In this episode of Interventional Mindset, Dr. Anat Galor, MD, MSPH, addresses the challenges of diagnosing and understanding ocular surface pain. Dr. Galor is a cornea and uveitis specialist at the University of Miami’s Bascom Palmer Eye Institute and the Miami VA Medical Center.
Pain points: finding the right terminology
Dryness. Burning. Stabbing. Aching. Patients use these descriptors time and time again. And in many cases, they are accompanied with a dry eye diagnosis. However, even if a patient says they have dry eye symptoms, dry eye is not always the cause of these sensations, says Dr. Galor.
Although symptoms are perceived at the ocular surface, they may arise from multiple locations and/or mechanisms. Nociceptive pain can result from injury or inflammation at the ocular surface, whereas neuropathic or nociplastic pain can originate from abnormal signaling anywhere along the sensory pathway from the cornea to the brain.
Regardless of where the signal begins, pain is ultimately constructed and experienced within the central nervous system. This helps explain why ocular pain can be clinically challenging: similar symptoms may reflect very different underlying mechanisms, and when symptom severity is disproportionate to observable ocular surface findings, neuropathic or nociplastic mechanisms should be considered.1,2
Types of ocular pain:
- Nociceptive: Tissue damage localized to the receptors at the ocular surface
- Neuropathic: Damage or disease disrupting peripheral or central nervous system
- Diabetic neuropathy, lesion, surgical procedure
- Nociplastic: Pain related to altered pain processing without clear evidence of ongoing tissue damage or a lesion of the somatosensory nervous system. It is thought to involve altered processing and modulation of pain within the central nervous system.
- Migraine, fibromyalgia
Dr. Galor recommends taking an agnostic approach to ask questions and find the right terminology to figure out the cause rather than assume based on the description. Upon hearing the words “dry” or “aching,” she chooses language addressing “pain” or “discomfort” to establish a dialogue with the patient to help guide further examination. The whole patient history and lived experience, along with the right testing, is crucial to determine how to diagnose and treat their individualized case.
Case study: A deeper dive beyond dry eye
A 55-year old patient was previously diagnosed with dry eye, and presented with itching and burning—no dryness. Artificial tears were applied multiple times daily but did not help. She also reported knee and neck pain, dry mouth, and a history of migraine and Hashimoto’s thyroid disease.
Asking the right questions
Two commonly used questionnaires to capture ocular symptoms are the OSDI and the DEQ-5, however it’s important to understand that their scores are composites of various symptoms, each of which may reflect a different underlying mechanism driving the patient’s complaints.3 The OSDI doesn’t even mention the word “dry”, notes Dr. Galor.
She instead focused on specific individual questions to help figure out the cause of the patient’s complaint. In this case, the patient’s OSDI responses were dominated by pain and sensory triggers rather than visual complaints. She reported painful or sore eyes and sensitivity to light all of the time and also reported consistent ocular discomfort in windy conditions.
In contrast, visual symptoms, namely blurred and poor vision, were reported less frequently. This pattern suggests that her elevated OSDI score was driven primarily by ocular pain and stimulus sensitivity rather than visual disturbance.
But complementing the questionnaires, it is also helpful to simply ask patients to rate the intensity of their pain or discomfort, regardless of the specific descriptor they use. When asked to rate her pain, the patient recalled over the course of 1 week, an average rating of 6 on the pain scale.
Ocular examination
Dr. Galor states that she approaches each case like a detective, and her examination starts the moment she steps into any room.
Initial clinical findings
- Physical exam: Periocular skin, eyelid anatomy, blink rate, and ability to close eyes are unremarkable
- MMP-9 immunoassay: Mild level of ocular surface inflammation
- Slit lamp: Meibomian gland dysfunction in the form of eyelid vascularity; meibum quality is “like toothpaste”
- Fluorescein and lissamine green staining: Diffuse corneal and conjunctival staining, low tear breakup time, low Schirmers, indication of dry eye
Going beyond what we can see
With the current information, Dr. Galor believed the findings raised concern for Sjögren's disease, prompting the question: is what we’re seeing at the ocular surface being driven by something else in the body?
However, SSA and SSB antibodies were negative for Sjögren’s, though the patient did have a family history of autoimmune disease—rheumatoid arthritis (aunt) and cerebral vasculitis (mother.)
Dr. Galor pursued serological testing for CA6, SP1, and PSP—biomarkers on the parotid gland and lacrimal gland that have been studied as early markers of Sjögren's, though their diagnostic significance is low due to findings of poor specificity.4 This patient’s serologies were elevated, supporting the presence of a systemic inflammatory process, although the findings were not specific to a single disease.
The initial treatment plan
In this case, the patient had ocular surface pain and dry eye disease, so Dr. Galor’s treatment plan focused on reducing inflammation. She emphasizes that patients do not respond equally to all anti-inflammatory therapies, and because we still cannot reliably predict which treatment will work best for which patient, having multiple options is important.
For short-term treatment, corticosteroids such as fluorometholone can be a useful option because they are primarily surface-directed and generally have a lower risk of off-target effects, including intraocular pressure elevation. For long-term treatment, Dr. Galor prefers T cell modulation, using immunosuppressants such as cyclosporine or lifitegrast.
However, after cycling through four different anti-inflammatory eye drops, the patient’s ocular pain did not improve, despite reduced inflammation and improved tear production.
Getting to the root
When anti-inflammatory treatment did not adequately relieve the patient’s ocular pain, Dr. Galor considered whether another mechanism might be contributing. Given the patient’s prominent sensitivity to wind and light, features that can suggest nerve dysfunction, she re-examined the patient’s nerve status to determine whether nerve-targeted treatment should be considered.
Dr. Galor recommends incorporating a nerve assessment into every ocular surface examination, as nerve abnormalities are one of several potential contributors to ocular pain. This assessment should include a corneal sensation check using a cotton tip, dental floss, or, when available, an esthesiometer.
Abnormally reduced or increased sensitivity may suggest altered corneal nerve function. However, even when pain is perceived at the ocular surface, the question remains whether it is being generated entirely there.
Assessing nerve function with the proparacaine test and imaging
The topical anesthetic challenge can provide additional insight. Dr. Galor asks the patient to rate their pain, applies a drop of proparacaine, and then asks them to rate their pain again. A substantial reduction in pain supports a peripheral contribution arising from the ocular surface.
In contrast, persistent pain despite adequate topical anesthesia suggests that mechanisms beyond the ocular surface may be contributing, including abnormal signaling in periocular sensory nerves or altered pain processing within the central nervous system.
The presence of cutaneous allodynia, or pain or sensitivity to light touch of the skin around the eye, provides another clue that pain mechanisms may extend beyond the ocular surface. This distinction is clinically important because pain driven primarily by ocular surface abnormalities may respond to topical therapies, whereas pain involving extraocular peripheral or central mechanisms may require additional nerve-targeted approaches.
Finally, in vivo confocal microscopy, when available, can provide additional information about corneal nerve morphology and complement the functional assessment. Here, the patient had some features that supported nerve abnormalities as contributing to her pain—low density and tortuosity of the nerves on in vivo confocal microscopy, and corneal hypersensitivity on testing.
Based on this information, a new treatment plan of multimodal therapy included autologous serum tears, oral low-dose naltrexone, and education on positive coping mechanisms to work through the often slow pace of improvement.
A path forward through neuromodulation
Dr. Galor emphasizes that one of the most important steps in this process is patient education. Patients need to understand that there is rarely a “magic cure” for chronic ocular pain and that improvement may take time. Neuromodulation, or the use of therapies to alter abnormal nerve signaling and pain processing, often requires a gradual and individualized treatment approach.
However, even if there isn’t a “quick fix,” Dr. Galor says multimodal therapy offers the patient plenty of options to continue to improve their quality of life. “I tell my patients, our goal is to achieve your own personal 'Goldilocks': not too little, not too much, that targets the mechanisms that are underlying your pain,” she explains.
Don’t say dry eye unless you mean it
In conclusion, Dr. Galor reemphasizes that even if patients complain of dry eye, consider it might be something else that warrants further investigation beyond the surface. In this case, the patient did have dry eye, and her ocular surface findings improved with treatment directed at inflammation. Her pain, however, persisted. This highlights an important point: even when dry eye is present, it may not fully explain the patient’s symptoms.
Dr. Galor emphasizes the need to take a broader, more holistic approach to ocular pain by considering the ocular surface, peripheral nerves, central pain processing, and relevant systemic co-morbidities. The goal is to identify which mechanisms are contributing in an individual patient and target treatment accordingly.
Rather than assuming that all “dry eye” symptoms arise from the ocular surface, clinicians should investigate further when symptoms persist or appear disproportionate to examination findings. A more individualized, mechanism-based approach can help guide treatment and ultimately improve patient outcomes.
This article was written by Mariel Mohns, MS, based on the video from Dr. Galor.
