The anterior lamella is delimited by the skin on the anterior surface and the gray line or Marx's line posteriorly. The anterior lamella is usually affected by staphylococcal species and/or seborrhea, which can lead to ocular surface disease. Posterior lamellar lid disease, or posterior marginal blepharitis, is a condition of the eyelid margin characterized by meibomian gland dysfunction, which may lead to ocular surface disease as well. Both forms of blepharitis may be inflammatory, noninflammatory, or even infectious. The majority of cases are associated with hyperemia and thickening of the lid margin.

Significant findings include lid-margin inflammation, dry flakes (dandruff) or oily secretion on the eyelashes and lid margins, and concomitant dandruff of the scalp, eyebrows, and external ears (Fig. 1). A mild, fine, medium, or blotchy epithelial keratitis can also occur. Seborrhea is frequently associated with Staphylococcus aureus infections (see later discussion on mixed blepharitis).

Controversy exists as to the role played by Pityrosporum ovale and Pityrosporum orbiculare in the etiology of seborrhea. These budding yeasts are plentiful in scrapings from seborrhea; in AIDS patients with severe seborrheic dermatitis, 2% ketoconazole cream significantly decreases the number of organisms and greatly improves the condition.¹

Mild forms of seborrhea require only control of the scalp seborrhea with over-the-counter antiseborrheic shampoos, such as Head and Shoulders, Selsun Blue, or Exsel.

In patients with severe seborrheic blepharitis, do the following:

1. Culture the lid margins to rule out superimposed S. aureus infections, and institute vigorous antiseborrheic lid-margin treatment.
   
2. Instruct the patient to remove the seborrheic flakes and oil at least once daily by vigorous scrubbing of the lid margin with a mild soap (e.g., Johnson's No Tears Shampoo, Dove soap, or Almay Non-Oily Eye Makeup Remover).
   
3. If S. aureus is present, treat the patient with a suitable antibiotic as well (see later discussion).
   

With increasing age, meibomian gland disease becomes a more common presentation in patients. Most patients have nonspecific complaints inconsistent with the degree of disease clinically evident on examination. Lid margins have focal or diffuse inflammation, with telangiectasia around the meibomian gland orifices. The orifices are pouting, obstructed, displaced, or reduced in number. Digital pressure on the lid margins reveals hyposecreting or hypersecreting glands with a foamy, turbid, granular, or pasty discharge. Chalazia, papillary conjunctival inflammation, and punctate staining of the ocular surface could also be present with abnormal tear break-up time. Clinical presentation may be compounded with associated staphylococcal lid infection, seborrhea, and acne rosacea.³

Management of this chronic condition consists of patient education and lid hygiene with warm compresses and expression of glands every day to alleviate symptoms. In severe cases, patients should take oral tetracycline (250 mg by mouth four times daily), doxycycline (50 mg by mouth twice daily), or minocycline (50 mg by mouth twice daily) for weeks to months. These medications decrease production of bacterial lipases and thus decrease fatty acid levels. Their use is contraindicated in children and in pregnant or lactating women. Associated lid bacterial infections, seborrhea, acne rosacea, and keratoconjunctivitis sicca should be diagnosed and treated appropriately (see later discussion).

STAPHYLOCOCCAL LID INFECTIONS

Staphylococcal blepharitis is not self-limited and is difficult to eradicate successfully.⁴ It is a common cause of chronic conjunctivitis, recurrent epithelial keratitis, and recurrent morbidity. The patient is frequently beset with symptoms of photophobia, pain, tearing, redness, blurred vision, and discharge.

The infection is characterized by one or more of the following features²:

1. Ulcerations at the base of the eyelashes: The ulceration is preceded by a folliculitis of the pilosebaceous unit. Fibrin, which exudes from the base of the ulcer, usually masks the presence of the ulcer.
   
2. Collarettes: Collarettes are small, thin, fibrinous scales that surround the eyelash like a small piece of paper impaled on a stick. The collarette is formed by the fibrin that covers the base of the ulcer. It usually surrounds the eyelash and may be carried away from the surface of the skin as the lash grows (Fig. 5).
   
3. Localized poliosis or canities (whitening) of individual eyelashes: Poliosis occurs from staphylococcal damage to the pilosebaceous unit (Fig. 6).
   
4. Short, misdirected, broken, sparse, or missing eyelashes: The hair follicles are often damaged by the staphylococcal infection. Lashes produced in damaged hair follicles are often short, misdirected, and broken. Large areas where eyelashes are absent are commonly found.
   
5. External hordeolum (style): An external hordeolum represents an abscess of a gland of Zeis. Pain, redness, and swelling occur. The pain is proportional to the degree of swelling. The abscess points to the skin at the lid margin.
   
6. Internal hordeolum: An internal hordeolum is often caused by a staphylococcal infection. The infection occurs within the meibomian gland and often produces intense pain and swelling. The lesion may eventually drain through the skin or conjunctiva.
   
7. Multiple, recurrent chalazia: Multiple or recurrent chalazia are often caused by staphylococcal infections of the meibomian glands. The staphylococcal infections cause inflammation and edema of the neck of the gland, with resulting inspissation of the meibomian gland and, eventually, chalazion formation.
   
8. Fine, epithelial keratitis: A fine, epithelial keratitis of the lower half of the cornea is commonly associated with staphylococcal blepharitis. The keratitis is more severe in the morning and often clears during the daytime.
   
9. Catarrhal corneal infiltrates or ulcers: Catarrhal corneal infiltrates usually occur at the 2-, 4-, 8-, and 10-o'clock areas of the peripheral cornea. They are usually separated from the limbus by a lucid interval and commonly progress to ulceration of the overlying epithelium. These lesions are sterile and represent immunologic responses to bacterial antigens. The clinical diagnosis of staphylococcal blepharitis is verified by culture, which reveals many S. aureus organisms on the lid margins. The bacterial cultures and antibiotic sensitivity patterns also are useful in suggesting the appropriate antibiotic for treatment.
   

To treat staphylococcal blepharitis, do the following:

1. Direct the patient to remove all fibrinous crusts and discharge from the lid margin with lid scrubs, as described under seborrheic blepharitis.
   
2. Have the patient then apply a suitable antibiotic ophthalmic ointment to the base of the eyelashes at nighttime.
   
3. Continue treatment for 6 weeks, and then reculture the lid margin and change antibiotics as necessary according to the results of the antibiotic sensitivity pattern.
   

In some instances, systemic antibiotics are necessary to control symptoms. Fusidic acid ointment has been shown to be an effective treatment for various staphylococcal species, but this ointment is not available in this country.

The skin of the eyelid may be involved by impetigo contagiosa, infectious eczematoid dermatitis, or staphylococcal scalded skin syndrome.

Impetigo Contagiosa

Impetigo contagiosa of the skin of the eyelid is usually associated with infection of the face. The infection begins as a small macule that enlarges, vesiculates, and then pustulates. Bullae can form and become crusted. The crusts are usually thin and varnish-like, which helps to differentiate the infection from streptococcal impetigo, in which the crusts are thick and honey-colored. The infection is more common in children younger than 6 years of age.

Local treatment of staphylococcal impetigo is usually sufficient. If the diagnosis of staphylococcal impetigo is in doubt, however, treat the patient with systemic antibiotics, since streptococcal skin infections can lead to glomerulonephritis.

For local treatment, do the following:

1. Cleanse the affected area with mild soap and water followed by warm soaks to help loosen the crusts.
   
2. Have the patient apply erythromycin or bacitracin ophthalmic ointment to the involved area two to four times daily.
   
3. If a favorable response is not obtained after 3 to 4 days, change the antibiotic. Systemic antibiotics are sometimes necessary.
   

Infectious Eczematoid Dermatitis

An infectious eczematoid dermatitis is similar to, and often confused with, contact dermatitis. Vesiculation, pustulization, crusting, and lichenification are characteristic. The skin of the entire eyelid may be involved. Conjunctivitis and keratitis can also occur. The patient is sensitized to the staphylococcal products, which serve as haptens.

Topical antibiotic ophthalmic ointment may suffice, although systemic antibiotics such as erythromycin or dicloxacillin (0.250 g) four times daily might be necessary. Topical corticosteroids are deemed by some practitioners to help control the skin eruption.

Staphylococcal Scalded Skin Syndrome

Staphylococcal scalded skin syndrome (Ritter's disease) occurs in young children. The entire body, beginning with the face and the flexural creases of the neck, axilla, and groin, is involved. The eruption is preceded by a short prodromal period of malaise, fever, irritability, and skin tenderness. A diffuse scarlatiniform erythema develops quickly, followed by separation of the epidermis. A positive Nikolsky's sign is characteristically present.

To treat staphylococcal scalded skin syndrome, do the following:

1. Give oral dicloxacillin (50 to 100 mg/kg/day) in four divided doses or erythromycin base (40 mg/kg/day) in four divided doses.
   
2. Keep the denuded areas moist with sterile Burow's solution or normal saline solution.
   

MIXED BLEPHARITIS

Mixed blepharitis is caused by seborrhea with superimposed staphylococcal infection. It is a common condition, and it is probably the most common form of blepharitis. The symptoms and signs of seborrhea and staphylococcal infection are both present. Both conditions are treated as outlined earlier.

ANGULAR BLEPHARITIS (DIPLOBACILLARY BLEPHARITIS, STAPHYLOCOCCAL BLEPHARITIS)

Angular blepharitis is usually associated with angular conjunctivitis of the medial or lateral conjunctiva. Fissuring, scaling, lichenification, and redness are evident at the external or internal canthus. There is usually also a mild mucoid discharge.

In warm climates, the diplobacillus of Morax-Axenfeld (Moraxella [Moraxella] lacunata), a large, gram-negative, square-ended bacillus that usually occurs in pairs, is implicated as causing the infection. In colder climates, however, S. aureus is commonly implicated.

Treat the angular blepharitis as outlined earlier under staphylococcal infections.

β-HEMOLYTIC STREPTOCOCCAL LID INFECTIONS

Impetigo contagiosa, caused by β-hemolytic streptococcus, may spread from the face to the eyelids. The infection is superficial and similar in many respects to staphylococcal impetigo, except that in the former the bullae tend to rupture more readily, the crusts are thicker and honey-colored, and there is usually a more pronounced regional lymphadenopathy. However, the two forms can be accurately differentiated only by cultures. Acute glomerulonephritis can be associated with streptococcal impetigo, mandating that the infection be treated with systemic antibiotics (e.g., oral dicloxacillin; erythromycin stearate or free base [0.250 g] four times daily).¹

Erysipelas is a comparatively deep skin infection caused by Streptococcus pyogenes. It is characterized by warm, red, swollen lesions with sharply raised, readily outlined borders. Vesicles or bullae are often present. Associated systemic symptoms and signs are headache, joint pains, chills, and fever. Treat erysipelas with systemic antibiotics, as outlined under impetigo contagiosa.

Infectious eczematoid dermatitis may be caused by streptococcal infections. It is similar to infectious eczematoid dermatitis caused by staphylococcal infections, and should be managed in a similar fashion.

PSEUDOMONAS SPECIES, PROTEUS SPECIES, AND COLIFORM ORGANISMS

The lid margin of the immunocompromised host occasionally is infected with gram-negative rods, such as Pseudomonas sp., Proteus sp., or coliform organisms. The diagnosis is made by culture, since the infection produces no identifying features. In many instances these organisms can be cultured from healthy-appearing lid margins.⁵

Have the patient use lid scrubs, as outlined earlier, followed by the application of gentamicin or other suitable antibiotic ophthalmic ointments, depending on the findings of the antibiotic sensitivity pattern.

In neonates and severely immunocompromised patients, ecthyma gangrenosum, a circumscribed, ulcerated, hemorrhagic lesion caused by Pseudomonas sp., can occur on the eyelid.⁵ The lesions can cause extensive sloughing of the eyelid. Patients with ecthyma gangrenosum must have their immunosuppression reversed, when possible, and should be treated with intravenous (IV) antibiotics, such as gentamicin (3 to 7 mg/kg/day IV) or ticarcillin (200 to 300 mg/kg/day IV).

TUBERCULOSIS

The Mycobacterium tuberculosis can infect the eyelid as a primary infection or by spread of lupus vulgaris from the face. A tuberculous tarsitis can also occur. The primary lesion causes ulceration and regional lymphadenopathy. Lupus vulgaris of the eyelid begins as a translucent nodule that ulcerates centrally and gradually increases in size. A tarsitis can be mistaken for a chalazion. Tuberculosis must be treated with the systemic antituberculous drugs isoniazid (300 mg) and rifampin (600 mg), each given once daily. Ethambutol (15 mg/kg/day) or streptomycin (0.75 to 1 g once daily) may be added as a third drug if isoniazid resistance is suspected.⁶

LEPROSY

Thinning or loss of the eyebrows or eyelashes often occurs in Hansen's disease. Lagophthalmos or anesthetic, infiltrated macules or nodules can also be seen. A combination of systemic dapsone and rifampin are the drugs of choice. The lagophthalmos is treated by a tarsal-strip procedure or a tarsorrhaphy.

SYPHILIS

The chancre of primary acquired syphilis rarely occurs on the lid or lid margin. The chancre begins as a small, firm, infiltrated lesion that erodes and oozes a stringy, nonpurulent exudate. The edges have a cartilaginous consistency. The lesions are painless, evolve slowly, and heal without treatment after 3 to 6 weeks.

The skin of the eyelids can develop a macular or papular eruption in association with the generalized rash of secondary syphilis. Pustules and ulcerative lesions can also occur, along with temporary syphilitic alopecia of the eyebrows and lashes. The skin eruption spontaneously fades as the secondary stage ends.

In rare cases, benign tertiary syphilis involves the eyelid in the form of a gumma. The lesion begins as a deep swelling, with minimal surrounding inflammation, which eventually ulcerates to form exuberant granulation tissue. Scarring, which can be severe, occurs centrally. A tarsitis can also occur, but characteristically without involvement of the overlying conjunctiva.

Prenatal (congenital) syphilis can involve the eyelid in the form of a papular eruption, ulceration, rhagades, or a gumma. Temporary madarosis is also possible. Penicillin remains the treatment of choice in syphilis.

Sexually transmitted diseases other than syphilis that affect the eyelids include chancroid (caused by Hemophilus ducreyi), which causes a soft chancre; granuloma inguinale (granuloma venereum), which produces a chronic granulomatous ulcer of the eyelid and progresses to severe destruction; and lymphogranuloma venereum, which produces elephantiasis by blocking the lymphatic drainage of the eyelid.

YAWS

The primary lesion of yaws is a nonindurated, moist papule surrounded by smaller papules. This lesion or secondary lesion, which develops into a granulomatous, fungating, cauliflower-like mass, can occur on the eyelids. Yaws responds to penicillin.

PINTA

The primary lesion of pinta (a scaly plaque resembling psoriasis) or the secondary lesion (a slate-blue, gray, or black papillary growth) can occur on the eyelids. Pinta also responds to penicillin.

DIPHTHERIA

Eyelid involvement in diphtheria can occur in association with a membranous or pseudomembranous conjunctivitis or as a primary skin infection. The latter usually begins as a clear vesicle with surrounding erythema, which quickly sloughs to form a gray membrane. Corynebacterium diphtheriae responds to penicillin or erythromycin, but the patient must be treated with antitoxin to prevent neurologic complications.

CUTANEOUS ANTHRAX

Anthrax appears as a circumscribed, carbuncle-like lesion when fully developed. The lesion begins as a small reddish macula that progresses to an indurated papule, and then vesiculates or pustulates to form the typical, carbuncle-like lesion with a black eschar. The surrounding edema is usually severe. The treatment of choice is penicillin, which must be started early.

GLANDERS

Glanders appears as a vesicular or carbuncular lesion. It can involve the upper or lower eyelids, or both. The lesion can spread progressively through the entire substance of the eyelid to involve the globe. Regional lymphadenopathy, with chronic draining sinus formation (farcy buds), is an associated finding. Signs of septicemia typically develop, followed by death.

Glanders may also manifest as a milder, more localized, chronic infection that develops on the eyelids and canthi; in some instances, other areas are involved. Glanders responds to systemic penicillin, erythromycin, or chloramphenicol. Surgical drainage should also be considered.

CLOSTRIDIAL INFECTIONS

Clostridium perfringens and Clostridium tetani can cause cellulitis of the eyelid. The infection develops after local lid trauma, especially when necrotic tissue is present. These organisms are anaerobic, gram-positive, spore-forming rods. These infections must be treated with specific antitoxin, as well as antibiotics.

CHLAMYDIAL INFECTIONS

The treatment of choice is systemic tetracycline or azithromycin (Zithromax). The eyelids are secondarily involved in lymphogranuloma venereum conjunctivitis through blockage of the lymphatic drainage system during the course of the conjunctivitis. Elephantiasis of the eyelids is commonly found. The organism is one of the causes of Parinaud's oculoglandular syndrome. The treatment of choice is systemic tetracycline.

RICKETTSIAL INFECTIONS

Occasionally, the primary lesions of scrub typhus occur on the eyelids. The lesions can be vesicular, ulcerative, or gangrenous. Secondary lesions on the eyelid include a petechial macular or maculopapular rash. Systemic tetracycline is the drug of choice.

Ringworm (tinea faciale) can affect the eyelid primarily or spread to the eyelid from other parts of the face. The early lesions begin as flattened, reddish papules that spread peripherally while the central area heals.⁷ The fully developed lesion has a ring-like appearance, with a reddish, scaly, sharply defined border and a central pinkish scaly area. The lesions usually respond to topical salicylic acid (1%) and precipitated sulfur (3%) in hydrophilic ointment twice daily for 3 to 5 days. Oral microcrystalline griseofulvin can also be of value.

The granulomatous lesions of coccidioidomycosis can affect the eyelid. The lesions can also be verrucous and can be associated with subcutaneous abscesses. Systemic amphotericin B is the drug of choice for treating disseminated coccidioidomycosis.

North American blastomycosis lesions of the eyelids are characterized by granulomatous ulcers with thick crusts and an underlying purplish color. The eyelids are usually involved by extension from lesions of the face. Amphotericin B or ketoconazole are effective in the treatment of blastomycosis.

Sporotrichosis, characterized by a primary ulcer and secondary nodular lesions that occur along the lymphatic channels draining the site of the primary lesion, is responsive to systemic iodides.

Cryptococcosis arises in immunosuppressed patients and can affect the skin of the eyebrow, forehead, and eyelids. Papules, nodules, infiltrative plaques, pustules, ulcers, or subcutaneous abscesses are possible. Attempts at reversing the immunosuppression should be undertaken, and systemic amphotericin B should be given.

Rhinosporidiosis rarely affects the eyelid. The lesion begins as a papilloma or subcutaneous nodule which, as it grows, becomes pedunculated, wart-like, or verrucous in character. The lesion should be removed surgically and the base cauterized.

Verruca vulgaris, the common wart, frequently appears on the eyelid, especially on the lid margin. The lesion may be pedunculated or broad-based, and it is often multilobulated. When located on the lid margin, a mild papillary conjunctivitis and a mild, fine, epithelial keratitis is often present. Excision of the lesion and cauterization of the base is often curative, although recurrences are possible.

Herpes simplex virus can infect the lid either as a primary or recurrent infection. The infection is characterized by vesicles on an erythematous base that usually progress to ulcers. Regional lymphadenitis usually occurs in the primary infection. An acute follicular or pseudomembranous conjunctivitis is often seen in the primary form of infection, but occurs only rarely in the recurrent form; corneal dendrites can occur in either form. Cleansing of the eyelid with cool saline solution is helpful. Many practitioners recommend a prophylactic topical antiviral agent (e.g., trifluridine 1% [Viroptic Ophthalmic Solution]), which is instilled into the conjunctival sac five times daily to prevent the development of corneal lesions.

Herpes zoster virus involvement of the ophthalmic branch of the fifth cranial nerve often affects the upper eyelid, whereas involvement of the maxillary branch often affects the lower eyelid. The lesions have a dermatomal distribution and are vesicular, and later ulcerative, in character. Pre-eruptive and posteruptive pain is often a predominant feature of the disease. The lesions often result in scarring. Treatment with systemic acyclovir is indicated.

The lesions of chickenpox (varicella zoster virus) can involve the lid and lid margin. The papulovesicular lesions, which lead to crusts, are in all stages of development during the infective phase of the disease.

Orf (ecthyma contagiosum), a large umbilicated, painless, dark-red papule, can involve the eyelid. The infection is self-limited and is caused by a poxvirus that produces contagious pustular dermatitis in sheep.

Measles and other childhood exanthemata can involve the eyelid during the disseminated phase of the illness. The macular, papular, ulcerative lesions are similar to the lesions in other parts of the body. Severe eyelid edema can also be evident.

Demodex folliculorum is commonly associated with blepharitis, but its true role in infection is unknown. It is perhaps sometimes associated with itching. The presence of “sleeves,” which are thin, tube-like processes that are transparent and that extend from the skin over the proximal end of the eyelash for 0.5 to 1 mm, is diagnostic. Periodic lid scrubs using Johnson's Baby Shampoo or ether can eradicate or reduce the number of organisms.

Leishmaniasis of the eyelid usually occurs in the form of cutaneous leishmaniasis (Oriental sore). The infection appears as a specific granuloma of the skin, and begins as a small, slow-growing papule that ulcerates and crusts. Secondary infection commonly causes severe destruction. The lesions occur in moist and dry form. The moist form is more acute, characterized by the formation of an ulcer; the dry form is chronic, characterized by the presence of fine, paper-like scales on the surface of the lesion. Solitary lesions of cutaneous leishmaniasis usually heal spontaneously, but healing might be accelerated by the use of metronidazole.

Loa loa, the African eyeworm, occasionally causes Calabar swellings in the eyelid during its period of wandering throughout the body. The drug of choice is diethylcarbamazine because it kills both adult and larval forms of the organism. When feasible, surgical removal of the adult worm is advisable.

Onchocerciasis is characterized by eyelid edema in the early phase of the infection. Later, severe pruritic dermatitis and intense photophobia can occur, followed by the development of subcutaneous nodules that occasionally involve the eyelid, especially in patients from Central and South America. Removal of nodules on or about the head help to reduce the worm load and, when combined with medical therapy, is valuable. Vermectin should also be used in therapy.

Ascaris lumbricoides and other roundworms usually affect the eyelid by producing an anaphylactic reaction causing edema and urticaria. The reaction responds to systemic treatment of the roundworm infection.

ATOPIC DERMATITIS

Atopic dermatitis presents as an acute, subacute, or chronic, itchy, erythematous eruption of the skin that is moist and becomes vesicular; often there are crusted areas. The face and lid margins are frequently involved, resulting in a blepharoconjunctivitis and keratitis.

S. aureus is frequently present as a secondary invader. Treatment consists of glucocorticoids, cold compresses, topical vasoconstrictors, and cromolyn. S. aureus, when present, must also be treated as discussed earlier.

CONTACT DERMATITIS

The thin and delicate lid tissues are particularly susceptible to a variety of irritants, including cosmetics, topical medications (e.g., neomycin, atropine, epinephrine), plants, and some industrial chemicals. In some cases, a mild follicular conjunctivitis is associated with the eczematoid lid inflammation. Management should be directed at identifying the offending agent, followed by avoidance of the agent. Topical glucocorticoids are also of value on a short-term basis.

ACNE ROSACEA

Acne rosacea is a chronic inflammatory disorder that is usually limited to the face, causing an acneiform eruption, telangiectasis, and hypertrophy of the skin (Fig. 7). Lid and conjunctival involvement are common, as manifested by hyperemia and dilation of the vessels and signs of staphylococcal infection of the lid margin. The condition should be managed by treatment of the staphylococcal infection and the use of oral tetracycline, ampicillin, or metronidazole. Triggers, such as hot or spicy foods, strong drinks, and sunlight, should be identified and avoided.

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