Lipids from ocular meibum and tears may serve as biomarkers for depression and post-traumatic stress disorder.

BACKGROUND: There is a need to develop biomarkers for diagnosis and prediction of treatment responses in depression and post-traumatic stress disorder (PTSD). METHODS: Cross-sectional study examining correlations between tear inflammatory proteins, meibum and tear sphingolipids, and symptoms of depression and PTSD-associated anxiety. Ninety individuals filled depression (Patient Health Questionnaire 9, PHQ-9) and PTSD-associated anxiety (PTSD Checklist-Military Version, PCL-M) questionnaires. In 40 patients, a multiplex assay system was used to quantify 23 inflammatory proteins in tears. In a separate group of 50 individuals, liquid chromatography-mass spectrometry was performed on meibum and tears to quantify 34 species of sphingolipids, encompassing ceramides, monohexosyl ceramides and sphingomyelins. RESULTS: The mean age of the population was 59.4 ± 11.0 years; 89.0% self-identified as male, 34.4% as White, 64.4% as Black, and 16.7% as Hispanic. The mean PHQ-9 score was 11.1 ± 7.6, and the mean PCL-M score was 44.3 ± 19.1. Symptoms of depression and PTSD-associated anxiety were highly correlated (ρ =0.75, p < 0.001). Both PHQ9 and PCL-M scores negatively correlated with multiple sphingolipid species in meibum and tears. In multivariable models, meibum Monohexosyl Ceramide 26:0 (pmol), tear Ceramide 16:0 (mol%), meibum Monohexosyl Ceramide 16:0 (mol%), and tear Ceramide 26:1 (mol%) remained associated with depression and meibum Monohexosyl Ceramide 16:0 (mol%), meibum Monohexosyl Ceramide 26:0 (pmol), tear Sphingomyelin 20:0 (mol%), and tear Sphingosine-1-Phosphate (mol%) remained associated with PTSD-associated anxiety. CONCLUSIONS: Certain meibum and tear sphingolipid species were related to mental health indices. These interactions present opportunities for innovative diagnostic and therapeutic approaches for mental health disorders.

Prevalence and Impact of Neuropathic and Nonneuropathic Pain in Chronic Spinal Cord Injury.

OBJECTIVE: To compare prevalence, intensity ratings, and interference ratings of neuropathic pain (NeuP) and nociceptive pain in people with chronic spinal cord injury (SCI) DESIGN: Cross-sectional survey. SETTING: Six SCI Model System centers in the United States. PARTICIPANTS: Convenience sample of 391 individuals (N=391) with traumatic SCI, 18 years or older, 81% male, 57% White. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Survey based on the International Spinal Cord Injury Pain Basic Data Set and the Spinal Cord Injury Pain Instrument, including 0-10 numeric ratings of pain intensity and pain interference with daily activities, mood, and sleep RESULTS: A total of 80% of those surveyed reported having at least 1 pain problem; 58% reported 2 or more pain problems; 56% had probable NeuP; and 49% had non-NeuP. When comparing ratings for all pains (n=354 for NeuP, n=290 for non-NeuP) across participants, probable NeuPs were significantly more intense (6.9 vs 5.7) and interfered more with activities (5.2 vs 3.7), mood (4.9 vs 3.2), and sleep (5.4 vs 3.6) than non-NeuPs (all P<.001). However, when comparing ratings for probable NeuPs and non-NeuPs within participants, for the subgroup of 94 participants with both pain types, only ratings for sleep interference were found to be significantly different between the pain types. Additionally, we found significantly greater prevalence of NeuP and non-NeuP for women compared with men and of NeuP for those with paraplegia compared with those with tetraplegia. CONCLUSIONS: Independent assessment of the pain conditions experienced by an individual with SCI is useful in understanding the differential effect that pain type has on quality of life. This is particularly important regarding sleep interference and should be kept in mind when determining treatment strategies for meeting patient-centered outcome goals.

Physical Function Recovery Trajectories After Spinal Cord Injury.

OBJECTIVE: To explore trajectories of functional recovery that occur during the first 2 years after spinal cord injury (SCI). DESIGN: Observational cohort study. SETTING: Eight SCI Model System sites. PARTICIPANTS: A total of 479 adults with SCI completed 4 Spinal Cord Injury-Functional Index (SCI-FI) item banks within 4 months of injury and again at 2 weeks, 3, 6, 12, and 24 months after baseline assessment (N=479). INTERVENTION: None. MAIN OUTCOME MEASURES: SCI-FI Basic Mobility/Capacity (C), Fine Motor Function/C, Self-care/C, and Wheelchair Mobility/Assistive Technology (AT) item banks. RESULTS: Growth mixture modeling was used to identify groups with similar trajectory patterns. For the Basic Mobility/C and Wheelchair Mobility/AT domains, models specifying 2 trajectory groups were selected. For both domains, a majority class exhibited average functional levels and gradual improvement, primarily in the first 6 months. A smaller group of individuals made gradual improvements but had greater initial functional limitations. The Self Care/C domain exhibited a similar pattern; however, a third, small class emerged that exhibited substantial improvement in the first 6 months. Finally, for individuals with tetraplegia, trajectories of Fine Motor Function/C scores followed 2 patterns, with individuals reporting generally low initial scores and then making either modest or large improvements. In individual growth curve models, injury/demographic factors predicted initial functional levels but less so regarding rates of recovery. CONCLUSIONS: Trajectories of functional recovery followed a small number of change patterns, although variation around these patterns emerged. During the first 2 years after initial hospitalization, SCI-FI scores showed modest improvements; however, substantial improvements were noted for a small number of individuals with severe limitations in fine motor and self-care function. Future studies should further explore the personal, medical, and environmental characteristics that influence functional trajectories during these first 2 years and beyond.

Characterizing the Experience of Spasticity after Spinal Cord Injury: A National Survey Project of the Spinal Cord Injury Model Systems Centers.

OBJECTIVE: To characterize the qualities that individuals with spinal cord injury (SCI) associate with their experience of spasticity and to describe the relationship between spasticity and perceived quality of life and the perceived value of spasticity management approaches. DESIGN: Online cross-sectional survey. SETTING: Multicenter collaboration among 6 Spinal Cord Injury Model Systems hospitals in the United States. PARTICIPANTS: Individuals with SCI (N=1076). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Qualities of Spasticity Questionnaire, modified Spinal Cord Injury-Spasticity Evaluation Tool (mSCI-SET), and the modified Patient-Reported Impact of Spasticity Measure (mPRISM). RESULTS: Respondents indicated that spasms most often occurred in response to movement-related triggering events. However, spontaneous spasms (ie, no triggering event) were also reported to be among the most common types. Frequency of spasms appears to decline with age. The highest frequency of spasms was reported by 56% of respondents aged <25 years and by only 28% of those >55 years. Stiffness associated with spasticity was reported to be more common than spasms (legs, 65% vs 54%; trunk, 33% vs 18%; arms, 26% vs 15%). Respondents reported negative effects of spasticity more commonly than positive effects. Based on their association with negative scores on the mSCI-SET and the mPRISM, the 5 most problematic experiences reported were stiffness all day, interference with sleep, painful spasms, perceived link between spasticity and pain, and intensification of pain before a spasm. Respondents indicated spasticity was improved more by stretching (48%) and exercise (45%) than by antispasmodics (38%). CONCLUSIONS: The experience of spasticity after SCI is complex and multidimensional, with consequences that affect mobility, sleep, comfort, and quality of life. Stiffness, rather than spasms, appears to be the most problematic characteristic of spasticity. Physical therapeutic interventions to treat spasticity warrant in-depth investigation.

Spinal Cord Injury-Functional Index/Capacity: Responsiveness to Change Over Time.

OBJECTIVE: To establish responsiveness of 3 Spinal Cord Injury-Functional Index/Capacity (SCI-FI/C) item banks in the first year after spinal cord injury (SCI). DESIGN: Longitudinal patient-reported outcomes assessment replicated through secondary analysis of an independent data set. SETTING: A total of 8 SCI Model Systems rehabilitation hospitals in the United States. PARTICIPANTS: Study 1 participants included 184 adults with recent (≤4 months) traumatic SCI and 221 community-dwelling adults (>1 year post injury) (N=405). Study 2 participants were 418 individuals with recent SCI (≤4 months) (N=418). INTERVENTIONS: In study 1, SCI-FI/C computer adaptive tests were presented in a standardized interview format either in person or by phone call at baseline and 6-month follow-up. Responsiveness was examined by comparing 6-month changes in SCI-FI scores within and across samples (recently injured vs community-dwelling) because only the recent injury sample was expected to exhibit change over time. Effect sizes were also computed. In study 2, the study 1 results were cross-validated in a second sample with recent SCI 1 year after baseline measurement. Study 2 also compared the SCI-FI/C measures' responsiveness to that of the Self-reported Functional Measure (SRFM) and stratified results by injury diagnosis and completeness. MAIN OUTCOME MEASURES: The SCI-FI Basic Mobility/C, Self-care/C and Fine Motor/C item banks (study 1 and study 2); Self-reported Functional Measure SRFM (study 2 only). RESULTS: In study 1, changes in SCI-FI/C scores between baseline and 6-month follow-up were statistically significant (P<.01) for recently injured individuals. SCI-FI Basic Mobility/C, Self-care/C, and Fine Motor/C item banks demonstrated small to medium effect sizes in the recently injured sample. In the community-dwelling sample, all SCI-FI/C effects were negligible (ie, effect size<0.08). Study 2 results were similar to study 1. As expected, SCI-FI Basic Mobility/C and Self-care/C were responsive to change for all individuals in study 2, whereas the SCI-FI Fine Motor/C was responsive only for individuals with tetraplegia and incomplete paraplegia. The SRFM demonstrated a medium effect size for responsiveness (effect size=0.65). CONCLUSIONS: The SCI-FI Basic Mobility/C and Self-care/C banks demonstrate adequate sensitivity to change at 6 months and 1 year for all individuals with SCI, while the SCI-FI/C Fine Motor item bank is sensitive to change in individuals with tetraplegia or incomplete paraplegia. All SCI-FI/C banks demonstrate stability in a sample not expected to change. Results provide support for the use of these measures for research or clinical use.

Treatments that are perceived to be helpful for non-neuropathic pain after traumatic spinal cord injury: a multicenter cross-sectional survey.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: The objective of the study was to identify the treatments that people with traumatic spinal cord injury (SCI) used for their non-neuropathic pains (nonNeuPs) and how they subjectively rated the helpfulness of those treatments. SETTING: Six centers from the Spinal Cord Injury Model Systems. METHODS: Three hundred ninety one individuals who were at least 1-year post-traumatic SCI were enrolled. A telephone survey was conducted for pharmacologic and non-pharmacologic treatments utilized in the last 12 months for each participant's three worst pains and the perceived helpfulness of each treatment for each pain. RESULTS: One hundred ninety (49%) participants reported at least one nonNeuP (Spinal Cord Injury Pain Instrument score < 2) in the previous 7 days. NSAIDs/aspirin, acetaminophen, opioids, and cannabinoids were the most commonly used and helpful pharmacologic treatments for overall nonNeuP locations (helpful in 77-89% of treated pains). Body position adjustment, passive exercise, massage, resistive exercise, and heat therapy were reported as the most commonly used non-pharmacological treatments for nonNeuPs. Heat therapy, aerobic exercise, massage, and body position adjustment were the most helpful non-pharmacological treatments for overall nonNeuP locations (helpful in 71-80% of treated pains). Perceived helpfulness of treatments varied by pain locations, which may be due to different mechanisms underlying pains in different locations. CONCLUSIONS: Results of the study may help guide clinicians in selecting pain-specific treatments for nonNeuPs. The self-reported helpfulness of heat therapy, exercise, and massage suggests a possible direction for clinical trials investigating these treatments of nonNeuP while limiting the side effects accompanying pharmacologic treatments.

Long-Term Trigeminal Nerve Stimulation as a Treatment for Ocular Pain.

OBJECTIVES: Ocular pain symptoms (e.g., hypersensitivity to light and wind, "burning" sensations) can be debilitating and difficult to treat. Neuromodulatory therapies targeting sensory trigeminal and central pain pathways may help treat chronic ocular pain refractory to traditional therapies. The current study evaluates the long-term effects of a trigeminal neurostimulator (TNS) on ocular pain. MATERIALS AND METHODS: Retrospective review of 18 individuals at the Miami Veterans Affairs Eye Clinic with chronic, severe ocular pain who were prescribed and used TNS at home for ≥3 months. The primary outcome measures were 1) ocular symptom intensity over a 24-hour recall period (dryness, pain, light sensitivity, wind sensitivity, burning; rated on 0-10 scales) captured pre-TNS and at monthly follow-up intervals and 2) side effects. The frequency and duration of TNS was a secondary outcome measure. RESULTS: The mean age of the population (n = 18) was 57.5 years (range, 34-85 years) with a male majority (67%). Two individuals discontinued use due to lack of efficacy and one due to confounding health issues. Initial mean weekly frequency of TNS use was 3.7 ± 1.9 sessions of 25.8 min at month 1 and 2.7 ± 2.3 sessions of 28.0 min at month 6. At six months, pain intensity (↓ 31.4%), light sensitivity (↓ 36.3%), wind sensitivity (↓ 32.6%), and burning sensation (↓ 53.9%) were all decreased compared to baseline (p < 0.01 for all); greater decreases in ocular pain were noted in individuals with migraine (n = 10) than those without migraine (n = 8). No significant change was noted in mean dryness scores. Fifteen subjects experienced sedation with TNS use, persisting throughout the follow-up visits. No other adverse effects were communicated by any subjects. CONCLUSION: Our study suggests TNS is a safe, adjunctive treatment option in individuals with severe, chronic ocular pain. Individuals demonstrated gradual, continual improvement in pain symptoms over time within a multimodal approach.

Oral Gabapentinoids and Nerve Blocks for the Treatment of Chronic Ocular Pain.

PURPOSE: There is a recognition that nerve dysfunction can contribute to chronic ocular pain in some individuals. However, limited data are available on how to treat individuals with a presumed neuropathic component to their ocular pain. As such, the purpose of this study was to examine the efficacy of our treatment approaches to this entity. METHODS: A retrospective review of treatments and outcomes in individuals with chronic ocular pain that failed traditional therapies. RESULTS: We started eight patients on an oral gabapentinoid (gabapentin and/or pregabalin) as part of their pain regimen (mean age 46 years, 50% women). Two individuals reported complete ocular pain relief with a gabapentinoid, in conjunction with their topical and oral medication regimen. Three individuals noted significant improvements, one slight improvement, and two others no improvement in ocular pain with gabapentin or pregabalin. We performed periocular nerve blocks (4 mL of 0.5% bupivacaine mixed with 1 mL of 80 mg/mL methylprednisolone acetate) targeting the periocular nerves (supraorbital, supratrochlear, infratrochlear, and infraorbital) in 11 individuals (mean age 54 years, 36% women), 10 of whom had previously used a gabapentinoid without ocular pain improvement. Seven individuals experienced pain relief after nerve blocks that lasted from hours to months and four failed to benefit. Five of the individuals who experienced pain relief underwent repeat nerve blocks, weeks to months later. CONCLUSIONS: Approaches used to treat chronic pain outside the eye can be applied to ocular pain that is not responsive to traditional therapies.

Transcutaneous Electrical Nerve Stimulation for the Long-Term Treatment of Ocular Pain.

PURPOSE: Ocular pain is a debilitating condition that is challenging to treat as therapies that target the ocular surface are often ineffective. We previously reported a short-term reduction in ocular pain after one periocular transcutaneous electrical nerve stimulation (TENS) session. The current study aims to elucidate the long-term effect of TENS on ocular pain. MATERIALS AND METHODS: Fourteen individuals with eye pain were identified as candidates for a TENS device (RS Medical, Vancouver) for home use after a successful trial in clinic between February 2018 and July 2019 at the Miami Veterans Administration Hospital or University of Miami. Ten of the 14 patients were included in this retrospective review, based on the inclusion of receiving and using the device for a minimum of three months. The median age of the ten patients was 47.5 years, range 32-73 years, and eight were male. The main outcome measures were 1) frequency of long-term integration of TENS into ocular pain management and 2) patient reported ocular pain intensity (0-10) pre- vs. post-treatment. RESULTS: Patients reported an initial median use of the device 14.0 times per week and over time reducing the frequency to 3.0 times per week. All reported that the TENS unit was successfully incorporated into their ocular pain management routine for at least three months (median duration of use 6.5 months, range 3-14 months). Nine of ten patients reported subjective pain reduction with use of the TENS device at home. Overall, pain intensity decreased by approximately 27.4% (mean rank = 5.6, Z = -2.1, p = 0.02) post- vs. pre-treatment. No adverse events associated with TENS were reported in any patient. CONCLUSION: Our preliminary data suggest that TENS can be integrated into the long-term management of ocular pain with improvements in overall pain intensity.

Relationship Between Hispanic Nativity, Residential Environment, and Productive Activity Among Individuals With Traumatic Brain Injury: A TBI Model Systems Study.

OBJECTIVE: To examine the influence of nativity and residential characteristics on productive activity among Hispanics at 1 year after traumatic brain injury (TBI). SETTING: Acute rehabilitation facilities and community follow-up. PARTICIPANTS: A total of 706 Hispanic individuals in the TBI Model Systems National Database. DESIGN: Secondary data analysis from a multicenter longitudinal cohort study. MAIN MEASURES: Nativity (foreign born or US native), productive activity derived from interview questions regarding employment status, and other demographic information. Census data were extracted by zip code to represent residential characteristics of aggregate household income and proportion of foreign language speakers (FLS). RESULTS: Among foreign-born individuals with TBI, those living in an area with a higher proportion of FLS were 2.8 times more likely to be productive than those living in areas with a lower proportion of FLS. Among individuals living in an area with a lower proportion of FLS, US-born Hispanics were 2.7 times more likely to be productive compared with Hispanic immigrants. CONCLUSION: The relationship between nativity and productive activity at 1 year post-TBI was moderated by the residential proportion of FLS. Findings underscore the importance of considering environmental factors when designing vocational rehabilitation interventions for Hispanics after TBI.

Longitudinal Examination of Resilience After Traumatic Brain Injury: A Traumatic Brain Injury Model Systems Study.

OBJECTIVES: To evaluate (1) the trajectory of resilience during the first year after a moderate-severe traumatic brain injury (TBI); (2) factors associated with resilience at 3, 6, and 12 months postinjury; and (3) changing relationships over time between resilience and other factors. DESIGN: Longitudinal analysis of an observational cohort. SETTING: Five inpatient rehabilitation centers. PARTICIPANTS: Patients with TBI (N=195) enrolled in the resilience module of the TBI Model Systems study with data collected at 3-, 6-, and 12-month follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Connor-Davidson Resilience Scale. RESULTS: Initially, resilience levels appeared to be stable during the first year postinjury. Individual growth curve models were used to examine resilience over time in relation to demographic, psychosocial, and injury characteristics. After adjusting for these characteristics, resilience actually declined over time. Higher levels of resilience were related to nonminority status, absence of preinjury substance abuse, lower anxiety and disability level, and greater life satisfaction. CONCLUSIONS: Resilience is a construct that is relevant to understanding brain injury outcomes and has potential value in planning clinical interventions.

Obesity and Overweight Problems Among Individuals 1 to 25 Years Following Acute Rehabilitation for Traumatic Brain Injury: A NIDILRR Traumatic Brain Injury Model Systems Study.

OBJECTIVE: Examine the prevalence of weight classifications and factors related to obesity/overweight among persons 1 to 25 years following traumatic brain injury (TBI) using the Traumatic Brain Injury Model Systems national database. DESIGN: Multicenter, cross-sectional, observational design. SETTING: Traumatic Brain Injury Model Systems inpatient rehabilitation facilities. PARTICIPANTS: Persons (N = 7287) 1, 2, 5, 10, 15, 20, or 25 years after TBI who required inpatient acute rehabilitation. MAIN OUTCOME MEASURES: Body mass index, demographic characteristics, functional, health, satisfaction with life, and global outcomes. RESULTS: Overall postinjury weight prevalence rates were 23% obese, 36% overweight, 39% normal, and 3% underweight. Higher rates for obesity and overweight problems were associated with increasing time since injury. Younger (18-19 years) and older (80+ years) age, those in a vegetative state, and those reporting excellent health were less likely to be obese. Individuals with a history of hypertension, heart failure, or diabetes were more likely to be obese. CONCLUSIONS: Being obese or overweight presents a health risk in the years following rehabilitation for TBI. The findings support the need for longitudinal studies and highlight the advisability of monitoring weight and promoting healthy lifestyle behaviors over time in survivors of TBI.

Race/Ethnicity and Retention in Traumatic Brain Injury Outcomes Research: A Traumatic Brain Injury Model Systems National Database Study.

OBJECTIVE: To investigate the contribution of race/ethnicity to retention in traumatic brain injury (TBI) research at 1 to 2 years postinjury. SETTING: Community. PARTICIPANTS: With dates of injury between October 1, 2002, and March 31, 2013, 5548 whites, 1347 blacks, and 790 Hispanics enrolled in the Traumatic Brain Injury Model Systems National Database. DESIGN: Retrospective database analysis. MAIN MEASURE: Retention, defined as completion of at least 1 question on the follow-up interview by the person with TBI or a proxy. RESULTS: Retention rates 1 to 2 years post-TBI were significantly lower for Hispanic (85.2%) than for white (91.8%) or black participants (90.5%) and depended significantly on history of problem drug or alcohol use. Other variables associated with low retention included older age, lower education, violent cause of injury, and discharge to an institution versus private residence. CONCLUSIONS: The findings emphasize the importance of investigating retention rates separately for blacks and Hispanics rather than combining them or grouping either with other races or ethnicities. The results also suggest the need for implementing procedures to increase retention of Hispanics in longitudinal TBI research.

Epidemiology of Comorbid Conditions Among Adults 50 Years and Older With Traumatic Brain Injury.

OBJECTIVES: Aging individuals with traumatic brain injury (TBI) experience multiple comorbidities that can affect recovery from injury. The objective of this study was to describe the most commonly co-occurring comorbid conditions among adults 50 years and older with TBI. SETTING: Level I Trauma centers. PARTICIPANTS: Adults 50 years and older with moderate/severe TBI enrolled in the TBI-Model Systems (TBI-MS) from 2007 to 2014 (n = 2134). DESIGN: A TBI-MS prospective cohort study. MAIN MEASURES: International Classification of Disease-9th Revision codes collapsed into 45 comorbidity categories. Comorbidity prevalence estimates and trend analyses were conducted by age strata (50-54, 55-64, 65-74, 75-84, ≥85 years). A dimension reduction method, Treelet Transform, classified clusters of comorbidities that tended to co-occur. RESULTS: The 3 most commonly occurring comorbid categories were hypertensive disease (52.6/100 persons), other diseases of the respiratory system (51.8/100 persons), and fluid component imbalances (43.7/100 persons). Treelet Transform classified 3 clusters of comorbid codes, broadly classified as (1) acute medical diseases/infections, (2) chronic conditions, and (3) substance abuse disorders. CONCLUSION: This study provides valuable insight into comorbid conditions that co-occur among adults 50 years and older with TBI and provides a foundation for future studies to explore how specific comorbidities affect TBI recovery.

The Association of Dry Eye Symptom Severity and Comorbid Insomnia in US Veterans.

PURPOSE: To investigate the association between dry eye (DE) and insomnia symptom severity. METHODS: Cross-sectional study of 187 individuals seen in the Miami Veterans Affairs eye clinic. An evaluation was performed consisting of questionnaires regarding insomnia (insomnia severity index [ISI]) and DE symptoms, including ocular pain, followed by a comprehensive ocular surface examination. Using a two-step cluster analysis based on intensity ratings of ocular pain, the patient population was divided into two groups (high and low ocular pain groups: HOP and LOP). A control group was ascertained at the same time from the same clinic as defined by no symptoms of DE (Dry Eye Questionnaire 5 [DEQ5], <6). The main outcome measure was the frequency of moderate or greater insomnia in the DE groups. RESULTS: The mean age of the study sample was 63 years, and 93% were male. All insomnia complaints were rated higher in the HOP group compared with the LOP and control groups (P<0.0005). Most (61%) individuals in the HOP group experienced insomnia of at least moderate severity (ISI≥15) compared with the LOP (41%) and control groups (18%) (P<0.0005). Black race (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.2-6.0; P=0.02), depression severity (OR, 1.2; 95% CI, 1.1-1.3; P<0.0005), and DE symptom severity (DEQ5; OR, 1.1; 95% CI, 1.01-1.2; P=0.03) were significantly associated with clinical insomnia (ISI≥15) after controlling for potential confounders. CONCLUSIONS: After adjusting for demographics and medical comorbidities, we show that DE symptom severity is positively associated with insomnia severity.

Evidence that Dry Eye Represents a Chronic Overlapping Pain Condition.

Abstract: Recent data suggest that corneal somatosensory dysfunction may be the underlying cause of severe dry eye symptoms in the absence of ocular surface pathology seen in a subset of patients diagnosed with "dry eye syndrome." This subset of patients tends to demonstrate a unique constellation of symptoms that are persistent, more severe, and generally respond poorly to current dry eye therapies targeting inadequate or dysfunctional tears. A growing body of literature suggests that symptoms in these patients may be better characterized as neuropathic ocular pain rather than dry eye. In these patients, dry eye symptoms are often associated with numerous comorbid pain conditions and evidence of central pain processing abnormalities, where eye pain is just one of multiple overlapping peripheral manifestations. In this review, we discuss the concept and potential mechanisms of chronic overlapping pain conditions as well as evidence for considering neuropathic ocular pain as one of these overlapping pain conditions.

Characteristics of Ocular Pain Complaints in Patients With Idiopathic Dry Eye Symptoms.

OBJECTIVE: The purpose of this study was to examine the severity and quality of ocular pain complaints in patients with dry eye symptoms. METHODS: Subjects with clinically relevant dry eye symptoms (dryness, discomfort, tearing) of unknown origin seen in the Miami Veterans Affairs eye clinic were administered questionnaires for dry eye symptoms and ocular pain and underwent a standardized ocular examination. Qualities and severity ratings of ocular pain in subjects with idiopathic dry eye were compared with similar measures from published data in other chronic pain populations. RESULTS: The study sample consisted of 154 subjects, of which 91% were men and ranged in age from 27 to 89 (mean age=61). Fifty-three percent of participants reported an average ocular pain of at least moderate intensity (numerical rating scale≥4), with specific characteristics (i.e., "burning" spontaneous pain) reported at frequencies comparable to prevalent chronic neuropathic pain syndromes as reported in the literature. Significant correlations were found between ocular pain metrics and dry eye symptom severity scores (r=0.57-0.66). Dry eye signs, however, did not generally correlate with ocular pain severity. CONCLUSIONS: A significant proportion of subjects with idiopathic dry eye symptoms reported moderate or greater ocular pain intensity, with most endorsing descriptors commonly used by patients with nonocular neuropathic pain conditions. Identifying subgroups of dry eye patients based on the presence and characteristics of ocular pain complaints may improve dry eye subclassification and better individualize treatment strategies.

Burning Eye Syndrome: Do Neuropathic Pain Mechanisms Underlie Chronic Dry Eye?

OBJECTIVE: Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This disorder may also involve neuroplasticity in response to neuronal injury. This review will emphasize the key characteristics of dry eye pain and its pathologic mechanisms, making the argument that a subset of dry eye represents a neuropathic pain disorder of the eye, more appropriately called "burning eye syndrome." METHODS: A literature review was conducted using a PubMed search focusing on dry eye, corneal nociception, and neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic ocular pain as related to dry eye were summarized. RESULTS: We found that there is a discordance between ocular pain and dryness on the ocular surface. Although tear dysfunction may be one of the initial insults, its persistence may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic pain transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. CONCLUSION: Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome."