Project description:Tear proteins are potential biomarkers, drug targets, and even biotherapeutics. As a biotherapeutic, a recombinant tear protein might physiologically rescue the ocular surface when a deficiency is detected. Such a strategy pays more attention to the natural prosecretory and protective properties of the tear film and seeks to alleviate symptoms by addressing cause, rather than the current palliative, non-specific and temporary approaches. Only a handful of tear proteins appear to be selectively downregulated in dry eye, the most common eye disease. Lacritin and lipocalin-1 are two tear proteins selectively deficient in dry eye. Both proteins influence ocular surface health. Lacritin is a prosecretory mitogen that promotes basal tearing when applied topically. Levels of active monomeric lacritin are negatively regulated by tear tissue transglutaminase, whose expression is elevated in dry eye with ocular surface inflammation. Lipocalin-1 is the master lipid sponge of the ocular surface, without which residual lipids could interfere with epithelial wetting. It also is a carrier for vitamins and steroid hormones, and is a key endonuclease. Accumulation of DNA in tears is thought to be proinflammatory. Functions of these and other tear proteins may be influenced by protein-protein interactions. Here we discuss new advances in lacritin biology and provide an overview on lipocalin-1, and newly identified members of the tear proteome.
Project description:Objectives: To investigate the changes of dry eye-related clinical manifestations, ocular surface parameters, and tear inflammatory cytokines after upper blepharoplasty. Methods: Forty eyes of 20 who underwent upper blepharoplasty were divided into either the group with or the group without preexisting dry eye before upper blepharoplasty. Ocular Surface Disease Index (OSDI), Schirmer I test, tear meniscus height, lipid layer thickness, non-invasive tear break-up time (NIKBUT), fluorescein tear film break-up time (FBUT), corneal fluorescein staining, meibum expression, lid margin changes, and tear inflammatory cytokines were assessed preoperatively and at 1, 3, and 6 months postoperatively. Correlations between inflammatory cytokines and dry eye-related parameters were determined. Results: The OSDI scores increased significantly at 1 month (p = 0.040) and subsequently decreased to the preoperative levels at 6 months postoperatively in subjects with dry eye. First (f)-NIKBUT and FBUT were significantly shortened at 1, 3, and 6 months postoperatively in subjects with dry eye (f-NIKBUT: p <0.001, p = 0.010, p = 0.042; FBUT: p = 0.002, p = 0.005, p = 0.037, respectively), but were only shortened at 1 month (p = 0.028, p = 0.005) and returned to baseline levels at 6 months postoperatively in subjects without preexisting dry eye. A significant increasing trend of interleukin (IL)-6 was found in both dry eye and subjects without preexisting dry eye (p = 0.016, p = 0.008), while IL-8 and tumor necrosis factor alpha (TNF-α) were only found to be increased in subjects with dry eye postoperatively (p = 0.031, p = 0.031). The levels of IL-8 and TNF-α were positively correlated with OSDI scores (p = 0.046, p = 0.043, respectively) and negatively correlated with f-NIKBUT and FBUT (p = 0.026, p = 0.006, respectively). Conclusions: Upper blepharoplasty might increase the release of tear inflammatory cytokines and tear film instability that contribute to the development of postoperative dry eye in the early postoperative period and the changes most relieved in 6 months. Preexisting dry eye is a higher risk factor for worse and persistent ocular surface damage after upper blepharoplasty.
Project description:Objectives: To investigate the efficacy of laser acupuncture (LA) therapy in patients with dry eye disease (DED). Design: A two-center randomized controlled trial. Settings/Location: The Department of Ophthalmology, Chinese Medicine at the Kaohsiung Chang Gung Memorial Hospital, and the Sunming Eye Clinic in South Taiwan. Subjects: Fifty-nine participants ages 20 to 65 years were enrolled and randomly assigned to the experimental group (LA plus conventional treatment) or the sham control group (LA without laser output plus conventional treatment). Interventions: Subjects underwent LA treatment three times a week for 12 weeks. The subjects in the experimental group sequentially received 0.375 J of energy at each of the following acupoints: BL2, TE23, ST2, LI4, ST36, and GB37. Subjects in the control group received a sham LA treatment, without any laser output. Outcome Measures: The primary outcome measure was ocular surface disease index (OSDI). The secondary outcome measures included tear film breakup time (TFBUT), Schirmer-I test finding, and visual analog scale (VAS) score. Results: At 4 and 12 weeks after the first visit, the experimental group showed significant improvement of dry eye symptoms as measured by OSDI, TFBUT, Shirmer-I test, and VAS. Compared with the control group, the OSDI (7.23, p = 0.001) and TFBUT (-1.78, p = 0.001) significantly improved in the experimental group at 12 weeks of treatment. Conclusions: LA improved the symptoms and tear stability related to DED in conjunction with conventional treatment. The authors suggest that LA be considered a complementary therapy for DED when conventional treatment does not provide satisfactory effects. Trial Registration: ClinicalTrials.gov Identifier NCT03204903.
Project description:Dry eye disease (DED) is a multifactorial syndrome that can be caused by alteration in the quality or quantity of the precorneal tear film. It is considered one of the most common ocular conditions leading patients to seek eye care. The current method for diagnostic evaluations and follow-up examinations of DED is a combination of clinical signs and symptoms determined by clinical tests and questionnaires, respectively. The application of powerful omics technologies has opened new avenues toward analysis of subjects in health and disease. Metabolomics is a new emerging and complementary research discipline to all modern omics in the comprehensive analysis of biological systems. The identification of distinct metabolites and integrated metabolic profiles in patients can potentially inform clinicians at an early stage or during monitoring of disease progression, enhancing diagnosis, prognosis, and the choice of therapy. In ophthalmology, metabolomics has gained considerable attention over the past decade but very limited such studies have been reported on DED. This paper aims to review the application of tear metabolomics in DED.
Project description:PurposeTo assess the relationship between tear osmolarity and dry eye symptoms in patients with diabetes.Patients and methodsFifty patients with diabetes were enrolled. Demographic information and past medical history were recorded. Symptoms were assessed using the ocular surface disease index (OSDI). Tear osmolarity of each eye was measured with the TearLab® Osmolarity System.ResultsThe majority of the subjects were female (76%), African American (56%), and/or had a diagnosis of type 2 diabetes (82%). The mean ± standard deviation (SD) for age was 54.6±13.4, and maximum tear osmolarity was 304.6±12.7 mOsm/L. Men had higher osmolarity than women (mean ± standard error (SE) 311.8±4.0 mOsm/L versus 302.3±1.9 mOsm/L, P=0.02). Age, race, use of artificial tears, years of diabetes, and hemoglobin A1c did not have a statistically significant association with tear osmolarity. Longer duration of diabetes was associated with lower (less severe) OSDI scores (r=-0.35, P=0.01). Higher tear osmolarity was associated with lower (less severe) OSDI scores (r=-0.29, P=0.04).ConclusionApproximately half of the diabetic subjects in our study had elevated tear osmolarity, and half of our population also reported symptoms consistent with dry eye disease. However, the two were slightly inversely related in that those with higher osmolarity reported fewer symptoms. Subjects with a longer duration of diabetes also reported fewer dry eye symptoms. Therefore, health care providers should be aware that patients who are most likely to have ocular surface disease, including those with long-standing diabetes, may not experience symptoms and seek care in a timely manner.
Project description:PurposeTo investigate accommodative microfluctuations (AMFs) and visual function in short tear break-up time (BUT)-type dry eye (DE) and non-DE subjects.MethodsThis prospective comparative study included 48 volunteers with DE symptoms (mean age 34.8 ± 5.5 years, age range 25-42 years) and 73 without DE symptoms (mean age 30.6 ± 4.7 years, age range 25-42 years). The eyes were divided into two groups: (1) DE group with DE symptoms and BUT ≤ 5 s and (2) non-DE group without DE symptoms and BUT > 5 s. We excluded eyes with Schirmer score ≤ 5 mm and positive keratoconjunctival epithelial damage. Tear evaluation, AMF, and functional visual acuity (VA) examinations were performed. AMF parameters included total high-frequency component (HFC), HFC with low accommodation for the task of staring into the distance (HFC1), and HFC with high accommodation for deskwork (HFC2). Functional VA parameters included starting VA, functional VA, visual maintenance ratio, and blink frequency.ResultsA total of 33 and 34 eyes were categorized in the DE and non-DE groups, respectively. Mean blink frequency and HFC1 values were significantly higher in the DE group than they were in the non-DE group.ConclusionsDEs with symptoms showed abnormal AMF and visual function, which may be associated with DE symptoms.
Project description:Knowledge about the variability of measurements using the TearLab Osmolarity System is necessary when evaluating the clinical utility of readings.To examine the variability of tear osmolarity measured by the TearLab Osmolarity System in patients with Sjögren syndrome (SS), patients with blepharitis, and control participants.Cross-sectional study at a tertiary care academic center from June 13, 2012, to March 21, 2013. Participants included 74 eyes of 37 patients from a volunteer sample (18 patients with SS, 11 patients with blepharitis, and 8 control participants) who were evaluated using the TearLab Osmolarity System, with 3 consecutive osmolarity measurements taken at 1-minute intervals in a session; 15 of these patients had the same measurements taken by the same examiner in 2 additional sessions on the same day (9 AM-10 AM, 12 PM-1 PM, or 3 PM-4 PM). Most patients with SS and patients with blepharitis were taking systemic or topical dry eye medications at the time of enrollment.Mean osmolarity and its variability calculated from a linear mixed model for each disease group that accounts for the variations attributable to different patients, eyes, and sessions and measurement error specific to each disease group.Mean tear osmolarity was 307 mOsm/L, 304 mOsm/L, and 301 mOsm/L in the SS, blepharitis, and control groups, respectively (P?=?.46). The error associated with repeated measurements within a session in the patients without dry eye (10.5 mOsm/L [95% CI, 9.0-12.4]) was significantly lower than in the patients with blepharitis (14.6 mOsm/L [95% CI, 12.5-17.5]; P?=?.006) and patients with SS (15.8 mOsm/L [95% CI, 14.2-17.8]; P?<?.001) but a difference in the error of repeated measurements between patients with blepharitis and patients with SS was not identified (P?=?.46).There was increased variability attributable to error in repeated measurements in patients with SS and patients with blepharitis compared with control participants. The high variability of TearLab osmolarity readings in all groups makes the clinical interpretation of measurements unclear.
Project description:Dry eye is a common clinical condition diagnosed by cumulative evidence of symptoms and signs. Many new treatments in dry eye are either expensive, invasive, have potential for side effects, or are not easily accessible. In severe dry eye, the ideal modality of treatment to begin with is often not clear as specific molecular disturbances are not evident from just examination of clinical manifestations. Assessing the effects of ongoing treatment is not straight forward since there is lack of agreement between clinical signs and symptoms. There is a need to have more objective methods of selecting treatment for dry eye and monitoring the effect of treatment. Recently, there are many new technologies applied to the discovery of tear biomarkers, for e.g., mass spectrometry based proteomics techniques and multiplex assays such as the bead-based sandwich indirect immunofluorescent assays. Tear proteins assays have even been made available as point-of-care devices. This review focuses on the evidence for the involvements of tear proteins in dry eye, possible changes in tear concentrations with therapy and the strength of evidence regarding dry eye pathology. Much remains to be done in terms of developing office-based assays and ascertaining their reliability, but current evidence suggests that tear proteins have a role in the clinical practice of dry eye.
Project description:Dry eye syndrome is caused by a reduction in the volume or quality of tears. Here, we show that pituitary adenylate cyclase-activating polypeptide (PACAP)-null mice develop dry eye-like symptoms such as corneal keratinization and tear reduction. PACAP immunoreactivity is co-localized with a neuronal marker, and PACAP receptor (PAC1-R) immunoreactivity is observed in mouse infraorbital lacrimal gland acinar cells. PACAP eye drops stimulate tear secretion and increase cAMP and phosphorylated (p)-protein kinase A levels in the infraorbital lacrimal glands that could be inhibited by pre-treatment with a PAC1-R antagonist or an adenylate cyclase inhibitor. Moreover, these eye drops suppress corneal keratinization in PACAP-null mice. PACAP eye drops increase aquaporin 5 (AQP5) levels in the membrane and pAQP5 levels in the infraorbital lacrimal glands. AQP5 siRNA treatment of the infraorbital lacrimal gland attenuates PACAP-induced tear secretion. Based on these results, PACAP might be clinically useful to treat dry eye disorder.
Project description:BackgroundThis study measured longitudinal changes in dry eye disease (DED) symptoms and signs following lifitegrast therapy and assessed their relationship to tear osmolarity to test the hypothesis that a decline in tear osmolarity is a reliable leading indicator of subsequent improvement in DED symptoms and signs after initiating lifitegrast treatment.MethodsThis phase IV, prospective, single-arm, open-label, 12-week study enrolled subjects aged ≥18 years with eye dryness score ≥40 (0-100 VAS) and tear osmolarity ≥308 mOsm/L. Subjects were prescribed lifitegrast ophthalmic solution 5%, twice daily in each eye. DED symptoms were assessed via VAS at baseline and 2, 6, and 12 weeks. Signs included tear osmolarity, meibomian gland dysfunction, tear breakup time, and fluorescein corneal staining. In post-hoc analysis, subjects with ≥5 mOsm/L decrease in osmolarity over 12 weeks were Responders.ResultsOf 26 subjects in the intent-to-treat population, 23 were female; mean age was 67.4 years. Baseline mean±SD eye dryness was 68.7±16.5 and tear osmolarity was 317.8±8.5 mOsm/L. All seven symptoms (dryness, burning, foreign body sensation, pain, photophobia, itching, blurred vision) declined significantly (P<0.01) from baseline to 6 and 12 weeks. Signs did not change significantly. For 13 Responders, tear osmolarity decreased from baseline to 12 weeks (319.2±8.5 to 300.6±12.3 mOsm/L, P<0.001) and corneal staining trended toward improvement (1.1±0.9 to 0.6±0.7, P=0.136). Among Nonresponders, osmolarity increased from 316.4+8.7 to 329.6+13.9 (P<0.01) and corneal staining showed no change (1.3±0.8 to 1.0±0.7 at 12 weeks, P=0.293).ConclusionsLifitegrast reduced DED symptoms among subjects with moderate-to-severe disease (severity defined by VAS for eye dryness). Potential reasons that may underlie the dichotomous effect of drug treatment on tear osmolarity are discussed.