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BACKGROUND: Pseudoexfoliative material is being implicated in causing tear film abnormalities, and the aim of the present study was to prove it and to compare with the normal healthy participants. METHODS: A total of 398 eyes of 200 participants were studied, and two groups were formed. The first, pseudoexfoliation syndrome (PEXS) group, included 198 eyes of 100 patients, and the second, age-matched control group, included 200 eyes of 100 participants. Tear film abnormalities were compared in the two groups by tear meniscus height (TMH), Schirmer test I, Schirmer test II and tear film break-up time (TBUT). RESULTS: On comparing the two groups using independent t-test, a significant difference was found in Schirmer test I, Schirmer test II, and TBUT between the PEXS group (Schirmer test I: 23.98 ± 10.68 mm, Schirmer test II: 17.11 ± 8.78 mm, and TBUT: 9.778 ± 5.54 s) and the age-matched control group (Schirmer test I: 27.08 ± 9.58 mm, Schirmer test II: 19.98 ± 8.48 mm, and TBUT: 13.495 ± 5.65 s) (p = 0.003 [Schirmer test I]; p = 0.001 [Schirmer test II]; and p

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.

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.

The aim of this study was to compare the Shirmer tear test (STT) and Standardized endodontic absorbent paper point tear test (PPTT) in ferrets and establish normal ophthalmic parameters for PPTT. A total of 66 eyes from 33 healthy ferrets (17 males and 16 females) aged 10 to 120 months were included in the study. Measurement for STT was 7.4 ± 1.9 mm/min and 12.6 ± 2.4 mm/min for PPTT. There were no significant differences between values obtained from left and right eyes (P = 0.29) or between age groups (P = 0.16), however there was a significant difference between sexes (P = 0.03). The results from this study can both serve as useful parameters for ophthalmologic evaluation in ferrets but less variable results, and therefore more precise measurements can be obtained using PPTT than STT.

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.

The Schirmer tear test (STT) is essential for estimation of ocular tear production. The present study aimed to establish reference values of STT I and II and study the effect of gender on tear production in donkeys (Equus asinus). Twenty-four donkeys (12 males and 12 females) that had no ocular abnormalities were included in this study. In each animal, 4 STT readings were obtained from each eye, with 1 week interval (2 for STT I and 2 for STT II), with a total of 96 readings for each test. The readings were obtained at a fixed time of the day, while the animals were in the standing position, and without tranquilization. Donkeys were more tolerant to STT II than STT I. Values of STT II were significantly lower than those of STT I (P = .0007). There were nonsignificant differences between the right and left eyes in STT I and STT II (P = .517 and .222, respectively). Regarding sex, there were significant differences between the male and female donkeys in STT I and II (P = .028 and .008, respectively). However, in the males or females, there were nonsignificant differences between the right and left eyes for STT I (P = .204 and .621, respectively) and STT II (P = .640 and .640, respectively). The gender of the animal had a significant impact on STT values. The obtained reference values of this study may be of clinical relevance in the diagnosis and monitoring of keratoconjunctivitis sicca (KCS) in donkeys.

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

Diabetes is associated with dysregulation of the Opioid Growth Factor (OGF) - OGF receptor (OGFr) regulatory pathway leading to elevated OGF levels in serum and tissues. This study was designed to investigate the role of sex on the magnitude of ocular surface complications by direct comparison of male and female type 1 diabetic (T1D) rats. Male and female adult Sprague-Dawley rats were rendered T1D; a cohort of T1D male and female rats received insulin (=T1D-INS). Tear production, corneal surface sensitivity, as well as serum levels of estrogen, testosterone, OGF and OGFr were measured. Multivariate analyses were performed for correlations between sex, condition and magnitude of ocular surface alterations. Significant differences were noted in all parameters tested between male and female Normal, T1D, and T1D-INS animals over the 8-week observation period. Multivariate analyses revealed that the magnitude of complications is greater in female T1D rats and has a strong negative correlation with serum estrogen and OGF. Ocular surface complications associated with T1D have an earlier onset and greater magnitude in female T1D rats than male diabetic animals, and are related to elevated levels of OGF.

© 2016 Elsevier B.V. A Schirmer tear test (STT) is commonly used to gauge human tear production, especially when dry-eye symptoms present. In an STT, the rounded tip of a standardized paper strip is inserted into the lower fornix of the eye, and the wetted length extending out from the lower lid is recorded after 5 min of eye closure. Longer wetted lengths suggest higher tear production rates. To date, however, there is no methodology to transform STT transient wetting lengths into basal tear- production rates. We develop a physical model to elucidate wetting kinetics in a Schirmer strip. Tear evaporation from the exposed portion of the strip and gravity are accounted for. Careful consideration of the initial depletion of tear in the closed-eye tear prism reveals an initial fast increase in wetted length followed by slower growth. Excellent agreement of the proposed model is achieved with experimental observation. When evaporation is negligible, the slow-growth regime exhibits a linear increase of wetted length in time. The linear-length-growth time regime permits simple calculation of quantitative tear-production rates. We suggest measuring several dynamic wetting lengths along a sheathed Schirmer strip and near the 5-min insertion duration followed by fitting to a straight line. The slope of the length-versus-time data gives the basal lacrimal-supply rate.

OBJECTIVES: Dry eye is a chronic condition associated with insufficient tear production and faster tear evaporation and commonly accompanied by inflammation that may lead to ocular surface damage. We have developed a multi-ingredient formulation containing lutein, zeaxanthin, curcumin, and vitamin D3 to address conditions associated with dry eye. The objective of this study was to evaluate the efficacy and safety of our formulation in subjects with mild to moderate dry eye symptoms. METHODS: This was a randomized, double-blind, parallel, placebo-controlled study. Sixty subjects with mild to moderate DES were randomly assigned in a 1 : 1 ratio to the test or placebo groups. Subjects consumed one capsule of the test or placebo product every morning through the study duration of 56 days. The test product comprised 20 mg lutein, 4 mg zeaxanthin, 200 mg curcuminoids, and 600 IU vitamin D3 in form of a capsule. The placebo product contained soybean oil. Changes in tear volume by Schirmer's test and severity of dry eye discomfort measured by Ocular Surface Disease Index (OSDI) score, changes in Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear film break up time (TBUT), corneal & conjunctival staining, tear osmolarity, Matrix Metalloproteinases (MMP)-9 levels in tear fluid, and artificial tear usage were evaluated. RESULTS: Thirty subjects in Test and 29 in Placebo group completed study. We observed statistically significant (P

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.

We report a rare case of a 4-year-old girl with involuntary watering of eyes and facial redness during painless voiding since early infancy. Here, we describe her response to urotherapy with improvement of involuntary tearing during micturition, which although neither life threatening nor debilitating, may be quite bothersome for children and their parents, leading to anxiety, emotional burden, or embarrassment. We hypothesize that the lacrimal glands and the bladder and bowel have common central nervous system pathways and that bladder retraining and bowel management might be a potential treatment for this rare condition.

Approximately 30% to 50% of contact lens (CL) wearers report dry eye symptoms. Meibomian gland dysfunction has been recognized as a possible cause of CL-related dry eye. This study investigated the influence of CL wear on the meibomian glands using a newly developed meibographic technique.Cross-sectional observational case series.Contact lens wearers (n=121; 47 men, 74 women; mean age+/-standard deviation, 31.8+/-8.0 years) and healthy volunteers (n=137; 71 men, 66 women; mean age+/-standard deviation, 31.4+/-15.1 years).The following tests were performed: slit-lamp examinations of the eyelids, corneal and conjunctival staining using fluorescein, measurement of the tear film breakup time, evaluation of the meibomian glands using noncontact meibography, and measurement of tear production using the Schirmer I test. Partial or complete loss of the meibomian glands was scored for each eyelid using 4 grades (meiboscores): grade 0 (no loss of meibomian glands) through grade 3 (the area characterized by gland dropout was more than 66% of the total area containing the meibomian glands). The meiboscores for the upper and lower eyelids were summed for each subject.Score of meibomian gland changes (meiboscore), tear film breakup time, and Schirmer test value.The meiboscore was significantly higher (P0.0001) in CL wearers (mean, 1.72; 95% confidence interval, 1.47-1.96) than in the control group (mean, 0.96; 95% confidence interval, 0.73-1.19). The average meiboscore of CL wearers was similar to that of a 60- to 69-year-old age group from the normal population. A significant positive correlation was observed between the duration of CL wear and the meiboscore.Contact lens wear is associated with a decrease in the number of functional meibomian glands. This decrease is proportional to the duration of CL wear.

Evaporation from the ocular surface is dramatically reduced by the lipid layer which covers it. With this layer intact, evaporation represents a small loss of water for which the lacrimal gland easily compensates. When tear production is compromised evaporation becomes important, especially since evaporation in almost all ocular surface disease states and any surface perturbation, including contact lens wear, increases evaporation significantly. How the barrier function of the lipid layer accomplishes this reduction in evaporation is not understood and is probably quite complex as is the structure of the lipid layer. Improving this barrier function remains an important and elusive goal.

Laser in situ keratomileusis (LASIK) can affect corneal sensation, aqueous tear production, wound healing, and the incidence of corneal erosions. Virtually all patients experience dry eye at least transiently after LASIK. Because intact corneal sensation drives tear production, denervation associated with the LASIK procedure is the most significant cause of post-LASIK dry eye. To prevent symptomatic postoperative dry eye, it is crucial to identify and treat pre-existing dry eye before surgery. This review addresses the pathophysiology and management of dry eye, as well as the relationship between LASIK and corneal erosions, and suggests intra- and post-operative management techniques to minimize complications and maximize the stability of the ocular surface. Contraindications to LASIK and alternative refractive surgical procedures are discussed.

The current study was undertaken to establish reference values for Schirmer tear test (STT) and intraocular pressure (IOP) in the Sanjabi sheep. Twenty apparently healthy Sanjabi sheep with no evidence of ocular disease were used in this study. Tear production was measured by STT by inserting standard sterile Schirmer tear test strip (Ophtechnics Inc., Carson City, NV, USA, Lot number: STR061203) in the ventral conjunctival fornix for 1 min. IOP was measured in both eyes with a Tono-Pen Vet™ (Reichert, Inc. USA). Mean (SD) STT values for all eyes ( n = 40) were 18.52 ± 2.55 mm/min with a range of 13.5–22 mm/min. Comparison of mean STT values between right ( n = 20) and left eyes ( n = 20) showed no differences ( P = 0.88). Mean (SD) IOP values by applanation tonometry were 9.37 ± 2.45 mmHg (range 6–14.5 mmHg). Comparison of mean IOP values between right ( n = 20) and left eyes ( n = 20) showed no differences ( P = 0.59). In conclusion, this study reports STT and IOP findings in Sanjabi sheep, and provide means and ranges for IOP and STT.

The mucolytic drug bromhexine hydrochloride (BH), was formulated in different ohthalmic dosage forms. The influence of the drug from the different formulations on tear flow rate in humans was investigated. The formulations tested were: BH aqueous solution, methylcellulose and carbopol934 hydrogels; and two polymeric inserts, namely; Gantrez AN 169 (G) and cellulose acetate (CA). The greatest influence on tear production was found using carbopol934. Although both polymeric inserts showed less influence than carbopol934, they sustained the action of BH in the human eye.

disappeared but the deposits remained, despite multiple scrapings with cotton-tipped applica­ tors and a No. 15 blade. The patient subse­ quently underwent scraping and anterior cham­ ber tap for cultures, which were negative. The patient continued to have a dense nonepithelialized superficial plaque with marked anterior chamber inflammation and resolving hemor­ rhage (Fig. 1). The patient underwent repeat penetrating keratoplasty and anterior vitrectomy to rule out persistent infection. Speci­ mens were sent for culture. Cultures were all negative. No organisms were seen on smear from the vitrectomy speci­ men. Microscopic sections of the nonhealing cornea disclosed an amorphous deposit replac­ ing the epithelium and parts of Bowman's layer and anterior stroma. The stroma beneath the plaque was normal without any evidence of inflammatory cells or any organism. Examina­ tion of the edge of the plaque showed epithelial cells crowding against the edge of the plaque and attempting to spread across the surface (Fig. 2). The persistence of the epithelial defect was caused by the accumulation of a precipitate tightly adherent to the anterior stroma. In con­ trast to the cases described by Leibowitz, the plaque in this case could not be removed by swabbing or even scraping. The mechanism for the formation of an adherent plaque is uncer­ tain. The patient's age and poor tear production were potential contributing factors. Clinicians should be aware that frequent use of ciprofloxacin in older patients with ocular surface dis­ ease may result in formation of dense precipi­ tates that interfere with corneal healing. References

Diurnal variations in tear evaporation in nine subjects were measured using resistance hygrometry at 2h intervals, fora 14h period. Evaporation is lowest on waking, and rises within 2h to a constant value for the rest of the day. Explanations for this pattern include low tear production during sleep and/or the presence of a thick tear film lipid layer on waking. These findings relate to observations of dry eye, lens adherence, corneal erosion, and tight lens syndrome in contact lens wear.

The following two letters address an article that appeared in the July 2001 issue of the Journal. Battat L, Macri A, Dursun D, Pflugfelder S. Effects of laser in situ keratomileusis on tear production, clearance, and the ocular surface (Ophthalmology 2001;108: 1230–5) .

Patients with undiagnosed problems in tear production who undergo cosmetic blepharoplasty can be extremely dissatisfied after the operation. Knowledge of methods for diagnosing such problems will allow the surgeon to better select patients for cosmetic eyelid surgery. Keratoconjunctivitis sicca is the most common abnormal tear film state, but there are other conditions of which the eye surgeon should be aware.

A concise review of current knowledge in the stimulation and regulation of tear production and its relationship to the ocular surface is presented. A discussion of treatment modalities, their benefits and drawbacks, follows. An approach to developing a rational treatment plan in the management of dry eyes is suggested with specific strategies. The application of these principles and the use of specific treatment modalities to manage the discreet manifestations of dry eye syndrome can lead to successful management in the majority of cases, with the preservation of useful vision and the relief of symptoms.

The bioavailability of topically applied ocular drugs is very poor, due largely to drug loss through drainage and tear turnover. The use of high viscosity solutions or solid matrixes to delay or eliminate drainage is the usual approach for decreasing drug loss but the alternative approach of chemically reducing tear turnover and/or solution drainage has not been investigated. By means of a simple isotopic dilution technique, using radioactive technetium sulfur colloid, the quantitative influence of topical anesthetics on tear production and instilled solution drainage was determined. The reduction in the rate of tear turnover and solution drainage varies for different anesthetics and is dose dependent. The implication of these results for some long accepted clinical procedures is discussed, and questions are raised regarding the present understanding of the mechanisms of tear production. Quantitation of precorneal drug loss through instilled solution drainage and tear turnover permits the establishment of a baseline for ocular drug bioavailability. Aqueous humor drug concentration versus time profiles of radioactive pilocarpine nitrate were obtained, both in the presence and absence of topical anesthesia. The results verify the importance of tear turnover and instilled solution drainage as a major route of drug loss in the eye. Moreover, the success of the present study in improving ocular drug bioavailability by the chemical approach of repressing solution drainage and tear turnover suggests that this approach is viable for improving drug bioavailability.

A 2-year-old boy had bilateral corneal ulceration with the Goldenhar-Gorlin syndrome. Initially, the patient received subconjunctival and topical antibiotics with minimal effect. With subsequent treatment of atropine, sterile ophthalmic petrolatum ointment, and humidification of the patient's crib, ulcers in both eyes healed in two weeks without further problems. He had a neuroparalytic keratitis with corneal anesthesia and decreased tear production bilaterally. Our evidence suggested that aplasia or hypoplasia of the trigeminal nuclei was the probable cause.

The effect of an orally administered diuretic, hydrochlorothiazide, on tear production in 11 normal young human subjects (five men and six women, 18 to 35 years old) was measured in a single-masked study. Schirmer tests with topical anesthetic showed a significant (P = .02) decrease in basal aqueous tear production on days when these subjects were taking the diuretic. The average decrease was 2.1 mm of wetting in five minutes.

Ten patients with superior limbic keratoconjunctivitis were examined. Eight patients were female and 9 had bilateral disease. Five of the 10 patients had a history of thyroid disease. Two of the patients had filaments and four had a significantly decreased tear production. A conjunctival resection was carried out in all of the patients. Postoperatively, eight of these patients were either asymptomatic or much improved. Two patients with decreased tear production showed no improvement. Preoperatively, a normal Schirmer's test is helpful in predicting the success of conjunctival resection.