Dry eye disease, also called keratoconjunctivitis sicca, affects more than 100 million people worldwide. Common symptoms of dry eye include dryness, grittiness, soreness, irritation, burning, watering, sensitivity to light and eye fatigue. These symptoms can significantly diminish the quality of life by hindering daily activities such as reading, computer usage, contact lens wear, enjoying outdoor activities, or working in an air conditioned environment. Many dry eye patients complain that those symptoms worsen throughout the day. The symptoms of dry eye disease are one of the most common reasons people visit the eye doctor. If left untreated, this condition can lead to pain, corneal scarring, and some loss of vision.
There are two predominant forms of dry eye – aqueous deficient and evaporative. Both forms are related to deficiencies in the tear film that covers the exposed portion of the eye, most importantly the cornea. A healthy tear film consists of three layers. The inner layer is primarily made up of mucin, which provides lubrication. The middle layer is the aqueous layer made up of tear fluids. The outer layer is made up of an oil or lipid that provides lubrication for the lids and also keeps the aqueous layer from evaporating.
The aqueous deficient form is caused by a lack of sufficient tear production. This can be treated by drugs (such as cyclosporine or Restasis) which increase tear production. It can also be treated by punctal plugs or cauterization, both of which seal off the tear ducts and thereby reduce drainage of tear fluid from the eye.
NORMAL EYELID ANATOMY
HEALTHY MEIBOMIAN GLAND
PARTIALLY BLOCKED GLANDS,
WITH THICKENED SECRETIONS
It is not yet clearly understood what causes MGD, but the progression of the condition typically starts with a thickening of the meibum and an increased sloughing of cells within the glands, leading to reduced meibum secretion and eventually blocked ducts. Once the glands reduce their meibum secretion and patients begin to feel the irritation associated with EDE, this can lead to inflammation of the eyelids, which further constricts the outlet ducts of the meibomian glands and increasingly restricts meibum secretion. In some patients, bacteria commonly found on the skin, which normally are kept away from the surface of the eye and eyelids by a healthy tear film, proliferate along the lid margins. These bacteria release byproducts which have irritating effects on the eye, resulting in increased inflammation. This inflammation can lead to additional constriction of the meibomian glands, which further degrades the tear film causing more inflammation, and so on.
When the eyelids become chronically inflamed, the patient is said to have blepharitis (which literally means inflammation of the eyelids). There are several forms of blepharitis – anterior and posterior. Anterior blepharitis is generally associated with inflammation resulting from skin disorders caused by bacteria, parasites or allergic reactions, and is usually accompanied by flaking and scaling (sometimes called seborrheic blepharitis). This form can often be treated with lid hygiene, including soaps, shampoos and topical antibiotics. Posterior blepharitis refers to inflammation resulting from meibomian gland dysfunction, as described above. Patients often have a mix of anterior and posterior blepharitis.
Another contributing factor in certain patients is a common mite (called Demodex) which is found on the faces of most humans, especially older adults. This mite has been shown to be more prevalent in patients who have acne or rosacea. The mites burrow into hair follicles and sebaceous glands on the face and near the eyes. A certain form of the mite has been shown to thrive in the eye lashes and in meibomian glands, and some studies have correlated an increased prevalence of these mites with the incidence of blepharitis.
It is often difficult to distinguish between the root causes and symptoms associated with evaporative dry eye, meibomian gland dysfunction and blepharitis. To help sort this out, the Tear Film and Ocular Surface Society (TFOS, a nonprofit organization) formed the International Workshop on Meibomian Gland Dysfunction made up of leading experts in the field. A recent report published by the Workshop included the diagram below, which summarizes the many facets of evaporative dry eye and related conditions:
Eye care professionals (ECPs) may use a variety of specialized equipment including slit-lamp microscopes, interferometers and osmolarity tests to diagnose dry eye disease and to help distinguish between the various forms.
A simple but important test is for the ECP to examine the meibomian gland orifices using a slit-lamp microscope or other means of magnifying the region, and to press gently on the lid margin to express (or squeeze out) some of the oily meibum. A grading scale is used to categorize the clarity and quantity of meibum that is expressed. Healthy glands produce high quantities of clear meibum, while diseased glands produce meibum that is thick and opaque. Atrophied glands or those with chronically blocked orifices do not produce any meibum.
Treatment of evaporative dry eye typically starts with warm compresses applied to the eyelids twice a day, followed by fingertip massage of the eyelids, and the use of a tear-free soap or shampoo to wash the eyelids and eyebrows. Warm compresses are intended to soften thickened meibum, and the fingertip massage is intended to help express the softened meibum and thereby keep the ducts clear. The soap or shampoo is intended to improve lid hygiene, by reducing bacteria and bacterial byproducts, and, in some cases, by reducing the presence of mites. Eye drops and supplemental omega-3 fatty acids are also sometimes recommended. Unfortunately, these initial recommendations rarely provide significant relief, for these reasons:
- Studies have shown that warm compresses rarely warm the meibum in the meibomian glands sufficiently to allow expression. The usual suggestion is to apply a cloth soaked in hot water to the eyes for about five minutes; however, unless extremely hot water is used (e.g., >120°F) for five to seven minutes, with the cloth being replaced with fresh hot water every minute or so, the glands do not get warm enough. Because of this, most patients do not find enough relief from this technique to justify the effort, and therefore they typically stop doing it within a month of their diagnosis.
- Fingertip massage can help to express the meibum (if heated properly), but recent studies suggest that excessive massaging of the eyelids over the cornea, especially after heating of the eyelids, can lead to a condition called keratoconus. Keratoconus is a degenerative disorder of the eye in which structural changes within the cornea cause it to thin and change to a more conical shape than its normal gradual curve, leading to substantial distortion of vision. A better method of self-expression of meibomian glands is to pinch a portion of the lid margin with the thumb and forefinger, allowing the lid to pucker away from the cornea, and then to squeeze until meibum is expressed from the pinched glands.
- Eye drops can help soothe irritated eyes for a short period of time, but for patients suffering from evaporative dry eye, they just mask the symptoms. EDE patients generally have plenty of tears; it’s the oily outer surface of the tear film that they are missing. Some newer eye drops contain lipids which are helpful in attempting to supplement abnormal lipid production, but they may not reproduce the complex action of the meibomian glands which secrete and deposit lipids onto the outer surface of the tear film each time the patient blinks.
- Although there seems to be little downside to supplementing diet with omega-3 fatty acids, there are few controlled clinical studies that have shown definitively that they reduce the symptoms of evaporative dry eye.
Some eye care professionals will also perform in-office expression of clogged meibomian ducts. This may be quite painful for most patients, but is better tolerated when topical anesthetics are applied. Clinicians sometimes insert a plastic or metal paddle behind the eyelid to provide a surface against which a cotton-tipped swap or other device can press until meibum is expressed.
In many cases, the above techniques do not provide adequate relief of symptoms, so the following next steps are often prescribed in order to find an effective combination of treatments:
- Oral antibiotics. Antibiotics such as tetracycline, doxycycline and minocycline can be prescribed either in an initial high dose (eg 100 mg capsules), or a lower-dose (such as 50 mg). These drugs reduce inflammation and diminish certain bacteria in and around the eyelids. Unfortunately, the higher doses have systemic antibiotic effects affecting natural flora of the digestive tract, and can also lead to antibiotic-resistant bacterial strain development. Lower doses, and slow-release doses such as Oracea, have been shown to be somewhat effective in reducing inflammation without having the negative systemic effects, but they may be quite expensive for patients without insurance.
- Topical antibiotics. Ointments and gels such as Azasite (azithromycin ophthalmic solution, 1%) may be prescribed, to be applied either to the lid, lid margin, or the eye itself. Azasite attacks certain bacteria and also seems to have anti-inflammatory properties. Azasite may be expensive for uninsured patients.
- Anti-inflammatory drops. Restasis (cyclosporine ophthalmic emulsion, 0.05%) has been prescribed for dry eye treatment for more than ten years. It stimulates tear production and has an anti-inflammatory effect. Restasis stings some patients’ eyes and may take up to six months for patients to notice significant benefit. Xiidra (lifitegrast ophthalmic solution, 5%) was recently approved for dry eye treatment, and works primarily by reducing inflammation. Both Restasis and Xiidra can be expensive, and neither drug helps to unblock meibomian glands.
- Steroid drops. Various formulations of steroidal suspensions, with and without antibiotic agents, are available to help reduce inflammation in patients with severe symptoms. These include Zylet (loteprednol and tobramycin), Lotemax (loteprednol) and Tobradex (dexamethasone and tobramycin). The side effects of these drugs can be severe, including increased ocular pressure (leading to glaucoma), and cataract formation. As such, they are only intended for short-term use, and may be quite expensive for self-paying patients.