severe dry eye disease

BRING TEARS TO THEIR EYES

A look at the current options for managing severe dry eye disease

AMBER GAUME GIANNONI, O.D., F.A.A.O., Houston, Texas

IT IS ESTIMATED THAT 10% TO 12% of our dry eye disease (DED) patients suffer from the severe form.¹ These individuals are often non-responsive to common treatment strategies and continue to suffer or seek alternative care. For these reasons, we must be aware of all treatment options to manage severe symptoms, even if considered non-traditional.

Severe meibomian gland dysfunction (MGD)

When warm compresses, omega-3 supplementation and oral and topical antibiotics aren’t enough to improve severe MGD, consider these options:

► LipiFlow Thermal Pulsation System (TearScience Inc.). This device liquefies and expresses obstructing oils from the meibomian glands (MG). Specifically, a topical anesthetic is instilled, and a sterile, single-use “activator” is placed over the eye to heat and apply pulsing pressure to the upper and lower lids. It takes 12 minutes per eye, and the therapy is given approximately once a year. Sustained relief depends on MGD severity, age, medication use and compliance with other dry eye therapies.

Supporting data: LipiFlow has been shown safe and efficacious, demonstrating significant improvement in MG secretions at two and four weeks post-treatment in a 139-subject study.²

Contraindications: These include ocular injury, surgery, herpetic infection or ocular inflammation within the past three months. Exercise caution in using it in those who have systemic conditions causing dry eye, including Sjogren’s syndrome, use drugs that exacerbate dry eye symptoms (e.g. antihistamines, etc.), or who have eyelid abnormalities, severe lid swelling, severe vernal or papillary conjunctivitis or ocular surface abnormalities that could compromise overall corneal integrity.³

Potential adverse events: These include thermal injury, eye or eyelid swelling, pain, irritation, stinging, redness or infection.³

Costs: $100,000 (device). You determine patient cost, which is 100% out-of-pocket.

Coding: This is 0207T (Category II CPT): Evacuation of meibomian glands, automated, using heat and intermittent pressure, unilateral.

► The Maskin Meibomian Gland Intraductal Probe (Rhein Medical). A thin, steel filament is used to penetrate the MG orifice and break-up fibrovascular tissue within the gland. An ophthalmic anesthetic ointment is applied to the lid margin, and once the lid is fully anesthetized, the probe is inserted into the affected gland. Often, a small “pop” is heard or felt, indicating successful fibro-vascular tissue penetration. Care must be taken not to pierce the gland’s distal end. The procedure takes approximately 15 minutes per lid, and a small amount of bleeding is normal. Dr. Maskin says a single treatment can last from 12 to 18 months.⁴

Supporting data: A total of 96% of 25 obstructive-MGD patients reported immediate relief post-procedure, 100% had symptom relief by four weeks post-probing, and 80% of these patients required just one retreatment an average of 11.5 months.⁵

Contraindications: None have been reported.

Potential adverse events: These include lid swelling, lid tenderness, infection and gland perforation.

Practitioner cost: Ten single-use probes (a box) cost $158.

Coding: Dr. Maskin recommends utilizing CPT codes for chalazian excision, which include 67800, 67801 and 67805. However, check with your insurance companies and state laws regarding proper coding and to determine whether you can perform this procedure.

Off-label topical therapies

Inform patients of the “experimental” nature of the following treatments, and have them sign an Advanced Beneficiary Notice (ABN) regarding out-of-pocket costs.

► Autologous serum tears (AST): These tears are developed by mixing serum from the patient’s own blood with non-preserved artificial tears. These tears are essentially hypo-allergenic and contain important nutritional components to promote corneal healing. Few O.D.s have a licensed phlebotomist or the proper lab certification or equipment to prepare ASTs in their offices, so this prescription often requires a referral to a local lab or university hospital.

Approximately 40ml of blood is drawn and centrifuged to prepare a three-month medication supply in your specified concentration. It must be freezer-stored, and open vials should be refrigerated between uses to avoid efficacy degradation and contamination. Initially, drops are often prescribed up to every q2h and then tapered to b.i.d. to q.i.d., as corneal health improves. Patients should be followed closely and are likely to stay on the ASTs long-term.

Supporting data: ASTs contain nutritional components for healing, such as vitamin A, epithelial growth factor (GF), transforming GF-?, platelet-derived GF, hepatocyte GF, fibronectin, albumin, ?-2 macroglobulin and neuropeptides.^6,7 Also, these tears appear to upregulate goblet cell production and stabilize the tear film.⁸

Ideal candidate: Patients who have persistent epithelial defects despite maximum standard DED therapy, those sensitive to over-the-counter tears or those at risk of DED-caused vision loss are ideal.

Contraindications: Due to reports of patients with autoimmune disease developing immune-related ocular inflammatory events with copious use of 100% formulations, some researchers recommend a 20% preparation every q2h and take caution in prescribing ASTs for this patient population.^9,10 Also, due to the potential for accidental inoculation by tears made from a donor infected with HIV or hepatitis, these diseases may be considered contraindications.

Potential adverse events: These include immune-related inflammatory events (i.e. limbitis, ulcer) in patients with autoimmune disease, and microbial keratitis secondary to bottle contamination, since ASTs are not preserved.

Patient cost: AST costs roughly $300 to $400 for a three-month supply.

Coding: N/A

► Dehydroepiandrosterone (DHEA). Compounded topical ophthalmic testosterone (3% cream or 1% suspension) may improve corneal health and ocular comfort in androgen-deficient individuals.^11,12 Very little is published on topical ophthalmic DHEA, so which formulation may provide the greatest benefit is unclear. Most patients are prescribed this medication b.i.d. and likely must continue it long-term to obtain sustainable effects.

Supporting data: Androgens are involved in the regulation of the meibomian and lacrimal glands, so it makes sense that individuals deficient in circulating androgens are at higher risk for DED. In androgen deficiencies, such as Sjogren’s syndrome and androgen insensitivity syndrome, this can result in catastrophic ocular surface disease.¹³

Ideal candidate: Androgen deficient patients, including those who are post-menopausal.¹⁴

Contraindications: Limited clinical data exists regarding topical DHEA contraindications and side effects for DED. Until more is known, err on the side of caution, and avoid prescribing it for pregnant patients and those who have an androgen-related malignancy history, such as prostate or breast cancer.

Potential adverse events: Oral DHEA ingestion may result in hair loss or excessive hair growth, acne, fluid retention, virilization, elevated cholesterol and heart and liver problems. These side effects are probably less likely with topical application, however, we simply don’t know. Counsel patients on the possibility of blurred vision, redness and stinging upon instillation.

Patient cost: DHEA costs approximately $80 per 10ml ($600 a year, depending on frequency).

Coding: N/A

► Non-preserved topical ophthalmic acetylcysteine. This compounded mucolytic may aid in reducing filamentary keratitis. Drops are usually prescribed q.i.d. in 5%, 10% or 20% concentrations, and patients initially return within a few days to a week for medication tolerance and response assessment. Filaments won’t likely completely vanish. However, those that do form are smaller and loosely attached. These drops, which smell like sulfur, are often prescribed long-term, and bottles should be discarded after 30 days.

Supporting data: Acetylcysteine has managed filamentary keratitis for decades.¹²

Ideal candidate: One who has persistent filamentary keratitis despite copious artificial tears, gels, hydroxypropyl cellulose inserts (Lacrisert, ATON Pharma, Inc.) cyclosporine ophthalmic emulsion 0.05% (Restasis, Allergan) and punctal occlusion use as well as scleral lens patients who accumulate mucous debris in the chamber between the cornea and the lens are ideal.

Contraindications: Known or suspected acetylcysteine sensitivity is a contraindication.

Potential adverse events: These include burning, stinging and micro-bial keratitis secondary to bottle contamination, as it is non- preserved.

Patient cost: This treatment costs $40 to $50/month depending on concentration.

Coding: N/A

On-eye protection options

Three options comprise this treatment category:

► Long-term therapeutic contact lens. These lenses, often called “bandage lenses,” are typically worn from a few days to several months to protect the cornea from filament adherence and to facilitate ocular surface healing. During lens wear, a prophylactic antibiotic is recommended to decrease the risk of microbial keratitis, which is higher in ocular surface disease patients.^15,16 For the prevention of filament formation alone, weekly follow-ups are recommended initially, if the patient can be trusted to contact you immediately upon redness, irritation, pain or reduced vision. For a concurrent epithelial defect, daily follow-up visits are necessary, which can be reduced to every few days, as the epithelium begins to heal.

Supporting data: The benefits of soft bandage lenses have been recognized for decades.¹⁷

Ideal candidate: Patients who have severe, persistent filamentary keratitis or non-healing epithelial defects are ideal.

Contraindications: These include cular infection or corneal ulcer.

Potential adverse events: Extended-wear increases the risk of microbial keratitis and corneal hypoxia, especially in patients who have poor tear film.

Patient cost: You set the fitting fees.

Coding: Use CPT code 92071 (fitting of contact lens for treatment of ocular surface disease). Unlike CPT code 92070, which is now extinct, 92071 does not include lens cost. Therefore, also use a materials code (99070). (Due to this new, narrower definition, some insurance carriers will deny this code if fitting for purposes other than ocular surface disease, such as corneal abrasion secondary to trauma. In this case, charge the patient for an office visit only.)

► Scleral contact lenses. These lenses cover a large surface area and vault the entire cornea, acting as a protective shield from environmental irritants. Since the lens is filled with non-preserved saline prior to application, the cornea is also constantly bathed in fluid, which can aid in healing. These lenses are worn during daytime only, and patients are typically followed quarterly unless complications arise.

Note this severe dry eye disease patient’s substantial fluorescein staining of 100% of the cornea, along with numerous filament strands.

Supporting data: Several studies have demonstrated the successful application of scleral lenses in various severe ocular surface disorders, including Stevens-Johnson syndrome, graft vs. host disease and exposure keratopathy.^18-20 In most cases, improved quality of life was experienced, and symptoms, such as poor visual acuity, photophobia and pain, were substantially reduced. ^19,20

Ideal candidate: One who has severe evaporative dry eye, filamentary keratitis, persistent epithelial defects or corneal irregularity is ideal.

Contraindications: Infection or corneal ulcer are common contraindications.

Potential adverse events: Foggy vision, usually secondary to mucous build-up behind the lens is an adverse event. Tell patients they may have to rinse and re-apply their lenses a few times a day for the best visual outcome and overall ocular health. Also, inform them they’ll most likely need to continue artificial tear use for lens wetting and comfort, although the frequency will likely be reduced. To minimize debris accumulation, try reducing the lens vault, prescribe topical acetylcysteine to aid in the breakdown of mucous strands, or fill the bowl with a thick solution combination, such as ½ non-preserved carboxymethyl cellulose and ½ non-preserved saline.²¹

Patient cost: You set the therapeutic fitting fees. Material costs range from $200 to $400 per lens, plus the supply of non-preserved saline ($10/month).

Coding: The codes are 92071: fitting of contact lens for treatment of ocular surface disease and 99070: supply of lenses.

► Prokera (Bio-Tissue, Inc.). This class II, sutureless medical device is comprised of a thermoplastic ring (similar to a symblepharon ring) that holds a thin, 16mm-wide amniotic membrane over the cornea. Although the membrane should facilitate the healing of most defects within five to 10 days, it can be left in place for up to a month or until it naturally dissolves, and the ring is removed. You can monitor corneal healing closely, as fluorescein staining can be easily visualized beneath the membrane.

Supporting data: Amnion has anti-bacterial, anti-inflammatory and anti-scarring properties and has shown promise as an effective treatment for persistent ocular surface disease treatment.²²

Ideal candidates: Those who have persistent corneal epithelial defects, such as recurrent corneal erosion, and those who have high-risk corneal transplants, Stevens-Johnson syndrome and chemical burns.²³

Contraindications: According to the product insert, the device is shipped in a storage medium containing ciprofloxacin and amphotericin B and, therefore, should not be used in patients who have a history of reactions to these drugs. says the product insert. Also, due to interference with device placement, Prokera is not compatible in eyes that have glaucoma blebs or drainage implants.²⁴

Potential adverse events: These are include discomfort from the ring’s thickness and risk of infectious agent transmission.

Coding: The code is CPT 65778: placement of amniotic membrane on the ocular surface for wound healing; self-retaining. Check your state laws to determine whether you can perform this procedure.

Surgical management

When all else fails, consider the following surgical options:

► Conjunctivoplasty. Redundant conjunctiva, or conjunctivochalasis, is removed to restore the normal tear outflow and reduce tear stagnation, which can exacerbate inflammation and ocular dryness. Conjunctivochalasis can have a significant negative impact on ocular surface health and can be a predictive factor for contact lens-related dry eye.²⁵

Supporting data: In one study, removal of redundant tissue greatly improved symptoms of irritation and dryness, while statistically improving corneal fluorescein staining scores.²⁶

Contraindications: Immunocompromised individuals or patients with uncontrolled diabetes patients who experience reduced wound healing capability are not ideal candidates for this procedure.

Potential adverse events: Risk of infection and irregular ocular surface, which can exacerbate DED, as tears won’t spread evenly.

► Autologous submandibular gland transplantation. The submandibular gland is transplanted into the temporal fossa to provide salivary secretions to the ocular surface through an excretory duct.

Supporting data: This has been performed on patients with cicatrizing conjunctivitis patients, as well as in severe DED secondary to Stevens Johnson syndrome and chemical burns.^27-29 Overall, researchers observed less ocular surface damage, and most patients reported a reduction in artificial tear instillation frequency, and improved ocular comfort.

Ideal candidate: A patient who has a Schirmer score <2mm.

Contraindications: A prior reaction to general anesthesia and reduced wound healing capability are contraindicated.

Potential adverse events: Corneal edema, from the low osmolarity composition of salivary secretions, which could compromise visual acuity, is a potential adverse event.

Cost: unknown

Coding: unknown

► Implantable pump reservoir. This is placed below the rib cage and contains an isotonic electrolyte solution. This solution is constantly delivered to the eye via two subcutaneous silicone catheters.

Supporting data: In one study, all subjects perceived dramatic symptom improvement. Also noted: a substantial reduction in signs of ocular surface disease, including improved corneal staining and tear break-up time.³⁰

Ideal candidate: Patients who have Schirmer scores of <2mm and require continuous ocular surface lubrication are ideal.

Contraindications: A prior reaction to general anesthesia and reduced wound healing capability are contraindications. Because the device must be refilled every 40 days in an operating room, this procedure is not ideal for patients unable to make this commitment.

Potential adverse events: Side effects in the aforementioned study were rare and reported as non-serious (i.e. skin ulceration due to the catheter). Although infection did not occur, it is always a potential side effect with any surgery.

Cost: unknown

Coding: unknown

Knowledge is power

It is imperative we be well-informed of new treatments and technologies for severe dry eye disease, even if considered off-label, so we can effectively meet our patient’s needs. OM

References are available in the online version of this article at optometricmanagement.com.

Dr. Gaume Giannoni is a clinical associate professor and co-director of the Dry Eye Center at the University of Houston College of Optometry. E-mail her at AGaume@optometry.uh.edu, or send comments to optometricmanagement@gmail.com.