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Man presents with persistent foreign body sensation and swollen eyelids
Exam findings include anterior and posterior blepharitis, lid margin telangiectasia and collarettes.
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A 39-year-old Caucasian man was seen in the Cornea Service at the New England Eye Center with complaints of sore and swollen eyelids and foreign body sensation in both eyes for several months. The patient had a history of recurrent herpes zoster endotheliitis and keratitis in the right eye, which following numerous recurrences had been controlled since the addition of oral acyclovir. History was also positive for dry eye disease, meibomian gland dysfunction, blepharitis, hordeolum in the left lower lid 1 year prior as well as pinguecula in the left eye.
Regarding treatment, he was compliant with prophylactic oral acyclovir, flax seed oil and artificial tears, and noncompliant with warm compresses and lid hygiene. He had not responded in the past to AzaSite (azithromycin ophthalmic solution 1%, Akorn), topical erythromycin and oral doxycycline for the treatment of blepharitis. Corneal in vivo confocal microscopy (IVCM) had shown decreased corneal nerve density in the right eye at baseline as a result of prior herpes zoster keratitis with stromal inflammation, which resolved on Lotemax (loteprednol etabonate ophthalmic suspension 0.5%, Bausch + Lomb). The patient was otherwise healthy.
Examination
Best corrected visual acuity was 20/20 in both eyes. The pupils were briskly reactive to light, and IOPs were 14 mm Hg in both eyes. Extraocular muscle movements were intact. The patient had full confrontational visual fields in both eyes.
Images: Morkin MI, Hamrah P
Anterior segment exam revealed anterior blepharitis, eyelid notching, lid margin telangiectasia (Figures 1a and 1b) and cylindrical collarettes (Figures 1c and 1d). Meibomian glands were partially obstructed and expressed thick meibum. Tear breakup time measured 2 seconds with faint superficial punctate keratitis in both eyes. The exam was also significant for peripheral corneal neovascularization in the right eye as a result of prior herpes zoster keratitis. The rest of the examination was negative for any other anterior or posterior segment abnormalities.
What is your diagnosis?
Refractory blepharitis
The differential diagnosis for refractory and long-standing blepharitis is large.
Infection of the eyelids by bacteria, including Staphylococcus, Streptococcus, Pseudomonas, Actinomyces and Moraxella, should be considered, especially when collarettes are present. These typically improve with antibiotic therapy. Viral lid infections, such as Molluscum contagiosum, herpes simplex and zoster, verrucae and less commonly fungi, can also present with blepharitis. Collarettes that encircle the lash shaft with a longer and cylindrical appearance may classically be the product of Demodex folliculorum infestation. Immune-mediated conditions, such as atopic keratoconjunctivitis, contact dermatitis, keratoconjunctivitis sicca, ocular rosacea and superior limbic keratoconjunctivitis, may involve the lids. Scurf, a term used for the greasy debris product of meibomian gland hypersecretion, is typical of seborrheic meibomian gland dysfunction. Other miscellaneous causes of eyelid inflammation are floppy eyelid syndrome and phthiriasis (pediculosis) of the lids. Cyanoacrylate glued false eyelashes can leave behind collarette-appearing material. A condition not to be missed, which frequently masquerades as chronic blepharitis, is sebaceous cell carcinoma, especially with asymmetric presentations.
IVCM is a noninvasive real-time imaging method that provides high-resolution images at a cellular level of all corneal layers, conjunctiva and eyelids. The cylindrical appearance of the collarettes on slit lamp examination lead to the suspicion of Demodex infestation, which was confirmed by IVCM (Figure 2a).
Discussion
The word Demodex derives from Greek, with demos meaning fat and dex meaning worm. This genus represents the most common parasite in humans, and its incidence rises with age. Demodex can reside in the eyelids, face, scalp, ear canals, thorax and buttocks. Because the eyelids are usually not part of routine hygiene, Demodex finds a naturally advantageous environment to proliferate in the lash follicles and eyelid glands.
Demodex has an oblong translucent figure that is divided into two segments. The anterior segment consists of the head, which gives rise to eight small legs, and neck. The posterior segment contains the body and tail. Among the various existent species of Demodex, only Demodexfolliculorum and Demodex brevis colonize humans. Interestingly, Demodex folliculorum is longer (0.35 mm to 0.4 mm) and resides in the eyelash follicles, leading to anterior blepharitis, while Demodex brevis is about half the length (0.15 mm to 0.2 mm) and is found in the meibomian and sebaceous glands, resulting mostly in posterior blepharitis.
Facial infestation with Demodex has been implicated in causing rosacea. Likewise, symptomatic blepharitis patients have a significantly higher incidence of Demodex infestation. Nevertheless, asymptomatic individuals may also be colonized with Demodex in the eyelids and face, suggesting that the mere presence of the parasite is not sufficient to guarantee the development of clinical manifestations. Symptoms typically consist of redness and crusting of the eyelid margin, itching, irritation, foreign body sensation and intermittent blurriness. Demodexbrevis tends to be more aggressive given that posterior blepharitis can induce blepharoconjunctivitis and ocular surface inflammation. In these cases, non-specific keratitis, marginal infiltration and scarring, as well as corneal neovascularization, can be observed.
A high level of clinical suspicion should be maintained for patients with refractory chronic blepharitis or inflammatory ocular surface disease. As mites consume and distend the inner layer of the follicles where they lay their eggs, thickening and distortion of the eyelid margin (tylosis), lash instability and trichiasis can be appreciated. Resultant debris and waste accumulate to form cylindrical dandruff around the eyelash shaft, which is pathognomonic of Demodex. Mites can be identified under microscopic examination of epilated eyelashes. In recent years, IVCM has been increasingly used to noninvasively image the mites, especially the masquerading Demodexbrevis, which burrows deep into meibomian and sebaceous glands. With this approach, adult forms are found in the eyelash follicles or meibomian glands or attached to the base of the lashes, along with the larvae. Surrounding inflammation such as meibomitis can also be captured with IVCM, seen as hyperreflective inflammatory cells on the palpebral epithelium, periductal inflammation or heterogeneous reflectivity of the gland lumen.
A number of treatment regimens are available to control Demodex mite infestation. The first step should always be whole body cleaning with regular shampoo or soap to avoid spread. It is also recommended to routinely clean the environment, such as bedding and pillows, once a week. Available on the market are many lid scrub cleansing agents to remove the collarettes. Traditionally, first-line treatment has consisted of 50% tea tree oil lid scrubs along with 5% tea tree oil ointment, which prevents Demodex mating and contiguous spread of mites. More recently, Terpinen-4-ol (T4O; Cliradex, Bio-Tissue) was discovered to be the most active component of tea tree oil but with a superior side effect profile. Other topical options, to which dermatologists similarly resort for the treatment of facial infestation, are permethrin cream and topical ivermectin or metronidazole.
In the setting of disease refractory to topical therapy or with evidence of deep follicular involvement, as well as in cases of concomitant rosacea, oral therapy with ivermectin or metronidazole has proven beneficial. In Holzchuh’s series of 12 patients with refractory posterior blepharitis secondary to Demodex, two doses of 200 g/kg of oral ivermectin were administered 1 week apart. Ivermectin successfully reduced the number of Demodex folliculorum found in the lashes, along with improvement of ocular surface health markers, such as tear breakup time and Schirmer’s I values. In another study by Salem and colleagues, ivermectin alone was compared with ivermectin plus metronidazole in the treatment of 120 therapy-resistant patients. Combined treatment was better at normalizing Demodex levels in rosacea and anterior blepharitis patients, which supports the role of combined therapies in the treatment of Demodex infestation. Of note, attention should be paid to ivermectin’s side effect profile. Similar to metronidazole, patients most commonly experience gastrointestinal symptoms and dizziness, which increase with higher dosage. Given its predominantly hepatic metabolism and teratogenic effects, ivermectin use is contraindicated in those with liver disease, children younger than 5 years of age or weight less than 33 lb., and nursing mothers.
Management
The patient was given 3 mg of ivermectin orally and was started on T4O scrubs twice a day in both eyes. At the 6-week follow-up, the patient reported improvement of symptoms but still had complaints of foreign body sensation. IVCM showed persistence of Demodex figures in the eyelash follicles (Figure 2b). An extra 3 mg dose of ivermectin was administered, and T4O scrubs continued. After 5 weeks, symptoms of foreign body sensation and discomfort, as well as eyelid margin erythema, were significantly improved. Per IVCM, significant decreased density of Demodex with only some remnants left in deep follicles was appreciated (Figure 2c). A third dose of ivermectin was prescribed, and a follow-up appointment for 2 months was scheduled.
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- For more information:
- Melina I. Morkin, MD, and Pedram Hamrah, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.
- Edited by Kendra Klein, MD, and Kristen E. Dunbar, MD. They can be reached at the New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; website: www.neec.com.