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

Remissions and exacerbations are common during the early stages of the disease. Even when symptoms initially affect only one side, bilateral involvement becomes the rule. BEB usually begins in individuals aged 50 to 70 years, with a mean age at onset of 56 years. Almost two-thirds of these patients are female.

Functional incapacitation can be significant, with visual disability as the most incapacitating functional defect in more than 10% of patients. In most patients symptoms become stable within 5 years.

External events can initiate or aggravate the episodes of spasm. These events include stress, driving (especially night driving when faced with oncoming headlights), and bright sunlight. Sleep and other stress-relieving forms of relaxation can alleviate the blepharospasm.

All patients with blepharospasm should receive dry eye testing, because dry eye can exacerbate the spasms. Appropriate dry eye therapy with ocular lubricants or lacrimal occlusion should accompany any other treatment for blepharospasm. The clinician should search for and correct other treatable problems that may exacerbate the disease, such as corneal erosion, foreign bodies, acute glaucoma, uveitis, entropion, eyelash abnormalities, and blepharitis. Emotional problems and neurosis usually are not a significant precipitating cause of blepharospasm in adults but may play a prominent role in affected younger individuals.

The term essential blepharospasm applies specifically to spasms localized to the orbicularis oculi, procerus, and corrugator musculature. Similar dyskinesias can occur in the entire distribution of the facial nerve and in muscles other than those innervated by the facial nerve. These dyskinesias can occur in the lower face, mouth, jaw, neck, and soft palate. Localized self-limited spasm of the orbicularis oculi muscle is termed eyelid myokymia (benign fasciculations).This condition differs from blepharospasm in that it causes a twitch of the lower or upper eyelid muscles and does not cause eye blinking. It is benign and does not progress to eye closure. However, if this eyelid twitching is associated with twitching of the ipsilateral facial muscles with or without eyelid involvement, this could be a potentially serious disorder called facial myokymia. Facial myokymia has been associated with brainstem tumors and demyelinating disease.

When blepharospasm is accompanied by periodic lower facial movement, the disorder is referred to as Meige’s syndrome or idiopathic orofacial dystonia. If the mandible also becomes involved, the disorder is referred to as Breughel’s syndrome or oromandibular dystonia. When several cranial nerves are involved, the disorder is called segmental cranial dystonia. Although often discussed as separate entities, these dystonic syndromes may be the same disease process with variable clinical manifestations.

Hemifacial spasm differs from blepharospasm in that the former is unilateral when fully developed. Hemifacial spasm may begin in the orbicularis oculi

muscle and then slowly spread to other ipsilateral facial muscles. Unlike blepharospasm, which sleep may relieve, hemifacial spasm continues during sleep. As with blepharospasm, hemifacial spasm occurs in middleaged individuals and is more common in women. Hemifacial spasm rarely may be associated with a posterior fossa tumor and therefore necessitates appropriate neuroimaging.

Management

Before appropriate treatment for blepharospasm can be administered, a correct diagnosis must be made. In the early stages of the disease a patient’s condition often is misdiagnosed, and he or she is assigned a diagnosis of a psychogenic disorder such as neurosis and is referred to a psychiatrist or psychologist. Ophthalmic therapy includes treating any underlying ocular condition and using spectacle-mounted ptosis crutches. Adjunctive pharmacotherapy may include such medications as antiparkinsonism drugs (e.g., levodopa with carbidopa [Sinemet], bromocriptine [Parlodel], orphenadrine [Norflex]), anticholinergic drugs (e.g., trihexyphenidyl [Artane] or benztropine [Cogentin]), muscle relaxants (e.g., baclofen [Lioresal]), benzodiazepines (diazepam [Valium] and clonazepam [Klonopin]), antidepressants (e.g., lithium [Lithobid]),anticonvulsants (e.g.,carbamazepine [Tegretol] or valproic acid [Depakene]), antihistamines, the antiserotonin cyproheptadine, tranquilizers (e.g., haloperidol [Haldol]), and beta-blockers (e.g., propranolol [Inderal]). Only one-third of patients may be satisfied with one or more of the listed medications. In addition to these measures, emotional or psychological counseling may prove effective for patients having difficulty adjusting to or accepting their condition or its treatment.

Information on emotional and psychological support can be obtained from the Benign Essential Blepharospasm Research Foundation, Inc., P.O. Box 12468, Beaumont, TX 77726-2468 or at its website (www.blepharospasm.org).

Botulinum Toxin. The most effective nonsurgical treatment for both BEB and hemifacial spasm is botulinum toxin. Botulinum toxin works by inhibiting calciumdependent release of acetylcholine at the neuromuscular junction, causing muscle paralysis. Of patients receiving botulinum toxin injection, 69% to 100% demonstrate clinically significant improvement. Currently, there are two U.S. Food and Drug Administration–approved botulinum toxins: botulinum toxin type A (Botox, Botox Cosmetic) and botulinum toxin type B (Myobloc).

Each vial of Botox contains 100 units botulinum toxin. In its nonreconstituted form, the toxin can remain stable for up to 4 years.The recommended diluent for reconstitution is sterile nonpreserved 0.9% sodium chloride. The reconstituted toxin deteriorates within a few hours and, if not used immediately, should be refrigerated (2 to 8°C).

378 CHAPTER 22 Neuro-Ophthalmic Disorders

Table 22-7

Dilution of Botulinum Toxin

aDiluent = 0.9% NaCl injection.

Modified from Physicians’ Desk Reference, ed. 59. Montvale, NJ:Thompson PDR, 2005:562–565.

The diluent of sterile normal saline is drawn up in a syringe and gently injected into the vial containing the Botox. Rapid forceful injection that causes frothing or other mechanical stress is discouraged because this can inactivate the toxin. Table 22-7 gives the recommended dilutions calculated for an injection volume of 0.1 ml.

Without previous anesthesia and avoiding penetration of the orbital septum, the diluted Botox typically is injected subcutaneously or intramuscularly, using a 27or 30-gauge needle. The most commonly used dilution is 2.5 units per 0.1 ml of volume at each injection site. In patients with blepharospasm, the initial injection sites should include the medial and lateral pretarsal orbicularis oculi of the upper eyelid and the lateral pretarsal orbicularis oculi of the lower eyelid (Figure 22-16). Patients with hemifacial spasm should receive similar injections to any affected muscles of the lower face (Figure 22-17). The cumulative dose of Botox in a 30-day period should not exceed 200 units.

Muscle mass affects the toxin’s response. More toxin is needed locally to produce a desired effect in areas of increased muscle mass. Histologic examination of orbicularis oculi musculature after treatment with botulinum toxin shows no evidence of alteration of muscle fiber diameter, disruption of internal muscle architecture, or pathologic changes in the motor end plates.

Figure 22-16 Sites of botulinum toxin injections in patient with blepharospasm.

Figure 22-17 Sites of botulinum toxin injection in patient with hemifacial spasm.

In addition to titrating the injection dose for desired effect, the practitioner can also modify the injection sites. If the corrugator and procerus muscles are affected, the toxin may be injected in the glabellar region.

The initial effect of the injections usually occurs within 3 days and is maximal 1 to 2 weeks after treatment. The therapeutic effectiveness of Botox in patients with blepharospasm lasts 6 to 28 weeks, with most patients becoming symptomatic again in approximately 3 months. The average interval between injections is longer in patients with hemifacial spasm, sometimes up to 6 months. With repeated injections the therapeutic interval decreases in some patients but appears to stabilize in most after the fourth or fifth injection.This reduction in efficacy may result from the toxin’s binding to the nonactive large protein chain, a resprouting of motor end plates, or the development of an antitoxin.

Unfortunately, there is no simple and readily available assay for botulinum antibodies. The frequency of detectable botulinum antibodies has been found to range from 3% to 5%, with evidence that increased dose and reduced interval between injections are related to the presence of antibodies. Often, the clinician must increase the botulinum toxin dose to maintain the same effect with subsequent treatments. A mean 50% increase in dose may be required for patients with BEB over the first six injections, with no further increase required with later treatments. If a treatment produces an unexpected shorter interval of relief after several good responses from earlier injections, it is likely that the former duration of effect will be reestablished with subsequent treatments. It is possible that the total cumulative toxin dose

might be a factor in the development of antibodies. The incidence of antibodies has been found to increase in a cumulative dose-dependent manner from 4% with a 1-year cumulative dose of less than 500 units to 100% at a dose of greater than 2,000 units.This suggests that even small doses of toxin given over very long periods might induce the development of antibodies. Repeat injections should be delayed as much as possible to avoid cumulative effects.

Myobloc is available premixed in a clear colorless to light yellow sterile solution. It is available in three dosing volumes: 2,500 units/0.5 ml, 5,000 units/1 ml, and 10,000 units/2 ml. It can remain stable under refrigeration for up to 21 months. Myobloc exists at pH 5.6 when in aqueous solution. This relatively acidic pH can cause increased discomfort in patients during injection. Myobloc has been found to have a less complete or shorter duration of muscle paralysis compared with Botox.

Botulinum toxin is contraindicated in patients with a known allergy to the drug or with infection or inflammation at the proposed injection sites. Safety for use during pregnancy or lactation has not been established. Other contraindications include poor patient cooperation, coagulopathy (including pharmacologic anticoagulation), and other neuromuscular diseases such as myasthenia gravis or amyotrophic lateral sclerosis (Lou Gehrig’s disease). Both Botox and Myobloc contain pooled human albumin to stabilize the active ingredient.Therefore individuals with allergy to eggs should not receive botulinum toxin.

The most frequently encountered local side effect, occurring in up to 40% of patients, is exposure keratitis resulting from decreased blinking and lagophthalmos. Ptosis is the second most common side effect and results from the toxin’s direct effect on the levator palpebrae superioris muscle. Avoiding injection of the middle of the upper eyelid and adjacent eyebrow region can reduce or eliminate this outcome. Effective treatment for the induced ptosis includes topical 0.5% apraclonidine (Iopidine), which is administered four times daily for approximately 1 month. Apraclonidine stimulates Müller’s muscle by activating the α1-adrenergic receptors. If allergy to apraclonidine develops, the patient may use naphazoline until the major effect of the botulinum toxin subsides and the ptosis resolves.

Other side effects include pain at the injection site, ecchymosis, increased tearing, ectropion, entropion, dry eye symptoms, and diplopia. Avoiding injection of the middle or the entire lower eyelid may alleviate some of these side effects.

Adverse events in patients who receive botulinum toxin injections for hemifacial spasm are virtually identical to those that occur in treatment of BEB. However, diplopia and lower facial weakness are more common in patients with hemifacial spasm.

Surgery. Surgical treatment is a viable option for patients who cannot tolerate repeated botulinum toxin injections or for those who have an inadequate response. Effective procedures for blepharospasm include selective facial myectomy involving removal of the muscles that close the eyelids and strengthening of the muscles that open the eyelids. In some individuals, modified upper eyelid surgery, such as blepharoplasty and limited myectomy or blepharoplasty with levator advancement, may prolong botulinum toxin’s duration of effect.

Surgery for hemifacial spasm involves microvascular decompression of the facial nerve by placement of a sponge under posterior fossa vessels (Jannetta procedure). Surgery for hemifacial spasm is associated with cure rates exceeding 80%, and beyond 2 years there appears to be little risk of relapse. However, surgical intervention can have serious complications such as permanent facial paralysis, deafness, stroke, and even death.

SELECTED BIBLIOGRAPHY

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Engel AG, ed. Myasthenia gravis and myasthenic disorders. New York: Oxford University Press, 1999.

The Ischemic Optic Neuropathy Decompression Trial Research Group. Optic nerve decompression surgery for non-arteritic arteriole ischemic optic neuropathy (AION) is not effective and may be harmful. JAMA 1995;273:625–632.

Kline LB, Bajandas FJ, eds. Neuro-ophthalmology review manual, ed. 5.Thorofare, NJ: SLACK Incorporated, 2004.

Lipham WJ. Cosmetic and clinical applications of botulinum toxin.Thorofare, NJ: SLACK Incorporated, 2004.

Loewenfeld IE.The pupil: anatomy, physiology, and clinical applications, vols. 1–2. Boston: Butterworth-Heinemann, 1999.

Miller NR, Newman JB, eds. Walsh & Hoyt’s clinical neuroophthalmology, ed. 6, vols. 1–3. Philadelphia: Lippincott Williams and Wilkins, 2005.

Optic Neuritis Study Group. Highand low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis.Arch Ophthalmol 2003;121:944–949.

Optic Neuritis Study Group.The clinical profile of optic neuritis. Experience of the optic neuritis treatment trial. Arch Ophthalmol 1991;109:1673–1678.

Skorin L, Larsen K, Eggers D.Temporal arteritis. Contemp Optom 2006;4:1–8.

Eyelid disorders are among the most common abnormalities encountered by primary eye care practitioners. Because of their high prevalence and the fact that eyelid diseases are often associated with significant symptoms, adjacent tissue involvement, or even systemic manifestations, the practitioner must be able to recognize and treat these disorders.This chapter considers the etiology, diagnosis, and management of the more clinically significant eyelid conditions.

CLINICAL ANATOMY AND PHYSIOLOGY OF THE EYELIDS

An understanding of eyelid anatomy and function aids in the diagnosis and management of lid pathology. Figure 23-1 shows the major anatomic features of the eyelid.The lids are mobile structures comprising three separate tissue layers; epithelium/conjunctiva, muscle, and connective tissue.They are lined anteriorly by the dermis and posteriorly by conjunctiva. Deep to the dermis is the muscular layer which comprises the orbicularis oculi, the levator palpebrae superioris, and Müller’s muscle. Cranial nerve VII innervates the orbicularis muscle, which is primarily responsible for normal involuntary blinking and tight eyelid closure. Cranial nerve III innervates the levator, which elevates the upper eyelid. Müller’s muscle is innervated by sympathetics carried on cranial nerve III; its function is to augment the action of the levator.

The eyelids play an important role in the production, excretion, and spreading of tears. Goblet cells within the palpebral conjunctiva are responsible for the mucin component of the tear film. The superior and inferior tarsal plates are composed of dense connective tissue. They are responsible for giving the lids their convex shape, which is necessary for adequate tear movement during each blink, and for protecting the orbital cavity from penetration by bacteria or other foreign material. Contained within the tarsal plates are the meibomian glands, sebaceous glands that secrete oil. They may be seen in a single row, which marks the mucocutaneous junction, termed the gray line, just posterior to the

eyelashes, and are responsible for the lipid component of the tear film. Riolan’s muscle, a smooth muscle that surrounds each gland orifice, is thought to play a role in secretion.The gray line delineates the lid into anterior and posterior lamella,which is an important landmark in defining eyelid margin disease. The eyelashes (cilia) emerge from individual follicles, surrounded by the glands of Zeis (sebaceous) and Moll (modified sweat glands).

Anterior Lid Margin

Blepharitis

Blepharitis is a broad term that refers to a collection of lid margin inflammatory disorders that cause changes in adjacent or surrounding structures and often includes, or is associated with, dermatologic conditions such as seborrhea and rosacea. The etiology remains poorly understood despite a strikingly high prevalence in the population; it has been reported that approximately 590,000 patients per year seek care due to blepharitis, and it is estimated that 20 million people suffer from this disorder worldwide.

Classifying blepharitis is a challenge. Many patients present on a continuum rather than in a specific disease category, and they tend to have varied and sometimes overlapping clinical signs and symptoms.There have been many proposed classification schemes over the years, yet none has gained widespread popularity. Currently, blepharitis in all its forms is usually defined by anatomic location: anterior/posterior to the gray line or lateral/ medial canthus. Secondary descriptors are usually attached that define potential etiology. Box 23-1 displays the descriptive scheme used in this chapter.Anterior blepharitis, also referred to as “marginal,”may be infectious and/or “seborrheic” in nature. Posterior blepharitis consists of two forms of meibomian gland dysfunction (MGD), meibomitis or meibomianitis, which is inflammatory, and meibomian seborrhea, which is not.Angular blepharitis is the term used when the inflammation is located in the lateral or medial canthal areas. It is most often infectious; however, it may also be associated with atopy.

Box 23-1 Eyelid Margin Disease

Anterior lid margin

Infectious, bacterial, staphylococcal blepharitis Angular

Medial

Lateral

Seborrheic blepharitis

Mixed seborrheic–staphylococcal blepharitis Posterior lid margin

Meibomian gland dysfunction

Meibomian seborrhea Meibomitis

Primary Secondary

Modified from Smith RE, Flowers CW Jr. Chronic blepharitis: a review. CLAO J 1995;21:200–207; McCulley JP, Dougherty JM, Deneau DG. Classification of chronic blepharitis. Ophthalmology 1982;89:1173–1180; and Wilhelmus KR. Inflammatory disorders of the eyelid margins and eyelashes. Ophthalmol Clin North Am 1992;5:187–194.

Care must be taken when diagnosing a patient with blepharitis, especially in the elderly.There are some striking morphologic changes that occur to the lids with aging that do not necessarily signify pathology. The lid margins become slightly thicker with advancing age, the lids become more vascularized, the upper lid may become more rounded, telangiectasia and hyperkeratinization are often more evident, and gland orifices may narrow and pout.

The exact etiology of eyelid margin disease remains poorly understood, making the diagnosis and treatment a frustrating endeavor for both the patient and the eye care professional. Blepharitis in most forms has no cure, and treatment is meant to quell the acute phase only.

Infectious, Bacterial, Staphylococcal Blepharitis

Etiology. Microbiologic studies of lid flora in control and blepharitis patients determined that the most common bacteria isolated from both groups were staphylococcal epidermidis (S. epidermidis), Propionibacterium acnes, and Corynebacterium sp. S. aureus was cultured more often in the infectious and mixed varieties of

blepharitis, thus suggesting its potential role as a causative agent in at least these patients.

Infectious blepharitis is thought to be caused by a direct infection from bacteria that are either found in greater quantity, are more virulent in nature, or are pathogenic in certain individuals. It has also been postulated that patients with atopy or other dermatologic conditions (e.g., rosacea) are more likely to have blepharitis and are more prone to staphylococcal infections. Currently, S. aureus remains the primary suspect in bacterial and mixed variety blepharitis, although the exact mechanism remains a mystery.

For many years S. aureus exotoxins have been considered the cause of associated conditions such as blepharokeratoconjunctivitis. It has been determined that all Staphylococcus species produce exotoxins, and because these species are found on the lids of both normal and blepharitis patients, they are most likely not primarily responsible for the findings. More recent evidence suggests that an abnormal blink mechanism or destabilization of the tear film due to bacterial lipolytic enzyme pathways and increased hydrolysis of phospholipids may be the cause. It has also been shown that a delayed hypersensitivity to these toxins can produce the marginal keratitis seen in many patients.

Diagnosis. Hard, “dry,” brittle, fibrinous scales, often called collarettes, found surrounding the lashes and on the lid margin, characterize staphylococcal blepharitis (Figure 23-2).These scales resemble a “collar”surrounding the lash at its base.This finding is not to be confused with the tubular “sleeves” found at the base of the eyelash typical of a Demodex infestation. Scurf is another commonly used term for flaking on the lashes and by definition is typically used to describe dandruff seen on the scalp or the greasy scales on the lids of seborrhea blepharitis patients. Typically, patients with infectious blepharitis

Figure 23-3 Telangiectasia or “rosettes” seen on the lower lid in infectious blepharitis.

show significant hyperemia of the lid margin, caused by the dilation of fine vessels, termed telangiectasia or “rosettes” (Figure 23-3), which appears much greater than that found in noninfectious blepharitis varieties. Symptoms include foreign body sensation, matting of the lids upon awakening, itching, burning, and tearing. Hard crusts surrounding the individual lashes at their base characterize the less common ulcerative type of staphylococcal blepharitis. Removing these crusts often exposes small ulcers, and bleeding may occur. In chronic staphylococcal blepharitis associated findings may include loss of lashes (madarosis),misdirection of lashes (trichiasis),irregular or thickened lid margins (tylosis ciliaris) (Figure 23-4), and poliosis (whitening of the cilia).

Associated conditions may include papillary conjunctivitis; keratoconjunctivitis sicca (KCS), present in as many as 50% of patients; superficial punctate keratitis (SPK), affecting predominantly the inferior quadrant of the cornea;

384 CHAPTER 23 Diseases of the Eyelids

marginal infiltrates or ulcers; and phlyctenular keratitis. Patients with staphylococcal blepharitis are also more prone to develop an acute infection in the glands of Zeiss (external hordeola or stye) or meibomian glands (internal hordeola).

Management. The most important step in successful management is comprehensive patient education and lid hygiene. Staphylococcal blepharitis can become chronic; thus it should be treated aggressively.The patient needs to understand that treatment is meant to control the condition rather than cure it.There are two phases of treatment: the initial acute phase and the long-term management phase.The first phase of therapy may be expected to last at least 2 to 8 weeks and consists of vigorous treatment to bring the condition under control. The long-term phase aims at keeping the signs and symptoms in check and should last indefinitely.

Lid hygiene consists of hot compresses, lasting 5 to 10 minutes and performed two to four times daily, followed by lid scrubs using a mild detergent cleanser such as baby shampoo and a washcloth or prepackaged commercially available lid scrubs (Box 23-2). Dilution of the shampoo is not necessary unless the patient has an unfavorable reaction to full strength. The hot compresses serve to loosen lid debris and dilate blood vessels to allow increased blood flow to the area. The scrubs not only facilitate removal of debris but also serve to lyse bacterial membranes and to reduce the bacterial load. Antibiotic ointment should then be applied directly to the lid margin two to four times daily. Antibiotic drops are used when a secondary conjunctivitis is also present.

Sulfonamides, though previously popular, are not recommended because only 30% of S. aureus strains cultured from the lids are sensitive. Bacitracin and erythromycin ointment are each effective against both S. aureus and S. epidermidis; therefore they have become the treatment of choice. Aminoglycosides, such as gentamicin and tobramycin, have also been used; however, many Staphylococcus isolates are now resistant to aminoglycosides and long-term treatment can lead to medicamentosa. The combination of trimethoprim and polymyxin B, as well as the fluoroquinolone ciprofloxacin 0.3%, has also been reported to be an effective treatment option. When writing the prescription it is important to specify that the drug should be applied to the lid margins two to four times daily and not simply placed into the cul-de-sac.

Treatment must be intense for 2 to 8 weeks and then tapered to the lowest effective dosage for maintenance. Whichever antibacterial agent is chosen as initial therapy, it is important to alternate treatment using a different antibiotic on consecutive weeks or months to avoid or minimize the development of resistant organisms. Prescribing below the recommended dosages can also

Box 23-2 Instructions for Lid Hygiene

Warm compresses

1.Dip a cloth washcloth in hot tap water, being careful to test the heat against your wrist to prevent a burn.

2.Place this compress against your closed eyelid for 45–60 seconds.

3.Repeat steps 1 and 2 for a total of ~10 minutes. Lid massage

1.Immediately after the warm compresses and with the eyes closed, place a finger on top of the closed upper eyelid just below the brow.

2.With a rolling motion, roll the finger in a downward direction toward the eyelashes. Continue this across the entire lid to be sure all glands are “milked” in a downward motion.

3.Follow the same procedure for the lower lid except roll the finger in an upward motion.

Lid scrubs

1.Immediately after applying the warm compresses and/or lid massage, wrap a finger or two in the washcloth.

2.Using a no-tears baby shampoo (dilute the solution if irritation occurs) form lather on the washcloth.

3.With the eyes closed, gently scrub the lids and eyelashes, in a horizontal motion from left to right, for approximately 20 passes across each lid.

4.Rinse the eye area with clean water.

Modified from McCulley JP. Blepharoconjunctivitis. Int Ophthalmol Clin 1984;24:65–77.

lead to resistance. In treatment-resistant cases a culture of the lids and conjunctiva should be performed.

Associated toxic epithelial keratitis should respond to blepharitis treatment. Topical steroids are generally not required unless the cornea is significantly involved or a phlyctenule is present. In this case prednisolone 0.12% used two or three times a day for a few days may be used. Combination steroid–antibiotic ointments, such as tobramycin–dexamethasone or the topical combination drop tobramycin–loteprednol, may prove to be useful for those patients complaining of excessive itching and burning. Steroids control the hypersensitivity component that is often present and reduce the congestion and irritation that often provoke the patient to rub the eye and aggravate the blepharitis.

Patients need to understand the importance of complying with the recommended therapy. Because of complications associated with chronic staphylococcal

blepharitis, the importance of early and effective treatment cannot be overemphasized.

Angular Blepharitis

Etiology. Angular blepharitis is caused by infection with

Staphylococcus, Moraxella, Candida, or, rarely, herpes simplex virus.

Diagnosis. The characteristic signs of angular blepharitis include chronic hyperemia, desquamation, and ulceration of the lateral,and sometimes medial,canthal regions (Figure 23-5). Simultaneous involvement of the conjunctiva often occurs. Symptoms include irritation and tenderness of the involved area.

Management. Angular blepharitis usually responds to classic blepharitis treatment; however, if this fails a suspected Moraxella infection must be considered. Topical fluoroquinolone ointments such as ciprofloxacin may be useful.

Seborrheic Blepharitis

Etiology. Seborrheic dermatitis is often associated with seborrheic blepharitis, which is typically low grade and chronic. Seborrheic dermatitis is a very common skin condition that involves sebaceous glands of the head (Figure 23-6), ears, and flexural creases. It is marked by a change in the quantity or quality of gland secretions, termed sebum on the body and meibum on the lids. Pityrosporum ovale (P. ovale), hormones, infection, nutrition, and/or stress may all be causative factors.Treatment that eradicates P. ovale improves seborrhea, but whether

the yeast is causative is still unclear and how eradication relates to blepharitis treatment is unknown. Previously, it was postulated that Demodex folliculorum played a large role in the lid disease process; however, there is no statistically significant difference in the isolation rates of D. folliculorum between seborrheic blepharitis patients and unaffected patients.

Diagnosis. Seborrheic blepharitis may be so minimal that the clinician must examine the face for further evidence of seborrhea or look for signs of dandruff, the most common presentation of seborrhea. History may also be helpful, because patients may recall episodes of erythema and tenderness, particularly in the areas of the forehead and the sides of the nose. Seborrheic blepharitis tends to have a long course with less obvious exacerbations and remissions than one sees when microbes are involved.The lid margins may or may not be particularly hyperemic. Greasy scales, called scurf, are noted on the lid margin (Figure 23-7) and often on the skin of the lid above. Patients report symptoms of a foreign body sensation, mattering, and burning that persists for a longer duration than reported in staphylococcal blepharitis.

Figure 23-5 Inflammation of temporal bulbar conjunctiva and excoriation of outer canthus (arrow), characteristic of angular blepharoconjunctivitis.

Figure 23-6 Seborrheic dermatitis in a classic distribution at hairline and between eyebrows and nasolabial folds. (From Habif TP. Psoriasis and other papulosquamous diseases. In: Clinical dermatology, a color guide to diagnosis and therapy, ed. 4. Philadelphia: Mosby, 2004:244.)

386 CHAPTER 23 Diseases of the Eyelids

Figure 23-7 Greasy lashes and scurf in seborrheic blepharitis. Note the external hordeolum (stye) on the lower lid margin (black arrow). (From Kanski JJ. Eyelids. In: Clinical ophthalmology: a systematic approach. Philadelphia: Butterworth-Heinemann, 2003:10.)

Seborrheic blepharitis may be found in isolation, in conjunction with staphylococcal infection, or with posterior blepharitis with or without inflammation of the glands.

Associated conditions may include KCS, SPK (typically over the lower one-third of the cornea), and/or marginal corneal infiltrates or ulcers.

Management. As with infectious blepharitis the first step in successful management is explaining the longterm nature of the condition and the importance of lid hygiene (refer to the treatment for staphylococcal blepharitis above).After improvement, the patient should continue daily warm water washcloth scrubs, preferably in the morning, to maintain control.

Seborrheic dermatitis on the scalp (dandruff) usually responds to frequent shampooing with over-the-counter products containing 3% to 5% sulfur and 2% to 3% salicylic acid. For the face and body topical cream preparations containing 3% sulfur and 3% salicylic acid or 1% topical glucocorticoids are effective. In addition, a topical preparation containing antifungal agents has also been used. A dermatologic consultation should be obtained if these are not effective or if seborrhea is reported elsewhere on the body. Follow-up is necessary, especially when topical medications are used around the eyes. In a reported case, the use of fluocinonide cream to the scalp and forehead along with ketoconazole shampoo caused a transient band-like keratopathy in a patient being treated for seborrheic dermatitis. Care should also be taken when using topical steroid cream on the face because prolonged contact with the skin can cause atrophy and telangiectasia formation.

In resistant cases of seborrheic blepharitis, bacterial superinfection must be considered and an antibiotic ointment may be added to the regimen if indicated.

Associated KCS should be treated using artificial tears and lubricants.

Mixed Seborrheic–Staphylococcal Blepharitis

Most cases of blepharitis involve a combination of staphylococcal and seborrheic changes. The patient should be instructed carefully in appropriate lid hygiene techniques and the application of antibiotics as previously described. In addition, the patient should be referred for treatment of the dermatitis. An over-the-counter dandruff shampoo should be recommended.

Posterior Lid Margin

Meibomian Gland Dysfunction

The meibomian glands are modified sebaceous glands that are imbedded in a single row within the tarsal plate. There are approximately 20 to 25 glands in the lower lid and 30 to 40 in the upper lid. Each meibomian gland orifice is surrounded by a muscle of Riolan that acts as a sphincter for the retention and release of meibum. Gland function is governed in part by neuronal control, vascular regulation, and hormones; blinking is also thought to contribute to the release of meibum.

Etiology. Meibomian gland secretions are responsible for the lipid component of the precorneal tear film. The chemical composition of meibum and/or the lipase action of the normal lid bacteria is thought to contribute to or cause blepharitis and in many cases the dry eye that accompanies it. The composition of meibum has been found to be different in normal and blepharitis patients, and there is a distinct difference between the types of MGD as well. Most studies of lid flora in bacterial blepharitis cases did not find any appreciable isolates from meibum that were not found as normal flora on the lids, therefore disproving the theory that the meibomian glands act as a bacterial reservoir.

There are two forms of clinically relevant MGD: meibomian seborrhea and meibomitis/meibomianitis. Meibomian seborrhea has been defined as either excessive secretion of or easily expressed meibum. The composition of the meibum makes the secretions in this group of patients very fluid and toxic to the cornea. In contrast, meibomitis is divided into two distinct clinical forms: secondary and primary. Secondary meibomitis is glandular dysfunction occurring in a random fashion, and primary meibomitis refers to MGD that affects all the meibomian glands. Either condition may be associated with staphylococcal blepharitis and with seborrhea or rosacea. Both entities are thought to be forms of obstructive MGD.This obstruction may be due to a blockage in the meibomian gland orifices by keratinized epithelial cells or due to an alteration in the meibum, leading to stagnation and perhaps infection.All forms of MGD cause multiple symptoms of varying degrees and should be considered carefully in all cases of dry eye syndrome.

Diagnosis. In meibomian seborrhea the symptoms frequently outweigh the clinical signs. Symptoms are described as being worse upon awakening. The glands and the easily expressed meibum appear normal; however, the clinical sign of bulbar injection and foam in the tear film support the likelihood that the chemical composition of the meibum has changed. Biomicroscopy may disclose a thickened oily layer of the precorneal tear film. Although meibum is released at a basal rate, further production occurs with blinking. It is theorized that nonblinking during sleep causes retention of secretions; upon first awakening the initial blinks release the stored secretions containing elevated levels of oleic acid, which causes the ocular irritation.

As mentioned previously, meibomitis is infectious in nature and may be primary or secondary. Either type may be associated with staphylococcal blepharitis and with seborrhea or rosacea. Meibomian gland changes are not always accompanied by significant inflammatory signs, and the condition may be easily overlooked.Although the clinical findings can vary considerably, symptoms usually consist of irritation, chronic burning, stinging, foreign body sensation, or mild conjunctival injection.

Signs of meibomitis include inspissated orifices of the meibomian glands (Figure 23-8A), cloudy or thickened yellow-white meibomian secretions on gland expression, “frothy” tear film (Figure 23-8B), hyperemia, mild papillary conjunctivitis, and thickened rounded eyelid margins. SPK of the cornea and conjunctiva in the interpalpebral space is associated with an unstable tear film evidenced by a markedly reduced tear breakup time.

Management. The most effective treatment for MGD involves relieving any obstruction of the meibomian ducts and orifices by digital massage and gland expression two

to four times daily. The practitioner can perform this treatment in the office and instruct the patient in the proper technique for meibomian expression at home. Digital massage involves manually “massaging” the glands by rolling a finger placed over the glands, in a downward motion for the upper lid and upward motion for the lower lid. The application of hot compresses before gland expression is usually more effective in promoting normal gland flow. In moderately severe cases, lid hygiene and meibomian gland expression bring immediate, albeit temporary, relief of symptoms.

Oral tetracycline has become adjunctive therapy for moderate to severe cases of MGD.The drug is prescribed at a dosage of 250 mg four times a day initially and then tapered over the course of 3 to 4 months. Once the condition is controlled, low maintenance dosages of 250 mg daily may be required to ensure long-term control. Tetracycline appears to reduce the quantity of enzymes produced by bacteria residing on the lid margin, which reduces free fatty acids in the sebum and thus stabilizes the tear film. This alteration of free fatty acids can be accomplished without dosages high enough to kill the organisms. Minocycline and doxycycline have also been shown to be effective. Pregnant women and children under 12 years of age should be given erythromycin rather than tetracycline due to its detrimental effect on bone formation and tooth discoloration. In a recent study, N-acetylcysteine was given orally at a dosage of 100 mg three times a day for 8 weeks and was found to improve tear film stability by altering lipid metabolism. More research is needed to support this claim but results look promising, and it may one day become a viable treatment option.

Recently, a commercially available all-in-one therapy became available that packages a foaming lid cleanser