Physicians examine treatment options for patient with blepharitis

A patient experienced complications with punctal plugs and oral doxycycline.

Issue: September 25, 2008

Eric D. Donnenfeld

Eric D. Donnenfeld, MD, FACS: This is a case that you might see in your office every day. A 57-year-old man has a history of ocular redness and irritation and complains of burning in the morning. That is a symptom that we hear a lot. Patients will complain of burning at night or burning during the day. Is there any difference in that symptom? Does that symptom tell you anything about the possible mechanism of this problem?

Christopher J. Rapuano, MD: As a general rule, when I hear of burning in the morning, I think blepharitis. When I hear of dryness, burning and irritation at night, I think dry eye. It is not black and white, but as a general rule, I think those hold pretty well.

Dr. Donnenfeld: I agree with that. It does not apply to every single patient. There are other things such as floppy eyelid syndrome, exposure keratitis and lid imbrication, among other diseases, that cause burning in the morning. But in general, when you hear burning in the morning, think meibomian gland dysfunction. When you hear burning at night, think conventional dry eye.

This patient, however, was originally diagnosed with dry eye, and given punctal plugs, which were placed in three puncta. He is currently on transiently preserved tears. The patient now walks in to your office, and his lid margins look like this (Figure 1).

Dr. Rapuano: I have a question about the plugs. Did he feel better with the plugs or worse with the plugs? That can give you another clue.

Dr. Donnenfeld: What would you think a patient who has eyelids like this, how would they feel with plugs in their eyes?

Dr. Rapuano: I think they would feel worse. They would come in and complain, “You made me worse, doc.”

Dr. Donnenfeld: Why would they feel worse if you put in plugs? I am a big advocate of plugs, and I think a lot of us use plugs. The problem with plugs is, a lot of times, they are used inappropriately. They are used too soon or they are used in patients with disease like this. Why would this patient feel worse, and what do you do when you see this?

Pro-inflammatory cytokines have increased contact with the cornea in eyes from punctal plugs.

Soapsuds-like material on the lower lid.

Images: Ophthalmic Consultants of Long Island

Marguerite B. McDonald, MD: Because you have now trapped, as I tell patients, the “nasty tears” on the top of the eye. All these pro-inflammatory cytokines now have increased contact time with the cornea due to the presence of the plugs; you need lid hygiene and topical and oral antibiotics in a moderately severe case like this before inserting plugs for concomitant dry eye disease, if that is indeed a secondary diagnosis.

I would put this patient on hot compresses, oral doxycycline 100 mg twice daily for 7 to 10 days followed by 20 mg a day for 3 to 4 months, and azithromycin 0.1% drops (AzaSite, Inspire Pharmaceuticals) in both eyes twice daily for 2 days, then every day for 28 days. The patient should be reminded to rub the azithromycin drop into the base of the lashes with a clean finger. This sort of patient may need the occasional repeat course of azithromycin treatment if flare-ups occur.

Back for a moment to the possibility of mild to moderate dry eye as a concomitant diagnosis: I would put the patient on cyclosporine emulsion (Restasis, Allergan) one drop in both eyes twice a day and gently preserved or unpreserved tears four to eight times a day until the cyclosporine effect — increased production of more and higher quality tears — allows for the patient to decrease the frequency of the artifical tears. Cyclosporine emulsion also has a beneficial effect on blepharitis, although it is not considered to be a first-line therapy for this diagnosis.

Dr. Donnenfeld: So the patient has a cesspool in the eye, you have trapped it with the plugs, and the patient feels toxic. The eyes go from irritated to bright red, and there is tremendous pain and photophobia associated with it.

Look carefully at the lid margin; I think this is an important finding (Figure 2). I am a big believer in pathognomonic findings. If I look at someone and I see this finding on the lid margin, this soapsuds-like material on the lower lid, that tells me something important. What is the soapsuds material on the lid? Is it Demodex exoskeletons? Is it soap? Or is it saturated fats?

Peter A. D’Arienzo, MD, FACS: I was fortunate to be one of your residents, and you always taught us that whenever you see soapy tear film, these are actually saponification of the free fatty acids, so it is actual soap. You are getting the lipase activity from the staphylococcal bacteria that are breaking down the meibomian gland secretions, so you are left with soap on the eyelid margin.

Dr. Donnenfeld: When you see this material on the lids, you are seeing soap. The normal meibomian glands are broken down by lipase to soaps and fatty acids. That is why patients’ eyes burn and sting so much. They have soap in their eyes, and when you see this, you do not have to go any further to know that this patient needs to be treated aggressively for meibomian gland dysfunction.

This patient was diagnosed with rosacea and had gastrointestinal distress with oral doxycycline, which is not uncommon. Tetracycline has a lot more distress. Doxycycline has intermediate distress. Minocycline has a little bit less distress.

How much doxycycline do you recommend when given orally for managing these patients?

Michael B. Raizman, MD: If patients have severe blepharitis, I like the maximal dose of 100 mg twice a day with food, but a lot of patients cannot tolerate that, as you have pointed out. Some patients do extremely well with low doses, so some of my patients may be on 20 mg, for instance. Or 100 mg two or three times a week is adequate for some patients, especially in the long run. So do not give up when a patient says, “I tried that doxycycline you prescribed, and I couldn’t tolerate it.” Try to work on different dosing schedules and lower doses.

Dr. Donnenfeld: There have been some issues in the literature about maintaining patients on long-term tetracycline family antibiotics. A major study came out that suggested that there might be some issues, especially in women. Does anyone have any comments about long-term doxycycline in women and what the potential problems might be?

Dr. McDonald: That study revealed an apparent relationship between oral antibiotic use and breast cancer in women; the results initially panicked everyone. You have to tell patients in advance that the one exception was the group of women on macrolide and tetracycline antibiotics for skin and dermatological/external disease conditions — there was no correlation. So you have to point that out to them in advance because your patients will find the study, and they will call you the next day about it.

Dr. Donnenfeld: This study was out of the Journal of the American Medical Association and made the point that long-term antibiotics increase a woman’s risk of breast cancer by about 30% or so, and they left it equivocal. They are not certain whether this long-term use for skin disease is a problem or not. But because of that study and because we have some new modalities that are available, I have moved doxycycline down the pecking order, and it is not my first-line therapy like it used to be. Hot compresses certainly have become important.

So this patient who has meibomian gland dysfunction is on hot compresses, which is first-line therapy. Now, let’s get some treatment options. How would you manage this doxycycline-intolerant patient who came to your office, other than with hot compresses?

Charles B. Slonim, MD, FACS: I will have them go directly with some topical antibiotics, sometimes an ointment at bedtime, just to make sure that they are getting an antibiotic in that regard. I have tried minocycline, which, of course, is another tetracycline. It is not supposed to be as upsetting to the stomach, but the few patients who I have started on minocycline recently seem to have more of a problem than they had with the doxycycline. But if they are having problems with doxycycline, other than an allergy to it, I think anything like a minocycline would be fine. Likewise, even just plain tetracycline may also be of benefit, but I use the lower anti-inflammatory doses and not the full antibiotic doses. I use 20 mg of doxycycline twice a day, so I think oral antibiotics, a little bit of ointment on the surface of the eye at bedtime only because otherwise they will be blurred, and the warm compresses and lid scrubs.

Dr. Donnenfeld: Which ointment would you recommend for this?

Dr. Slonim: Usually an erythromycin, sometimes a bacitracin, although I find that I go in spurts with one or the other. I also find that using a combination antibiotic steroid will sometimes be effective in these patients because the steroid frequently does more for their lids than the topical antibiotic does.

Dr. Donnenfeld: I agree. Steroids are sometimes important.

There are so many different options. Where do you start, and how do you progress in your therapy?

Dr. Raizman: I think just about every patient should be using hot compresses. That is easy and safe. If you see terrible meibomian gland obstruction, those patients need doxycycline, minocycline or tetracycline.

Most patients are much more mild. You start to talk to them about antibiotics, and right away they are worried about taking a chronic antibiotic therapy, and justifiably so. And now we have good data to support the use of oils taken orally that are quite helpful for the mild to moderate cases of meibomian gland disease. So I’ll have patients take flax or fish oil, about 2,000 mg a day. I do not think it is critical to focus on one particular type of oil. I think patients get benefits from using any of these products, but that would be my second line of treatment.

I like to avoid steroids. This is a chronic disease. Yes, you can clear them up temporarily. None of us want our patients on steroids for blepharitis for months or years, so I will use them for an occasional flare-up, but I like to stay away from that.

I do not find Restasis to be especially helpful. Occasionally, some patients will get benefit from it, but that is definitely low on my list of treatments, as are topical antibiotics to the lid margins. I do not find that to be as effective, either. So using that combination of strategies, more or less in that order, I get good results on the majority of my patients.

For more information:

Peter A. D’Arienzo, MD, FACS, can be reached at Manhasset Eye Physicians, PC, 1615 Northern Blvd., Manhasset, NY 11030; 516-627-0146; e-mail: eyedoc63@aol.com.

Eric D. Donnenfeld, MD, FACS, can be reached at OCLI, 2000 North Village Ave., Rockville Centre, NY 11570; 516-766-2519; e-mail: eddoph@aol.com.

Marguerite B. McDonald, MD, can be reached at OCLI, 266 Merrick Road, Lynbrook, NY 11563; 516-593-7709; e-mail: margueritemcdmd@aol.com.

Michael B. Raizman, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; e-mail: mraizman@tufts-nemc.org.

Christopher J. Rapuano, MD, can be reached at Wills Eye Institute, 840 Walnut St., Suite 920, Philadelphia, PA 19107; 215-928-3180; e-mail: cjrapuano@willseye.org.

Charles B. Slonim, MD, FACS, can be reached at Older and Slonim Eyelid Institute, 4444 East Fletcher, Suite D, Tampa, FL 33613; 813-971-3846; fax: 813-977-2611; e-mail: slonim@eyelids.net.

Reference:

Velicer CM, Heckbert SR, et al. Antibiotic use in relation to the risk of breast cancer. JAMA. 2004;291:827-835.