Lower cost therapies available for many ocular conditions
Consider over-the-counter options, generics and nutritional supplementation when cost is a concern.
by Milton M. Hom, OD, FAAO
PCON Editorial Board member
This course is jointly sponsored by PCON, the State University of New York State College of Optometry and Vindico Medical Education. It is COPE-approved for 2 continuing education credits.
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As I lecture across the country, practitioner questions about care for the uninsured are more and more common. Costs of drugs are preeminent concerns on the minds of many patients. Most of the newer drugs work faster, require lower dosing and perform better than older drugs.
For many conditions, however, there are other lower cost therapies available. Complementary and alternative medicine (CAM) usually does not have the efficiency of the newer drugs but can sometimes mitigate the cost.
This article will cover allergy, dry eye, infection (bacterial keratitis and conjunctivitis) and glaucoma. For each disease state, treatments will be discussed in three categories: first class, economy (generic/over-the-counter) and low to no cost. The categories are meant to be general guidelines; there are many variations due to brand vs. generic versions, online pricing, manufacturers availability and dosing instructions. All available treatments will not be covered here. Many practitioners will find the last two categories appropriate for the new economy.
Ocular allergy medications
Topical allergy drops are the mainstay treatment for the eye care professional. The combination mast-cell stabilizers and antihistamines have great efficacy and require once daily or twice daily dosing. The safety margins are high with few side effects.
One combination medication, Zaditor (ketotifen fumarate, Novartis) is available OTC. Ketotifen can also be found in Bausch & Lombs Alaway, Allergans Refresh Eye Itch Relief and Zyrtec Itchy Eye Drops (McNeil). An older generic drug is Naphcon A (Alcon), with naphazoline as the active ingredient. The dosing is much more frequent and it is actually a vasoconstrictor.
The performance of naphazoline pales in comparison to combination drugs. Because it is a vasoconstrictor, it suffers from a host of warnings if used in patients with hypertension or cardiac conditions.
Steroids work well for ocular allergy. Alrex (loteprednol etabonate, Bausch & Lomb) does not have the safety issues of other steroids. Loteprednol has small chances of IOP increase and cataract formation as compared with other steroids.
As an alternative, Pred Forte (prednisolone acetate, Allergan) is available as a generic. The efficacy is high, but so are the risks for glaucoma and cataracts. Although more economical, prednisolone has a low safety margin and therefore should not be used more than 7 to 10 days. Other steroids such as dexamethasone, have the same cautions.
Loteprednol can be used as monotherapy or in combination. In severe cases, adding loteprednol twice daily concomitantly to a topical works extremely well, reported Luchs.
Nasal sprays are used to reduce rhinitis, but they are also effective in relieving ocular allergy symptoms, according to Bielory. Most of the prescribed nasal sprays are corticosteroids. Because the sprays are directed into the nose toward the eye, cataract risk has been called into question.
Conclusions from studies of corticosteroid nasal sprays are mixed. Some studies show risks, while other studies show none, according to Smeeth and colleagues and Derby and Maier.
An alternative to corticosteroids is NasalCrom (cromolyn sodium, McNeil). It is not a steroid and therefore has no reported cataract risks. It is available as an OTC spray and used twice daily.
In my practice, nasal sprays play an important role in ocular allergy management. They are cost-effective and usually reduce the need for topical allergy drops or oral non-sedating antihistamines. If more nasal sprays were prescribed, the entire topical ocular allergy market would shrink.
Butterbur is an herbal alternative that may better suit the preferences of some patients. Although it is a CAM treatment, it has the clinical potency of a pharmaceutical. Lee and colleagues have shown that 50 mg two or three times daily is as effective as Zyrtec without drowsiness.
Avoidance is the number one recommended treatment for allergy. Avoidance of allergens makes a lot of sense but, unfortunately, is often impractical.
Alternative treatments such as cool soaks help decrease inflammation when applied to the eye. Artificial tears can help flush the pollen or lower the pollen concentration in the tear film. Air cleaners can filter dust and other particles from the air.
Dry eye, lid disease treatments
Dry eye has been referred to as a chronic disease. For most cases there is no cure, only relief of signs and symptoms. There are many categories and sub-categories of dry eye. In simple terms, most dry eye patients suffer from aqueous deficient or evaporative (anterior or posterior blepharitis) causes. A third, less common, classification is distribution problems (lagophthalmos or incomplete blink), where lubrication is the primary treatment.
For inadequate production of lacrimal tears, Restasis (cyclosporine, Allergan) or loteprednol works well. Restasis is actually two components: emulsion vehicle and cyclosporine. Because the emulsion vehicle has strong clinical efficacy, Allergan versioned the vehicle for the OTC market as Refresh Dry Eye Therapy.
Another choice for aqueous deficient dry eye is loteprednol. Prednisolone is a lower cost option and has similar efficacy. Unfortunately, as mentioned before, there are numerous side effects associated with longer-term use. Another alternative with lower IOP risk is FML (fluorometholone, Allergan), also available as a generic.
Punctal plugs are also used for aqueous deficiency. LASIK patients generally suffer from dryness post-procedure, and plugs are standard treatments.
Lipid layer deficiencies usually stem from poor functioning meibomian glands (posterior blepharitis). AzaSite (azithromycin, Inspire) with lid therapy (warm compresses) is highly effective.
Erythromycin, available as a generic, is in the macrolide class similar to azithromycin. Erythromycin does not have the residence time or the half-life in the conjunctiva of topical azithromycin. The efficacy is greatly reduced and it takes at least 3 months to show any effect, according to John and Shah. Erythromycin is available in an ointment and may cause blurring.
Oral antibiotics such as doxycycline are used for lid disease. Their anti-inflammatory effects decrease lipase production of the bacteria in the meibomian glands. Typically, low-dose doxycycline or minocycline produces the anti-inflammatory effect.
OcuSofts Alodox Convenience Kit packages low dose doxycycline with lid therapy, including lid scrubs and eyelid cleanser. Doxycycline is available as a generic, but two low dosage forms have been branded: Periostat (20 mg, CollaGenex) and Oracea (40 mg, Galderma). If low-dose generic doxycycline is not readily available, we have some patients using a pill cutter (about $10) to divide the 100-mg tablets into smaller doses.
Lid therapy can be performed in many ways. Prepackaged lid therapy is offered by many companies. Some experts prefer uncooked rice microwaved 30 seconds in a sock over wet sterile gauze for applying moist heat to the lids. The patient can self-express the meibomian glands twice a day.
The benefits of artificial tears are to relieve burning, irritation and discomfort of the eyes due to dryness, as well as being economical. Artificial tears use different mechanisms of action to relieve signs and symptoms of dryness. They usually add viscosity to the tear film. The advantages of adding viscosity is tear film thickening and increased residence time. Because the tear washes out in minutes, increased residence time helps the patient retain the tears benefits. A disadvantage of viscosity is too much can lead to blurring.
HP guar in the Alcons Systane family is pH activated. It is thinner (lower viscosity) in the bottle and thickens (higher viscosity) when it hits the tear film. As the severity of dryness increases, the tear film pH becomes more alkaline (higher). When exposed to more alkaline tears, the viscosity of HP guar increases.
From a mechanism of action standpoint, there are basically two types of Systane: Systane Classic and Systane Ultra. Both are pH-activated and contain HP guar. The primary difference is the location of the viscosity curve. The viscosity curve for Systane Ultra is shifted to a higher pH than Systane Classic. The result is better performance (lower amounts of blurring) in more severe dry eye (higher pH).
Carboxymethylcellulose (CMC) in Allergans Refresh family adds viscosity and is muco-adhesive. The muco-adhesive property helps increase residence time. Allergans Refresh and Optive have CMC and rely on compatible solute technology. When the corneal cells dehydrate, salt is taken from the hypertonic tear film. Optive contains compatible solutes, L-carnitine, glycerin and erythritol. Instead of salt, the desiccated cells take the compatible solutes and form an osmoprotection effect.
Advanced Vision Researchs TheraTears works to influence the osmolarity of the tears. The tear film in dry eyes is hyperosmotic (high salt content). Tear osmolarity is a significant indicator for dry eyes according to the Dry Eye Workshop report. TheraTears is hypotonic and lowers the tonicity of the tear film, referred to by the manufacturer as osmocorrection.
Abbott Medical Optics Blink tears increases viscosity but circumvents the associated blurring with sodium hyaluronate acid (HA). HA is also found in Oasis Tears and in the contact lens rewetters CIBA Visions Aquify Long-Lasting Comfort Drops (CIBA Vision) and Blink Contacts (AMO). HA is blink activated; it thins while the patient blinks and thickens when the eye is open. As the lids close, the molecular chains line up and thin the viscosity. When the eye opens, the chains resume their original form and thicken the tear film.
Many speakers from the podium advocate emulsion drops for evaporative dry eye. Emulsion eye drops usually contain oils or lipids. Instead of adding viscosity, emulsions add to the inadequate lipid layer seen in evaporative dry eye.
Emulsions are a mixture of oil and water. A crude example is salad dressing. When placed on the shelf for extended periods of time, the dressing separates into an oil top layer and a water layer. Shaking the bottle breaks up the oil into small droplets and mixes the layers together into an emulsion.
Another method is to add emulsifiers to keep the oil and water from separating and maintain the emulsion. In the bottle, the artificial tear remains an emulsion. When placed into the eye, the emulsion breaks and the oil is released into the tear film. The oil fortifies the lipid layer. In addition to Allergans Refresh Dry Eye Therapy, there are other emulsions such as Bausch & Lombs Soothe XP Emollient Eye Drops. Focus Labs FreshKote, a prescription drop, also adds to the lipid layer. Most artificial tears (including emulsions) are economical treatment choices.
Nutritional support such as essential fatty acids (EFA) or omega-3 and omega-6 are often prescribed for dry eye. Both are needed for a healthy tear film. Miljanoviæ and colleagues analyzed data from more than 30,000 women enrolled as part of the Womens Health Study. They showed that women who consumed the highest amounts of omega-3 fats (primarily from tuna) had the lowest incidence of dry eye.
Other studies showed that targeted omega-6 intake may help with managing dry eye in symptomatic contact lens wearers and in those undergoing refractive surgery. Evidence continues to indicate the positive role of diet in managing various forms of dry eye.
The ratio between omega-3 and omega-6 may be important. Advising patients to keep their ratio of omega-3:omega-6 intake to greater than 1:3 may help minimize both signs and symptoms of dry eye. Patients can achieve this by consuming increased amounts of oily fish and minimizing consumption of fatty foods and meat.
The drawback to nutritional support is that it takes a few weeks to make a difference for patients. There are many philosophies and debates as to which type of nutritional support to prescribe. Practitioners debate the merits of flaxseed oil and dry eye. Flaxseed oils thin the meibomian oils. However, they are unstable and become rancid easily. The most dependable sources of omega-3s are cold water fish and cod liver oil. The conversion rate of flaxseed oil to beneficial forms is also low.
The environment can significantly influence the tear film. Altering it with sunglasses, moisture goggles and humidifiers can relieve symptoms. The treatments listed in the accompanying table are usually one-time purchases for the appliances. The most cost effective treatment is making sure the patient is drinking enough water. The 8 x 8 rule is that eight 8 oz. glasses of water are required each day.
Bacterial keratitis, conjunctivitis
Antibiotics are the core treatment for bacterial infections of the eye. The fluoroquinolones (FQs) have great effectiveness against corneal infection. The third-generation FQs were known as the corneal specialist in the bottle when introduced. The newer-generation FQs have lower resistance rates and greater clinical performance.
Prior to the introduction of the third-generation FQs, tobramycin was the drug of choice for corneal infections. Both third-generation FQs and tobramycin are economical options for corneal infections.
Over time, tobramycin has not been used as much because of toxicity and resistance. Keep in mind, resistance is also a local phenomenon. Some drugs may have high resistance in some areas, while others do not. Tobramycin resistance patterns can vary according to area. In your local area, there may be low resistance and high susceptibility to tobramycin and third-generation FQs. Many studies have pointed to Pseudomonas as the primary culprit behind corneal ulcers in contact lens patients. Both tobramycin and third-generation FQs work well against Pseudomonas when there is no resistance.
Farhi and Kowalski looked at coverage to cost relationship for bacterial conjunctivitis. The newer-generation and third-generation FQs yielded coverages of 84% to 86% for more than 1,100 isolates tested. Of note, sulfacetamide had 84% and polytrim had 80% coverage. Both are available in generic forms.
Sulfacetamide has fallen out of favor in the past because of sulfa allergies and high resistance. One major factor behind bacterial resistance is the overuse of the antibiotic. The more an antibiotic is used, the greater chance for resistance to occur. Because sulfacetamide use has decreased in recent years, resistance has diminished, as evidenced by its strong 84% coverage. The coverage is close to the newer, more expensive FQs.
Polytrim is a combination antibiotic (polymyxin B sulfate and trimethoprim sulfate, Allergan) and does not have a systemic equivalent. Because most resistance comes from systemic use, Polytrim is another good choice as far as resistance is concerned. It is cost-effective and available in generic forms.
For discomfort, the American Optometric Association Web site recommends warm soaks for conjunctivitis. Warm soaks can increase the blood flow and enhance healing. Irrigation can also help clear the associated mattering and discharge. Both are not cures, but if there are no other alternatives, offer palliative relief.
Methicillin-resistant staphylococcus aureus (MRSA) and methicillin-resistant staphylococcus epidermidis (MRSE) infections have been increasing at alarming rates. MRSA and MRSE are known as superbugs because of their resistance to multiple classes of antibiotics. MRSA ulcers are starting to occur in contact lens wearers. They appear no different than average infectious keratitis, only they are more aggressive.
Most of the MRSA isolates are resistant to FQs. Oral vancomycin is the antibiotic of choice. Trimethoprim, found in Polytrim, has been shown to be effective against MRSA, at 93.9%, according to Ta and Sahm. A new FQ, Bausch & Lombs Besivance (besifloxacin), shows promise as being effective against MRSA in in vitro testing when compared to other newer-generation FQs. Besifloxacin has never been used systemically, according to Ward and colleagues.
Rylander and Vold performed a cost analysis of glaucoma medications. Based on average wholesale price and common dosing patterns, they calculated the theoretical annual cost of glaucoma medications. On the higher end was Mercks Cosopt (dorzolamide and timolol) and Allergans Alphagan P 0.15% (brimonidine) three times daily. Generic beta-blockers consistently were more economical than their brand-name counterparts. The lowest cost was generic timolol maleate 0.5%. Cosopt is available as a generic, and another alternative is generic brimonidine tartrate 0.2%. It is different than Alphagan P because of the preservative. Alphagan P is preserved with the chlorine based disappearing preservative Purite. Generic brimonidine is preserved with benzalkonium chloride. The authors concluded that nonselective beta-blockers remain the most inexpensive class of glaucoma medications.
Prostaglandin analogs are commonly used for glaucoma. These drugs include: Pfizers Xalatan (latanoprost), Allergans Lumigan (bimatoprost) and Alcons Travatan (travoprost). Another way to manage costs is by reducing dosing.
Kurtz and Shemesh showed that a once-a-week prostaglandin was as effective as once a day, with fewer side effects. The drug tested was latanoprost, and the patients were followed for 3 months. Melton and Thomas recommend a variation of dosing to Mondays, Wednesdays and Fridays instead of once daily.
Low cost treatment can be timolol. Generic timolol in a 5-mL bottle costs about $4, and it can be dosed once daily in the morning.
Patient assistance programs
Many of the eye care drug companies have implemented patient assistance programs for the uninsured. For these programs, the eye care professional and patient fills out a PDF form and submits it electronically. Patient income documentation is usually required. Prescribed drugs are shipped to the doctor for dispensing.
RxHope (https://www.rxhope.com/) offers many drugs from many manufacturers for qualified patients. Allergan has many drugs listed at RxHope including Restasis, Lumigan and Alphagan P. Alcon offers Alcon Cares (http://www.alcon.com/en/corporate-responsibility/patient-clinic-inst-assistance.asp or (800) 222-8103). In addition to their full line of prescribed medications, Alcon also offers OTC products. With these programs, the drug companies have made an effort to help patients in need.
For more information:
- Milton M. Hom, OD, FAAO, is in private practice and is also a member of the Primary Care Optometry News Editorial Board. He recently authored Mosbys Ocular Drug Consult. He can be reached at 1131 East Alosta Ave., Azusa, CA 91702-2740; (626) 963-7100; e-mail: email@example.com. Dr. Hom is a paid consultant for Allergan, AMO, Inspire and Bausch & Lomb.
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- Conjunctivitis. American Optometric Association Web site. http://www.aoa.org/conjunctivitis.xml. Accessed October 29, 2009.
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- Rylander NR, Vold SD. Cost analysis of glaucoma medications. Am J Ophthalmol. 2008;145(1):106-113.
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- National Institutes of Health. Safety and efficacy pilot study of AzaSite (azithromycin) in subjects with blepharitis. http://clinicaltrials.gov/show/NCT00629590. Published May 8, 2009. Accessed October 30, 2009.
- Smeeth L. Boulis M. Hubbard R, et.al. A population based case-control study of cataract and inhaled corticosteroids. British Journal of Ophthalmology. 2003;87(10):1247-1251.
- Ta CN, Sahm DF, Ocular TRUST antimicrobial susceptibility patterns in MRSA vs MSSA eye infection: Results from Ocular TRUST. Paper presented at: Association for Research in Vision and Ophthalmology; May 2007; Fort Lauderdale, FL.
- Ward KW, Lepage JF, Driot JY. Nonclinical pharmacodynamics, pharmacokinetics, and safety of BOL-303224-A, a novel fluoroquinolone antimicrobial agent for topical ophthalmic use. Journal of Ocular Pharmacology and Therapeutics. 2007;23(3):243-256.