Cornea: Best practices
July 2023

by Ellen Stodola
Editorial Co-Director

According to Vincent de Luise, MD, blepharitis is one of the most common conditions seen by ophthalmologists. “In one large study of ophthalmology offices, almost 40% of patients had a diagnosis of blepharitis on initial examination,” he said.¹ This inflammation of the eyelid margins can be acute or chronic and has a multitude of etiologies, including allergic, infectious, immune, systemic, and neoplastic causes. Something that adds to the complexity of diagnosing blepharitis is the fact that it may not be symptomatic at presentation. Additionally, blepharitis and dry eye disease often co-exist, which can make diagnosis and stratification confusing and difficult, Dr. de Luise said.

For years, people have been talking about blepharitis, dry eye disease, and meibomian gland disease, said Henry Perry, MD. “Most of us have noticed that sometimes it’s a combination of all three in patients.” He said that James Rynerson, MD, developed a theory that unites dry eye, meibomian gland disease, and blepharitis. They are all related and variations on the same theme. “He thought they all come from bacteria forming biofilm,” he said. Bacteria colonization starts to affect everyone between 2–4 years old. These bacteria continue to increase during one’s lifetime and form biofilms on the eyelid margins that slowly progress. “If they’re on eyelid margins, the first place biofilm would go is the lash follicles, and the lash follicles get inflamed during the teenage or early adult years,” Dr. Perry said, adding that this inflammation of the lash follicles is anterior blepharitis.

The bacterial biofilm continues to migrate into meibomian glands, which leads to meibomian gland dysfunction. Later in life, it reaches into the accessory lacrimal glands and leads to dry eye syndrome (aqueous deficiency). This was discussed in a study by Dr. Perry and Dr. Rynerson in 2016 in Clinical Ophthalmology.²

As far as how common blepharitis is, Dr. Perry said it is basically universal after age 70. The largest studies that have been done were in the military, and they showed that in recruits, usually around age 20, the incidence was 7%. Looking at retirees in their 50s, the incidence went up to 70%.

Breakdown of blepharitis and types

Dr. Perry said the main types of blepharitis were originally described by James McCulley, MD. “Most of us look at blepharitis in terms of being anterior or posterior, and that refers to the lid margin,” he said.

The lid margin can be divided into two parts. The anterior contains the lashes, and the posterior contains the meibomian glands. Anterior blepharitis occurs in younger people, Dr. Perry said, and posterior usually occurs in older people, but it becomes relatively common after the age of 30. For example, 30% of people over age 30 have posterior blepharitis, and 50% of people age 50 have posterior blepharitis. “The way to distinguish them is anterior blepharitis has edema and redness of the lash margin and will form anterior abscesses at the lash margin,” Dr. Perry said. Posterior blepharitis will have pouting of the meibomian gland orifices and often has inspissation of dried secretions and will sometimes form caps of meibum over the gland openings. If left untreated, this will usually cause chalazia or abscesses of the meibomian glands.

Dr. Perry said one of the reasons that blepharitis is tricky to diagnose is because there are five main factors: a microbiologic factor, dermatologic factor, allergic factor, nutritional factor, and meibum quality factor.

Dr. de Luise said that anterior blepharitis due to staphylococcal organisms and posterior blepharitis due to meibomian gland dysfunction are among the most common forms. Another system is to describe the eyelid findings as ulcerative or non-ulcerative. Ulcerative blepharitis tends to be infectious in etiology, and non-ulcerative blepharitis is more likely inflammatory.

Dr. de Luise offered a useful mnemonic device for the presentations and causations of blepharitis by remembering the letters ABCD.

“A” is for anterior and allergic. This group includes allergic eczematoid blepharodermatitis, contact dermatitis, and atopic dermatitis. Allergic anterior blepharitis usually manifests as an eczematoid blepharodermatitis. Symptoms of anterior blepharitis include irritation, itching, and redness and scaling of the eyelid skin.

“B” is for bacteria and viruses. These are the infectious causes, which include bacteria such as staphylococci and blepharitis due to viruses such as Herpes simplex, Herpes zoster, or Molluscum contagiosum.

“C” is for cancer, chemical, clogging, and complex. This group includes papilloma, sebaceous cell carcinoma, melanoma, and basal cell carcinoma. Chemical refers to burns or thermal blepharitis. Clogging refers to the blockage of the meibomian glands in meibomian gland dysfunction. Complex refers to hybrid forms of blepharitis, which manifest both in the anterior and posterior lid.

“D” is for Demodex and dermatologic. These etiologies include Demodex folliculorum (anterior blepharitis), Demodex brevis (posterior blepharitis), oculocutaneous rosacea, psoriasis, Stevens-Johnson syndrome, and cicatricial pemphigoid.

In 2011, the International Workshop on Meibomian Gland Dysfunction stratified blepharitis into anterior and posterior types. It defined anterior blepharitis as inflammation of the lid margin anterior to the gray line and centered around the eyelashes. The gray line represents the location of the marginal region of the orbicularis muscle seen through the lid skin. The line divides the eyelid into an anterior lamella (eyelid skin and muscle) and posterior lamella (tarsus and conjunctiva). Anterior blepharitis may be accompanied by squamous debris or collarettes around the base of the lashes and vascular change.³

The International Workshop defined posterior blepharitis as inflammatory conditions of the posterior lid margin, including meibomian gland dysfunction. The posterior lid margin contains the marginal mucosa, the mucocutaneous junction, the meibomian gland orifices and the terminal ductules, and the neighboring keratinized skin. Posterior blepharitis is a term used to describe inflammatory conditions of the posterior lid margin, of which meibomian gland dysfunction is only one cause, Dr. de Luise said. Other causes include infectious or allergic conjunctivitis and systemic conditions, such as oculocutaneous rosacea.³

Presentation

According to Dr. de Luise, in order to properly diagnosis blepharitis, it is essential to describe what one sees on slit lamp examination and distinguish among the following observations.

• Crusts: Keratinized plaques on the eyelid surface often seen in staphylococcal blepharitis
• Scales: Greasy flakes seen in seborrheic blepharitis
• Scurf: Dandruff-like excrescences seen in seborrheic blepharitis
• Sleeves: Cylindrical tubes of material around the lash base
• Collarettes (cylindrical dandruff): Cylindrical tubes of material that go higher up the eyelash base than sleeves, usually associated with Demodex infestation

Anterior blepharitis is a nonspecific term that identifies the location of the eyelid inflammation, and it is usually caused by seborrhea or by staphylococcal overabundance. Demodex organisms have also been associated. The two most common bacteria that cause anterior blepharitis are Staphylococcus epidermidis and Staphylococcus aureus.

Dr. de Luise said that staphylococcal blepharitis typically presents with crusting on the eyelid surface and debris in the tear film meniscus. Patients usually complain of eyelid irritation, and the eyelid margins are red and often crusted. If these crusts are removed, there is often oozing and bleeding. “In chronic and recurrent cases, there can be lid margin ulceration, misdirected eyelashes, trichiasis, whitening of the lashes, and loss of eyelashes, as well as an associated conjunctival hyperemia,” he said. “Severe cases often display an associated limbal keratitis or keratoconjunctivitis.”

Patients with anterior blepharitis may present with visual blurring and irritation. External ocular evaluation and slit lamp examination usually disclose eyelid margin erythema. Lid margin and eyelash crusts, scales, sleeves, scurf, or collarettes can be seen, depending on the type of blepharitis.

The workup for blepharitis is similar to that for dry eye disease, Dr. de Luise said. Obtaining a comprehensive history is essential. What are the patient’s symptoms? Does the vision worsen during the day (more likely dry eye disease) or improve during the day (more likely blepharitis)? Testing should include visual acuity, symptom score such as SPEED, SANDE, or OSDI, tear film breakup time, analysis of the blink rate, vital dye corneal staining with fluorescein and conjunctiva with lissamine green, evaluation of tear film meniscus, analysis of eyelids and lashes to look for erythema, crusts, scales, scurf, sleeves, and collarettes, evaluation of meibomian gland orifices, and a careful analysis of the lash base under high magnification slit lamp to look for Demodex mites.^4,5

Dr. Perry noted that patients with infectious blepharitis may present with diffuse edema. That’s less common than a diffuse erythema along the upper lid margin associated with the presence of scurf, cylindrical dandruff, or other deposits on the lid margins or lashes. That is often associated with itching, redness, swelling, foreign body sensation, and burning. Symptoms may be very subtle, he added.

“The most common reason for blepharitis is meibomian gland dysfunction, so the meibomian glands, instead of secreting long chain fatty acids that are compressible and expand and contract with each blink, start to secrete more free fatty acids.” This causes a premature break in the tear film. As time goes by, with the increase in free fatty acids, combined with inflammation, little bubbles start to form in the tear film. Even one or two little bubbles is significant for advanced meibomian gland disease, Dr. Perry said.

When evaluating a patient for blepharitis, Dr. Perry will do a slit lamp evaluation to look at the lid margins and eyelashes and look at marginal tear strip and conjunctiva. “I’m looking at their eyelashes for cylindrical dandruff (Demodex) and lid margins for neovascularization and/or obscuration of the meibomian gland orifices to see if the lid margin has been covered by new vessels or if there’s capping of the meibomian glands,” Dr. Perry said. “I’m also looking at how the eyelid closes [to see] if there’s conjunctivochalasis.” He also looks for the presence of nocturnal lagophthalmos, which can be subtle. After making note of what is found on the slit lamp exam, Dr. Perry moves on to testing, noting that he uses the osmolarity test, MMP-9 testing, the Schirmer 1 test (which can show if the patient has significant aqueous deficiency), lissamine green staining (to see if there are changes on the ocular surface), and meibography. “I will frequently express the lower meibomian glands to look at the meibum, and this is usually helpful and somewhat therapeutic as it often helps increase the flow of the meibum again,” he said.

Treatments

Dr. Perry noted a study that he was a part of where patients with symptomatic blepharitis were treated with warm saltwater soaks and preservative-free tears.⁶ This was done for 6 weeks, and patients were reevaluated. Dr. Perry said 88% of patients got better. “It was heartening to realize that patients could get better with non-medicinal therapy,” he said.

This saltwater method helps with lid hygiene, he said. The heat helps melt fats in the eyelid, the saline solution is calming for the eye, and the action of the cotton ball on and off cleans the eyelid and debrides some allergens that might be stuck to the eyelid skin.

It’s helpful to have a non-medicinal option, he said, because corticosteroids can cause thinning of the eyelid skin and can lead to the complications of glaucoma and cataract formation.

For those patients who need additional treatment, Dr. Perry said there are options like Prokera (BioTissue) and several cyclosporine medications.

Additionally, Dr. Perry said it’s important to consider nutritional therapy. He recommends patients take fish oil supplements. Most patients with severe meibomian gland dysfunction have associated acne rosacea and don’t eat any fish, he said.

Speaking specifically about staphylococcal blepharitis, Dr. de Luise said it is often chronic and recurrent; patient education is essential as the condition is rarely curable. Therapeutic strategies include warm compresses and saltwater lid scrubs. Do not use shampoos or soaps in lid scrubs as blepharitis is a condition in which the eyelid surface is already saponified, and the shampoos can worsen the condition. Hypochlorous acid cleansers can be helpful. In more severe cases in which the patient is not a steroid responder, the short-term use of an antibiotic- steroid ointment or drop can be effective.^4,5

In terms of new therapies in development, Dr. Perry said that Novaliq is working on a cyclosporine product with a new type of excipient (fluorinated alkanes) that will also treat meibomian dysfunction. Dr. Perry is studying some new drugs that are similar to Oxervate (cenegermin-bkbj, Dompé) that have healing qualities on the ocular surface. “We’re looking at two other agents, one with germ cell properties and one with a different growth factor compound,” he said.

Are some types of blepharitis harder to treat?

Anterior blepharitis due to staphylococcal overgrowth can be recurrent, Dr. de Luise said. Additionally, posterior blepharitis due to meibomian gland dysfunction can be chronic and recalcitrant to treatment. These types of blepharitis may require ongoing episodic treatment over months to years.

Complex cases of blepharitis, Dr. de Luise said, include blepharitis from neoplastic etiologies, such as sebaceous cell carcinoma or basal cell carcinoma. These cases require individualized treatment including cryosurgical or surgical removal with wide margins and eyelid plastic reconstruction. Blepharitis from Stevens-Johnson syndrome is often cicatrizing. Stevens-Johnson syndrome is often associated with cicatrizing conjunctivitis and requires coordinated management of the eyelids and the conjunctival sequelae. Oculocutaneous rosacea can be associated with blepharitis. Topical corticosteroids should be used with caution in the management of rosacea keratitis as corneal melts can occur.

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About the physicians

Vincent de Luise, MD
Assistant Clinical Professor of Ophthalmology
Yale University School of Medicine
New Haven, Connecticut

Henry Perry, MD
Chief, Cornea Service
Nassau University Medical Center
East Meadow, New York

References

1. Lemp MA, Nichols KK. Blepharitis in the United States 2009: a survey-based perspective on prevalence and treatment. Ocul Surf. 2009;7:S1-S14.
2. Rynerson JM, Perry HD. DEBS – a unification theory for dry eye and blepharitis. Clin Ophthalmol. 2016;10:2455–2467.
3. Nelson JD, et al. The International Workshop on Meibomian Gland Dysfunction: report of the Definition and Classification Subcommittee. Invest Ophthalmol Vis Sci. 2011;52:1930–1937.
4. Amescua G, et al. Blepharitis Preferred Practice Pattern. Ophthalmology. 2019;126:P56–P93.
5. Bouchard C. Diagnoses and management of blepharitis. Review of Ophthalmology. 2022.
6. Romero JM, et al. Conservative treatment of meibomian gland dysfunction. Eye Contact Lens. 2004;30:14–19.
7. Shah PP, et al. Update on the management and treatment of Demodex blepharitis. Cornea. 2022;41:934–939.
8. Heczko J, et al. Evaluation of a novel treatment, selenium disulfide, in killing Demodex folliculorum in vitro. Can J Ophthalmol. 2022. Online ahead of print.

Relevant disclosures

de Luise: None
Perry: Azura Ophthalmics, BlephEx, Novaliq, Tarsus Pharmaceuticals

Contact

de Luise: vdeluisemd@gmail.com
Perry: hankcornea@gmail.com