Clinical imperatives of ocular infection

Primary Care Optometry News gathered a group of experts to discuss the theme of our issue: "Treatment of Ocular Infections." Led by Editor Michael D. DePaolis, OD, the panelists addressed differential diagnosis of adenoviral and conjunctival infections, when to culture and treatment protocols

Participants included: Nick Holdeman, MD, OD; Paul Ajamian, OD; Linda Casser, OD; and Joseph P. Shovlin, OD.

--- Michael DePaolis, OD

Michael D. DePaolis, OD: What is the clinical differential between adenoviral and bacterial infections?

--- Paul Ajamian, OD, is the center director of Omni Eye Services of Atlanta, an optometric consultation comanagement center.

Paul Ajamian, OD: First of all, the optometrist should use gloves whenever he or she sees a red eye. Take a careful but brief history and determine how many days into the disease the patient is, so that if infiltrates are present, you'll know whether it is adenoviral or perhaps a contact lens hypersensitivity infiltrate.

There are three basic things to check with red eyes. The first is preauricular nodes. This will immediately distinguish adenoviral from bacterial in most cases. The second is to get a big-picture view of the injection, having the patient look up, down, left and right. The third is to evert the lids because sometimes you find some surprises and get led down the wrong path.

The classic presentation for adenoviral is the preauricular node, watery discharge, follicular response and, 7 to 10 days into the course of the disease, infiltrates. The acute bacterial conjunctivitis presents with a mucopurulent discharge. I don't see this very often.

DePaolis: I agree wholeheartedly. In my clinical experiences, the number of bacterial conjunctivitis cases we have seen pales by comparison to the number of adenovirals.

How long do you tell patients the disease lasts? Our classic teaching is that these are 21-day diseases. We have seen our share of patients who go through the cycle and still have some lingering symptoms--some dryness, some irritation, some inability to return to contact lenses--for what seems more than 3 weeks.

--- Joseph P. Shovlin, OD, is a Clinical Associate at the Northeastern Eye Institute in Scranton, PA, and is an Adjunct Faculty member of the Pennsylvania College of Optometry.

Joseph P. Shovlin, OD: We usually tell them they need a 7-day vacation from whatever they are doing to avoid spreading the infection. We have seen infiltrates linger for months. As long as patients have a quiet eye and there is no superficial irritation, I will allow them to go back to contact lenses at least with a short wearing time. If we wait for the infiltrates to go away completely in a white eye, we are going to wait for a long time.

--- Linda Casser, OD, is director of the Indianapolis Eye Care Center for the Indianapolis University School of Optometry, and an associate professor at the university.

Linda Casser, OD: In our facility in Indianapolis, we see many more bacterial than adenoviral infections. We run cycles of epidemic keratoconjunctivitis (EKC). We see a lot of rhinovirus involvement, which is less severe than the adenovirus with the EKC presentation as Dr. Ajamian described it.

DePaolis: Rochester has become the ultimate managed care environment. Some of the HMOs have mandated that primary care physicians, internists and pediatricians treat all conjunctivitis. So, many patients who end up in the ophthalmic practice, whether it is the OD's practice or the MD's practice, are the patients who were tentatively diagnosed as bacterial and did not respond to the first line treatment. I think there is a selective process by which those who are the bacterial conjunctivitis are aptly treated by the pediatrician or the general practitioner, respond well, then don't end up in our chairs.

Casser: They also tend to be self-limiting and the symptoms are obviously less severe than an EKC, so that would make sense.

DePaolis: Dr. Ajamian, do you think that is why at the Omni center you see more adenoviral infection as well?

Ajamian: Managed care has certainly changed things, and when we got our therapeutic bill, that markedly decreased the number of red eyes that we saw. But, I always think there must be something wrong with our patient population because we rarely see acute bacterial conjunctivitis.

If you add staphylococcal lid disease to the category of bacterial conjunctivitis, then we see a great deal of it. The common presentation is of the patient who complains of chronically red, irritated, burning eyes with a mucoid discharge on awakening. The patient may have seen several practitioners and given drops which helped temporarily. Unfortunately, no one examined the lids and prescribed lid scrubs and a topical antibiotic ointment. This is a much more common scenario than acute bacterial disease and can turn you into a hero in your patient's eyes.

DePaolis: Dr. Holdeman, is it ever appropriate to add topical steroids when treating adenoviral patients, such as when the patient is significantly symptomatic and the visual acuity is down?

Dr. Shovlin mentioned seeing infiltrates linger for months. Maybe what we are looking at months later is a residual scarring; maybe it is an immune response to antigen dead virus.

--- Nick Holdeman, OD, MD, is chief of Medical Services, director of the University Eye Institute at the University of Houston College of Optometry.

Nick Holdeman, OD, MD: I use steroids for adenoviral infections in about 20% of cases. And I agree that adenoviral infections or viral infections, in general, will probably outnumber bacterial infections, at least in adults. Our corneal disease specialist, for a period of time, cultured all cases of conjunctivitis, and about 90% of them were culture-negative. He believes that viral infections are much more common in adults.

I counsel patients concerning the fact that a viral condition might get worse before it gets better. And I advise using cold or warm compresses--whichever feels best to them and--artificial tears.

About the only time I would use steroids is if the patient is very symptomatic or if infiltrates are overlying the visual access and it is a detriment to the patient. It also depends on the patient's occupation and how reliable and compliant I think he or she will be in coming back; tapering patients off steroids is difficult because the infiltrates will often return and you must be concerned about immunocompromising the cornea and IOP elevations.

Casser: I have used low potency steroids for 18 years routinely on EKC patients with good success. I find that when patients are in that very miserable phase--their lids are swollen, they're tearing, they're very photophobic--I get good results by putting them on something like Blephamide (sulfacetamide-prednisolone acetate, Allergan) or if I'm using an antibiotic for some reason--if the eye is really irritated and inflamed and I feel I need a prophylaxis component--I'll use an antibiotic and Pred Mild (prednisolone acetate 0.12%, Allergan).

With the lower potency, we don't run into problems with lingering infiltrates. I keep it a short course to get them through that miserable stage and then taper them off as quickly as I can.

DePaolis: One of our corneal specialists in town uses them rarely, but whenever he does use them, he almost inevitably slowly tapers a fluorometholone over a prolonged period of time.

Holdeman: Dr. Casser brings up a good point. I placed one of my patients on steroids, she came back with 20/80 vision due to central infiltrates, I put her back on steroids and it cleared up almost immediately, but I had a difficult time getting her to return for progress exams. You need to be concerned about noncompliant patients who are out there with a bottle of steroids.

Most cases do fairly well, without many complications. I think it depends a lot on the virulence of the strain they happened to contract.

Ajamian: It's easy for us to prescribe cold compresses and tears, but that's usually when patients leave and go to other doctors looking for help. They'll finally get a bottle of Blephamide, and maybe by then things are getting better, and the last doctor is the hero. There is no magic cure, but you should do everything you can; and sometimes steroids will make patients feel well enough to at least stay in your care.

I've also tried a disposable lens as a bandage lens during the day to get patients through that nasty, foreign-body, pseudomembrane sensation.

DePaolis: We have also used bandage lenses for symptomatic patients with reasonably good results.

What should we look at from a differential diagnosis standpoint?

Holdeman: If you're going use steroids on those types of infections, you must be aware how certain diseases can be indistinguishable at certain stages.

The virus that practitioners are most concerned about is herpes simplex. With simplex you can get a follicular response, a preauricular node, watery discharge and a superficial punctate keratopathy that looks very similar to adenovirus. You hate to inadvertently prescribe steroids for these cases and have the patient be noncompliant on follow-up visits.

Chlamydia at times can also look very similar, but steroids won't help, either.

Casser: I've seen what seems to be a mixed mechanism: maybe a viral infection with superimposed mattering in the morning that is not a chlamydial presentation. I have believed these are cases where an inflamed eye becomes susceptible to a bacterial superinfection.

There are times--when even though I wouldn't think about an antibiotic for a mild low-grade viral infection--I would use the antibiotic because there seems to be a mixed presentation. Has anyone heard of using nonsteroidal anti-inflammatory drugs (NSAIDs) on adenovirus?

Ajamian: I have not tried it or heard of anyone who has.

Holdeman: I have not either. I concur with what Dr. Casser said about the antibiotics. That is why when I do use a steroid, I use something like Blephamide, or I will use Polysporin Ophthalmic Ointment (polymyxin B-bacitracin, Burroughs Wellcome) at night. When the epithelium is compromised, a secondary bacterial infection is more likely. The nonsteroidals are very good; it would not surprise me if they would be helpful in some patients to lessen discomfort.

Shovlin: Without trying them on patients with adenoviral infection, I can't say for certain, but we are probably working on the wrong cascade. For inflammatory disease, especially certain contact lens-related problems, I have found little benefit from NSAIDs. They have found their place in pain reduction, but I doubt there would be much value for that type of inflammation.

DePaolis: I agree. The NSAID in the short term perioperative phase for pain control works wonders, whereas the steroid in the long term--wound healing and presumably refractive outcome modulation--works well. I never thought of using them in an adenoviral patient in terms of modifying the degree of inflammation, but maybe there is merit from a discomfort standpoint.

Dr. Holdeman mentioned that one of the cornea specialists he practices with had cultured conjunctivitis and finds most culture-negative. In routine clinical practice, most of us would agree that to expedite patient care and contain health care costs, we do not routinely culture conjunctivitis. When should you culture?

Holdeman: The only time I culture blepharoconjunctivitis is in patients who have been to numerous practitioners and I feel they probably have a resistant staphylococcal type of infection. Maybe they have been placed on an aminoglycoside, sulfacetamide, tetracycline and/or erythromycin. In those cases I will stop everything for about 5 days to exclude toxicity and, if it doesn't go away, I will culture and then start the patient on something else. I have found that a lot of staph are resistant to many drugs.

DePaolis: Dr. Shovlin?

Shovlin: We culture very little, but we recommend it for certain conditions. Foremost need would be for ulcerative keratitis. In addition to that, I would recommend culturing anything that is ulcerative on the conjunctiva. We also culture dacryocystitis routinely, primarily to rule out fungal infection using Sabourauds media. I would suggest neonatal conjunctivitis as well.

DePaolis: What do you keep in your office for culturing?

Ajamian: We always have a fresh set of sheep blood and chocolate plates. When we see patients with conjunctivitis, they have usually been referred to us through several practitioners, so we culture the lid and conjunctiva in most cases to be sure we are not missing anything.

Our cornea specialist has started doing more routine viral cultures, with success. As far as first-time conjunctivitis, we do what most doctors do, and that is to treat it empirically.

DePaolis: Would anyone like to comment on differential diagnosis of adenovirus? The herpes simplex virus patient? The Chlamydia patient? These infections may create the chronic conjunctivitis you see. Might chronic conjunctivitis patients actually have a noninfectious or systemic infection such as Chlamydia?

Ajamian: One of my favorites is "mucus fishing syndrome." For every patient who comes in complaining of chronic mucus production, yet you don't see a lot, I ask them if they go into their eye and fish it out. It is important, because they can be creating that vicious cycle of goblet cell damage that creates more mucus. If you don't ask, they won't tell you.

Shovlin: So many of the patients with red eyes that we see, contact lens-related in particular, begin with a tentative diagnosis of persistent adenoviral infection, and it is nothing more than a contact lens-related infiltrative keratitis.

Holdeman: When I see patients with chronic conjunctivitis, I first look for a follicular reaction, because that helps in my differential diagnosis. If they've got a condition that's existed for more than 4 weeks and they've got a follicular conjunctivitis, one should be thinking about Chlamydia or some kind of toxic medicomentosa. Follicles are very helpful in establishing a differential diagnosis. Acutely, that's where simplex would be considered.

As far as culturing is concerned, I don't culture often, although I probably culture more than most because I have been surprised by the organisms and sensitivity patterns.

I culture all contact lens wearers if they have an infectious infiltrate or an early ulcer, regardless of where it is located. If patients are not contact lens wearers, have community-acquired infections and have a small, peripheral shallow ulcer or infiltrate, I treat empirically.

We keep blood, chocolate, Sabourauds and thioglycolate in the clinic at all times. We use them fairly often.

Shovlin: We do, as well. We also have the ability to incubate those culture plates, so we will hold them to avoid the cost of lab analysis, and if the patient is not responding well to empiric treatment, then we will send the plates to the lab for confirmation of microbial growth and sensitivity testing. From a medicolegal standpoint, you have something to fall back on.

Holdeman: We do the same thing.

Casser: My setting is not as well-equipped for culturing as some of the main campus university settings, so we take the empirical route. There's always the comanagement approach or referral option when the clinical condition warrants.

DePaolis: There are differences in scope of licensure from state to state. Depending on where you practice and in what mode, you may or may not want to do this. The key is to ensure that if patients need these services, they can be rendered, whether they are done in your office or in a comanagement venture.

Let's address treatment protocols. What do you consider a first-line drug, and when do you use it? When are you more apt to use a fluoroquinolone?

Ajamian: We aren't left with a lot of choices these days. The rule of thumb is to use the least potent thing you can, so that you have a big gun left. We use fluoroquinolones strictly for infectious keratitis. I would start with either Tobrex (tobramycin, Alcon) or Polytrim (trimethoprim sulfate; polymyxin B sulfate, Allergan) on a bacterial conjunctivitis.

DePaolis: Dr. Holdeman, what is your drug of first choice in a bacterial conjunctivitis? And in those more resistant cases, what do you move to?

Holdeman: We have to remember that when we get our cultures and sensitivities back, they are based on blood levels of antibiotics, and there is no standardized way to report ocular cultures. When we are putting drugs directly on the site we may get a different response than the lab is getting. We also can't factor in the patient's ability to fight infection. Most cases of conjunctivitis get better in 7 days, and if they don't, you treat them.

In a pure bacterial conjunctivitis, I usually use Polytrim. I have been staying away from the aminoglycosides because I think they are a bit more toxic and their spectrum of activity is not quite as good, particularly for the gram-positive organisms, which cause most bacterial conjunctivitis infections.

Casser: My preference these days is Polytrim drops during the day, Polysporin ointment at bedtime. I find that the sensitivity reactions have been fewer. However, a large portion of my patient population cannot afford Polytrim, so in those instances I go with tobramycin generic drops during the day, and ointment at bedtime.

I'll move up to the fluoroquinolones if I see a bacterial conjunctivitis in a contact lens wearer. Then I will go with a Ciloxan (ciprofloxacin HCl, Alcon) or Ocuflox (ofloxacin, Allergan).

DePaolis: Dr. Shovlin?

Shovlin: We use fluoroquinolones a lot. The concern is that widespread use has led to resistance, but I don't think it is a big issue with ocular infections, at least not yet with this class of drug. For kids, we use Polytrim.