Ocular Damage Index, Ocular Pain and Subjective Visual Rating in Patients with Behçet's Uveitis: A Study of Impact on Health-Related Quality of Life.

PURPOSE: The aim of our study is to assess subjective disease burden parameters (SVR and OP) as well as objective ones (BCVA and ODI) as predictors of HRQoL in Egyptian patients with BD uveitis. METHODS: Ninety-six patients with BD uveitis were recruited in this cross-sectional study from the Rheumatology Department, Cairo University Hospital. HRQoL was assessed using RAND-36 item health survey 1.0, subjective visual rating (SVR) was measured on a 6-point Likert scale. Ocular pain (OP) was rated on a numeric rating scale. The Ocular Damage Index (ODI) was calculated using the ocular domain of the BD damage index. Linear regression was performed to determine predictors of HRQoL metrics. RESULTS: SVR predicted Vitality (ß = 0.15, p = 0.004), Emotional Well-being (EW) (ß = 0.13, p = 0.005), General Health (ß = 0.18, p = 0.012) and Mental Component Summary (ß = 0.22, p = 0.002). OP predicted Social Function (ß = -3.18 p < 0.001), General Health (ß = -1.55, p = 0.004), Physical Component Summary (ß = -2.00, p = 0.007) and Mental Component Summary (ß = -1.53, p = 0.005). BCVA predicted Physical Function (ß = 31.1, p = 0.02) and Emotional Well-being (ß = 7.94, p = 0.01). ODI failed to predict any HRQoL metrics. ODI was independent predictor of legal blindness adjusted for uveitis duration and severity. Legally blind patients had worse HRQoL metrics than patients with better vision. CONCLUSION: In BD uveitis patients, subjective disease burden parameters were more informative about HRQoL metrics than objective ones. Longitudinal studies are needed to elucidate the utility of ODI as an outcome measure in BD uveitis. PRECIS: In Behcet's uveitis patients, health-related quality of life was related to visual outcome, ocular pain, and subjective visual rating. Ocular damage was an independent predictor of legal blindness, adjusted for uveitis duration and severity.

Potential Risk Factors for Ocular Pain in Patients Undergoing Multiple Intravitreal Injections of Anti-Vascular Endothelial Growth Factor.

Purpose: To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity. Methodology: This is a prospective, observational, case series study involving patients who underwent multiple (≥3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF. Results: In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (>550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively). Conclusion: Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections.

Early Real-World Patient and Staff Experience with an Intracanalicular Dexamethasone Insert.

Purpose: To evaluate both the early experience of real-world patients treated with dexamethasone ophthalmic insert (0.4 mg; DEXTENZA®), hereafter referred to as DEX, after cataract surgery as well as staff/practice integration of DEX relative to eyedrops. Patients and Methods: This was a cross-sectional survey study of 23 cataract practices in the United States. Respondents were patients and practice staff who had experience with DEX following cataract surgery. Both patients and practice staff completed an online survey. Descriptive statistics summarized the survey responses to portray the experience of the respondents. Results: Surveys were completed by 62 patients and 19 practice staff. Almost all patients (93%) were satisfied or extremely satisfied with DEX. Patients highly preferred DEX (93%) to topical steroid drops (7%) based on past experiences with topical steroid drops. Most practice staff (95%) were satisfied or highly satisfied with DEX, reporting a 45% reduction in time spent educating patients on postoperative drop use and a 46% decrease in time spent addressing calls from pharmacies regarding postoperative medications. Conclusion: Incorporating the DEX insert into clinical practice in cataract surgery practices can improve patient adherence, while potentially providing significant savings to practices in terms of time spent educating patients and responding to patient and pharmacy call-backs.

Varenicline Solution Nasal Spray for the Treatment of Dry Eye Disease Following LASIK.

INTRODUCTION: The purpose of this study is to evaluate the use of a varenicline solution nasal spray (VNS) for reducing the signs and symptoms of dry eye following laser in situ keratomileusis (LASIK). METHODS: Subjects electing to undergo LASIK were randomized to VNS (study group) or placebo/vehicle (control group) and initiated treatment with the nasal spray twice daily 28 days prior to surgery with continued treatment for 84 days following LASIK. After initiation of treatment, subjects were seen on the day of surgery and postoperatively on Days 1, 7, 28, 84 (3 months) and 168 (6 months). The primary outcome measure was the mean change in NEI-VFQ-25, a 25-item dry eye questionnaire, from baseline to 3 months. The second primary outcome measure was the mean change in corneal fluorescein staining. Secondary outcome measures included evaluation of tear break-up time, Schirmer testing, tear osmolarity and eye dryness score (EDS). RESULTS: Twenty subjects were enrolled in each group and successfully underwent LASIK. Both groups demonstrated an improvement in the National Eye Institute Visual Function Questionnaire (NEI-VFQ) at 3 months. The study group demonstrated improved corneal staining scores at months 1 and 3. Similarly, the study group demonstrated improvement in tear osmolarity scores versus the placebo group at the same time points. Although the study group was numerically greater than placebo for each time point for both corneal staining and tear osmolarity, the differences were not statistically significant for any primary or secondary outcome measures. CONCLUSION: VNS is a dry eye treatment option for patients following LASIK and may have potential benefit for patients hoping to avoid additional topical medications. The results were not statistically significant compared to placebo in this trial, and further investigation of the use of VNS following LASIK in a larger trial would be beneficial.

Laser in situ keratomileusis (LASIK) is a very successful refractive surgery option for patients hoping to reduce or eliminate their need for spectacles. Signs and symptoms of dry eye disease are very common after LASIK owing to the transection of corneal nerves that occurs during the procedure, and many patients are advised to manage it with frequent instillation of artificial tears. This study evaluated the use of a varenicline solution nasal spray, a recently introduced pharmacologic option that stimulates natural tear production through activation of the trigeminal nerve pathway. This is the first study to evaluate the use of the varenicline solution nasal spray in patients after refractive surgery and demonstrates that it could represent a favorable, ocular surface-sparing option for patients to minimize the signs and symptoms of dry eye following LASIK, a procedure known to trigger symptoms of dry eye disease.

Evaluating GlicoPro Tear Substitute Derived from Helix aspersa Snail Mucus in Alleviating Severe Dry Eye Disease: A First-in-Human Study on Corneal Esthesiometry Recovery and Ocular Pain Relief.

Background: To evaluate the effects of 10% GlicoPro tear substitute therapy in patients with severe dry eye disease (DED). Methods: In this prospective longitudinal study, 30 individuals receiving 10% GlicoPro four times daily for DED were evaluated. The ocular surface disease index (OSDI) questionnaire, average non-invasive break-up time (A-NIBUT), non-anesthetic and anesthetic corneal esthesiometry (CE), ocular pain, and the presence of conjunctivochalasis (CCH) were used as clinical endpoints. Treatment compliance using dosing diaries and AEs was assessed. Results: A significant improvement was observed in the clinical endpoints: the ΔOSDI questionnaire was -39.27 ± 13.22 [-65 to -15] points, ΔA-NIBUT was 3.10 ± 1.31 [1 to 5] s, Δnon-anesthetic CE was 14 ± 6.35 [5 to 25] mm, and Δanesthetic CE was 13 ± 5.35 [5 to 20] mm (p < 0.001 for all comparisons). Ocular pain was reduced in 92.5% of the patients at the end of the follow-up. However, there was no change in the presence of CCH. In addition, all the patients were fully compliant with the dosing and no AEs related to the use of the 10% GlicoPro tear substitute were reported. Conclusions: The 10% GlicoPro tear substitute has the potential to achieve beneficial effects in ocular surface treatments.

Patient Experiences and Insights on Chronic Ocular Pain: Social Media Listening Study.

BACKGROUND: Ocular pain has multifactorial etiologies that affect activities of daily life, psychological well-being, and health-related quality of life (QoL). Chronic ocular surface pain (COSP) is a persistent eye pain symptom lasting for a period longer than 3 months. OBJECTIVE: The objective of this social media listening study was to better understand COSP and related symptoms and identify its perceived causes, comorbidities, and impact on QoL from social media posts. METHODS: A search from February 2020 to February 2021 was performed on social media platforms (Twitter, Facebook, blogs, and forums) for English-language content posted on the web. Social media platforms that did not provide public access to information or posts were excluded. Social media posts from Australia, Canada, the United Kingdom, and the United States were retrieved using the Social Studio platform-a web-based aggregator tool. RESULTS: Of the 25,590 posts identified initially, 464 posts about COSP were considered relevant; the majority of conversations (98.3%, n=456) were posted by adults (aged >18 years). Work status was mentioned in 52 conversations. Patients' or caregivers' discussions across social media platforms were centered around the symptoms (61.9%, n=287) and causes (58%, n=269) of ocular pain. Patients mentioned having symptoms associated with COSP, including headache or head pressure, dry or gritty eyes, light sensitivity, etc. Patients posted that their COSP impacts day-to-day activities such as reading, driving, sleeping, and their social, mental, and functional well-being. CONCLUSIONS: Insights from this study reported patients' experiences, concerns, and the adverse impact on overall QoL. COSP imposes a significant burden on patients, which spans multiple aspects of daily life.

Refinement and revalidation of the Equine Ophthalmic Pain Scale: R-EOPS a new scale for ocular pain assessment in horses.

This study addresses the refinement and revalidation of a composite pain scale that focuses on equine facial expressions and behavioural indicators as exhibitions of ophthalmic pain. This scale included only Behavioural and Facial and Ocular expression indicators and, compared to the first version of Equine Ophthalmic Pain Scale (EOPS), item descriptors and related ratings were changed. Thirteen horses with ocular diseases that required medical or surgical treatment were enroled (group P). In each animal, the refined EOPS (R-EOPS) was applied prior to any treatment (T0) and one week later (T7). The R-EOPS was applied twice, 7 days apart, to 16 healthy control horses (group C). Two 30-second videos were recorded each time to allow the retrospective analysis by eight observers. Inter-observer reliability of items was moderate or substantial (Krippendorff's alpha, Kα>0.40) while their intra-observer reliability was substantial or almost perfect for most items (Kα ≥0.61). Both inter- and intra-observer reliability of Total Score (TS) were however excellent (Intraclass Correlation Coefficients, ICC>0.75). The TS also showed good reproducibility (Kendall coefficient=0.786, ICC=0.684) and high consistency of its items (Cronbach's α=0.847). The comparison between groups as well as the sensitivity and specificity values supported the validity of the R-EOPS. In particular, for each extra point added to the TS, the risk of the horse having pain increased by more than two times (Odds Ratio=2.079, 95%CI=1.542-2.804; P<0.001). The Receiver Operating Characteristic analysis identified 6 as the threshold value of R-EOPS for discriminating horses with ocular pathology (sensitivity=83%, specificity=100%). This scale may be an effective tool for reliably assessing the pain level in horses with ophthalmic diseases and potentially guiding pain management although it still requires large-scale application and external validation.

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.

Analysis of Clinical Characteristics and Neuropeptides in Patients with Dry Eye with and without Chronic Ocular Pain after FS-LASIK.

INTRODUCTION: Chronic ocular pain, particularly prevalent in patients with dry eye disease and post-femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) surgery, presents with unclear clinical characteristics and an undefined pathogenesis. In this study, we aimed to compare clinical characteristics and tear neuropeptide concentrations in patients with dry eye disease (DED) with and without chronic ocular pain following FS-LASIK, and investigate correlations between ocular pain, clinical characteristics, and tear neuropeptide levels. METHODS: Thirty-eight post-FS-LASIK patients with DED were assigned to two groups: those with chronic ocular pain and those without chronic ocular pain. Dry eye, ocular pain, and mental health-related parameters were evaluated using specific questionnaires and tests. The morphology of corneal nerves and dendritic cells (DCs) was evaluated by in vivo confocal microscopy. Function of corneal innervation was evaluated by corneal sensitivity. Concentrations of tear cytokines (interleukin [IL]-6, IL-23, IL-17A, and interferon-γ) and neuropeptides (α-melanocyte-stimulating hormone, neurotensin, ß-endorphin, oxytocin, and substance P [SP]) were measured using the Luminex assay. RESULTS: Most patients with chronic ocular pain experienced mild to moderate pain; the most common types included stimulated pain (provoked by wind and light), burning pain, and pressure sensation. More severe dry eye (P < 0.001), anxiety symptoms (P = 0.026), lower Schirmer I test values (P = 0.035), lower corneal nerve density (P = 0.043), and more activated DCs (P = 0.041) were observed in patients with ocular pain. Tear concentrations of SP and oxytocin were significantly higher in patients with ocular pain (P = 0.001, P = 0.021, respectively). Furthermore, significant correlations were observed among ocular pain severity, SP, and anxiety levels. CONCLUSIONS: Patients with DED after FS-LASIK who have chronic ocular pain show more severe ocular and psychological discomfort and higher tear levels of neuropeptides. Furthermore, ocular pain severity is correlated with tear SP levels. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05600985.

Dry eye symptoms and signs in United States Gulf War era veterans with myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND: To examine ocular symptoms and signs of veterans with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) diagnosis, ME/CFS symptoms, and controls. METHODS: This was a prospective, cross-sectional study of 124 South Florida veterans in active duty during the Gulf War era. Participants were recruited at an ophthalmology clinic at the Miami Veterans Affairs Hospital and evaluated for a diagnosis of ME/CFS, or symptoms of ME/CFS (intermediate fatigue, IF) using the Canadian Consensus criteria. Ocular symptoms were assessed via standardised questionnaires and signs via comprehensive slit lamp examination. Inflammatory blood markers were analysed and compared across groups. RESULTS: Mean age was 55.1 ± 4.7 years, 88.7% identified as male, 58.1% as White, and 39.5% as Hispanic. Ocular symptoms were more severe in the ME/CFS (n = 32) and IF (n = 48) groups compared to controls (n = 44) across dry eye (DE; Ocular Surface Disease Index [OSDI]: 48.9 ± 22.3 vs. 38.8 ± 23.3 vs. 19.1 ± 17.8, p < 0.001; 5 item Dry Eye Questionnaire [DEQ-5]: 10.8 ± 3.9 vs. 10.0 ± 4.6 vs. 6.6 ± 4.2, p < 0.001) and pain-specific questionnaires (Numerical Rating Scale 1-10 [NRS] right now: 2.4 ± 2.8 vs. 2.4 ± 2.9 vs 0.9 ± 1.5; p = 0.007; Neuropathic Pain Symptom Inventory modified for the Eye [NPSI-E]: 23.0 ± 18.6 vs. 19.8 ± 19.1 vs. 6.5 ± 9.0, p < 0.001). Ocular surface parameters and blood markers of inflammation were generally similar across groups. CONCLUSION: Individuals with ME/CFS report increased ocular pain but similar DE signs, suggesting that mechanisms beyond the ocular surface contribute to symptoms.

Genome Wide Association Study of Neuropathic Ocular Pain.

Purpose: To conduct a genome-wide association study (GWAS) of individuals with neuropathic ocular pain (NOP) symptoms to identify genomic variants that may predispose to NOP development. Design: Prospective study of individuals with NOP. Participants: Three hundred twenty-nine patients recruited from the Miami Veterans Affairs eye clinic. Methods: The Neuropathic Pain Symptom Inventory modified for the eye (NPSI-Eye) was completed to calculate a NPSI-Eye-Sub-Score (summed ratings of burning and wind sensitivity) as an indicator of NOP severity. A GWAS was performed for the NPSI-Eye-Sub-Score with a significance threshold of P < 5 × 10-8. A gene-based analysis was performed using the multimarker analysis of genomic annotation software (in the functional mapping and annotation of GWAS online platform). The 13 865 778 single nucleotide polymorphisms (SNPs) from our GWAS analysis were mapped to 10 834 protein coding genes, and significant genes were run through gene set enrichment analysis. Main Outcome Measures: Identification of SNPs and protein products that may be associated with the development of NOP. Results: One hundred seventy-one SNPs reached a threshold of P < 10-5, of which 10 SNPs reached the suggestive level of significance of P < 5 × 10-7 and 1 SNP met our genome-wide significance threshold of P < 5 × 10-8. This lead SNP, rs140293404 (P = 1.23 × 10-8), is an intronic variant found within gene ENSG00000287251 coding for transcript ENST00000662732.1. Rs140293404 is in linkage disequilibrium with exon variant rs7926353 (r2 > 0.8) within ENSG00000279046 coding for transcript ENST00000624288.1. The most significant genes from gene-based tests were matrix metalloproteinase-19 (MMP19) (P = 1.12 × 10-5), zinc finger RNA-binding motif and serine/arginine rich-1 (ZRSR1) (P = 1.48 × 10-4), CTC-487M23.8 (P = 1.79 × 10-4), receptor expression-enhancing protein-5 (REEP5) (P = 2.36 × 10-4), and signal recognition particle-19 (SRP19) (P = 2.56 × 10-4). From gene set enrichment analysis, the sensory perception (false discovery rate = 6.57 × 10-3) and olfactory signaling (false discovery rate = 1.63 × 10-2) pathways were enriched with the most significant genes. Conclusions: Our GWAS revealed genes with protein products that may impact sensory perception, lending biological plausibility to a role for SNPs identified by our GWAS in the development of NOP. A better understanding of the biological relevance of these genes and pathways in the pathophysiology associated with NOP may facilitate future novel mechanism-based treatments. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Topical fosaprepitant for the treatment of 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.

A novel animal model of neuropathic corneal pain-the ciliary nerve constriction model.

Introduction: Neuropathic pain arises as a result of peripheral nerve injury or altered pain processing within the central nervous system. When this phenomenon affects the cornea, it is referred to as neuropathic corneal pain (NCP), resulting in pain, hyperalgesia, burning, and photoallodynia, severely affecting patients' quality of life. To date there is no suitable animal model for the study of NCP. Herein, we developed an NCP model by constriction of the long ciliary nerves innervating the eye. Methods: Mice underwent ciliary nerve constriction (CNC) or sham procedures. Safety was determined by corneal fluorescein staining to assess ocular surface damage, whereas Cochet-Bonnet esthesiometry and confocal microscopy assessed the function and structure of corneal nerves, respectively. Efficacy was assessed by paw wipe responses within 30 seconds of applying hyperosmolar (5M) saline at Days 3, 7, 10, and 14 post-constriction. Additionally, behavior was assessed in an open field test (OFT) at Days 7, 14, and 21. Results: CNC resulted in significantly increased response to hyperosmolar saline between groups (p < 0.0001), demonstrating hyperalgesia and induction of neuropathic pain. Further, animals that underwent CNC had increased anxiety-like behavior in an open field test compared to controls at the 14- and 21-Day time-points (p < 0.05). In contrast, CNC did not result in increased corneal fluorescein staining or decreased sensation as compared to sham controls (p > 0.05). Additionally, confocal microscopy of corneal whole-mounts revealed that constriction resulted in only a slight reduction in corneal nerve density (p < 0.05), compared to naïve and sham groups. Discussion: The CNC model induces a pure NCP phenotype and may be a useful model for the study of NCP, recapitulating features of NCP, including hyperalgesia in the absence of ocular surface damage, and anxiety-like behavior.

Electroacupuncture Alleviates Dry Eye Ocular Pain Through TNF-ɑ Mediated ERK1/2/P2X3R Signaling Pathway in SD Rats.

Purpose: This study aimed to examine electroacupuncture's influence on ocular pain and its potential modulation of the TNF-ɑ mediated ERK1/2/P2X3R signaling pathway in dry eye-induced rat models. Methods: Male Sprague-Dawley rats with induced dry eye, achieved through extraorbital lacrimal gland removal, were treated with electroacupuncture. Comprehensive metrics such as the corneal mechanical perception threshold, palpebral fissure height, eyeblink frequency, eye wiping duration, behavioral changes in the open field test, and the forced swimming test were employed. Additionally, morphological changes in microglia and neurons were observed. Expression patterns of key markers, TNF-ɑ, TNFR1, p-ERK1/2, and P2X3R, in the trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (SpVc) regions, were studied with etanercept serving as a control to decipher the biochemistry of electroacupuncture's therapeutic effects. Results: Electroacupuncture treatment demonstrated a notable decrease in the corneal mechanical perception threshold, improvement in palpebral fissure height, and significant reductions in both eyeblink frequency and eye wiping duration. Moreover, it exhibited a promising role in anxiety alleviation. Notably, the technique effectively diminished ocular pain by curbing microglial and neuronal activation in the TG and SpVc regions. Furthermore, it potently downregulated TNF-ɑ, TNFR1, p-ERK1/2, and P2X3R expression within these regions. Conclusion: Electroacupuncture attenuated damage to sensory nerve pathways, reduced pain, and eased anxiety in dry eye-afflicted rats. The findings suggest a crucial role of TNF-ɑ mediated ERK1/2/P2X3R signaling pathway inhibition by electroacupuncture in these benefits.

[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.

Disentangling the neurological basis of chronic ocular pain using clinical, self-report, and brain imaging data: use of K-means clustering to explore patient phenotypes.

Introduction: The factors that mediate the expression of ocular pain and the mechanisms that promote chronic ocular pain symptoms are poorly understood. Central nervous system involvement has been postulated based on observations of pain out of proportion to nociceptive stimuli in some individuals. This investigation focused on understanding functional connectivity between brain regions implicated in chronic pain in persons reporting ocular pain symptoms. Methods: We recruited a total of 53 persons divided into two cohorts: persons who reported no ocular pain, and persons who reported chronic ocular pain, irrespective of ocular surface findings. We performed a resting state fMRI investigation that was focused on subcortical brain structures including the trigeminal nucleus and performed a brief battery of ophthalmological examinations. Results: Persons in the pain cohort reported higher levels of pain symptoms relating to neuropathic pain and ocular surface disease, as well as more abnormal tear metrics (stability and tear production). Functional connectivity analysis between groups evinced multiple connections exemplifying both increases and decreases in connectivity including regions such as the trigeminal nucleus, amygdala, and sub-regions of the thalamus. Exploratory analysis of the pain cohort integrating clinical and brain function metrics highlighted subpopulations that showed unique phenotypes providing insight into pain mechanisms. Discussion: Study findings support centralized involvement in those reporting ocular-based pain and allude to mechanisms through which pain treatment services may be directed in future research.

Self-reported symptoms of everyday executive dysfunction, daytime sleepiness, and fatigue and health status among adults with congenital aniridia: a descriptive study.

Background: Congenital aniridia is a rare genetic disorder of the eye characterized by visual impairment and progressive vision loss. While prior research has focused on ocular manifestations in individuals with aniridia, there is a dearth of research on impacts on cognition and mental health. The aims of this study were to describe subjective symptoms of everyday executive functioning, fatigue and sleepiness in adults with aniridia and to compare self-reported health status with that of a normative reference group. Methods: Twenty-nine adults (aged 18-79 years) with congenital aniridia were included in this online survey, of whom 52% were females. Participants completed self-report measures of executive functioning (The Behavior Rating Inventory of Executive Function-Adult Version), sleepiness, fatigue, and health status (EQ-5D-5L). Results: Participants reported relatively few problems in everyday executive functioning, with only 14% experiencing impaired executive functioning. Scores on the five EQ-5D-5L domains (mobility, self-care, usual activities, pain, and anxiety/depression) did not differ from those of the normative reference group. The frequencies of excessive daytime sleepiness and severe fatigue were 17% and 38%, respectively. Ocular pain was experienced by 62% of participants. Conclusions: The findings show that cognitive problems are related to and reflect self-reported health status and extent of fatigue. Moreover, those who suffered from ocular pain reported more difficulties with executive functioning, sleepiness and fatigue. These findings are important for understanding this disorder and supporting patients.

Pain control and subconjunctival haemorrhage after intravitreal injection using cooled anaesthetic eyedrops and antiseptics: A prospective, double-blind, randomized controlled trial.

PURPOSE: To evaluate whether cooled anaesthetic eyedrops and antiseptics alleviate pain and minimise subconjunctival haemorrhage following intravitreal injection. METHODS: A prospective, double-masked, randomised controlled trial of 100 participants receiving either cooled (n = 50) or room temperature (n = 50) topical anaesthetic eyedrops and antiseptics before receiving an injection of bevacizumab. Baseline tolerability was estimated using a self-reported pain sensitivity questionnaire. RESULTS: Overall tolerability was comparable between the study group and the control group (0.75 ± 0.13 vs. 0.74 ± 0.14, respectively, p = 0.99). Subconjunctival haemorrhage incidence was similar in both groups (80% vs. 86%, respectively, p = 0.113), as was subconjunctival haemorrhage size (2.75 ± 5.51 mm2 vs. 5.53 ± 10.72 mm2 , respectively, p = 0.11). Sub-group analysis demonstrated that the participants taking daily ocular eyedrops who received cooled anaesthetic eyedrops and antiseptics reported less pain at 10 min and less burning sensation at 24 h compared with matched controls (0.67 ± 1.50 vs. 2.50 ± 3.03, respectively, p = 0.040 and 0.00 ± 0.00 vs. 1.44 ± 2.96, respectively, p = 0.045). Participants who received cooled eyedrops and did not use antithrombotic therapy had smaller-sized subconjunctival haemorrhages compared with matched controls (1.55 ± 1.87 mm2 vs. 8.29 ± 14.61 mm2 , respectively, p = 0.038). Participants with hypertension who received cooled eyedrops had smaller-sized subconjunctival haemorrhage compared with matched controls (2.33 ± 4.99 mm2 vs. 6.89 ± 12.41 mm2 , respectively, p = 0.045). CONCLUSION: The benefit of using cooled anaesthetic eyedrops and antiseptics to alleviate pain and minimise subconjunctival haemorrhage following intravitreal injection was not proven in the general population. It may be beneficial in part for some patients, such as those who regularly use eyedrops, patients with hypertension or those not on antithrombotic therapy.

Estimating the Dose-Response Relationship for Ocular Pain after Radiotherapy of Head and Neck Cancers and Skull Base Tumors based on the LKB Radiobiological Model.

Background: Radiotherapy is considered a compromise between the amount of killed tumor cells and the damage caused to the healthy tissue. Regarding this, radiobiological modeling is performed to individualize and optimize treatment strategies. Objective: This study aimed to determine the normal tissue complication probability (NTCP) of acute ocular pain following radiotherapy. Material and Methods: In this prospective observational study, the clinical data were collected from 45 patients with head and neck cancers and skull-base tumors, and dosimetric data were recorded after contouring the eye globe. Acute ocular pain was prospectively assessed with a three-month follow-up. The Lyman-Kutcher-Berman (LKB) parameters were estimated using the Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) maximization and Maximum Likelihood (MLH) methods, and the NTCP of acute ocular pain was then determined using generalized LKB radiobiological model. The model performance was evaluated with AUC, Brier score, and Hosmer-Lemeshow tests. Results: Six out of 45 (13.33%) patients developed acute ocular pain (grade 1 or more). LKB model showed a weak dose-volume effect (n=0.09), tolerance dose for a 50% complication (TD50) of 27.54 Gy, and slope parameter (m) of 0.38. The LKB model showed high prediction performance. The LKB model predicted that NTCP would be less than 25% if the generalized equivalent uniform dose (gEUD) was kept below 20 Gy. Conclusion: The LKB model showed a high performance in determining the NTCP of ocular pain so that the probability of ocular pain will be less than 25% if the eye globe mean dose is kept below 12 Gy.

Exoftalmos y dolor ocular como presentación clínica de linfoma de Hodgkin con afectación intracraneal al diagnóstico / Exophthalmos and ocular pain as clinical debut of intracranial Hodgkin's lymphoma at diagnosis

La afectación intracraneal del linfoma de Hodgkin (LH) es extremadamente rara, especialmente como forma de presentación de la enfermedad. Muestra un patrón radiológico inespecífico, pudiendo ser confundido con otras entidades de mayor frecuencia y pronóstico radicalmente distinto. Anatomopatológicamente se caracteriza por la presencia de células grandes binucleadas (células de Reed-Sternberg) eIntracranial involvement in Hodgkin's lymphoma (HL) is extremely unusual, especially at the time of diagnosis. Because of its non-specific radiological behaviour, it can be confused with more common entities with a radically different prognosis. Pathologically, large and bi-nucleated cells, called Reed-Sternberg cells, embedded in an inflammatory network.

In this report we describe the clinical case of a patient, with no medical history, with left ocular pain and exophthalmos as presentation of intracranial HL at diagnosis and review the most current literature. Intracranial involvement is often associated with extracranial disease. Therefore, a systemic study including body computed tomography, bone marrow biopsy and ophthalmological evaluation is necessary. Intracranial lesions respond favourably to treatment and the prognosis depends on the extracranial involvement. To date, there is no standardised management scheme for these patients. For us, the primary role of surgery in this context is to perform a biopsy to confirm the histological diagnosis (AU)mbebidas en un entramado inflamatorio. Presentamos el caso de una paciente con dolor ocular y exoftalmos izquierdo como presentación clínica de afectación intracraneal por LH al diagnóstico de su enfermedad y revisamos la literatura más reciente al respecto. En pacientes con LH intracraneal es necesario realizar un estudio de extensión con tomografía computarizada corporal, biopsia de médula ósea y examen oftalmológico. Se asocia con gran frecuencia a enfermedad extracraneal, que marca el pronóstico. La lesión intracraneal presenta buena respuesta al tratamiento, que no sigue un esquema estandarizado. El papel de la cirugía es la realización de una biopsia para confirmar el diagnóstico (AU)