Panelists discuss identifying, treating corneal infiltrates

SAN DIEGO – Primary Care Optometry News gathered a group of clinicians here during the American Optometric Association Annual Congress to discuss corneal infiltrates usually associated with contact lens wear. They shared diagnostic tips, debated terminology issues and reviewed their treatment regimens.

Jennifer L. Smythe, OD, MS, FAAO Jennifer L. Smythe, OD, MS, FAAO, is an associate professor of optometry at Pacific University College of Optometry, Forest Grove, Ore., and a Primary Care Optometry News Editorial Board Member.

Michael D. DePaolis, OD, FAAO: Recent literature has suggested that approximately 50% of all infectious infiltrates after LASIK are atypical mycobacteria. This underscores the fact that a little white spot in the cornea isn’t always just inflammatory cells. So, when you look at an infiltrate in the cornea, what are you thinking on a cellular level?

Bobby J. Christensen, OD, FAAO: On a cellular level, I usually don’t know for the first 24 hours. I treat these patients aggressively for the first 24 hours. After that, if it’s a sterile infiltrate, it’s usually much better. From an objective standpoint, I know it’s probably an inflammatory process. At that point, I usually back off and let it take care of itself.

Infectious vs. sterile infiltrates

Dr. DePaolis: When you look at an infiltrate at the slit lamp, are there any signs that suggest infection? Do infectious infiltrates look different from sterile infiltrates?

Peter D. Bergenske, OD, FAAO: Everything is a matter of degree. What we call CLPU [contact lens-induced peripheral ulcer] tend to be remarkably symmetrical, perfectly round lesions. However, if you have one like that, it doesn’t necessarily mean it’s still sterile.

If the infiltrate is perfectly round and there is little inflammation and redness, chances are that it’s sterile. On the other hand, if the infiltrate is a little bit irregular, the eye is a little bit redder and the patient has more discomfort, chances are that it’s infectious. The only sign that is unique to the infection is a hypopyon, and that’s very rare.

Dr. DePaolis: Let’s talk about different clinical presentations. Let’s discuss the patient who presents with an acute red eye, wearing contact lenses and who has a disseminated, infiltrative keratitis. There’s some asymmetry, and one eye may be more symptomatic. What causes this presentation?

Jennifer L. Smythe, OD, MS, FAAO: The first thing I think of is a viral cause, especially if it’s a bilateral presentation. I think we have to rule that out first through our case history. Second would be solution toxicity. Sometimes, the only way to differentiate the two is to discontinue lens wear, have the infiltrate resolve and then re-challenge the patient. That may be the only way we know 100%.

Dr. DePaolis: Good point. Before we blame the contact lens, we should be sure that it’s really the contact lens. What else helps you make that determination?

Harue J. Marsden, OD, MS, FAAO: Recent illness.

Dr. Smythe: I look for a recent upper respiratory illness in particular. During the history taking, I ask the following questions: What’s going on in the household? Are there children? Has anyone else had a red eye?

Dr. Marsden: Do they work in a school or preschool?

Dr. DePaolis: What about during the examination?

Dr. Marsden: I palpate nodes.

Dr. DePaolis: I think that’s important. Lens-related causes rarely result in adenopathy, but viral causes often do.

Causes of toxic responses

Peter D. Bergenske, OD, FAAO Peter D. Bergenske, OD, FAAO, is chief of contact lens services at Pacific University College of Optometry, Forest Grove, Ore.

Dr. DePaolis: Let’s now talk about toxic responses. Is this presentation solution related, due to lens contamination, the result of an old lens or all of the above?

Dr. Christensen: It could be all of the above. It could be an old lens that’s gradually become contaminated. Solutions are a very common cause.

Dr. Marsden: The solutions could have become contaminated.

Dr. Christensen: The patient may have changed solutions. He or she may have gone to the store and bought a solution that you didn’t recommend. Once you rule out the viral entity, more times than not, it’s solution related. Many times, a solution reaction takes a lot longer to resolve than we may expect. Some clinicians are confused or concerned when the solution reaction takes a number of weeks to go away.

Dr. Marsden: We can’t forget that there are still patients who are not replacing lenses regularly. So, even though they physically change the bottle, they may still have a lens that’s been saturated with the chemical that created the toxicity.

Dr. Bergenske: It is often confused with viral causes because, typically, if it’s viral, you expect it to linger on. If it’s something else, you expect it to go away very quickly.

Dr. DePaolis: Can someone comment on private label solutions and how formulations can change?

Dr. Smythe: Typically, a company will have about a 1-year contract to manufacture private-label solutions. A patient can walk into the store, and one bottle of solution can be extremely different from the bottle behind it with the exact same label. So, just reading labels doesn’t give us all the information about what a patient is using. Manufacturers don’t have to name ingredients. They don’t have to give them the exact same name that they give them in their name-brand solution.

Another confounding factor is that there are some generic solutions that are approved for no-rub. A patient will use a formulation that’s no-rub and then grab an older bottle that wasn’t approved for no-rub.

Then, there is the issue of rinsing cycles. Is it strictly no-rub with one rinse? Is it no-rub with pre- and post-rinse? So, as a practitioner, just knowing that they’re using a generic solution doesn’t mean that we know exactly which one they’re using.

Dr. DePaolis: So these types of reactions don’t necessarily implicate the solution. They could also be due to how the patient is using the solution.

Dr. Smythe: Exactly.

Mechanical phenomena

Dr. DePaolis: Is disseminated infiltrative keratitis ever mechanical in nature?

Dr. Christensen: Yes, but rarely. If it’s mechanical, it’s usually localized. If a lens gets coated, the patient quits wearing it.

Dr. Smythe: We are all focusing on soft contact lens wear, but the best example of a mechanical-induced infiltrate with gas-permeable lens wear is vascularized limbal keratitis (VLK). That is definitely mechanical in nature. Another thing we haven’t talked about are silicone hydrogels. With the stiffer modulus lens that moves more, we may be seeing some sort of a mechanical effect in the infiltrative response.

Dr. Bergenske: When we see SEALs [superior epithelial arcuate lesions], it’s not uncommon to have an infiltrate along with that, and that’s almost certainly a mechanical phenomenon.

Dr. DePaolis: Is disseminated infiltrative keratitis ever hypoxic?

Dr. Bergenske: Remember the good old days when we used to fit a lot of aphakes and you had them in a +16 D or +18 D Permalens (CooperVision)? That was where you would see exactly that type of response. You’d lift up the lid, and vessels would be coming down. There would be a little wave of infiltrate.

Dr. Christensen: Interestingly, we could manage the infiltrate process to a large degree with low-dose steroids.

With a prism ballast soft lens, not much oxygen gets through. Most of the time, we see corneal warpage and a shift downward of the apex on topography. When it’s serious enough, you sometimes get corneal degradation. I am always concerned when I have prism ballast, especially a higher minus or higher plus lens.

Dr. Bergenske: It’s difficult for us to justify having toric patients in anything resembling extended wear.

Dr. Smythe: If they have deposits on the lenses, it’s just a breeding ground.

Dr. DePaolis: How do you treat infiltrates? Let’s discuss four distinct clinical entities: #1 will be the disseminated infiltrative keratitis that you suspect is toxic in nature, #2 will be contact lens acute red eye [CLARE], #3 would be CLPU and #4 would be an infectious ulcer. How would you treat the first presentation?

Disseminated infiltrative keratitis

Bobby J. Christensen, OD, FAAO Bobby J. Christensen, OD, FAAO, is senior vice president for Vision Source and is in private group practice in Midwest City, Okla.

Dr. Christensen: I would use supportive therapy and lubrication. If the redness is an issue for the patient, that may be the time to use a decongestant to make the patient look better.

Dr. Bergenske: I would remove the lenses for now.

Dr. DePaolis: For how long do you discontinue lens wear?

Dr. Christensen: They need to stay out of their lenses for however long it takes the epithelium to replicate itself. It can take up to 6 weeks for the toxic keratitis to completely clear.

Dr. DePaolis: Do you treat a patient differently if there is no epithelial defect?

Dr. Marsden: I don’t even necessarily take the patient out of contact lenses. I will refit him or her into silicone to somewhat bandage the epithelium. Then, I will monitor the patient frequently. A lot of artificial tears and decongestants have preservatives in them, and that preservative has some low-grade microbial activity, which can actually be a benefit.

Dr. Smythe: I still find a role for steroids in these patients. Once the epithelium is completely recovered, which usually takes about 5 to 7 days, I put them on steroids three or four times a day. If the epithelium is intact, I want to see that cornea resolve as quickly as possible, because many of my contact lens wearers can’t stand wearing their spectacles. They want to get back into contact lenses as soon as possible. I keep them out of contact lenses while they’re on steroids except for in unique circumstances where the individual does not have backup spectacles or refuses to wear them. In these cases, I put them in daily disposables while they are being treated.

Defining, treating CLARE

Dr. DePaolis: Let’s transition to CLARE. How do we define this condition?

Dr. Smythe: Typically, it’s a unilateral response. A patient who sleeps in contact lenses wakes up one morning with a red eye that is uncomfortable and feels congested. At the slit lamp, we typically don’t see those large, focal infiltrates. We might see what looks like salt specks near the limbus. The hallmark sign is bulbar hyperemia. This is an inflammatory response to gram-negative endotoxins.

Dr. Bergenske: This condition comes on suddenly, and the cornea is almost always clear. You just have a very red eye. You’ll get an irregular, negative stain pattern, but you don’t see much on the cornea.

We rarely see this condition in its hottest form. Nine times out of 10, the patient removes the contact lens before he or she gets to the office.

Dr. Smythe: This is primarily an overnight wear phenomenon. These individuals aren’t using solutions on a regular basis, so I’d be less apt to point a finger at the solution in a unilateral overnight wear type of presentation.

Dr. DePaolis: How do you treat CLARE?

Dr. Christensen: I use a steroid-antibiotic combination four times daily for 2 to 3 days.

Dr. Bergenske: I question whether we need to use the steroid, because very often it clears in 24 hours with just the removal of the lens.

Dr. Marsden: The steroid makes the patient feel better because the eye looks better.

Dr. Smythe: The risk of recurrence is about 25%. But this isn’t what we call a serious adverse response. So I will put the patient back into contact lens wear and overnight wear. If we have a second recurrence, then I will reduce the number of nights that the patient sleeps in the contact lens, or I will put the patient in daily wear only.

Dr. Christensen: You’ve got to evaluate the lens fit. If the lens is adhering or is tight and if it’s a 58% water lens, then you prescribe a silicone lens material.

Harue J. Marsden, OD, MS, FAAO Harue J. Marsden, OD, MS, FAAO, is an associate professor at Southern California College of Optometry.

Dr. Marsden: If the patient has poor tear composition, you’re keeping the cesspool alive. Another consideration is the deposits that are stored on the lens.

Dr. Bergenske: Another factor is the patient. This patient has a sensitivity. Even if you alter the flora for a short period of time, that’s not going to change the fact that the patient is sensitive to it. I think we have to be a little cautious. I would have a discussion with the patient about the way he or she wears the lens. Patients will often admit that their eye didn’t feel right the night before. Tell them to take the lens out if they get that feeling again.

Dr. Smythe: The same microorganisms that have been found on the lens or in the tear film have also been found in the nasolacrimal system. This is why we take the conservative approach of asking patients not to sleep in their lenses when they are sick, particularly if they have an upper respiratory infection. I think we should be discontinuing continuous wear for any type of illness.

Dr. Christensen: I totally agree.

Defining, treating CLPU

Dr. DePaolis: Let’s move to CLPU, or contact lens-induced peripheral ulcer. What’s the definition of CLPU? Is this really an appropriate term?

Dr. Christensen: This is just a personal opinion, but when I see the word “ulcer” used, I’m always concerned from a medicolegal standpoint, because the connotation is that we’ve got an extremely serious condition. I believe that if it says “ulcer” in the record, you’re suddenly committed to a fairly aggressive treatment. If you say sterile peripheral infiltrate, the connotation is different.

Dr. Bergenske: Maybe we should just call it peripheral infiltrate, because we don’t know if it’s sterile, either, without testing.

Dr. Christensen: As soon as we put “contact lens-induced peripheral ulcer,” I think we’re doing an injustice to the contact lens field. I also think that we are creating a set of legal circumstances that dictate how we have to treat that patient.

Dr. DePaolis: You don’t want to call something an ulcer unless you’re fairly certain that it is, because you’re committing yourself to a more stringent level of care. With the diagnosis of ulcer you must at least consider culturing and the role of fortified antibiotics. What are your thoughts when you encounter a 1.5-mm focal infiltrate near the limbus?

Dr. Christensen: I have a mental checklist that I go through when I see these. It starts with symptomatology. Pain is a significant symptom, and if this eye is much more uncomfortable than it looks like it should be, that’s a red flag. If the patient has been sick, I’m more concerned. If he or she is using a nasal steroid spray, there may be some bugs that have mutated or are resistant. I’ve seen some corneal peripheral infiltrates that were really infectious with patients using nasal sprays.

If the eyelid has blepharitis, I will start to lean toward the diagnosis of infiltrate because of the toxins that flow onto the cornea. Circumscribed injection concerns me much more than a quadrant injection.

Cells in the anterior chamber worry me more than a clear anterior chamber. When you instill fluorescein and see stain diffusing into the surrounding tissue, there’s probably necrotic tissue.

Dr. Smythe: We also have to look at other clinical factors. How deep is the epithelial defect? Typically, with a sterile presentation, Bowman’s membrane remains intact, which is why you don’t get that diffuse infiltration of the sodium fluorescein.

If I see discharge, especially if it’s white or purulent, I’m definitely thinking that it is infectious. Additionally, it would be extremely uncommon to have lid edema as a noninfectious entity.

Dr. DePaolis: If it’s not infectious, how are you going to treat it?

Dr. Christensen: Treatment depends on whether you’re an optometrist or an ophthalmologist, but the outcomes are probably the same. Generally, the optometrist needs to treat with an antibiotic and wait 24 hours before steroids are introduced. However, you know that a steroid with an antibiotic may provide the quickest recovery.

Dr. Smythe: But what’s the role of the steroid? If you have a peripheral lesion, there’s no evidence that introducing a steroidal anti-inflammatory will reduce the risk of scarring. If the patient has a scar, it doesn’t affect best-corrected visual acuity, because it’s peripheral. I don’t use the steroid.

Dr. Bergenske: We can’t afford to be so cavalier as to start throwing a steroid just because chances are that it’s going to be OK.

Dr. Christensen: Steroids have been linked with secondary herpes simplex keratitis.

Dr. Bergenske: Some practitioners treat CLPU with TobraDex (tobramycin dexamethasone, Alcon), and some treat it with artificial tears. If I had to choose one of those two stances, I would take the artificial tears approach and see the patient tomorrow. Ninety-nine percent of the time, the infiltrate will be better tomorrow, and I haven’t put the patient at any undue risk.

Dr. DePaolis: If you suspect an ulcer how will you treat?

Dr. Christensen: It’s a tough question. I feel that you probably should prescribe Vigamox (moxifloxacin, Alcon), which is an off-label use. I would prescribe one drop every 30 to 60 minutes, even though it’s only approved for three times daily dosing.

You may still want to cover the bases with something like Polysporin Ointment (polymyxin B-bacitracin, Burroughs Wellcome) to be sure lids are taken treated. I would also prescribe a cycloplegic, and an oral prostaglandin inhibitor. I put these patients on a therapeutic dose of ibuprofen, which is from 2,400 mg/day depending on body size, up to 3,600 mg. I will usually prescribe 400 to 600 mg every 3 to 4 hours.

Dr. Smythe: If the patient has a corneal defect, is photophobic or is uncomfortable, whether it’s with CLPU, contact lens acute red eye or diffuse infiltrative keratitis, it’s not uncommon for me to cycloplege him or her. That does a world of good for those symptoms as well.

Do we still need to add our loading dose?

Dr. Christensen: Probably not, because the kill curve looks really good with this drug.

Dr. DePaolis: The tissue retention studies are impressive with both moxifloxacin and gatifloxacin. You may not need a loading dose; however, when in doubt, defer to the most conservative approach.

Dr. Smythe: Because it is an off-label use, we don’t have dosage indications yet. We should be using its closest counterpart, which would be second- and third-generation agents.

Dr. Christensen: Toxicity studies are very good, so we probably won’t create any epithelial or conjunctival problems by using a lot of the drug. So, when in doubt, it’s better to overtreat than undertreat.

The role of silicone hydrogels

Dr. DePaolis: Let’s talk about silicone hydrogels. Do they improve the prognosis for all of these conditions?

Dr. Bergenske: The rates for CLPU and contact lens acute red eye are comparable to what we saw with hydrogel lenses. We’re just seeing more of these conditions because more people are wearing lenses overnight. One thing that really stands out is the incredibly low rate of reported cases of microbial keratitis. There are different theories on why that is, but I think they’re probably underreported.

Dr. Smythe: If you fit lenses on an overnight wear basis, you’ll see inflammatory responses. You still have a foreign body in the eye that covers the limbus 360°. You’re always going to have the potential for an inflammatory response.

Dr. Marsden: The mechanism just becomes different.

Another type of keratitis?

Dr. DePaolis: The newer silicone hydrogels, by virtue of increased oxygen permeability, protein resistance and on-eye mobility, have significantly lessened the risk of infectious keratitis and hypoxic-related issues. However, because there’s still the propensity for inflammation, we’re going to see some infiltrates.

Is it possible that these materials and the way they interact with the ocular surface may actually create a different type of infiltrative keratitis than previously seen?

Dr. Smythe: I don’t see anything different, other than maybe a higher rate of epithelial arcuate lesions. The infiltrates don’t look different in someone who wears a silicone hydrogel overnight as opposed to a low-Dk lens overnight.

They present exactly the same way, and none of them have the potential to reduce best-corrected visual acuity when they’re inflammatory. We’re not going to see anything different than what we saw before.

Dr. Marsden: That’s important, because practitioners look at this as the cure-all, end-all. That’s being naive.

Dr. Bergenske: You have to worry about some patients, and they are the same patients who you would have had to worry about before.

Dr. Smythe: The difference is that they’re wearing the lenses overnight with your approval.

Dr. Christensen: Do you see a higher incidence of problems in patients who have quite a few mucin balls under the lenses compared to patients who don’t have any mucin balls?

Dr. Smythe: I haven’t seen any correlation between adverse response and that type of debris.

Dr. Christensen: It seems like there should be, but I haven’t either.

For Your Information:

• Bobby J. Christensen, OD, FAAO, can be reached at 6912 East Reno #1, Midwest City, OK 73110; (405) 732-2277; fax (405) 737-4776; e-mail: vsourcebc@cox.net. Dr. Christensen has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any of the companies mentioned.
• Peter D. Bergenske, OD, FAAO, can be reached at Pacific University College of Optometry, 2043 College Way, Forest Grove, OR 97116; (503) 352-2278; fax: (503) 359-2929; e-mail: berg1101@pacificu.edu. Dr. Bergenske has no direct financial interest in the products mentioned in this article. He is a paid consultant for both Alcon and CIBA Vision.
• Jennifer L. Smythe, OD, MS, FAAO, can be reached at Pacific University College of Optometry, 2043 College Way, Forest Grove, OR 97116; (503) 359-2770; fax: (503) 359-2929; e-mail: smythej@pacificu.edu. Dr. Smythe has no direct financial interest in the products mentioned in this article, nor is she a paid consultant for the companies mentioned.
• Harue J. Marsden, OD, MS, FAAO, can be reached at the Southern California College of Optometry, 2575 Yorba Linda Blvd., Fullerton, CA 92831; (714) 449-7433; fax: (714) 992-7833; e-mail: hmarsden@scco.edu. Dr. Marsden has no direct financial interest in the products mentioned in this article. She is a paid consultant for CooperVision.