Article Date: 6/1/2007

Manage Dry Eye Secondary to Systemic Disease
dry eye

Manage Dry Eye Secondary to Systemic Disease

You must consider four main factors before deciding on management for these patients.

ANDREW S. MORGENSTERN, O.D., Rockville, Md. & PAUL M. KARPECKI, O.D., F.A.A.O., Edgewood, Ky.

Managing patients who have dry eye or dysfunctional tear syndrome (DTS) secondary to systemic disease (see "Common Systemic Conditions Associated with Dry Eye," page 50) can be challenging because four primary factors affect the course of treatment. They are: the duration the patient has had the disease, the patient's family medical history, current medication use and how the primary-care physician (PCP) is managing the the disease process.

To ensure you take all these factors into account, prior to deciding on a treatment plan, you must ask three specific questions during the patient-history portion of the exam, and actively consult with the patient's PCP.

Fluorescein staining reveals severe dry eye in a Thyroid Eye Disease patient.

Three's a charm to prevent harm

Obtain answers to these three questions:

How long have you had your condition? The answer to this question plays a part in your treatment decision because the signs of ocular surface disease in systemic-disease patients can vary depending on the duration of the condition.

For example, it's more likely that a patient who has had rheumatoid arthritis for 15 years will manifest more signs of ocular surface disease than a patient who was recently diagnosed with the condition.

Does anyone in your family have this condition, and if so, how has the condition progressed? If the patient's family members have had serious complications as a result of the disease process, you may choose to treat him more aggressively than if this wasn't the case to ensure he doesn't follow in his family member's footsteps.

What medications are you currently using? This is an important question to ask, as several drugs used to treat both systemic disease and other conditions, such as allergies, can cause dry eye and worsen existing dry eye. This knowledge may enable you to reduce, discontinue or switch the patient to another drug to help decrease his dry-eye symptoms (see "Commonly Used Medications That Can Cause Dry Eye," page 53.)

For example, oral antihistamines, such as loratadine (Claritin, Schering-Plough HealthCare Products Inc.) and cetirizine HCL (Zyrtec, Pfizer Inc.) contribute to dry eye and could actually exacerbate pre-existing ocular surface problems.1 So, if such a patient presents, it may be better to discontinue his oral antihistamine until the dry eye and ocular surface improves.

Another example: menopausal dry eye and the use of conjugated estrogen tablets, USP. Hormonal changes during menopause can contribute to dry eye.2 And, estrogen-only replacement drugs have been shown to increase the incidence of dry eye seven-fold.3 As a result, you may want to talk with this patient and her PCP about other treatment options. In many cases, however, these drugs are vitally necessary.

If the PCP decides to prescribe a new drug, alert the patient that there is sometimes a lag time before the maximal effect of the drug occurs. So, alter your follow-up schedule to match the disease course and the expected time it takes to "wash-out" the old medication and see the results of the new treatment.

Tag-teaming systemic disease

Once you've obtained answers to the three aforementioned questions, consult with the patient's PCP. You will have limited success in treating the secondary dry eye or DTS if the PCP is not effectively and appropriately managing the patient's systemic disease.

Common Systemic Conditions Associated with Dry Eye
  • Rheumatoid Arthritis
  • Systemic Lupus Erythematosis
  • Sjogrens Syndrome
  • Thyroid dysfunction
  • Stevens-Johnson Syndrome
  • Sarcoidosis
  • Acne Rosacea
  • Herpes Zoster
  • Diabetes Mellitus
  • Lyme Disease
  • Multiple Sclerosis

For example, a patient with acne rosacea will respond well to an aggressive dry-eye therapy, but the dry eye may not successfully resolve if you or the PCP haven't prescribed a systemic drug, such as 50mg of oral doxycycline b.i.d. (or 20mg of Aldox) for two to three months, as part of the management.

Likewise, a diabetic patient with poor glucose control will manifest significantly greater dry-eye problems and slower resolution of the ocular surface disease, even with adequate ocular therapy.

Deciding on treatment

Now, you're ready to decide on dry-eye treatment. Our step-ladder of treatment is based on the Delphi panel results. The Delphi panel is made up of 17 international experts in dry eye who together developed a consensus regarding both the diagnosis and management of dry-eye syndrome.4

Start with palliative options. Instruct the patient to consider placing a humidifier in his bedroom to improve the osmotic gradient between the ocular surface and the environment. Tell the patient to clean and disinfect the humidifier filters — bleach is adequate — regularly. Clean the humidifier out every day, as it is known to exude mold and other debris.

Another palliative option: Talk with your patient about decreasing his intake of multivitamins, caffeine and cigarettes, as all have been shown to cause the dehydration that leads to dry eye. And, tell him to add Omega-3 essential fatty acids (flaxseed oil, fish, etc.) to his diet. Or, prescribe Omega-3 fatty acid supplements, which produce natural substances that lubricate the eye, keeping lid disease and inflammation at bay.

Finally, prescribe artificial tears and a more viscous artificial tear gel prior to bedtime. This is mainly for patients who have severe dry-eye conditions, such as lagophthalmos, to help lubricate the exposed areas at night.

Prescribe a combination of corticosteroids and cyclosporine. Unfortunately, almost all systemic diseases that manifest as dry eye or DTS have some sort of inflammatory component. Many also manifest in the eye in other presentations including iritis, scleritis, episcleritis and lacrimal gland inflammation. So, the palliative options mentioned above may not be enough to quell the symptoms of dry eye.

Thus, when dye staining of the conjunctiva or cornea is evident, a combination of corticosteroids and cyclosporine may be more effective. Our typical regimen: loteprednol 0.5% (Lote-max, B&L) q.i.d. for two weeks, with a reduction to b.i.d. dosing for an additional four to six weeks. We also employ cyclosporine b.i.d. either starting concomitantly with the steroid or after two weeks for a six-month duration, depending on the severity of symptoms.

The steroid reduces the inflammation, including the swelling of the lacrimal gland, and the cyclosporine maintains the long-term effects of increasing tear production, goblet cell density and prevents T-cell mediation.5 If a patient presents with a case of rheumatoid arthritis and a concurrent iritis, we prescribe a steroid to suppress the inflammation and a cycloplegic agent to relax the ciliary body.

Commonly Used Medications That Can Cause Dry Eye
  • Venlafaxine HCL (Effexor, Wyeth)
  • Amitriptyline (Elavil, AstraZeneca)
  • Escitalopram oxalate (Lexapro, Forest Laboratories)
  • Paroxetine HCL (Paxil, GlaxoSmithKline),
  • Fluoxetine hydrochloride (Prozac, Eli Lilly)
  • Bupropion HCL (Wellbutrin XL, GlaxoSmithKline)
  • Sertraline (Zoloft, Pfizer)
  • Doxazosin mesylate extended release tablets (Cardura XL, Pfizer)
  • Clonidine (Catapres, Boehringer-Ingelheim)
  • Amlodipine besylate/benazepril HCI (Lotrel, Novartis)
  • Amlodipine besylate (Norvasc, Pfizer)
  • Metoprolol succinate extended release tablets (Toprol-XL, AstraZeneca)
  • Bisoprolol and Hydrochlorothiazide (Ziac, Duramed Pharmaceuticals)
Hormone Replacement Therapy
  • Estradiol tablets (Estrace, Warner Chilcott Laboratories)
  • Conjugated estrogens tablets (Premarin, Wyeth)
  • Conjugated estrogens and medroxyprogesterone tablets (Prempro, Wyeth)
  • Medroxyprogesterone acetate injectable suspension (Depo-Provera, Pfizer)
  • Norelgestromin/ethinyl estradiol transdermal system (Orthoevra, Ortho-McNeil Pharmaceutical, Inc.)
  • Norgestimate/ethinyl estradiol (Ortho Tri-cyclen, Ortho-McNeil Pharmaceutical, Inc.)

Since most systemic diseases are chronic, these patients often require never-ending management of the associated dry-eye disease and may be best served with indefinite cyclosporine 0.05% b.i.d. and/or Omega-3 supplements and artificial tears.

Insert punctal plugs. These are often very beneficial in dry-eye related to systemic disease if you manage the patient's inflammation and lid disease first.

Using punctal plugs before the administration of anti-inflammatory or immunomodulatory drugs has been shown to be much less effective for treatment.4 This is because the inflammation and cytokines in the tears and lacrimal glands are the agents that cause the dry-eye in the first place. So, the punctual plugs will simply produce more of the bad tear layer.

Last resort treatments for dry eye are moisture goggles, contact lenses to manage filamentary keratitis, acetylcysteine to dissolve the filaments in filamentary keratitis and punctal cautery.

Adding systemic disease into the treatment equation makes these disorders even more complex. But, by following these tips, you'll have a better shot of determining the best course of treatment for these patients and ensuring their quality of life. OM

References available upon request.

Dr. Morgenstern practices in Rockville, Md. and teaches at the Ophthalmology Residency Program at The Georgetown University School of Medicine, Department of Ophthalmology. E-mail him at
Dr. Karpecki works in the Cornea/External Disease and Advanced Ocular Surface Disease Research Center at the Cincinnati Eye Institute in Edgewood, Ky. E-mail him at

Optometric Management, Issue: June 2007