Painful Eyes in Neurology Clinic: A Guide for Neurologists.

Eye pain is a common complaint among patients presenting to the neurology clinic. It can be related to neurologic diseases, but it can also be a localized eye condition. Such disorders can be misleading, as their benign appearance might mask more grave underlying conditions, potentially leading to misdiagnoses or delayed treatment. Clinicians should be aware of the specific neurologic or systemic disorders (eg, demyelinating diseases or vascular abnormalities) that might first manifest as eye pain. Formal ophthalmic consultation is recommended for patients presenting with eye pain as the predominant complaint especially when red flags for more serious pathology are present.

Proparacaine Overuse in Corneal Abrasions at the Emergency Department: A Case Series.

ABSTRACT: Corneal abrasions are among the most common ophthalmic injuries in the emergency department (ED) and primarily present as severe ocular pain. Topical anesthetics provide temporary analgesia, but overuse is associated with complications including further corneal injury, infection, and vision loss. This case series describes three patients who used a 15-mL bottle of 0.05% proparacaine hydrochloride ophthalmic solution after discharge from the ED and returned within three days with corneal injury and pain. Although the use of topical anesthetics is traditionally discouraged by ophthalmologists, publications in the emergency medicine literature support their use. We review the literature surrounding topical anesthetic use in the ED setting and caution against prescribing patients topical anesthetics for corneal abrasions, particularly without patient counseling and significant restriction of anesthetic supply.

Vision-related quality of life in patients with retinal vein occlusion.

PURPOSE: This study aims to assess the vision-related quality of life in patients with retinal vein occlusion (RVO) among those referred to Labbafinejad Medical Center and Imam Hossein Hospital between 2019 and 2021. METHODS: This comparative study included 37 eligible patients diagnosed with various types of RVO, with an average age of 61 ± 9. To ensure data validity, we included 74 age- and sex-matched healthy individuals. Only cases with a definitive diagnosis of RVO, confirmed by two retina specialists (ND and RN), were included. We assessed the vision-related quality of life of our participants using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). All participants underwent interviews. RESULTS: In our study, we examined the vision-related quality of life in different subgroups of RVO patients. Overall, RVO patients had a significantly lower total VRQoL score compared to healthy individuals (P < 0.001), except in the subscale analysis of specific factors such as ocular pain, color vision, and driving, where no statistically significant difference was observed. A statistically significant difference was found in the comparison of subgroups, indicating lower VRQoL in central retinal vein occlusion (CRVO) patients (P = 0.010). Furthermore, a significant correlation was observed between lower VRQoL and decreased vision (P = 0.009) as well as longer disease duration (P = 0.011). CONCLUSION: Retinal vein occlusion can significantly reduce vision-related quality of life, particularly in more severe cases.

An experimental model for primary neuropathic corneal pain induced by long ciliary nerve ligation in rats.

ABSTRACT: Neuropathic corneal pain (NCP) is a new and ill-defined disease characterized by pain, discomfort, aching, burning sensation, irritation, dryness, and grittiness. However, the mechanism underlying NCP remain unclear. Here, we reported a novel rat model of primary NCP induced by long ciliary nerve (LCN) ligation. After sustained LCN ligation, the rats developed increased corneal mechanical and chemical sensitivity, spontaneous blinking, and photophobia, which were ameliorated by intraperitoneal injection of morphine or gabapentin. However, neither tear reduction nor corneal injury was observed in LCN-ligated rats. Furthermore, after LCN ligation, the rats displayed a significant reduction in corneal nerve density, as well as increased tortuosity and beading nerve ending. Long ciliary nerve ligation also notably elevated corneal responsiveness under resting or menthol-stimulated conditions. At a cellular level, we observed that LCN ligation increased calcitonin gene-related peptide (neuropeptide)-positive cells in the trigeminal ganglion (TG). At a molecular level, upregulated mRNA levels of ion channels Piezo2, TRPM8, and TRPV1, as well as inflammatory factors TNF-α, IL-1ß, and IL-6, were also detected in the TG after LCN ligation. Meanwhile, consecutive oral gabapentin attenuated LCN ligation-induced corneal hyperalgesia and increased levels of ion channels and inflammation factors in TG. This study provides a reliable primary NCP model induced by LCN ligation in rats using a simple, minimally invasive surgery technique, which may help shed light on the underlying cellular and molecular bases of NCP and aid in developing a new treatment for the disease.

Efficacy of topical 0.05% cyclosporine A and 0.1% sodium hyaluronate in post-refractive surgery chronic dry eye patients with ocular pain.

BACKGROUND: The management of post-refractive surgery dry eye disease (DED) can be challenging in clinical practice, and patients usually show an incomplete response to traditional artificial tears, especially when it is complicated with ocular pain. Therefore, we aim to investigate the efficacy of combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment in post-refractive surgery DED patients with ocular pain unresponsive to traditional artificial tears. METHODS: We enrolled 30 patients with post-refractive surgery DED with ocular pain who were unresponsive to traditional artificial tears. Topical 0.05% cyclosporine A and 0.1% sodium hyaluronate were used for 3 months. They were evaluated at baseline and 1 and 3 months for dry eye and ocular pain symptoms and objective parameters, including Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), corneal sensitivity, and corneal nerve morphology. In addition, tear levels of inflammatory cytokines and neuropeptides were measured using the Luminex assay. RESULTS: After 3 months of treatment, patients showed a statistically significant improvement in the ocular surface disease index (OSDI), TBUT, SIt, CFS, and corneal sensitivity (all P < 0.01) using linear mixed models. As for ocular pain parameters, the NRS and NPSI-Eye scores were significantly reduced (both P < 0.05) and positively correlated with the OSDI and CFS scores. Additionally, tear IL-1ß, IL-6, and TNF-α levels were improved better than pre-treatment (P = 0.01, 0.03, 0.02, respectively). CONCLUSION: In patients with post-refractive surgery DED with ocular pain, combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment improved tear film stability, dry eye discomfort, and ocular pain, effectively controlling ocular inflammation. TRIAL REGISTRATION: Registration number: NCT06043908.

Influence of controlled environmental conditions in potential salivary ocular pain biomarkers for enhancing the assessment of ocular pain.

PURPOSE: We endeavored to identify objective salivary biomarkers for pain, a subjective sensation with a biological basis, using molecules already described related to pain. The study aimed to analyze inter-individual differences and intersession variability in salivary potential ocular pain biomarkers on healthy subjects, in samples obtained under the influence of controlled environmental conditions. METHODS: Thirty-four healthy subjects, 20 male, 14 female, median age 35.44 years (range 30-40) were exposed for 30 minutes under standard environmental conditions (T: 22°C, 50% relative humidity) in the Controlled Environmental Research Laboratory (CE-Lab, Vision R&D, Valladolid Spain) in two separate visits (V1, V2) at least 24 hours apart. Saliva was collected after the exposure in each of the visits, and cortisol, α-amylase (sAA), secretory IgA (sIgA), testosterone, and soluble fraction of TNFα receptor II (sTNFαRII) were analyzed by ELISA. Repeatability of inter-subject inter-session measurements was assayed by intraclass correlation coefficient (ICC). RESULTS: There were no significant inter-session differences in testosterone (p = 0.2497), sTNFαRII (p = 0.6451) and sIgA (p = 0.9689) salivary levels. The reproducibility for salivary cortisol, sAA, testosterone, sTNFαRII and sIgA were 0.98 ng/ml, 20.58 U/ml, 21.07 µg/ml, 24.68 pg/ml and 0.19 pg/ml, respectively. Salivary cortisol, sAA, testosterone, sTNFαRII and sIgA yielded the following ICCs: 0.506, 0.569, 0.824, 0.870 and 0.4295, respectively; all these ICCs (except that for cortisol and sIgA) were found to be improved compared to those found previously by our group in a previous study in salivary samples obtained from healthy subjects under non-controlled environmental conditions; Cortisol´s ICC didn´t improve and was in both cases at the limit of acceptability. CONCLUSION: Environmental factors such as temperature and relative humidity affect the reproducibility of measurement of some salivary molecules which have been proposed as potential pain biomarkers. The exposure of subjects to standard controlled environmental conditions before salivary sample obtention would improve the reproducibility of these molecule measures' as potential biomarkers of chronic ocular pain.

Associations between dry eye disease and sleep quality: a cross-sectional analysis.

BACKGROUND/AIMS: To investigate relationships between dry eye (DE) disease and sleep quality, with a focus on which aspects of sleep most closely relate to DE. METHODS: 141 veterans (mean age: 56±5) seen at the Miami Veterans Affairs eye clinic filled out questionnaires to quantify the severity of DE symptoms (5-Item Dry Eye Questionnaire (DEQ-5) and Ocular Surface Disease Index (OSDI)) and ocular pain (Numerical Rating Scale (NRS) and Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-E)). All individuals also underwent an ocular surface examination. Aspects of sleep quality were assessed using the Pittsburgh Sleep Quality Index (PSQI). DE metrics were examined by PSQI scores and subscores. RESULTS: Most participants (76%) reported mild or greater DE symptoms (DEQ-5 ≥6). Overall, ocular symptoms were more related to sleep metrics than signs. The strongest DE symptom association was between the OSDI and sleep disturbances (PSQI subscore 5, r=0.49, p<0.0005). For DE signs, ocular surface inflammation and meibum quality were related to subjective sleep quality (PSQI subscore 1, r=0.29, p=0.03, for both). On linear regression analyses, most ocular symptom questionnaires remained associated with sleep disturbances (PSQI subscore 5: NRS (r=0.52, p<0.0005), DEQ-5 (r=0.36, p<0.0005), and OSDI (r=0.31, p<0.0005)). For DE signs, ocular surface inflammation and meibum quality remained associated with subjective sleep quality (r=0.26, p=0.01; r=0.46, p<0.0005, respectively). CONCLUSION: DE symptom and ocular pain intensity were closely related to sleep metrics, most strongly to sleep disturbances. Relationships were weaker for DE signs, with subjective sleep quality relating to inflammation and meibum quality.

Coexistence of neuropathic corneal pain, corneal nerve abnormalities, depression, and low quality of life.

PURPOSE: To evaluate the quality of life (QoL), mental health conditions and corneal morphology in neuropathic corneal pain (NCP) subjects without a significant ocular surface disease. METHODS: A composite questionnaire was administered to 228 consecutive subjects, assessing the pain intensity, duration, and quality using a modified version of the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and Pain Detect (PD) questionnaires. Subjects diagnosed with possible central NCP and two sub-groups of patients diagnosed with peripheral ocular pain completed an additional battery of mental health questionnaires and were examined by In Vivo Confocal Microscopy (IVCM). RESULTS: Of the 76 subjects that reported chronic ocular pain (duration >1 month), 53 were classified with probable NCP. Nine subjects without signs that justify the pain and non-responding to topical anaesthesia, were considered affected by central NCP. In these patients, a significant negative correlation was found between the presence pain and the mental component of the QoL (R2 = 0.733), and a positive correlation between the severity of pain the presence post-traumatic stress disorder (R2 = 0.83) and depression (R2 = 0.93). Although neuromas and sprouting had higher frequency in the central NCP group compared the control groups, these differences was not statistically different. CONCLUSIONS: The assessment of ocular pain characteristics using multiple questionnaires and IVCM may help to recognize differences between nociceptive and neuropathic pain. An association between pain intensity and mental health condition may guide the therapeutical choices.

FL-41 Tint Reduces Activation of Neural Pathways of Photophobia in Patients with Chronic Ocular Pain.

PURPOSE: To assess the therapeutic effect of tinted lenses (FL-41) on photophobia and light-evoked brain activity using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular surface pain. DESIGN: Prospective case series. METHODS: 25 subjects from the Miami veterans affairs (VA) eye clinic were recruited based on the presence of chronic ocular pain, dry eye symptoms, and photophobia. Using a 3T MRI scanner, subjects underwent 2 fMRI scans using an event-related design based on light stimuli: one scan while wearing FL-41 lenses and one without. Unpleasantness ratings evoked by the light stimuli were collected after each scan. RESULTS: With FL-41 lenses, subjects reported decreased (n = 19), maintained (n = 2), or increased (n = 4) light-evoked unpleasantness ratings. Group analysis at baseline (no lens) revealed significant light evoked responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral insula, bilateral frontal pole, visual, precuneus, paracingulate, and anterior cingulate cortices (ACC) as well as cerebellar vermis, bilateral cerebellar hemispheric lobule VI, and bilateral cerebellar crus I and II. With FL-41 lenses, light-evoked responses were significantly decreased in bilateral S1, bilateral S2, bilateral insular, right temporal pole, precuneus, ACC, and paracingulate cortices as well as bilateral cerebellar hemispheric lobule VI. CONCLUSION: FL-41 lenses modulated photophobia symptoms in some individuals with chronic ocular pain. In conjunction, FL-41 lenses decreased activation in cortical areas involved in processing affective and sensory-discriminative dimensions of pain. Further research into these relationships will advance the ability to provide precision therapy for individuals with ocular pain.

Does SARS-CoV-2 infection cause persistent ocular symptoms?: A cross-sectional study after the lifting of lockdown in Chongqing, China.

To confirm whether ocular symptoms and complaints related to the COVID-19 infection persist after recovery. A cross-sectional study was conducted on people who came to the healthcare center for regular physical examinations when the lockdown lifted for nearly 1 month. Ophthalmologists performed comprehensive ocular examinations. The infection history of COVID-19 was identified by a self-reported reverse transcription-PCR (RT-PCR) test of a nasopharyngeal swab sample for SARS-CoV-2 or a novel coronavirus antigen test with self-reported typical infection symptoms. Demographic data was collected from their healthcare reports. Ocular history and ocular symptoms were collected through face-to-face interviewing. Of a total of 308 participants, 264 (85.7%) reported COVID-19 infection; 73 (27.65%) of infected persons complained of various ocular symptoms during or after infection; and only 15 (5.68%) persons reported ocular symptoms after recovery. Infection significantly increased the complaints of red eye and eye pain compared to the time before knockdown. There were no significant differences between infections and noninfectious infections in various ocular examinations at the time of examination. The duration between the day of infection onset and examination day was unrelated to all ocular examinations. COVID-19 infection can lead to some ocular symptoms, especially conjunctival congestion and ocular pain in the infective stage, but may not cause persistent ocular symptoms in about 1 month after recovery. The results of this study may help relieve public concerns about coronavirus infection in the eyes. However, more studies on various coronavirus infections, with large sample sizes, are warranted in multi-center and community-based populations.

[Differential diagnostics of chronic eye pain from a neurological perspective-What can also lie behind it]. / Differenzialdiagnosen chronischer Augenschmerzen aus neurologischer Sicht ­ Was auch dahinterstecken kann.

Periorbital pain and pain in the eye may arise from nociceptive processes such as chronic ocular surface destruction and inflammation, from neuropathic processes or often from a combination of different mechanisms. An important differential diagnosis are primary headache disorders and other neurological diseases, for example of inflammatory origin, which trigger secondary pain. Chronic eye pain therefore requires interdisciplinary collaboration in the diagnostics and treatment.

[Chronic eye pain]. / Der chronische Augenschmerz.

Numerous conditions in the field of ophthalmology are associated with pain in or around the eye. Chronic pain associated with the eye is a common finding in the daily routine of ophthalmologists and can be associated with primary ocular or extraocular diseases as well as with other conditions. Appropriate diagnostic assessment and management of people with chronic pain requires an understanding of the condition based on the biopsychosocial model in which the interactions of biological/somatic, psychological and social factors are determining pain and suffering. Beyond the ophthalmological findings,  close interdisciplinary cooperation and assessment are required. Therefore, if eye pain is insufficiently responsive to treatment or if symptoms of chronic pain are evident, pain medicine expertise should be involved. The management of chronic ocular pain is based on interdisciplinary multimodal approaches, in addition to the ophthalmologist-specific approaches. These focus on self-efficacy, patient competence and acceptance of pain as central goals of treatment rather than pain relief. Patient information, education and the development of a suitable concept by the interdisciplinary team are essential therapeutic aspects in this context.

Evaluation of ocular neuropathic pain.

AIM: To identify and assess the quality of current validated questionnaires that could be used to evaluate ocular neuropathic pain and its associated aetiologies. METHODS: A literature search was performed on MEDLINE, PubMed, EMBASE, PsycINFO and The Cochrane Library. Articles evaluating questionnaires for ocular neuropathic pain and its associated aetiologies were included. Data on psychometric properties, validity, and reliability of the questionnaires was extracted and analysed using a set of quality criteria. Clinical and demographical associations with ocular neuropathic pain were also reviewed. RESULTS: The search generated 1738 results with 61 publications meeting the inclusion criteria. The 61 publications covered 28 questionnaires including 3 ocular pain, 12 dry eye disease, 2 blepharitis, 2 refractive surgery, 3 contact lens wear, 3 Sjogren's Syndrome, and 3 that were non-disease-specific. Only 57 publications provided enough data on psychometric properties and validity of the questionnaire to be included for quality assessment. The Contact Lens Discomfort Index (CLDI) had the highest rated psychometric properties, whereas the English version of the Ocular Comfort Index (OCI) provided the most data on psychometric properties (9 out of 10 criteria). Most ocular pain and disease-specific questionnaires contained appropriate items to assess ocular pain in specific populations. However, non-disease-specific ophthalmic questionnaires demonstrated poor reliability and validity when evaluating ocular pain. CONCLUSION: Ocular pain questionnaires can potentially diagnose ocular neuropathic pain. Disease-specific questionnaires were limited to their target populations, and non-disease-specific ophthalmic questionnaires were unreliable. Further studies are required to determine the most appropriate questionnaire to evaluate ocular neuropathic pain.