Dry eye is a type of disease in which any cause of abnormal tear quality or quantity and kinetics leads to tear film instability and/or abnormalities on the ocular surface, accompanied by ocular discomfort. The main symptoms of dry eye include ocular dryness, foreign body sensation, visual fatigue, photophobia and vision loss, which can affect work and life in mild cases, and can lead to dryness, melting and perforation of the ocular surface, especially the corneal tissue in severe cases, which can seriously endanger visual function. At present, the number of dry eye patients is increasing, and the age distribution range is gradually widening, so it is extremely important to make a clear diagnosis and correct treatment for dry eye.
1.Diagnosis of dry eye
1.1 Medical history
Possible causes or contributing factors for the development of dry eye include: (1) the working environment and nature of the patient: long-term work in an environment with open air conditioning and poor air circulation can cause dry eye symptoms, such as “sick building syndrome” (SBS), “office eye disease syndrome” (SBS), and “office eye disease syndrome” (SBS). Office eye syndrome (OES); often engaged in concentrated work or activities can also cause dry eye, such as prolonged use of computers, working in front of fluorescent screens, reading can form “video display terminal syndrome” (video In addition, watching movies in a dark room or driving for a long time can cause a decrease in transients, which can increase the exposure of the eye surface area and accelerate the evaporation of tears, which can also lead to dry eye. (2) Local and systemic medications: long-term use of anti-hypertensive and antidepressant drugs can reduce tear secretion; long-term local use of antibiotics, antiviral and other eye medications can aggravate dry eye due to the toxicity of the drugs themselves or preservatives. (3) History of ocular trauma, surgery and past medical history: Ocular surface corneal rim stem cells are an important source of corneal epithelial renewal and are an important part of maintaining the health of the ocular surface epithelium. Ocular surface chemical injuries, thermal burns, long-term corneal contact lens wear, multiple surgeries or condensation of the corneal conjunctival rim, ocular aspergillosis and severe infections of the ocular surface can cause destruction or dysfunction of corneal rim stem cells. In addition, head radiation therapy and trigeminal nerve decompression may alter the corneal limbal stem cell stromal microenvironment. (4) Patients with systemic immune diseases may have dry eye symptoms, such as rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus and Wegner’s granulomatosis, etc. Therefore, the inquiry of systemic conditions should not be neglected.
1.2 Symptoms
The presence of dry eye symptoms is the most important and essential condition for the diagnosis of dry eye. The main symptoms include ocular dryness, foreign body sensation, burning sensation, visual fatigue, photophobia and varying degrees of visual acuity loss. Since the rate of positive clinical objective examinations is not parallel to the rate of dry eye symptoms, dry eye should be diagnosed when one or more of the above symptoms are frequently or persistently present. The inquiry of dry eye symptoms should be paid attention to, and for those with severe symptoms, the systemic medical history and concomitant symptoms such as dry mouth should be inquired in detail to determine whether there is a systemic disease, such as Sjogren’s syndrome (SS).
1.3 Clinical examination
1.3.1 Slit lamp examination
The following aspects should be noted: (1) tear river width: normal ≥ 0.3 mm; (2) corneal changes: epithelial keratosis, blisters, ulcers, turbidity, vascular opacities, etc.; (3) debris on the corneal surface and inferior vault; (4) lid adhesions; (5) conjunctival abnormalities: congestion, papillomatous hyperplasia, relaxation of the conjunctival sac piling up to form folds; (6) eyelid abnormalities: meibomian (6) eyelid abnormalities: Meibomian glands dysfunction (MGD) is a condition in which the lid margin is congested, irregular, thickened, blunted, and ectropioned, and the gland mouth is obstructed by yellow mucous secretions and the ducts are obscured. Compression of the gland reveals either no lipid secretion or excessive discharge of abnormal lipid morphology.
1.3.2 Schirmer’s test
The Schirmer I test (SIt) examines the basal secretion of tears by taking a 5 mm × 35 mm graduated test paper with one end folded back 5 mm and gently placing it in the outer and outer 1/3 of the conjunctival sac under the tested eye, removing the paper after 5 minutes and measuring the wet length, generally ≥ 10 mm/5 min is normal. Secretion, the method is to use a cotton swab (length 8mm, tip width 3.5mm) along the temporal wall of the nasal cavity parallel upward gently inserted into the nasal cavity, stimulate the nasal mucosa, and then placed filter paper (the same method as SIt test), five minutes later remove the filter paper, record the wet length, generally ≥ 10mm/5min is normal.
1.3.3 Tear film break-up time (tearbreak-up time, BUT)
Reflects the stability of the tear film. The method is to put a drop of 1% sodium fluorescein in the conjunctival sac of the subject, ask him to blink several times, and the time from opening the eye after the last transient to the appearance of the first black spot on the cornea is the BUT. non-contact BUT is to apply the tear film mirror to directly observe the break-up time of the tear film. Generally BUT>10s is normal.
1.3.4 Ocular surface staining in vivo
Positive fluorescein staining reflects corneal epithelial cell defects, the scoring method divides the cornea into 4 quadrants, specifying no staining as 0 points, with staining in 3 levels: light, medium and heavy, 1 as staining less than 5 points, 3 as appearing blocky staining or filaments, 2 points between the above two, with a total of 0 to 12 points. Positive tiger red and lissamine green staining reflects dry and necrotic corneal epithelial cells. Tiger red staining also shows epithelial cells without mucin coverage, dividing the ocular surface into 3 areas: nasal lid fissure bulbar conjunctiva, temporal lid fissure bulbar conjunctiva and cornea.
1.3.5 Tear clearance rate (TCR)
To find out whether there is a delay in tear clearance. Detected using fluorophotometric method, called flurescein clearance test (FCT).
1.3.6 Tear osmolality
This method is currently used for laboratory diagnosis, but there is no simple and practical method for clinical use.
1.3.7 Other tests
Tear lactoferrin content measurement, tear fern test, dry eye or tear film interferometry examination, conjunctival blot cytology, corneal topography and serology examination, etc.
1.4 Diagnostic criteria
There is no unified international and domestic diagnostic criteria for dry eye. According to the latest research reports and our clinical studies, we suggest that the diagnosis can be made according to the following criteria.
(1) Subjective symptoms (positive for one or more of the first five of the following): dryness, foreign body sensation, burning sensation, visual fatigue, photophobia, pain, tearing, blurred vision, and eye redness.
(2) Tear film instability: BUT(s) tear film rupture time: ≤10 seconds is abnormal.
(3) Tear reduction: SchirmerTest tear secretion test: ≤10mm/5min; lactoferrin content: ≤0.9ug/ml as abnormal.
(4) Ocular surface damage: fluorescein staining ≥ 3 and/or tiger red staining ≥ 3; blot cytology showing decreased cuprocyte density, decreased nucleoplasmic ratio, presence of serpentine chromatin, and increased squamous epithelial hyperplasia.
(5) Increased tear osmolarity: ≥312mOsm/L. Excluding other causes while having 1+2 (≤5 sec) or 1+2 (≤10 sec) +3 can make the diagnosis of dry eye, and the diagnosis can be strengthened if 3 and 4 are present at the same time.
2.Treatment of dry eye
The etiology of dry eye is complex, and finding and treating the etiology is undoubtedly the key to dry eye treatment. We should actively search for the cause and combine multiple treatments according to the symptoms and causes, with the ultimate goal of improving the inflammation of the ocular surface, restoring the normal tear film structure and function, and maintaining the normal environment of the ocular surface.
2.1 Physical therapy
Lipid-deficient dry eyes are caused by low lipid secretion or abnormal lipids that lead to rapid tear evaporation. The most common form is MGD, which is common in oily skin and older individuals, and has been increasing in recent years in women who have undergone cosmetic eyeliner surgery. For this condition, lid cleansing is essential, including hot compresses, massage, and scrubbing: (1) first apply a hot compress to the eyelid for 5 to 10 minutes; (2) massage the eyelid with a rotating motion of the fingers on the lid margin; and (3) scrub the lid margin with a milder cleansing solution.
2.2 Topical medication
2.2.1 Replacement of tear components
Aqueous-deficient dry eye is caused by the lack of aqueous layer in the tear film due to various reasons, and this type of dry eye is mainly treated by the replacement of tear components, and the replacement needs to be close to the normal tear components, divided into two types of artificial tears and homologous serum. (1) Artificial tears: There are many types of artificial tears available in China, and clinicians should be familiar with the advantages and disadvantages of each artificial tear component, viscosity, mechanism of action, type of preservative, etc., and make a corresponding choice according to the type and degree of dry eye, economic status of the patient and the patient’s response to treatment. (2) Autologous serum: its composition is closest to normal tears, but due to its complicated preparation and restricted source, it is less commonly used, and is generally applied only when severe dry eye will cause corneal complications.
2.2.2 Anti-inflammatory and immunosuppressive therapy
Patients with dry eye often have a non-infectious immune-based inflammatory response on the ocular surface that may be associated with reduced sex hormone levels, reduced lymphocyte apoptosis, and an injury-healing response due to minor friction on the ocular surface. Many scholars have identified this inflammatory response as a common pathogenesis for all types of dry eyes. Therefore, anti-inflammatory and immunosuppressive treatment is an important measure in the treatment of dry eye. (1) Corticosteroid eye drops: lower concentrations of hormone drops are effective in reducing dry eye symptoms and ocular surface inflammation, and the number of doses and duration of dosing are determined by the degree of dry eye, but should be minimized to avoid hormone-induced complications. (2) Immunosuppressive eye drops: Local application of low concentration of immunosuppressive eye drops to suppress ocular surface inflammation. At present, the commonly used drugs in China are 0.05% cyclomycin A (CsA) ophthalmic solution and FK506 ophthalmic solution.
2.2.3 Lipid replacement therapy
Lipid deficiency is common in patients with inadequate lipid secretion from the lid gland. Lipid replacement therapy may be effective in such patients, but no ideal drug is available.
2.3 Preservation of tears
Tear replacement therapy can replenish some of the tears, but it is still important to preserve as much of one’s own tears as possible, to prolong their stay on the ocular surface, and to reduce the use of artificial tears.
2.3.1 Silicone eye shields and wet room lenses
Providing an airtight environment that reduces air flow over the ocular surface and tear evaporation for the purpose of preserving tears is very effective for patients with dry eye and corneal exposure, and in some patients, artificial tears can even be discontinued.
2.3.2 Therapeutic corneal contact lenses
For patients with mild dry eye, such treatment with artificial tears can be more effective, but the contact lens needs to be kept moist when used. In patients with moderate to severe dry eye, the lenses worn are prone to dry out and fall off, so they are less often used.
2.3.3 Tear punctal plugs and tear punctal closure
Tear punctal plugs can temporarily block the tear ducts, prolonging the residence time of tears on the ocular surface itself and reducing the frequency of artificial tears. Studies have shown that tear punctal plugs are more effective in patients with mild to moderate dry eyes, and the frequency of artificial tears is significantly reduced, even if artificial tears are discontinued. For patients with severe dry eye, permanent tear punctal closure, including thermal cautery and surgical excision, can be considered after the use of pessary is ineffective.
2. 4 Surgical treatment
In patients with severe dry eye, surgical treatment can be considered when the condition does not improve with any medication. Current surgical treatment includes autologous submandibular gland transplantation, but this procedure is only used to treat very severe dry eyes and may result in severe corneal lesions.
2.5 Systemic drug therapy
2.5.1 Sex hormone therapy
The incidence of dry eye in postmenopausal women is significantly higher, suggesting that changes in sex hormone levels may be an important cause of dry eye. Some studies have found a decrease in both estrogen and androgen levels in menopausal women, and it has also been shown that reduced androgen levels are one of the main causes of reduced lacrimal gland function in SS patients. Therefore, topical application of androgens has been used to improve the secretory function of the lacrimal and lid glands, with good results in some patients.
2.5.2 Oral antibiotics
Tetracycline 250 mg orally 4 times a day or Doxycycline 50 mg orally twice a day. These two drugs are lipophilic and can reduce the synthesis of fatty acids and cholesterol esters by inhibiting the production of bacterial lipase, which is necessary for the development of blepharitis, so the above oral antibiotics can be used in the evaporative overactive dry eye caused by blepharitis.
2.5.3 Treatment of systemic immune diseases
Sjogren’s syndrome is often associated with a number of autoimmune diseases and patients are advised to combine medical-surgical, rheumatologic or dermatologic treatment.
There are more treatment options for dry eye, but all patients have poor outcomes. Different treatments are suitable for different patients with dry eye, therefore, the current treatment of dry eye should be individualized and combined.