Early detection of malignant and pre-malignant peripheral nerve tumors using cell-free DNA fragmentomics.

Early detection of neurofibromatosis type 1 (NF1) associated peripheral nerve sheath tumors (PNST) informs clinical decision-making, potentially averting deadly outcomes. Here, we describe a cell-free DNA (cfDNA) fragmentomic approach which distinguishes non-malignant, pre-malignant and malignant forms of NF1 PNST. Using plasma samples from a novel cohort of 101 NF1 patients and 21 healthy controls, we validated that our previous cfDNA copy number alteration (CNA)-based approach identifies malignant peripheral nerve sheath tumor (MPNST) but cannot distinguish among benign and premalignant states. We therefore investigated the ability of fragment-based cfDNA features to differentiate NF1-associated tumors including binned genome-wide fragment length ratios, end motif analysis, and non-negative matrix factorization deconvolution of fragment lengths. Fragmentomic methods were able to differentiate pre-malignant states including atypical neurofibromas (AN). Fragmentomics also adjudicated AN cases suspicious for MPNST, correctly diagnosing samples noninvasively, which could have informed clinical management. Overall, this study pioneers the early detection of malignant and premalignant peripheral nerve sheath tumors in NF1 patients using plasma cfDNA fragmentomics. In addition to screening applications, this novel approach distinguishes atypical neurofibromas from benign plexiform neurofibromas and malignant peripheral nerve sheath tumors, enabling more precise clinical diagnosis and management.

The environment and dry eye-manifestations, mechanisms, and more.

Dry eye disease (DED) is a multifactorial condition that often presents with chronic symptoms of pain (that can be characterized as "dryness," "burning," and "irritation," to name a few) and/or fluctuating or poor-quality vision. Given its multifactorial nature, several pathophysiologic mechanisms have been identified that can underlie symptoms, including tear film, ocular surface, and/or corneal somatosensory nerve abnormalities. Research has focused on understanding how environmental exposures can increase the risk for DED flares and negatively impact the tear film, the ocular surface, and/or nerve health. Given that DED is a common condition that negatively impacts physical and mental functioning, managing DED requires multiple strategies. These can include both medical approaches and modulating adverse environmental conditions, the latter of which may be a cost-effective way to avoid DED flares. Thus, an understanding of how environmental exposures relate to disease is important. This Review summarizes research on the relationships between environmental exposures and DED, in the hope that this information will engage healthcare professionals and patients to consider environmental manipulations in their management of DED.

Neuropathic ocular surface pain: Emerging drug targets and therapeutic implications.

INTRODUCTION: Dysfunction at various levels of the somatosensory system can lead to ocular surface pain with a neuropathic component. Compared to nociceptive pain (due to noxious stimuli at the ocular surface), neuropathic pain tends to be chronic and refractory to therapies, making it an important source of morbidity in the population. An understanding of the options available for neuropathic ocular surface pain, including new and emerging therapies, is thus an important topic. AREAS COVERED: This review will examine studies focusing on ocular surface pain, emphasizing those examining patients with a neuropathic component. Attention will be placed toward recent (after 2017) studies that have examined new and emerging therapies for neuropathic ocular surface pain. EXPERT OPINION: Several therapies have been studied thus far, and continued research is needed to identify which individuals would benefit from specific therapies. Gaps in our understanding exist, especially with availability of in-clinic diagnostics for neuropathic pain. A focus on improving diagnostic capabilities and researching gene-modulating therapies could help us to provide more specific mechanism-based therapies for patients. In the meantime, continuing to uncover new modalities and examining which are likely to work depending on pain phenotype remains an important short-term goal.

A multinational study of acute and long-term outcomes of Type 1 galactosemia patients who carry the S135L (c.404C > T) variant of GALT.

Patients with galactosemia who carry the S135L (c.404C > T) variant of galactose-1-P uridylyltransferase (GALT), documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L.

The reciprocal relationship between episodic memory and future thinking: How the outcome of predictions is subsequently remembered.

Evidence suggests that memory is involved in making simulations and predictions about the future (i.e., future thinking), but less work has examined how the outcome of those predictions (whether events play out as predicted or expected) subsequently affects episodic memory. In this investigation, we examine whether memory is better for outcomes that are consistent with predictions, or whether memory is enhanced for outcomes that are inconsistent with predictions, after the predicted event occurs. In this experiment, participants learned a core trait associated with social targets (e.g., high in extroversion), before making predictions about behaviors targets would perform. Participants then were shown behaviors the social targets actually performed (i.e., prediction outcome), which was either consistent or inconsistent with predictions. After that, participants completed a memory test (recognition; recall) for the prediction outcomes. For recognition, the results revealed better memory for outcomes that were consistent with traits associated with targets (i.e., trait-consistent outcomes), compared to outcomes that were inconsistent (i.e., trait-inconsistent outcomes). Finding a memory advantage for trait-consistent outcomes suggests that outcomes that are in line with the contents of memory (e.g., what one knows; schemas) are more readily remembered than those that are inconsistent with memory, which may reflect an adaptive memory process. For recall, memory did not differ between trait-consistent and trait-inconsistent outcomes. Altogether, the results of this experiment advance understanding of the reciprocal relationship between episodic memory and future thinking and show that outcome of predictions has an influence on subsequent episodic memory, at least as measured by recognition.

DAB-quant: An open-source digital system for quantifying immunohistochemical staining with 3,3'-diaminobenzidine (DAB).

Here, we describe DAB-quant, a novel, open-source program designed to facilitate objective quantitation of immunohistochemical (IHC) signal in large numbers of tissue slides stained with 3,3'-diaminobenzidine (DAB). Scanned slides are arranged into separate folders for negative controls and test slides, respectively. Otsu's method is applied to the negative control slides to define a threshold distinguishing tissue from empty space, and all pixels deemed tissue are scored for normalized red minus blue (NRMB) color intensity. Next, a user-defined tolerance for error is applied to the negative control slides to set a NRMB threshold distinguishing stained from unstained tissue and this threshold is applied to calculate the fraction of stained tissue pixels on each test slide. Results are recorded in a spreadsheet and pseudocolor images are presented to document how each pixel was categorized. Slides can be analyzed in full, or sampled using small boxes scattered randomly and automatically across the tissue area. Quantitation of sampling boxes enables faster processing, reveals the degree of heterogeneity of signal, and enables exclusion of problem areas on a slide, if needed. This system should prove useful for a broad range of applications. The code, usage instructions, and sample data are freely and publicly available on GitHub (https://github.com/sarafridov/DAB-quant) and at protocols.io (dx.doi.org/10.17504/protocols.io.dm6gpb578lzp/v1).

Acute and early developmental outcomes of children with Duarte galactosemia.

A recent study demonstrated that children with Duarte galactosemia (DG) do not show increased prevalence of detectable developmental complications when 6-12 years old. However, that study left unanswered whether infants with DG might be at increased risk for acute problems when drinking milk or whether children with DG younger than 6 years might show increased prevalence of perhaps transient developmental challenges. Here, we have addressed both of these questions by analyzing parent/guardian-reported data collected retrospectively for 350 children, 206 with DG and 144 unaffected siblings from the same families. The variables analyzed included whether each child had experienced (1) acute complications in infancy, (2) early intervention services when <3 years old, and/or (3) special educational services when 3-5 years old. For each case-control comparison, or case-by-diet comparison, we used logistic regression that included the following potential covariates: age, sex, race, family income, and parent education, as appropriate. We found that none of the three outcome variables tested showed significant differences between cases and controls, or among cases as a function of galactose exposure in infancy. To the limits of our study, we therefore conclude that regardless of whether a child with DG drinks milk or low-galactose formula as an infant, they are not at increased risk for acute complications or early childhood developmental challenges that require intervention.

Prevalence and risk factors for chalazion in an older veteran population.

BACKGROUND: Chalazia are common inflammatory eyelid lesions, but their epidemiology remains understudied. This retrospective case-control study examined the prevalence, risk factors and geographic distribution of chalazia in a large veteran population. METHODS: Data on all individuals seen at a Veterans Affairs (VA) clinic between October 2010 and October 2015 were extracted from the VA health database. Subjects were grouped based on International Classification of Diseases, Ninth Revision (ICD-9) code for chalazion. Univariable logistic regression modelling was used to identify clinical and demographic factors associated with chalazion presence, followed by multivariable modelling to examine which factors predicted risk concomitantly. All cases were mapped across the continental US using geographic information systems modelling to examine how prevalence rates varied geographically. RESULTS: Overall, 208 720 of 3 453 944 (6.04%) subjects were diagnosed with chalazion during the study period. Prevalence was highest in coastal regions. The mean age of the population was 69.32±13.9 years and most patients were male (93.47%), white (77.13%) and non-Hispanic (93.72%). Factors associated with chalazion risk included smoking (OR=1.12, p<0.0005), conditions of the tear film (blepharitis (OR=4.84, p<0.0005), conjunctivitis (OR=2.78, p<0.0005), dry eye (OR=3.0, p<0.0005)), conditions affecting periocular skin (eyelid dermatitis (OR=2.95, p<0.0005), rosacea (OR=2.50, p<0.0005)), allergic conditions (history of allergies (OR=1.56, p<0.0005)) and systemic disorders (gastritis (OR=1.54, p<0.0005), irritable bowel syndrome (OR=1.45, p<0.0005), depression (OR=1.35, p<0.0005), anxiety (OR=1.31, p<0.0005)). These factors remained associated with chalazion risk when examined concomitantly. CONCLUSION: Periocular skin, eyelid margin and tear film abnormalities were most strongly associated with risk for chalazion. The impact of environmental conditions on risk for chalazion represents an area in need of further study.

Neonatal GALT gene replacement offers metabolic and phenotypic correction through early adulthood in a rat model of classic galactosemia.

Classic galactosemia (CG) results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Despite early detection by newborn screening and lifelong dietary restriction of galactose, most patients grow to experience a range of long-term complications. Recently, we developed and characterized a GALT-null rat model of CG and demonstrated that AAV9-hGALT, administered by tail vein injection to neonatal pups, dramatically improved plasma, liver, and brain galactose metabolites at 2 weeks posttreatment. Here we report a time-course study of GALT restoration in rats treated as neonates with scAAV9-hGALT and harvested at 8, 14, 30, and 60 days. Cohorts of rats in the two older groups were weaned to diets containing either 1% or 3% of calories from galactose. As expected, GALT activity in all treated animals peaked early and then diminished over time, most notably in liver, ostensibly due to dilution of the nonreplicating episomal vector as transduced cells divided. All treated rats showed dramatic metabolic rescue through 1 month, and those weaned to the lower galactose diet showed continued strong metabolic rescue into adulthood (2 months). Prepubertal growth delay and cataracts were both partially rescued by treatment. Finally, we found that UDP glucose pyrophosphorylase (UGP), which offers a metabolic bypass around missing GALT, was 3-fold more active in brain samples from adult rats than from young pups, offering a possible explanation for the improved ability of older GALT-null rats to metabolize galactose. Combined, these results document promising metabolic and phenotypic efficacy of neonatal GALT gene replacement in a rat model of classic galactosemia.

Heat Exposure and Multiple Sclerosis-A Regional and Temporal Analysis.

Multiple sclerosis (MS) is a neurological disorder that progressively distorts the myelination of axons within the central nervous system (CNS). Increased core body temperature or metabolism as a result of exercise are common causes of short-term exacerbations of neurological symptoms in MS. About 60-80% of patients with MS experience a worsening of their symptoms when exposed to heat. In comparison, less data are available on the relationship between ambient meteorological conditions (e.g., temperature and relative humidity (RH)) and fluctuations in such variables in relation to MS symptoms. Thus, this study examined associations between time-lagged exposure to meteorological conditions and risk of a clinic visit due to MS among US veterans between 2010 and 2013. This study leveraged data from the Veterans Affairs (VA) and National Climactic Data Center (NCDC) for the continental US, partitioned into eight climate zones. We used a case crossover design to assess the risk of a MS clinic visit with respect to several meteorological conditions. Location-specific time-lagged daily (ambient) exposure to temperature, RH, and temperature variations (standard deviation (SD) of temperature) were computed (up to 30 days) for each case (i.e., day of MS visit) and control (a randomly assigned date ± 90-270 days prior to visit). Statistical analyses were conducted to examine independent associations between the selected meteorological conditions and risk of MS visits at the national and regional levels. A total of 533,066 patient visits received a MS diagnosis (International Classifications of Diseases (ICD)-9 code = 340). The Northeast (NE) and Upper Midwest (UMW) regions reported the highest frequency of clinic visits due to MS. Clinic visits were 9% more likely to occur in the spring, summer, and fall months (March-October) than in the winter (OR = 1.089; 95% CI = 1.076-1.103; p < 0.01). In the univariate analyses, the SD of temperature, temperature, and temperature-RH interaction were positively associated with an elevated risk of a MS clinic visit, while the RH was negatively associated with the risk for a clinic visit. In multivariate analyses, the strongest association of a MS clinic visit was observed with the SD of the temperature (OR = 1.012; 95% CI 1.008-1.017; p < 0.01). These associations between MS clinic visits and meteorological conditions varied across climate regions, with the strongest associations being observed in the LMW, UMW, DSW, and NE zones. The SD of the temperature was again the strongest associated predictor when examined regionally. Temperature variations and temperature-RH interactions (a proxy of the heat index) showed significant associations with MS clinic visits. These associations varied across climate regions when examined geographically. Our findings have implications for the management of MS in severe or recurrent cases, especially considering the impending changes in the daily temperature variations and intensity of the heatwaves expected with the intensification of global warming.

The Role of Temperature Change, Ambient Temperature, and Relative Humidity in Allergic Conjunctivitis in a US Veteran Population.

PURPOSE: Studies have implicated temperature and humidity in the pathogenesis of allergic conjunctivitis (AC), as these conditions facilitate air particulate and aeroallergen dispersion and tear film instability. Research also suggests that variation in temperature is associated with risk of asthma, but similar data are limited for AC. This study examined associations between several meteorologic conditions, including temperature variation, and AC visit risk. DESIGN: Retrospective, case-crossover study. METHODS: Data on individuals diagnosed with AC (via International Classification of Diseases-Ninth Edition [ICD-9]) at a Veterans Affairs clinic from January 2010-December 2013 was extracted. Local climate data were obtained from the National Climactic Data Center. Utilizing a case-crossover design, all cases were assigned a random control date 90-250 days prior to diagnosis. Daily time-lagged exposures were computed for 30-day lags. The associations between temperature, temperature variation (standard deviation [SD] of temperature), relative humidity (RH), and temperature-RH interaction with visit risk were examined via multivariate logistic regression models both at the national level and across domestic climate regions. RESULTS: Overall, 74,951 subjects made 116,162 visits for AC. Prevalence was highest in spring (>10% April-May) in the Northeast (NE) and Southeast (SE) (>15%), and lowest in winter (<6.1% December-February) in the Pacific Northwest (PNW) (<5%). AC visit risk was positively associated with temperature (OR 1.028, P < .001), SD of temperature (OR 1.054, P < .01), and temperature-RH interaction (OR 1.0003, P < .01), whereas it was negatively associated with RH (OR 0.998, P < .001). Regionally, the PNW, NE, and Lower Midwest (LMW) accounted for the strongest associations. CONCLUSION: Temperature, temperature variation, and RH associated with AC visit risk. Observed associations were strongest in northern regions, like the PNW.

Alternative therapies for dry eye disease.

PURPOSE OF REVIEW: Dry eye disease (DED) is a multifactorial disease affecting approximately 5-50% of individuals in various populations. Contributors to DED include, but are not limited to, lacrimal gland hypofunction, meibomian gland dysfunction (MGD), ocular surface inflammation, and corneal nerve dysfunction. Current DED treatments target some facets of the disease, such as ocular surface inflammation, but not all individuals experience adequate symptom relief. As such, this review focuses on alternative and adjunct approaches that are being explored to target underlying contributors to DED. RECENT FINDINGS: Neuromodulation, stem cell treatments, and oral royal jelly have all been studied in individuals with DED and lacrimal gland hypofunction, with promising results. In individuals with MGD, devices that provide eyelid warming or intense pulsed light therapy may reduce DED symptoms and signs, as may topical Manuka honey. For those with ocular surface inflammation, naturally derived anti-inflammatory agents may be helpful, with the compound trehalose being farthest along in the process of investigation. Nerve growth factor, blood-derived products, corneal neurotization, and to a lesser degree, fatty acids have been studied in individuals with DED and neurotrophic keratitis (i.e. corneal nerve hyposensitivity). Various adjuvant therapies have been investigated in individuals with DED with neuropathic pain (i.e. corneal nerve hypersensitivity) including nerve blocks, neurostimulation, botulinum toxin, and acupuncture, although study numbers and design are generally weaker than for the other DED sub-types. SUMMARY: Several alternatives and adjunct DED therapies are being investigated that target various aspects of disease. For many, more robust studies are required to assess their sustainability and applicability.

Hand fine motor control in classic galactosemia.

Classic galactosemia (CG) is a rare inborn error of metabolism that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Despite early detection and rapid and lifelong dietary restriction of galactose, which is the current standard of care, most patients grow to experience a broad range of complications that can include motor difficulties. The goal of this study was to characterize hand fine motor control deficit among children and adults with classic galactosemia (CG). Specifically, we used Neuroglyphics software to collect digital Archimedes spiral drawings on a touch screen from 57 volunteers with CG (cases) and 80 controls. Hand fine motor control was scored as root mean square (RMS) of spirals drawn relative to an idealized template. Presence of tremor was defined as a peak in periodicity of changes in drawing speed or direction in the 4-8 Hz range. We observed a highly significant difference (P < .001) in RMS scores between cases and controls, with almost 51% of cases showing at least 1 of 4 spirals scoring outside the 95th percentile for controls. The corresponding prevalence for controls was 10%. Similarly, more than 35% of cases, and almost 14% of controls, showed at least 1 of 4 spirals with a tremor amplitude above the 95th % cutoff for controls. Our results both confirm and extend what is known about hand fine motor control deficit among children and adults with CG and establish digital assessment as a useful approach to quantify this outcome.

How Should Corneal Nerves be Incorporated Into the Diagnosis and Management of Dry Eye?

PURPOSE: a)Confocal microscopy and aethesiometry have allowed clinicians to assess the structural and functional integrity of corneal nerves in health and disease. This review summarizes literature on nerves in dry eye disease (DED) and discusses how this data can be applied to DED diagnosis and treatment. RECENT FINDINGS: b)Subjects with DED have a heterogenous symptom and sign profile along with variability in nerve structure and function. Most studies have reported lower nerve density and sensitivity in aqueous tear deficiency, while findings are more inconsistent for other DED subtypes. Examining nerve status, along with profiling symptoms and signs of disease, can help categorize subjects into disease phenotypes (structural and functional patterns) that exist under the umbrella of DED. This, in turn, can guide therapeutic decision-making. SUMMARY: c)Due to the heterogeneity in symptoms and signs of DED, corneal nerve evaluations can be valuable for categorizing individuals into disease sub-types and for guiding clinical decision making.

Differential Effects of Treatment Strategies in Individuals With Chronic Ocular Surface Pain With a Neuropathic Component.

Background: Dysfunction at the ocular system via nociceptive or neuropathic mechanisms can lead to chronic ocular pain. While many studies have reported on responses to treatment for nociceptive pain, fewer have focused on neuropathic ocular pain. This retrospective study assessed clinical responses to pain treatment modalities in individuals with neuropathic component ocular surface pain. Methods: 101 individuals seen at the University of Miami Oculofacial Pain Clinic from January 2015 to August 2021 with ≥3 months of clinically diagnosed neuropathic pain were included. Patients were subcategorized (postsurgical, post-traumatic, migraine-like, and laterality) and self-reported treatment outcomes were assessed (no change, mild, moderate, or marked improvement). One-way ANOVA (analysis of variance) was used to examine relationships between follow up time and number of treatments attempted with pain improvement, and multivariable logistic regression was used to assess which modalities led to pain improvement. Results: The mean age was 55 years, and most patients were female (64.4%) and non-Hispanic (68.3%). Migraine-like pain (40.6%) was most common, followed by postsurgical (26.7%), post-traumatic (16.8%) and unilateral pain (15.8%). The most common oral therapies were α2δ ligands (48.5%), the m common topical therapies were autologous serum tears (20.8%) and topical corticosteroids (19.8%), and the most common adjuvant was periocular nerve block (24.8%). Oral therapies reduced pain in post-traumatic (81.2%), migraine-like (73%), and unilateral (72.7%) patients, but only in a minority of postsurgical (38.5%) patients. Similarly, topicals improved pain in post-traumatic (66.7%), migraine-like (78.6%), and unilateral (70%) compared to postsurgical (43.7%) patients. Non-oral/topical adjuvants reduced pain in postsurgical (54.5%), post-traumatic (71.4%), and migraine-like patients (73.3%) only. Multivariable analyses indicated migraine-like pain improved with concomitant oral α2δ ligands and adjuvant therapies, while postsurgical pain improved with topical anti-inflammatories. Those with no improvement in pain had a shorter mean follow-up (266.25 ± 262.56 days) than those with mild (396.65 ± 283.44), moderate (652 ± 413.92), or marked improvement (837.93 ± 709.35) (p < 0.005). Identical patterns were noted for number of attempted medications. Conclusion: Patients with migraine-like pain frequently experienced pain improvement, while postsurgical patients had the lowest response rates. Patients with a longer follow-up and who tried more therapies experienced more significant relief, suggesting multiple trials were necessary for pain reduction.

Corneal Nerve Abnormalities in Ocular and Systemic Diseases.

The trigeminal nerve gives rise to the corneal subbasal nerve system, which plays a crucial role in sensations of touch, pain, and temperature and in ocular healing processes. Technological advancements in instruments, in particular in vivo confocal microscopy and aethesiometry, have allowed for the structural and functional evaluation of corneal nerves in health and disease. Through application of these technologies in humans and animal models, structural and functional abnormalities have been detected in several ocular and systemic disorders, including dry eye disease (DED), glaucoma, migraine, and fibromyalgia. However, studies across a number of conditions have found that structural abnormalities do not always relate to functional abnormalities. This review will discuss instruments used to evaluate corneal nerves and summarize data on nerve abnormalities in a number of ocular and systemic conditions. Furthermore, it will discuss potential treatments that can alleviate the main manifestations of nerve dysfunction, namely ocular surface pain and persistent epithelial defects.

Pregabalin Failed to Prevent Dry Eye Symptoms after Laser-Assisted in Situ Keratomileusis (LASIK) in a Randomized Pilot Study.

PURPOSE: Perioperative pregabalin administration has been found to reduce the risk of persistent pain after a variety of surgical procedures. However, this approach has not been tested in relation to eye surgery. As such, the purpose of this study was to evaluate whether perioperative pregabalin can reduce the presence of dry eye (DE) symptoms, including eye pain, six months after laser-assisted in situ keratomileusis (LASIK). METHODS: Prospective, masked, randomized single-center pilot study. Patients were treated with either pregabalin (oral solution of pregabalin 150 mg twice daily, first dose prior to surgery, continued for a total of 28 doses over 14 days) or placebo solution. The primary outcome was dry eye symptoms as measured by the Dry Eye Questionnaire 5 (DEQ-5). Secondary outcome measures included pain-related eye symptoms. RESULTS: In total, 43 individuals were enrolled in the study and randomized to pregabalin (n = 21) or placebo (n = 22). Of those, 42 individuals completed the final visit after six months of follow-up. Some differences were noted between the two groups at baseline, including a higher frequency of females in the pregabalin group. At 6-months, there were no significant differences in the percentage of patients with DE symptoms (DEQ5 ≥ 6, 57% vs. 33%, p = 0.14), DE symptom severity (DEQ5, 6.6 ± 5.0 vs. 4.5 ± 4.2, p = 0.14), ocular pain intensity (numerical rating scale, 1.10 ± 1.48 vs. 0.38 ± 0.97, p = 0.08), or neuropathic pain complaints (Neuropathic Pain Symptom Inventory-Eye, 2.81 ± 4.07 vs. 3.14 ± 5.85, p = 0.83) between the pregabalin and control groups. Ocular signs were likewise similar between the groups, and of note, did not correlate with DE symptoms. The strongest predictor of DE symptoms six months post-surgery was the presence of DE symptoms prior to surgery. CONCLUSIONS: Perioperative pregabalin did not reduce the frequency or severity of DE symptoms at a six month follow-up after LASIK in this small pilot study.

Dysfunctional Coping Mechanisms Contribute to Dry Eye Symptoms.

Dysfunctional coping behaviors, such as catastrophizing, have been implicated in pain severity and chronicity across several pain disorders. However, the impact of dysfunctional coping has not been examined under the context of dry eye (DE). This study evaluates relationships between catastrophizing and measures of DE, including pain severity and pain-related daily interference. The population consisted of patients seen at Miami Veterans Affairs eye clinic between April 2016 and October 2017. Patients filled out standardized questionnaires assessing symptoms of DE and eye pain, non-ocular pain, mental health, coping behaviors (Pain Catastrophizing Scale, PCS), and pain-related daily interference as a perceived impact on quality of life (Multidimensional Pain Inventory, Interference Subscale, MPI-Interference), and all patients underwent an ocular surface examination. In total, 194 patients participated, with a mean age of 58.8 ± 9.6 years, the majority being male, non-Hispanic, and black. PCS (catastrophizing) was correlated with DE symptom severity, including Dry-Eye Questionnaire 5 (DEQ5; r = 0.41, p < 0.0005), Ocular Surface Disease Index (OSDI; r = 0.40, p < 0.0005), and neuropathic-like eye pain (Neuropathic Pain Symptom Inventory-Eye (NPSI-Eye; r = 0.48, p < 0.0005). Most tear metrics, on the other hand, did not correlate with PCS. Linear regressions showed that PCS, non-ocular pain intensity, and number of pain conditions were significant predictors of DEQ5 (overall DE symptoms), while PCS and non-ocular pain intensity were predictors of NPSI-Eye scores, as were insomnia scores and analgesic use. In a separate analysis, PCS and DE symptoms (OSDI) associated with pain-related interference (MPI-Interference) along with non-ocular pain intensity, post-traumatic stress disorder (PTSD), number of pain conditions, and non-Hispanic ethnicity. These findings suggest that catastrophizing is not significantly related to signs of DE, but is strongly associated to pain-related symptoms of DE and daily interference due to pain.

Use of a preference-based measure of health (EQ-5D) in COPD and asthma.

BACKGROUND: EQ-5D is a generic preference-based measure of health that can help to understand the impact of asthma and chronic obstructive pulmonary disease (COPD). The purpose of this paper was to synthesize literature on the validity and reliability of EQ-5D use in studies of asthma and COPD, and estimate EQ-5D utility scores associated with stage of disease. METHODS: A structured search was conducted in EMBASE and MEDLINE (1988-2007) using keywords relevant to respiratory disease and EQ-5D. Original research studies in asthma or COPD that reported EQ-5D results and/or psychometric properties were included. RESULTS: Studies that reported psychometric properties supported the construct validity, test-retest reliability, and responsiveness of EQ-5D in asthma (seven studies) and COPD (nine studies), although some evidence of ceiling effects were observed in asthma studies. In asthma studies that reported summary scores (n=11), EQ-5D index-based scores ranged from 0.42 (SD 0.30) to 0.93 (SD not reported). In COPD studies (n=8), scores ranged from 0.52 (SD 0.16) to 0.84 (SD 0.15). While few asthma studies reported scores by severity level, sufficient studies in COPD were available to calculate pooled mean utility scores according to GOLD stage: stage I=0.74 (0.62-0.87), stage II=0.74 (0.66-0.83), stage III=0.69 (0.60-0.78) and stage IV=0.61 (0.44-0.77) (most severe). CONCLUSIONS: Evidence generally supported the validity and reliability of EQ-5D in asthma and COPD. Utility scores associated with COPD stage may be useful for modeling health outcomes in economic evaluations of treatments for COPD.