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Eye (London, England) Mar 2015Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including... (Review)
Review
Dry eye has gained recognition as a public health problem given its prevalence, morbidity, and cost implications. Dry eye can have a variety of symptoms including blurred vision, irritation, and ocular pain. Within dry eye-associated ocular pain, some patients report transient pain whereas others complain of chronic pain. In this review, we will summarize the evidence that chronicity is more likely to occur in patients with dysfunction in their ocular sensory apparatus (ie, neuropathic ocular pain). Clinical evidence of dysfunction includes the presence of spontaneous dysesthesias, allodynia, hyperalgesia, and corneal nerve morphologic and functional abnormalities. Both peripheral and central sensitizations likely play a role in generating the noted clinical characteristics. We will further discuss how evaluating for neuropathic ocular pain may affect the treatment of dry eye-associated chronic pain.
Topics: Dry Eye Syndromes; Eye Pain; Humans; Neuralgia
PubMed: 25376119
DOI: 10.1038/eye.2014.263 -
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 -
Journal of Patient-centered Research... 2021Keratoconjunctivitis sicca ("dry eye") is a common (14%-30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with... (Review)
Review
Keratoconjunctivitis sicca ("dry eye") is a common (14%-30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with associated dryness, pain, and visual disturbances. Etiology is not clearly understood but is likely varied, with a subset of patients suffering from chronic neuropathic pain referred to as "burning eye syndrome." This review of existing literature summarizes the clinical presentation, natural history, pathophysiology, and treatment modalities of burning eye syndrome. Chronicity of burning eye syndrome is likely secondary to increased nociception from the cornea, decrease in inhibitory signals, and nerve growth factor expression alterations. Treatment centers around symptomatic alleviation and reduction of inflammation. Conservative treatments focus on well-being and perception and include exercise, acupuncture, and cognitive behavioral therapy. Topical treatment consists of the anti-adhesion T-cell antagonist lifitegrast, corticosteroids, and cyclosporine; all have moderate efficacy and good safety. Autologous serum eye drops are a second-line topical that may promote corneal and neural healing on top of symptomatic relief. When these treatments fail, patients may trial neuromodulation with transcranial magnetic stimulation. Despite general treatment safety, more research is needed to develop novel approaches to this condition, possibly focusing more directly on the neurological component.
PubMed: 34322578
DOI: 10.17294/2330-0698.1813 -
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 -
The Ocular Surface Oct 2021To illustrate that ocular pain may occur in patients with neurotrophic keratopathy (NK) that typically are thought to lack symptoms of discomfort, and that aa subset of...
PURPOSE
To illustrate that ocular pain may occur in patients with neurotrophic keratopathy (NK) that typically are thought to lack symptoms of discomfort, and that aa subset of these patients may also present with neuropathic corneal pain (NCP).
METHOD
Retrospective Case series of 7 stage 1 NK patients who presented with concurrent ocular pain, as confirmed by clinical examination, proparacaine challenge test, and in vivo corneal confocal microscopy (IVCM). Records were assessed for results of ocular surface disease index (OSDI), pain on visual analog scale (VAS), ocular pain assessment survey (OPAS), best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS) score, and IVCM findings. IVCM findings were compared to that of 20 healthy reference controls.
RESULTS
Mean age of patients was 63.7 ± 11.6 (range 44-76) years and 56.9 ± 8.6 (range 42-74) years in reference controls (p = 0.11). At presentation, ocular discomfort was 8.0 ± 1.3 (range 7-10) on VAS and mean OSDI scores were 72.26 ± 6.81 (range 62.50-79.54). Mean BCVA was 20/40, and mean CFS scores were 3.43 ± 0.79 (range 2-4) on the Oxford scale. IVCM analysis showed significant decrease in mean total, main and branch nerve densities in ranges consistent with NK as compared to normal controls (p < 0.001 for all), increased dendritiform cell density in three patients (p < 0.001), and the presence of microneuromas in six of the patients.
CONCLUSION
Patients with NK are thought to present with hypoesthesia. However, nerve damage and inflammation, which play a role in the development of NK may result in the development of chronic ocular pain, such as NCP, resulting in potential underdiagnosis of either disease.
Topics: Adult; Aged; Cornea; Eye Pain; Humans; Microscopy, Confocal; Middle Aged; Neuralgia; Retrospective Studies; Trigeminal Nerve Diseases
PubMed: 34411735
DOI: 10.1016/j.jtos.2021.08.003 -
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 -
Frontiers in Pharmacology 2016The endocannabinoid system (ECS) has emerged as an important regulator of both physiological and pathological processes. Notably, this endogenous system plays a key role... (Review)
Review
The endocannabinoid system (ECS) has emerged as an important regulator of both physiological and pathological processes. Notably, this endogenous system plays a key role in the modulation of pain and inflammation in a number of tissues. The components of the ECS, including endocannabinoids, their cognate enzymes and cannabinoid receptors, are localized in the eye, and evidence indicates that ECS modulation plays a role in ocular disease states. Of these diseases, ocular inflammation presents a significant medical problem, given that current clinical treatments can be ineffective or are associated with intolerable side-effects. Furthermore, a prominent comorbidity of ocular inflammation is pain, including neuropathic pain, for which therapeutic options remain limited. Recent evidence supports the use of drugs targeting the ECS for the treatment of ocular inflammation and pain in animal models; however, the potential for therapeutic use of cannabinoid drugs in the eye has not been thoroughly investigated at this time. This review will highlight evidence from experimental studies identifying components of the ocular ECS and discuss the functional role of the ECS during different ocular inflammatory disease states, including uveitis and corneal keratitis. Candidate ECS targeted therapies will be discussed, drawing on experimental results obtained from both ocular and non-ocular tissue(s), together with their potential application for the treatment of ocular inflammation and pain.
PubMed: 27695415
DOI: 10.3389/fphar.2016.00304 -
Pain Medicine (Malden, Mass.) Apr 2016Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This... (Review)
Review
OBJECTIVE
Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This disorder may also involve neuroplasticity in response to neuronal injury. This review will emphasize the key characteristics of dry eye pain and its pathologic mechanisms, making the argument that a subset of dry eye represents a neuropathic pain disorder of the eye, more appropriately called "burning eye syndrome."
METHODS
A literature review was conducted using a PubMed search focusing on dry eye, corneal nociception, and neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic ocular pain as related to dry eye were summarized.
RESULTS
We found that there is a discordance between ocular pain and dryness on the ocular surface. Although tear dysfunction may be one of the initial insults, its persistence may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic pain transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain.
CONCLUSION
Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome."
Topics: Dry Eye Syndromes; Humans; Hyperalgesia; Neuralgia
PubMed: 26814296
DOI: 10.1093/pm/pnv070 -
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 -
Eye & Contact Lens Nov 2018To evaluate the association between dry eye (DE) symptoms and neuropathic-like ocular pain (NOP) features, chronic pain conditions, depression, and anxiety in patients...
OBJECTIVE
To evaluate the association between dry eye (DE) symptoms and neuropathic-like ocular pain (NOP) features, chronic pain conditions, depression, and anxiety in patients presenting for routine ophthalmic examinations.
METHODS
Two hundred thirty-three consecutive patients ≥18 years of age presenting to a comprehensive eye clinic between January and August 2016 were included in this study. Information on demographics, chronic pain conditions, medication use, DE symptoms (dry eye questionnaire, DEQ5), NOP complaints (burning; wind, light, and temperature sensitivity), depression, and anxiety indices (patient health questionnaire 9, PHQ-9 and symptom checklist 90-revised, SCL-90-R) were collected for each individual. Pearson correlation was used to evaluate strengths of association. Logistic regression analysis examined risk factors for any (DEQ5≥6) and severe (DEQ5≥12) DE symptoms.
RESULTS
The mean age of the population was 46.3 years (±13.0); 67.8% (n=158) were female. Per the DEQ5, 40.3% (n=94) had mild or greater DE symptoms and 12% (n=24) had severe symptoms. Severity of DE symptoms correlated with NOP complaints: burning (Pearson r=0.37, P<0.001); sensitivity to wind (r=0.37, P<0.001), sensitivity to light (r=0.34, P<0.001), and sensitivity to temperature (r=0.30, P<0.001). Sex, race, and ethnicity were not significant risk factors for DE symptoms. Risk factors for mild or greater DE symptoms included a greater number of chronic nonocular pain conditions (odds ratio [OR]=1.38, P<0.001), arthritic pain (OR=6.34, P<0.001), back pain (OR=2.47, P=0.004), headaches (OR=2.14, P=0.02), depression (OR=1.17, P<0.001), and anxiety (OR=1.13, P=0.02).
CONCLUSION
Dry eye severity positively associated with NOP complaints, comorbid chronic pain conditions, and symptoms of depression and anxiety.
Topics: Adult; Aged; Anxiety; Comorbidity; Cross-Sectional Studies; Depression; Dry Eye Syndromes; Eye Pain; Female; Humans; Male; Middle Aged; Neuralgia; Odds Ratio; Pain Measurement; Quality of Life; Risk Factors; Young Adult
PubMed: 29227460
DOI: 10.1097/ICL.0000000000000463