Article

DEFY DRY EYE...

…with the following therapy options for aqueous and evaporative DED

When it comes to the treatment of DED, the individual treatment plan varies among patients, depending on the underlying problem. Whether the signs and symptoms are worsened by an aqueous deficiency, evaporative DED, secondary to MGD, or a combination of both, it is important to be familiar with the different treatment options to tackle this progressive disease.

Here, I’ll take you through treatment options, based on the causation of DED.

Corneal and conjunctival edema secondary to chronic contact lens overwear.
Photo courtesy of Jade Coats, O.D.

AQUEOUS-DEFICIENT

Aqueous-deficient DED typically can be best managed by the following treatments:

Artificial Tears

Ideal patients: Those who have reduced tear film stability due to aqueous-deficient and/or evaporative DED, artificial tears help provide the quality tear replacement necessary for mild, moderate and severe DED.

Current formulations: Depending on the severity of ocular surface disease, a range of substances from low-viscosity drops to high-viscosity gels and ointments are offered. While preservative-free artificial tears are recommended throughout the day, ointments and gels are often used nightly for moderate to severe DED. Preservative-free artificial tears are typically preferred because they contain fewer toxic additives, such as benzalkonium chloride. For evaporative DED or prolonged dryness, a lipid-based artificial tear may be necessary to supplement the tear film with the needed oil component.

Contraindications/adverse events: Although a safe stand-alone treatment option for mild DED, sometimes artificial tears mask the symptoms of DED and can disguise the root cause of the problem. For example, contact lens wearers are often recommended an artificial tear; however, this can also, unfortunately, disguise a contact lens sensitivity or intolerance.

Dosing: For symptomatic patients, artificial tears are typically recommended two to six times daily, but can safely be used as often as needed. Patients with moderate and severe aqueous-deficient DED may need additional therapies to experience maximum relief, such as in the case of Sjögren’s syndrome.

• Cyclosporine

Ideal patients: Patients who have presumed keratoconjunctivitis sicca caused by reduced lacrimal tear production due to auto-immune disorders, such as Sjögren’s syndrome, can benefit. Also, patients who chronically use medicines (i.e. antihistamines, antidepressants, hormone replacement therapy, etc.) that can cause side effects, such as decreased lacrimal tear production can see results.

Current formulations: As an ophthalmic emulsion, cyclosporine 0.05% is offered in both preservative-free vials and multi-dose bottles. CsA cyclosporine 0.1% is also available via a compounding pharmacy.

Contraindications/adverse events: The most frequently reported adverse event is temporary ocular burning, redness and tearing.1

Dosing: Recommended twice a day with 12 hours between uses. Cyclosporine is often used in conjunction with artificial tears. It takes about 90 days for patients to experience relief.

Punctal plugs

Ideal patients: Patients who have aqueous deficiencies caused by Sjögren’s syndrome, contact lens wear or medicines (described above) that decrease tear production can benefit. In addition, patients who are non-compliant with artificial tears, or those affected by dexterity issues may see relief from plugs.

Current formulations: Inserting punctal plugs involves a quick non-invasive procedure that typically includes a collagen or silicone plug inserted into the lower and/or upper puncta. Often ranging from 0.4 mm to 0.8 mm, plugs help delay tear drainage and allow tears to stay in contact with the cornea for a longer duration. Collagen plugs provide a temporary solution that may help determine whether the patient is a good candidate for semi-permanent silicone punctal plugs or permanent punctal cautery. Permanent punctal cautery is typically reserved for patients who have severe aqueous-deficient DED and have previously tried the temporary plugs with success.

Contraindications/adverse events: Although plugs can help alleviate the symptoms of aqueous-deficient DED, they do not treat the underlying problem. Rarely, punctal plugs have a small chance of causing epiphora, conjunctival epithelial erosion or pyogenic granulomas that can form if the plug migrates into the nasolacrimal duct.

Dosing: Collagen plugs typically dissolve within a week; silicone plugs last three to six months.

Nasal neurostimulation

Ideal patients: Patients who desire an alternative, at-home DED treatment choice and who prefer a drug-free, drop-free DED treatment option can benefit. (For information on the current system, see p.50.)

Current formulation: Via the nasal canal, nasal neurostimulation stimulates the trigeminal nerve to increase natural tear production. By targeting goblet cells, meibomian glands and lacrimal glands, it causes an immediate production of mucin from goblet cells, meibum from the meibomian gland, and aqueous from the main lacrimal gland.2

Contraindications/adverse events: The most common side effects are nasal pain, irritation post-stimulation or nose bleeds, which occurred in 5% to 10% of patients. The device cannot be used for more than 30 minutes in a 24-hour period.2 (The device is not covered by insurance.)

Dosing: Nasal neurostimulation is recommended at least twice a day for no more than three minutes per session, as needed.2

FROM THE ARCHIVES

MORE DRY EYE COVERAGE FROM OM

→ Autologous Serum: The natural tear is loaded with mediators and proteins that create homeostasis. Read more in “DED Symptom Solutions” in July 2016 or http://bit.ly/2sQ0vSm .

→ Mild to severe. Dr. Ami Ranani breaks down his treatment plan among patients who have mild, intermediate and severe DED in “Manage Dry Eye Disease,” from July 2016, available at http://bit.ly/2Jxb3jS .

→ “How to Offer Ocular Nutritional Supplements.” Dr. Douglas K. Devries takes the reader through the steps he uses to offer this therapy in his office from April’s magazine, available at http://bit.ly/2uOPBQq .

→ TFOS DEWS II: Guest editor Dr. Whitney Hauser has offered her in-depth analysis of the TFOS DEWS II report in her regularly occurring “Dry Eye” column. Published pieces appeared in January, http://bit.ly/2EWvK27 , and April, http://bit.ly/2F4qwAG .

Search Optometricmanagement.com for “dry eye disease” for even more insights.

EVAPORATIVE

Evaporative DED contributes to the large majority of DED cases and can be managed by the following treatments:

Hot compress/eye mask

Ideal patients: Patients who have MGD can benefit.

Current formulations: Eyelid warming masks heat the meibomian glands to soften the thickened meibum. Some patients opt for the hot compress alternative, which involves the ‘bundle method,’ to heat several moistened cloth towels at once. This option provides a heat supply for a 10-minute treatment and eliminates time and the inconvenience of having to reheat during the treatment.

Contraindications/adverse events: Unless done properly with extremely hot water (>120 F) used for 10 to 15 minutes, the maximum effectivity to sufficiently allow expression isn’t reached.3

Dosing: Typically recommended nightly, but twice daily is even better.

Lid scrubs and sprays

Ideal patients: Patients with poor lid hygiene and/or lid margin disease can benefit.

Current formulations: Lid scrubs are used along the lid margin for mild to moderate anterior blepharitis. Alternatively, lid sprays are for more moderate to severe blepharitis.

Contraindications/adverse events: Although these scrubs and sprays effectively remove eyelid debris and bacteria, they do not address the underlying chronic inflammation of DED.

Dosing: Typically recommended twice daily.

Ocular nutritional supplements

Ideal patients: Those interested in an oral supplementation to increase goblet cell density, thus decreasing the incidence of DED, can benefit.

Current formulations: Supplementation of omega-3 and omega-6 fatty acids help to promote anti-inflammatory activity and provide benefits to those who have inadequate tear film stability.

Contraindications/adverse events: Before recommending an ocular nutritional supplement, it’s important to ask patients whether they are taking anticoagulants or blood thinners, as supplements with EPA may increase bleeding time.4

Dosing: Typically recommended by mouth twice or three times a day, it commonly takes up to a month for a patient to notice effectiveness. The FDA generally considers 3 g of omega-3, EPA and DHA fatty acids, per day as safe.5 Adequate intake of omega-6 for adults, ages 19 to 50 is 17 g/day for men and 12 g per/day for women.6

Lifitegrast

Ideal patients: Post-surgical patients, contact lens wearers and patients who have mild, moderate and severe DED can benefit. Lifitegrast 5% ophthalmic solution is indicated for the treatment of the signs and symptoms of DED.

Current formulation: The solution acts as an LFA-1 antagonist directly on the surface of the cornea. It is available in preservative-free vials.

Contraindications/adverse events: Dysgeusia, decreased VA and a temporary burning on instillation occur in 5% to 25% of patients.7

Dosing: It is recommended twice a day with a spacing between drops of 12 hours.7

Topical corticosteroids

Ideal patients: Patients who have symptoms of moderate to severe DED and, specifically, associated inflammation that can’t be controlled by cyclosporine or LFA-1 alone can benefit.

Current formulations: Corticosteroids are generally used short-term to quickly manage symptoms of ocular inflammation. They often are used in conjunction with artificial tears and as a complement to other more long-term treatments.

Contraindications/adverse events: Long-term treatment of steroids can lead to complications, such as cataracts.

Dosing: Typically, topical steroids are tapered from four times a day to once a day over the course of seven to 14 days for mild to moderate DED.

Antibiotics

Ideal patients: those with blepharitis and MGD can benefit.

Current formulations: For most who have anterior blepharitis, topical antibiotic ointments work effectively. Oral tetracyclines are used in patients who have more severe disease.8

Contraindications/adverse events: Oral tetracyclines are not suitable for pregnant or female patients of childbearing age.8 Sometimes, oral minocycline may be considered over doxycycline to decrease the incidence of sunburn and photosensitivity.8

Dosing: Ointments are often recommended every day up to three times a day. Oral tetracyclines are typically recommended 50 mg to 100 mg twice a day for one to four weeks, depending on the severity of the inflammation.

Meibomian gland debridement

Ideal patients: Patients who have blepharitis and chronic eyelid inflammation causing a secondary evaporative DED and those who are non-compliant with lid scrubs can benefit.

Current formulation: Handheld tool that removes lid debris and microbial biofilm along the lid margins.

Contraindications/adverse events: Some patients report a mild “tickling” of the lids during the use of the tool.9 (This procedure is not currently covered by health or vision insurance.)

Dosing: The cleaning procedure should be applied to the upper and lower lids, and should be repeated every four to six months, as needed.

Thermal pulsation

Ideal patients: Patients who have MGD can benefit.

Current formulations: By providing the eyelid with a gentle heated massage, thermal pulsation devices help unblock the meibomian glands to resume the natural production of lipids needed for a stable tear film.

Contraindications/adverse events: Transient blurred vision, corneal abrasions and eyelid irritation, among others have been noted.10 (The procedure is not covered by insurance.)

Dosing: One procedure lasts about 12 minutes per eye, but both eyes are typically done simultaneously.11 Treatment is typically every nine months as needed.11 The other procedure is recommended for three treatments, lasting under 20 minutes, two weeks apart.12 The results tend to be best when repeated every 12 months as needed.12

Intense pulsed light (IPL)

Ideal patients: Patients who have dilated blood vessels and telangiectasia near the eyelids and adnexa caused by ocular rosacea and/or blepharitis can benefit. Also, patients who would like an alternative dropless DED treatment can benefit.

Current formulation: IPL uses non-coherent light (from visible, 515 nm to infrared spectrum, 1,200 nm), applied to the lower lid/lateral canthal area to be absorbed by blood vessels to reduce inflammation.13-14 Special eye shields should be worn for protection.

Contraindications/adverse events: Patients have reported that the zaps may be temporarily uncomfortable, and warmth/redness may be experienced where the IPL is applied. IPL is currently used with caution in patients who have darker pigment, as it can cause lightening of the treated skin area.14

Dosing: Treatment parameters can be customized based on the severity of DED and are often recommended every two to four weeks until the meibomian glands have been normalized. Once the glands have improved, maintenance treatments are suggested every six months.14

Amniotic membrane

Ideal patients: Patients who have moderate to severe DED and who have tried other therapies with minimal improvement can benefit.

Current formulations: Amniotic membranes effectively and rapidly accelerate corneal healing. Offered in dehydrated and cryopreserved, both options are suture free and can be applied in-office to provide a biological bandage.

Contraindications/adverse events: Insurance may or may not cover the service. (For more, see “Membranes” p.41.)

Dosing: Typically, patients wear the membrane for three to five days for mild ocular surface reconstruction or seven to 14 days for more moderate-severe DED.

MULTIFACTORIAL DISEASE

DED is a naturally multifactorial disease. As such, the treatments listed above may be appropriate in the treatment of a patient who exhibits signs and symptoms of both evaporate and aqueous-deficient DED. This listing is provided as a guide, but you, as the patient’s doctor, in concert with the diagnostic findings, decide what treatments may be in the best interest. OM

REFERENCES

  1. Restasis Product Information. Restasis website. Restasis.com. Accessed June 5, 2018.
  2. Allergan. Patient Guide to the TrueTear intranasal tear neurostimulator. Accessed May 1, 2018.
  3. Kenrick CJ, Alloo SS. The Limitation of Applying Heat to the External Lid Surface: A Case of Recalcitrant Meibomian Gland Dysfunction. Case Rep Ophthalmol. 2017; 16: 7-12.
  4. Omega-3 Supplements: In Depth. National Center for Complementary and Integrative Health website. https://nccih.nih.gov/health/omega3/introduction.htm . Updated May 2018. Accessed June 5, 2018.
  5. US Food and Drug Administration. Substances affirmed as generally regarded as safe. Federal Register. 1997; 62: 30757-7.
  6. Food and Nutrition Board, Institute of Medicine. Dietary Fats: Total Fat and Fatty Acids. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: National Academies Press; 2002: 422-541. (National Academy Press)
  7. Prescribing Information for XIIDRA. Shire website. https://www.shirecontent.com/PI/PDFS/XIIDRA_USA_ENG.pdf Revised Dec. 2017. Accessed June 5, 2018.
  8. Ezuddin NS, Alawa KA, Galor A. Therapeutic Strategies to Treat Dry Eye in an Aging Population Drugs & Aging. 2015; 32: 505–13.
  9. BlephEx. Rysurg website. http://www.rysurg.com/doctors/index.php/how-does-blephex-work.html Accessed June 5, 2018.
  10. LipiFlow Thermal Pulsation System. Johnson & Johnson Vision website. https://tearscience.com/lipiflow/ Accessed June 5, 2018.
  11. Greiner JV. A Single LipiFlow Thermal Pulsation System Treatment Improves Meibomian Gland Function and Reduces Dry Eye Symptoms for 9 Months, Curr. Eye Res., 2012; 37: 272-78.
  12. MiBo Thermoflo. MIBO Medical Group website. http://www.mibomedicalgroup.com/mibothermoflo.html Accessed June 5, 2018.
  13. Craig JP, Chen YH, Tunbull PR. Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction. Invest Ophthal Vis Sci. 2015; 56: 1965-1970.
  14. Toyos R, McGill W, Briscoe, D. Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; A 3- year retrospective study. Photomed Las Surg. 2015; 33 41-6.

The following products may aid in your management and treatment of dry eye disease:

  • Artificial Tears (including gels and ointments)
    Refresh Optive Advanced (Allergan)
    Refresh Mega 3 (Allergan)
    Systane Ultra (Alcon)
    Systane Complete (Alcon)
    Soothe XP (Bausch + Lomb)
    Blink (Johnson & Johnson Vision)
    TheraTears (Akorn)
    NanoTears MXP (OcuSci)
    Retaine (OcuSoft)
  • Cyclosporine
    Restasis (Allergan)
    CsA (Imprimis)
  • Punctal Plugs
  • Hot Compresses/Eye masks
    TheraPearl (Bausch + Lomb)
    d.e.r.m. (Eyeeco)
  • Lid Scrubs
  • Topical corticosteroids
    Lotemax, Bausch + Lomb
    Alrex
  • Antibiotics
  • Amniotic Membrane
    ProKera (Bio-Tissue)
    AmbioDisk (IOP Ophthalmics)
    BioDOptix (BioD)
    OculoMatrix (Skye Biologics)
    VisiDisc (Skye Biologics)
    Aril (Seed Biotech)
  • Nasal neurostimulation
    TrueTear (Allergan)
  • Lifitegrast
    Xiidra (Shire)
  • Meibomian gland debridement
    BlephEx (Rysurg)
  • Thermal pulsation
    LipiFlow (TearScience)
    Thermoflo (MiBo Medical Group)
  • Intense Puled Light
    M22 (Lumenis)
  • Nutritional Supplements
    A full list of ocular nutritional supplements for the treatment of DED can be found at bit.ly/DryEyeSupp