CLINICAL

  ANTERIOR

AQUEOUS-DEFICIENT DED

BE JUDICIOUS ABOUT MANAGING BOTH FORMS OF DRY EYE DISEASE

JOSH JOHNSTON, O.D., F.A.A.O.

A FEW months ago, a 77-year-old female presented for a second opinion on her dry eye disease (DED). She said she travelled four hours from her home to see me after reading online about the DED services my practice offers. (No pressure, right?)

The patient explained she had seen several eye care practitioners through the years and tried numerous treatments, such as artificial tears, a lid hygiene product, warm compresses, doxycycline, omega-3 fatty acid supplementation and, most recently, thermal pulsation treatments OU, with minimal relief.

A full bevy of diagnostic tests revealed both meibomian gland dysfunction (MGD) and aqueous-deficient DED, the latter of which was apparently overlooked by her previous eye doctors.

Here, I discuss the etiology, symptoms, clinical signs, diagnosis/management options, as well as the ICD-10 codes for aqueous-deficient DED and what happened with this patient.

ETIOLOGY

Aqueous-deficient DED results from a failure of tear production and is divided into two subcategories, Sjögren’s syndrome DED and non-Sjögren’s DED, based on the 2007 Report of the International Dry Eye Workshop (DEWS). (Incidentally, DEWS II is in the works.)

Sjögren’s syndrome DED occurs when an autoimmune process causes the lacrimal and salivary glands to become inundated with activated t-cells. These cells, in turn, induce acinar and ductular cell death, which leads to diminished tears and saliva.

Sjögren’s syndrome DED is comprised of two categories: Primary SS and Secondary SS. Primary SS is aqueous-deficient DED and dry mouth (from a decrease in salivary secretions). Secondary SS is primary SS with an autoimmune connective disease, such as systemic lupus erythematosus.

Non-Sjögren’s DED is lacrimal gland dysfunction that is not due to autoimmune disease. It includes primary lacrimal gland deficiencies (e.g. age-related DED), secondary lacrimal gland deficiencies (e.g. sarcoidosis), obstruction of lacrimal gland ducts (e.g. erythema multiforme) and reflex hyposecretion from, for example, contact lens wear.

The common risk factors for aqueous-deficient DED are advancing age; sex (it affects both men and women, with women suffering more than men, due to hormonal changes); medication use (antihistamines, decongestants, oral contraceptives, ACE-inhibitors, diuretics and anti-depressants); and poor diet (low amounts of fatty acids, low water intake and excess caffeine and alcohol consumption). Additional common risk factors: low humidity environments (ceiling fans, air vents); excessive visual tasking (reading and digital screen use decrease blink rates and increase tear film evaporation); autoimmune disease (diabetes, rheumatoid arthritis, lupus, Sjögren’s syndrome, etc.); and refractive surgeries.

SYMPTOMS

• Blurred vision

• Burning

• Contact lens discomfort

• Dryness

• Fatigue

• Foreign-body sensation

• Grittiness

• Stinging

CLINICAL SIGNS

• Conjunctival staining

• Corneal staining

• Hyperemia

• Increased ocular surface inflammation

• Increased tear osmolarity

• Punctate keratitis

DIAGNOSIS/MANAGEMENT

The following can be used to diagnose aqueous-deficient DED:

• Lissamine green and rose bengal staining viewed under white light. Rose bengal stains living, damaged and dead corneal and conjunctival cells that occur with DED. It does burn, so other dyes are preferred. Lissamine green stains membrane-damaged and devitalized cells and is mainly used to view conjunctival staining from dry eye.

• Matrix Metalloproteinase-9 (MMP-9) test. MMP-9 is a proteolytic enzyme and a non-specific inflammatory marker associated with DED. A positive test occurs when there is >40 ng/ml of MMP-9 detected in the tears.

• NaFL staining viewed with cobalt blue light. NaFL can show punctate keratitis, and it is used to conduct TBUT testing.

• Phenol red thread test. This test measures tear production in 15 seconds. Wet lengths less than 10 mm are considered DED test results.

The top photo shows diffuse punctate epithelial keratitis stained with sodium flourescein. The bottom photo shows staining of severe keratoconjunctivitis sicca.

• Sjö diagnostic test (Bausch + Lomb). This is a blood test that combines four traditional biomarkers with three propriety biomarkers to detect Sjögren’s syndrome early.

• Schirmer test. This measures basal and reflex tear production. Normal results are indicated by wetting of >15 mm in five minutes. Shorter measures of wetness indicate increased severity of dry eye and reduced tear production.

• Tear osmolarity testing. This test looks at the concentration of electrolytes in the tear film. High osmolarity numbers >308 and differences between the eyes >8 can indicate DED.

Aqueous-deficient DED requires a treatment plan that decreases inflammation and increases natural tear production. Such treatments, in order of association with least to most severe disease:

• Artificial tears. These offer short-term relief. For aqueous-deficient DED, many traditional tears are aimed at replacing decreased levels of aqueous to add comfort and symptomatic relief, and they can be used q.i.d. When needed more frequently, I recommend a more viscous tear or a non-preserved artificial tear because frequent use of preservatives can cause corneal toxicity. Also, more viscous tears have a long residence time, which relieves the symptoms of more severe patients.

• Immunosuppressive drops. Cyclosporine ophthalmic emulsion 0.05% (Restasis, Allergan) decreases ocular surface inflammation and increases mucin levels by reducing goblet cell apoptosis and increasing goblet cell density and proliferation.

• Ester-based steroids. Prescribe these four weeks or longer (hopefully less than six weeks) as long as they aren’t causing an IOP increase. They decrease inflammation, which is the root cause of aqueous-deficient DED.

• Punctal occlusion. These work by reducing tear clearance and increasing tear residence time.

• Environmental changes. Recommend the use of a humidifier by the patient’s bed or near his or her work environment to reduce low humidity environments.

• Nutritional supplements. Prescribe omega-3 supplements, which have been shown to decrease ocular surface inflammation and increase tear production. They are beneficial in both evaporative and aqueous-deficient dry eye.

• Dietary changes. Recommend increased water intake and the decrease of alcohol and caffeine consumption, as the latter can exacerbate the symptoms associated with aqueous-deficient DED.

• Autologous serum drops. Natural human tears are best for the ocular surface. By having a patient undergo a blood draw, plasma can be separated from the serum to make tears. This process gets close to recreating tears produced by the lacrimal gland.

• Amniotic membranes. These bandage biologic contact lenses help decrease ocular surface inflammation, promote healing and can be used to improve severe ocular surface disease. The healing properties in the membrane allow for the healing and repair of damaged corneas.

• Medication changes. Evaluate the patient’s systemic medications, such as beta-blockers and diuretics, to see whether they are associated with aqueous-deficient DED and whether the patient should discuss with his or her primary care provider altering systemic medication use to lessen symptoms.

Possible future treatments: Oculeve (Allergan), Lifitegrast (Shire), CyclASol (Novaliq), Thymosin beta-4 (Tβ4) (RegeneRX) and Tavilermide (Mimetogen).

THAT PATIENT

That patient’s medical history revealed many risk factors for aqueous-deficient DED, including several systemic diseases, such as rheumatoid arthritis. As a result, I shifted her treatment focus from exclusively MGD to both MGD and aqueous-deficient DED. I added cyclosporine and topical steroids to her plan. (She was well covered with MGD treatments, but the most common on-label and off-label treatments for aqueous-deficient DED were not previously prescribed.) I’m pleased to report that the patient’s symptoms have slowly improved.

Many patients, like this one, have multi-factorial DED. As clinicians, we must perform the appropriate tests to ensure all DED is identified and treated. OM

DR. JOHNSTON practices at Georgia Eye Partners. He has relationships with Alcon, Allergan, BioTissue and Shire. Email him at drj@gaeyepartners.com, or visit tinyurl.com/OMcomment to comment.