is normal. In osteogenesis imperfecta type 1, the sclera is much thinner, revealing the blue choroid. The sclera is almost avascular but is surrounded by both the vascular episclera externally and the richly vascular choroid internally. At the limbus, however, there is an intrascleral venous plexus, which is contiguous with the episcleral veins and ciliary venous plexus. The sclera does contain sensory nerves, which cause pain with inflammation.
Conjunctivitis (“pink eye”) refers to inflammation of the bulbar conjunctiva. Common etiologies include inflammatory conditions, irritants/allergens, and infections (viral and bacterial). Viral conjunctivitis is the most common etiology in both pediatric and adult populations. Adenovirus is common and is usually associated with other viral symptoms such as fever, pharyngitis, and cough, although isolated ocular symptoms may also occur. Viral conjunctivitis is highly contagious and spread by direct contact of ocular secretions.
Keratitis refers to inflammation of the cornea. Ultraviolet keratitis occurs from exposure in the absence of eye protection (eg, welders, skiers/snowboarders). Keratitis can also be caused by autoimmune diseases (eg, rheumatoid arthritis, lupus, Wegener granulomatosis), dry eye syndrome (keratoconjunctivitis sicca), vitamin A deficiency, and infection. Most infectious keratitis is bacterial. However, viral, fungal, and protozoal infections can also occur (outbreaks of Acanthamoeba have been reported). A delay in diagnosis and treatment may result in ocular complications, including corneal perforation, cornea scar, persistent infiltrates and/or vascularization of the cornea, and even blindness.
Episcleritis usually presents with mild episcleral inflammation that is usually diffuse (>80%) but can be nodular and is considered generally benign. The inflammation is confined to the superficial episcleral tissue with hyperemia, dilated and congested vessels, and nongranulomatous infiltrates consisting of lymphocytes and plasma cells. Patients may present with a bright red or salmon pink eye from vascular dilation, epiphora, mild pain, photophobia, foreign body sensation, and decreased vision, which usually resolve within a few days to weeks. Uncommon complications include decreased vision, anterior uveitis, and ocular hypertension. Episcleritis is not thought to progress to scleritis.
Scleritis, inflammation and edema of the sclera, is an uncommon, severe inflammatory disorder often associated with ocular complications. Scleritis can often be the first manifestation of an underlying systemic disease, such as rheumatoid arthritis. The inflammation can involve a
nongranulomatous or granulomatous process with or without necrosis. Scleritis may be delineated as anterior, posterior, or diffuse, which is most common (approximately 75%). Anterior scleritis can be subdivided as diffuse, nodular, necrotizing with or without inflammation, and scleromalacia perforans (especially with rheumatoid arthritis).
nongranulomatous or granulomatous process with or without necrosis. Scleritis may be delineated as anterior, posterior, or diffuse, which is most common (approximately 75%). Anterior scleritis can be subdivided as diffuse, nodular, necrotizing with or without inflammation, and scleromalacia perforans (especially with rheumatoid arthritis).
In the anterior group, diffuse is most common and least severe. Necrotizing anterior scleritis is the least common type but most dangerous with ocular complications. It is more often associated with systemic inflammatory diseases and more likely to lead to ocular complications. Purely posterior scleritis (posterior to the insertion of the medial and lateral rectus muscles) is uncommon (10%-20%) but potentially dangerous given that it may lack anterior signs that suggest the diagnosis, may affect the retina and optic nerve, and usually requires intensive immunosuppressive therapy.1 Complications of scleritis are common and include permanent decreased visual acuity, anterior uveitis, peripheral keratitis, choroiditis, and glaucoma. These complications may also require additional therapy.
Differentiating episcleritis from scleritis is important mainly because of the differences in ocular complications. The two conditions have many similarities, including rare frequency, mostly monocular, female predominance, middle-aged patient distribution, and association with systemic connective tissue or vasculitis disease. The most common etiology for both processes is idiopathic.2
Other benign conditions that can cause a red eye are pinguecula and pterygium. These are both acquired, raised lesions of the submucosal conjunctiva. There is controversy about the etiology. Exposure to UV radiation is thought to be one of the most common risk factors. Both conditions occur more commonly in populations closer to the equator and rural populations. There may be genetic predispositions, and both are more common with advancing age and in men. Pinguecula lesions represent collagen, elastic tissue, and other connective tissue degeneration associated with lipid and lipofuscin deposition,3 calcium deposits, fibrosis, and scar tissue.4,5 Pterygia additionally exhibit significant squamous metaplasia and angiogenesis that invades the cornea and may cause astigmatism as well as obstruction of vision if invasion crosses the visual axis. Both conditions occur near the limbus and are usually at the 3-o’clock and 9-o’clock positions, with the nasal side being more common for both.
APPROACH/THE FOCUSED EXAM
The approach to the history and exam for the red eye is somewhat straightforward given that, except for isolated posterior scleritis, all the associated conditions will have abnormalities on physical examination. Important features of the history include timing, associated features, and exacerbating features. In addition to the ocular examination, inspection of the head, face, and neck for abnormalities, including swelling, erythema, rash, trauma, or infection, should be performed. A neurologic exam including visual acuity, extraocular muscle function, and visual field testing is helpful to exclude other causes. The slit-lamp examination allows an examination of the eye with magnification. Whenever pain or visual impairment is present, measuring intraocular pressure is essential. The use of fluorescein staining is helpful to identify corneal abrasions and other epithelial changes, such as dendritic lesions or punctate epithelial erosions.
Conjunctivitis
In most of the red eye conditions, there will be some degree of conjunctival injection, making the history and exam critical to rule out other etiologies. In isolated conjunctivitis, patients may describe watery, serous, or purulent discharge with crusting around the eyelids in the morning. Usually, there are minimal vision complaints. The patient may report a history of recent exposure to sick contacts or recent travel history. If both eyes are involved, usually one eye developed symptoms first. Upper respiratory symptoms may indicate a viral etiology.
Allergic conjunctivitis is usually bilateral, symmetric, and characterized by itching and tearing. The exam will demonstrate a diffusely injected red eye or eyes (including both the bulbar and palpebral conjunctiva). The eyelids may be swollen, and discharge may be apparent (Figure 36.1).
Purulent discharge may indicate a bacterial etiology or epidemic keratoconjunctivitis (EKC), a severe and highly contagious adenoviral infection. In cases of copious discharge, gonococcal or
chlamydial conjunctivitis should also be considered. In addition to examination of the eyes, palpable preauricular lymph nodes may also support the diagnosis of EKC.
chlamydial conjunctivitis should also be considered. In addition to examination of the eyes, palpable preauricular lymph nodes may also support the diagnosis of EKC.