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BMJ Open Ophthalmology 2021Though corneal collagen cross-linking (CXL) is an increasingly available and effective treatment for keratoconus, few reports have considered its impact on pain-related... (Review)
Review
Though corneal collagen cross-linking (CXL) is an increasingly available and effective treatment for keratoconus, few reports have considered its impact on pain-related physiology in depth. This comprehensive narrative review summarises mechanisms underlying pain in CXL and clinical care possibilities, with the goal of future improvement in management of CXL-related pain. Postoperative pain associated with CXL is largely due to primary afferent nerve injury and, to a smaller extent, inflammation. Chronification of pain after CXL has not been reported, even as long-term nerve damage without regeneration following standard CXL treatment is frequently observed. The lack of pain chronification may be due to the minimally invasive nature of the procedure, with its rapidly recovering superficial corneal wound, and to the positive anti-inflammatory changes of the tear film that have been described after CXL. Different CXL approaches have been developed, with the transepithelial epithelial-on technique (epi-on) associated with less postsurgical pain than the gold standard, epithelial-off technique (epi-off). After the first few days, however, the difference in pain scores and need for analgesics between epi-on and epi-off disappear. Patients experience relatively high-intensity pain the first few days post-CXL, and many strategies for acute pain control following CXL have been studied. Currently, no method of pain management is considered superior or universally accepted. Acute pain following CXL is a recognised and clinically significant side effect, but few CXL studies have systematically investigated postoperative pain and its management. This review aims to improve patient pain outcomes following this increasingly common procedure.
PubMed: 34901466
DOI: 10.1136/bmjophth-2021-000878 -
The British Journal of Ophthalmology Aug 2022Throughout the body, damage to peripheral nerves normally involved in nociception may produce a constellation of symptoms-including irritation, itchiness and pain. The... (Review)
Review
Throughout the body, damage to peripheral nerves normally involved in nociception may produce a constellation of symptoms-including irritation, itchiness and pain. The neurobiological processes involved in corneal symptoms of dry eye (DE) and neuropathic corneal pain (NCP) have not been clearly considered in terms of nociceptive processing. The conventional underlying presumption is that a labelled line principle is responsible; that these distinct perceptions are hard coded by primary afferent inputs to the central nervous system. This presumption oversimplifies the neurobiological mechanisms underlying somatosensory perception. The labelled line perspective that DE represents a chronic pain condition does not make intuitive sense: how can an eye condition that is not painful in most cases be considered a pain condition? Does not chronic pain by definition require pain to be present? On the other hand, NCP, a term that clearly denotes a painful condition, has historically seemed to resonate with clinical significance. Both DE and NCP can share similar features, yet their differentiation is not always clear. As is often the case, clinical terms arise from different disciplines, with DE evolving from ophthalmological findings and NCP inspired by pain neurophysiology. This review evaluates the current definition of these terms, the rationale for their overlap and how the neurophysiology of itch impacts our understanding of these conditions as a continuum of the same disease. Despite the complexity of nociceptive physiology, an understanding of these mechanisms will allow us a more precise therapeutic approach.
Topics: Chronic Disease; Chronic Pain; Cornea; Dry Eye Syndromes; Eye Pain; Humans; Neuralgia; Nociception
PubMed: 33931393
DOI: 10.1136/bjophthalmol-2020-318469 -
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 -
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 -
Ophthalmology Feb 2021
Topics: Acupuncture Therapy; Dry Eye Syndromes; Eye Injuries, Penetrating; Eye Pain; Female; Humans; Retina; Retinal Hemorrhage; Retinal Perforations
PubMed: 33485474
DOI: 10.1016/j.ophtha.2020.09.024 -
Minerva Gastroenterology Mar 2021Inflammatory bowel diseases (IBD), that includes ulcerative colitis and Crohn's disease, can affect not only the gastrointestinal tract but a wide spectrum of organs.... (Review)
Review
Inflammatory bowel diseases (IBD), that includes ulcerative colitis and Crohn's disease, can affect not only the gastrointestinal tract but a wide spectrum of organs. The extra-intestinal manifestations (EIMs) are one of the most challenging aspect of IBD, playing a significant role for the lifetime care and the quality of life of patients. Ocular manifestations are the third most frequent EIMs, preceded by articular and dermatological ones. The aim of this narrative review is to describe the different types of ocular involvements, focusing on their clinical management. Uveitis and episcleritis are the most common ocular EIMs, differing for many aspects. Uveitis are unrelated with IBD activity and they even precede the onset of the intestinal disease, while episcleritis are common defined as a good mark of IBD activity. Pain is uncommon in most cases of episcleritis, while severe eye pain and photophobia are the most frequent onset of anterior uveitis. Less common but even more severe, are orbital pseudotumor or posterior segment involvement. Most of the ocular EIMs can be successfully treated with topic and oral steroids and the underlying therapy for IBD can reduce or cut out at all the recurrence of these manifestations. Symptoms are commonly not specific, in some cases being unnoticed for years leading to permanent ocular consequences. Cooperation between different specialists is crucial to avoid all the possible consequences of a non-treated EIMs, especially for ocular ones.
Topics: Eye Diseases; Gastroenterology; Humans; Inflammatory Bowel Diseases
PubMed: 32677418
DOI: 10.23736/S2724-5985.20.02727-0 -
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 -
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 -
BMJ Open Ophthalmology 2021Dry eye disease (DED) is a multifactorial disease that manifests in patients with a variety of symptoms and signs such as ocular pain, visual issues, rapid tear... (Review)
Review
Dry eye disease (DED) is a multifactorial disease that manifests in patients with a variety of symptoms and signs such as ocular pain, visual issues, rapid tear evaporation and/or decreased tear production. It is a global health problem and is the leading cause of optometry and ophthalmology clinic visits. The mainstay therapy for DED is artificial tears (ATs), which mimics tears and improves tear stability and properties. ATs have been found to improve symptoms and signs of disease in all DED subtypes, including aqueous deficient DED and evaporative DED. However, given the heterogeneity of DED, it is not surprising that ATs are not effective in all patients. When AT fails to relieve symptoms and/or signs of DED, it is critical to identify the underlying contributors to disease and escalate therapy appropriately. This includes underlying systemic diseases, meibomian gland dysfunction, anatomical abnormalities and neuropathic dysfunction. Thus, this review will discuss the benefits and limitations of ATs and review conditions when escalation of therapy should be considered in DED.
PubMed: 33907713
DOI: 10.1136/bmjophth-2020-000697 -
SAGE Open Medical Case Reports 2023Acute lymphoblastic leukemia is the most common childhood malignancy. Despite many advances in therapy, about 15%-20% of children with acute lymphoblastic leukemia...
Acute lymphoblastic leukemia is the most common childhood malignancy. Despite many advances in therapy, about 15%-20% of children with acute lymphoblastic leukemia experience a disease relapse. Isolated ocular relapse is relatively rare. A 14-year-old male with T-cell acute lymphoblastic leukemia in remission presented with sudden onset of right eye pain and visual acuity impairment. Fundoscopic examination of the eye and magnetic resonance imaging of the orbits were consistent with optic nerve infiltration. The patient was treated with salvage chemotherapy, orbital radiation and eventual bone marrow transplantation, with notable improvement in vision and regression of retinal and optic nerve findings. Optic nerve infiltration represents an ophthalmic emergency and requires urgent management. The use of radiation therapy is a helpful adjunct with systemic chemotherapy in obtaining disease remission.
PubMed: 37250823
DOI: 10.1177/2050313X231175020