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Dry eye disease (DED) affects up to one-third of the global population. Traditional therapies, including topical lubricants, have been employed with variable success in the treatment of DED. Recently, neurostimulation of the lacrimal functional unit (LFU) has emerged as a promising alternative therapy for DED. In this review, we describe the neuroanatomical and pathophysiological considerations of DED and the LFU that make neurostimulation a viable therapeutic alternative. We further detail the various neurostimulatory approaches taken thus far—from implanted stimulators to external devices to chemical neurostimulation. Existing studies reveal the strengths of the neurostimulatory approach in increasing tear volume and improving dry eye symptoms, but further studies are needed to elucidate its true potential in treatment of DED.

Impaired tear production - a common sign of keratoconjunctivitis sicca (KCS) - is associated with qualitative or quantitative tear deficiency. OTX-101 0.09% is a novel, nanomicellar formulation of cyclosporine A approved in the US for increasing tear production in patients with KCS. We present a pooled analysis of the phase 2b/3 and phase 3 studies evaluating the effect of OTX-101 on tear production in a subgroup of patients with keratoconjunctivitis sicca with severely impaired tear production (Schirmer's score5 mm in either eye at baseline).In these randomized, double-masked studies, patients instilled 1 drop OTX-101 or vehicle per eye twice daily for 84 days. Pooled efficacy endpoints included percent (%) of patients with ≥10 mm change from baseline and mean change from baseline in Schirmer's score at day 84. Pooled safety endpoints included adverse event monitoring.Subgroup analyses included 133 and 113 patients receiving OTX-101 and vehicle, respectively. Mean baseline (BL) Schirmer's score ± standard deviation was 2.7 ± 1.2 for OTX-101 and 2.5 ± 1.1 mm for vehicle (OTX-101 administered twice daily for 84 days significantly improved tear production vs vehicle in patients with severely impaired tear production, as evidenced by significantly larger proportion of patients with ≥10 mm increases from baseline and higher mean change from baseline in Schirmer's scores.

Background A great number of sedatives and anaesthetics have been used to perform surgeries or routine ophthalmologic examinations in animals and sometimes the combination of these medicines has more suitable effects than each one alone. Objectives This paper aims to explore the main effects of Medetomidine + Acepromazine, Dexmedetomidine + Acepromazine on intraocular pressure, tear secretion and pupil diameter. Methods To accomplish the aforementioned aim, 32 adult dogs (aged one‐to‐three‐years‐old) were clinically examined. Dogs were divided into four groups consisting of group DA, Dexmedetomidine (5 µg/kg) + Acepromazine (0.05 mg/kg); Group D, Dexmedetomidine (5 µg/kg); Group M, Medetomidine (10 µg/kg); Group MA, Medetomidine (10 µg/kg) + Acepromazine (0.05 mg/kg). The ocular factors including tear production, pupil diameter and intraocular pressure of both right and left eyes were first measured and then recorded in each dog at time T0 (−15 min). Afterwards, the drugs were administered intramuscularly, based on which the ocular factors were re‐measured at T1 (+5 min), T2 (+15 min) and T3 (+20 min). All four groups showed a reduction in intraocular pressure, which was significant in DA, D and M groups. Results Furthermore, there was a fluctuation in the amount of tear secretion in DA and D groups (increase and then decrease), as well as a significant reduction in M and MA groups. Decreasing in pupil diameter also occurred in all four groups, but the reduction was significant only in DA and MA groups. Conclusion According to the results obtained, as the changes caused by the systemic administration of the above drug compounds did not exceed the physiological range, it can be concluded that these combinations could be utilized as suitable sedatives or pre‐anaesthetic compounds in the eye surgeries., This paper aims to explore the main effects of Medetomidine + Acepromazine, Dexmedetomidine + Acepromazine on intraocular pressure, tear secretion and pupil diameter.

Hormone replacement therapy (HRT) is used by women to get relief from menopausal symptoms, including dry eyes. However, it is not entirely certain that HRT helps relieve dry eye disease (DED). The focus of this study is to systematically review the literature of the relevant studies to understand and determine the correlation between HRT and DED. Literature was systematically reviewed using Distiller SR. Meta-analysis was conducted using STATA 15.0. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was assessed using statistics. Fixed-effect and random-effects models were computed based on heterogeneity. Subgroups analysis was done by follow-up. Our meta-analysis results indicated significant reduction in dry eye with HRT treatment at 1-month follow-up (SMD = −1.97; CI: −3.83, −0.11), a nonsignificant increase in tear breakup time at 3-month (SMD = −0.91; CI: −3.26, 1.44) and 6-month (SMD = −1.05; CI: −3.91, 1.82) follow-ups. Our meta-analysis results indicated a nonsignificant improvement in DED with HRT treatment at 1-month (SMD = −0.97; CI: −2.35, 0.4), 3-month (SMD = 0.19; CI: −0.91, 1.29), and 6-month (SMD = −0.48; CI: −1.39, 0.43) follow-ups.Overall, nonsignificant improvement in postoperative tear production, as well as tear breakup time, was seen after HRT treatment at follow-ups in dry eye patients. More good-quality randomized control trials are needed to make accurate conclusions.

Objective To analyze the relationship between dry eye symptoms and modern dry eye tests, including the Schirmer I test, lipid layer thickness (LLT), and blinking pattern by LipiView interferometer. Design Cross-sectional study. Participants 115 dry eye outpatients. Methods Dry eye symptoms were quantified by questionnaire scores, such as Ocular Surface Disease Index (OSDI) and Standard Patient Evaluation of Eye Dryness (SPEED). LLT, complete, and incomplete blinking rate were recorded by the LipiView interferometer. Results 115 patients (229 eyes, mean age = 60.5 ± 13.6 years) were enrolled in this study. The mean value of the SPEED and OSDI scores was 9.5 and 10.2, respectively. A total of 44.3% of all subjects had severe dry eye syndrome (SPEED, OSDI ≥ 10). LLT (mean = 71.2 nm) was inversely correlated with both the SPEED and OSDI (p = 0.003 and 0.004, respectively). The incomplete-to-complete ratio of blinking rate (i/c ratio) was correlated with both the SPEED and OSDI (p = 0.0048 and 0.0234, respectively). Patients with LLT less than 69 nm were more likely to have severe dry eye syndrome. There was no significant relationship between the Schirmer I test and the SPEED or OSDI. However, LLT was inversely related to the Schirmer I test (linear regression, p = 0.0002, r = −0.1857). Conclusions LLT and the i/c ratio were significantly correlated to dry eye symptoms. Eyes with thinner LLT are more likely to have better aqueous tear production. The role of the reciprocal influence between each tear component in the maintenance of tear function warrants further investigation.

Common age-related changes in the human eye contribute to the development of dry eye, including decreases in aqueous tear production. Although the infiltration of lymphocytes into the lacrimal glands occurs with age, age-related increases in tear production have also been observed in mice; however, the mechanisms underlying this increase remain unclear. We herein demonstrated that increases in tear production were not dependent on body weight gain or systemic conditions, such as insulin resistance, using aged mice and high-fat diet-fed mice. The results obtained also showed that senescence-associated T (SA-T) cells accumulated in the lacrimal glands of aged mice, particularly females. Expression levels of the nuclear transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) in whole lacrimal glands and epithelial cells isolated from lacrimal glands were significantly higher in aged mice than in young mice. The expression levels of adiponectin and one of its receptors, AdipoR2, also increased in the lacrimal glands of aged mice, but not in those of high-fat diet-fed mice. Collectively, the present results indicate that PPARγ and adiponectin-mediated signaling contribute to age-related increases in tear production in mice and have potential as therapeutic targets for the treatment of dry eye in humans.

The aim of this work was to design and evaluate novel cationized hyaluronic acid coated spanlastics (CHASVs), with the immunosuppressive peptide cyclosporine A (CsA) as the model drug. CHASVs exhibited ideal size, zeta potential, pH, osmolarity and entrapment efficiency. The developed CHASVs provided a surface tension of 34.98 ± 0.19 mN/m, a contact angle of 21.07 ± 3.56° and a viscosity of 9–12 mPa·s, which reflected favorable wetting and bioadhesion properties. From the in vitro release study, the sustain release property could also be seen. These proved the availability of CsA by ocular delivery was improved. With an apparent permeation coefficient of 5.22 × 10−6 cm/s and CsA residual of 312.18 ± 1.34 μg/g, CHASVs proved to enhance corneal permeation and accumulation of CsA compared with commercial emulsions. In vivo Draize test showed no signs of acute and chronic ocular toxicity of CHASVs formulations to the eyes of rabbits. Finally, schirmer tear test, tear ferning test and histologic analysis reflected that CHASVs showed significant therapeutic effect and improved tear production in dry eye. Results revealed that CHASVs could be a promising delivery system for CsA and employed as an ideal alternative to commercial emulsions for the treatment of dry eye syndrome.

Dry eye disease (DED) is a multifactorial disease that manifests in patients with a variety of symptoms and signs such as ocular pain, visual issues, rapid tear evaporation and/or decreased tear production. It is a global health problem and is the leading cause of optometry and ophthalmology clinic visits. The mainstay therapy for DED is artificial tears (ATs), which mimics tears and improves tear stability and properties. ATs have been found to improve symptoms and signs of disease in all DED subtypes, including aqueous deficient DED and evaporative DED. However, given the heterogeneity of DED, it is not surprising that ATs are not effective in all patients. When AT fails to relieve symptoms and/or signs of DED, it is critical to identify the underlying contributors to disease and escalate therapy appropriately. This includes underlying systemic diseases, meibomian gland dysfunction, anatomical abnormalities and neuropathic dysfunction. Thus, this review will discuss the benefits and limitations of ATs and review conditions when escalation of therapy should be considered in DED.

The purpose of this study was to determine and compare the effects between injecting botulinum toxin A (BTX-A) transconjunctivally into the palpebral lobe and transcutaneously into the orbital lobe of the lacrimal gland in patients with epiphora due to lacrimal outflow obstruction. This randomized controlled study included 53 eyes of 31 patients with unilateral or bilateral epiphora. Patients were randomly allocated to receive an injection of BTX-A (3 units) either transconjunctivally (n = 15, 25 eyes) or transcutaneously (n = 16, 28 eyes). For objective assessments, the tear meniscus height and Schirmer&rsquo, s I test with topical anesthesia were measured at baseline and after 2, 6, 12, and 24 weeks of follow-up. Subjective evaluations were performed using the Munk score. After BTX-A injection, patients in both groups experienced significant objective and subjective reductions in tearing at all follow-up times compared to pre-injection (success rate 86.8%), and the effect lasted for a mean duration of 5.63 months. The two delivery routes showed similar clinical effectiveness for a single injected dose of BTX-A. In conclusion, injecting BTX-A via either a transconjunctival or transcutaneous route helps to reduce normal tear production and results in significant improvements in the symptoms in patients with epiphora.

This study is aimed at comparing the effects of tea tree oil (TTO) shampoo with regular eyelid shampoo on the treatment of meibomian gland dysfunction (MGD) signs and symptoms.Double-masked randomized clinical trial METHODOLOGY: Forty patients with MGD were treated by daily eyelid scrubbing with TTO shampoo in one eye and regular eyelid shampoo in the other one. Before treatment and then after 1 and 3 months, the effect on ocular surface symptoms, tear production and stability, and conjunctival and eyelid signs of the 2 eyes were compared.Plugging and capping of meibomian gland orifices, foamy tear, glands expressibility, 5-Item Dry Eye Questionnaire score (DEQ5), and tear breakup time were improved more significantly in TTO shampoo-treated eyes (capping P = .050, plugging and glands expressibility P = .001, others P.001). In spite of improvement in both eyes, scores of meibum quality, conjunctival hyperemia, corneal and conjunctival staining, and Schirmer1 test value showed no statistically significant difference between the eyes (P = .06, .187, .192, .19, respectively). Moreover, eyelid margin telangiectasia resolved only in TTO shampoo-treated eyes (P.001). Trichiasis and distichiasis changed in neither group (P.99). Furthermore, ocular surface irritation during scrubbing was more common with TTO shampoo (P = .002).TTO shampoo was found to be more efficient than regular eyelid shampoo in controlling MGD signs and symptoms although ocular surface irritation during its application was more frequent.

Purpose To investigate long-term correlations between Matrix Metalloproteinase-9 (MMP-9) testing and dry eye (DE) parameters. Additionally, to evaluate variability in MMP-9 results over time and with anti-inflammatory treatment. Methods Retrospective cohort study of DE patients with equal MMP-9 testing results (positive or negative) in both eyes and a minimum of 6 months of follow up. Our main outcome measure was to examine whether initial MMP-9 status affected change in DE parameters over time. Secondarily, we evaluated the frequency of MMP-9 status change over time and examined whether MMP-9 status change was impacted by treatment. Results 67 patients (76% female) fit the inclusion criteria. Mean age was 63 years with a mean follow up of 10.6 months. The majority (37/67, 55%) had concomitant systemic immune disease. MMP-9 testing was positive in both eyes in 39 individuals (58%) and negative in both eyes in 27 (42%) individuals. Of all DE parameters, initial MMP status predicted change in tear production. Individuals in the MMP-9 positive group had a greater decrease in production from baseline to final visit compared to the negative group (−2.6 vs 2.1, P = 0.013). In those initially MMP-9 positive, the frequency of becoming MMP-9 negative was higher in eyes treated with anti-inflammatory therapy compared to artificial tears (22.9% vs 3.3%, P = 0.106). However, only Lifitegrast 5% showed statistical significance compared to artificial tears (31.3% vs 3.3%, P = 0.044). Conclusions Eyes with detectable MMP-9 had significantly decreased tear production over time compared to those without detectable MMP-9. Anti-inflammatory treatment more frequently normalized MMP-9 compared to PFATs.

To identify reference values for the Schirmer tear test I (STT I) in Japanese black cattle, investigate the effects of variables (sex, age, time of day, and environment in the barn including environmental temperature, humidity, illuminance, and ammonia concentration) on tear production, and determine total tear protein concentration. One-hundred-and-thirty-seven Japanese black cattle (67 females and 70 males, age 3-90 days) were evaluated. The mean STT I values was 18.9 ± 2.9 mm/min (n=263) and significant effects were age and ammonia concentration in the barn. Mean total tear protein concentration was 1.18 ± 0.30 mg/ml in healthy cattle older than 15 days (n=38). It was suggested that age and ammonia concentration are related to fluctuation of tear volume.

Neuromodulation is a novel approach that utilizes electrical signals, pharmaceutical agents, or other forms of energy to modulate abnormal neural function through neurostimulation. Neurostimulation is a novel technique that uses electrical currents to stimulate the nervous system. During the recent few decades, neuromodulation has gained significant attention, in particular for the treatment of chronic neurological diseases, due to its success in treating patients unresponsive to conventional pharmacological therapies. Dry eye disease (DED) is a chronic, multifactorial disease that affects millions of people worldwide. Recent data have demonstrated that neurosensory abnormalities contribute to the pathogenesis of DED. Current mainstays of dry eye therapy include lubrication, tear retention, and anti-inflammatory therapies, among others. The recent development of intranasal neurostimulation therapy for DED utilizes the nasolacrimal reflex as an alternative pathway, not only to increase tear production via increased lacrimation, but also to target other tear film components, such as mucin and meibum secretion, promoting tear film homeostasis. This review aims to describe the different types of neuromodulation devices available and their application for non-ocular diseases, as well as to review recent advances and literature on ocular neurostimulation.

OBJECTIVE To assess reliability of the Schirmer tear test-1 (STT-1) for measurement of tear production in cats in various environments, investigate whether sympathetic stimulation impacts measurements, and determine whether meaningful conclusions regarding lacrimation in cats can be drawn from STT-1 measurements obtained with STT strip placement for < 1 minute. ANIMALS 176 cats examined in a private practice (n = 100), a feral cat clinic (56), or a veterinary teaching hospital (20). PROCEDURES The STT-1 was performed in both eyes of each cat. Measurements were recorded at 10− or 30-second intervals for 1 minute. Cats at the teaching hospital were tested once in a quiet examination room (unstimulated conditions) and once in the same room with loud prerecorded noises (stimulated conditions), with a 30-minute interval between tests and evaluation of cats’ heart rates before and after STT-1. Data were analyzed with parametric statistical tools and a nonlinear mixed-effect model. RESULTS 30− and 60-second STT-1 measurements were significantly correlated (r = 0.94). The STT-1 measurements did not differ under nonstimulated versus stimulated conditions, despite significant changes in heart rates that indicated sympathetic stimulation. A hyperbolic model of STT-1 kinetics was validated, allowing for extrapolation of measurements obtained in < 60 seconds and generation of reference values (95% predictive intervals) for various test durations. Median (95% predictive interval) 30− and 60-second STT-1 measurements were 9.1 mm (4.8 to 15.6 mm) and 14.3 mm (8.2 to 22.3 mm), respectively. CONCLUSIONS AND CLINICAL RELEVANCE The STT-1 was a reliable diagnostic test in all settings; results were not affected by sympathetic stimulation, and a shorter duration of testing could be considered in selected cases.

Dry eye disease (DED) is a common multifactorial disease linked to the tears/ocular surface leading to eye discomfort, ocular surface damage, and visual disturbance. Antiinflammatory agents (steroids and cyclosporine A), hormonal therapy, antibiotics, nerve growth factors, essential fatty acids are used as treatment options of DED. Current therapies attempt to reduce the ocular discomfort by producing lubrication and stimulating gland/nerve(s) associated with tear production, without providing a permanent cure for dry eye. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. This review presents an overview, pathophysiology, prevalence and etiology of DED, with an emphasis on preclinical and clinical studies involving the use of nanocarrier systems in treating DED. Lay Summary: Lay Summary: Dry eye disease (DED) is a multifactorial disease associated with tear deficiency or excessive tear evaporation. There are several review articles that summarize DED, disease symptoms, causes and treatment approaches. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. Very few review articles summarize the findings on the use of nanotherapeutics in DED. In this review, we have exclusively discussed the preclinical and clinical studies of nanotherapeutics in DED therapy. This information will be attractive to both academic and pharmaceutical industry researchers working in DED therapeutics.

Tear production is an important factor in maintaining proper function of the cornea and conjunctiva. The purpose of this study was to determine the effects of bolus followed by infusion of fentanyl, lidocaine and ketamine on tear production as measured by the Schirmer I Tear Test (STT-I) in dogs. A prospective, randomized, “double-blind” study was performed. A total of 55 healthy conscious client-owned dogs were included in the study. Dogs were randomly allocated to one of four groups and given intravenous fentanyl 0.005 mg kg-1 followed by 0.005 mg kg-1 hour−1 (FEN-group), ketamine 0.6 mg kg−1 followed by 0.6 mg kg−1 hour−1 (KET-group), lidocaine 1 mg kg-1 followed by 1 mg kg−1 hour−1 (LID-group), or saline 0.3 mL kg−1 followed by 2 mL kg−1 hour−1 (SAL-group). The STT-I was performed prior to (baseline) and again 30 minutes (T30) after initiation of drug administration. Data were expressed as the median (minimum – maximum) and analyzed by Wilcoxon and Steel-Dwass tests (p

A careful examination of cornea and ocular surface eliciting the basic signs will help a clinician toward an accurate diagnosis. Flipping the upper lid or pulling the lower lid to look at the inferior fornix may help to pick up any subtle clinical sign. Meticulous documentation by diffuse and slit view will help in following up the disease. Eyelids and ocular surface are evaluated externally and by slit lamp. Slit-lamp examination with the use of the stains such as fluorescein, rose bengal, or lissamine green provides extensive knowledge about the ocular surface. Tests of tear production are also detailed herein. This review is intended to help the eye practitioners in eliciting common clinical signs seen in cornea and ocular surface diseases.

Purpose To evaluate the effect of twice daily aqueous 0.02% sirolimus drops on tear production in normal dogs and dogs with refractory keratoconjunctivitis sicca (KCS). Methods Two groups of dogs were studied. Ten normal dogs with no signs of ocular disease were administered topical 0.02% sirolimus ophthalmic solution in right eye, and a vehicle control in the left eye twice daily for 4 weeks. Complete ophthalmic examinations, including Schirmer tear test were performed weekly. Eighteen dogs with refractory KCS were randomly assigned to receive 0.02% sirolumus ophthalmic solution or 0.02% tacrolimus ophthalmic solution twice daily. Complete ophthalmic examinations were was performed at 2 and 6 weeks following treatment. Results Tear production in the sirolimus-treated eyes of normal dogs was greater when compared to vehicle controls with a mean difference over all time points of 3.46 mm (95% CI 1.17, 5.75; P = 0.006). After 4 weeks of treatment, the mean difference was 5 mm (95% CI 1.95, 8.05; P = 0.002). In dogs with refractory dry eye, 37.5% of eyes treated with sirolimus exhibited increased tear production >4 mm/min after 6 weeks of treatment, compared to 20% of eyes receiving tacrolimus (P = 0.433). One normal dog experienced topical irritation to both sirolimus and vehicle-treatment. Side effects were not reported in any treated eyes with chronic KCS. Conclusion Topical 0.02% sirolimus might be an alternative treatment for canine patients with keratoconjunctivits sicca. The drug appears safe when applied topically in an aqueous suspension for up to 6 weeks. While initial results are promising, further studies are warranted.

Dry eye disease can compromise the patient’s quality of life. Few studies assessed the ocular surface (OS) in Ankylosing Spondylitis (AS) patients. This study aimed to evaluate the clinical and cytological findings of the OS in patients with AS, classify dry eye disease (DED) severity grade and conjunctival impression cytology (IC), and the effects of TNF inhibitors (TNFi) in a one-year follow-up. A baseline (BL) evaluation included 36 AS patients and 39 healthy controls. They fulfilled the Ocular Surface Index Disease questionnaire and underwent the Schirmer I test, break-up time, vital staining, and conjunctival IC. A DED severity grade, as well as IC rating, was applied. Fourteen of these patients received TNFi and analysis of ocular and systemic AS disease parameters occurred at BL and three months (3 M), and 12 months (12 M) after treatment. The AS patients presented a higher frequency of DED (p = 0.01), a worse score of severity (p = 0.001), and a higher frequency of altered IC (p = 0.007) when compared to controls. The 14 patients under TNFi presented an improvement in all the clinical disease activity parameters throughout the one-year treatment (p

Dry eye disease (DED) is a chronic multifactorial disease that affects millions of people worldwide. Despite ongoing research, treatment for DED remains a challenge. Neurostimulation for tear production is a rapidly evolving field that culminated in the development of the intranasal tear neurostimulator (ITN). In this article, we review the neuroanatomy and pathophysiology of tear production and the evolution of neurostimulation for the treatment of DED.The ITN was approved for commercial use in April 2017. This innovation stemmed from the success of lacrimal nerve and anterior ethmoid nerve stimulation animal studies. Since then, numerous pilot studies and multicenter randomized controlled trials demonstrate increased aqueous tear production, improved DED-related symptoms, and device safety. Recent studies also report the positive effects of intranasal stimulation on mucin and lipid secretion.Neurostimulation for enhanced tear production is a promising new treatment option for DED. Stimulation of the lacrimal nerve and anterior ethmoid nerve both effectively increase tear volume. The ITN is a noninvasive device that effectively increases aqueous tear volume and may improve tear composition, including mucin and lipid concentrations. Further studies are needed to determine proper patient selection and the long-term efficacy of neurostimulation for DED.

To investigate the role of lymphotoxin (LT) in Sjogren's syndrome (SS) and in mucosal associated lymphoid tissue (MALT)-lymphoma, we made transgenic mice (Amy1-LTαβ) that targeted LTα and LTβ to the salivary and lacrimal glands. Amy1-LTαβ mice developed atrophic salivary and lacrimal glands that contained tertiary lymphoid organs (TLOs) and had reduced tear production. Amy1-LTαβ mice developed cervical lymphadenopathy but not MALT-lymphoma. TLO formation in the salivary and lacrimal glands of Amy1-LTαβ was not sufficient to induce autoimmunity as measured by autoantibody titres.

The exact contribution of the orbital lacrimal gland (OLG) is unknown and is still a subject of debate and inconsistency in literature. Currently, there are no detailed studies addressing the influence of the OLG removal on tear production in equines. This study aimed to address the influence of surgical excision of the OLG on aqueous tear production and ocular surface health in donkeys. The study was conducted on six clinically healthy donkeys with no ophthalmic abnormalities. In each donkey, the OLG of the left eye was surgically excised, whereas the right eye was served as a control. External ophthalmic examination, Schirmer tear test (STT) I and II, tear pH, fluorescein staining test were conducted on both eyes, preoperatively and at one-week intervals for 60 days, postoperatively. There were significant decreases in STT I and II values (P = .0001 and .0001, respectively), whereas tear pH values showed a significant increase (P = .0001) in the operated eyes compared with the control ones. There were no overt clinical signs characteristics of keratoconjunctivitis sicca (KCS) in the operated eyes. However, there was evidence of microinjury of the keratoconjunctival epithelium evidenced by positive fluorescein uptake, postoperatively. Surgical excision of the OLG significantly diminished the aqueous tear production and threatened the corneal epithelium as a result of corneal dehydration. On the contrary to the recommendations of other studies, eyes subjected to this procedure should receive treatment of dry eye to prevent development of KCS, postoperatively.

Biomarkers in tear fluid have attracted much interest in daily healthcare sensing and monitoring. Recently, surface-enhanced Raman scattering (SERS) has enabled highly sensitive label-free detection of small molecules. However, a highly stable straightforward tear assay with superior sensitivity is still under development in tear collection and analysis. Here we report a plasmonic Schirmer strip for on-demand, rapid, and simple identification of biomarkers in human tears. The diagnostic strip features gold nanoislands directly and evenly formed on the top surface of cellulose fibers, which maintain a hygroscopic nature for an efficient collection of tear production as well as provide plasmonic enhancement in SERS signals for identification of tear molecules. The uric acid in human tears was quantitatively detected at physiological levels (25-150 μM) by using SERS. The experimental results also clearly reveal a strong linear correlation between uric acid level in both human tears and blood for gouty arthritis diagnosis. This functional paper strip enables noninvasive diagnosis of disease-related biomarkers and healthcare monitoring using human tears.

PURPOSE To determine if the Schirmer test is affected by environmental humidity, to quantify any effects, and to consider the ways in which this may affect the diagnosis of dry eye disease. METHODS All experiments took place within a controlled environment chamber at a range of 5% to 95% relative humidity (RH). In vitro testing immersed Schirmer strips at 5 mm depth in water for 5 minutes. In vivo tests were conducted using the standard clinical method. All experiments were conducted using both standard Schirmer strips and Schirmer strips sheathed in a plastic film in order to reduce the possible effects of evaporation. RESULTS In vitro results showed a clear decrease in Schirmer wetting length as RH was reduced. Schirmer test strips that were encased within a plastic sheathing were less affected by changing RH. As well as wetting length, the rate of wetting of Schirmer strips was also affected by changes in RH. In vivo data showed that Schirmer results in participants with severe dry eye disease were less affected by changes in RH than "normal" participants. CONCLUSIONS Patients with severe dry eye disease produce Schirmer test results which are unaffected by environmental humidity. However, patients with moderate Schirmer wetting lengths may be falsely diagnosed as having dry eye disease if their test is undertaken in a low-humidity environment. This phenomenon may be overcome with the use of plastic sheathing. Previous studies investigating the effects of environmental conditions on the tear film may have been affected by this phenomenon.

Background The Schirmer tear test (STT) is widely used in both human and veterinary ophthalmology. Two types of STTs have been developed: STT I and SST II. The STT I measures the basal and reflex tear production and is the most widely used STT. However, several factors influence the STT results such as the person performing the test and the location of the strip placement within the conjunctival sac. The aim of this study was to measure the basal and reflex tear production (STT I) in clinically normal horses with open versus closed eyes. Results Forty clinically healthy horses without any ocular diseases were included. On day 1, the STT I was first performed on all the horses with the eyes open followed by an STT I with closed eyes performed 30 min later. On day 2, all horses had their eyes closed during the first STT and the eyes open during the second test performed 30 min later. The mean value of the STTs performed on open eye was significantly less than the STT performed on closed eye on both days of examination. Conclusion This study showed a small but statistically significant difference between STT values obtained with open versus closed eyes in clinically normal horses.

Background: Dyslipidemia may be linked to meibomian gland dysfunction (MGD) and altered meibum lipid composition. The purpose was to determine if plasma and meibum cholesteryl esters (CE), triglycerides (TG), ceramides (Cer) and sphingomyelins (SM) change in a mouse model of diet-induced obesity where mice develop dyslipidemia. Methods: Male C57/BL6 mice (8/group, age = 6 wks) were fed a normal (ND, 15% kcal fat) or an obesogenic high-fat diet (HFD, 42% kcal fat) for 10 wks. Tear production was measured and meibography was performed. Body and epididymal adipose tissue (eAT) weights were determined. Nano-ESI-MS/MS and LC-ESI-MS/MS were used to detect CE, TG, Cer and SM species. Data were analyzed by principal component analysis, Pearson&rsquo, s correlation and unpaired t-tests adjusted for multiple comparisons, significance set at p &le, 0.05. Results: Compared to ND mice, HFD mice gained more weight and showed heavier eAT and dyslipidemia with higher levels of plasma CE, TG, Cer and SM. HFD mice had hypertrophic meibomian glands, increased levels of lipid species acylated by saturated fatty acids in plasma and meibum and excessive tear production. Conclusions: The majority of meibum lipid species with saturated fatty acids increased with HFD feeding with evidence of meibomian gland hypertrophy and excessive tearing. The dyslipidemia is associated with altered meibum composition, a key feature of MGD.

OBJECTIVES The purpose of this study was to determine if a circadian rhythm exists in Schirmer's tear test (STT-1) values in a group of healthy adult cats. ANIMALS STUDIED Twenty adult neutered Domestic Short-haired cats (DSH) were used in the study. PROCEDURES Tear production was measured with the Schirmer tear test (STT-1) at 12 different time points over a 48-hour period. RESULTS A significant difference (approximately 4.3 mm/min) was noted between STT-1 values measured between 4 pm (lowest) and 12 am (highest) on both day 1 (P = 0.02) and day 2 (P = 0.01), and substantial variation in STT-1 values was observed at different times during the 48-hour period. CONCLUSIONS Significant variation in mean STT-1 values demonstrates that there is a circadian rhythm in tear production in cats and thus shows the importance of taking the time of day into account when measuring STT-1 in cats.

Purpose: To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. Methods: Patients (n = 1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15 mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p ≤ 0.05). Results: The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). Conclusions: Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited. KEYWORDS: Dry eye disease, Schirmer I test, tear production levels, clinical tests, large population of patients

In 1980, botulinum toxin type A (BTX-A) was introduced for the treatment of strabismus and benign essential blepharospasm. Since then, a number of additional indications have been introduced, which continue to expand, providing less invasive solutions in managing different ophthalmic conditions.Successful trials of BTX-A injection into the lacrimal gland have been reported for the treatment of epiphora caused by primary lacrimal gland hyperlacrimation, functional tearing, gustatory tearing, and lacrimal outflow obstruction. This is achieved through blockage of the cholinergic receptors by BTX-A at the glandular level. Interestingly, BTX-A has also been found to be useful in treating patients with dry eyes by compromising the tear drainage from the eye through injection of BTX-A in the medial part of the lower eyelid. BTX-A may help provide effective relief for patients who have two different ophthalmic comorbidities such as benign essential blepharospasm and dry eye.Better understanding of the mechanism of BTX-A action in the treatment of the growing applications in ophthalmology helps provide relatively noninvasive solutions for patients. Full awareness of possible side effects of BTX-A and the optimal way to manage them is vital for the success of this treatment option.

Dry eye disease is a disorder of the tear film. In this study, the effect of Viola odorata L. oily extract was examined for the treatment of patients suffering from dry eye disease.A randomised, double-blind, placebo-controlled study was designed. During the trial, Schirmer's test, tear breakup time, Oxford staining and the Ocular Surface Disease Index were assessed. Overall, 105 patients with dry eye symptoms between the ages of 18 and 60 years were allocated to the violet-almond oil, almond oil and placebo (1% w/v hydroxypropyl methylcellulose solution) groups. The treatment and placebo were administered intranasally, two drops three times a day for one month. The patients were followed up for four weeks. A total of 91 patients (32, 29 and 30 in the violet-almond oil, almond oil and placebo groups, respectively) completed the study.At baseline, there was no difference between the three groups in terms of demographic data and the measurement parameters. After the intervention, the results revealed that the Schirmer's score without local anaesthesia and the tear breakup time results significantly improved in the violet-almond oil group. One-way ANOVA indicated a significant improvement in the Schirmer's score, tear breakup time and Ocular Surface Disease Index of the treatment group, as compared with the other groups (p 0.05). However, the obtained results did not present any significant mean difference between and within the groups of the Oxford staining grade (p 0.05).This trial showed that the intranasally administered V. odorata L. oily extract enhances tear production and improves tear film stability.

Background Dry eye disease (DED) is a prevalent complication of diabetes and presents as reduced tear production and/or increased corneal surface sensitivity often with secondary ocular surface changes. This study examined the safety and efficacy of a proprietary new eye drop formulation for topical treatment of DED. Methods Type 1 diabetes (T1D) was established in male Sprague-Dawley rats to study the efficacy and safety of the investigational compound that contained 20 μg/ml of naltrexone (NTX). Tear production was measured by the Schirmer’s 1 test, and ocular surface sensitivity was measured using an aesthesiometer. Diabetic rats received twice daily applications of a single drop (~ 0.02 ml) of the proprietary formulation (NTX-001) or vehicle onto one eye. For comparison, some diabetic rats received eye drops containing NTX in sterile Vigamox®. Safety was monitored by assessment of ocular histopathology in naïve male rats and naïve male rabbits receiving twice daily treatment of two drops for 30 days. Results Dry eye in T1D rats was reversed within hours of a single treatment of NTX-001, and over a period of 10 days NTX-001 restored corneal sensitivity and reversed dry eye relative to values measured in diabetic rats receiving vehicle. In comparison to NTX dissolved in Vigamox®, the proprietary NTX-001 was more effective at reversing dry eye. Safety studies in naïve rats and rabbits revealed no visible ocular pathology after 30 days of treatment. Conclusions An investigational new eye drop containing 20 μg/ml NTX effectively reversed tear film deficits and restored corneal surface sensitivity in diabetic animals without causing toxic side effects.