November 2018

COVER FEATURE

Improving the ocular surface for cataract and refractive surgeons
Pain without stain


by Rich Daly EyeWorld Contributing Writer


“We hope more research is done on this topic and on developing preventative strategies that will minimize the likelihood of developing postop neuropathic pain in susceptible individuals.”
—Rony Sayegh, MD

Key steps for physicians to aid in the diagnosis of keratoneuralgia and when to refer patients for additional care

Patients with keratoneuralgia can present unique challenges for the comprehensive ophthalmologist.
The pain they experience without staining suggests neuropathic etiology. Keratoneuralgia specifically is when the nerve endings in the cornea become more sensitive to normal environmental stimuli. Increased sensitivity may be due to inflammatory mediators. This condition could also be triggered by various types of ophthalmic surgery.
For Anat Galor, MD, associate professor of ophthalmology, Bascom Palmer Eye Institute, University of Miami, diagnosis of keratoneuralgia stems from a combination approach, but she specifically looks for risk factors, including a history of LASIK, fibromyalgia, and the presence of chronic pain conditions.
“Those are red flags that there could be a nerve problem component,” Dr. Galor said.
Specific questions Dr. Galor asks when dealing with potential nerve problems include whether patients characterize the ocular pain as burning or whether the eye is sensitive to wind and light. She also conducts a standardized exam to identify any connections between symptoms and signs. Dr. Galor asks patients to rate anything they perceive as painful, such as dryness or burning, then administers a drop of anesthetic and again has patients rate their pain.
“When ocular pain persists after placement of a topical anesthetic, that indicates that at least in part, nerve dysfunction contributes to the ocular pain,” Dr. Galor said. “Overall, I look at a combination of clinical symptoms and signs to decide if nerve dysfunction is a likely contributor to eye symptoms.”
Rony Sayegh, MD, assistant professor, Department of Ophthalmology, Case Western Reserve University School of Medicine, Cleveland, said the diagnosis of ocular neuropathic pain remains primarily clinical.
“It is suspected in patients presenting with severe dry eye-like symptoms in the absence of signs of dry eye,” Dr. Sayegh said.
Dr. Sayegh also routinely uses various questionnaires on patients presenting with dry eye, including the Ocular Surface Disease Index and the Numeric Pain Rating Scale. An elevated pain score—especially in the presence of eye burning, sensitivity to light and wind, and in the absence of ocular signs—increases Dr. Sayegh’s suspicion for a neuropathic pain component. Additionally, a diagnosis of depression and anxiety is commonly reported by patients with keratoneuralgia.
Unfortunately, anterior segment OCT is of no diagnostic value in such patients, Dr. Sayegh said. Meanwhile, in vivo confocal microscopy holds great promise in demonstrating corneal nerve damage, which is important in making the diagnosis of neuropathic pain. Its value remains limited, however, given the limited access to the technology, significant discomfort in this patient population, and the lack of a standardized way to acquire and interpret the images.
Dr. Galor uses a standardized workup to try to put patients in groups based on underlying etiologies. She looks for insufficient tear production, ocular surface inflammation, meibomian gland dysfunction, anatomical abnormalities, and nerve issues. She tries to identify the most likely cause of symptoms understanding that “patients often have more than one contributing factor.” In general, Dr. Galor tries to address ocular surface issues (inflammation, meibomian gland dysfunction) before targeting the nerves. “However, when a patient comes in with severe symptoms and the ocular surface and anatomy look good, that’s the group I consider to have keratoneuralgia.”

Dry eye

A number of patients with ocular neuropathic pain have underlying dry eye disease or ocular inflammation and benefit from treatment.
“Although the effect is limited and patients with ocular neuropathic pain typically lack response to most traditional dry eye therapies, a treatment trial remains warranted and can be helpful diagnostically,” Dr. Sayegh said.
Dr. Sayegh has found autologous serum tears are the most effective treatment an ophthalmologist can prescribe for the condition, with a significant improvement in pain scores reported by two-thirds of patients. In contrast, Dr. Sayegh’s experience with Prokera (Bio-Tissue, Miami) has not been favorable, with the associated hyperalgesia making the level of discomfort unbearable. Scleral contact lenses can be helpful, especially if used in conjunction with the autologous serum tears.
Dr. Galor treats a patient with suspected keratoneuralgia with traditional dry eye therapies because her first goal is to treat all known sources of pain.
“If I see inflammation, I will try to treat it,” Dr. Galor said. “Nerve sensitization and inflammation go hand in hand, but many of my patients come in already having tried most available dry eye therapies.”
However, in patients naive to dry eye treatments, Dr. Galor uses typical therapies based on exam results. In those who do not respond well to topical therapies and in which keratoneuralgia is suspected, Dr. Galor often uses gabapentin and/or pregabalin. In patients who do not respond or cannot tolerate systemic therapy, Dr. Galor considers adjuvant therapies such as botulinum toxin injection and/or transcutaneous electrical stimulation. Serum tears have been reported to have a wide range of potential benefits, but Dr. Galor has not found them as helpful in her patients with presumed keratoneuralgia. Intrathecal drug delivery systems have been shown to be effective in various pain syndromes and work well for pain localized to the eyes, Dr. Sayegh said.
“It is a last resort operation that is reserved for severe cases that do not achieve adequate relief with other treatments,” Dr. Sayegh said.
A trial is performed first and if patients respond well, an intrathecal catheter is inserted with the tip positioned at the C1–C2 level, delivering drugs to the area of synapse between the nociceptive afferents from the cornea and second order neurons. The catheter is attached to a pump that is implanted in the abdomen. Successful, long-lasting control of the pain can be achieved with this modality.

Mental health consult

Dr. Galor takes a holistic view of the condition as ocular manifestations are often one component of a systemic disease.
“Corneal nerves are connected to the brain, both to the sensing part as well as the limbic system, which is responsible for the emotional response to pain,” Dr. Galor said. “That is why it is important to consider emotional status when treating patients with keratoneuralgia.”
Many patients with keratoneuralgia often readily acknowledge depression and anxiety associated with their chronic pain.
“I tell them that those emotions need to be managed by a psychologist, psychiatrist, or primary care physician,” Dr. Galor said.
Dr. Sayegh said a psychiatric consultation is beneficial for patients whose pain is generalized rather than localized to the eye, especially if it is associated with significant depression or anxiety or if the patient is suicidal.
Every patient undergoes a psychiatric evaluation prior to implantation of the intrathecal delivery system, Dr. Sayegh noted.

Preop screening

Unfortunately, there is no reliable way to screen for patients who will develop ocular neuropathic pain postoperatively, Dr. Sayegh said.
“We hope more research is done on this topic and on developing preventative strategies that will minimize the likelihood of developing postoperative neuropathic pain in susceptible individuals,” Dr. Sayegh said.
Despite the lack of universally predictable screening, Dr. Galor noted that chronic pain doesn’t exist in isolation, so patients with a long history of pain—especially chronic widespread pain like fibromyalgia—are likely at higher risk for developing eye pain.
“Any surgery damages corneal nerves. We think that abnormal nerve healing occurs in some individuals, with resultant persistent pain. While the incidence of severe pain after surgery is low, when it does occur, it can significantly impact a patient’s quality of life,” Dr. Galor said.

Editors’ note: Drs. Galor and Sayegh have no financial interests related to their comments.

Contact information

Galor: agalor@med.miami.edu
Sayegh: rony.sayegh@case.edu

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