When Your Patient Complains of Ocular Pain
Asking the right questions is key to successfully sizing up this common symptom.
By Alison Bozung, OD
Release Date: September 15, 2021
Expiration Date: September 15, 2024
Estimated Time to Complete Activity: 2 hours
Jointly provided by Postgraduate Institute for Medicine (PIM) and Review Education Group
Educational Objectives: After completing this activity, the participant should be better able to:
- Recognize the various ocular conditions that can present with pain.
- Understand how to localize the source of the pain.
- Ask the right questions when a patient complains of ocular pain.
- Narrow the diagnosis through clinical exam findings.
Target Audience: This activity is intended for optometrists engaged in ocular pain management.
Accreditation Statement: In support of improving patient care, this activity has been planned and implemented by the Postgraduate Institute for Medicine and Review Education Group. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education, the Accreditation Council for Pharmacy Education, and the American Nurses Credentialing Center, to provide continuing education for the healthcare team. Postgraduate Institute for Medicine is accredited by COPE to provide continuing education to optometrists.
Reviewed by: Salus University, Elkins Park, PA
Faculty/Editorial Board: Alison Bozung, OD
Credit Statement: This course is COPE approved for 2 hours of CE credit. Activity #122340 and course ID 74032-GO. Check with your local state licensing board to see if this counts toward your CE requirement for relicensure.
Author: Dr. Bozung has no financial interests to disclose.
Managers and Editorial Staff: The PIM planners and managers have nothing to disclose. The Review Education Group planners, managers and editorial staff have nothing to disclose.
Discomfort in and around the eye is one of the most common complaints we receive in clinical practice. However, it’s also one of the least useful in terms of diagnostic guidance. How can we localize the cause? Which instances might be more troubling than others? How can we filter out the patient’s subjective experience—some are far more pain-tolerant than others—when determining the urgency of our response?
The process begins by understanding what the term “pain” actually entails. Pain is defined as “a localized or generalized unpleasant bodily sensation or complex of sensations that causes mild to severe physical discomfort and emotional distress and typically results from bodily disorder (such as injury or disease).”1 It is a type of somatic sensation that is recognized when a stimulus supersedes a particular “pain threshold.”
When a stimulus is determined to be of a severity that could cause tissue damage, an afferent protective reaction is triggered. This reaction, for example, could include a person pulling their arm away from an abrasive surface or blinking their eyes when discomfort is felt. In the body, nociceptors are the specialized, unencapsulated nerve endings responsible for receiving and relaying information that is thought to be potentially harmful to the body. These stimuli include high and low temperatures, mechanical touch and exposure to chemical or inflammatory mediators.2
The first division of the trigeminal nerve, the ophthalmic branch (CN V1), is responsible for transmitting sensory information from the conjunctiva, sclera, cornea and upper eyelid. The ocular surface specifically detects noxious stimuli through mechanoreceptors, polymodal nociceptors and thermoreceptors.3
CN V1, however, is not limited to the ocular structures. It also provides innervation for the scalp, dura of the anterior cranial fossa, tentorium cerebelli, falx cerebri, superior sagittal sinus and some intracranial vessels. Therefore, inflammation or dysregulation in any of these associated areas can be referred and thereby perceived by an individual as eye pain.4,5
Due to the non-localizing symptom of eye pain, our examination of the patient becomes critical in determining the trigger. This article will help us answer the perennial question, “Doc, can you explain my eye pain?”
|Fig. 1. This patient presented with blurred vision but did not complain of significant pain. His examination revealed a geographic area of corneal haze with an overlying epithelial defect. He has a past medical history of recent irradiation to the ipsilateral jaw for adenoid cystic carcinoma of the salivary gland. Due to the geographic appearance of the defect, this patient was started on an oral antiviral along with intense lubrication of the eye. Click image to enlarge.|
Categorizing and Qualifying Ocular Pain
When evaluating a patient who presents with eye pain, qualifying their symptoms should guide the practitioner’s examination. For example, a patient presenting with eye pain after working on the computer for eight hours is likely experiencing dry eye. If the patient describes pain that is significantly worse when exposed to bright light, the doctor should assess them for corneal ulceration or abrasion or uveitis.
The patient’s ophthalmic history is also a critical piece of the puzzle. If this patient recently experienced ophthalmic trauma, what was the mechanism of said injury? Did they recently have cataract surgery and are they experiencing discomfort after tapering corticosteroid drops too quickly? Additionally, ask qualifying questions regarding the pain to determine the length of time for which it has been present and if there are any relieving factors.
We can mentally categorize ocular discomfort into external or internal ocular, orbital or referred pain. External ocular pain includes causes such as corneal abrasions, dry eye and corneal ulcers. Internal ocular pain refers to conditions such as acute angle closure, uveitis and acutely elevated intraocular pressure (IOP). Orbital pain can result from periocular trauma, inflammation or a retrobulbar mass.
Referred ocular pain does not originate within the periocular structures; rather, it is caused by a stimulus from somewhere within the ophthalmic division of the trigeminal nerve’s innervation territory.4 Below, we will introduce and discuss common causes of ocular pain in relation to the structure of the eye and adnexa.
|Fig. 2. This patient presented with a history of recent ocular trauma. He denied significant pain but eventually sought eye care due to blurred vision. Despite the relative “quiet” appearance of his eye, the corneal culture revealed Fusarium species. Click image to enlarge.|
External Causes of Ocular Pain
The first category we will explore is external pain, which can be associated with a number of causes:
Corneal epithelial defect. The cornea is the most densely innervated tissue in the body. There are an estimated 7,000 nociceptors per square millimeter, meaning the cornea is an impressive 300 to 600 times more sensitive to pain than the skin.6 It is therefore no surprise that even a very small defect of the cornea can lead to immense discomfort.
Corneal epithelial defects can be seen with white light but are more easily visualized by sodium fluorescein under the illumination of a blue light. A careful history may also elucidate recent trauma to the ocular surface.
Intense eye pain upon awakening is commonly present in patients suffering from recurrent corneal erosion syndrome. In these cases, assessment of the cornea may reveal clinical evidence of prior trauma such as a scar, epithelial basement membrane dystrophy or a small area of nascent epithelium in erosions that have already begun to heal.
When an epithelial defect is present without pain, the physician should be suspicious of a neurotrophic component. The most common causes of a neurotrophic or desensitized cornea include herpetic keratitis, corneal nerve damage from trauma or surgery, chronic diabetes, chronic contact lens wear, chemical burns or cases such as head and neck radiation (Figure 1).7 When neurotrophic keratitis is suspected, corneal sensation should be assessed prior to anesthetic drop instillation.
Dry eye and neuropathic pain. Patients with dry eye frequently experience ocular discomfort. In fact, dry eye has been reported as the number one ophthalmic cause of ocular pain that presents to an ophthalmologist.4
Dry eye is an over-arching term to describe a very heterogenous disease. In many settings, the clinician can visualize obvious signs of dry eye. These may include decreased tear breakup time, low tear prism height, meibomian gland atrophy, eyelid ectropion and punctate staining of the cornea and conjunctiva.
Pain, though experienced by all, is highly subjective. Pain modulation is a complex, higher-order process that is impacted by various individualized factors such as psychological stress, anticipation, past experiences and genetics, to name a few.8,9 Furthermore, central sensitization is a maladaptive process thought to begin after an initial insult to peripheral (in our case, usually corneal) nerves. This insult can “prime” the pain pathways in the brain, decreasing the threshold needed to elicit a sensation of pain.
When a patient is experiencing significant symptoms of ocular discomfort or pain, yet there is a paucity of clinical findings to support the diagnosis of dry eye, neuropathic ocular pain (NOP) must be on our radar. Often, the discomfort is not relieved by topical anesthetics as one would anticipate with classic dry eye, making this a useful clinical probe in diagnosing this condition.10 Allodynia, a term used to describe pain experienced from a stimulus that is not typically painful, is a common finding in patients with NOP.
NOP is challenging to treat in that it typically does not respond as well to classic dry eye therapies and can be triggered by weak stimuli such as a light breeze. There continues to be significant ongoing research investigating the pathologic underpinnings and best treatment strategies for this condition.
|Fig. 3. This young contact lens wearer presented with significant eye pain and had diffuse corneal epithelial irregularity. There was no infiltrate or anterior chamber reaction. Due to clinical suspicion for Acanthamoeba, she was monitored closely. At her two-day follow-up, early perineuritis was visible and the patient was treated with antiamoebic therapy. Her symptoms resolved quickly. Click image to enlarge.|
Infectious keratitis. The estimated incidence of corneal ulcers in the United States is between 30,000 and 75,000 annually.11 Risks include but are not limited to contact lens wear, ocular trauma, dry eye, ocular surface disease, trichiasis and ophthalmic surgery. Clinical signs of corneal infections include an epithelial defect over an inflammatory stromal infiltrate, stromal edema, conjunctival injection and anterior chamber reaction.
Ocular pain from infectious keratitis is often coincident with photophobia, reduced visual acuity, redness and tearing. When evaluating a suspected corneal infection, the level of pain is a key component. A patient’s level of pain over the course of treatment for infectious keratitis can be helpful, as reduced pain typically signifies a positive response to treatment. In addition, though not always a reliable tell, pain may also provide some clue as to the pathogen.
Classically speaking, there are some infections that tend to cause less pain than one may anticipate. As mentioned previously, herpes simplex and herpes zoster are two viruses often implicated in the pathogenesis of neurotrophic corneal disease. Interestingly, fungal keratitis has also been frequently associated with decreased pain sensation, though the reason for this is not yet fully understood. One study of patients with hyphal fungal keratitis suggests this could be the result of decreased corneal nerve density and branching (Figure 2).12 Regardless of the mechanism, this reduction in pain detection can lead to a delay in seeking care and, ultimately, receiving a proper diagnosis for these indolent infections. Longer time to detection and progression of disease can lead to a worse diagnosis in these difficult-to-manage infections.
On the other side of the coin are corneal infections that create pain out of proportion to the clinical examination. The most recognizable of these infections is Acanthamoeba keratitis (AK). The clinician must always have this in mind when evaluating a patient with a non-specific keratitis. It should be a red flag when the patient in question has a history of contact lens wear, especially while swimming or showering in fresh water. Early clinical signs include diffuse epithelial roughness, pseudodendrites and perineural inflammation (Figure 3). This perineural inflammation is likely the reason for increased pain levels. Perineuritis, which presents as whitish haze along stromal corneal nerves, can be seen in up to 63% of cases at six weeks, though its existence is easily overlooked without the provider’s specific intention to find it.13
A “classic” finding of AK is a ring infiltrate, but this is not pathognomonic for AK alone and, when present, denotes an advanced stage of disease. Due to this infection’s ability to persist despite treatment, the best outcomes occur when it is diagnosed early by corneal culture or in vivo confocal microscopy.
Internal Causes of Ocular Pain
A variety of conditions and issues can be a source of internal ocular discomfort:
Uveitis. Photophobia is a close acquaintance of ocular pain, and one of the most common etiologies of these joint symptoms is uveitis. This condition refers to inflammation of the uveal tract and can be classified as anterior, intermediate or posterior depending on the structures involved. Pain is secondary to ciliary spasm, and therefore, cases of posterior uveitis involving primarily the retina and choroid may not be as painful as anterior uveitis. Since the iris and ciliary body are innervated by V1, the pain can “radiate,” or be felt in a larger area than the eye itself. Many patients with anterior uveitis will also complain of an ipsilateral frontal headache, for example.
A thorough front-to-back ophthalmic examination is necessary to determine the level of involvement, as the treatment strategy will vary depending on the involved tissues. Even in first-time occurrences, a broad review of systems should investigate recent ophthalmic surgeries, ocular trauma, systemic autoimmune or inflammatory conditions and general systemic symptoms.
Treatment ranges from instillation of topical corticosteroid and cycloplegic agents to initiation of systemic immunosuppressive agents in chronic or non-responsive cases. Any underlying systemic disease should also be addressed.
|Fig. 4. This male in his mid-30s presented with severe eye pain bilaterally that was worse on eye movement. A CT scan was completed during the initial visit due to suspected myositis but was unremarkable. The patient returned to the emergency department three days later with a sudden and drastic decline in his visual acuity from 20/15 in each eye at the initial visit to no light perception in the right eye and 20/400 in the left eye. An MRI obtained that day (seen here) revealed bilateral ON. Labs eventually returned with elevated anti-MOG antibody titers. Click image to enlarge.|
Elevated IOP. Acutely elevated IOP, as seen in conditions such as angle closure or hyphema, can cause significant eye pain, bulbar injection, blurry vision from acute corneal edema and headache. Interestingly, there is also an association of evelated IOP with nausea and vomiting. The oculocardiac reflex, in which extraocular muscle manipulation leads to nausea and bradycardia, has been well documented in cases of strabismus surgery and trap-door orbital fractures.14
The understanding between acutely elevated IOP and nausea, however, is not well understood. It is thought that rapidly increasing IOP can act as a noxious stimulus to the ophthalmic division of the trigeminal nerve, perhaps by way of swiftly altered corneoscleral stretch. Because rapid IOP changes are not associated with cardiac complications, it has been postulated that there may exist a direct “oculo abdominal reflex” arc involving the trigeminal nerve and specific vagus nerve branches to the visceral organs.15 Our examination should ultimately focus on determining the cause of the elevated IOP and treating comorbid conditions. Ocular pain will subside significantly with normalization of the IOP in these cases.
Orbital (and Cavernous Sinus) Causes of Ocular Pain
Orbital—and cavernous sinus—pain can present as a result of a number of different issues:
Optic neuritis (ON). A hallmark of this condition is optic nerve inflammation. Though it can occur at any age and can be secondary to infectious or autoimmune conditions, the most common subset of ON is demyelinating disease that affects middle-aged females. The inflammation is most often located along the retrobulbar/intraorbital segment but may also be visible anteriorly as optic disc edema in about a third of cases. ON is associated with pain in over 90% of cases, and this typically intensifies with eye movement.16 Though all four recti muscles attach to the annulus of Zinn near the orbital apex, the superior and medial recti muscles share close attachments with the optic nerve sheath itself. Eye movement is thought to cause tractional forces on the inflamed nerve sheath and meninges, worsening symptoms.17
Visual symptoms in ON tend to follow the onset of pain within a matter of days. At that point, our clinical exam will often reveal an afferent pupillary defect, mildly decreased visual acuity, a central scotoma and dyschromatopsia of the affected eye. A high index of suspicion must be maintained in early presentations, as there may be a lack of objective findings to support the diagnosis initially. It is also important to note that our differential list should include atypical forms of ON, such as those related to infections, neuromyelitis optica spectrum disorder or myelin oligodendrocyte glycoprotein (MOG) syndromes if the condition presents bilaterally or is associated with severe visual deficits (Figure 4).
Extraocular muscle injury. Damage to the extraocular muscles occurs mainly via blunt orbital trauma or a sharp, penetrating object. In these cases, patients usually experience diplopia and pain, especially when moving their eye. The eye itself often manifests some evidence of trauma, such as a subconjunctival hemorrhage, traumatic iritis or commotio retinae. When evaluating a patient for orbital trauma, pay close attention to motility deficits, eye misalignment, enophthalmos and maxillary hypoesthesia, as these can all be red flags for an orbital fracture.
If you suspect an orbital fracture with or without extraocular muscle entrapment, obtaining computed tomography (CT) imaging is helpful to ascertain the extent of involvement (Figure 5). CT imaging is quicker, less expensive and better at bone imaging when compared with magnetic resonance imaging (MRI), making it the method of choice for these cases. Pain after orbital trauma arises from muscle contusion, hematoma or entrapment. Discomfort from a hematoma will likely resolve as inflammation subsides, but patients with entrapped tissue should be referred to oculoplastics for a surgical evaluation.
|Fig. 5. This patient sustained blunt ocular trauma to the right side of his eye and developed eye pain and diplopia afterward. CT imaging revealed right medial wall and floor fractures with extraocular muscle deviation. He underwent surgical repair with a floor implant. Click image to enlarge.|
Orbital inflammation. Orbital pain, though not necessarily specific to the orbit for reasons discussed above, is a salient feature of orbital inflammation, which can occur secondary to an underlying systemic pathology such as thyroid dysfunction, granulomatosis with polyangiitis, sarcoidosis, IgG-4-related disease, Sjögren’s syndrome, metastatic disease or other lymphoproliferative disorders.18 Orbital inflammation can be caused by an infection such as orbital cellulitis, which should be ruled out by a careful history and imaging of the adjacent sinuses.
When no underlying pathology can be deemed responsible, the condition is aptly termed idiopathic orbital inflammation (IOI). Under the umbrella category of IOI, inflammation most commonly involves the extraocular muscles (myositis), lacrimal gland (dacryoadenitis) or orbital fat. IOI is the second most common inflammatory orbital disorder, after thyroid eye disease.19 Patients with IOI are more likely to be female and in their fourth decade of life. Most commonly, when IOI affects muscles, the horizontal recti are the most commonly involved.20 The most common symptom, therefore, is pain on eye movement, typically in the gaze directed away from the affected muscle. These cases will also likely exhibit motility restriction and conjunctival injection over the recti insertion.
When clinical suspicion supports this diagnosis, additional imaging with orbital ultrasonography, CT or MRI can be helpful, though some suggest MRI is the most sensitive diagnostic study.21 A careful review of systems and medications should be performed, and inflammatory and autoimmune labs are often completed to rule out a systemic etiology. Depending on the severity, oral non-steroidal anti-inflammatory drugs may be a first-line therapy, but most cases will require the use of oral corticosteroids. For non-responsive cases, orbital biopsy and steroid-sparing agents are considered and often comanaged with rheumatology.
Cavernous sinus pathology. The cavernous sinuses are paired sinuses located directly posteromedial to the superior orbital fissures. The sensory ophthalmic (V1) and maxillary divisions (V2) of the trigeminal nerve pass through the cavernous sinus. Therefore, pathology in the cavernous sinus can cause pain or headache. Some examples of cases presenting with periocular pain are those secondary to carcinoma with perineural spread through the cavernous sinus, carotid-cavernous fistula, cavernous sinus aneurysms or thromboses and Tolosa-Hunt syndrome.22-24
Since the oculomotor, trochlear and abducens cranial nerves as well as a portion of the internal carotid artery pass through the cavernous sinus with such close proximity, it is common to see multiple cranial nerve palsies co-present when there is a mass or inflammation in the cavernous sinus. Neuroimaging is vital and should be completed on an emergent basis for an ultimate diagnosis in these cases.
What We Gain from Pain
Ocular pain can be an onerous symptom, but as primary eye care providers, we are well-equipped to assess these complaints. Starting with a comprehensive history, we can focus our evaluation to determine the cause of pain for the patient in our chair. When we can help a patient in pain, there is a lot to gain for us as well as our patients.
Dr. Bozung practices at the Bascom Palmer Eye Institute in Miami, where she primarily sees patients in the hospital’s 24/7 ophthalmic emergency department. She serves as the associate director of the optometric residency program and is the clinical site director of the optometric student externship program. She has no financial interests to disclose.
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