Ординатура / Офтальмология / Английские материалы / Clinical Ocular Pharmacology 5th edition_Bartlett, Jaanus_2008

470 CHAPTER 25 Diseases of the Conjunctiva

and bandage lenses. Scleral contact lenses have been used in some cases. These techniques should be considered on an individual basis when topical therapy alone is inadequate.

Although the ocular consequences of SJS and TEN are successfully managed with topical therapy and adjunctive procedures in most patients, some cases require surgical intervention. Tarsorrhaphy, partial or complete, prevents excessive drying of the ocular surface. Other procedures to manage the sequelae of entropion or trichiasis, such as diathermy or cryosurgery, are effective for short-term resolution but frequently regress with time and must be repeated. Ocular surface reconstruction using amniotic membrane and stem cell transplantation has met with good, and in some cases startling, success.

an individual organ defines the specialized roles that connective tissues play within the body. Collagen and glycoproteins make up basement membranes and, as such, occur throughout the body as unique biologic and physical barriers. Little evidence exists that primary disease of these tissues is the precipitating pathologic event. On the contrary, the connective tissue and vascular systems are secondarily involved as sites of inflammation. The traditional term collagen vascular disease still is used to describe this broad category of disease, although it is no longer considered an acceptable description. Most of these conditions have widespread and diffuse effects on a variety of organs and tissues.The American College of Rheumatology has developed a series of diagnostic criteria that are used to identify each of these clinical entities.

CONNECTIVE TISSUE DISORDERS (COLLAGEN VASCULAR DISEASES)

The connective tissue disorders comprise a unique family of systemic diseases that have distinctive yet nonspecific systemic manifestations associated with organ involvement.Such diseases as rheumatoid arthritis (RA),rheumatic fever, systemic lupus erythematosus (SLE), scleroderma, and periarteritis nodosa all demonstrate the typical histologic and clinical findings characteristic of this category of diseases.

The histologic changes noted in affected patients involve diffuse inflammatory damage to connective tissue and vascular systems. Nonspecific deposition of fibrin material in connective tissue and blood vessels typifies this damage.This grouping of diseases is somewhat arbitrary, relating to the general acceptance of an autoimmune mechanism as an etiologic factor. Though many of the diseases share common clinical findings, each also has unique and differentiating elements. Because Reiter’s syndrome is believed to be autoimmune in nature, it too is considered in this discussion.

Most disorders in this group do not present with significant ocular involvement. However, SLE, periarteritis nodosa, Reiter’s syndrome (reactive arthritis), juvenile RA, and, in some instances, RA can be clinically identified by their ophthalmic presentation at an early stage in the disease.There is evidence that early treatment can reduce morbidity and have a positive impact on the course of these disorders.

RA is a crippling potentially lethal disease that affects connective tissue and the vascular system throughout the body. It affects the eye in a variety of ways, notably through autoimmune damage to the lacrimal gland and with resultant dry eye syndrome. Indeed, Sjögren’s syndrome and KCS are common threads that tie these disorders together.

The term connective tissue describes a diverse group of structural elements that include collagen, elastin, proteoglycans, and other typical glycoproteins. The unique distribution of these individual elements within

Systemic Lupus Erythematosus

SLE is a chronic inflammatory disease of unknown etiology and unpredictable course that primarily affects the skin, cardiovascular system, nervous system, mucous membranes, and kidneys.The prevalence of this disease is approximately 1 per 1,000 population. Although the occurrence is slightly greater in blacks than in whites, the most notable epidemiologic factor is the remarkably high incidence among women, particularly of childbearing age. Both juvenile and later onset SLE may occur. Disease activity tends to be lower in patients with late-onset disease; however, they tend to accrue more damage and experience higher mortality than patients with earlyonset lupus.These findings probably reflect the contribution exerted by other comorbid conditions in the overall impact of lupus in these patients. SLE may be triggered by exposure to sunlight, infection, and stress. Other factors include endocrine, genetic, and autoimmune mechanisms; medications; and exogenous antigens. Druginduced SLE resolves on cessation of the causative agent. Pregnancy, use of a variety of medications, and use of contraceptives have all been associated with exacerbations of the disease. Conversely, there have been reports of disease remission during pregnancy, with exacerbation postpartum.

Diagnosis

Systemically, SLE may masquerade as many different conditions, in some cases simultaneously, and thus may present a daunting diagnostic challenge. Differential diagnosis of the disease is based on the presence of 4 of the 11 diagnostic criteria listed by the American College of Rheumatology. Ocular effects can include a variety of clinical manifestations,but KCS is most common. Other ocular findings are chemosis, recurrent episcleritis, scleritis, conjunctival scarring, and symblepharon (Figure 25-29). There is also a relatively high incidence of anterior uveitis and, in a small percentage of patients, the presence of eyelid plaques. Other common findings are infiltrative keratitis and marginal corneal ulcers.

Figure 25-29 Episcleritis in patient with systemic lupus erythematosus.

Although ocular manifestations may contribute to the diagnosis of SLE, it is important to evaluate the patient for systemic manifestations as well. These include fever, weight loss, arthralgia, nephritis, and the typical malar butterfly rash seen on the face.This cutaneous presentation is evident in less than one-half of patients with SLE. In many instances more subtle signs may include a blush and swelling of the skin on the cheeks after exposure to the sun. These lesions frequently scale and are termed discoid when they present in this fashion. Subsequent episodes can produce either a hyperor hypopigmented state and atrophy of the epidermal tissue. Raynaud’s phenomenon is not uncommon, and many individuals develop ulcerative changes of the extremities in association with this aspect of the disease. Patients can show evidence of purpura and ecchymosis. Antiphospholipid antibodies, or lupus anticoagulant, may play a role in retinal vaso-occlusive disease in the formation of either branch retinal or central retinal vein occlusion.

Management

Therapy for SLE is both complex and, in many instances, disappointing for both patient and practitioner. Management of the systemic signs and symptoms may not improve the ocular manifestations of the disease. The most common therapy for the arthritic and cardiac complications is NSAID use. Hydroxychloroquine and chloroquine are particularly effective in treating the discoid rash associated with the disease. In some cases oral steroids are used either alone or in combination with other immunosuppressive agents. Methotrexate can effectively reduce the need for systemic steroids in the treatment of mild to moderate SLE. Cyclophosphamide and

azathioprine have been used for more severe disease for which steroid therapy is inadequate. Hematopoietic stem cell transplantation was used successfully to treat severe life-threatening SLE. Rituximab, previously approved by the U.S. Food and Drug Administration for non-Hodgkin’s lymphoma, is a genetically engineered antibody that targets B cells and eliminates them from the blood. Clinical trials for SLE have proved successful; however, the risk of infections of the brain has raised some concerns. Other novel treatments are currently under investigation.

Treatment of the ocular manifestations of SLE primarily involves the management of associated ocular surface disease. Maintenance of the tear film using lubricants is an important therapeutic adjunct. To reduce toxicity nonpreserved lubricants should be used. Management of associated bacterial conjunctivitis should be undertaken with appropriate antibiotic therapy, but long-term antibiotic therapy should be avoided, because it can complicate disease management. In some instances clinicians have used bandage lenses, punctal or intracanalicular occlusion, and other methods to support the ocular surface. However, these are often of limited effectiveness in longterm management.

Polyarteritis Nodosa

Polyarteritis nodosa (PAN) is an uncommon systemic necrotizing vasculitis that predominantly affects small and medium-size arteries.The lesions generally are distributed diffusely throughout the vascular system and often are asymmetric in presentation. The necrotizing inflammatory component is fairly evident in the acute stage and is accompanied by infiltration of inflammatory cells throughout the vessel walls and surrounding tissue. Vascular damage from the inflammatory process usually causes thrombosis and fibrosis, with subsequent blockage of blood flow and infarction of the affected tissue. Unlike SLE, PAN occurs more frequently in men than in women. Although patients of all ages are affected, the onset most commonly occurs in the third to sixth decade of life. Many etiologies have been postulated, including hypersensitivity reactions and response to such microorganisms as Streptococcus species and viral entities.

Diagnosis

Like SLE, PAN has a wide range of clinical manifestations. These include fever, weight loss, severe abdominal and musculoskeletal pain, tachycardia, acute glomerulonephritis, polyneuritis, myocardial infarction, and such pulmonary manifestations as bronchial asthma. The frequency of this disease is approximately 8 per 1,000 population, but the clinical diagnosis rate is considerably lower than postmortem studies suggest. In the United States incidence is reported to range from 3 to 4.5 cases per 100,000 population per year. Renal involvement is one of the most common and devastating aspects of

472 CHAPTER 25 Diseases of the Conjunctiva

the disease. It can be manifested by simple hematuria or, in more severe cases, painful infarction and acute decompensation. Renal disease occurs in approximately 75% of patients, and hypertension occurs in more than 50%.

Typical findings of the ocular anterior segment include KCS, lacrimal gland atrophy, conjunctival hyperemia, subconjunctival hemorrhages, and chemosis. Peripheral ulcerative keratitis may mark the onset of systemic disease. Nongranulomatous uveitis and necrotizing sclerokeratitis may also occur. Retinal vaso-occlusive disease in the form of cotton-wool spots, edema, hypertensive retinopathy, and hemorrhage is typical, and some instances of more extreme disease display nonrhegmatogenous retinal detachments (Figure 25-30). Other less common findings include optic nerve involvement and extraocular muscle palsies. Episcleritis may be a presenting sign of PAN. In severe cases nodular episcleritis or scleritis can progress to a necrotizing state. As is common in connective tissue diseases, anterior uveitis can occur.

Ocular involvement relates primarily to the vascular inflammatory aspect of the disease. In the central nervous system the disease manifests itself as neurologic deficits and in the retina, as typical vaso-occlusive episodes.

Management

The underlying etiology of the disease determines the treatment of PAN. The survival rate over 5 years for patients with untreated PAN is approximately 10%. Thus the use of aggressive systemic management is of vital importance. Corticosteroid therapy has demonstrated improvement in the mortality rate and, in some studies,

Figure 25-30 Nonrhegmatogenous retinal detachment in polyarteritis nodosa.

has increased the 5-year survival to approximately 50%. Regimens for steroid therapy can be as high as 1 to 2 mg/kg daily. This type of management requires following the patient carefully and tapering steroid therapy as rapidly as possible. However, even high-dose steroids are not adequate for some patients.

The addition of immunosuppressive therapy can dramatically increase survival. As with SLE, cyclophosphamide and azathioprine are the two most commonly used agents. Methotrexate has also been used successfully. Immunosuppressants are generally administered with steroids. In many instances they allow significant reduction in steroid dosage while patient symptomatology is stabilized. However, the morbidity associated with this disease is significant, and management of the complications related to systemic hypertension and organ failure can be extremely important in allowing the patient to maintain a more normal lifestyle. Because of the persistent presence of joint and muscle discomfort associated with the disease,analgesic agents can be helpful in minimizing symptoms.

As with other connective tissue diseases, ocular therapy focuses on the management of ocular surface disease. If uveitis is present, the use of topical steroids along with a cycloplegic agent is appropriate. The most effective means of controlling ocular complications generally is aggressive management of systemic components of the disease. In some instances patients are relatively asymptomatic systemically while being treated with steroids and immunosuppressive therapy but still demonstrate active disease. In these individuals determining the status of ocular inflammatory changes can be helpful in assessing the effectiveness of systemic therapy.

Reiter’s Syndrome

Classically, Reiter’s syndrome has been defined as a triad of arthritis, urethritis, and conjunctivitis. In 1981 the American Rheumatism Association revised its defining criteria for Reiter’s syndrome to describe the disorder as an episode of peripheral arthritis of more than 1 month’s duration occurring in association with urethritis or cervicitis (or both). Reiter’s syndrome recently was termed reactive arthritis; however, some authors qualify this as an incomplete presentation. It is the most common type of inflammatory polyarthritis seen in young men. Infectious agents appear to play a critical role in the initiation or perpetuation of Reiter’s syndrome.The syndrome most frequently follows genitourinary infection with C. trachomatis, although a variety of other organisms and mechanisms have also been implicated. It may present as a complication of nonspecific urethritis, postgonococcal urethritis, or gastrointestinal disease involving such organisms as Salmonella, Clostridium, and Yersinia. An HLA-B27 genotype is a predisposing factor in more than two-thirds of patients. A relation to human immunodeficiency virus infection has been reported, although this

remains uncertain. In the United States the frequency of Reiter’s syndrome is estimated at 3.5 per 100,000, although the actual incidence is hard to gauge due to difficulty in establishing a definitive diagnosis.

Diagnosis

Affected patients generally experience genitourinary or gastrointestinal disturbances that precede ocular findings. In some patients the onset of ocular disease can be delayed for several months.A low-grade fever and malaise are frequent findings. Mucocutaneous findings, such as aphthous ulcers and balanitis, may be seen. The polyarthritis commonly associated with the disease is generally asymmetric and shows a predilection for the joints of the lower extremities. In most cases remission occurs within several weeks to months after onset. Only a small number of individuals progress to a chronic or recurrent form of the disease. Heel pain from plantar fasciitis and low back pain caused by sacroiliitis may be helpful diagnostic clues. Less typical complications include cardiac and neurologic involvement, ankylosing spondylitis, amyloid disease, and aortic incompetence.

An unusual but clinically important finding is that of painful deformity of the feet in the form of keratoderma blennorrhagica (Figure 25-31), which is primarily confined to the plantar surfaces. Although it occurs in a

Figure 25-31 Blennorrhagica in Reiter’s syndrome. (Courtesy William Wallace, O.D.)

small percentage of patients (5% to 7%), when seen in conjunction with other findings it can be extremely helpful in making the diagnosis.

Nonspecific laboratory findings in patients with Reiter’s syndrome include an increase in peripheral blood leukocytosis and an elevated sedimentation rate. Radiographic abnormalities are typical of RA.

Conjunctivitis is the most common ocular presentation of Reiter’s syndrome, unlike in the aforementioned entities. The conjunctivitis is generally bilateral, with papillary hypertrophy and a mucopurulent discharge. Most cases are transient and mild. Subepithelial corneal opacities, SPK, and edema may occur along with the typical conjunctivitis. An acute-onset unilateral anterior uveitis may occur and recur during the course of Reiter’s syndrome. The anterior uveitis is typically severe and of relatively long duration. Up to 50% of patients with lumbar inflammatory disease develop recurrent uveitis, whereas only 10% of those who do not have lumbar involvement develop recurrent episodes. Other less typical ocular findings include the presence of optic nerve inflammation in the form of optic neuritis or papillitis. Patients may also present with macular edema, which is thought to be secondary to the inflammatory process.

Management

Initial treatment of the systemic manifestations of Reiter’s syndrome consists of high doses of NSAIDs. Patients with large joint involvement may also benefit from intra-articular corticosteroid injection. The use of antibiotics in treating Reiter’s syndrome is controversial; however, treatment with tetracycline or its analogues sometimes shortens the course or aborts the onset of the arthritis. The current recommended treatment is oral tetracycline, 250 mg four times daily for a minimum of 3 to 4 weeks.The long-acting tetracyclines, such as doxycycline, can also be used. The use of erythromycin is recommended in individuals sensitive to tetracycline, in pregnant women, or in children. The normal adult dosage is 500 mg every 12 hours. A 3-month course of ciprofloxacin did not show any significant benefit. Children can be comanaged in conjunction with their pediatrician. In instances of Reiter’s syndrome that have been precipitated by enteric organisms, treatment with trimethoprim-sulfamethoxazole should be instituted.

Management of the ocular aspects of Reiter’s syndrome is directed toward control of inflammation.The uveitis can be fairly severe and resistant to therapy. In most instances such topical steroids as 1% prednisolone acetate or 0.1% dexamethasone are recommended. Dosage is variable but in severe cases should be administered initially every 1 to 2 hours and accompanied by such cycloplegic agents as 5% homatropine or 0.25% scopolamine two to three times daily.Aggressive treatment reduces formation of synechiae and subsequent secondary glaucoma. In patients who have severe uveitis, either sub-Tenon’s capsule or oral steroids may be used in conjunction with topical management.

474 CHAPTER 25 Diseases of the Conjunctiva

The conjunctivitis associated with Reiter’s syndrome is usually mild and transient.A topical aminoglycoside, erythromycin, or a combination agent such as trimethoprimpolymyxin B (Polytrim) may be used to treat more severe conjunctivitis.

With any of the connective tissue diseases the potential for recurrence is relatively high, and in most instances the disease becomes chronic. Therefore the practitioner must educate the patient to the potential for long-term involvement with the disease. Also, treatment of the ocular disease should not be undertaken in isolation:The ophthalmic practitioner should consult with the patient’s primary physician to optimize therapeutic management.

TOXIC CONJUNCTIVITIS

Etiology

Conjunctivitis caused by toxic agents can occur as either a primary or a secondary finding. Toxicity most commonly results from exposure to medications, contact lens care products, or cosmetics. However, any agent can cause a toxic response. Toxic conjunctivitis may have a wide variety of presentations. When superimposed over infection or allergic reaction,toxicity to a medication may complicate the diagnosis.

Diagnosis

Affected patients frequently complain of a hot gritty feeling in the eye. Itching is not a common complaint unless allergy is a part of the overall clinical picture. Patients often have a history of use of the suspected agent. Preservatives are a frequent cause of toxic reactions. Thimerosal, benzalkonium chloride, and chlorhexidine are common culprits. Topical antibiotics such as gentamicin and tobramycin can also cause toxic conjunctivitis. Antiviral medications are commonly associated with toxicity.When a specific agent cannot be identified, investigation of the patient’s environment often is productive in finding the cause. Environmental agents are often obvious once the nature of the conjunctivitis is identified.The temporal relation of exposure and response can serve as a valuable clue in such cases. Chronic exposure to toxic agents, as occasionally occurs with glaucoma medications, typically produces a follicular reaction.

Management

Elimination of the toxin is the only totally effective means by which to eliminate toxic conjunctivitis. Often, products that contain different preservatives from those contained in the offending product can be substituted, typically resulting in complete cure. Once the toxin is identified, patients should be advised to avoid agents to which they are sensitive. Dilution of environmental toxins may reduce symptoms; however, this is only palliative.

LOCALIZED CONJUNCTIVAL

INFLAMMATION

A variety of conditions present with localized inflammation or other focal changes of the conjunctiva.These entities have a variety of causes, diagnoses of which range from simple to extremely challenging.

Phlyctenulosis

Etiology

Phlyctenular conjunctivitis is an allergic hypersensitivity response of the conjunctiva and, occasionally, of the cornea.Although the disease is worldwide in distribution, the etiologic factors vary considerably depending on geographic location. In general, phlyctenular conjunctivitis occurs more commonly in areas of poor sanitation and health care. It is typically more common in women (60% to 70%) than in men and occurs with greater frequency in children.This condition can have numerous causes. In populations where poverty is endemic, tuberculosis is a common cause. In patient populations with access to health care and appropriate sanitation, the bacterial protein from the staphylococcal organism may be the causative agent. Other agents, such as intestinal parasites, are also potential sources of phlyctenular disease.

Diagnosis

Although phlyctenular conjunctivitis can occur without obvious associated disease, patients with phlyctenules may exhibit concurrent evidence of either dermatologic or systemic disease, such as rosacea and seborrheic blepharoconjunctivitis. The symptoms associated with phlyctenulosis are similar to those of a mild to moderate conjunctivitis. The patient frequently has foreign body sensation as well as ocular discomfort and injection. Although not common, mucopurulent discharge may also occur simultaneously with bacterial infection. In most instances, the patient complains of the stringy mucouslike discharge seen in ocular allergy.

Phlyctenules appear as small, raised, nodular lesions that are usually pinkish white and surrounded by dilated blood vessels. The conjunctival lesions are self-limiting and rarely produce significant symptoms beyond those already mentioned. The more typical response occurs when the lesion develops at the limbal margin and encroaches onto the corneal surface. These junctional lesions are generally more symptomatic, causing photophobia, ciliary spasm, and tearing. Limbal phlyctenules resemble those of the conjunctiva, but they bridge the corneal limbus (see Figure 26-26). Limbal lesions usually occur in the inferior aspect of the eye near the eyelid margin, whereas the conjunctival lesions develop within the interpalpebral aperture (Figure 25-32).

The diagnosis of phlyctenular conjunctivitis is based primarily on the typical appearance of the lesion,

Figure 25-32 Conjunctival phlyctenule (arrow) in interpalpebral aperture. (Courtesy William Wallace, O.D.)

its location, and a thorough ocular examination and health history. Differential diagnosis includes such entities as chlamydial conjunctivitis, pterygium, pinguecula, nodular episcleritis, and VKC. Phlyctenulosis has a relatively acute presentation; pterygium and pinguecula do not. Chlamydial infection presents with a much more chronic course and a follicular reaction typical of the disease. In its early phases rosacea can appear subtle, but typical dermatologic changes allow easy differentiation. Limbal VKC, by producing similar allergy-like mucous discharge, can be difficult to diagnose in its early phase but has a seasonal component that helps to differentiate it from phlyctenulosis. Trantas’ dots, associated with limbal VKC, are also much smaller than phlyctenules.

Management

Therapy depends on etiology. In individuals who are suspected of having tuberculosis, diagnosis should make use of a purified protein derivative skin test, chest radiograph, and sputum cultures if necessary.These individuals should be referred for comanagement to their primary physician or to an infectious disease specialist. Though antituberculin agents are systemically administered, the ocular lesions are appropriately treated with topical steroids. In most instances, patients respond to 1% prednisolone acetate every 3 to 4 hours for the first day, subsequently tapered rapidly on the basis of the clinical response.

When patients are suspected of having underlying staphylococcal disease, both inflammatory and bacterial components can be managed with a steroid–antibiotic combination. Initial doses should be administered every 2 to 4 hours, depending on severity, for the first 24 to 48 hours. In most instances, patients obtain dramatic relief from symptoms and can diminish use of the drug in 7 to 10 days. Because of the association of Staphylococcus with eyelid disease, lid therapy should be instituted. Antibiotic ointments such as erythromycin, bacitracin,

or bacitracin-polymyxin B can be used twice daily in conjunction with warm compresses and eyelid scrubs. Oral tetracycline is effective in treating phlyctenular keratoconjunctivitis. Tetracycline is typically prescribed 250 mg four times daily for approximately 4 to 6 weeks; alternatively, doxycycline, 100 mg twice daily for 4 to 6 weeks, is administered. When other etiologic agents, such as intestinal parasites, Chlamydia, gonococci, and HSV are suspected, patients should receive appropriate systemic medications.

Superior Limbic Keratoconjunctivitis

Etiology

Superior limbic keratoconjunctivitis (SLK) is a chronic inflammatory disorder involving the superior bulbar conjunctiva and cornea.The superior tarsal conjunctiva is diffusely inflamed, with a pronounced papillary response. It is a disorder primarily of middle age, with women more often and more severely affected than men. SLK is usually bilateral, though significant asymmetry can exist. Patients may be highly symptomatic, complaining of burning, foreign body sensation, irritation, pain, and photophobia. The disease is often episodic; exacerbations may resolve within days or can wax and wane over many years. One of the unusual aspects is varying intensity between eyes without significant remission taking place in either. This course frequently is accompanied by fluctuating ocular discomfort. Although there is no established etiology for this disease, dry eye was a common finding in the original study. Thyroid dysfunction is another common finding. Recently, SLK has been attributed to superior limbal stem cell damage, perhaps related to chronic hypoxia, lid-induced microtrauma, and conjunctivochalasis.

Diagnosis

The diagnosis of SLK is aided by several unique factors. Patients tend to be more symptomatic than the clinical examination justifies. The clinical picture is that of a sectional area of inflammation at the limbal margin (at the 10 o’clock to 2 o’clock position; Figure 25-33), demonstrating mild to moderate injection and, in more advanced cases, a gelatinous thickening of the limbal conjunctiva. Some individuals may also have filamentary keratitis and a mild mucous discharge, but these findings may be more related to associated dry eye and increased mucin content of the tears.The classic clinical picture is of intense punctate rose bengal staining of the affected ocular surface. The staining pattern is typically more severe than the conjunctival involvement would suggest and frequently correlates well with the patient’s symptoms. The cornea, although it can demonstrate punctate staining, filament development, and, occasionally, pannus, is usually not as severely involved as the conjunctiva.

A variant of the classic form of SLK is that of soft contact lens–induced SLK. Although affected individuals typically show findings very similar to patients with SLK,

476 CHAPTER 25 Diseases of the Conjunctiva

Figure 25-33 Superior limbic keratoconjunctivitis.

they almost universally respond to aggressive use of nonpreserved artificial tears, elimination of preserved care products, or discontinuation of contact lens wear.

Management

The etiology of SLK remains uncertain, but the most appealing hypothesis suggests a mechanical cause. For many years therapy has consisted of a wide variety of agents, including steroids, antibiotics, and ocular lubricants, followed by other more aggressive forms of treatment.Topical pharmacotherapy has not been particularly successful, but because some patients do respond, it is a prudent course of treatment before initiating more aggressive therapeutic intervention.A recent study found topical cyclosporine emulsion helpful in the management of SLK.

Other topical therapy used with some success includes 10% to 20% acetylcysteine applied four times daily, especially when corneal filaments are present, and 4% cromolyn sodium used every 4 hours. Both these agents have demonstrated modest success and should be considered before more aggressive intervention. If these topical agents give no relief, the current recommended therapy is 0.25% to 0.50% silver nitrate solution followed by irrigation, selectively applied to the tarsal and bulbar conjunctival surfaces. Such therapy may not result in permanent resolution, but most patients achieve reasonably prolonged relief after chemical cautery. Similar treatments include scraping of the tarsal conjunctiva, electrocautery, diathermy, cryotherapy, or laser therapy. Other less invasive forms of therapy include pressure patching of the affected eye and bandage contact lenses. Punctal occlusion has shown promise in managing SLK. Though none of these treatments has been universally successful, all have demonstrated some capacity to relieve symptoms in patients for finite periods.

In individuals who do not respond to these therapeutic regimens, resection of the involved conjunctiva should be considered. This surgery involves the removal of a 5- to 6-mm section of conjunctiva in the affected area. However, no single remedy has proved consistently

successful, and the patient frequently demonstrates symptomatic relief followed by exacerbation. For this reason the clinician must provide adequate counseling to the patient regarding the potential chronicity of the disease. Any associated problems (e.g., dry eye, bacterial conjunctivitis) that develop during the course of therapy must also be treated, because they may produce an increase in symptoms.

Pinguecula

Pingueculae are well-demarcated yellowish to yellowwhite elevated lesions that appear within the intrapalpebral bulbar conjunctiva, typically adjacent to the limbus. Pingueculae can present on the nasal or temporal conjunctiva or, less frequently, on both. There is a predilection for the nasal side, which is most likely caused by increased reflectance of UV rays from the nose. Histologically, pingueculae consist of accumulations of an amorphous material that is believed to arise from the degeneration of collagen within the substantia propria of the conjunctiva. Additional degeneration can occur, including calcific inclusions and concretions.The epithelium overlying a pinguecula can vary from atrophic and thinned to hyperplastic and thickened. Pingueculae are unlikely to undergo malignant conversion. However, a lesion that looks atypical should be approached with suspicion. Actinic keratosis, dysplastic changes, and even carcinoma can arise within the epithelium overlying a pinguecula.

Pingueculae may become inflamed, resulting in so-called pingueculitis. The most common causes of such inflammation are mechanical irritation or ocular surface disease. Irritation by the edge of a contact lens is a frequent cause (Figure 25-34).Treatment includes elimination of the causal factor, increased lubrication, and a short course of topical steroids when inflammation is significant.

Figure 25-34 Irritated pinguecula adjacent to edge of a soft contact lens.

Pterygia

Etiology

Recent thinking about pterygia suggests that they are an active, invasive, inflammatory process associated with focal limbal failure. In a two-stage process,“conjunctivalization” of the cornea occurs, in which tissue is characterized by extensive chronic inflammation, cellular proliferation, connective tissue remodeling, and angiogenesis. Histologically, pterygia are identical in cellular composition to pingueculae.

The primary etiologic factors may relate to both heredity and environment. UV radiation to the limbal area may contribute to the genesis of these lesions. The incidence of pterygia increases with proximity to the equator. Pterygia also typically occur in individuals who spend significant amounts of time outdoors and therefore are exposed to high levels of UV light. Other agents that may contribute to the development of pterygia include external stimuli, such as allergens, noxious chemicals, and irritants. Because of the marked similarity in cellular composition, a pinguecula may, in many instances, be a precursor to a pterygium.

The term pterygium means “wing,” which is descriptive of its typical appearance in most patients. Pterygia are primarily located in the interpalpebral area and more frequently occur in the nasal aspect of the bulbar conjunctiva. They appear as a wedge-like structure with its base toward the medial or lateral canthus and its apex toward the corneal surface (Figure 25-35).

Diagnosis

A thorough history and examination of the anterior segment can readily establish a diagnosis of pterygia. The typical interpalpebral wedge-like elevated mass of a pterygium is not characteristic of other lesions.The only exception is a pseudopterygium (Figure 25-36), which can arise after long-standing chronic peripheral corneal

Figure 25-35 Pterygium. Note base toward canthus and apex on corneal surface.

Figure 25-36 Pseudopterygium associated with long-term use of a rigid gas-permeable contact lens.

desiccation associated with rigid contact lens wear. Pseudopterygium has also been described as vascularized limbal keratopathy.A true pterygium firmly adheres to the underlying corneal and conjunctival tissue, whereas the pseudopterygium does not.

The actual clinical presentation of a pterygium depends on the length of time during which the lesion has been present and any inflammatory component. Pterygia are usually quiescent, but patients can present with significant inflammation and marked injection of the conjunctiva and associated tissue overlying the cornea. In advanced cases,pterygia can produce up to 4.00 to 6.00 D of corneal curvature change.Another important and clinically significant finding is a dellen, an area of drying and tissue loss adjacent to the elevated edge of the pterygium. This lesion may result from inadequate eyelid–cornea or eyelid– conjunctiva contact on blinking and a subsequent lack of mucin coverage and wetting of the involved area.

When they encroach on the cornea, pterygia often have visual consequences. Most associated refractive change is generally correctable to normal visual levels unless the pterygium has encroached on the visual axis. In such cases a rather marked reduction in visual acuity can occur. Moreover, once pterygia reach a critical size, they induce visually significant central with-the-rule astigmatic changes that may not be apparent by subjective refraction. Such changes may be more apparent on corneal topography. This finding helps to identify those patients who may benefit from surgical intervention. Significant visual disturbance is a primary reason for surgical intervention. In some instances patients can have pterygia on both the nasal and temporal aspect of each eye and have remarkable injection of the interpalpebral area, with a relatively quiet conjunctiva beneath the upper and lower eyelids.

Management

In the early stages the management of pterygia usually involves palliative therapy. Patients show significant relief of symptoms with the use of artificial tears and ointments. When these are insufficient, mild steroids, such as

478 CHAPTER 25 Diseases of the Conjunctiva

fluorometholone four times daily, can be administered to combat the inflammatory component. Chronic use of steroids, however, is not recommended. Topical indomethacin solution has been proposed as an alternative to topical steroid treatment, because it was found to be as effective as a steroid for treating inflamed pterygia. Pterygia and cataract development have been associated. Patients exposed to excessive sunlight or the elements should be advised to wear protective eyewear and wide-brimmed hats.

Surgical treatment of the disease generally is considered only when cosmesis or visual compromise becomes an issue. Because pterygia often recur after surgical removal,various strategies have been developed to prevent recurrence. Simple resection, rotation and reimplantation of the head of the pterygium, conjunctival autografts, conjunctival rotation autografts, and buccal mucosal grafts have all been applied with varying degrees of success. Currently, primary resection alone has a 40% to 50% recurrence rate. Amniotic membrane transplantation has proved a helpful adjunct in pterygium surgery. Strontium 90 irradiation and thiotepa application have also been used to prevent recurrence.

Mitomycin C has gained favor as a surgical adjunct. By inhibiting fibroblast proliferation, mitomycin C may decrease the rate of pterygium recurrence after surgical excision. The drug has been applied intraoperatively by holding a sponge soaked in 0.02% to 4.00% mitomycin against the sclera for 3 to 5 minutes.The medication has also been administered postoperatively with success. Long-term complications include delayed epithelialization and degenerative calcification of conjunctiva. The recent increase in awareness of the role of localized limbal epithelial stem cell damage in the pathogenesis of pterygia has led to limbal allograft surgery. Success with this method has been comparable with that of conventional surgical approaches.

NUTRITIONAL DEFICIENCIES

Although rare in the United States, malnutrition and nutritional deficiencies may affect the conjunctiva and should be kept in mind in unusual presentations.

Etiology

Generalized malnutrition may produce conjunctival keratinization.Vitamin B deficiency can cause abnormal dilatation of the conjunctival vasculature.Vitamin C deficiency can produce petechial or spontaneous subconjunctival hemorrhages. Avitaminosis A can cause severe drying of the ocular surface and the appearance of Bitot’s spots on the temporal conjunctiva.

Diagnosis

Nutritional deficiency is identified after recording a careful social history. Blood work confirms the presence

and extent of any vitamin deficiency. In some settings, malnutrition and nutritional deficiency may be associated with abusive situations; thus, the clinician should be aware of the possible social and legal implications of these findings. Of note, vitamin A deficiency may be associated with Bitot’s spots, triangular, paralimbal, foamy, grayish plaques of keratinized conjunctival debris. Loss of conjunctival goblet cells and subsequent squamous metaplasia of conjunctival epithelial cells leads to profound drying and damage to the ocular surface. Impression cytology may be used to diagnose the conjunctival changes associated with vitamin A deficiency. It is important to consider that vitamin A deficiency not in keeping with the patient’s social situation may be associated with disorders that interfere with vitamin absorption, such as gastrointestinal or liver disease.

Management

Supplementation with appropriate vitamins and the addition of sufficient protein generally resolve nutritionally based disorders. Severe corneal disease caused by prolonged vitamin A deprivation is typically more resistant to treatment.Topical treatment with lubricants or retinoic acid may be helpful in combating vitamin A deficiency.

CONJUNCTIVAL TRAUMA

Injuries to the conjunctiva may arise from a variety of different household, school, sports, or workplace activities. Children and young adults are particularly at risk. Conjunctival and corneal foreign bodies cause 40% of eye injuries. A disproportionate number of severe injuries occur in children and young adults. Clinical findings may include foreign bodies, chemical or thermal burns, and abrasions, lacerations, and contusions from blunt trauma. Conjunctival trauma should cause concern because of the risk of concurrent corneal injury or the possibility of penetration of the globe by a foreign body involved in a high-speed impact.

Foreign Bodies

Etiology

Environmental foreign bodies, such as dirt, dust, glass, metal, or other material, may contact and adhere to the conjunctiva. Often, patients report that something blew into the eye on a windy day. The workplace is also a frequent source of foreign body material, particularly for individuals not wearing protective eyewear.

Diagnosis

Recording a thorough history and performing a biomicroscopic examination are crucial steps in the diagnosis of all conjunctival injuries, both to assess the degree of conjunctival damage and to determine the extent of any corneal or scleral involvement. The case history should

Figure 25-37 Foreign body (arrow) on upper palpebral conjunctiva. (Courtesy of Larry J.Alexander, O.D.)

determine painstakingly the source, mass, trajectory, and impact speed of the foreign material, because this information guides the clinician’s examination and helps to determine the need for adjunctive testing, such as radiologic studies.The eyelids must be everted to assess the palpebral conjunctiva carefully (Figure 25-37). Occasionally, double eyelid eversion may be required. In some cases topical anesthesia may be necessary to evaluate the eye adequately.The evaluation should also include a Seidel test using sodium fluorescein dye to rule out any aqueous leakage from penetration of the globe. The anterior chamber depth should also be evaluated. A flat chamber would indicate a penetrating injury even in the absence of an apparent entry wound. Most conjunctival foreign bodies are superficial and usually are found on the superior palpebral conjunctiva (see Figure 25-37). Depending on the length of time the foreign body has been present, the wound site may have some surrounding hyperemia. When foreign bodies become embedded in the conjunctiva, a subconjunctival hemorrhage or conjunctival granuloma may envelop the impact site, in some cases entrapping the object.

Management

Copious lavage of the conjunctiva with normal saline or extraocular irrigating solution may loosen and remove some foreign bodies. Swabbing the affected area with a moistened cotton-tipped applicator is often effective when the foreign body is only partially adhered. When visualizing the foreign material is difficult, as with fiberglass particles, swabbing the fornices is often necessary to remove the foreign material. Any swabbing should be

followed by a saline lavage. Embedded foreign bodies may be removed with a sterile needle or spud. A broad-spec- trum topical antibiotic, such as trimethoprim-polymyxin B (Polytrim) solution or bacitracin-polymyxin B ointment, should be applied to the eye after removal of the foreign body to prevent secondary infection. The antibiotic may be continued for 24 hours, if necessary, after the removal of embedded foreign bodies. Semipressure patching with cycloplegia and a topical antibiotic may be indicated after removal of deeply embedded foreign bodies.

Burns

Etiology

Chemical burns of the conjunctiva usually result from inadvertent splashes of chemicals into the face or from hydrogen peroxide contact lens solutions. Occasionally, patients may instill a chemical irritant directly into the eye, resulting in severe injury. Cigarettes, curling irons, and overexposure to UV radiation frequently cause thermal burns.

Diagnosis

The diagnosis of conjunctival burns requires essentially all the procedures outlined for diagnosing foreign bodies. For chemical burns the clinician must determine whether the offending chemical is acid or alkaline. If the chemical is not familiar to the clinician, the local poison control center can provide information. The conjunctival fornix and tear film can be tested with pH paper to determine whether an acid or base is present.The conjunctiva must then be carefully assessed to determine the depth of the burn. Most acid burns cause superficial epithelial damage, as indicated by punctate staining with sodium fluorescein. In severe cases, however, blanching of the conjunctiva is possible. Alkaline burns from chemicals, such as lye or lime, usually blanch the conjunctiva and cause more severe injury, due to their collagenolytic effects. Thermal burns may cause either superficial or severe injury, depending on contact time of the offending agent. Specific management is discussed in more detail in Chapter 26.

Abrasions, Contusions, and Lacerations

Etiology

Direct trauma is the most frequent cause of conjunctival abrasions, contusions, or lacerations. The nature of the contact usually determines what type of wound the patient suffers. For example, a thrown object may cause only a contusion, whereas a sharp pencil point can lacerate the conjunctiva.

Diagnosis

The diagnosis of conjunctival injuries is determined through the history and careful biomicroscopic examination. Symptoms usually consist of mild irritation or foreign body sensation. Clinical findings accompanying