March 2015




Cornea editors corner of the world

Corneal pain without stain

by Ellen Stodola EyeWorld Staff Writer


Every so often, ophthalmologists are faced with cases where they have limited treatment options. This can be extremely frustrating. It is even more difficult when the diagnosis is challenging. Imagine a patient who has severe dry eye complaints but minimal signs on slit lamp examination, i.e., pain without stain. The patient may have a history of LASIK surgery or herpes zoster, but not necessarily. This months Cornea editors corner of the world explores the condition of keratoneuralgia. Stephen Pflugfelder, MD, discusses details of the diagnosis and management of this challenging condition.

Clara C. Chan, MD, FRCSC, FACS, cornea editor


Patients with corneal pain who have little to no signs can be frustrated by a problem that is often challenging to treat

Corneal pain can be a real problem for patients, but it can be even worse when there are little or no signs. Pain without stain was the topic that Stephen Pflugfelder, MD, Baylor College of Medicine, Houston, focused on at the 2014 American Academy of Ophthalmology (AAO) meeting last October. This is defined as symptomatic patients with minimal or no signs, he said. The symptoms may be typical of dry eye, such as burning, foreign body sensitivity, photophobia, and exquisite sensitivity to dry, drafty environments. These patients also have minimal or no relief from conventional dry eye treatments. Rapid tear break-up time (TBUT) is often the only objective sign in these cases. Chronic pain symptoms may lead to central sensitization.


One characteristic feature of pain without stain is that there is disconnect between signs and symptoms that may be dismissed or considered as hysterical or psychosomatic.

Patients are often depressed and feel less productive, Dr. Pflugfelder said. Pain without stain suggests neuropathic pain, also termed keratoneuralgia, he said. The cornea is very vulnerable to developing neuropathic pain, he said. It is the most exposed mucosal tissue in the body and is susceptible to environmental and surgical stress and trauma.

The term keratoneuralgia was initially coined by Perry Rosenthal, MD, Dr. Pflugfelder said, and is an appropriately descriptive term. This issue can also be referred to as corneal neuralgia or neuralgia pain.

With keratoneuralgia, the nerve endings in the cornea become more sensitive to normal environmental stimuli, and increased sensitivity may be due to inflammatory mediators. The diagnosis of keratoneuralgia is primarily clinical or by abnormal nerve by confocal microscopy.


There are a number of steps to treat this condition, including shielding the cornea from the environment, using autologous plasma or serum drops, gabapentin or pregabalin, tricyclic antidepressants, counseling to improve coping with the pain, or referring to a colleague. Unfortunately the outcome is often poor no matter what you do, he said.

Dr. Pflugfelder discussed the topic after the AAO meeting, speaking about the number of patients with this problem and how he handles these cases. Its not that common, he said. But most cornea specialists I know see 1 or 2 patients a month with this problem. It may be easiest to identify the problem in patients who have a history of LASIK who come in complaining of symptoms similar to those of dry eye or saying they are sensitive to air drafts. Additionally, patients may be suffering from pain without stain or keratoneuralgia if they do not have any other objective findings. Dr. Pflugfelder said that many of the patients he sees for this come to him having already been treated with a number of medications but little to no improvement. Its usually a diagnosis of exclusion, he said. Often rapid TBUT is the only sign, or perhaps there is a mild amount of fluorescein staining. Dr. Pflugfelder has not found any treatment that consistently works for these patients, and it often has to be trial and error to attempt to alleviate the pain. In at least 50% of the cases, I still havent adequately addressed their symptoms, he said.

Sometimes patients suffering from keratoneuralgia can have other ocular problems as well, like a history of shingles or herpes zoster. They might have some other manifestations of zoster in the eye like corneal opacities, but most often they do not have much.

Doctors should have an awareness of [keratoneuralgia], he said. Unfortunately, its turned out to be a rare but serious side effect of LASIK. The issue is a particular problem because it can affect productive people whose quality of life is being diminished. The pain can sometimes be so intense that people may want to commit suicide. Usually their vision is fine, but they have eye pain they are unable to deal with. It is analogous to other conditions where objective tests show minimal problems, but the patient is experiencing severe pain, he said.

Editors note: Dr. Pflugfelder has financial interests with GlaxoSmithKline (Brentford, U.K.), Bausch + Lomb (Bridgewater, N.J.), and Allergan (Irvine, Calif.).

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