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Indian Journal of Ophthalmology Jul 2020Ocular pain is a common complaint which forces the patient to seek immediate medical attention. It is the primeval first response of the body to any severe condition of... (Review)
Review
Ocular pain is a common complaint which forces the patient to seek immediate medical attention. It is the primeval first response of the body to any severe condition of the eye such as trauma, infections and inflammation. The pain can be due to conditions directly affecting the eye and ocular adnexa; or indirect which would manifest as referred pain from other organ structures such as the central nervous system. Paradoxically, there are several minor and non-sight threatening conditions, which also leads to ocular pain and does not merit urgent hospital visits. In this perspective, we intend to provide guidelines to the practising ophthalmologist for teleconsultation when a patient complains of pain with focus on how to differentiate the various diagnoses that can be managed over teleconsultation and those requiring emergency care in the clinic. These guidelines can decrease unnecessary hospital visits, which is the need of the hour in the pandemic era and also beyond. Patients who are under quarantine and those who are unable to travel would be benefitted, and at the same time, the burden of increased patient load in busy hospital systems can be reduced.
Topics: Acute Pain; Betacoronavirus; COVID-19; Coronavirus Infections; Diagnosis, Differential; Disease Transmission, Infectious; Eye Pain; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Telemedicine
PubMed: 32587167
DOI: 10.4103/ijo.IJO_1267_20 -
Cornea Jan 2022This study characterized ocular pain symptoms in individuals with and without a history of refractive surgery (RS) using a cross-sectional survey of individuals with...
PURPOSE
This study characterized ocular pain symptoms in individuals with and without a history of refractive surgery (RS) using a cross-sectional survey of individuals with ocular pain.
METHODS
A link to an anonymous survey was posted on a corneal neuralgia Facebook group that included individuals with ocular pain from any etiology and sent to individuals seen in our clinic with ocular pain. The survey asked about medical history, ocular pain symptoms (using standardized questionnaires), and treatment responses. Respondents were split into 2 groups based on a history of RS.
RESULTS
One hundred one individuals responded to the survey. The mean age for all respondents was 41.6 ± 15.6 years, and 50% reported a history of RS. A total of 46% of individuals with a history of RS reported that their ocular pain started within 1 month of surgery, with median pain duration of 36 (interquartile range 22-84) months. The median Dry Eye Questionnaire-5 (range 0-22) scores were 16 and 15 for the RS and no-RS groups, respectively. Most individuals in both groups characterized their pain as burning (score ≥1: RS, 86%; no-RS, 80%) and reported evoked pain to wind, light, or temperature (score ≥1: RS, 97%; no-RS, 85%). Fifty-nine of 101 individuals responded to treatment questions. Individuals in both groups reported >30% improvement in pain symptoms with some topical and systemic approaches.
CONCLUSIONS
Individuals with a history of RS developed ocular pain soon after surgery, which persisted for years. Symptom profiles were similar between those with and without RS. Topical and systemic approaches can treat pain in both groups.
Topics: Adult; Cross-Sectional Studies; Eye Pain; Female; Florida; Humans; Incidence; Male; Pain Measurement; Refractive Surgical Procedures; Retrospective Studies; Surveys and Questionnaires
PubMed: 33560674
DOI: 10.1097/ICO.0000000000002675 -
Frontiers in Pharmacology 2021Protons reaching the eyeball from exogenous acidic substances or released from damaged cells during inflammation, immune cells, after tissue injury or during chronic... (Review)
Review
Protons reaching the eyeball from exogenous acidic substances or released from damaged cells during inflammation, immune cells, after tissue injury or during chronic ophthalmic conditions, activate or modulate ion channels present in sensory nerve fibers that innervate the ocular anterior surface. Their identification as well as their role during disease is critical for the understanding of sensory ocular pathophysiology. They are likely to mediate some of the discomfort sensations accompanying several ophthalmic formulations and may represent novel targets for the development of new therapeutics for ocular pathologies. Among the ion channels expressed in trigeminal nociceptors innervating the anterior surface of the eye (cornea and conjunctiva) and annex ocular structures (eyelids), members of the TRP and ASIC families play a critical role in ocular acidic pain. Low pH (pH 6) activates TRPV1, a polymodal ion channel also activated by heat, capsaicin and hyperosmolar conditions. ASIC1, ASIC3 and heteromeric ASIC1/ASIC3 channels present in ocular nerve terminals are activated at pH 7.2-6.5, inducing pain by moderate acidifications of the ocular surface. These channels, together with TRPA1, are involved in acute ocular pain, as well as in painful sensations during allergic keratoconjunctivitis or other ophthalmic conditions, as blocking or reducing channel expression ameliorates ocular pain. TRPV1, TRPA1 and other ion channels are also present in corneal and conjunctival cells, promoting inflammation of the ocular surface after injury. In addition to the above-mentioned ion channels, members of the K and P2X ion channel families are also expressed in trigeminal neurons, however, their role in ocular pain remains unclear to date. In this report, these and other ion channels and receptors involved in acid sensing during ocular pathologies and pain are reviewed.
PubMed: 34899333
DOI: 10.3389/fphar.2021.773871 -
Investigative Ophthalmology & Visual... Jan 2022Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to...
PURPOSE
Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy.
METHODS
We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain.
RESULTS
Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation.
CONCLUSIONS
These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.
Topics: Administration, Ophthalmic; Analgesics; Animals; Astrocytes; Calcium Channels, L-Type; Chronic Disease; Cornea; Disease Models, Animal; Dry Eye Syndromes; Eye Pain; Hyaluronic Acid; Hyperalgesia; Male; Microglia; Neuralgia; Neurons; Ophthalmic Solutions; Pregabalin; Rats; Rats, Sprague-Dawley; Trigeminal Nerve
PubMed: 34989761
DOI: 10.1167/iovs.63.1.7 -
Klinische Monatsblatter Fur... Nov 2014Optic neuritis is a frequent neuro-ophthalmological disease in which the diagnosis can be based on just a few symptoms and findings. It is not only important to... (Review)
Review
Optic neuritis is a frequent neuro-ophthalmological disease in which the diagnosis can be based on just a few symptoms and findings. It is not only important to differentiate from other optic nerve disorders but also to recognise special types of optic neuritis, which is mostly only possible during the course of the disease. This article presents a review of the current state in diagnosis and therapy from the authors' personal point of view.
Topics: Anti-Inflammatory Agents; Diagnosis, Differential; Eye Pain; Humans; Multiple Sclerosis; Optic Neuritis; Vision Disorders
PubMed: 25285570
DOI: 10.1055/s-0034-1382930 -
Scientific Reports Jun 2023This study aimed to determine the reliability and validity of the Japanese version of the Ocular Pain Assessment Survey (OPAS-J) to measure ocular pain and quality of...
This study aimed to determine the reliability and validity of the Japanese version of the Ocular Pain Assessment Survey (OPAS-J) to measure ocular pain and quality of life. A multi-institutional cross-sectional study was conducted on participants with and without ocular pain. The Wong-Baker FACES® Pain Rating Scale served as the gold standard for measuring the intensity of ocular pain. Sixty-four participants who visited two clinics located in Japan between May 2019 and October 2019 were included in the study. The OPAS was translated and culturally adapted to Japanese. The internal consistency of the OPAS-J was assessed using Cronbach's alpha coefficient. Twenty-four (37.5%) and 40 (62.5%) participants were classified as having ocular pain and no ocular pain, respectively. All dimensions of the OPAS-J had good reliability, with a Cronbach's alpha coefficient of 0.870 for ocular pain intensity over the past 24 h and 0.874, 0.899, 0.874, 0.871, and 0.876 for ocular pain intensity over the past 2 weeks, non-ocular pain, interference with quality of life, aggravating factors, and associated factors, respectively. The OPAS-J is a reliable and responsive tool that can be used to quantify ocular pain intensity.
Topics: Humans; Cross-Sectional Studies; East Asian People; Eye Pain; Japan; Pain; Pain Measurement; Psychometrics; Quality of Life; Reproducibility of Results; Surveys and Questionnaires
PubMed: 37353644
DOI: 10.1038/s41598-023-36740-x -
Journal of Clinical Medicine Jul 2019Dry eye and glaucoma are two frequently encountered ocular conditions, which can lead to substantial morbidity and decreased quality of life. Patients on topical...
Dry eye and glaucoma are two frequently encountered ocular conditions, which can lead to substantial morbidity and decreased quality of life. Patients on topical glaucoma medications are known to be at greater risk for ocular surface symptoms. Veterans seen in the eye clinics at the Miami Veterans Affairs Hospital from January to July 2016 completed surveys assessing dry eye and ocular pain symptoms, including the five item Dry Eye Questionnaire (DEQ5). A total of 62 patients with glaucoma completed the survey. Of those, 52 were on glaucoma medications at the time of the survey, with the majority requiring more than one medication to control intraocular pressure. The frequency of mild or greater dry eye symptoms (defined as DEQ5 >6) tended to increase with increasing medication burden, and patients on brimonidine were more likely to report a DEQ5 >6. Patients on three or more glaucoma medications were more likely to report symptoms of shooting pain, dryness, and itchiness. Patients using timolol were more likely to report throbbing and pain by light, while those on latanoprost reported stinging. Our data support an association between increasing number of glaucoma medications and worsening of dry eye symptoms. Patient and medication-associated symptoms can be used to tailor individual medication regimens.
PubMed: 31336584
DOI: 10.3390/jcm8071076 -
Investigative Ophthalmology & Visual... Mar 2021The purpose of this study was to test the role of substance P (SP) and its receptor neurokinin 1 (NK1R) on ocular surface pain.
PURPOSE
The purpose of this study was to test the role of substance P (SP) and its receptor neurokinin 1 (NK1R) on ocular surface pain.
METHODS
Eight-week-old C57BL6/N (wild type [WT]) and B6.Cg-Tac1tm1Bbm/J (TAC1-KO) male mice were used. 5 M NaCl was topically applied on the cornea, followed by topical fosaprepitant 2, 10, and 50 mg/mL; 4 mg/mL oxybuprocaine chloride, or 0.1% diclofenac. Th eye wiping test was used to quantify ocular surface pain. SP content was quantified in the tear fluid and trigeminal ganglia (TG), and TAC1 mRNA was assessed in the cornea. Corneas were immunostained for β3-tubulin and NK1R, or CD45, to quantify leukocyte infiltration.
RESULTS
TAC1-KO mice displayed a significant reduction of ocular pain (P < 0.001). Similarly, a single dose of 10 or 50 mg/mL fosaprepitant applied topically to WT mice reduced ocular pain as compared to vehicle (P < 0.001). Fosaprepitant 2 mg/mL, instead, induced corneal analgesia only when it was administered for 10 days, 6 times/day (P < 0.05). Diclofenac or oxybuprocaine reduced corneal nociception when compared to vehicle or fosaprepitant (P < 0.05). Fosaprepitant or oxybuprocaine groups showed lower SP content in tear secretions and TG (P < 0.05), and reduction in TAC1 mRNA (P < 0.05), and leukocyte infiltration (P < 0.05) in the cornea. Colocalization of NK1R and β3-tubulin was detected in mouse corneas.
CONCLUSIONS
Topical administration of the NK1R antagonist fosaprepitant effectively reduces ocular surface nociception by decreasing SP release in the tear fluid and TG, and corneal leukocyte infiltration. Fosaprepitant repurposing shows promise for the treatment of ocular pain.
Topics: Administration, Ophthalmic; Animals; Cornea; Corneal Diseases; Disease Models, Animal; Eye Pain; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Morpholines; Neurokinin-1 Receptor Antagonists; Nociception; Ophthalmic Solutions; Substance P; Tears; Trigeminal Nerve
PubMed: 33729475
DOI: 10.1167/iovs.62.3.26 -
Frontiers in Neuroscience 2023To examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in...
INTRODUCTION
To examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular pain.
METHODS
Twelve subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: (1) chronic ocular pain; (2) presence of ocular pain over 1 week recall; and (3) presence of photophobia. All individuals underwent an ocular surface examination to capture tear parameters before and 4-6 weeks after BoNT-A injections. Using an event-related fMRI design, subjects were presented with light stimuli during two fMRI scans, once before and 4-6 weeks after BoNT-A injection. Light evoked unpleasantness ratings were reported by subjects after each scan. Whole brain blood oxygen level dependent (BOLD) responses to light stimuli were analyzed.
RESULTS
At baseline, all subjects reported unpleasantness with light stimulation (average: 70.8 ± 32.0). Four to six weeks after BoNT-A injection, unpleasantness scores decreased (48.1 ± 33.6), but the change was not significant. On an individual level, 50% of subjects had decreased unpleasantness ratings in response to light stimulation compared to baseline ("responders," = 6), while 50% had equivalent ( = 3) or increased ( = 3) unpleasantness ("non-responders"). At baseline, several differences were noted between responders and non-responders; responders had higher baseline unpleasantness ratings to light, higher symptoms of depression, and more frequent use of antidepressants and anxiolytics, compared to non-responders. Group analysis at baseline displayed light-evoked BOLD responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, midcingulate cortex (MCC), bilateral frontal pole, bilateral cerebellar hemispheric lobule VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, S2 cortices, cerebellar hemispheric lobule VI, cerebellar crus I, and left cerebellar crus II. BoNT-A responders displayed activation of the spinal trigeminal nucleus at baseline where non-responders did not.
DISCUSSION
BoNT-A injections modulate light-evoked activation of pain-related brain systems and photophobia symptoms in some individuals with chronic ocular pain. These effects are associated with decreased activation in areas responsible for processing the sensory-discriminative, affective, dimensions, and motor responses to pain.
PubMed: 37404468
DOI: 10.3389/fnins.2023.1202341 -
Frontiers in Cellular Neuroscience 2020The cornea is the most densely innervated and sensitive tissue in the body. The cornea is exclusively innervated by C- and A-delta fibers, including mechano-nociceptors... (Review)
Review
The cornea is the most densely innervated and sensitive tissue in the body. The cornea is exclusively innervated by C- and A-delta fibers, including mechano-nociceptors that are triggered by noxious mechanical stimulation, polymodal nociceptors that are excited by mechanical, chemical, and thermal stimuli, and cold thermoreceptors that are activated by cooling. Noxious stimulations activate corneal nociceptors whose cell bodies are located in the trigeminal ganglion (TG) and project central axons to the trigeminal brainstem sensory complex. Ocular pain, in particular, that driven by corneal nerves, is considered to be a core symptom of inflammatory and traumatic disorders of the ocular surface. Ocular surface injury affecting corneal nerves and leading to inflammatory responses can occur under multiple pathological conditions, such as chemical burn, persistent dry eye, and corneal neuropathic pain as well as after some ophthalmological surgical interventions such as photorefractive surgery. This review depicts the morphological and functional changes of corneal nerve terminals following corneal damage and dry eye disease (DED), both ocular surface conditions leading to sensory abnormalities. In addition, the recent fundamental and clinical findings of the importance of peripheral and central neuroimmune interactions in the development of corneal hypersensitivity are discussed. Next, the cellular and molecular changes of corneal neurons in the TG and central structures that are driven by corneal nerve abnormalities are presented. A better understanding of the corneal nerve abnormalities as well as neuroimmune interactions may contribute to the identification of a novel therapeutic targets for alleviating corneal pain.
PubMed: 33362474
DOI: 10.3389/fncel.2020.610342