Recombinant human nerve growth factor (cenegermin) for moderate-to-severe dry eye: phase II, randomized, vehicle-controlled, dose-ranging trial.

BACKGROUND: Dry eye disease (DED) includes neurosensory abnormalities as part of its multifactorial etiology. Nerve growth factor is important for maintaining corneal nerve integrity and wound healing. Cenegermin (recombinant human nerve growth factor) is a topical biologic that promotes corneal healing in patients with neurotrophic keratitis. The purpose of this study was to evaluate efficacy and safety of cenegermin in moderate-to-severe DED and identify an optimal dosing strategy. METHODS: This was a phase II, multicenter, randomized, double-masked, vehicle-controlled, dose-ranging clinical trial in patients with moderate-to-severe DED, including Sjögren's DED (NCT03982368). Patients received 1 drop of cenegermin 3 times daily (t.i.d.; 20 mcg/mL), cenegermin 2 times daily (b.i.d.; 20 mcg/mL) and vehicle once daily, or vehicle t.i.d. for 4 weeks. Follow-up continued for 12 additional weeks. The primary endpoint was change in Schirmer I score from baseline to week 4. Other key endpoints included rate of responders (Schirmer I test > 10 mm/5 min) after treatment and change in Symptoms Assessment iN Dry Eye (SANDE) scores from baseline to end of follow-up. A 1-sided test (α = 0.025) was used to evaluate statistical significance. RESULTS: At week 4, mean changes in Schirmer I scores were not statistically significantly different in either cenegermin group versus vehicle (cenegermin vs vehicle [treatment difference; 95% CI]: t.i.d., 2.60 mm and b.i.d., 3.99 mm vs 1.68 mm [t.i.d.: 0.93; -1.47 to 3.32, P = 0.078; b.i.d.: 2.31; -0.08 to 4.70, P = 0.066]). More patients responded to treatment with cenegermin t.i.d. and b.i.d. versus vehicle (t.i.d.: 25.9% [21/81, P = 0.028]; b.i.d.: 29.3% [24/82, P = 0.007] vs 11.9% [10/84]), with statistical significance (set at P < 0.025) observed in the b.i.d. group. Only cenegermin t.i.d. yielded statistically significant (P < 0.025) reductions in SANDE scores versus vehicle, which were sustained up to the end of follow-up (P value range, 0.002-0.008). Eye pain, primarily mild and transient, was the most frequently observed treatment-emergent adverse event with cenegermin. Similar results were observed in patients with Sjögren's DED. CONCLUSIONS: Cenegermin was well tolerated and although this study did not meet its primary endpoint, significant improvement in patient-reported symptoms of dry eye was observed through follow-up. Larger studies evaluating cenegermin in patients with DED are warranted. TRIAL REGISTRATION: NCT03982368; registered May 23, 2019.

Characterization of ophthalmic lesions and normal ocular parameters in a flock of captive MacQueen's (houbara) bustards (Chlamydotis macqueenii).

OBJECTIVES: To determine normal ocular parameters of the MacQueen's bustard (Chlamydotis macqueenii) and describe ophthalmic lesions in a captive bred population. ANIMALS STUDIED: Captive breeding population of 257 Macqueen's bustards. METHODS: All birds were screened for ocular abnormalities using direct ophthalmoscopy. Abnormalities were photographed. Normative values for Schirmer tear test-1 (STT-1), applanation tonometry, aerobic and anaerobic bacterial culture, fungal culture, and transcorneal ocular ultrasonography were derived from multiple cohorts of clinically normal adult birds. Five birds with ocular pathology also underwent transcorneal ultrasonography. Statistical comparisons for normative values between OD and OS, and males and females were made using a paired t-test or Mann-Whitney U-test, with a significance level of p < .05. RESULTS: Mean tear production based on Schirmer tear test 1 (STT-1) was 10.16 ± 4.61 mm/min (3-21 mm/min). Mean intraocular pressure (IOP) was 12.42 ± 4.94 mm Hg (5-26 mm Hg). Staphylococcus species were the most isolated bacteria from the conjunctival surfaces of normal birds (85%). Significant differences were found in transcorneal ultrasonographic measurements between males and females for axial globe length (p = .032), vitreous body depth (p = .049) and lens thickness (p = .0428). Corneal fibrosis was the most observed ocular abnormality amongst eyes with pathological changes (39%). CONCLUSIONS: Schirmer tear testing, tonometry and transcorneal ultrasound can easily be utilized in MacQueen's bustards and provide reproducible results. Normal parameters for these tests were determined, and common pathological ocular changes were described in this species.

Proportion of dry eye in type II diabetics.

Introduction: Diabetes mellitus is a multisystem disorder, which is one of the most prevalent and important non-infectious causes of morbidity and mortality worldwide. While diabetic retinopathy (DR) and diabetic cataracts are well-known complications, dry eye syndrome (DES), also referred to as keratoconjunctivitis sicca, is also common in the diabetic population. If left untreated, severe dry eye may lead to eye inflammation, abrasion of the corneal surface, corneal ulcers, and vision loss. So, it is very important to diagnose it earlier as these devastating complications can be prevented. Materials and Methods: A total of 200 adult patients diagnosed with type II diabetes of either sex with an age more than 40 years were selected. Complete ophthalmological examination was done. Dry eye was diagnosed on the basis of various objective tests, and proportion of dry eye and its relation with glycemic control were studied. Conclusion: Patients with uncontrolled type II diabetes had a higher proportion of dry eye disease. A significant co-relation was found among the FBS levels, the HbA1c levels, age, duration of disease, and dry eye in patients with diabetes. No significant co-relation was found between the sex of the patient and dry eye in patients with diabetes. Hence, our study recommends that primary care physicians should advise their patients to get clinical evaluation for dry eye done along with diabetic retinopathy in uncontrolled diabetes.

[Current possibilities for the diagnosis and treatment of pterygium]. / Sovremennye vozmozhnosti diagnostiki i lecheniya pterigiuma.

Pterygium is a common inflammatory-proliferative disease characterized by the invasion of degeneratively altered fibrovascular tissue into the cornea. This literature review analyzes the etiological factors and pathogenetic concepts of its development, describes modern methods of diagnostics and surgical treatment of pterygium, and pays particular attention to the assessment of structural and functional changes in the cornea occurring during the growth of pterygium and after its excision.

Peripheral hypertrophic subepithelial corneal opacification - Role of tear secretion, medication and systemic diseases.

BACKGROUND: Peripheral hypertrophic subepithelial corneal opacification (PHSCO) is a corneal disease that may severely affect vision. The major goal of this study was to test the hypothesis that tear secretion, medication and systemic diseases are associated with PHSCO. METHODS: This is a retrospective, case-control study conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. We analysed medical records of patients diagnosed with PHSCO. Sex, age, Schirmer's test II, general medication and medical history were assessed and compared to an age- and sex-matched control group from the Gutenberg Health Study (GHS). RESULTS: One hundred ninety-five eyes of 112 patients with PHSCO were included. Eighty-eight patients were female with a mean age of 55.3 ± 14.7 years (23-89 years) and 24 patients were male with a mean age of 59.3 ± 12.6 years (38-84 years). In 83 patients (74.1%) both eyes were involved. The Schirmer's test II was significantly reduced in patients with PHSCO compared to the GHS control group (p < 0.001). Patients with PHSCO were more frequently administered artificial tears and steroid eye drops (p < 0.001) and were more hyperopic than healthy controls (p = 0.01). Systemic diseases or medication did not differ markedly between PHSCO and healthy controls. CONCLUSION: Reduced tear secretion and more frequent use of artificial tears in patients with PHSCO suggest a link between PHSCO and dry eye disease. The results of the study do not support our hypothesis that PHSCO is associated with systemic diseases. Interestingly, patients with PHSCO were less frequently on ß-blockers than control subjects.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

Characterizing the Robustness of Distinct Clinical Assessments in Identifying Dry Eye Condition of Animal Models.

PURPOSE: The study aims to characterize the robustness of distinct clinical assessments in identifying the underlying conditions of dry eye disease (DED), with a specific emphasis on the involvement of conjunctival goblet cells. METHODS: Seven rabbits receiving surgical removal of the lacrimal and Harderian glands were divided into two groups, one with ablation of conjunctival goblet cells by topical soaking of trichloroacetic acid (TCA) to the bulbar conjunctiva (n = 3) and one without (n = 4), and the conditions of DED were assessed weekly using Schirmer test, tear breakup time (TBUT), tear osmolarity, and National Eye Institute (NEI) fluorescein staining grading. After 8 weeks, the rabbits were sacrificed, and the eyes were enucleated for histopathological examination. RESULTS: Histopathological analysis revealed corneal epithelial thinning in both groups. While TCA soaking significantly decreased the density of conjunctival goblet cells, DED rabbits without TCA also showed a partial reduction in goblet cell density, potentially attributable to dacryoadenectomy. Both groups showed significant decreases in Schirmer test and TBUT, as well as an increase in tear osmolarity. In DED rabbits with TCA soaking, tear osmolarity increased markedly, suggesting that tear osmolarity is highly sensitive to loss and/or dysfunction of conjunctival goblet cells. Fluorescein staining was gradually and similarly increased in both groups, suggesting that fluorescein staining may not reveal an early disruption of the tear film until the prolonged progression of DED. CONCLUSION: The Schirmer test, TBUT, tear osmolarity, and NEI fluorescein grading are distinct, yet complementary, clinical assessments for the evaluation of DED. By performing these assessments in definitive DED rabbit models, both with and without ablation of conjunctival goblet cells, the role of these cells in the homeostasis of tear osmolarity is highlighted. Characterizing the robustness of these assessments in identifying the underlying conditions of DED will guide a more appropriate management for patients with DED.

Evaluation of Main Lacrimal Gland through Shear-wave Ultrasound Elastography in Patients with Low Schirmer Value

OBJECTIVE: To compare main lacrimal gland values through shear-wave elastography (SWE) in patients with low Schirmer value and unspecified Sjögren's syndrome (SS) with healthy controls. MATERIAL AND METHOD: Admitted to the ophthalmology department with Schirmer value <10 mm, randomly selected 46 eyes of 46 patients evaluated for Sjögren's syndrome (SS) in the rheumatology department between December 2022 and April 2023 were classified as low Schirmer group (LSG). Randomly selected 48 eyes of 48 patients at a similar age with Schirmer value >10 mm were included as controls. Main lacrimal gland SWE measurements in LSG and control groups were recorded and compared as meter/second (m/sec). RESULTS: Mean SWE values of the main lacrimal gland were measured as 2.78 ± 0.66 m/sec and 2.26 ± 0.29 m/sec in LSG and controls. SWE measurements were significantly higher in LSG patients than in controls (p<0.001). No significant correlation was found in the analysis between the Schirmer and the main lacrimal gland SWE values in LSG patients (p=0.702, r=0.058). No significant correlation was also detected between the Schirmer and main lacrimal gland SWE values in controls (p=0.097, r=0.242). No significant relationship was also found between age, gender, body mass index (BMI), and SWE values (p=0.351, p=0.493, p=0.328, respectively). CONCLUSION: Mean SWE value of the main lacrimal gland was determined as significantly higher in patients with aqueous lacrimal insufficiency without SS than in controls. We consider that SWE measurements may be an imaging method to support the diagnosis of aqueous lacrimal insufficiency and used in follow-ups of those with dry eye syndrome (DES) in the future.

The association of pre-photorefractive keratectomy Schirmer-1 test value with postoperative corneal epithelial thickness, ocular surface discomfort, and visual acuity

ABSTRACT Purpose: To investigate the association of pre--photorefractive keratectomy Schirmer-1 test value with post--photorefractive keratectomy central corneal epithelial thickness, ocular surface disease index score, and uncorrected distance visual acuity. Methods: Patients were categorized according to preoperative Schirmer-1 value: the normal Schirmer Group (n=54; Schirmer-1 test value, >10 mm) and the low Schirmer Group (n=52; Schirmer-1 test value, between 6 and 10 mm). We analyzed ablation depth, visual acuity, result of Schirmer-1 test (with anesthesia), tear film break-up time, ocular surface disease index score, central corneal epithelial thickness, and spherical equivalent refraction. Results: We found significant differences between the groups in Schirmer-1 test value, tear film break-up time, and ocular surface disease index score, both preoperatively and postoperatively (p<0.001). The preoperative central corneal epithelial thicknesses of the two groups were similar (p>0.05). After photorefractive keratectomy, the Schirmer-1 test value and spherical equivalent refraction decreased in both groups (p<0.05), and ocular surface disease index scores and central corneal epithelial thickness values increased in the low Schirmer Group (p<0.001) but not in the normal Schirmer Group (p>0.05). The postoperative central corneal epithelial thicknesses of the low Schirmer Group were significantly higher than those of the normal Schirmer Group (p<0.001). Postoperative uncorrected distance visual acuity did not differ significantly between the two groups (p>0.05). Conclusions: In patients with low Schirmer-1 test values before photorefractive keratectomy, the corneal epithelium thickened and ocular surface complaints increased during the postoperative period. However, changes in the corneal epithelium did not affect the postoperative uncorrected distance visual acuity. To reduce postoperative problems on the ocular surface in these patients, we recommend that dry eye be treated before photorefractive keratectomy.

Seasonality of Tear Meniscus Volume and Dry Eye-Related Symptoms - A Cross-Sectional Retrospective Cohort Study.

Purpose: We aimed to determine the seasonal variation in the tear meniscus level on strip meniscometry and its association with ocular parameters and symptoms. In Japan, there are four distinct seasons characterized by marked differences in temperature and humidity, which may contribute to an observed seasonality of ocular surface symptoms. Methods: We conducted a cross-sectional study in two Japanese clinics and recruited first-visit patients for 3 years. Tear strip meniscometry, tear break-up time (BUT), Schirmer test, and corneal staining were examined, and major ocular symptoms (dryness, irritation, pain, fatigue, blurred vision, and photophobia) were determined through interviews. Results: The 1196 participants had a mean age of 58.9±15.2 years; 37.1% were of male sex. Strip meniscometry values and BUT revealed significant seasonality with one-way analysis of variance. The mean strip meniscometry value (mm) was 2.15±2.59 in spring (p=0.025 vs winter), 2.37±2.79 in summer (p<0.001), 2.38±2.80 in fall (p<0.001), and 1.64±2.29 in winter. Regression analysis indicated that strip meniscometry levels were correlated with BUT (p<0.001), Schirmer test values (p<0.001), corneal staining scores (p=0.022), and presence of dryness (p<0.001). Conclusion: Strip meniscometry values exhibited distinct seasonality, being lowest in winter when the ambient condition is dry and cool, and were correlated with BUT, Schirmer test values, corneal staining scores, and the presence of subjective dryness.

Prevalence and risk factors of dry eye disease in patients treated with aromatase inhibitors for breast cancer.

CLINICAL RELEVANCE: Treatment with aromatase inhibitors (AIs) in patients with breast cancer can lead to dry eye disease (DED). BACKGROUND: The purpose of the study is to determine the prevalence and risk factors of DED in patients treated with AIs for breast cancer. METHODS: Participants in this cross-sectional study were patients with breast cancer treated with AIs. Demographic and clinical data, including age, sex, type of cancer, stage, grade, duration of treatment and adjuvant chemotherapy and/or radiotherapy were collected. All patients underwent a detailed ophthalmic examination, as well as Tear Break up Time (TBUT) and Schirmer test, while Ocular Surface Disease Index (OSDI) questionnaires were administered. Based on the clinical findings, a diagnosis of DED was made, and prevalence was calculated. Univariate analysis of the association of different variables with DED was performed. A logistic regression analysis was done to identify risk factors for DED among study population. RESULTS: A total of 102 participants were included in the study. The mean age of patients was 62.4 ± 10.8 years. A total of 77 out of 102 patients (75.5%) had ductal, 16 (15.7%) lobular and 9 (8.8%) other types of breast cancer. A total of 83 patients (81.4%) received chemotherapy and 70 patients (68.6%) received radiotherapy. The mean duration of treatment was 24.4 ± 18.9 months. The prevalence of DED in the study sample was 69.6%. Patients who received radiotherapy (OR = 3.31, 95%CI = 1.30-7.82, p = 0.01) or were under treatment with AIs for more than 24 months (OR = 3.53, 95%CI = 1.47-9.21, p = 0.002) were found to have an increased risk of DED. CONCLUSION: There was a high prevalence of DED among the study population. Radiotherapy and duration of treatment with AIs were independently associated with DED.

Ultrasound abnormalities of the major salivary glands in Egyptian patients with systemic sclerosis.

INTRODUCTION/OBJECTIVES: systemic sclerosis (SSc) is an autoimmune disorder with multiple organs destruction. This study aimed to identify the ultrasonographic changes of major salivary glands in Egyptian scleroderma patients and to detect their association to different disease manifestations. METHODS: Forty-seven SSc patients and 43 apparent healthy volunteers were enrolled. Demographics, inflammatory markers, and autoimmune status were recorded. Ultrasound evaluation of salivary glands was performed. Salivary gland changes' associations were statistically examined with SSc susceptibility and disease manifestations. RESULTS: Thirty-one SSc patients exhibited glandular pathology (p < 0.0001), compared to controls. Of these abnormalities, SSc patients showed a total parotid gray scale of 2, total submandibular gray scale of 2, total glandular gray scale of 4, and total glandular Doppler signal of 1 at p < 0.0001, compared to the control group. Patients with SSc and glandular pathology had a higher prevalence of arthritis (p = 0.029) and ESR (p = 0.002) than those with normal glandular ultrasound. Significant associations were reported between gray scale ultrasound (GSUS) of total parotid (odds ratio "OR" = 0.4), total submandibular (OR = 0.36), and total glandular (OR = 0.53) with susceptibility to SSc at p < 0.0001. Total glandular GSUS (p = 0.039) and total submandibular power Doppler (p = 0.044) correlated with the SSc duration. Total parotid GSUS (p = 0.008) and total glandular GSUS (p < 0.0001) correlated with Schirmer's test. CONCLUSIONS: Major salivary glands are affected in SSc. Hence, scanning these glands with ultrasound is an additive tool besides the current practice. Key Points • Major salivary gland changes, observed by ultrasonography, are new findings in Egyptian SSc patients. • Ultrasound changes of major salivary glands are associated with inflammatory markers and clinical manifestations of SSc. • Scleroderma ultrasonography scans of the main salivary glands could be added to the routine work.

Serum Vitamin D Levels and Dry Eye Disease in Postmenopausal Women: A Case-Control Study at a Tertiary Care Center in Rural Haryana.

Background: Despite the high prevalence of Vitamin-D insufficiency and high susceptibility to dry eye disease (DED) in postmenopausal women (PMW), correlation between DED and Vitamin D has not been explored in PMW in any Indian study. Aims and Objectives: To explore the correlation between serum Vitamin D levels in PMW with and without DED, in a hospital-based population in rural Haryana. Materials and Methods: Subjective (ocular surface disease index [OSDI] questionnaire) and objective clinical tests were undertaken for DED diagnosis. 25(OH) Vitamin D was measured in serum using enzyme-linked immunosorbent assay; insufficient (10-30 ng/ml) and deficient (<10 ng/ml). Descriptive statistics were analyzed by mean ± standard deviation for continuous and frequencies for the categorical variables; Student's t-test used to find out mean difference in Vitamin D levels; P < 0.05 was considered statistically significant. Results: One hundred and forty PMW (60.1 ± 5.32 years) were included; Group-A (Controls; no DED; n: 70); Group-B (Cases; DED diagnosed by OSDI scores; n: 70); Subgroup-B1 (clinical tests negative; n: 30) and B2 (clinical tests positive; n: 40). There was no statistically significant difference in OSDI scores between B1 and B2. Significantly lower mean Vitamin D levels were found in cases (14.36 ± 4.08 ng/ml) as compared to controls (19.19 ± 6.4 ng/ml) (P = 0.001) and in B2 (13.15 ± 3.51 ng/ml) as compared to B1 (15.57 ± 4.66 ng/ml) (P = 0.01). Conclusion: There were significantly low levels of Vitamin-D in clinically established DED. Evaluating Vitamin D levels as a part of the dry eye workup in PMW is recommended. OSDI scores were not aligned with the clinical test scores; questionnaire-based tests alone may not be sufficient for diagnosing DED.

Tear fluid and complement activation products in tears after ocular surgery.

PURPOSE: Due to technological advancements, surgical invasiveness has been reduced. However, cataract surgery has been implicated in causing postoperative inflammation, including dry eye syndrome. The innate immune system may be involved in postoperative inflammation, and complement activation could potentially play a crucial role in defense against pathogens, homeostasis, and wound healing. To investigate changes in the tear film complement activation products (CAPs) and ocular surface after vitrectomy combined with cataract surgery. METHODS: Forty-three patients (23 women; median age, 69 years) were enrolled in this prospective study and underwent phacoemulsification and vitrectomy. We measured Schirmer's test (ST) and CAPs in the tears at baseline (the day before surgery), 4 days and 1 month after the surgery. Tears were collected in microtubes. The CAPs in the tear fluid were analyzed by cytometric bead array. RESULTS: The median ST (8.5 mm) at baseline increased to 16 mm at 4 days ( P < 0.001) and 10 mm at 1 month (P = 0.44). The C3a levels (1202 pg/ml) at baseline increased to 2753 pg/ml at 4 days (P < 0.001), and 1763 pg/ml at 1 month (P = 0.049). The C4a levels (476 pg/ml) at baseline increased to 880 pg/ml at 4 days (P < 0.001), and 657 pg/ml at 1 month (P = 0.013). The C5a levels (22.6 pg/ml) at baseline increased to 470.9 pg/ml at 4 days (P < 0.001), and 38.3 pg/ml at 1 month (P = 0.0048). The surgical eyes were divided into the short ST group (≦ 10 mm, n = 22) and long ST group (> 10 mm, n = 21) based on the preoperative ST values. At 1 month postoperatively, the C3a levels were 2194 pg/ml in the preoperative short ST group and 1391 pg/ml in the long ST group, with significantly higher C3a concentrations in the short ST group (P < 0.001). CONCLUSIONS: The CAPs levels in tears increased after vitrectomy combined with cataract surgery. A preoperative deficit in tear secretion might induce prolonged complement activation and delayed recovery of ocular surface parameters postoperatively.

Intranasal Schirmer Test in Allergic Rhinitis: Relationship to Symptom Scores and Role in Determining Response to Treatment.

OBJECTIVES: The Intranasal Schirmer test (INS) is an easy to administer test that can yield objective measurement of the quantity of nasal secretion and has been studied in patients with various nasal and systemic pathologies; however, the role of INS in patients with allergic rhinitis remains unclear. Our aim was to determine the relationship between various allergic symptoms and the Intranasal Schirmer Test (INS) score and to evaluate the utility of INS in determining treatment effect in patients with allergic rhinitis. METHODS: This prospective study included patients with allergic rhinitis who were randomly divided into 3 treatment groups (nasal steroid only, oral antihistamine only, nasal steroid and oral antihistamine). For all patients, Total Nasal Symptom Score (TNSS) was used to measure symptom severity and INS was administered before and after treatment. Pre-treatment and post treatment TNSS and INS scores were compared between different treatment groups and within each group. RESULTS: The study included 120 patients, with 40 patients in each group. There were significant differences both in pre-treatment and post-treatment symptom severity score with changes of INS scores between treatment groups (P < .001 and P = .002, respectively). There was a significant difference between pre-treatment and post-treatment symptom severity scores and the INS score in each treatment group (P < .001). There was also a significant positive correlation between INS score and TNSS (r = .591 and P < .001). CONCLUSION: The Intranasal Schirmer Test can be used as an objective tool for patients with allergic rhinitis as an adjunct to subjective patient symptom reports and can also be used to determine the response to treatment.

Repeatability of corneal pachymetry and epithelial thickness measurements with spectral-domain optical coherence tomography (SD-OCT) and correlation to ocular surface parameters.

PURPOSE: To assess the repeatability of corneal pachymetry and epithelial thickness measurements with spectral-domain optical coherence tomography (SD-OCT) and identify correlations between epithelial thickness and ocular surface parameters. METHODS: Adults who happened to have prolonged computer use were recruited, excluding those with conditions interfering with corneal measurements or tear production. All subjects filled in the ocular surface disease index (OSDI) questionnaire. Three consecutive measurements of central and peripheral corneal and epithelial thickness were performed with SD-OCT (RTVue XR). Schirmer test I and tear film break-up time (TBUT) were performed. Repeatability was evaluated with intraclass correlation coefficient (ICC), coefficient of variation and repeatability limit. Spearman correlation was used for non-parametric variables. RESULTS: 113 eyes of 63 subjects were included in the study. ICC was ≥ 0.989 for all corneal and ≥ 0.944 for all epithelial pachymetry segments. The best repeatability was found centrally and the worst superiorly both for corneal and epithelial measurements. Central epithelial thickness was weakly correlated with Schirmer test I (rho = 0.21), TBUT (rho = 0.02), OSDI symptoms and OSDI score (rho <|0.32|). OSDI symptoms and OSDI score were weakly correlated with Schirmer test I (rho <|0.3|) and TBUT (rho <|0.34|). CONCLUSION: RTVue XR measurements of corneal and epithelial thickness are highly repeatable in all segments. The lack of correlation between epithelial thickness and ocular surface parameters could suggest the assessment of epithelial integrity with reliable methods such as SD-OCT.

A simple technique of meibography for morphological and functional evaluation of meibomian glands in dry eye conditions.

Purpose: Dry eye disease (DED) is because of a decrease in the tear film's volume or a change in the composition of tears. Evaporative dry eye is the most common type, which is due to meibomian gland dysfunction (MGD). In this study, the morphology of meibomian glands was evaluated in all kinds of dry eyes to look for any loss of meibomian glands, assess the function of remaining glands, and investigate the relationship between anatomy, function, and severity of DED. Methods: A total of 300 patients were included in the study, with 150 eyes in the study group and 150 in the control group. Meibomian gland morphology was assessed by examining the tarsal plate after everting the eyelids. Tear film function was evaluated using tear film break-up time (TBUT) and Schirmer's test (SCH I and II). Meibomian gland morphology was examined with a slit-lamp under magnification, a transilluminator using a small light emitting diode (LED) bulb, and non-contact meibography using an auto refracto-keratometer (ARK). Results: Females had a higher prevalence of dry eyes in our study. In all, 103 eyes (68.6%) in the study group had evaporative dry eye, making it the most prevalent type. Among the 150 controls, 104 controls with 69.3% had no dry eye symptoms, and in those with symptoms, the evaporative type was the most common, with a 28% prevalence. Conclusion: TBUT should be performed in all patients with detectable MG abnormality. Meibography has high specificity and sensitivity to diagnose MGD and in turn dry eyes and should be considered a routine screening modality.

Evaluation of the ocular surface in asymptomatic glaucoma patients on topical medications and following trabeculectomy - A cross-sectional study.

Purpose: This present prospective, cross-sectional study aims to comprehensively evaluate the ocular surface in asymptomatic patients with diffuse blebs after trabeculectomy versus chronic anti-glaucoma medication use and compare it with the age-matched normal population. Methods: Objective clinical evaluation was done by tear film break-up time (TBUT) and Schirmer's test (ST) in the three groups-trabeculectomy >6 months with a diffuse bleb (Wurzburg bleb classification score ≧10), chronic anti-glaucoma medication (AGM >6 months) group, and normal population. In all groups, tear film osmolarity was checked with the TearLab® device (TearLab Corp., CA, USA), and subjective evaluation was performed by administering Ocular Surface Disease Index (OSDI) questionnaire. Patients already on chronic lubricants or any other drug for the treatment of dry eyes (viz. steroids, cyclosporin) or having symptoms suggestive of an abnormal ocular surface, who had undergone refractive or intraocular surgery, and contact lens users were excluded. Results: In total, 104 subjects/eyes were recruited over 6 weeks. Thirty-six eyes recruited in the trab group were compared with 33 eyes studied in the AGM group, and both these groups were compared to 35 normal eyes. When compared to normals, TBUT and ST were significantly lower (P = 0.003 and 0.014) and osmolarity and OSDI were statistically significantly higher (P = 0.007 and 0.003) in the AGM group, whereas only TBUT was statistically significantly different (P = 0.009) when the trab group was compared to normals. Also, when the trab group was compared to the AGM group, ST was found to be higher (P = 0.003) and osmolarity was lower (P = 0.034). Conclusion: To conclude, ocular surface is affected even in asymptomatic patients on AGM but near normalcy is possible following trabeculectomy when blebs are diffuse.

OC-01 (Varenicline Solution) Nasal Spray for the Treatment of Dry Eye Disease Signs and Symptoms in Subjects with Autoimmune Disease: Integrated Data from ONSET-1 and ONSET-2.

Purpose: We evaluate the treatment effect of OC-01 (varenicline solution) nasal spray (VNS) in dry eye disease (DED) subjects from two randomized trials who self-reported autoimmune disease (AID). Patients and Methods: Post hoc subgroup analysis of subjects reporting a history of AID from the integrated OC-01 VNS 0.03 or 0.06 mg and vehicle control (VC) treatment groups of the ONSET-1 and ONSET-2 trials. Mean change in Schirmer test with anesthesia score (STS, mm) and Eye Dryness Score (EDS) from baseline to 28 days was compared between OC-01 VNS and VC groups. Consistency of treatment effect in subjects with and without AID was evaluated using treatment-subgroup interaction terms in ANCOVA models for mean changes from baseline STS and EDS, and in a logistic regression model for proportion achieving ≥10 mm STS improvement. Results: Of the 891 participants, 31 reported comorbid AID. In all models, the treatment-subgroup interaction terms were not significant (p>0.05), indicating consistency of therapeutic effect of OC-01 VNS in subjects with and without AID. In subjects with AID, the treatment difference for STS was 11.8 mm and -9.3 for EDS and difference for proportion of subjects with ≥10 mm STS improvement was 61.1%. The most common adverse event was sneeze (82-84%), graded as mild by 98% of subjects. Conclusion: OC-01 VNS demonstrated consistency in improving both tear production and patient-reported symptoms in subjects with AID, consistent with pivotal ONSET-1 and 2 trial results. Further investigation is warranted, and results may further support use of OC-01 VNS for DED in AID patients.

Risk factors for peripheral hypertrophic subepithelial corneal opacification.

BACKGROUND: To evaluate the phenotype, tear secretion and refractive changes of patients diagnosed with peripheral hypertrophic subepithelial corneal opacification (PHSCO). METHODS: This is a retrospective, interventional case series conducted at the Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz. Medical records of patients diagnosed with PHSCO were analysed. Sex, age, fluorescein tear film breakup time (FTBUT), Schirmer Test II, iris colour and hair colour were assessed. Objective refraction was evaluated at different time points and, in case of surgery, 1 month and 1 year postoperatively. RESULTS: One hundred ninety-five eyes of 112 patients (78.6% female, 21.4% male; mean age 56.2 ± 14.3) were included. The median FTBUT was 6 sec. (Q1: 4/Q3: 8.75; range 1-20 s) (measured in 70 eyes of 36 patients), the median Schirmer Test II was 8 mm (Q1: 5/ Q3:15; range 1-35 mm). In 83 patients (74.1%) both eyes were involved. In 86 eyes of 64 patients (55.3%) superficial keratectomy was performed. Sphere and cylinder changed significantly 1 month and 1 year postoperative compared to the pre-operative objective refraction, while there was no significant change between 1 month and 1 year postoperatively. CONCLUSION: We found that PHSCO occurs mostly bilaterally in middle-aged women and appears to be associated with decreased tear production and reduced tear film stability.