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Clinical Ophthalmology (Auckland, N.Z.) 2020This paper reviews ocular pain with the main focus on ocular surface discomfort and dry eye pain. Anatomy, physiology, epidemiology, assessment, and treatment are... (Review)
Review
OBJECTIVE
This paper reviews ocular pain with the main focus on ocular surface discomfort and dry eye pain. Anatomy, physiology, epidemiology, assessment, and treatment are discussed in this paper.
METHODS
A PubMed search was conducted for studies published from 2000 to 2019 on the anatomy, pathophysiology, epidemiology, assessment, and treatment of ocular pain. Reviews, meta-analyses, and randomized clinical trials were included. Inclusion criteria focused on ocular surface discomfort, dry eye pain and neuropathic pain.
RESULTS
A total of 112 articles were found through searches, 45 of which were selected and studied in this review.
DISCUSSION
Pain in general can be acute or chronic. Acute pain is usually a physiologic response to a serious damage to the tissues and alleviates with pain relief treatments. Chronic pain is defined as the persistence of pain for more than three months. From another point of view, pain has been classified into either nociceptive or neuropathic. Nociceptive pain is a physiologic response to a noxious stimulus. Both central and peripheral nervous systems can be involved in the development of a neuropathic pain, which is characterized by positive or negative sensory signs, a pain perceived disproportionate to a noxious stimulus, and/or not responsive to analgesics. Chronic pain usually has a neuropathic component. Ocular surface pain is a well-known complaint after any corneal surgery. This is mainly due to abnormal regeneration of damaged corneal nerve endings and abnormal connections with adjacent nerve endings which produce spontaneous activity. Tear hyperosmolarity and the resultant ocular surface inflammation can also trigger voluntary activity of corneal nerve endings. Referral pain to the first and second division of the trigeminal nerve has been reported. Interference with vision and even sleep, which is out of proportion to the examination are among patients' complaints. All of these elements proposed the new concept of ocular neuropathic pain syndrome. The first step in conventional evaluation of ocular discomfort is search for tear insufficiency. Pathologies of lid and blinking as well as conjunctival irregularities should be addressed. Anti-inflammatory agents and, in resistant cases, systemic neuromodulators are shown to be helpful. Education on behavioral changes and reassurance are essential steps. Considering the neuropathic origin for the ocular pain, treatment modalities used for such pain in other parts of the body can be considered for this syndrome.
PubMed: 33061269
DOI: 10.2147/OPTH.S262060 -
Investigative Ophthalmology & Visual... May 2023Patients with dry eye disease (DED) sometimes complain of ocular pain. DED-related ocular pain has many similarities with neuropathic pain. Mirogabalin, a novel ligand...
PURPOSE
Patients with dry eye disease (DED) sometimes complain of ocular pain. DED-related ocular pain has many similarities with neuropathic pain. Mirogabalin, a novel ligand for the α2δ subunit of voltage-gated calcium channels, is approved for treating neuropathic pain in Japan. This study aimed to investigate the effect of mirogabalin on hyperalgesia and chronic ocular pain in a rat DED model.
METHODS
DED was induced in female Sprague Dawley rats by unilaterally excising the external lacrimal gland (ELG) and Harderian gland (HG). After 4 weeks of ELG and HG removal, tear production (pH threads) and corneal epithelial damage (fluorescein staining) were evaluated. Corneal hyperalgesia and chronic pain were analyzed, respectively, by measuring capsaicin-induced eye-wiping behavior and c-Fos expression in the trigeminal nucleus. Mirogabalin (10 or 3 mg/kg) was evaluated for effects on DED-induced hyperalgesia and chronic ocular pain.
RESULTS
Tear production was significantly lower in DED-induced eyes than in control eyes. Corneal damage was significantly higher in DED eyes than in control eyes. Hyperalgesia and chronic ocular pain were detected 4 weeks after ELG and HG removal. Five days of mirogabalin administration significantly suppressed capsaicin-induced eye-wiping behavior, which indicated the suppression of ocular hyperalgesia. Administration of 10 mg/kg mirogabalin significantly reduced c-Fos expression in the trigeminal nucleus, which indicated the amelioration of chronic ocular pain.
CONCLUSIONS
Mirogabalin suppressed DED-induced hyperalgesia and chronic ocular pain in a rat DED model. Our findings suggested that mirogabalin might effectively alleviate chronic ocular pain in patients with DED.
Topics: Rats; Female; Animals; Chronic Pain; Hyperalgesia; Rats, Sprague-Dawley; Capsaicin; Tears; Dry Eye Syndromes; Eye Pain; Neuralgia
PubMed: 37233999
DOI: 10.1167/iovs.64.5.27 -
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 -
Current Opinion in Allergy and Clinical... Oct 2017This review aims to describe the recent findings on epidemiology, pathophysiology, and management of neuropathic symptoms of the ocular surface, with a focus on... (Review)
Review
PURPOSE OF REVIEW
This review aims to describe the recent findings on epidemiology, pathophysiology, and management of neuropathic symptoms of the ocular surface, with a focus on potential similarities between sensations of dry eye, pain and itch.
RECENT FINDINGS
A narrative review of the literature was undertaken. Key references from research in dry eye, neuropathic symptoms of the ocular surface, ocular pain and itch, as well as general references on itch and pain neurobiology were included. Recent findings suggest aspects of dry eye, chronic ocular pain and itch symptomatology are driven by neuropathic pain mechanisms involving peripheral and central sensitization processes.
SUMMARY
Ocular dryness, pain, and itch are prevalent complaints with several of shared features. Multiple lines of evidence suggest that peripheral and central neuronal sensitization processes are involved in generating and maintaining ocular sensory symptoms. Research is warranted on the epidemiology of ocular sensations, molecular mechanisms involved in nociception and pruriception in the eye, electrophysiological alterations in animal models of eye conditions, and therapeutic modalities that can alleviate unpleasant ocular sensations.
Topics: Animals; Central Nervous System; Disease Models, Animal; Dry Eye Syndromes; Eye; Eye Pain; Humans; Neuralgia; Ocular Physiological Phenomena; Peripheral Nervous System; Pruritus; Sensation
PubMed: 28858914
DOI: 10.1097/ACI.0000000000000389 -
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 -
The Ocular Surface Oct 2022Chronic ocular surface pain (COSP) may be defined as a feeling of pain, perceived as originating from the ocular surface, that persists for >3 months. COSP is a complex... (Review)
Review
Chronic ocular surface pain (COSP) may be defined as a feeling of pain, perceived as originating from the ocular surface, that persists for >3 months. COSP is a complex multifactorial condition associated with several risk factors that may significantly interfere with an individual's daily activities, resulting in poor quality of life (QoL). COSP is also likely to have a high burden on patients with substantial implications on global healthcare costs. While patients may use varied terminology to describe symptoms of COSP, any ocular surface damage in the ocular sensory apparatus (nociceptive, neuropathic, inflammatory, or combination thereof) resulting in low tear production, chronic inflammation, or nerve abnormalities (functional and/or morphological), is typically associated with COSP. Considering the heterogeneity of this condition, it is highly recommended that advanced multimodal diagnostic tools are utilized to help discern the nociceptive and neuropathic pain pathways in order to provide targeted treatment and effective clinical management. The current article provides an overview of COSP, including its multifactorial pathophysiology, etiology, prevalence, clinical presentation, impact on QoL, diagnosis, current management, and unmet medical needs.
Topics: Humans; Quality of Life; Dry Eye Syndromes; Eye Pain; Eye; Neuralgia
PubMed: 35970433
DOI: 10.1016/j.jtos.2022.08.005 -
Indian Journal of Ophthalmology Jun 2023Painful-blind eye (PBE) is a challenging and debilitating condition that greatly affects the quality of life of patients. Although PBE can result from a variety of... (Review)
Review
Painful-blind eye (PBE) is a challenging and debilitating condition that greatly affects the quality of life of patients. Although PBE can result from a variety of etiologies, currently there is no guideline or consensus on how to approach therapeutically these patients, and most treatments are experience-based. We summarized the evidence from available studies to investigate the current state of PBE treatment strategies. This review revealed that the information available about therapeutic approaches in patients with PBE is insufficient and outdated, therefore, new experimental and larger studies are needed to reach an agreement about this condition.
Topics: Humans; Palliative Care; Eye Enucleation; Eye Evisceration; Quality of Life; Eye Pain
PubMed: 37322649
DOI: 10.4103/IJO.IJO_3063_22 -
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 -
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 -
BMJ Open Sep 2023Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED pathology.
BACKGROUND
Diabetes mellitus has been associated with increased dry eye disease (DED) and exacerbates DED pathology.
OBJECTIVE
To investigate the potential relationship between corneal nerve loss and ocular pain among diabetic patients with dry eye (DE).
DESIGN
A cross-sectional study.
SETTING
He Eye Specialist Hospital, Shenyang, China.
PARTICIPANTS
This study recruited 124 eyes of 62 diabetic patients diagnosed with DED between August and October 2022.
MAIN OUTCOME MEASURES
Best-corrected visual acuity, intraocular pressure, non-invasive tear breakup time, tear meniscus height, tear film lipid layer, conjunctival hyperaemia (redness score), conjunctivocorneal epithelial staining (CS score), central corneal sensitivity and vitro confocal corneal microscopy was assessed in all subjects. The Ocular Surface Disease Index Questionnaire assessed DE symptoms and ocular pain.
RESULTS
The study's final analysis included 26 patients (52 eyes) without ocular pain and 36 patients (72 eyes) with ocular pain. The corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL) in patients with ocular pain were significantly lower than those without (p<0.001, p=0.004, and p<0.001, respectively). CNFD, CNBD and CNFL negatively correlated with ocular pain (r=-0.385, r=-0.260, r=-0.358, respectively). Moreover, CNFD, CNBD and CNFL have a significant (p<0.05) positive correlation with corneal sensitivity (r=0.523, r=0.330, r=0.421, respectively).
CONCLUSIONS
Corneal nerve loss was associated with ocular pain and decreased corneal sensitivity in diabetic patients with DE. Further studies into the neurological role of ocular surface diseases can elaborate diagnostics, prognosis and treatment of diabetic patients with DE.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov (NCT05193331).
Topics: Male; Humans; Cross-Sectional Studies; Cornea; Diabetic Neuropathies; Dry Eye Syndromes; Pain; Diabetes Mellitus
PubMed: 37751961
DOI: 10.1136/bmjopen-2023-076932