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

Management

Any infiltrative event necessitates discontinuation of contact lens wear. With significant corneal involvement and an anterior chamber reaction, cycloplegia with a long-acting agent such as 5% homatropine enhances patient comfort and helps to relieve iris congestion.

Once contact lens wear is discontinued, mild infiltrative events are self-limiting over a few days to a week. The infiltrates take longer to resolve than the associated

conjunctival hyperemia and injection.Topical prophylactic antibiotic therapy is appropriate to protect the inflamed eye from infection as it heals.With the potential for gram-negative pathogens in a soft contact lens wearer, especially extended wear, broad-spectrum agents should be used, such as 0.3% ciprofloxacin drops, or the newer generation of fluoroquinolones such as 0.5% moxifloxacin or 0.3% gatifloxacin four times a day, and 0.3% ciprofloxacin ointment at bedtime. If bacterial keratitis is

542 CHAPTER 26 Diseases of the Cornea

Figure 26-55 Giant papillary conjunctivitis secondary to rigid gas-permeable contact lens wear. (Courtesy of Pat Caroline.)

suspected or while waiting for culture results, more aggressive dosage intervals may be initiated.

Some clinicians advise against the use of topical steroid therapy in this condition. However, the addition of a topical steroid, such as 1% prednisolone or newer site-specific steroids such as loteprednol 1% four times a day, accelerates resolution of the stromal infiltrates and the accompanying inflammatory response of the eye. The use of these steroids also treats any anterior chamber reaction that may be present. The addition of topical steroids should be judicious pending the definitive

diagnosis issues discussed previously. Drug therapy usually is needed for 5 to 7 days. The patient should be monitored closely for the development of new signs or symptoms that alter the initial diagnosis of contact lens–associated infiltrative event.

The infiltrative event may recur if contact lens wear is reinstituted too soon and the eye has not been given adequate time to heal. Ideally, contact lens wear should not be resumed until all infiltrates, epithelial defects (including microcysts and subtle negative staining), and signs of inflammation have resolved, which may take up to several weeks. It is not uncommon, however, for prominent anterior stromal infiltrates to leave a persistent opacity (Figure 26-59) that does not preclude resumption of contact lens wear after complete resolution of the acute signs and symptoms.

Once contact lens wear is resumed, it is important to evaluate the lens fit, wearing time, and cleaning regimen in an effort to avoid recurrences of the infiltrative event. Contact lens replacement, a temporary or ongoing switch from extended to daily wear, refitting to a flatter lens, changing to disposable lenses, or refitting with rigid gas-permeable lenses may be needed, singly or in combination. It also is important to remind the patient of appropriate contact lens follow-up care intervals in an effort to minimize the development of acute problems.

Epithelial Microcysts

Etiology

Epithelial microcysts are an abnormal corneal response at the cellular level to chronic hypoxia from contact lens wear. When present, they tend to be observed in soft contact lens wearers, particularly those wearing extended-wear lenses. A hypoxic state can result in the development of microcysts due to such causes as

Figure 26-57 Microbial keratitis. (Courtesy of Pat Caroline.)

excessive wearing time, aging lens material, a tight-fitting lens, or excessive coating and depositing on the lenses.

Epithelial microcysts likely represent small pockets of cellular debris and disorganized cell growth arising from the basement membrane and basal layers of the cornea. The inciting event to microcyst development may be the accumulation of fluid in the intracellular spaces of the epithelium. Microcysts appear as tiny, refractile, spheroidal dots in the central and paracentral corneal epithelium. Because of normal cell turnover, the microcysts tend to migrate through the corneal epithelium where they may rupture and erode onto the epithelial surface. Although an occasional epithelial microcyst may be noted in an asymptomatic extended-wear soft contact

lens patient, a patient who develops large numbers of densely aggregated microcysts eventually develops symptomatology. It is the latter patient who requires therapeutic intervention.

Diagnosis

The soft contact lens patient who becomes symptomatic from epithelial microcysts tends to develop symptoms rather suddenly after uneventful contact lens wear. It is not uncommon for the patient with microcysts to have been remiss in timely follow-up care, when the formation of microcysts may have been detected before symptoms developed. Symptoms associated with this condition include burning, foreign body sensation, tearing, and photophobia, all likely related to the disrupted epithelium. Decreased visual acuity results, even with the best spectacle correction in place, because of the now irregular corneal surface.

Mild to moderate conjunctival injection occurs and may be enhanced in the perilimbal area. Careful slit-lamp examination reveals a dense collection of tiny, clear, epithelial cysts in the central cornea. This appearance is best viewed using indirect illumination and retroillumination techniques (Figure 26-60). Instillation of NaFl reveals an irregular central epithelial surface with almost a discoid collection of punctate “positive’’ and “negative’’ stains. Positive stains occur when the microcysts have emptied onto the epithelial surface and caused microerosions; negative stains occur over the tiny “bumps’’ in the epithelium where the microcysts have invaded the epithelium but not yet eroded it.

544 CHAPTER 26 Diseases of the Cornea

Figure 26-59 An anterior stromal scar remains (arrow) after resolution of infiltrative keratitis and associated corneal infiltrate.

Management

Treatment requires discontinuation of contact lens wear until the epithelial microcysts resolve. Therapeutic measures are primarily supportive in nature while the tissue heals and returns to a normal state. Patients who are acutely symptomatic may benefit from cycloplegia, using long-acting agents such as 5% homatropine for several days. Prophylactic topical antibiotic therapy, such as 0.3% tobramycin drops or 0.3% ciprofloxacin,or the newer generation fluoroquinolones, moxifloxacin 0.5% and gatifloxacin 0.3%, instilled four times daily, protect the cornea from secondary infection. A topical ophthalmic ointment, such as 0.3% tobramycin or 0.3% ciprofloxacin, instilled at bedtime, provides a cushioning layer between the lid and the irritated epithelium. Additionally, the instillation of a mild topical steroid drop, such as 0.12% prednisolone, 0.1% fluorometholone, or 0.5% loteprednol four times a day, enhances patient comfort. Patient compliance can be increased by prescribing combination products such as tobramycin–dexametha- sone or tobramycin–loteprednol four times daily.

Epithelial microcysts may take weeks to months to resolve,although the therapy described above is generally needed only for the first 1 or 2 weeks after acute presentation. Once the patient becomes asymptomatic, it can be a challenging management issue to convince the patient that contact lens wear should be discontinued until the corneal tissue is healed. While corneal healing is being

monitored, it is important to observe closely for subtle positive and negative staining, which is indicative of persistent epithelial disruption.

Once the microcysts resolve completely, contact lens wear may be reinstituted carefully. If age of the lens material, deposited lenses, tight-fitting lenses, or low water content was related to the development of the microcysts, then pursue contact lens refitting. Patient education must be addressed regarding the need for proper lens hygiene, wearing time, and follow-up care. Once contact lens wear is resumed, careful periodic corneal examination is needed to monitor for recurrence of epithelial microcysts.

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Allergic eye disease, with its many varieties and types of presentations, affects people of all ages and has varying degrees of severity and clinical manifestation. These presentations manifest in the conjunctiva as allergic conjunctivitis, giant papillary conjunctivitis (GPC), vernal keratoconjunctivitis (VKC), and atopic keratoconjunctivitis (AKC). Dermatologic manifestations include contact dermatitis and atopic dermatitis. The immunologic basis is undeniable in allergic eye disease, and recognizing it allows one to understand the disease’s pathogenesis, clinical presentation, and how best to treat and manage the condition. Chapter 13 provides an overview of the immune component in allergic eye disease, with the pertinent points to the clinical manifestations described below.

ALLERGIC IMMUNOLOGY: THE CLINICAL FOUNDATION

When the immune system has an exaggerated response to the allergen, a hypersensitivity or allergic reaction occurs. Allergens are antigens that initiate this hypersensitivity response and may include pollen, ragweed, mold, dust, trees, and animal dander. Hypersensitivity reactions may also result from food, insect venom, and drugs, including local anesthetics, sulfonamides, and penicillin.The respiratory system, gastrointestinal tract, skin, and eyes may be affected. Local clinical manifestations include hay fever (conjunctivitis), eczema, asthma, and hives. A systemic response may also occur that results in anaphylactic shock and possibly death.

Susceptible or atopic individuals often have a hereditary or familial predisposition to allergic responses. A genetic defect may account for the IgE response. When both parents are atopic,their child has a 50% chance of developing type I allergic reactions, and when only one parent is atopic the likelihood is 30%.

Allergic eye disease may result from a type I or type IV hypersensitivity reaction.Typically, on initial exposure to the allergen,there are no clinical manifestations.In contrast, clinical manifestations occur in sensitized individuals or

individuals who have already been exposed to the antigen. An immediate hypersensitivity reaction or humoral response (type I) occurs within minutes to hours in sensitized individuals. In comparison, cell-mediated immunity (type IV) is a delayed-type hypersensitivity that may take days to occur.

Ocular Immunology

Allergens may dissolve in the tears, thereby providing an avenue of antigen exposure to the ocular structures. Blinking and flushing actions of the precorneal tear film are protective.The conjunctiva provides an environmental barrier characteristic of innate or nonspecific immunity. The conjunctiva contains a variety of cells, including T and B lymphocytes, that are necessary for a specific immunologic response. In the normal state, mast cells and plasma cells are present in the substantia propria, with mast cells numbering 10,000/mm3. In response to abnormal conditions, the distribution and number of mast cells change. Evidence of this response is found in GPC, seasonal allergic conjunctivitis, and AKC, in which an increased number of mast cells are found in the substantia propria. Mast cells normally are not found in the epithelium; however, they are found in the epithelium of patients with GPC and VKC. Mast cells have been subclassified into tryptase-containing mast cells and tryptaseand chymase-containing mast cells. Both types have been found in the conjunctival substantia propria, with tryptaseand chymase-containing mast cells predominant in healthy persons. In patients with vernal conjunctivitis, the total concentration of both mast cells and tryptasecontaining mast cells is higher than that in healthy individuals. Although patients with GPC and atopic conjunctivitis have slightly increased mast cell concentration in the substantia propria compared with healthy persons, the distribution of mast cell types is similar to that of healthy individuals.These findings provide a basis for a better understanding of the pathogenesis, clinical variation, and potential treatment modalities for different allergic diseases.

550 CHAPTER 27 Allergic Eye Disease

Other cells that are not normally found in the conjunctiva are eosinophils and basophils. Both play an important role in allergic disease and its associated inflammatory process. Eosinophilic chemotactic factor, released by the mast cell, attracts eosinophils to the site of inflammation. In addition to this local eosinophilia, blood eosinophil levels may be elevated in those affected by chronic allergic conjunctivitis. Eosinophils may play a greater and more detrimental role in AKC and palpebral VKC than in other ocular allergies. In AKC and VKC, eosinophils are involved in the sight-threatening corneal changes.

Allergic disease also affects the lids and ocular adnexa. Contact dermatitis is an example of a delayed hypersensitivity reaction that affects the ocular adnexa. In contact dermatitis, exposure to antigen results in the infiltration of T cells and macrophages into the dermis within approximately 3 hours. Over a 48to 72-hour period the peak response occurs,withT cells and macrophages spreading to the epidermis in an attempt to eliminate the antigen. Clinically,eczema or dermatitis develops.Even with the antigen removed, dermatitis may continue for up to 3 weeks.

Immunologic Considerations in

Treating Allergic Eye Disease

Management of allergic eye disease begins with identifying the allergen. Eliminating or avoiding the allergen is the optimal management strategy; however, this is often not possible. Lubricating drops may assist by diluting the allergen, but this alone may not provide adequate treatment, so that drug intervention is required.Various types of drugs interrupt specific stages of the immunologic response brought on by allergens.Table 27-1 lists various drugs used in the treatment of allergic disease.

Different types of drugs affect various stages of the allergic response. Decongestants cause vasoconstriction and alleviate signs of hyperemia. Antihistamines block histamine from binding to the H1 receptor. Mast cell stabilizers prevent mast cell degranulation. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit cyclooxygenase, an enzyme involved in the conversion of arachidonic acid to prostaglandins, prostacyclin, and thromboxane, thereby preventing the inflammatory reaction.

Steroids suppress inflammation by inhibiting phospholipase A2, preventing the formation of arachidonic acid and the synthesis of prostaglandins, prostacyclin, thromboxane, and leukotrienes. Steroids also inhibit degranulation of neutrophils, mast cells, and basophils, as well as histamine synthesis. These drugs decrease capillary permeability, decrease B and T lymphocytes, decrease vasodilation, and inhibit neovascularization and leukocyte migration. Side effects of steroids can limit their use.These adverse effects include elevated intraocular pressure, cataracts, delayed wound healing, increased susceptibility to infection, and rebound anterior uveitis. The potential for producing increased intraocular pressure is reduced with steroids

such as fluorometholone, which has less corneal penetration, as well as the “site-specific” steroids, such as rimexolone and loteprednol.

Cyclosporine A is an immunosuppressive agent that quells inflammation by inhibiting T helper cell proliferation and cytokine production. It also inhibits eosinophil and mast cell activation.

ALLERGIC CONJUNCTIVAL DISEASE

Allergic conjunctivitis affects approximately 15% of the population. The incidence is found to be increasing in developed countries and may be related to genetics, air pollution, pet ownership, and the hygiene hypothesis. This hypothesis proposes that when the immune system is not exposed to allergens early in life, there is a greater likelihood to develop allergies later in life.

The various types of allergic diseases that affect the conjunctiva include allergic conjunctivitis (hay fever conjunctivitis), GPC, VKC (spring catarrh), and AKC (eczematous conjunctivitis).The clinical manifestations of each of these allergic diseases vary in severity and duration, ranging from mild to severe. Loss of vision is a serious complication that may occur in AKC and VKC.

The pathophysiology of allergic disease involves the immune system and its components, which include mast cells, eosinophils, and lymphocytes. Diagnosis is predominantly based on history and clinical findings.Treatment is based on severity. Initial treatment is best achieved by avoiding the allergen and providing supportive therapy, followed by the use of antihistamines, antihistamine/ decongestant combinations, NSAIDs, and steroids as needed.The various types of allergic conjunctival inflammatory response and their etiology, diagnosis, treatment, and management are presented in Tables 27-2 and 27-3.

Allergic Seasonal or Perennial Conjunctivitis

Conjunctival allergy most commonly affects people seasonally and is known as seasonal allergic conjunctivitis or hay fever conjunctivitis.Airborne allergens, such as pollen, are the cause of seasonal allergic conjunctivitis. Less commonly, allergic conjunctivitis may be present year round, and this form is known as perennial allergic conjunctivitis. This variety results from ubiquitous allergens, which include dust mites and animal dander. Frequently, nasal symptoms or rhinitis occur along with the ocular symptoms, and the combination is known as allergic rhinoconjunctivitis. Allergic conjunctivitis affects both genders and all age groups.

Etiology

Allergic conjunctivitis results from a type I immediate allergic reaction. The clinical manifestations reflect the immune response, and this response is discussed above and in Chapter 13.