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

388 CHAPTER 23 Diseases of the Eyelids

with an oral antibiotic for the treatment of blepharitis. This kit is available by prescription only.

Topical antibiotic use in MGD is controversial. Some authors recommend against topical applications to avoid further disruption of the tear film and also because efficacy is questionable.Topical steroids are unlikely to have any benefit. During the course of therapy, attention should be given to the KCS that occurs in nearly every case.Artificial tears or lubricating ointments are indicated to ensure improvement in symptoms. More recent treatment options include topical cyclosporine A 0.05% as well as “soft steroids” such as loteprednol or rimexolone.

Blepharitis in Rosacea

Etiology. Acne rosacea, better described as rosacea, may be associated with acne but is not caused by it. Rosacea is a chronic, facial, inflammatory skin disorder frequently related to infectious blepharitis. Rosacea affects the face, nose, chin, and forehead. It has been reported to occur in up to 10% of the population and roughly 14 million Americans. It affects mostly fair-skinned individuals with an onset of between 20 and 50 years. It is characterized by periods of exacerbation that may be mild to very severe. One of the many forms of rosacea is ocular rosacea.

Diagnosis. The diagnosis of rosacea depends on the presence of one or more of the following signs found on the face:transient or persistent flushing,papules,pustules, and telangiectasia (Figure 23-9). Up to 58% of patients with rosacea develop eye signs or ocular rosacea. The exact etiology of ocular rosacea is unknown; however, the possible causative factors may be D. folliculorum infestation, staphylococcal infection, chronic meibomitis, or blood vessel dysfunction. In its severe form rosacea often

affects the cornea, leading to significant symptoms and visual impairment. Facial erythema and telangiectasia with MGD suggests the need for dermatologic consultation, even without the more obvious signs of papules and pustules.The most common eye findings are conjunctivitis and meibomitis. Corneal signs include neovascularization, scarring or thinning, and/or SPK (Figure 23-10).The patient may have a history of recurrent hordeola or chalazia. Other less common ocular signs include episcleritis/scleritis and iritis. Ocular rosacea may precede cutaneous signs, and in 20% of patients it is the only clinical sign. However, in most cases the presentation is concurrent or the skin findings occur first. Ocular rosacea is under-diagnosed in the population, partly because facial signs may be subtle, but also because eye care practitioners often fail to look for facial signs in patients with nonspecific complaints.

Management. Recently, a few randomized clinical trials have evaluated the efficacy of various ocular rosacea treatments. Oral therapy is the mainstay because there is better follicular penetration than with topical treatments. Oral tetracycline, minocycline, or doxycycline remains the treatment of choice, along with erythromycin, azithromycin, and clindamycin. Oral tetracycline is prescribed at 250 mg four times a day for at least 3 weeks and then tapered when the condition begins to respond. It may also be cycled with a pattern of 3 weeks on and 1 week off the medication.Although slower acting, doxycycline is often better tolerated and has better gastrointestinal tract absorption. Doxycycline is effective at 100 mg once a day for 6 to 12 weeks, tapered to 50 mg once a day for 4 weeks and then 50 mg every other day and gradually discontinued. Many patients require a maintenance dosage to prevent relapse. Currently, low-dose or submi- crobial-dose doxycycline at 20 mg twice daily used for its anti-inflammatory property is under investigation. A formulation of controlled-release, 40 mg doxycycline

Figure 23-9 Rosacea of the face with flushing, papules, pustules, and telangiectasia of the nose. (From Palay DA, Krachmer JH. Conjunctival abnormalities. In: Primary care ophthalmology, ed. 2. Philadelphia: Mosby, 2005:99.)

Figure 23-10 Rosacea with severe blepharitis. Note the thickened lid margins and the corneal neovascularization. This is the same patient as seen in Figure 23-9.(From Palay DA, Krachmer JH. Conjunctival abnormalities. In: Primary care ophthalmology, ed. 2. Philadelphia: Mosby, 2005:98.)

monohydrate, taken once daily, is available. Warm compresses, lid expression, and lid hygiene are also important.

KCS is more prevalent in rosacea, so attention to this aspect of management is crucial. The use of artificial tears, lubricating ointments, or topical cyclosporin is often required to ensure improvement in symptoms.

Topical preparations for the treatment of rosacea include metronidazole 0.75% or 1% cream, 0.75% gel, or lotion. None of these preparations is FDA-approved for ophthalmic use, but they have been beneficial for some patients.

INFLAMMATORY DISEASES

Hordeola are extremely common typically self-limiting infections of the meibomian glands or the glands of Zeis and Moll.There are two distinct clinical types of hordeola defined by the glands involved, either external or internal.

External Hordeolum

External hordeolum, also called a stye, is often self-treated by the patient. However, the optometrist or other primary care clinician may be consulted because of its painful and cosmetically displeasing course.

Etiology

An external hordeolum is an acute focal inflammation with abscess formation, most often caused by a S. aureus infection of the glands of Zeis and Moll. It may occasionally be associated with staphylococcus blepharitis and can be recurrent.

Diagnosis

The lesion usually appears as a localized area of redness, tenderness, and swelling adjacent to or surrounding an eyelash (Figure 23-11).The primary symptom is localized pain of recent onset. Within a few days the lesion develops a yellow point on the surface of the lid margin. In most cases the abscess spontaneously drains within 3 or 4 days after pointing. Rarely do external hordeola cause any other tissue damage.

Management

The application of hot compresses several times daily serves to hasten pointing and drainage. Generally, this is all that is necessary for resolution.Topical application of antibiotic solutions or ointments may prevent infection of surrounding lash follicles but does not affect the course of the external hordeolum itself. One of the best methods to hasten drainage is to epilate the involved lash, which creates an effective drainage channel.

For lesions resistant to the usual therapy, a stab incision can be made with a sterile needle or blade into the area of pointing, allowing the abscess to drain. The area

Figure 23-11 External hordeolum (stye). Presents as a localized area of redness, pain, and swelling adjacent to an eyelash. (From Kanski JJ. Eyelids. In: Clinical ophthalmology: a systematic approach. Philadelphia: ButterworthHeinemann, 2003:14.)

should then be treated with a topical antibiotic ointment, such as tobramycin or polymyxin B/bacitracin. If the external hordeolum is recurrent despite topical antibiotic therapy, a lid culture should be obtained to identify the organism so that specific antibiotic therapy can be instituted.

Internal Hordeolum

Etiology

An internal hordeolum is a localized staphylococcal infection of the meibomian glands. The infection may result from blockage of the gland and is found more frequently in the upper lid. A specific change in meibomian gland secretion has been linked to internal hordeolum formation.

Diagnosis

Inspection and palpation of the affected lid reveal a localized area of infectious inflammation with swelling, warmth, redness, and tenderness within the tarsus (Figure 23-12). The lesion may point toward the surface of the lid or toward the palpebral conjunctiva.The onset and course of an internal hordeolum are usually more prolonged than that of an external hordeolum. Internal hordeola may represent an extension of infection from a primary site and are often associated with a preexisting condition such as blepharitis. If not treated adequately, an internal hordeolum may extend into surrounding tissues, causing preseptal or orbital cellulitis.

Management

Because the infection is deep within the lid tissue, topical antibiotics are usually ineffective. If the lesions are small and without significant pain and tenderness, the application of hot compresses several times daily is usually sufficient for resolution. If the lesion is causing moderate to

Figure 23-12 Small internal hordeolum of the upper eyelid (arrow). (Courtesy Dr. Katrina Parker, University of Houston, College of Optometry.)

severe symptoms and is large in size, oral antibiotics are indicated. Because most internal hordeola are caused by Staphylococcus species, primary therapy should consist of a penicillinase-resistant synthetic penicillin such as dicloxacillin. Dosages of 125 to 250 mg every 6 hours for 1 to 2 weeks usually results in prompt resolution of the infection. Second-line oral therapies include erythromycin, azithromycin, or cephalosporins if the patient is not allergic to PCN (penicillin). In cases resistant to such oral therapy, incision and drainage may be necessary. Topically applied antibiotic solution or ointment after drainage serves to prevent secondary infection. One should carefully inspect the surrounding lid tissue for edema and hyperemia because of the high incidence of preseptal cellulitis, which requires an oral antibiotic.

Chalazion

Etiology

A chalazion is a chronic, sterile, lipogranulomatous inflammation of the meibomian gland due to retention of normal secretions. Such duct obstruction and granuloma formation may occur during Demodex brevis invasion of the meibomian glands, but the precise role of this organism in the formation of chalazia has not been established. Chalazia occur spontaneously or may follow an acute internal hordeolum.

Diagnosis

The lesion usually develops over several weeks and is more common in the upper lid, appearing as a hard, painless, immobile mass (Figure 23-13). Examination of the lesion reveals noninfectious inflammation. Palpation discloses a hard, mobile, painless growth without redness, an important feature differentiating it from an internal hordeolum. If the chalazion enlarges it may produce mild discomfort, be cosmetically displeasing,or induce corneal astigmatism. Twenty-five percent of chalazia resolve spontaneously within 6 months of onset, but most require treatment.

Figure 23-13 A large chalazion located at the lateral aspect of the lower eyelid.

Management

In most cases chalazia can be treated successfully by the application of hot compresses, followed by vigorous digital massage several times daily for 2 to 4 weeks. Topical and systemic antibiotics are not necessary because the lesion is sterile. The longer a chalazion is present the more resistant it will be to conservative treatment; however, even lesions present for over 6 months may respond to warm compresses and digital massage. Consequently, local measures should be implemented before seeking more aggressive therapy.

Chalazia that fail to respond to conservative management may be treated with an intralesional injection of steroids; 0.1 to 0.2 ml of triamcinolone acetonide is injected into the center of the lesion, using a 1-ml tuberculin syringe fitted with a 27or 30-gauge 5/8-inch needle. If the chalazion points anteriorly, the injection is given through the skin of the lid. If the chalazion points posteriorly, a topical anesthetic is applied and the injection is given through the conjunctiva.The patient is seen in 1 week; if the chalazion persists, a second injection is indicated. Chalazia typically resolve within 1 or 2 weeks after a single injection of steroid, but larger lesions (>6 mm in diameter) often require a second injection. The overall success rate is 77% to 93% after one or two injections. If the chalazion persists after the second injection, surgical excision and curettage is indicated (see Surgical Treatment of the Lids, below).

Complications after steroid injection are minimal but can occur.The patient can expect slight discomfort at the injection site and occasionally subcutaneous white (steroid) deposits in the treated area. Depigmentation of the eyelid at the injection site, especially in dark-skinned individuals, and temporary skin atrophy can also occur. Skin depigmentation can be minimized by using a transconjunctival rather than a transepidermal injection in persons of color. When depigmentation occurs, it is

usually reversible.Very rarely, retinal and choroidal vascular occlusions immediately after a steroid injection have been reported.These occlusions are due to embolization and may be reduced by aspirating for blood before injecting, injecting slowly, and avoiding heavy digital pressure during and after injection. Other rare cases of globe penetration have been reported; however, this can be avoided by using a chalazion clamp that has a solid footplate.

If after 1 or 2 months of conservative therapy or 2 to 4 weeks of intralesional steroid injection the chalazion has not resolved,surgical resection can be recommended. In atypical cases or lesions that recur after surgical removal, the chalazion should be submitted for pathologic examination to exclude the possibility of sebaceous gland carcinoma or Merkel cell tumor. Chalazia presenting in the elderly are more likely to be associated with malignancy. Coexisting blepharoconjunctivitis that is resistant to therapy and has associated lymphadenopathy, especially involving the preauricular and submandibular nodes, also suggests the possibility of malignancy and warrants histologic examination of excised tissues.

Preseptal (Periorbital) Cellulitis

Etiology

Preseptal or periorbital cellulitis is an infectious process involving lid structures anterior to the orbital septum. The condition generally occurs due to one of three clinical scenarios: (1) secondary to a localized infection or an inflammation of the eyelids or adjacent structures (i.e., sinusitis, conjunctivitis, blepharitis, and/or internal hordeolum), (2) secondary to eyelid or facial trauma, and

(3) after an upper respiratory tract infection.

Profound inflammation and edema of the eyelid may accompany infection of the skin of the face (i.e., impetigo), eyelids, or conjunctiva. Infection occurs by invasion of the organism into the subcutaneous tissue through an abrasion or ulceration. In most patients,

S. aureus, group A Streptococcus pyogenes, or β-hemolytic streptococci cause the infection. These organisms can also accompany infected lacerations and abrasions, insect stings or bites, foreign bodies, or bacterial infection of viral lesions caused by herpes simplex or varicella-zoster virus (VZV). There has been an increase in preseptal cellulitis caused by uncommon bacteria such as Acinetobacter, a gram-negative coccobacilli, and at least one reported case caused by Trichophyton (ringworm). Erysipelas, a rare form of preseptal cellulitis, is caused by S. pyogenes group A and is mainly found in children. Anaerobic organisms such as Peptostreptococcus and Bacteroides species, which are part of the normal oral flora, can be the causative organisms in patients with preseptal cellulitis associated with human or animal bites. Foul-smelling discharge, necrotic tissue, gas in the tissue, or severe toxemia suggests an anaerobic infection.

In patients without evidence of local infection or trauma, preseptal cellulitis is often secondary to a respiratory tract

infection and/or sinusitis or ethmoiditis in most cases; the causative pathogen is usually S. aureus, Streptococcus pneumoniae, or Haemophilus influenzae. Cellulitis may result from a direct extension of infection from the sinus cavity.Although the most likely primary focus of infection is the nasopharynx and sinuses, cellulitis may also develop by spread of organisms from the middle ear to the preseptal space via the vascular or lymphatic systems. Young children with a sinusitis and secondary cellulitis pose a very serious health risk, because the infection can cause severe orbital or intercranial complications.

Before the introduction of the H. influenzae type B vaccine in 1985, nearly all children under 6 years of age with preseptal cellulitis were found to have H. influenzae type B or a S. pneumoniae infection.This condition was of great concern due to the mortality from secondary meningitis. Because H. influenza is no longer of primary concern in children, the most common causative bacteria are the group A streptococci. An important component in the history of young children with cellulitis should be to confirm or exclude H. influenzae type B vaccination.

Diagnosis

Cellulitis can pose a significant risk for morbidity and mortality if undiagnosed. For this reason the practitioner needs to differentiate preseptal cellulitis from the more serious orbital cellulitis (Table 23-1). Chemosis, conjunctival injection, and pain on eye movement occur more often in orbital cellulitis; both conditions present with redness and swelling of the eyelid. When a swollen lid

Table 23-1

Differential Diagnosis: Preseptal and Orbital Cellulitis

IOP, intraocular pressure, aRelative afferent pupillary defect.

Modified from Jones DB, Steinkuller PG. Microbial preseptal and orbital cellulitis. In: Tasman W, Jaeger EA, eds. Duane’s clinical ophthalmology, vol. 4. Philadelphia: JB Lippincott, 1993:1–24; and Holdeman NR. Preseptal cellulitis/orbital cellulitis. In: Onofrey BE, Skorin Jr L, Holdeman NR, eds. Ocular therapeutics handbook; a clinical manual, ed. 2. Philadelphia: Lippincott Williams and Wilkins, 2005:189–193.)

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occurs without evidence of proptosis, the diagnosis is invariably preseptal cellulitis (Figure 23-14). In addition to proptosis, other signs of orbital cellulitis include limited extraocular motility, reduced visual acuity, an afferent pupillary defect, and systemic involvement. Occasionally, fever and headache occur in patients with preseptal infection; however, when these occur in conjunction with proptosis, decreased visual acuity, and restrictions on eye movement, orbital cellulitis is typically the cause.

The eyelid and adnexal tissues should be carefully examined for the presence of puncture wounds, trauma, or infectious lesions of the skin. Facial tenderness, nasal discharge, and malodorous breath are signs of paranasal sinusitis. Focal medial canthal tenderness and tearing may indicate acute dacryocystitis.

In distinguishing preseptal from orbital cellulitis, if the eyelids cannot be separated to look for proptosis, limited ocular motility, afferent pupillary defect, or vision loss, computed tomography of the orbit should be considered to exclude the presence of orbital involvement. Moreover, computed tomography helps to detect the presence of orbital foreign bodies and sinusitis. A computed tomography is recommended if orbital involvement cannot be excluded on the basis of the clinical examination; if there is progression of disease despite antibacterial treatment; if there is ophthalmoplegia, deteriorating visual acuity, or color vision; or if the infection is bilateral.

In cases that do not resolve or become worse, in the absence of overt signs of orbital involvement, laboratory evaluation should include a complete blood count with differential as well as blood cultures. Cultures often show positive growth in children under the age of 4 years (usually streptococci) but are rarely positive in older children or adults. In patients with skin lesions, specimens should be obtained for culture onto blood, chocolate, and

Sabouraud’s agar plates. Although cultures of draining wounds may be useful in cases of preseptal cellulitis related to trauma or local infection, cultures of the conjunctiva, eyelids, and nasal mucosa are generally misleading.

As previously stated, H. influenzae is no longer a major cause of cellulitis in children. However, when present, the condition is characterized by significant fever, leukocytosis, and unilateral hyperemia and edema of the eyelids. There is a sharply demarcated dark purple discoloration of the eyelid skin and adnexal area. Mild conjunctival hyperemia and chemosis may also occur. Unless the patient has received antibiotics, blood cultures are the most effective means of establishing the diagnosis. If meningeal signs are present, a lumbar puncture should be performed, because 12% to 25% of patients with Haemophilus preseptal or orbital cellulitis have concomitant meningitis.

In cases where there is sudden onset, with swelling and pruritus, an allergic reaction should be considered and is often the result of an insect bite (Figure 23-15). These patients respond well to oral antihistamines, and the condition usually resolves within 24 to 48 hours without further intervention.

Management

The initial choice of antibiotic for treatment of preseptal cellulitis is largely empiric, as the causative pathogen is not identified. Thus appropriate therapy must take into consideration the most plausible etiologic organisms. Because preseptal cellulitis associated with local trauma or infections is not usually serious, treatment often consists of oral antibiotics. Mild to moderate infections usually respond to oral penicillinase-resistant synthetic penicillins, such as dicloxacillin (250 mg orally every 6 hours) or amoxicillin–clavulanic acid (250 to 500 mg orally three times a day or 875 mg orally twice daily), or to a first-generation cephalosporin, such as cephalexin (250 to 500 mg orally three times a day). If the patient is allergic to penicillin, trimethoprim-sulfamethoxazole (one double-strength tablet orally twice daily), azithromycin “Z-Pak,” or levofloxacin (500 mg orally every day) is recommended.Therapy should continue for at least 7 to 10 days.Topical antibiotic therapy is indicated

Figure 23-14 Preseptal cellulitis of the upper eyelid secondary to an internal hordeolum. Note the shallow skin fissure (arrow) secondary to the significant swelling. (Courtesy Dr.Anastas Pass, University of Houston, College of Optometry.)

Figure 23-15 Sudden onset of preseptal cellulitis of left eye in a 3-year-old child secondary to an insect bite.

when there is external lid involvement or a secondary conjunctivitis. In severe cases, when the patient is under 5 years of age, or if the patient is immunocompromised, hospitalization and intravenous antibiotics are warranted.

VIRAL EYELID DISORDERS

Herpetic Ocular Disease

Herpes simplex virus (HSV), the most common virus found in humans, and VZV have both been known to cause serious ocular complications. Generally speaking, primary disease occurs as a blepharoconjunctivitis in HSV and as chickenpox in VZV but may recur in older children and adults. Both viruses typically manifest as a unilateral ocular disease.

Herpes Simplex Blepharoconjunctivitis

Etiology. HSV type 1 causes most of the ocular simplex infections. Type 2 HSV is predominantly a genital pathogen, although there has been an increase in the number of ocular cases caused by this strain of HSV. Blepharoconjunctivitis, caused by type 1 HSV, usually occurs as a primary infection in children, between the ages of 6 months and 5 years, without significant systemic signs or symptoms. The infection is usually spread via contact with cold sores, saliva, or other fomites; it may also be passed onto the neonate during vaginal delivery. Once the primary infection is quelled, the virus lies dormant in the trigeminal ganglion, cornea, or sclera until reactivation occurs. Reactivation may be triggered by stressors such as illness, fatigue, trauma, and ultraviolet sun exposure, although none of these factors has specifically been proven.There have been several reported cases of recurrent HSV blepharitis; however, recurrence typically presents as a dendritic keratitis, not as an eyelid manifestation. Approximately one-fifth of patients with ocular herpes simplex have lid involvement as the only sign of infection. Recurrence rates for HSV are approximately 20% within 2 years, 40% within 5 years, and 67% within 7 years.

Diagnosis. In the classic form, vesicles form along the eyelid margin and/or periocular skin (Figure 23-16). The lesions are clear, pinhead in size, and have an inflamed erythematous base. Typically, within 1 week of presentation the vesicles break and ulcerate, resulting in a painful edematous blepharitis or dermatitis.The involved portion of the lid usually demonstrates mild swelling and tenderness. Pronounced conjunctival injection, a secondary follicular conjunctivitis, a “weepy” wet eye, and a regional lymphadenopathy may all be present.

Management. Because topically administered antiviral agents have little or no effect on skin lesions, treatment of HSV infection of the eyelid is nonspecific. In the

Figure 23-16 Herpes simplex blepharoconjunctivitis. Note the open vesicles in the medial canthus and the lower lid margin with secondary viral conjunctivitis. (Courtesy Dr. Ralph Herring, University of Houston, College of Optometry.)

immunocompetent host, the vesicular lesions from a primary herpetic infection of the lids remain localized, are generally self-limited, and resolve without scarring, usually within 10 to 14 days. If the lesions are near the lid margins, topical trifluridine can be administered prophylactically several times daily to prevent corneal infection. If corneal involvement occurs, vigorous antiviral therapy should be instituted (see Chapter 26).

Palliative treatment of lid lesions includes lid hygiene with warm compresses. Drying agents can be applied to periocular skin lesions, carefully avoiding those on the lid margins. These agents include calamine lotion, spirits of camphor, or 70% alcohol.Another reported treatment for viral skin lesions is the application of topical povidoneiodine, thought to have an antibacterial and a drying effect, though not yet clinically proven. If the lesions become secondarily infected, a topical antibiotic ointment should be applied. Steroids are contraindicated because they may predispose the patient to serious corneal involvement.

Herpes simplex infection in the immunocompromised host, especially the patient infected with the human immunodeficiency virus (HIV), requires careful comanagement with the patients’ physician.

Herpes Zoster Ophthalmicus

Etiology. VZV is a DNA virus that causes two separate but distinct clinical entities: varicella (chickenpox) and zoster (shingles). It is estimated that over 90% of all adults in the United States are seropositive for VZV and almost all carry latent virus.

Primary disease, termed chickenpox (varicella), is benign and usually occurs before the age of 10 years. It is estimated that 3 million new cases of chickenpox occur in the United States each year, with a peak incidence in the spring. Once infected, the virus lays dormant in the

394 CHAPTER 23 Diseases of the Eyelids

dorsal root ganglion or trigeminal ganglion until reactivation occurs, typically in otherwise healthy adults between the ages of 50 and 70 years.

Recurrent disease is termed zoster or shingles and spreads via a spinal nerve or cranial nerve to the affected dermatome. Zoster affects one-fifth of the population with an incidence of 2.2 to 3.4/1,000 per year. The incidence of zoster in the elderly is reported to be as high as 10/1,000 per year in those over 80 years; however, recurrent zoster in younger immunocompetent patients is low and is estimated to be about 4%.The total lifetime risk for developing shingles is estimated to be 10% to 20%.In recent years the incidence and severity of varicella-zoster infection has increased because of the growing number of immunosuppressed patients, including transplant patients and those with Hodgkin’s disease, chronic lymphocytic leukemia, and acquired immunodeficiency syndrome. The diagnosis of herpes zoster in patients younger than 45 years warrants testing for HIV, because herpes zoster ophthalmicus (HZO) can be the initial manifestation.The relative risk of VZV is 15 times greater in patients infected with HIV than in those who are not. Identification of HIV status is extremely important because ocular involvement can be rapidly progressive and potentially blinding, thus requiring aggressive treatment.

Reactivation of VZV is thought to be related to an inciting or predisposing event or condition.These factors include trauma,surgery,advanced age,stress,corticosteroids,

infection, underlying neoplasm, ultraviolet light or irradiation, and heavy metal or chemical exposure or toxicity.

Frequently, HZV affects the cranial nerves. When the first (ophthalmic) division of the fifth cranial nerve is affected, the resultant disease is considered to be HZO; eye involvement occurs in 10% to 20% of all cases of zoster. One or all of the branches of cranial nerve V1 may become involved.The frontal nerve is the most frequently affected, involving the upper lid, forehead, and superior conjunctiva. The virus may also involve the nasociliary branch of cranial nerve V1, which innervates the sclera, cornea, iris, ciliary body, and choroids as well as the side and tip of the nose. Lesions affecting the tip of the nose are termed Hutchinson’s sign and signify a greater risk of ocular involvement. It is estimated that if Hutchinson’s sign is present, there is a 50% to 80% greater risk for developing HZO.

Diagnosis. The prodromal phase is characterized by headache, malaise, fever, and chills, followed in 1 or 2 days by neuralgic pain and 2 or 3 days later by hot, flushed, hyperesthesia and edema of the involved dermatome(s).The skin overlying the affected area then erupts with a single crop of clear vesicles. The vesicles are distributed on only one side of the face and almost never cross more than 1 to 2 mm beyond the midline (Figure 23-17). These vesicles then become yellow and turbid and by day 7 to 10 form deep scab-like eschars,

which may leave permanent pitted scars. Viable viruses can be cultured from the vesicles for up to 14 days after appearance of the rash. Health care workers are advised to know their immune status with regard to varicella and, if necessary, to seek immunization. It is advisable to caution families and/or partners of patients regarding the contagion.

Some patients experience only relatively minor tingling and numbness, but often excruciating neuralgic pain accompanies the disease. In most cases the severe pain subsides during the first several weeks, but many patients develop postherpetic neuralgia (PHN), a chronic condition caused by scarring of the nerves.Although the cause of PHN is not well understood, the prevalence is important in management decisions. More than 50% of patients over the age of 60 develop PHN after an episode of herpes zoster. Once established, the pain often becomes intractable and management is, at best, difficult. PHN is one of the most common causes for presentation at pain clinics. Involvement of the trigeminal nerve is a predictive factor for PHN as well as advanced age, the presence of prodromal pain, and unusually severe pain at the onset of the dermatitis. Such patients experience persistent aching and burning, which can interrupt daily activities and in some instances can lead to severe depression or even suicide. Thus one of the most important aspects of therapy is to prevent scarring and subsequent neuralgia. Although the acute inflammatory stage lasts only 2 to 3 weeks, the skin ulceration may require many weeks to heal and can result in the equivalent of thirddegree burns.As a result serious complications can arise, including total lid retraction, ptosis, madarosis, entropion, or cicatricial ectropion.

Management

Dermatitis. In most cases the skin and lid lesions of varicella-zoster are self-limited and benign. The primary concern should be coincident keratitis, and thus the swollen lids must be carefully separated so that the cornea can be examined.The treatment of corneal lesions is discussed in Chapter 26.

Optimal antiviral treatment is begun within 48 to 72 hours of the first skin eruption to reduce further ocular involvement and perhaps decrease the duration of associated pain; it has not been proven to prevent PHN. This optimal time course, however, should not detract from the value of antiviral therapy begun late, which may still be beneficial when initiated 3 to 7 days after eruption. Oral antivirals effectively hasten resolution of signs and symptoms, reduce viral shedding and formation of new skin lesions, and decrease both the incidence and severity of ocular complications. Controversy remains as to the best choice of oral therapy.Acyclovir 800 mg five times a day for 7 to 14 days has been the standard. Alternatively, valacyclovir, a prodrug of acyclovir, is administered at 1,000 mg three times a day and is considerably less expensive than acyclovir. Famciclovir, a prodrug of penciclovir,

is administered at 500 mg three times a day for 7 days. Dosing compliance is easier with valacyclovir or famciclovir than with acyclovir; therefore they may be considered as first-line treatment options.

The main side effect associated with oral acyclovir, valacyclovir, and famciclovir is intestinal disturbance such as nausea and vomiting. Acyclovir is available in an 800-mg tablet that does not contain lactose; therefore it is less likely to cause lactose-related diarrhea. Lower dosages are recommended for treatment of elderly patients with impaired creatinine clearance. Perhaps the most significant factor in favor of antivirals is that they minimize the common complications of the disease, including dendriform keratopathy, stromal keratitis, and anterior uveitis.

Drying lotions should not be used on skin lesions because they may increase scarring. In the child or adult for whom the skin lesions itch or are irritating, an oral antihistamine may help to prevent scratching, which can lead to secondary infection and thereby scarring. Recommended agents include oral chlorpheniramine or diphenhydramine.The use of cimetidine is controversial; as an H2 blocker, oral cimetidine has an immunosuppressive action. The effects are not always consistent, however, and use of cimetidine is risky in autoimmune disorders and organ transplant patients.

In patients with severe lid involvement, lubricating ointments should be instilled into the cul-de-sac to prevent complications arising from exposure or trichiasis. An oculoplastic surgeon should manage scarring and contraction of lid tissue that creates cicatricial ectropion, lid retraction, lid margin deformity, or severe corneal complications.

It is important to note that the acute lid edema occurring soon after the onset of viral invasion does not result from bacterial cellulitis and typically resolves within a few days without antibiotic therapy.

Acute and Postherpetic Neuralgia. In addition to antivirals, oral analgesics are recommended for pain. If the pain is severe, an opioid analgesic may be prescribed. A stellate ganglion block, administered by an anesthesiologist within 14 days of the rash, may also be helpful.

Although oral corticosteroids have had an established use in herpes zoster treatment, their value has become controversial.They are clearly contraindicated in HIV and while the virus is still present in immunocompetent patients. Some authors report increased quality of life and decreased acute pain with oral steroid use in the elderly, but this value is offset by potential risk. Significant relief may be obtained with early antiviral therapy so that oral steroids are an unnecessary risk. Oral steroids are of no value in preventing PHN as was previously believed.The duration of PHN, however, is significantly shortened by early and aggressive use of oral antiviral agents in the acute phase of herpes zoster. Tricyclic antidepressants may also be useful when prescribed at the time of acute

396 CHAPTER 23 Diseases of the Eyelids

onset of herpes zoster for treatment of PHN that develops later; however, due to their anticholinergic, sedation, and postural hypotensive effects, they have limitations. It has also been reported that preemptive treatment with an anticonvulsant (i.e., gabapentin) may reduce the incidence of PHN. Only one-third of patients with PHN of 6 months duration find adequate pain relief. For this reason PHN is best comanaged by an ophthalmologist and/or pain specialist. Oral H2 blockers have been suggested as treatment for PHN and for the dermatologic sequela of HZO; however, this has yet to be conclusively proven.

Topical therapy may be of some benefit to the PHN patient. They are used after the skin lesions have healed but cannot be used on periocular tissue.Topical lidocaine patches for analgesia is one such treatment. Capsaicin cream has also been used and may provide pain relief within 2 to 4 weeks of treatment. The cream is applied three to four times daily to the area of painful skin. Approximately 30% of treated patients experience burning, stinging, or redness of the skin on initial application, but with repeated use these reactions usually diminish or subside.

Immunocompromised Patients and HZO. In the immunosuppressed patient, especially the HIV patient, the risk of virus dissemination is higher,postherpetic pain can be greater, and ocular/systemic complications can be more severe. Hospitalization for intravenous acyclovir ensures higher drug concentrations than with oral agents. Outpatient therapy with oral antivirals may be considered for mild localized herpes zoster in some immunosuppressed patients, home intravenous acyclovir therapy may be considered for slightly more immunosuppressed patients, and hospitalization with isolation and intravenous ganciclovir is the treatment of choice for HIV patients who are already receiving acyclovir. HIV patients develop retinitis, which can advance to progressive outer retinal necrosis or endogenous endophthalmitis. Periodic fundus examinations are necessary in these patients, and prophylaxis treatment is often maintained for life. Although triple drug therapies including antiretrovirals and protease inhibitors have thus far resulted in fewer cases of herpes zoster in the HIV population, this trend is not expected to endure because triple therapy also allows patients to live longer, and zoster cases may merely be postponed.

Varicella-Zoster Immunization. Immunization against varicella was approved in the United States in 1995 and is administered to children 12 to 18 months of age or older if they have not had chickenpox. It has been shown to be most effective in the year after vaccination; however, breakthrough disease was noted but found to be mild. Varicella vaccination reduces the number of related deaths, especially in children aged 1 to 4 years,

and reduces the overall hospitalization and ambulatory visit rates in children and adolescents. It does not affect the age-specific rate of developing shingles.

In May 2006 the U.S. Food and Drug Administration approved a live attenuated VZV vaccine. It is indicated for patients 60 years of age and older who have had a history of chickenpox but not shingles. It has been shown to reduce the incidence of VZV, PHN, and the duration and severity of illness.

Molluscum Contagiosum

Molluscum contagiosum is a relatively common viral infection of the skin that may be problematic when located near or around the eyes. It is seen most often in children but may be found in adults, especially if immunocompromised.

Etiology. Molluscum contagiosum is a localized selflimiting skin infection caused by a human-specific pox virus. Infection is most often due to autoinoculation or by direct contact; it is rarely sexually transmitted.

Diagnosis. Diagnosis is typically made based on the clinical appearance of the skin and eyelid lesions; however, occasionally it is made after excision and histology is performed. The lesions, called mollusca, are multiple, dome-shaped, pearly, or flesh-colored papules with a central depression or umbilication (Figure 23-18). Lesions range between 1 and 10 mm in size with an average of 2 to 3 mm. Mollusca typically occur over the trunk or flexural areas of the body but may also be found on the skin of the face, eyebrows, and eyelids. Incubation, on average, takes 2 weeks but may be as long as 6 months, with a mean duration of 6 to 8 weeks. Lid lesions frequently go unnoticed unless they shed virus into the cul-de-sac, causing a follicular conjunctivitis (see Chapter 25). Patients

Figure 23-18 Molluscum contagiosum showing the typical dome-shaped lesions with central depression (arrows). (Courtesy Dr. Mona Younes,University of Houston,College of Optometry.)

often complain of a red watery eye and occasionally blurry vision.

Management. Treating molluscum is controversial. The condition is typically benign and self-limiting with little or no residual sequela. However, to speed the process some recommend piercing the lesion with a sterile needle and expressing the umbilicated core and cautery, excision, or destruction of the lesion with phenol. Some of the more invasive treatment options can cause scarring, and unless the condition is causing extensive patient discomfort these are not recommended. Antivirals have little effect and are therefore not recommended.

LID INFESTATIONS

Demodex

The Demodex mite is an ectoparasite that is found on many different hosts. Of all the many different species of Demodex, only two infest humans: D. folliculorum and

D. brevis. D. folliculorum is 0.35 to 0.40 mm long and is found in small hair follicles such as the eyelashes. D. brevis is 0.15 to 0.20 mm long and is found deep within sebaceous glands of the eyelashes and in the meibomian glands. Both organisms are extremely prevalent on the skin of the face, especially the forehead, cheeks, nasolabial folds, and the nose. Each parasite has eight small stumpy legs and an elongated body.They typically are found head down toward the lash root or gland. Infestation is much more common in adults than in children and can be quite severe in an immunocompromised individual. Controversy exists as to the prevalence and pathogenicity of Demodex, especially in patients with rosacea and blepharitis. Studies have shown that D. folliculorum is not more prevalent in blepharitis than in normal control patients, thus suggesting it is not an etiologic factor in the disease process. Other research seems to refute this theory. D. brevis has not been as extensively studied; therefore its pathogenicity remains relatively unknown. Current theory holds that in certain adult populations, Demodex can cause granulomatous or suppurative reactions and inflammation.

Etiology

Demodicosis is thought to be caused by an over-infestation of the mite in the follicles and pilosebaceous glands of the eyelids. These parasites cause destruction of the epithelial and glandular tissue, producing follicular distension, hyperplasia, increased keratinization, and acute inflammation. Dead mites and keratinization may play a role in the stagnation of secretions, which adds to the overall disease process. No current studies adequately prove the minimum number of mites necessary to produce symptoms; therefore their role in pathogenesis remains unclear. It has been postulated that Demodex

may play a role in chalazion formation, blepharitis, and rosacea.

Diagnosis

Clinically, demodicosis of the lids manifests as a form of blepharitis with patients complaining of itching and burning, although many patients remain asymptomatic. In one recent study it was determined that although Demodex is found in all age groups and subpopulations, there is a higher prevalence of recoverable mites (D. folliculorum) in eyelashes with “cylindrical dandruff” than in eyelashes without.This finding correlates to that seen clinically as the typical “sleeve” or “cylinder” that covers the base and lower one-third of the lash and rests on the surface of the lid margin (Figure 23-19). In severe or persistent cases it is recommended that a few of the involved lashes be epilated and viewed with a light microscope to confirm the diagnosis. Saline is generally used as the fixing fluid for microscopy; however, in cases where the sleeve is compacted, it is recommended that 100% alcohol be added to facilitate migration of the organism out of the casing.

Management

Many studies have determined that lid hygiene appears to be quite beneficial, and less toxic, in treating superficial Demodex infestations. However, the mites buried deep within the glands are not eradicated to any great extent, and therefore more research must be conducted to find an alternative treatment. Others suggested therapies include cleansing the lid and lid margins with diethylene ether, applying pilocarpine gel, or 1% ophthalmic mercury ointment. None of these methods has proven to be totally effective.

Phthiriasis Palpebrarum

Phthiriasis palpebrarum is an uncommon eyelid infestation by Phthirus pubis (crab louse) and,less commonly,by the Pediculus humanus species, P. humanus var. capitis

(head louse) and P. humanus var. corporis (body louse). The term pediculosis refers to infestation by the two P. humanus species and should not generally be used when referring to eyelid manifestations.

Etiology

Phthiriasis palpebrarum results from lid infestation by P. pubis, the pubic louse. In postpubescent individuals infestation typically occurs in the pubic area, and in children the eyelashes and eyebrows are most commonly involved. In adults phthiriasis is usually transmitted by sexual contact, but in children infestation usually occurs from contact with an infested parent, usually the mother. The lice may also be transferred by fomites such as bedding and towels.The parasite is well equipped for the pubic area or eye region because of its wide body and