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International Journal of Molecular... Apr 2021Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of... (Review)
Review
Choline is essential for maintaining the structure and function of cells in humans. Choline plays an important role in eye health and disease. It is a precursor of acetylcholine, a neurotransmitter of the parasympathetic nervous system, and it is involved in the production and secretion of tears by the lacrimal glands. It also contributes to the stability of the cells and tears on the ocular surface and is involved in retinal development and differentiation. Choline deficiency is associated with retinal hemorrhage, glaucoma, and dry eye syndrome. Choline supplementation may be effective for treating these diseases.
Topics: Acetylcholine; Animals; Choline; Choline Deficiency; Diabetic Retinopathy; Dry Eye Syndromes; Eye Diseases; Eye Pain; Glaucoma; Glycerylphosphorylcholine; Humans; Lacrimal Apparatus; Lens, Crystalline; Nociception; Optic Nerve; Parasympathetic Nervous System; Phosphatidylcholines; Phospholipids; Receptors, Nicotinic; Retina; Retinal Vessels; Tears
PubMed: 33946979
DOI: 10.3390/ijms22094733 -
Frontiers in Pharmacology 2021Neuropathic ocular pain is a frequent occurrence in medium to severe dry eye disease (DED). Only palliative treatments, such as lubricants and anti-inflammatory drugs,...
Neuropathic ocular pain is a frequent occurrence in medium to severe dry eye disease (DED). Only palliative treatments, such as lubricants and anti-inflammatory drugs, are available to alleviate patients' discomfort. Anesthetic drugs are not indicated, because they may interfere with the neural feedback between the cornea and the lacrimal gland, impairing tear production and lacrimation. Gabapentin (GBT) is a structural analog of gamma-amino butyric acid that has been used by systemic administration to provide pain relief in glaucomatous patients. We have already shown in a rabbit model system that its topic administration as eye drops has anti-inflammatory properties. We now present data on rabbits' eyes showing that indeed GBT given topically as eye drops has analgesic but not anesthetic effects. Therefore, opposite to an anesthetic drug such as oxybuprocaine, GBT does not decrease lacrimation, but-unexpectedly-even stimulates it, apparently through the upregulation of acetylcholine and norepinephrine, and by induction of aquaporin 5 (AQP5) expression in the lacrimal gland. Moreover, data obtained on a primary human corneal epithelial cell line also show direct induction of AQP5 by GBT. This suggests that corneal cells might also contribute to the lacrimal stimulation promoted by GBT and participate with lacrimal glands in the restoration of the tear film, thus reducing friction on the ocular surface, which is a known trigger of ocular pain. In conclusion, GBT is endowed with analgesic, anti-inflammatory and secretagogue properties, all useful to treat neuropathic pain of the ocular surface, especially in case of DED.
PubMed: 34163358
DOI: 10.3389/fphar.2021.671238 -
The Ocular Surface Jul 2017Pain associated with mechanical, chemical, and thermal heat stimulation of the ocular surface is mediated by trigeminal ganglion neurons, while cold thermoreceptors... (Review)
Review
Pain associated with mechanical, chemical, and thermal heat stimulation of the ocular surface is mediated by trigeminal ganglion neurons, while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of meibomian gland secretion or mucin release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in vivo confocal microscopy.
Topics: Animals; Cornea; Dry Eye Syndromes; Nociceptors; Pain; Sensation; Thermoreceptors
PubMed: 28736339
DOI: 10.1016/j.jtos.2017.05.002 -
American Journal of Ophthalmology Case... Dec 2023To assess whether topical administration of fosaprepitant improves intractable chronic ocular pain and inflammation.
PURPOSE
To assess whether topical administration of fosaprepitant improves intractable chronic ocular pain and inflammation.
METHODS
We report three clinical cases of female patients with drug-resistant ocular pain associated with inflammatory diseases of the ocular surface. The patients were treated for 3 (case 1) and 4 (cases 2-3) weeks with fosaprepitant eyedrops (0.1 mg/mL for case 1; 10 mg/mL for case 2-3). Patients were then followed up for at least 3 weeks. We measured ocular pain with the Visual Analogue Scale (VAS), the Ocular Surface Disease Index (OSDI), and corneal sensitivity with the Cochet-Bonnet esthesiometry. Slit-lamp photography and corneal confocal imaging were used to assess ocular surface integrity/conjunctival hyperemia and corneal nerve morphology, respectively.
RESULTS
All three patients had severe ocular pain (score higher than 6/10 VAS scale). All patients reported a significant improvement in ocular pain after 1 week of treatment. We also observed reduced corneal epitheliopathy (case 1) and conjunctival hyperemia (cases 1-2). In two patients (cases 2-3) the treatment was repeated after 1 year and 9 weeks, respectively, and pain reduction was similar in magnitude to what we observed after the first administration.
CONCLUSIONS
Topical administration of fosaprepitant ameliorates ocular pain and clinical symptoms in three patients with intractable ocular pain associated with inflammatory diseases of the ocular surface, without adverse effects.
IMPORTANCE
Fosaprepitant instillation holds promise as a treatment of chronic ocular pain, an area of unmet medical need.
PubMed: 38077782
DOI: 10.1016/j.ajoc.2023.101964 -
Tidsskrift For Den Norske Laegeforening... Sep 2019Typical optic neuritis is a demyelinating inflammation of the optic nerve, often associated with multiple sclerosis and with a relatively good prognosis. A small... (Review)
Review
Typical optic neuritis is a demyelinating inflammation of the optic nerve, often associated with multiple sclerosis and with a relatively good prognosis. A small percentage of optic neuritis cases have divergent clinical characteristics and a different underlying aetiology. These atypical cases of optic neuritis must be treated more intensively and followed up more closely in order to preserve visual function. It is important to be aware of the atypical features, so that correct assessment and treatment is initiated.
Topics: Adult; Aged; Chronic Disease; Eye Pain; Humans; Middle Aged; Neuromyelitis Optica; Optic Neuritis; Young Adult
PubMed: 31556528
DOI: 10.4045/tidsskr.18.0967 -
Nature Medicine Aug 2018Itch and pain are refractory symptoms of many ocular conditions. Ocular itch is generated mainly in the conjunctiva and is absent from the cornea. In contrast, most...
Itch and pain are refractory symptoms of many ocular conditions. Ocular itch is generated mainly in the conjunctiva and is absent from the cornea. In contrast, most ocular pain arises from the cornea. However, the underlying mechanisms remain unknown. Using genetic axonal tracing approaches, we discover distinct sensory innervation patterns between the conjunctiva and cornea. Further genetic and functional analyses in rodent models show that a subset of conjunctival-selective sensory fibers marked by MrgprA3 expression, rather than corneal sensory fibers, mediates ocular itch. Importantly, the actions of both histamine and nonhistamine pruritogens converge onto this unique subset of conjunctiva sensory fibers and enable them to play a key role in mediating itch associated with allergic conjunctivitis. This is distinct from skin itch, in which discrete populations of sensory neurons cooperate to carry itch. Finally, we provide proof of concept that selective silencing of conjunctiva itch-sensing fibers by pruritogen-mediated entry of sodium channel blocker QX-314 is a feasible therapeutic strategy to treat ocular itch in mice. Itch-sensing fibers also innervate the human conjunctiva and allow pharmacological silencing using QX-314. Our results cast new light on the neural mechanisms of ocular itch and open a new avenue for developing therapeutic strategies.
Topics: Animals; Conjunctiva; Cornea; Eye; Humans; Mice, Inbred C57BL; Neurons, Afferent; Pain; Pruritus; Sensory Receptor Cells
PubMed: 29988128
DOI: 10.1038/s41591-018-0083-x -
Frontiers in Pharmacology 2021Corneal neuropathic pain can be difficult to treat, particularly due to its lack of response to standard dry eye therapies. We describe a variety of topical therapeutic... (Review)
Review
Corneal neuropathic pain can be difficult to treat, particularly due to its lack of response to standard dry eye therapies. We describe a variety of topical therapeutic options that are available to treat corneal neuropathic pain with a significant or primary peripheral component. We also describe possible mechanisms of action for such topical therapies. Topical corticosteroids and blood-derived tear preparations can be helpful. Newer therapies, including topical lacosamide and low-dose naltrexone are emerging therapeutic options that may also be considered. Corneal neuropathic pain with a significant peripheral component may be managed with a variety of topical therapeutic options.
PubMed: 35173607
DOI: 10.3389/fphar.2021.769909 -
Clinical & Experimental Optometry Mar 2022Dry Eye Disease (DED) is a complex and multifactorial disorder of tear homoeostasis that results in pain, visual disturbance, and ocular surface damage. It is highly... (Review)
Review
Dry Eye Disease (DED) is a complex and multifactorial disorder of tear homoeostasis that results in pain, visual disturbance, and ocular surface damage. It is highly prevalent around the world and is associated with many co-morbidities that may contribute to or exacerbate symptoms and signs of disease and affect disease phenotype. However, DED is not one disease and can manifest with a variety of symptoms and/or signs. In this review, we discuss relationships between various co-morbidities and DED phenotypes. For example, individuals with immune mediated diseases, like Sjögren's Syndrome and Graft versus Host Disease, often present with aqueous tear deficiency (ADDE) in the setting of lacrimal gland dysfunction. Individuals with disorders that affect the periocular skin, like rosacea and seborrhoeic dermatitis, often present with evaporative dry eye (EDE) in the setting of eyelid and/or meibomian gland abnormalities. Individuals with pain related disorders, such as chronic pain syndrome and migraine, often present with ocular pain out of proportion to tear film abnormalities, often with accompanying corneal nerve hypersensitivity. Individuals with diabetes mellitus often present with an epitheliopathy in the setting of decreased sensation (neurotrophic keratitis). While not absolute, understanding relationships between co-morbidities and DED phenotypes can help tailor a therapeutic plan to the individual patient.
Topics: Dry Eye Syndromes; Humans; Meibomian Glands; Morbidity; Phenotype; Tears
PubMed: 34369296
DOI: 10.1080/08164622.2021.1962210 -
Ophthalmology Nov 2017Neuropathic pain is caused by a primary lesion or dysfunction of the nervous system and can occur in the cornea. However, neuropathic corneal pain (NCP) is currently an... (Review)
Review
Neuropathic pain is caused by a primary lesion or dysfunction of the nervous system and can occur in the cornea. However, neuropathic corneal pain (NCP) is currently an ill-defined disease. Patients with NCP are extremely challenging to manage, and evidence-based clinical recommendations for the management of patients with NCP are scarce. The objectives of this review are to provide guidelines for diagnosis and treatment of patients with NCP and to summarize current evidence-based literature in this area. We performed a systematic literature search of all relevant publications between 1966 and 2017. Treatment recommendations are, in part, based on methodologically sound randomized controlled trials (RCTs), demonstrating superiority to placebo or relevant control treatments, and on the consistency of evidence, degree of efficacy, and safety. In addition, the recommendations include our own extensive experience in the management of these patients over the past decade. A comprehensive algorithm, based on clinical evaluation and complementary tests, is presented for diagnosis and subcategorization of patients with NCP. Recommended first-line topical treatments include neuroregenerative and anti-inflammatory agents, and first-line systemic pharmacotherapy includes tricyclic antidepressants and an anticonvulsant. Second-line oral treatments recommended include an opioid-antagonist and opiate analgesics. Complementary and alternative treatments, such as cardiovascular exercise, acupuncture, omega-3 fatty acid supplementation, and gluten-free diet, may have additional benefits, as do potential noninvasive and invasive procedures in recalcitrant cases. Medication selection should be tailored on an individual basis, considering side effects, comorbidities, and levels of peripheral and centralized pain. Nevertheless, there is an urgent need for long-term studies and RCTs assessing the efficacy of treatments for NCP.
Topics: Cornea; Corneal Diseases; Eye Pain; Humans; Neuralgia; Trigeminal Nerve
PubMed: 29055360
DOI: 10.1016/j.ophtha.2017.08.004 -
Ugeskrift For Laeger Jan 2023Sudden pain of the eye, nose or face can be a symptom of stroke located to the pons. This case report is about a 73-year-old women with acute debut of right-sided...
Sudden pain of the eye, nose or face can be a symptom of stroke located to the pons. This case report is about a 73-year-old women with acute debut of right-sided hemiparesis, ataxia, gait disturbance, dysarthria, hemisensory defects and contralateral burning eye pain. MRI showed acute ischaemia of the left pons. The case adds to the growing literature of this rare presentation of posterior circulation stroke.
Topics: Humans; Female; Aged; Eye Pain; Pons; Stroke; Brain Stem Infarctions; Magnetic Resonance Imaging
PubMed: 36760190
DOI: No ID Found