One of the most challenging aspects of eye care is the patient who presents with a non-healing corneal wound.

Because the etiology of this presentation is so diverse and complex, it presents both diagnostic and interventional challenges to clinicians at all levels of ophthalmic practice.

In the debut installment of this new column devoted to corneal health, we’ll focus on how to differentially diagnose non-healing corneal wounds and how to treat such cases using appropriate therapeutic agents.

The most common causes of non-healing corneal wounds or defects are relatively simple, commonly seen conditions, but rarely are they readily attributed to the process.

These include entities such as significant posterior lid disease and ocular surface disease in the form of moderate to severe dry eye, including the autoimmune conditions Sjögren’s syndrome, lupus, thyroid and rheumatoid disease.

Differentially diagnosing non-healing corneal wounds can sometimes be challenging, but if clinicians develop a standardized approach to assessing the history, ocular tissue and the response to intervention, arriving at an accurate diagnosis and implementing appropriate therapeutic care will be made easier.

While all clinicians routinely screen for this problem due to the frequency of occurrence, it is actually sometimes overlooked as a potential source of loss of epithelial integrity.

It is important that the lids be thoroughly assessed for inflammatory disease of an anterior etiology. It is even more important that they are assessed for significant posterior blepharitis with involvement of the meibomian glands.

In patients who have complications secondary to a decrease in tear break-up time, an increase in evaporative tear film loss can show persistent epithelial defects when the remainder of the eye appears normal.

The treatment of this problem is directed toward improving posterior lid function, and most typically involves the use of oral doxycycline, or an equivalent treatment, such as minocycline.

A significant change has been made in the treatment patterns relative to dosing and concentration, and in most circumstances clinicians have moved to a lower dose per day of 20mg to 50mg PO QD, as opposed to the more traditional 100mg PO BID that had previously been used.

The use of doxycycline to treat posterior lid disease is critical because it improves meibomian gland function, which directly impacts the causative problem responsible for the persistent epithelial defect.

Other alternatives in the management of this condition involve the use of oral omega-3 fatty acids. The dosing ranges from 2000 to 3000mg per day, preferably a triglyceride formulation, as it offers increased absorption and bioavailability.

These treatment regimens can be prolonged in their response time and frequently need to be accompanied by adjunctive topical therapy in the form of non-preserved tears and non-preserved bland ointments.

The goal is to create a healthier meibomian gland system that will be able to sustain normal epithelial physiology.

Anterior Basement Membrane Disorder
ABMD is one of the most common corneal dystrophies—so common, in fact, that it is frequently overlooked as a potential cause of non-healing epithelial defects.

In cases of true ABMD, the diagnosis can be made via corneal topography, which is an excellent method of demonstrating irregular surface epithelium profile and allows clinicians to discern the presence of the underlying disease state.

Alternatively, slit-lamp examination can be a helpful diagnostic technique, but is best performed with topical fluorescein to allow the irregular patterning of the corneal epithelium to be observed.

Treatment of ABMD as a cause of non-healing corneal defects is directed towards rehabilitation of the damaged tissue and the reduction of the propensity on the part of ABMD patients to have irregular wound healing (epithelial hyperplasia).

In many instances, this requires intervention with debridement, a bandage lens, topical antibiotics and anti-inflammatories.

In individuals with reduced visual acuity due to ABMD and non-healing or poorly healing epithelial wounds, this treatment can be very effective.

It is recommend that oral doxycycline therapy be added to the regimen in most patients who present with this concern, to decrease matrix metalloproteinase-9 induction and to block the development of collagenase, a mediator of poor wound healing in patients who present with persistent defects. 

Herpes Simplex
In differentiating corneal wound concerns, clinicians should always be vigilant for the presence of herpes simplex virus (HSV). As one of the three mimicking diseases, along with syphilis and Lyme disease, HSV is capable of affecting all ocular tissue.

HSV is typically insidious and, in most instances, diagnosed as a result of failure of more common interventions to produce successful results, with herpes becoming the de facto diagnosis.

It is not uncommon for patients who present with HSV to have epithelial defects for weeks, if not months. Once initiation of oral antiviral therapy is instituted, the wound typically heals relatively quickly and responds favorably to interventional therapy.

In patients in which herpetic complications are suspected, the use of oral antiviral agents—typically Valtrex 500mg PO TID or acyclovir 400mg five times a day—is an appropriate initial dose to reduce the viral population and begin the wound resolution process.

Additionally, topical adjunctives such as non-preserved tears and non-preserved ointments, including Refresh PM, DuoLube or Lacri-Lube, are frequently useful in the healing process.

A typical associated finding is that the patient has been on topical agents such as antibiotics, nonsteroidals or others for weeks prior to the change in diagnosis.

It is important to remember that these agents can be very toxic, and are capable of dramatically slowing the wound healing process. This is particularly true of NSAIDs, which have a well-established history of impacting wound healing. As a result, NSAIDs should be avoided in all circumstances in which non-healing epithelial lesions are present.

Treatment for non-healing corneal defects as a result of toxicity varies from completely discontinuing the culprit drug to markedly reducing the dosing concentration of the topical agents.

In addition, one should implement a regimen designed to support the corneal epithelium in the form of non-preserved tears and ointments. This method can be complemented with an oral agent such as doxycycline to decrease the inflammatory process and stromal involvement by blocking collagenase development.

Epithelial insults that are secondary to toxicity typically respond very rapidly to discontinuation of the toxic agents and the institution of the bland regimen designed to promote epithelial healing.

Rarely is it the case that a cornea made toxic by topical therapy takes as long as weeks to months to heal. Patients who have that type of response may possibly have underlying systemic issues, such as diabetes, herpes and ABMD.

Neurotrophic corneas are one of the most challenging clinical presentations at any level of ophthalmic care: complex in etiology and frequently difficult to diagnose.

Neurotrophia implies that the normal cycle of epithelial stimulation of the 5th cranial nerve to produce epithelial cell regeneration has been interrupted and the area of the cornea involved has a decreased level of epithelial cell production that begins to show initially an epithelial defect and then eventually stromal involvement, which can result in perforation if allowed to progress.

The treatment of neurotrophic disease can be extremely complex. In all instances other than those in which the patient had allergies to the primary therapy, use a full dose (100mg PO BID) of doxycycline during the acute phase.

Additionally, the use of a bandage contact lens can be extremely helpful in treating the underlying disease state, and in many instances will be sufficient to bring the patient back to a normal epithelial presentation, as it blocks the evaporative loss that is part of the process of epithelial cell damage.

Non-preserved topical therapy administered adjunctively at a rate of qh to q2h is appropriate. The patient also needs to be managed carefully with office visits on a regular basis in the initial treatment period to assure that the lesion is responding favorably.

In some patients, the neurotrophic lesions are non-responsive, and as a result, require greater interventional management.