Search

OBJECTIVE To assess the response to topical and/or systemic pilocarpine in dogs with neurogenic dry eye. METHOD Medical records of dogs diagnosed with dry eye between 2015 and 2018 were reviewed. Cases were excluded if STT values were decreased bilaterally, if dogs were lost to follow-up, or if surgical measures (parotid duct transposition) were undertaken within thirty days of presentation. Dogs were on treatment with topical pilocarpine (0.1%, every 6 hours) and/or oral pilocarpine (starting dose 2%, one drop per 10 kg every twelve hours). RESULTS Eleven cases were included in the study, seven females and four males with mean age of 10 years. Seven cases had xeromycteria, two cases had facial nerve paralysis, and one case had Horner's syndrome. Seven cases (63.6%) had successful outcome following pilocarpine treatment, return to normal STT (15-25mm/minute), in an average of 24 ± 5.1 days. Of these cases, five had both systemic and topical treatment, one had just topical treatment, and one had just systemic treatment. The average time to normal tear production on treatment with topical pilocarpine ± systemic was 23 days (range 9-48 days). The number of systemic drops until a positive response varied between individuals from 0.8drops/10kg to 7drops/10kg. CONCLUSION Pilocarpine treatment (topical ± systemic) is an effective therapy for unilateral dry eye disease in cases suspected to be neurogenic in origin. Most cases responded within 30 days. Side effects included topical irritation to the ophthalmic solution and systemic effects from oral pilocarpine, such as diarrhea and regurgitation.

Clinical data on new directions in combined treatment of neurotrophic keratitis, including anti-inflammatory therapy are presented.Purpose. To compare the effectiveness of bromfenac 0.09 %, nepafenac 0.1 % and indomethacin 0.1 % eye drops in the treatment of neurotrophic keratitis (NK).Materials and methods. 22 NK patients, aged 34 to 78, were divided into three groups. Group I received bromfenac 0.09 %, group II, nepafenac 0.1 %, and group III, indomethacin 0.1 %. Ophthalmic tests included visometry, biomicroscopy, corneal sensitivity determination, as well as diagnostic tests to determine indicators of tear production (Schirmer test, Norn test, LIPCOF test), and measuring lacrimal meniscus height.Results. Between visits V2 and V3, patients of group III showed an increase in conjunctival irritation to an average of 2.3 points, while groups I and II revealed the condition of the conjunctiva at 0.9 and 1.1 points, respectively. The lesion area was evaluated in points (max = 20) and averaged on V1 6.8 points in group I, 5.9 points in group II and 7.2 points in group III. Keratopathy in group I which was estimated at 3.8 points before V2, dropped to 1.4 points by V3. In group III it was 1.7 points by V3. In group II, keratopathy showed only 4.1 points by V3. The average Norn test on the day of treatment showed 2.7 seconds in group I, 2.5 seconds in group II, and 3.1 seconds in group III. No significant increase in Schirmer's test results in all groups was recorded.Conclusion. The use of non-steroidal anti-inflammatory eye drops of various groups — bromfenac 0.09%, nepafenac 0.1 % and indomethacin 0.1 % — gave a positive result in NK therapy. However, bromfenac 0.09% instillations administered once a day produce a higher anti-inflammatory effect then the same quantity of nepafenac 0.1% and indomethacin 0.1 % instillations.

Periorbital burns generate contraction and distortion of periorbital soft tissue, causing eyelid malfunction, further contributing to loss of vision from corneal scarring or perforation. We present our multidisciplinary algorithm to restore vision in patients with burn-related bilateral corneal blindness with light perception. Chart review was performed for four consecutive burn patients requiring periocular reconstruction and keratoprosthesis. Initial treatment included globe coverage with eyelid releases and grafts. Strategy of corneal replacement was determined by eyelid position and function and sufficiency of tear production. All patients were corneal blind with light perception only and cicatricial ectropion. The eye with better visual prognosis was reconstructed. Eyelid reconstruction procedures consisted of lid releases with full-thickness skin graft (FTSG) or split-thickness skin graft (STSG). Two patients regained adequate lid function and underwent standard keratoprosthesis placement. Two underwent mucous membrane grafts followed by keratoprosthesis. All patients experienced improved postoperative vision in their reconstructed eye. Corneal injury due to periocular burns can lead to blindness. Early involvement of ophthalmology, protective measures, and early ectropion release are critical. For severe burns, a multidisciplinary approach, where adequate globe protection is followed by keratoprosthesis placement, can effectively restore vision in patients with burn-related corneal blindness.

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.

Purpose To determine whether reliance on eyelid margin vascularization as a diagnostic criterion for meibomian gland dysfunction (MGD) results in underdiagnosis of MGD in individuals with dark skin pigmentation. Patients and methods This cross-sectional study enrolled consecutive cornea clinic patients in Buffalo, New York. Eyelid margin vascularization was graded qualitatively from slit-lamp photos. Skin pigmentation was quantified from digital photos using red/green/blue (RGB) pixel analysis and dichotomized using the RGB median. MGD was defined as abnormal quantity or quality of meibum or increased pressure required to express meibum. Additional testing included infrared meibography, Schirmer's testing, and a dry eye questionnaire. Sensitivity of MGD diagnosis by visualization of vascularization, compared to diagnosis by expression of meibum, was estimated with and without stratification by skin pigmentation. Results Among 47 participants, 15-79 years old, meibomian gland truncation/dropout, abnormal tear production, and dry eye symptoms affected individuals of all skin pigmentations. Eyelid margin vascularization was less common in subjects with dark (n=21%) compared to light pigmentation (65%; p=0.002), although the prevalence of MGD assessed via clinical evaluation did not vary significantly between those groups. Use of eyelid margin vascularization alone was not sensitive (33%) for MGD diagnosis. The sensitivity was 17% when limited to those with dark pigmentation. Conclusion Our findings highlight the importance of gland expression and suggest limiting reliance on eyelid margin vascularization for MGD diagnosis, especially in those with dark eyelid skin pigmentation.

Purpose. To study the dynamics of tear production and morphometric parameters of cornea after phacoemulsification of senile cataract (SC) at different postoperative terms. Material and methods. 123 patients (123 eyes) aged from 62 to 83 years were examined after phacoemulsification of SC. All patients were divided into 2 groups depending upon the level of tear production (TP): 1st group – 61 patients with normal and insufficiently lowered TP, 2nd group consisted of 62 patients with moderate and severe TP suppression. Besides standard examination methods, all patients underwent Schirmer’s – 1 test, tear breakup time (TBUT), cornea OCT, corneal endothelial cell density (CECD) before operation and on the 1st, 10th , 20th and 30th postoperative day. Results. Indices of TBUT, corneal epithelium and stromal thickness (CET and CST), CECD turned out to be lower in the eyes of patients from the second group in comparison with the 1st. Conclusion. The conducted research showed that postoperative changes of CET occur 4 times and CST 1,5 times more often in patients with moderate and severe decrease of TP rather than in eyes with normal TP. The recovery of TP on the final stage of research was found 2.6 times less in eyes of patients from the 2nd group in comparison with the 1st, which can be the evidence of possible neurotrophic corneal disorders in patients with reduced TP.

Dry eye disease (DED) is a commonly diagnosed disorder in small animals. It has been historically described as a quantitative or qualitative deficiency in tear production; however, the pathogenesis of the disease is much more complex than previously recognised. Ocular inflammation is the hallmark of DED, reflected in early nonspecific conjunctivitis and later in dramatic changes of the ocular surface. Prompt recognition of the disease, accurate diagnostics and appropriate treatment are paramount in preserving the ocular surface integrity and the patient's comfort. Part 1 discussed the aetiopathogenesis of the condition and described the clinical signs. This second article looks at diagnostics and treatment of ocular surface disorders in dogs.

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 commonly diagnosed disorder in small animals. It has been historically described as a quantitative or qualitative deficiency in tear production; however, the pathogenesis of the disease is much more complex than previously recognised. Ocular surface disorders in people are currently investigated as a dysfunction of what is termed the ‘lacrimal functional unit’, consisting of the ocular surface, including Meibomian glands and conjunctiva, in addition to lacrimal glands, eyelids and sensory and motor innervation. A loss of homeostasis of the tear film leads to the vicious cycle of increased osmolarity and inflammation, with dreadful consequences for the ocular surface in both dogs and humans. Ocular inflammation is the hallmark of DED, reflected in early nonspecific conjunctivitis and later in dramatic changes of the ocular surface. Prompt recognition of the disease, accurate diagnostics and appropriate treatment are paramount in preserving the ocular surface integrity and the patient's comfort. This article discusses the aetiopathogenesis of the condition, and describes the clinical signs, while the second article will look at diagnostics and treatment of ocular surface disorders in dogs.

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.

The aim is to evaluate the effectiveness of Stillavit in the treatment of dry eye syndrome (DES) and its effect on the density of conjunctival goblet cells and the functional parameters of tear production. Methods. There were analyzed treatment results of 18 patients (36 eyes) with DES at the age of 48 to 80 years (average 60.6 ± 1.3 years) including 17 women and 1 male before and after 1 and 3 months after Stillavit prescription. In all patients in addition to a standard ophthalmological examination the results of Schirmer I, Norn, as well as the LIPCOF test were evaluated and the density of conjunctival goblet cells was examined. Results. After 1 and 3 months there was a significant improvement in the results of the Norn test: from 5.17 ± 0.22 seconds to 7.18 ± 0.17 seconds which indicated an increase in the stability of the tear film. After 3 months there was a significant increase in the density of conjunctival goblet cells, improvement in the Schirmer sample: from 9.26 ± 0.89 to 11.7 ± 0.6 mm (t = 2.28, p < 0.05) and LIPCOF test (t = 2.18, p < 0.05) which indicated an increase in tear production and a significant decrease in the inflammatory process and edema of the conjunctiva. Conclusion. Treatment of DES with the use of Stillavit leads after 3 months to a significant increase in the density of conjunctival goblet cells, increases tear production and stability of the tear film.

Currently, there are many studies on the effectiveness of ointment ophthalmological medicines. Ophthalmic ointments are unique because they have a multi-component action mechanism. On the one hand, the action of the medicinal substance itself is prolonged due to the ointment base, and on the other hand, due to the structural features of the conjunctival cavity mucosa, these medicinal substances are very rapidly absorbed. In the treatment of ocular surface pathology, including as meibomiitis, barley and chalazions, local therapy and ointment forms are preferred. The purpose of the study was the investigation the antibacterial eye ointment effectiveness of domestic production Oftocipro — a fluoroquinolone derivative for the treatment of acute and chronic eyelid and conjunctiva diseases. During the study patients were divided into 2 groups with acute and chronic inflammatory diseases of the eyelids and conjunctiva in the acute stage. It is known that chronic pathological processes are often stopped in longer periods. This fact was a prerequisite for assessing the effectiveness of Ontocipro with a comparative analysis of the dynamics of subjective (patient complaints) and objective (biomicroscopy, tear production tests) indicators characterizing the severity of the inflammatory process. The study has showed a high drug efficacy, when it is applied topically 3–4 times a day. The average time to relieve the inflammatory process was 3–7 days. The possibility of using the drug Oftocipro locally, when it is applied to the eyelid area, without affecting the conjunctival cavity, allows to minimize the impact area due to the ointment base and limit the risk of side effects in the form of a violation of the natural conjunctival microflora. Considering high level of tolerance and low allergenicity of the drug Oftotsipro, it can be recommended for widespread use for the treatment of acute and chronic blepharoconjunctivitis, barley and chalazion in the acute stage, as well as meibomiitis.

Background: Aqueous deficiency dry eye is considered one of the main categories of dry eye syndrome. Many tech-niques have been developed to assess tear production and monitor tear film turnover. Methods such as Schirmer test, phenol red thread (PRT) test, and tear function index (TFI), have been widely used to diagnose aqueous deficient dry eye. All these tests are based on the principle of absorption of the tear from the lacrimal sac and then measuring the wetting length of the paper strip or cotton thread. The wetting length can be affected by environmental factors, particularly relative humidity, that could exert a strong effect on the absorption mechanism of the strips or threads used to measure tear production.Aim of the Work: The aim of this study was to investigate the effect of changing room relative humidity on the absorption properties of phenol red thread (PRT) and Schirmer strips, and their accuracy of measuring tear film production.Methods: Twenty healthy subjects (40 eyes) were recruited for this study. Tear film production was assessed using PRTs and Schirmer strips in two different environmental conditions. Two visits were required to conduct this study. One visit was used to measure tear production in a room without installing a humidifier. The other visit was used to measure tear film production after the room was humidified using portable air humidifiers.Result: Mean tear production measurements in non-humidified room were 16.04-}4.09 and 16. 12±9. 10mm using PRTs and Schirmer strips respectively. At high humidity visit, mean measurements was 20-}8.03mm and 19.35-}8.35mm.Conclusion: The physical properties of the examination strips and threads used for measuring tear quantity could be affected by environmental conditions. Eye care practitioners should be aware of the variation in tear production measure-ments that may result from external factors.

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.

This study was performed to investigate the effects of cyclopentolate on ultrasonographic parameters of eye structures, intraocular pressure (IOP), tear production, and pupil size in normal donkeys. Sixteen eyes of eight clinically healthy adult donkeys (2–2.5 years old) weighing 295 ± 34 kg (mean ± standard deviation) were used in this study. Cyclopentolate hydrochloride 1% was instilled in a randomly selected eye and the other eye received normal saline drops as a control. The effect of cyclopentolate was evaluated by ultrasonography. Additionally, changes in IOP and tear production were evaluated for 2 hours post-instillation by tonometry and Schirmer tear test (STT), respectively. Vertical and horizontal pupil diameters were recorded pre-instillation (0), and 15, 30-, 45-, 60-, and 120-minutes post-instillation. After cyclopentolate 1% instillation, iridocorneal angle and width of the entry of ciliary cleft were significantly increased as observed by ultrasonography. IOP was significantly increased starting from 30 minutes till 60 minutes post-instillation of cyclopentolate 1%. Non-significant alteration in the STT was observed in the cyclopentolate-treated eyes compared to the control eyes. Both vertical and horizontal pupil diameters began to significantly increase 30 minutes after cyclopentolate 1% instillation compared to the control saline group. In conclusion, cyclopentolate 1% could be used as a potent cycloplegic drug in donkeys without systemic or ocular side effects.

This study aims to determine the intraocular pressure (IOP) of healthy Turkish Eastern Anatolian Red (EAR) cattle eyes using the iCare® Rebound Tonometer (RT). In addition, we aimed to evaluate whether there is a difference in the IOP values depending for the left or right eyes, time of day, gender, and age of animals. The research was carried out on 42 EAR cattle. The cattle were divided into 3 groups, group I (7 male, 7 female, n=14), group II (7 male, 7 female, n=14), and group III (7 male, 7 female, n=14) 6, 12, 24 months old, respectively. Measurements were performed, in the morning (6:00 a.m.), in the noon, and the evening (6:00 p.m.). The average IOP values for groups I, II and III was 24.51±0.91 mm Hg (P=0.520), 24.23±0.87 mm Hg (P=0.621) and 23.98±0.82 mmHg (P=0.772). According to the findings of this research for the values, the IOP of EAR cattle using the RT no statistically significant differences between right and left eyes, time of day, gender, and age were found for any of the results (P>0.05). In this study, the IOP reference value for EAR cattle was determined as 24.24±0.54 mm Hg using RT, regardless of any variable. In addition, this study is the first research article in which the intraocular pressure in Turkish Eastern Anatolian Red cattle was measured by the iCare® Rebound Tonometer. © 2021, Israel Veterinary Medical Association. All rights reserved., This study was presented at the 4th International Conference on Advances in Natural and Applied Sciences, 19-22 June 2019, Ağrı, Turkey.

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.

Measurements of intraocular pressure (IOP) and tear production are key components of ophthalmic examination. Chimpanzees (Pan troglodytes) were anesthetized using either tiletamine-zolazepam (TZ; 2 mg/kg) combined with medetomidine (TZM; 0.02 mg/kg), or, TZ alone (6mg/kg). Tear production was lower (P = 0.03) with TZM (5.63 ± 6.22 mm/min; n = 16) than with TZ (11.13 ± 4.63 mm/min; n = 8). Mean IOP, measured using rebound tonometry in an upright body position (n = 8) was 18.74 ± 3.01 mm Hg, with no differences between right and left eyes. However, positioning chimpanzees in left lateral recumbency (n = 27) resulted in higher IOP in the dependent (left) eye (24.77 ± 4.49 mm Hg) compared to the nondependent (right) eye (22.27 ± 4.65 mm Hg) of the same animal (P < 0.0001). These data indicate medetomidine anesthesia markedly lowers tear production in chimpanzees, and that body position should be taken into consideration when performing rebound tonometry.

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.

The frequency and structure of ophthalmopathology in workers of the Novokuznetsk Metallurgical Combine (NMC) have been studied. In total 1911 workers of NMC have been examined. The control group comprised 1801 people working in hazardous industrial conditions. The experimental group consisted of employees dealing with management, engineering center, accounting (110 people). Their work was not connected with the impact of unfavorable factors of metallurgical production. In the control group, the hazard classes ranged from 3.2 to 3.4. The difference between the classes of hazard impact consisted in an increase of the intensity of the hazardous factors exposure. In the structure of conjunctival diseases we have diagnosed chronic conjunctivitis (198.3 ‰), chronic blepharoconjunctivitis (109.4 ‰), pinguecula (266.7 ‰) and pterygium (7.2 ‰) in metallurgical workers. Pengucules in the control group of workers was not only more often than in engineers, but also larger, often located in the inner and outer corner of the eye, and was detected in workers under 30–35 years. The workers of the main shops suffered more severely from the function of tear production and the stability of the pre-corneal tear film. The miners suffered from the highest frequency of cataract development — 301 ‰. Thus, a high incidence of inflammatory and dystrophic diseases of the eyelids and conjunctiva, cataracts in metallurgy has been established. An increase in the frequency of ophthalmopathology was noted with an increase in the length of service under harmful conditions of metallurgical production. The authors suggest the term “metallurgy ophthalmopathy”, which includes manifestations of chronic conjunctivitis and / or blepharoconjunctivitis against the background of unstable precorneal film and frequent formation of posterior-subcapsular opacities of the lens.

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.

Vinod Burade,1 Rishit Zalawadia,1 Alpesh Patel,1 Abayomi Ogundele2 1Sun Pharmaceutical Industries Limited, Vadodara, Gujarat, India; 2Sun Pharmaceutical Industries, Inc, Princeton, NJ, USACorrespondence: Abayomi OgundeleSun Pharmaceutical Industries, Inc, Princeton, NJ, USATel +1 (609) 720-5389Email Abayomi.Ogundele@sunpharma.comIntroduction: Cyclosporine ophthalmic solution 0.09% (CsA 0.09% sol) is approved to increase tear production in patients with keratoconjunctivitis sicca. This study evaluated the efficacy of CsA 0.09% sol vs cyclosporine ophthalmic emulsion 0.05% (CsA 0.05% eml) vs ciclosporin ophthalmic emulsion 0.1% (CsA 0.1% eml) in a NOD mice model.Methods: Mice were randomized and administered placebo, CsA 0.09% sol twice daily, CsA 0.05% eml twice daily, CsA 0.09% sol once daily, or CsA 0.1% eml once daily in the conjunctival sac of both eyes for 60 days. Tear volume was measured with phenol red threads at baseline and 4 hours after treatment every 15 days. On day 58, the corneal surface was observed under a slit-lamp after staining with 3% lissamine green administered into the inferior lateral conjunctival sac. On day 61, mice were euthanized, globes excised, sliced into 4 μm sections in 3 areas per section, and stained. Total number of stained goblet cell/μm was counted, and the sum per eye was averaged. Lacrimal gland tissues were removed and interleukin (IL) 1-β cytokine levels estimated.Results: Groups comprised 11 mice each, including an untreated normal and untreated diseased control group (7 groups total). CsA 0.09% sol twice daily significantly increased tear volume on day 30, 45, and 60 vs CsA 0.05% eml (P< 0.05, < 0.001, < 0.001, respectively) and vs CsA 0.1% eml on day 60 (P< 0.05); CsA 0.09% sol once daily significantly increased tear volume on day 45 vs CsA 0.05% eml (P< 0.05). Goblet cell density significantly increased with CsA 0.09% sol twice daily vs placebo and NOD control (P< 0.01 both). There was no significant difference in corneal staining and IL-1β levels with CsA 0.09% sol.Conclusion: Sixty-day treatment with CsA 0.09% sol showed comparatively improved preclinical results vs CsA 0.05% eml and CsA 0.1% eml.Keywords: cyclosporine A, goblet cell density, keratoconjunctivitis sicca, preclinical, tear production

Background Sjogren syndrome (SS) is an autoimmune disease which involves the nervous system in about 20% of SS cases, whilst in 25-92% neurological symptoms may precede the onset of sicca syndrome. Methods A 65-year-old male came to our observation due to a 7-month history of near-syncope episodes, constipation, hypohidrosis, fatigue and asthenia. Past history revealed hypothyroidism due to Hashimoto's thyroiditis, under treatment with levothyroxine. Physical examination showed: temperature 36.5 °C, blood pressure 90/60 mmHg and respiration rate 20 breaths per minute. The ECG revealed sinus bradycardia with 55 beats per minute (bpm) and right bundle-branch block (RBBB). Laboratory exams showed: lymphocytopenia (WBC 9008/μL, with 90% granulocytes and 3% lymphocytes); CRP (0.3 mg/dL), ESR (20mm/hr). In order to investigate endocrine disorders, hormone tests were also performed, showing: euthyroidism (FT3 2.0 pg/mL, FT4 12.6 pg/mL, TSH 1.685 µUI/mL, Ab anti-thyroglobulin 1630.0 UI/mL, Ab anti-thyreoperoxidase 592.5 UI/mL), hypogonadotropic hypogonadism (LH 1.6 mIU/mL, FSH 2.7 mIU/mL, prolactin 15.9 ng/mL, testosterone 133 ng/dL) and normal adrenocortical function (serum cortisol 8 am 17.5 µg/dL, aldosterone 6.8 pg/dL, ACTH 8.5 pg/mL). Brain-MRI showed anterior pituitary hypoplasia. Results In order to assess a potential autonomic neuropathy, deep breathing test (E/I 1.02) , lying to standing test (R/R’ 0.95) and orthostatic hypotension tests (at 120 seconds systolic reduction was >20 mmHg and diastolic reduction >10 mmHg) were performed, all resulting pathological. ECG Holter monitoring revealed sinus bradycardia, with a mean heart rate of 55 bpm and RBBB. Holter blood pressure 24-hour monitoring showed a diurnal hypotensive profile. The echocardiogram revealed a mild mitral and tricuspid insufficiency. A paraneoplastic syndrome was also excluded by total body-CT with mean of contrast and tumor markers, which resulted normal. On a further assessment, the patient reported a 3-month history of worsening dry mouth and persistent dehydrated tongue. Signs of anisocoria in response to light stimulation, were observed as well. Tests for autoimmune diseases showed ANA (1:320 speckled pattern), Ro/SS-a (>240U/l) and La/SS-b (162 U/ml) antibodies. Though symptoms such as dry eyes were not reported, “Shirmer test” revealed an insufficient tear production in both eyes (RE 5 mm, LE 3 mm). The patient was discharged with the diagnosis of autonomic neuropathy most likely due to primary Sjögren’s syndrome and started therapy with Prednisone 25 mg/die and Hydroxychloroquine 200 m/bid o.d. After one month, he reported a significant improvement in symptoms such as asthenia, fatigue and dry mouth. Orthostatic hypotension symptoms were also significantly decreased and no further near-syncopal events occurred. Conclusion This case underlines the clinically importance of dys-autonomic symptoms, antecedent to the onset of sicca syndrome, and highlights the favorable response to immune-modulating therapy in the treatment of autonomic dysfunction arising from SS. Disclosures F. Masini None. K. Gjeloshi None. F. Danzo None. E. Pinotti None. L. Monaco None. G. Cuomo None.

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.

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.

The aim of this study was to determine of the effects of midazolam, ketamine and isoflurane anesthetic agents on tear production and intraocular pressure in rabbits. In this study twenty healthy (n=20) male white New Zealand rabbits (mean weight 2.20 ± 0.50 kg, age 16 weeks) were used. Anesthesia was performed intramuscular (IM) midazolam 3 mg/kg, and ketamine 30 mg/kg in group I. In second group (Group II), after midazolam and ketamine injections isoflurane 2% was used for general anesthesia. After anesthesia means intraocular pressure (IOP) decreased in both groups. Intraocular pressure in first group (Group I) was 10.3 ± 0.85 mmHg (right eyes), 11.4 ± 0.95 mmHg (left eyes) while it was 8.5 ± 0.85 mmHg (right eyes), 8.3 ± 0.85 mmHg (left eyes) n group II. The result of this study show that systemically used midazolam, ketamine and isoflurane anesthetic agents decrease IOP and tear secretion in rabbits.

Normal values for intraocular pressure (IOP) and tear production in conscious cervids have not been reported to date. Based on trends in zoological institutions to perform non‐anaesthetized health exams, it is applicable to establish normal values in conscious animals, as anaesthesia and sedation can alter these parameters. The goal of this study was to estimate intraocular pressures using rebound tonometry and measure tear production values in a group of healthy, conscious, European fallow deer utilizing chute restraint. Evaluation of these values with regards to instrumentation and restraint variables will be assessed. Complete ophthalmic examinations, including estimation of IOP with rebound tonometry and measurement of tear production with Schirmer tear tests (STT) were performed on nine conscious European fallow deer (Dama dama) restrained in a chute. Correlations between IOP on the unspecified (P) and the equine (H) settings, as well as IOP and STT differences between left (OS) and right (OD) eyes were evaluated, in addition to assessment of correlations between right and left lateral recumbency on IOP and STT. Tear production measurements were 18.7 ± 5.1 mm min−1 with a 95% confidence interval (CI) range of 16.4–21.1 mm min−1. Intraocular pressure measurements for the P setting were 16.1 ± 4.5 mmHg with a 95% CI range of 14.1–18.2 mmHg, and for the H setting were 21.5 ± 5.1 mmHg with a 95% CI range of 19.1–23.9 mmHg. No statistically significant difference (P > 0.05) was found between OS and OD in any test. Neither left nor right lateral recumbency was found to have a statistically significant effect on IOP or STT. This study represents the first assessment of ophthalmic parameters in conscious fallow deer with rebound tonometry and STT.

Purpose. To investigate the tear production (TP) dynamics in patients with age-related cataract before and after phacoemulsification (PE). Material and methods. 136 patients (136 eyes) admitted for age-related cataract treatment. Age 69.3 6.4 years. 64 men and 72 women. Besides standard ophthalmological examination, in all patients Schirmer`s I test was performed before surgery on the next day, 7, 14 and 30 days after surgery. Patients were divided into 4 groups. The 1st group consisted of 32 patients (32 eyes) with TP 15 mm and more. The 2nd group 48 patients (48 eyes) with TP from 10 to 15 mm. The 3rd group 40 patients (40 eyes) with TP from 5 to 10 mm. The 4th group 16 patients (16 eyes) with TP less than 5 mm. In all patients, PE was performed according to standard technology. Results. All surgeries were performed without complications. In 56 eyes of groups 3 and 4 (41.2%) there was depression of TP of moderate and severe degree before surgery. The first day after surgery in all study groups there was twofold increase of Schirmer`s test indices. Starting from 7th day after surgery, in all groups, a 22-35% decrease of TP from baseline was observed. Later on, a gradual increase of TP was noted. On the 30th day after PE, Schirmer`s test indices were lower than those of baseline in 4 eyes (13%) of the 1st group, 10 eyes (21%) of the 2nd group, 31 eyes (77%) of the 3rd group, and 10 eyes (63%) of the 4th study group. Conclusions. The study of TP in patients with age-related cataract showed that during one month after surgery TP returned to baseline indices only in 59.6% of patients. Regardless of its baseline indices, after the surgery, there is an universal TP dynamics, which is characterized by its initial increase, subsequent decrease and gradual return to baseline indices. Patients with initial low TP indices have potentially high risk of developing clinically significant dry eye syndrome.