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Blepharitis, Meibomitis, and Hordeola

Establishing the diagnosis

Etiology

  • Chronic lid margin inflammation is likely multifactorial
    • Staphylococcal blepharitis
      • Chronic colonization with low grade infection and/or inflammatory reaction to bacterial antigens and toxins
      • Includes aerobic and anaerobic species – Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, Corynebacterium
    • Seborrheic blepharitis
      • Mechanical obstruction caused by scaling of eyelid margin
      • Cyclical process with obstruction causing inflammatory changes of the eyelid
      • From overproduction of sebum, causing greasy scaling
    • Demodicosis
      • Demodex mites are common incidental inhabitants of lash follicles.
      • Mites may introduce bacteria or primarily exacerbate inflammation.
      • Mites are frequently seen in eyelid colarettes (Gao, 2005).
    • Meibomian gland dysfunction (MGD)
      • Similar processes cause inflammation of the posterior eyelid margin.
      • Altered meibomian gland secretions result in gland blockage.
      • Decreased lipid layer in tear film and abnormal lipids contribute to ocular and eyelid inflammation and dry eyes.
      • Can be associated with rosacea or seborrheic dermatitis
    • Chalazion
      • Plugging/inspissation of a meibomian or Zeis gland results in trapping of sebaceous material.
      • The trapped material elicits inflammation, typically granulomatous.
      • May have an infectious component, as described for staph blepharitis
      • Staphylococcus aureus is most common pathogen
      • Lash sampling was performed to microscopically count mite populations
        • In 44 adult and 47 pediatric patients with chalazia and 34 adult and 30 pediatric age- and sex-matched patients without chalazia (Liang, 2014)
        • Demodicosis was defined as presence of mites, present in 69% of chalazion patients, compared with 20% of controls. 
        • Demodex brevis was significantly more prevalent than demodex folliculorum in patients with chalazia.
        • Chalazia with demodicosis had signficantly more common recurrence after excision
        • Patients with past history of rosacea were excluded from the study.  
      • Terminology can be confusing – hordeolum is inspissation and infection of sebaceous glands
      • Anterior lid (glands of Zeis, lash follicles): external hordeolum or stye
      • Posterior lid (meibomian glands): internal hordeolum

Epidemiology

  • Blepharitis
    • May be changing as the epidemiology of staph species continues to change
    • Role of community acquired MRSA is increasingly important
    • Older literature suggested that staphylococcal disease occurs in younger individuals (McCulley 1985)
    • Overall, blepharitis incidence increases in incidence with age (Driver 1996)
    • In 1982, 590,000 patient visits were due to blepharitis (NDTI 1982).
    • Blepharitis is observed in 37–47% of ophthalmologists’ and optometrists’ practices (Hom 1990, Lemp 2009)
    • Keratoconjunctivitis sicca was found to be associated in 25–50% of cases (McCulley 1982 and 1985).
  • Chalazia occurs in all ages, races, and sexes.

History

  • Blepharitis and meibomitis
    • Burning, itching, and foreign body sensation
    • Usually worse in the morning
    • Redness of the eyelids
    • Crusting of the eyelids
    • Filmy, blurred vision
    • Recurrent chalazia/hordeola
  • Chalazia
    • Acute inflammation: rapid onset, mild pain, focal tenderness, and erythema
    • Resolution can occur prior to the development of the chronic phase.
    • Can fluctuate in size
    • Can spontaneously drain posteriorly or anteriorly
    • Blurred vision secondary to induced astigmatism with lid swelling
    • Chronic form can follow, consisting of a painless, well-circumscribed mass within the tarsal/pretarsal eyelid
    • Can present with pyogenic granuloma as mass or bleeding

Clinical features

  • Blepharitis
    • Hard scales and crusts around eyelid cilia called “sleeves” or “collarettes.”
    • Staphylococcal debris and white blood cells congealed together and colonization by Demodex folliculorum (Favier, 2017)
    • Seborrheic inflammation causes oily or greasy crusting
    • There is a 95% incidence of associated seborrheic dermatisis (McCulley 1985). Manifests as yellow crusting also on eyebrows and scalp
    • Erythema and telangiectasis of eyelid margins
    • Poliosis
    • Madarosis
    • Trichiasis
    • About 1/3 have keratoconjunctivitis sicca (Edwards 1987)
    • Ocular surface inflammation can cause abnormal tear meniscus, abnormal tear break up time, foamy discharge, debris in tear film
    • Conjunctival hyperemia and papillary reaction of tarsal conjunctiva
    • Corneal changes such as punctate epithelial keratopathy, marginal infiltrates, phlyctenules
    • Notching and thickening of the eyelid
  • Meibomian gland dysfunction or meibomitis
    • Inflammation of posterior lid margin
    • Eyelid margin irregularity, scalloping, and thickening
    • Prominent telangiectasis
    • Pouting or plugged meibomian gland orifices
    • Turbid, thick secretions (“toothpaste-like”)
    • Foamy tear meniscus
    • Conjunctival hyperemia, and often papillary reaction
    • Corneal changes such as punctate epithelial keratopathy, marginal infiltrates, pannus
    • Can have margin rounding, notching, dimpling, thickening, irregularity
    • Arita et al (2016) developed a grading scale to describe severity of meibomitis
      • Telangiectasia – 0 = no findings; 1 = mild telangiectasia; 2 = moderate telangiectasia or redness; 3 = severe telangiectasia or redness.
      • Meibomian gland collapse – 0 = minimal; 1 = moderate; 2 = severe
      • Irregularity, plugging, foaming, and thickness (each graded separately) – 0 = none; 1 = mild; 2 = severe. 
      • Gland dropout was the most consistent evidence of severity. 
  • Chalazia
    • Overlying skin can have erythema
    • Important to evert eyelid; nodule on the tarsal conjunctival surface
    • Loculation of inflammatory material can cause chronic cyst-like nodule 
    • Can localize anteriorly
    • Elevated nodules may be near lid margin or up to 10 mm away (upper eyelid)
    • Surrounding edema, erythema might indicate treatment fopreseptal cellulitis

Testing

  • Usually diagnosed clinically
  • Several techniques to quantify meibomian gland dropout:
    • Meiboscopy — clinical examination with transilluminated biomicroscopy of the glands (Robin 1985)
    • Meibography — near-infrared light and camera capture images of the glands (Figure 1)

Figure 1. Top: Meibography of a normal eyelid. Bottom: Abnormal dilation of meibomian glands in a patient with meibomian gland dysfunction.

    • Confocal microscopy
  • Cultures are generally not helpful
    • Yield is higher with frank purulence
    • Staph epidermidis may be interpreted as normal flora even if clinically significant
    • Culture for MRSA can support treatment, if oral antibiotics prescribed for acute signs of infection
    • Demodex mites can be visualized by epilating lash, place on a glass slide, add a drop of fluorescein, place cover slip (Kheirkhah, 2007)
    • Histopathologic confirmation of demodicosis for atypical, persistent, or recurrent lesions.

Risk factors

Blepharitis

  • Dry eye syndrome
  • Dermatologic conditions: e.g., seborrheic dermatitis
  • Rosacea
  • Oral retinoid therapy
  • Demodicosis
  • Giant papillary conjunctivitis

Chalazia/Hordeola

  • Rosacea
  • Chronic posterior blepharitis (meibomian gland dysfunction)
  • Demodex might be a risk factor (Yam 2014).

Differential diagnosis

Malignant tumors

  • Sebaceous gland carcinoma
  • Basal cell carcinoma
  • Squamous cell carcinoma
  • Merkel cell carcinoma (Rawlings 2007)
  • Hemangioendothelioma (Al-Faky 2011)
  • Plasmacytoma (Maheshwari 2009)
  • Renal cell carcinoma (Tailor 2008)
  • Pleural mesothelioma (Tsina 2006)

Benign tumors

  • Pleomorphic adenoma (Ramlee 2007)
  • Granular cell tumor (Scruggs 2014)
  • Solitary neurofibroma (Shibata 2012)
  • Plexiform neurofibroma (Tey 2006)
  • Pilomatrixoma (Katowitz 2003)
  • Keratoacanthoma
  • Papilloma
  • Ruptured epithelial inclusion cyst

Inflammatory disorders

  • Sarcoidosis
  • Atypical mycobacterial infection
  • Wegener granulomatosis (Ismail 2007)
  • Ruptured epithelial inclusion cyst
  • Hyperimmunoglobulinemia E (Job) syndrome (Destefano 2004, Crama 2004)

Infectious

  • Preseptal cellulitis
  • Canaliculitis (Almaliotis 2013)
  • Tuberculosis (Mittal 2013)
  • Leishmaniasis (Rahimi 2009)

Other

  • Retained soft contact lens (Agarwal 2013)
  • Trichilemmal cyst (Meena 2012)
  • Lacrimal gland duct stones (Kim 2014)

Patient management: treatment and follow-up

Natural history

  • Blepharitis
    • Chronic, with periods of exacerbation and remission
    • Can begin in childhood, although typically onset is in middle age
    • If severe, can cause eyelash loss, scarring of eyelids, trichiasis, secondary corneal scarring
  • Chalazia
    • Typically self-limiting, resolving in 1–2 weeks
    • Chronic form may develop which can take many months to years to resolve.
    • Eventually, virtually all chalazia resolve, even after years (Honda 2010).

Medical therapy

Blepharitis

  • Eyelid hygiene
    • Warm compresses
    • Scrubs with water, dilute baby shampoo or commercially available eyelid wipes once or twice daily depending on severity
  • Olenik study (Olenik 2013):
    • Randomized double-blinded trial of baby-shampoo eyelid cleaning and preservative-free artificial tears with placebo or 1.5 gram of a composition (DHA, EPA, vitamins A, C, and E, tyrosine, cysteine, glutathione, zinc, copper, manganese, selenium, DPA)
    • Measurements of staining, tear breakup time, Schirmer test, eyelid inflammation, ocular surface disease index (OSDI), meibomian gland expression
    • After 3 months (64 patients), there was significant improvement of OSDI, TBUT, eyelid margin inflammation, meibomian gland expression, Schirmer test.
    • For staphylococcal blepharitis treat with topical antibiotics, for example, erythromycin or bacitracin ophthalmic ointment
  • Topical azithromycin ophthalmic solution 1%
    • Has anti-inflammatory properties
    • Studies have shown improvement for anterior and posterior blepharitis — open label studies (John 2008, Luchs 2008, Haque 2010, Opitz 2011).
    • Dosing schedules are varied – 1 gtt BID x 2 days, then qday for 7–28 days (Opitz 2012)
  • A multicenter, randomized study comparing Tobradex ST (4x/day x 14 days) to Durasite (2x/day x 12 days) for blepharitis favored Tobradex (Torkildsen 2011)
  • Ivermectin cream 1% can reduce demodecosis (Favier, 2017)
  • Ivermectin can be administered orally at a dose of 200 mcg/kg once, repeated in 7 days
    • Reduces demodex folliculorum in refractory blepharitis (Holzchuh, 2011)
    • Available as 3 mg tablet – 170 lb. (77 kg) adult would take 15 mg or five pills
  • Minocycline or doxycycline 50–100 mg BID can be considered for chronic meibomitis
    • Can taper to qday after the first month
    • Slow-release formulation (50 mg qday) might be effective
    • Alternatives include tetracycline 500 mg BID or azithromycin 250–500 mg, 1–3x/week; or 1g qweek x 3 weeks (caution in patients with cardiac conduction abnormalities)
    • Treatment based on small clinical trials on symptoms improvement with ocular rosacea (Frucht-Pery 1993, Sobolewska 2014)
      • Evidence of improving blepharitis symptoms (Dougherty 1991, Shine 2003)
  • Short course of topical corticosteroids can be used when inflammation is severe.
  • Eyelid thermal pulsation system (LipiFlow)
    • Device uses pulsatile “milking” movements and application of heat to each eyelid
    • A single treatment (12 minutes) can have improvement in ocular surface disease index (OSDI).
    • Has been shown to be more effective than heat (warm compresses) alone
    • No randomized controlled studies
  • Xdemvy (lotilaner 0.25%, Tarsus Pharmaceuticals, Irvine, CA) was approved in 2023 for the treatment of Demodex blepharitis.
  • 6-week treatment course, administered as 1 drop two times per day into the affected eye.
  • GABA-receptor inhibitor that directly targets the parasite causing paralysis and eventual death of the mite.

Meibomitis

  • 150 patients with clinical evidence of meibomitis were randomized into three groups, treated for one month with doxycycline 200 mg BID, doxycycline 20 mg BID, or placebo (Yoo, 2005).
    • The study did not assess lid changes.
    • Both treatment groups had improvement in tear breakup time and Shirmer test, compared with placebo.
  • Quaterman reported improvement in eyelid inflammation at 12 weeks in open label trial of doxycycline 100 mg daily for 12 weeks (Quaterman, 1997). 
  • Aronowicz (2006) treated 16 meibomitis patients with 50 mg minocycline daily for 2 weeks, followed by 10 weeks of 100 mg daily.
    • Assessed appearance of the eyelids, degree of meibomian gland plugging and amount of secretion
    • Noted improvement in eyelid margin thickening and vascularization
    • Decrease in eyelid margin debris and less meibomian gland obliteration
    • Effect continued three months after cessation of the medication.
  • Igami (2011) treated 13 meibomitis patients who had not responded to topical corticosteroids and antibiotics with oral azithromycin.
    • In 3 cycles of 500 mg/day for 3 consecutive days at 7-day intervals
    • Using eyelid scoring system that measured severity of eyelid debris, telangiectasias, mucous secretion, and eyelid margin edema and erythema
    • Found clinical improvement, except eyelid edema, thirty days after completion of therapy
  • Once weekly azithromycin, 1 gram orally for three weeks, was assessed in 32 patients with meimobitis, using subjective improvement as the primary end point (Greene, 2014).
    • Concurrently continued treatment with topical steroid drops and compresses
    • At mean 5 week follow-up 75% reported symptomatic improvement
    • GI upset was the most common side effect (9%)
  • Literature assessment by the American Academy of Ophthalmology concluded that there is no level I evidence to support use of oral antibiotics including doxycycline, minocycline or azithromycin for meibomian gland related ocular suface disease (Wladis, 2016).

Chalazia/Hordeola

  • Warm compresses and eyelid massage
  • Eyelid hygiene/scrubs
  • Topical antibiotics may be of value in treating staphylococcal blepharitis component.
  • Systemic antibiotics are active against Staphylococcus aureus for accompanying preseptal cellulites.
  • Systemic tetracyclines for treatment of chronic accompanying meibomitis, rosacea
  • Topical or systemic tetracyclines can help improve meibomian secretions.
  • Topical steroid can be used to decrease inflammatory component of skin (although not demonstrated in any studies).

Surgery

Blepharitis

  • Intraductal meibomian probing (that is, Maskin probe) (Maskin 2010)
    • Topical anesthetic or injected local anesthetic placed into the eyelid
    • Start with 2-mm probe (Figure 2)

Figure 2. Maskin probe usage. Penetration through orifice with 2-mm probe. Note hemorrhage at orifice of adjacent gland.

    • Can encounter resistance at meibomian gland orifice and within gland (fibrovascular tissue)
    • Normal to have droplet of blood at orifice
    • Then repeat with 4-mm probe
    • Can be also done with hyfrecation tip (Figure 3) (Wladis 2012)
  • Anatomic changes resulting in trichiasis or entropion might require surgical correction.

Figure 3. Meibomian probing. Image courtesy Edward J. Wladis, MD.

Chalazia/Hordeola

  • Intralesional/perilesional corticosteroid injection
    • Can be used for small marginal lesions or other lesions
    • Multiple randomized controlled studies assessing injection versus excision (Ben Simon 2011, Goawalla 2007, Jacobs 1984)
      • Can have similar rates of resolution, although Jacobs reported much higher rate of complete resolution with surgery (60% versus 8.7%)
      • Multiple injections may be needed
    • Can use 40 mg/mL or 10 mg/mL triamcinolone and inject 0.05 to 0.15 cc
    • Most studies do not use a chalazion clamp at time of injection.
  • Surgical drainage via a transconjunctival or cutaneous route
    • Anesthetic
      • Especially with small lesions, consider marking the skin prior to injection; otherwise, the location of the chalazion can be masked after infiltration.
      • Consider using a pledget with 4% lidocaine (plain) between the globe and chalazion to help dull the pain of injection.
    • Incision and curettage
      • Chalazion clamp is placed on the eyelid to isolate the chalazion, and the eyelid is everted.
      • Bard Parker #15 or #11 blade is used to make a stab incision through the posterior tarsal plate.
      • Can be vertical or an “x;” some surgeons excise the flaps of the “x;” others leave them.
      • Liquid and gelatinous material is expressed.
      • Curettage can be performed with a chalazion curette.
      • Excise granulomatous tissue and cyst wall especially in chronic forms with little or limited liquid/gelatinous material
      • Caution to prevent violation of the skin.
    • Cutaneous excision
      • In cases of cutaneous changes (erythema, infiltration, thinning), limited excision of skin might be needed to resolve the lesion.
      • Use caution in dark-pigmented patients because the visible scar can be more pronounced.
      • Because the source of the chalazion is in the tarsal plate, this must also be addressed in addition to the skin.
    • Trephination
      • Through the conjunctival surface, a “punch” biopsy trephine can be used (Leachman).
      • With the trephine (2–5 mm diameter), center it over the visible lesion, and then slowly rotate the trephine while applying pressure.
      • Be careful to prevent penetration past the tarsal plate.
      • Once through the full thickness of tarsus, use scissors and forceps to excise.
  • Margin lesions
    • Some suggest marginal curettage (Dubey).
      • After placement of an appropriately sized clamp, the curette is placed into the chalazion and curetted.
      • The remainder of the proximal chalazion is approached in the “standard” fashion.
      • Care should be taken not to communicate the 2 areas to prevent notching.
  • Combined excision and corticosteroid injection
    • After excision is completed, some authors advocate for intratarsal injection of steroid.
    • Best done with clamp in place to prevent embolization of steroid material
  • Biopsy for recurrent or atypical lesions
    • Caution for any atypical lesions in either appearance or history
    • Concern for malignancy or other atypical lesions

Preventing and managing treatment complications

Topical corticosteroids

  • Increased intraocular pressure, cataract, infection
  • Prevent by using lowest strength and dose possible for only brief period when inflammation severe

Systemic tetracyclines

  • Photosensitization, gastrointestinal (GI) upset, azotemia, candidiasis
  • Use is contraindicated in children and pregnant or nursing women.
  • Taper based on clinical response and use the lowest dose possible.
  • Cases of doxycycline induced Stevens-Johnson syndrome have been reported (Cac, 2007; Lau, 2011).
  • Pseudotumor cerebri has been reported (Winn 2007).

Pyogenic granuloma formation

  • Occurs in the presence of an underlying chalazion/hordeolum
  • After excision of pyogenic granuloma, also excise the chalazion.

Globe perforation

  • Results in severe visual loss
  • Perforation during excision — 2 cases (Shiramizu 2004)
  • Perforation during injection — 1 case (Hosal 2003)

Eyelid margin scarring or notching

  • Use care when removing tissue at or near the lid margin because there is a risk for eyelid scarring or notching.
  • Can revise severe scar or notch with full-thickness pentagonal wedge resection
  • Horizontal scarring of tarsal plate
    • Some suggest prevention by making only vertical incisions along meibomian gland.
    • Make an enlarged excision of involved tarsus to prevent vertical shortening of eyelid.
  • Repeated episodes or surgical treatments can lead to posterior lamellar scarring and misdirected eyelashes or eyelash loss.

Damage to surrounding meibomian glands

  • Prevent by making vertical cuts through tarsal conjunctival surface.

Intralesional corticosteroid injection for chronic lesions (chalazion)

  • Skin depigmentation
    • Maintain deep (intratarsal or suborbicularis oculi) level of medication.
    • Caution in dark-skinned patients
  • Visible steroid (white sediment of triamcinolone) (Cohen 1979)
    • Maintain deep (intratarsal or suborbicularis oculi) level of medication.
  • Embolization of steroid to retina
    • Extremely rare — 2 case reports (Yagci 2008, Thomas 1986)
    • Consider use of chalazion clamp during injection to prevent emboli.

Damage to punctum or canaliculus

  • Use caution when excising peripunctal or pericanalicular chalazia.
  • If punctum or canaliculus is violated, repair with silicone stent intubation.

Disease-related complications

Blepharitis

  • Corneal neovascularization and scarring
  • Madarosis
  • Trichiasis, marginal entropion
  • Cicatricial entropion
  • Chalazion
  • Reflex epiphora
  • Can have increased association with some inflammatory diseases, psychologic conditions, hypothyroidism, cardiovascular disease (Nemet 2011)

Chalazia/Hordeola

  • Rarely eyelid scarring with or without trichiasis
  • Eyelid malposition (for example, ptosis from longstanding lesion of upper eyelid)
  • Recurrent lesions
  • Preseptal/orbital cellulitis — with superinfection

Patient instructions

Blepharitis

  • Cure is often not possible eyelid hygiene will likely need to be performed indefinitely.
  • Intermittently, the patient might need more aggressive therapy with topical or systemic medications.
  • Return for recurrence of symptoms
  • Follow-up in 3 to 4 weeks when symptoms severe and new medication is started

Chalazia/Hordeola

  • Prevention of new chalazia with warm compresses, eyelid hygiene
  • Return if chalazion/hordeolum recurs

Historical perspective

  • Meibomian glands first described by Heinrich Meibomius in 1666 (Meibomius)
  • Blepharitis first described by Elschnig in 1908 (Mathers 1991)
  • Radiation therapy has been described, without support of clinical trials

References and additional resources

  1. American Academy of Ophthalmology Cornea/External Disease Panel. Preferred Practice Pattern Guidelines. Blepharitis. 2013. Available at aao.org/ppp.
  2. Basic and Clinical Science Course. Section 4: Ophthalmic Pathology and Intraocular Tumors; Section 6: Pediatric Ophthalmology and Strabismus; Section 7: Orbit, Eyelids, and Lacrimal System; Section 8: External Disease and Cornea, 2013-2014. San Francisco: American Academy of Ophthalmology.
  3. Focal Points: Diagnosis and Treatment of Chronic Blepharitis, Module 10, 1989. San Francisco: American Academy of Ophthalmology.
  4. Monograph 8, Surgery of the Eyelids, Lacrimal System, & Orbit, 2nd edition, 2011. San Francisco: American Academy of Ophthalmology.
  5. Agarwal PK, Ahmed TY, Diaper CJ. Retained soft contact lens masquerading as a chalazion: a case report. Indian J Ophthalmol. 2013;61(2):80-81.
  6. Al-Faky YH, Al Malki S, Raddaoui E. Hemangioendothelioma of the eyelid can mimic chalazion. Oman J Ophthalmol. 2011;4(3):142-143.
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