Prospective cohort study investigating frequency and risk factors for acute pain 1 day after refractive surgery.

BACKGROUND/AIMS: To examine demographic and clinical factors associated with ocular pain 1 day after refractive surgery. METHODS: Prospective study of individuals undergoing refractive surgery. Participants rated their ocular pain on a 0-10 numerical rating scale (NRS) presurgery and 1 day after surgery. Presurgery, participants completed questionnaires on demographics, comorbidities, medications and dry eye and ocular pain symptoms; and an anaesthetised Schirmer test was performed. Acute ocular pain 1 day after surgery was defined as an NRS score of worst pain since surgery ≥3 and this group was compared with individuals with NRS scores<3. RESULTS: 251 individuals underwent refractive surgery (89% laser-assisted in situ keratomileusis, n=222; 11% PRK, n=29). Mean age was 35±8 years (range 19 to 60); 60% (n=150) self-identified as female, 80% (n=203) as White, and 36% (n=89) as Hispanic. Thirteen (5%) individuals reported ocular pain (NRS ≥3) prior to surgery and 67% (n=168) reported ocular pain 1 day after surgery (nine individuals had pain at both time points). Factors that were associated with pain 1 day after surgery included Hispanic ethnicity (adjusted relative risk (aRR) 1.42, 95% CI 1.21 to 1.68, p<0.001) and the presence of eye pain presurgery (aRR 1.10, 95% CI 1.02 to 1.18, p=0.02). CONCLUSION: A majority of individuals report moderate or greater pain within 24 hours of refractive surgery. Hispanic ethnicity and eye pain prior to surgery were associated with self-reported acute postsurgical pain.

Tear Proteins Altered in Patients with Persistent Eye Pain after Refractive Surgery: Biomarker Candidate Discovery.

Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (n = 16)] and patients with no pain [NRS ≤ 1 at 3 months (n = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.

Childhood Reading Ability and Pain in Childhood Through to Midlife.

Dyslexia and pain have recently been shown to correlate on a genetic level, but there has been little exploration of this association on the phenotypic level despite reports of increased pain in Attention Deficit Hyperactivity Disorder, which commonly co-occurs with dyslexia. In this study we test for an association between reading ability, which is the primary feature of dyslexia, and pain both in childhood and adulthood. Logistic regression modeling was used to test associations between reading ability in childhood and pain from childhood to midlife in a large UK birth cohort; the 1958 National Child Development Study. Associations were found between poor childhood reading ability and increased headache and abdominal pain in childhood, and between poor childhood reading ability and headache, eye pain, back pain, and rheumatism in adulthood. Mediation analyses indicated that socioeconomic status (defined by employment) fully mediated the association between poor reading ability in childhood and back pain at age 42. By contrast, the association between reading ability and eye pain acted independently of socioeconomic status. Different mechanisms were thus indicated for the association of reading with different pain types, including manual labor and a potential shared biological pathway. PERSPECTIVE: This study found a relationship between poor reading ability in childhood and pain in childhood and adulthood. Those with reading difficulties should be monitored for pain symptoms. Future research may uncover shared biological mechanisms, increasing our understanding of pain and potential treatments.

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.

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.

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.

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)

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.