Blepharitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Blepharitis is characterized by inflammation of the eyelid margins. Blepharitis may be classified according to the anatomic location of the disease into 2 subtypes: anterior and posterior. Additionally, blepharitis may be classified based on the duration of symptoms into either acute or chronic.^[1] The exact pathogenesis of blepharitis is not fully understood. It is thought that blepharitis is caused by either bacterial colonization (Staphylococcus aureus or Staphylococcus epidermidis) in the eyelids or meibomian gland dysfunction. Blepharitis may also caused by allergens and mites that affect the eyelashes.^[2] Blepharitis must be differentiated from conjunctivitis, trichiasis, dry eye syndrome, keratitis, hordeolum, and chalazion.^[3] Blepharitis is usually asymptomatic until the disease progresses. As it progresses, the patient begins to notice a foreign body sensation, itching, irritation, and crusting of the eyelids. Blepharitis can frequently be improved but is rarely eliminated. If left untreated, severe blepharitis may cause loss of eyelashes, scarring of the eyelids, corneal involvement, and ultimately blindness. Common complications of blepharitis include loss of eyelashes, hordeolum, chalazion, corneal ulcer, and conjunctivitis. Blepharitis is associated with a favorable long-term prognosis.^[4] Physical examination of patients with blepharitis is usually remarkable for irritated eyelid edges, crusting of the lashes, entropion, ectropion, poliosis, and diffuse conjunctival injection.^[5] In general, blepharitis is diagnosed based on clinical features alone. There are no diagnostic lab findings associated with blepharitis. Blepharitis is diagnosed based on clinical features alone.^[5][6] Eyelid hygiene and regular cleaning are the mainstay of therapy for blepharitis. Antimicrobial topical therapy may be indicated in some cases depending on the causative pathogen and the underlying cause.^[7][8]

Blepharitis was first described in the late 19th century as “conjunctivitis meibomianae” in a patient with accumulated sebaceous-like material in the meibomian glands.^[3]

Blepharitis may be classified according to the anatomic location of the disease into 2 subtypes: anterior and posterior. Additionally, blepharitis may be classified based on the duration of symptoms into either acute or chronic.^[1]

The exact pathogenesis of blepharitis is not fully understood. It is thought that blepharitis is caused by either bacterial colonization (Staphylococcus aureus or Staphylococcus epidermidis) in the eyelids or meibomian gland dysfunction. Blepharitis may also caused by allergens and lice that affect the eyelashes.^[2][9]

Common causes of blepharitis include bacterial infections, dysfunctional meibomian glands, allergies (less common), and Demodex folliculorum (small parasitic mites).^[3]

Blepharitis must be differentiated from allergic contact dermatitis, conjunctivitis, trichiasis, dry eye syndrome, keratitis, hordeolum, chalazion, rosacea, and sebaceous carcinoma.^[10]

Blepharitis is one of the most common ocular disorders encountered in clinical practice. Up to 20,000 per 100,000 adults over the age of 45 report some discomfort from blepharitis and meibomian gland dysfunction (MGD).^[11]

Common risk factors in the development of blepharitis are dry eye syndrome, dermatologic conditions (acne rosacea, seborrheic dermatitis), demodicosis (chronic blepharitis), lice, and allergies.^[12][13][14]

Screening for blepharitis is not recommended.^[15]

Blepharitis is usually asymptomatic until the disease progresses. As it progresses, the patient begins to notice a foreign body sensation, itching, irritation, and crusting of the eyelids. Blepharitis can frequently be improved but are rarely eliminated. If left untreated, severe blepharitis may cause alterations in the eyelid margin, loss of eyelashes, scarring of the eyelids, conjunctivitis, corneal involvement, superficial keratopathy, and ultimately blindness. Common complications of blepharitis include loss of eyelashes, hordeolum, chalazion, corneal ulcer, and conjunctivitis. In general, blepharitis is associated with a favorable long-term prognosis. Severe blepharitis is rarely associated with permanent alterations in the eyelid margin or vision loss from superficial keratopathy. Therefore, severe blepharitis ​is associated with a poor p​rognosis​.^[4]

A detailed and thorough history from the patient is necessary. Specific areas of focus when obtaining a history from the patient include history of smoking, use of retinoids, prior history of acne rosacea, and history of seborrheic dermatitis. Common symptoms of blepharitis include red, swollen,and itchy eyelids, burning sensation, crusting or matting of eyelashes in the morning, light sensitivity, blurred vision, and oily skin.^[16][8]

Physical examination of patients with blepharitis is usually remarkable for irritated eyelid edges, hard crusting of the lashes, entropion, ectropion, poliosis, and diffuse conjunctival injection.^[5]

There are no diagnostic lab findings associated with blepharitis. Blepharitis is diagnosed based on clinical features alone. Culture of eyelid margins may be indicated for some patients with blepharitis who have recurrent anterior blepharitis with severe inflammation, as well as patients who are not responding to therapy.^[5][6]

Posterior blepharitis overlaps with meibomian gland dysfunction (MGD). Dynamic meibomian imaging (DMI) can be used to obtain a distinct picture of the entire everted inferior tarsal plate in a patient with blepharitis.^[17][18] There are no electrocardiogram, X ray, CT scan, MRI, and ultrasound findings associated with blepharitis.

Other diagnostic studies for blepharitis include Slit lamp examination, tear break up time (TBUT), and measurement of tear osmolarity.^[18][19][20]

Eyelid hygiene and regular cleaning are the mainstay of therapy for blepharitis. Antimicrobial topical therapy may be indicated in some cases depending on the causative pathogen and the underlying cause.^[7]

Surgery is not the first­line treatment option for patients with blepharitis. Surgery is usually reserved for patients with complications, such as chalazion, entropion, ectropion, or horizontal eyelid laxity.^[7][21]

Effective measures for the primary prevention of blepharitis include good self-hygiene and anti-dandruff shampoo.^{[22] [23]}

Secondary prevention strategies following blepharitis include good self-hygiene, anti-dandruff shampoo, removing eye makeup before bedtime, and avoiding eyeliner.^[24]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Blepharitis was first described in the late 19^th century as “conjunctivitis meibomianae” in a patient with accumulated sebaceous-like material in the meibomian glands.

The terminology for blepharitis has evolved alongside the advance in its pathophysiology and treatment. Early terms used to describe related meibomian gland conditions include ophthalmia tarsi, puriform palpebral flux, polyadenitis meibomiana chronica suppurativa, conjunctivitis meibomianae, meibomian seborrhea, keratitis meibomiana, seborrheic blepharoconjunctivitis, meibomian keratoconjunctivitis, meibomianitis, and meibomitis.

The earliest description of blepharitis dates back to 1894, when Lydston reported the clinical entity “conjunctivitis meibomianae” in a patient with accumulated sebaceous-like material in the meibomian glands.^[1]

In 1901, Maklahoff reported another case characterized by dilated meibomian gland openings with pus formation in the glands.^[2]

In 1908, Elschnig described the symptom of meibomian gland hypersecretion which could be relieved by emptying of the glands and the use of astringents.^[3]

In 1921, Gifford isolated Staphylococcus aureus and Bacillus xerosis from meibomian gland cultures of young and elderly individuals, respectively.^[4]

In 1922, Cowper reported a case of “meibomian seborrhea” treated by astringents, yellow oxide, and radiation with only temporary relief.^[5]

In 1942, Scobee noted frequent isolation of staphylococci from meibomian gland cultures in both conjunctivitis patients and normal controls.^[6] This finding suggested that colonization of microorganisms may play a role in the pathogenesis. Scobee also recommended the use of lid massage and adrenalin in conjunction with antiseptic eyedrops to promote drainage of the meibomian glands.

Several terms indicating the site of involvement have been used extensively in the later studies. The term “meibomian gland dysfunction”, suggested by Gutgesell et al. in 1982, gained general acceptance and has been used to describe the spectrum of meibomian gland abnormalities associated with blepharitis.^[7]

Several classifications for blepharitis have been developed on the basis of etiology, anatomy, clinical manifestations, meibography findings, tear osmolarity, and Schirmer testing.

In 1921, Gifford proposed the earliest classification of blepharitis, which divided chronic meibomian gland disease into six categories: 1) hypersecretion, 2) chronic meibomitis, 3) chronic meibomitis with hypertrophy, 4) chronic meibomitis with chalazia, 5) chronic meibomitis secondary to chronic conjunctivitis, and 6) chronic meibomitis with concretions.^[8]

In 1946, Thygeson developed a classification system according to the etiology: 1) seborrheic, 2) staphylococcal, 3) mixed seborrheic and staphylococcal, and 4) blepharitis due to Hemophilus duplex.^[9]

In 1982, the classification was superseded by a more precise scheme developed by McCulley et al. on the basis of clinical criteria: 1) staphylococcal, 2) seborrheic, 3) mixed seborrheic/staphylococcal, 4) seborrheic with meibomian seborrhea, 5) seborrheic with secondary meibomitis, 6) primary meibomitis (also known as meibomian keratoconjunctivitis), and 7) other including atopic, psoriatic, and fungal.^[10]

In 1991, Mathers et al. classified meibomian gland dysfunction based on meibomian gland morphology, tear osmolarity, and Schirmer test: 1) seborrheic, 2) obstructive, 3) obstructive with sicca, and 4) sicca.^[11] Bron et al. utilized morphologic features on slit-lamp biomicroscopy to categorize meibomian gland diseases.^[12]

In 1992, Wilhelmus described a clinically useful approach to classify blepharitis based on the affected location of the lid margin delineated by the gray line (the muscle of Riolan): anterior blepharitis vs. posterior blepharitis.^[13]

In 2003, Foulks and Bron devised a classification for meibomian glad dysfunction that integrated anatomic changes, gland expressibility, biochemical alterations of meibomian gland lipids, and the underlying etiology.^[14]

In 2011, the International Workshop on Meibomian Gland Dysfunction presented a detailed classification system that distinguishes among the subgroups by the level of secretions and further subdivides those categories by potential consequences and manifestations.^[15]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Blepharitis may be classified according to the affected lid structure delineated by the gray line (the muscle of Riolan) into anterior and posterior blepharitis. Blepharitis may be acute or chronic, depending on the acuity of onset and time course of clinical presentation. Alternatively, blepharitis can be classified based on meibomian gland morphology, tear osmolarity, and Schirmer test result into (1) seborrheic, (2) obstructive, (3) obstructive with sicca, and (4) sicca.

A clinically useful approach is to classify blepharitis based on the affected location of the lid margin delineated by the gray line (the muscle of Riolan), which divides the area into the anterior lamella (skin, muscle, eyelash follicles, and glands of Zeis) and posterior lamella (tarsus, conjunctiva, and meibomian glands). According to the affected lid structure and the location of the predominant inflammation, marginal blepharitis can be divided into:^[1][2][3][4]

• Anterior blepharitis

• Anterior blepharitis describes an inflammation of the lid margin anterior to the gray line and concentrated around the lashes. It may be accompanied by squamous debris or collarettes around the lashes, and inflammation may spill onto the posterior lid margin.

• Posterior blepharitis

• Posterior blepharitis describes an inflammation of the posterior lid margin, which may have different causes, including meibomian gland dysfunction, conjunctival inflammation (allergic or infective), and/or other conditions, such as acne rosacea.

Blepharitis can also be classified as acute or chronic, depending on the acuity of onset and time course of clinical presentation:^[5]

• Acute blepharitis

• Acute ulcerative blepharitis

• Acute ulcerative blepharitis is typically caused by staphylococcal infection. It may also be caused by herpes simplex virus or varicella zoster virus.
• Acute nonulcerative blepharitis is usually caused by an allergic reaction (e.g., atopic blepharodermatitis and seasonal allergic blepharoconjunctivitis) or contact hypersensitivity (e.g., dermatoblepharoconjunctivitis).

• Chronic blepharitis

• Chronic blepharitis refers to non-infectious inflammation of unknown cause.

Alternatively, blepharitis may be classified based on three objective criteria—meibomian gland morphology, tear osmolarity, and Schirmer test result:^[6]

• Seborrheic

• Characterized by hypersecretion, normal gland morphology, and low or normal tear osmolarity

• Obstructive

• Characterized by low excretion or high gland dropout on meibography, increased tear osmolarity, and normal Schirmer test result

• Obstructive with sicca

• Characterized by low excretion or high gland dropout on meibography, increased tear osmolarity, and low Schirmer test result

• Sicca

• Characterized by normal gland morphology, increased tear osmolarity, and low Schirmer test result

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

The exact pathogenesis of blepharitis is not fully understood. It is thought that blepharitis is caused by either bacterial colonization in the eyelids or meibomian gland dysfunction. Blepharitis may also be caused by allergens and mites that affect the eyelashes.^[1][2]

The exact pathogenesis of blepharitis is not fully understood. It is thought that blepharitis is caused by either bacterial colonization in the eyelids or meibomian gland dysfunction. However, in most cases of blepharitis, there is a considerable pathogenesis overlap between anterior and posterior blepharitis.

Anterior blepharitis is often associated with staphylococcal infection or seborrhoeic dermatitis. The exact pathogenesis of anterior blepharitis is not fully understood. It is thought that blepharitis is caused by bacterial colonization (Staphylococcus aureus or Staphylococcus epidermidis) in the eyelids. Following bacterial colonization, bacterial lipase changes meibomian gland secretions and increases cholesterol concentration. These changes may result in an environment that affects the ocular surface and tear evaporation. It is thought that anterior blepharitis may also be caused by allergic response to bacterial antigens (mostly staphylococcal antigens).^[1][2]

The exact pathogenesis of posterior blepharitis is not fully understood. It is thought that the abnormal meibomian gland secretions may result in posterior blepharitis. Posterior blepharitis is often associated with skin conditions, such as rosacea or seborrhoeic dermatitis. These conditions are associated with sebaceous glands and gland orifices abnormalities. It is thought that the abnormal meibomian gland secretions may cause a direct toxic effect on the ocular surface. Sebaceous glands abnormalities may also result in an environment that affect bacterial growth.^[3]

Acute blepharitis may be caused by irritant or allergen exposure.^[4]

Demodex folliculorum is an external parasite in hair follicles, sebaceous glands, and meibomian glands. It may cause either anterior or posterior blepharitis. The exact pathogenesis of chronic blepharitis caused by the Demodex mites is not fully understood. It is thought that over-proliferation of Demodex folliculorum in meibomian glands may result in lid-margin infection and ocular discomfort. It is also thought demodex blepharitis may be caused by immune system reactions to the mites leading to inflammation. ^[5][6]

Many diseases are associated with blepharitis such as skin, systemic, and ocular disease. These include:

• Systemic or skin disease:^[7][8]
  • Rosacea
  • Seborrheic dermatitis
  • Atopy
  • Systemic lupus erythematosus (SLE)
  • Sjögren’s syndrome
• Ocular disease:^[7][8][9]
  • Conjunctivitis
  • Meibomianitis (inflammation of the meibomian glands)
  • Keratitis
  • Dry eye syndrome
  • Chalazion
  • Trichiasis

On gross pathology, lid margin swelling, misdirection of lashes, loss of lashes, oily or greasy deposits and crusting of anterior lid margin, , and conjunctival hyperaemia are characteristic findings of blepharitis.^[10]

On microscopic histopathological analysis, non granulomatous inflammation with neutrophils, acanthosis, or parakeratosis are characteristic findings of staphylococcal blepharitis.^[11]

On microscopic histopathological analysis, hyperkeratinization of the meibomian gland ductal epithelium, mononuclear cellular infiltrates, and spongiosis in eyelids are characteristic findings of seborrheic blepharitis.^[12]

On microscopic histopathological analysis, chronic inflammatory changes, epithelial hyperplasia, and follicular plugging are characteristic findings of chronic blepharitis.^[13]

The following are gross images associated with blepharitis:

• 
  Blepharitis of the right eye – By clubtable – Own work (Original text: eigenes Foto), Public Domain, https://commons.wikimedia.org/w/index.php?curid=20138102
• 
  Infant with blepharitis – By Sage Ross – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8978907

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogheneochuko Ajari, MB.BS, MS [2], Sara Mehrsefat, M.D. [3]

Common causes of blepharitis include bacterial infections, dysfunctional meibomian glands, allergies, and Demodex folliculorum.^[1][2]

Common causes of blepharitis include:^{[1][2][3][4][5]}

• Bacterial colonization
  • Staphylococcus aureus (most common)
  • Corynebacterium
  • Staphylococcus epidermidis
• Dysfunctional meibomian glands
• Allergies
• Demodex folliculorum

Blepharitis may be also caused by:^[6]

• Lipoid proteinosis (autosomal recessive condition)
• Periorbital cellulitis
• Dipivefrin

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Blepharitis must be differentiated from other diseases that cause eye itching, irritation, burning, and foreign body sensation such as allergic contact dermatitis, conjunctivitis, trichiasis, dry eye syndrome, keratitis, hordeolum, chalazion, rosacea, and sebaceous carcinoma.

Blepharitis must be differentiated from other conditions associated with eyelid inflammation, including:^[1]

Blepharitis must be differentiated from other diseases that cause red, swollen, and itchy eyes, including:^{[2][3][4][5][6][7]}

• Allergic contact dermatitis
• Allergic conjunctivitis (atopic keratoconjunctivitis)
• Bacterial conjunctivitis
• Viral conjunctivitis
• Trichiasis
• Dry eye syndrome
• Keratitis
• Hordeolum
• Chalazion
• Rosacea
• Superior limbic keratoconjunctivitis
• Contact lens complications
• Sebaceous carcinoma

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Blepharitis is one of the most common ocular disorders encountered in clinical practice and affects more than 180 million people in the United States.

Blepharitis is one of the most common ocular disorders encountered by eye care practitioners.^[1] In the United States, blepharitis is estimated to affect more than 180 million people.^[2] In a United States survey of ophthalmologists and optometrists, it was estimated that 37% and 47% of the patients presented with certain form of blepharitis in clinical practice, respectively.^[3]

The true incidence of blepharitis remains undetermined.

Blepharitis can affect all age groups.^[4][5][6] A single-center study of patients with chronic blepharitis reported a mean age of 50 years.^[7] Compared with other forms of blepharitis, patients affected by staphylococcal blepharitis are relatively young, with a mean age of 42 years.^[8]

Compared with other forms of blepharitis, patients affected by staphylococcal blepharitis are mostly female.^[9]

Blepharitis can affect all ethnic groups.^[10][11][12] There is no racial predilection for blepharitis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Common risk factors for the development of blepharitis include dry eye, acne rosacea, seborrheic dermatitis, and demodicosis.

Risk factors for the development of blepharitis include:

• Dry eye^[1]
• Dermatologic conditions (acne rosacea, seborrheic dermatitis)^[2]
• Demodicosis^[3]
• Isotretinoin^[4][5]
• Giant papillary conjunctivitis^[6]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Screening for blepharitis is not recommended.^[1]

Screening for blepharitis is not recommended.^[1]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sara Mehrsefat, M.D. [2]

Blepharitis is usually asymptomatic until the disease progresses. As it progresses, the patient begins to notice a foreign body sensation, eyelid crusting, itching and irritation of the eyelids. If left untreated, severe blepharitis may cause alterations in the eyelid margin, loss of eyelashes, scarring of the eyelids, conjunctivitis, corneal involvement, superficial keratopathy, and ultimately blindness. Common complications of blepharitis include loss of eyelashes, hordeolum or stye, chalazion, corneal ulcer, and conjunctivitis. Blepharitis is generally associated with a favorable long-term prognosis.

Earlier in the course of blepharitis, patients may be asymptomatic and present with findings of eyelid margin telangiectasia and meibomian gland orifice narrowing.^[1] As the disease progresses, patients usually develop symptoms of foreign body sensation, eyelid crusting, matting of the lashes, tearing, and burning. If left untreated, blepharitis may lead to alterations in the eyelid margin, loss of eyelashes, scarring of the eyelids, corneal involvement (corneal neovascularization and scarring), superficial keratopathy, and eventually blindness.^[2][3]

Complications to blepharitis include:^[4][5][6]

• Hordeolum or stye
• Chalazia
• Corneal ulcer
• Conjunctivitis

In general, blepharitis is associated with a favorable long-term prognosis. Severe blepharitis is rarely associated with permanent alterations in the eyelid margin or vision loss from superficial keratopathy. However, severe blepharitis cases with these complications are generally associated with a poor p​rognosis​.^[7][8]