- 1 Introduction
- 1.1 1. Disease Entity
- 1.2 2. Diagnosis
- 1.3 3. Management
- 1.4 4. References
Photo-Oculodynia is an idiopathic chronic eye pain syndrome characterized by hypersensitivity and pain in response to light without inflammation. It may be sympathetically mediated and is usually preceded by a history of ocular trauma that can be minor. Topical anesthesia and cycloplegia do not provide relief, but improvement has been seen with cervical sympathetic ganglion block, botulinum toxin, and prophylactic migraine medications.
1. Disease Entity
Photo-Oculodynia is eye pain and/or discomfort from a light source that is not typically a source of pain and/or discomfort (e.g. ambient lighting). It is different from photophobia or photoaversion. Photophobia is more broadly defined as discomfort without pain in the eye or head that causes an avoidance reaction, and photoaversion is the avoidance of light due to discomfort with or without impaired visual acuity. Although there is a distinction between these terms, oftentimes photophobia and photo-oculodynia are concomitant phenomena.
The pathogenesis of Photo-Oculodynia is not fully characterized. It is an uncommon idiopathic syndrome that is often triggered by ocular trauma. The stimulus for the pain is light, which surprisingly can be perceived by blind patients. This suggests that image formation is not needed in order to cause the pain. Photo-Oculodynia’s pain has some support that it may be sympathetically mediated, as shown when sympathectomies have demonstrated some relief from the pain. However, the specific mechanism of relief is not well understood.
1.3 Risk Factors
Photo-Oculodynia risk factors have not been well characterized; however, as stated above, ocular trauma often triggers photo-oculodynia. In addition, conditions that have been found to be associated with photophobia include agoraphobia, anxiety disorder, depression, hangover headache, neurasthenia, fibromyalgia, measles, rabies, inflammatory bowel disease, ichthyosis follicularis with alopecia and photophobia, psoriasiform lesions and palmoplantar keratoderma, Trisomy 18, zinc deficiency with exocrine insufficiency, and medication use including the use of barbiturates, benzodiazepine, chloroquine, methylphenidate, haldol, and zoledronate.
1.4 General Pathology
One general pain pathway of the eye comes through the ophthalmic V1 division of the trigeminal nerve, where its nuclei are the primary mediators of pain sensation to the eye. The nociceptive afferents travel along cranial nerves III, IV, and VI leading to pain with orbital myositis. When activated by a nociceptive stimulus, there is a positive feedback loop through the trigemino-vascular reflex where the cranial vessels dilate. In this reflex, calcitonin gene related peptide and nitric oxide are released. It is a multisynaptic reflex, in which superior salivatory outputs activate parasympathetic effectors in the pterygopalatine ganglion which causes dilation of vessels. In addition, the trigemino-vascular and trigemino-autonomic reflexes are thought to underlie the conjunctival injection, tearing and periorbital pain of migraine and cluster headaches which also accompany photophobia. This reflex goes through the superior salivatory and Edinger-Westphal nucleus by collaterals from the trigeminal nucleus caudalis. The orbit is also densely innervated by sympathetic efferents, where the short ciliary nerves carry sympathetic supply to the blood vessels. Stimulation of the superior cervical ganglion causes pain in humans, and pharmacologic blockage of sympathetic innervation has been shown to produce relief in patients with intractable facial pain who have failed trigeminal section.
The stimulus for photo-oculodynia is light and as such the pathway for light processing is a potential area to better characterize photo-oculodynia. Rods and cones are the primary light sensors of the eye, and they transmit signals via bipolar and amacrine cells to retinal ganglion cells, which sends the signal through the optic nerve to the lateral geniculate of the nucleus of the thalamus and then to occipital cortex. The olivary pre-tectal nucleus also receive efferents in the Edinger-Westphal nucleus to help mediate parasympathetic pupillary constriction and accommodation. In addition, other visual information processing fibers will project to the suprachiasmatic nucleus which contributes to the functioning of the circadian cycle.
A separate set of photo-sensors has also been identified called intrinsically-photosensitive retinal ganglion cells (ipRGCs). These cells contain melanopsin rather than rhodopsin, and they both detect light and project the photo-signal to the olivary pretectal and suprachiasmatic nuclei. These cells have been found in the retina as well as the iris.
In addition to the processing of light, the sensory pathway of pain stimulation is another pathway that may elucidate a more precise characterization of photo-oculodynia. There are two distinct circuits that have been identified, with a possible third pathway that is not as well understood. In the first pathway, a nociceptive response to light exposure has been identified where the firing rate of neurons in the trigeminal nucleus caudalis increases in response to light exposure. These neurons in the trigeminal nucleus caudalis send nociceptive information to the parabrachial and thalamic nuclei, which is then relayed to the sub-cortical and cortical centers. Interestingly, lidocaine anesthetic injection at both the intraocular afferent site and trigeminal neuron site were required to eliminate light-evoked nociceptive discharge into either the globe of the eye or the trigeminal ganglion. An additional aspect of this pathway was found through experimentally injecting lidocaine anesthetic into the superior salivatory nucleus and injecting vasoconstrictors into the globe, with pain relief observed. This demonstrated that contribution from parasympathetic efferents is also involved. It is currently hypothesized that these neurons are “photophobia neurons” considering they are responsive to painful stimulation as well as to light, and because they get convergent input from trigeminal and retinal afferents on the same thalamic neurons.
A second circuit that was found was through the ipRGC neurons, which were identified to have a direct connection to thalamic nuclei including the posterior, lateral posterior, and intergeniculates, which are not typical relay centers for vision. They experimentally found that these neurons responded to painful nociceptive stimulation to light, and also traced the pathway of this signaling to the visual cortical and sub-cortical areas.
The third circuit that is currently proposed relates the thalamic-cortical relationship, where the reciprocal relationship between the cortex and the thalamus suggests that once the relationship and function of alterations and deeper processing between these two structures is better identified, their role in photo-oculodynia is likely to be more precisely understood.
Lastly, possible molecular targets in photophobia-related photo-oculodynia include those involved with intracranial nociception in migraine, which prominently involve activity of the calcium gene related peptide receptor (CGRP). This is a target for migraine treatment, where antagonists to the CGRP receptor alleviate acute migraines. Mice with gain-of-function mutations in the CGRP signaling pathway demonstrate symptoms consistent with migraine.
The diagnosis of photo-oculodynia is established in the history taking of the patient, along with neurological and neuro-ophthalmic examination. Currently, no specific diagnostic criteria have been set for photo-oculodynia; however, Bossini et al. developed and validated a related photophobia questionnaire and self-assessment tool for an Italian population with 16 items. In addition, Choi et al. also validated a related photophobia in migraine patients.
In 1995, PG Fine and KB Digre distinguished photophobia and photo-oculodynia, defining photo-oculodynia as the presence of eye pain in response to light that typically does not cause pain, and defining photophobia as the presence of discomfort and aversion to light. Currently, photophobia is more commonly used, even in the presence of pain, and the characterization of photo-oculodynia is still limited.
2.2 Physical Examination
Physical examination findings on assessment of photo-oculodynia are typically normal with no pertinent negative or positive findings. Diagnosis relies more heavily on history taking of the patient and the previously mentioned validated assessment tools. However, notable pertinent positive and negative physical examination findings of associated diseases can be present.
Signs of photo-oculodynia are the presence of pain in response to light that typically does not cause a pain sensation.
Symptoms of photo-oculodynia include pain in response to light that typically does not cause a pain sensation.
2.5 Clinical Diagnosis
Clinical diagnosis is reached through taking a patient history as well as performing neuro-ophthalmic examinations.
3.1 General Treatment
Pharmacotherapeutic treatment remains unknown; however, treating the underlying condition is considered the first steps towards treatments. This can be beta-blockers, calcium channel blockers, anticonvulsants, and CGRP inhibitors for patients with migraine associated with photophobia. Botulinum neurotoxin is also a treatment of choice for blepharospasm and has some effect on migraine headache. Another treatment is to use lenses that block specific wavelengths of lights, such as FL-41 lens which blocks wavelengths around 480 nm which is the wavelength at which ipRGCs exhibit the greatest response. In addition, avoiding intense light and avoiding exposure to triggers that contribute to associated symptoms is often part of behavioral modification that naturally occurs for those with painful response to light. In addition, referral to a neuro-ophthalmologist would be helpful in order to treat and diagnose the conditions that often are associated with and accompany photo-oculodynia.
Sympatholysis has been conducted in a controlled trial for treatment of photo-oculodynia with promising results, but surgery is currently not first line treatment.
Treatment of photo-oculodynia includes medications that treat associated pathology, botulinum neurotoxin, as well as sympatholysis. In addition, lenses that block certain wavelengths of light have been shown to be effective. Current prognosis in response to treatment of photo-oculodynia has not been well characterized and is a potential direction of further research.
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