What’s new in dry eye disease diagnosis? Current advances and challenges [version 1; referees: 3 approved]

Dry eye disease (DED) is a commonly encountered condition in general ophthalmology practice and imparts a significant socioeconomic burden. Despite its prevalence, there remain challenges regarding its diagnosis and management. A major reason behind these challenges is the fact that DED represents an umbrella term that encompasses many different underlying conditions and pathophysiological mechanisms. The purpose of this article is to highlight aspects of DED pathophysiology and focus on targeted diagnostic and therapeutic approaches to this multifactorial, chronic condition

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 \u3c 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 \u3c 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 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

Transient band keratopathy associated with ocular inflammation and systemic hypercalcemia

Anat Galor, Henry A Leder, Jennifer E Thorne, James P DunnThe Wilmer Eye Institute, Department of Ophthalmology, the Johns Hopkins University School of MedicinePurpose: To report a case of visually significant band keratopathy associated with ocular inflammation and systemic hypercalcemia which markedly decreased in severity after treatment of these underlying factors.Methods: Retrospective case report.Results: A 53-year-old Asian female with granulomatous panuveitis in the left eye presented with diffuse band keratopathy through the central cornea. The serum calcium was elevated. The patient was treated with topical prednisolone acetate 1% and oral prednisone with marked improvement in inflammation. The band keratopathy lessened in severity with clearing of the central cornea and improvement in visual acuity.Conclusions: Early medical treatment of underlying factors may allow reversal of band keratopathy.Keywords: ocular inflammation, transient band keratopath

Dynamic assessment of the tear film muco-aqueous and lipid layers using a novel tear film imager (TFI)

Purpose The objective of the study was to assess a new technology, the tear film imager (TFI), which can dynamically image the muco-aqueous and lipid layers. Methods Prospective pilot case series of individuals with and without dry eye (DE). Two sequential images were obtained with the TFI. Measurements were assessed for reproducibility and compared with clinically derived DE metrics. Individuals were grouped into DE categories based on signs of DE. Results 49 patients participated in the study with a mean age of 58.8 years (SD 15.9) and a female majority (69%). Reproducibility of the muco-aqueous layer thickness (MALT) was excellent (r=0.88). MALT measurements significantly correlated with the Schirmer score (r=0.31). Lipid break up time (LBUT) as measured by the TFI significantly correlated with the clinical measure of tear break up time (TBUT) (r=0.73). MALT and LBUT were significantly thinner and shorter, respectively, in the DE groups (mild–moderate and severe) compared with the control group. When comparing TFI parameters to clinically assessed signs, sensitivity of the device was 87% and specificity was 88%. Conclusion The TFI is the first machine capable of reproducibly measuring muco-aqueous thickness in human subjects which correlates with Schirmer score. In parallel, it assesses other important aspects of tear film function which correlate with clinician assessed DE metrics

Racial Disparities in Quality-Adjusted Life-Years Associated With Diabetes and Visual Impairment

OBJECTIVE Compare differences in health-related quality of life among blacks and whites to examine if race, diabetes, and visual impairment (VI) present a triple disadvantage in terms of quality-adjusted life expectancy. RESEARCH DESIGN AND METHODS Data were analyzed from the 2000–2003 Medical Expenditure Panel Survey, a nationally representative survey that contains the EuroQol 5D (EQ-5D). The EQ-5D generates health utility values that provide a measure of the morbidity associated with various health states, such as having moderate or severe problems with mobility. The EQ-5D score can be linked with life expectancy data to calculate quality-adjusted life-years (QALYs), the number of years of optimal health an individual is expected to live. Multivariate analyses were conducted to estimate and compare differences in QALYs by diabetes status, VI status, and race. RESULTS Whites had a higher quality-adjusted life expectancy across all diabetes/VI comparisons. Overall, blacks with diabetes and VI had the fewest number of QALYs remaining (19.6 years), and whites with no impairment had the greatest number of QALYs remaining (31.6 years). Blacks with diabetes only had 1.7 fewer years of optimal health (fewer QALYs) than whites with diabetes. Within individuals with both diabetes and VI, however, this gap more than doubled, with blacks experiencing 3.5 fewer QALYs than whites. CONCLUSIONS Although efforts to target and reduce racial health disparities associated with diabetes appear to be effective, black communities may be contributing to a greater overall burden of illness given poorer infrastructure and less accommodation for disabilities such as VI

Intrinsic Disorder in BAP1 and Its Association with Uveal Melanoma.

BACKGROUND: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM. METHODS: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein-protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms. RESULTS: We show that BAP1\u27s structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value \u3c 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1\u27s intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p-value \u3c 1.0 × 10-16). CONCLUSION: These findings show that BAP1 contains IDPRs and an intricate PPI network. Mutations in UM that are associated with the BAP1 gene may alter the function of the IDPRs embedded into its structure. These findings develop the understanding of UM and may provide a target for potential novel therapies to treat this aggressive neoplasm

Botulinum toxin A decreases neural activity in pain-related brain regions in individuals with chronic ocular pain and photophobia

IntroductionTo examine the effect of botulinum toxin A (BoNT-A) on neural mechanisms underlying pain and photophobia using functional magnetic resonance imaging (fMRI) in individuals with chronic ocular pain.MethodsTwelve subjects with chronic ocular pain and light sensitivity were recruited from the Miami Veterans Affairs eye clinic. Inclusion criteria were: (1) chronic ocular pain; (2) presence of ocular pain over 1 week recall; and (3) presence of photophobia. All individuals underwent an ocular surface examination to capture tear parameters before and 4–6 weeks after BoNT-A injections. Using an event-related fMRI design, subjects were presented with light stimuli during two fMRI scans, once before and 4–6 weeks after BoNT-A injection. Light evoked unpleasantness ratings were reported by subjects after each scan. Whole brain blood oxygen level dependent (BOLD) responses to light stimuli were analyzed.ResultsAt baseline, all subjects reported unpleasantness with light stimulation (average: 70.8 ± 32.0). Four to six weeks after BoNT-A injection, unpleasantness scores decreased (48.1 ± 33.6), but the change was not significant. On an individual level, 50% of subjects had decreased unpleasantness ratings in response to light stimulation compared to baseline (“responders,” n = 6), while 50% had equivalent (n = 3) or increased (n = 3) unpleasantness (“non-responders”). At baseline, several differences were noted between responders and non-responders; responders had higher baseline unpleasantness ratings to light, higher symptoms of depression, and more frequent use of antidepressants and anxiolytics, compared to non-responders. Group analysis at baseline displayed light-evoked BOLD responses in bilateral primary somatosensory (S1), bilateral secondary somatosensory (S2), bilateral anterior insula, paracingulate gyrus, midcingulate cortex (MCC), bilateral frontal pole, bilateral cerebellar hemispheric lobule VI, vermis, bilateral cerebellar crus I and II, and visual cortices. BoNT-A injections significantly decreased light evoked BOLD responses in bilateral S1, S2 cortices, cerebellar hemispheric lobule VI, cerebellar crus I, and left cerebellar crus II. BoNT-A responders displayed activation of the spinal trigeminal nucleus at baseline where non-responders did not.DiscussionBoNT-A injections modulate light-evoked activation of pain-related brain systems and photophobia symptoms in some individuals with chronic ocular pain. These effects are associated with decreased activation in areas responsible for processing the sensory-discriminative, affective, dimensions, and motor responses to pain

Why Internists Should Care About Dry Eye Disease

Dry eye disease (DED) has been diagnosed and managed under the purview of the eye care professional, with internists typically not paying much attention to the condition [...]