Ophthalmologists should keep blepharitis on their diagnostic radar due to the negative impact eyelid margin disease has on patients. Not only does blepharitis disrupt ocular health, it has far reaching consequences on the emotional state of patients who suffer from this disease process. (See “Blepharitis: An Overview,” below.)
In this article, we explain how, specifically, blepharitis affects the ocular and emotional well-being of patients, and the action steps ophthalmologists can take to diagnose and treat blepharitis to prevent these adverse effects.
How Blepharitis Affects Patients
• Ocular health. The long-term consequences of untreated blepharitis and eyelid margin disease from an ocular health standpoint can include the following chronic processes: epithelial basement membrane disease (EBMD), which can lead to recurrent corneal erosions, inaccurate biometry, mechanical dry eye disease (DED), conjunctivochalasis, or neurotrophic keratitis (NK). The latter can cause complete cornea anesthesia and, thus, extremely poor vision due to the instability of the cornea epithelium. (See “Building a Case for Neurotrophic Keratitis,” at bit.ly/3XYupQQ .)
Management of EBMD may require a superficial keratectomy with an amniotic membrane placement to press the “restart” button on corneal epithelial stability.1 Mechanical DED, or conjunctivochalasis may necessitate a fornix reconstruction with an amniotic membrane graft to restore the tear reservoir.2 NK can require intervention both pharmacologically (Oxervate 0.002% [cenegermin-bkbj, Dompé]) and surgically (using an amniotic membrane or even corneal neurotic action).3
BLEPHARITIS: AN OVERVIEW
Blepharitis is characterized by inflammation of the eyelid margin. The disease can affect the eyelid skin, lid margin, eyelashes, tarsal conjunctiva, and meibomian glands, further contributing to dry eye disease.10,11
The most common clinical features of blepharitis are eyelid itching or burning, foreign body sensation, eyelash crusting or flakes, watery eyes, fluctuating vision and redness.12
In 2022, a multicenter, retrospective study comprised of over 1,000 consecutive patients revealed that 69% of the patients had a blepharitis diagnosis, with 58% having Demodex blepharitis (DB).10
Another large case-control prospective study carried out from 2007 to 2016 that sampled 10 eyelashes from each of 553 blepharitis patients and 115 healthy volunteers without a history of ocular pathologies, showed Demodex species were found in 62.4% of the study group patients and in 24.3% of the controls. The overall prevalence was 55.8% in all the examined participants.13
DB is known to reduce TBUT.14 Additionally, Demodex infestation can occur in both the lash follicles and in the meibomian glands. A mixed form of Demodex infestation with meibomian gland dysfunction appears significantly correlated with greater gland structural atrophy.15,16
Inflammatory biproducts are created by the Demodex mites through its external chemical digestion. This creates secondary issues, which can further propagate unwanted comorbidities, including seborrhea, rosacea, and marginal blepharokeratitis, in its more severe form.17,18
The Demodex mite is known to harbor and serve as a vector for bacteria within its gut, as well as within the collarettes.19 Early pilot work suggested that the lid flora of patients with DB were twice as likely to harbor multiple (≥2) strains of lid margin bacteria, while some harbored more virulent strains, including Enterococcus faecalis, Staphylococcus (Staph.) hominis, Staph. warneri, Staph. lugdunensis, bacillus and diphtheroid.20 Eyelids with DB eyelids were almost twice as common to test positive for methicillin-resistant Staph. epidermidis (MRSE), which is concerning because MRSE generally carries multiple resistances to multiple antibiotics.20
These conditions are just 2 examples of why ophthalmologists must attempt to identify and treat blepharitis during the initial patient encounter.
Poor cataract and refractive surgery outcomes are another consequence of untreated blepharitis and eyelid margin disease. Evaporative DED can cause an irregular corneal surface. This reduces the efficacy and safety of limbal relaxing incisions, is more likely to cause postoperative glare and halo, reduce the quality of vision, and is a relative contraindication for advanced technology IOLs. Limiting surgical options for patients detracts from the surgeon’s ability to provide the best possible visual outcomes. Therefore, addressing blepharitis and ocular surface health prior to offering surgical intervention is imperative. (See “Managing Dry Eye Before Cataract Surgery” at bit.ly/4042UXE .)
• Emotionally. The burden this condition has on patients is far reaching and can impact both their physical appearance and their mental health and social lives.4
A multicenter, prospective study revealed the emotional impact of the symptoms of blepharitis, including 47% of patients being conscious of their eyes all day, 23% constantly worrying about their eyes, and 23% citing the disease gives their eyes a negative appearance.5
• Diagnosis. One of the first steps to arriving at a diagnosis of blepharitis is to use a DED patient questionnaire, such as the Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire.6 This helps to reveal symptoms and elicit specific complaints related to blepharitis-induced DED, enabling the ophthalmologist to determine whether additional diagnostic testing is needed.
Next, we recommend a careful, exam of the eyelid margin, with the patient looking down, so we can focus on the base of the eyelashes and the tarsal conjunctiva to look for signs of blepharitis. Then we have the patient look up to better illuminate the meibomian glands (MG), pushing of the MG for the quality and expressibility of the meibum, and then look for telangiectasis and notching across the lower lid margin. Elasticity of the eyelid should be checked here by pulling.
Other diagnostic testing can include Schirmer’s test, corneal staining, tear osmolarity tests (I-Pen, I-Med Pharma; TearLab Osmolarity System, TearLab), matrix metalloproteinases-9 (MMP-9) tests (InflammaDry, Quidel; Rapid Quantitative Tear Test, Axim Biotech), and meibography (TearScience LipiScan and LipiView II, or the Meibomian Gland Evaluator, Johnson & Johnson Vision; Meibox, Box Medical Solutions; Oculus Keratograph 5M, Oculus; OPD Scan III, Marco; Orbscan III, Bausch + Lomb; Spectralis, Heidelberg).
Regarding prerefractive surgery patients, we find that corneal topography with epithelial mapping enables us to assess whether the patients’ visual complaints stem from tear film instability, corneal surface irregularities, cataracts, or a combination of these findings. Topography aids in detecting signs of blepharitis-induced DED and other pathologies, including irregular astigmatism, EBMD, and keratoconus, that can cause inaccurate biometry readings leading to poor refractive outcomes.
• Treatment. There are many strategies for managing blepharitis. First, we must identify the type of blepharitis. In our experience, a combination of factors lend themselves to the development of DED and, ultimately, a symptomatic patient.
Tea tree oil has been shown to improve symptoms, signs, and tear film instability in patients who have blepharitis and meibomian gland dysfunction.7 Tea tree oil–based products used in high concentrations may induce ocular irritation, and a recent study demonstrated that it can be toxic to meibomian gland epithelial cells.8
Oral doxycycline, off-label or compounded topical metronidazole gel, and/or off-label topical or itraconazole cream can all be used for various forms of rosacea and Demodex blepharitis.
Pulse dosing of oral ivermectin (off label) can be used concurrently for severe Demodex blepharitis to help. Of note: Oral ivermectin can be difficult to obtain. Additionally, its half-life requires multiple dosing every few weeks. Sun sensitivity and gastrointestinal issues are well-known side effects at higher or prolonged exposure to oral tetracyclines. Off-label and compounded medications can be challenging because of difficulty to access, cost, and limitation of peer-reviewed literature on frequency and dosing.
If the eye is “hot” -angry or inflamed with a mixed blepharitis appearance-we prescribe a combination steroid/antibiotic ointment b.i.d. for 3 weeks, with adjunctive conservative lid scrubs, a moist heat compress both morning and night, and preservative-free artificial tears.
Patients who have secondary squamous disease can be served with an oral tetracycline if topical therapy is not enough. It can improve the patients’ symptoms and allow us to give the patient a better quality of life. After a few weeks, patients may complain that their symptoms have returned. This is because the mite is creating a locally immunosuppressed state for it to survive and thrive.
Patients who have evidence of meibomian gland dysfunction (MGD) should consider undergoing an in-office treatment. Microblepharoexfoliation (MBE), available via AbMax (Myco Industries) and BlephEx (BlephEx), can be an excellent co-adjunctive mechanical debridement for blepharitis to remove the collarettes and other lash debris, and to allow for better penetration of the other topical therapeutics into the lash follicles. Additionally, MBE allows for the debridement and removal of the overlying lid margin biofilm, for better egress of the meibum.
In our experience, a combination of MBE with an MGD-focused intervention, such as thermal treatment (i.e., iLux [Alcon], LipiFlow [Johnson & Johnson Vision], and TearCare [Sight Sciences]) and intense pulse light therapy (e.g., the Quadra Q4 Platinum Series IPL [Dermamed Solutions] and OptiLight [Lumenis]) can manage the chronic state of DED. Patients can experience noticeable symptomatic improvement from these interventions, and require less maintenance therapy at home. We have found that this improves patient compliance and allows patients to extend time between office visits from symptom flareups.
In late fall 2022, Tarsus Pharmaceuticals Inc. submitted a New Drug Application (NDA) to the FDA for TP-03 (lotilaner ophthalmic solution, 0.25%) for the treatment of Demodex blepharitis (DB). This occurred on the heels of a phase 2b/3 clinical trial.9 Specifically, TP-03 was shown effective and safe: One 6-week course of b.i.d. treatment of topical TP-03, without any additional mechanical rubbing or conservative blepharitis management, led to a clinically meaningful cure of DB in 85% of the patients; thus less than <10 collarettes (as compared to 30% vehicle group, P<0.0001). Extension data showed that after that single 6-week course, 70% of patients continued to sustain the clinically meaningful cure at post-treatment month six, and the same durability effect was observed in 60% of patients at month 12, demonstrating its potential long-standing efficacy. All treatment-related ocular adverse events from the TP-03 group were mild, with the most common being instillation site pain/burning/stinging, according to Tarsus Pharmaceuticals. In over 800 patients studied, 90% of patients found the lotilaner 0.25% solution to be neutral to very comfortable.
Optimizing the ocular surface and treating blepharitis is usually the first step in the refractive surgeon’s surgical process. Patients tend to appreciate this stepwise approach and are eager to be compliant with the presurgical treatment regimen when they know the goal is to ensure they are happy, and have excellent postop vision.
Strict attention to every component of the patient’s ocular health, including blepharitis, enables us to provide excellent clinical and surgical care to them. Regarding cataract surgery, in particular, the high patient expectations of visual outcomes postop far exceed what they were a decade ago. Ophthalmologists should position themselves to meet those expectations by utilizing the rapidly evolving technologies and therapies available. CP
References are available in the online version of this article.