Herpes Simple:

A Review of the Clinical Challenges

Of Herpes Simplex Keratitis

For many eye care professionals, three weeks won't pass without at least one suspect case of herpes simplex keratitis. While most cases of simplex keratitis are straightforward in diagnosis and treatment, a small portion of cases can be rather challenging to notice and may even test your abilities to catch a few Z's when you really need them.

Mark Twain once said, ìIf you have to swallow two frogs, swallow the big one first. However weíre going to diss that notion and review the straightforward easy stuff first. 

The initial or primary infection is usually sub clinical and goes unnoticed. If you were to encounter a primary infection, you would probably find skin vesicles on the upper and lower lid accompanied with lymphadenopathy. Most cases of primary herpetic infection find their way into the dermatologistís office where they are treated with topical anti-virals such as acyclovir (Zovirex) ointment. It is the recurrence of this primary infection, which brings the patient to your office.

Most cases of simplex keratitis tend to report with a persistent red eye with moderate irritation. Many have already been treated by someone else or have been self-treating their problem with medicine left over from Aunt Winnieís cataract surgery. Most report this festering period has been going on for about 4 to 7 days. Your first suspicions of simplex keratitis should arise due to relative tolerance to a rather ìhotî looking eye. This is due to corneal desensitization, a hallmark sign of simplex keratitis.

Visual acuity is usually mildly reduced, and slit lamp examination reveals a follicular conjunctivitis with moderate hyperemia. The cornea usually shows a classic dendritic or geographic ulcer (see figs. 1&2). The dendrite is usually linear with branches terminating in end-bulbs, similar to those found on toy pick-up jacks. Careful examination of the anterior chamber should follow to rule out the possibility of a subsequent anterior uveitis.

Figure 1. Classic Dendritic Ulcer

Figure 2. A More Severe Geographic Ulcer

Treatment usually begins with a cycloplegic, such as 5% Homatropine q12H, to either quell or prevent an anterior chamber reaction. The drug of choice for the simplex infection is trifluridine (Viroptic), initially used q2H for 48 hrs., then qid for the following 7 days. A follow-up visit 48 hrs. after initiation of treatment is strategic to determine if progress is being made against the dendrite. If so, the reduction of Viroptic to qid is prudent as this agent is fairly toxic to the eye because it inhibits healthy cell division.

Because a bacterial infection is rarely involved, the addition of an antibiotic is not necessary. However, if the disease runs a long course and other signs of bacterial infection occur, such as a mucopurulent discharge, initiating a broad-spectrum antibiotic is advisable.

Patient education should include the recurrent nature of the beast and how that happens. Just about all adults carry a titer of the herpes simplex virus, (from a primary infection which usually occurs in childhood). The virus is a large complex DNA virus, which lies dormant in corneal cells, but is primarily found in the trigeminal nerve. Here, the virus is like a sleeping bear until something disturbs its rest. That something is anything that disturbs the hostís immune system. E.g.- fevers, menses, prolonged illness, exposure to sunlight, psychiatric disturbances, prolonged use of steroids or other immunosuppressive agents, or physical disturbance of the nerve from injury or refractive surgery.

The likelihood of recurrence is 1 out of 4 during the first 5 years. If a second attack occurs, the risk of further recurrence within the next 2 years is increased to 50%.

If the patient is currently under any treatment for prolonged or chronic illness, communication of your findings and treatment with the patientís primary physician would be advised. Your findings may represent one more piece in the puzzle as the primary physician tries to manage the whole case.

With all of the above as the backdrop, now we are going to look with a little more detail into what to do when the case gets a little off the beaten path. The patientís greatest enemy, (and therefore your greatest enemy), in dealing with simplex keratitis is the possibility of advancing stromal keratitis. If left to fester, stromal keratitis will probably lead to permanent loss of corneal transparency.

A simplex keratitis represents on infective inflammation. The problem arises because this inflammation cannot be treated with our usual weapon of choice, the corticosteroids. The abilities of the virus to replicate in the presence of steroids has been well documented.

Stromal herpetic keratitis usually occurs in patients who have had previous attacks of epithelial herpes. Use your slit lamp to evaluate the stroma directly under the dendrite, using a narrow slit to identify depth. The deeper the edema, the greater the risk of stromal keratitis.

Persistent stromal edema may eventually lead to tissue disruption, a.k.a. stromal scarring. Therefore, steroid use should begin as soon as the epithelial defect is gone if persistent stromal edema is present. This can be like walking on a tightrope and requires frequent monitoring (q24H). Care should be given to use the least amount of steroid necessary, and compliment this treatment with an anti-viral med, (Viroptic qid). Consider starting prednisolone acetate (Pred forte 1%) bid and increasing to qid if necessary.

Figure 3. Disciform Keratitis with Stromal Edema and KPís

If not recognized and treated, stromal keratitis can spill over into disciform herpetic disease. At this point, we are no longer talking about a simple cold sore on the eye. Disciform herpetic keratitis presents as a pattern of local stromal corneal edema with underlying folds in Descemetís membrane and keratic precipitates (KPís) on the endothelium (see fig. 3). The KPís are concentrated beneath the involved area of the cornea, presumably due to the increased ìstickinessî of the diseased endothelium. At this point, you can count on a rather severe anterior chamber reaction.

If an anterior chamber reaction begins to accelerate, the risks for developing secondary glaucoma also climbs. Careful attention must be paid to the IOP and timolol (Timoptic XE) may be instilled to manage the pressure if no contraindications exist.

A detailed fundus evaluation is also important in all cases of herpetic eye disease to rule out the possibility of posterior vasculitis. This frothy finding along the vessel walls of the retina could point to vitritis, optic neuritis, or even acute retinal necrosis. These patients are almost always suffering from severe immune compromise, (e.g.- AIDS). 75% of these patients will go on to have retinal detachments. A referral to a retinal specialist is critical for patients with posterior pole involvement.

The treatment of disciform keratitis is similar to that mentioned above for stromal keratitis. However the patient is now at a much greater risk of corneal thinning (melting) due to a greater degree of inflammation. These risks are amplified if the lesion is centrally located. If severe desiccation occurs, consideration could be given for a bandage soft contact lens. Cases which are non-responsive to the above treatment regimen will probably require a penetrating keratoplasty (corneal transplant), and therefore should be promptly referred to a corneal specialist.

Occasionally, the literature will speak of treating cases of simplex keratitis with corneal debridement. The efficacy of Viroptic has made this treatment scarce unless you were trapped on Gilliganís Island and Ginger had a dendritic keratitis. (Undoubtedly, the Professor probably would have brought some Viroptic anyway).

However, if you were to attempt a corneal debridement, this would be best accomplished using ample topical anesthesia and brushing the lesion with a cotton-tipped applicator. Healing should occur in the 24-48 hours. Any more aggressive instrument could lead to unnecessary damage.

Ultimately, if all topical methods have failed and the cornea has lost its transparency or a perforation is imminent, a penetrating keratoplasty (PK) may be necessary. If perforation occurs, corneal adhesives and a soft contact lens may help to reform the anterior chamber in preparation for a PK. If permanent corneal haze is the issue, PKís are approached with caution. Many surgeons would prefer the cornea to remain without recurrent disease for 6 to 12 months before considering the procedure.

A word about treatment agents:

All topical anti-viral medications are toxic. Signs of this toxicity include punctate epithelial keratopathy, limbal follicles, ptosis, and punctual stenosis. You can pretty much count on signs of toxicity after 10 to 14 days of therapy. While trifluridine (Viroptic) is one of the least toxic, you should anticipate that the patientís eye will look irritated at the conclusion of 10 days of therapy.

If improvement is not noted at the 48-hour follow-up visit using Viroptic q2H, consideration could be given to qH therapy augmented by vidarabine ointment (Vira-A) at night.

Even if no anterior chamber reaction is found, a cycloplegic agent should be initiated to aid in patient comfort and possibly head off a subsequent uveitis. This concept should be considered any time the cornea is under assault, and is particularly important in this situation because of the desire to avoid steroids.

While the use of topical steroids should largely be avoided in cases of dendritic keratitis, you must be on guard to use corticosteroids if the stoma becomes threatened. Inappropriate use of steroids may result in severe epithelial disease and increased tendency for recurrence. These complications can be minimized by concurrent use of topical anti-viral therapy. 

Conclusions

 Most cases of simplex keratitis are straightforward in diagnosis and treatment. An anti-viral, a cycloplegic, and good patient education usually provides a happy ending. However close attention should be paid to the stromal tissue directly under the presenting lesion. Increasing stromal haze could mean concurrent therapy of a steroid and an anti-viral, accompanied by close observation. 

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Questions or concerns about courses should be directed to the individual authors and/or the Continuing Education Department at the College of Optometry at kundart@pacificu.edu.