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.

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.

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.

[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.

Impact of stress on the tear production of healthy cats.

OBJECTIVES: This study aimed to determine the impact of acute stress on tear production in companion cats to provide a basis for minimizing stress-inducing stimuli during ophthalmic evaluations. METHODS: A total of 24 healthy owned cats (12 males, 12 females) of mixed breed, aged 8 months to 7 years, with no history of ocular diseases, were selected for the study. The cats were housed in individual cages under controlled conditions for 6 days. The Schirmer tear test-1 (STT-1) was performed in the morning (between 9:00 am and 11:00 am) using test strips from the same batch. The first test (without stress) was conducted on the fifth day of acclimation, and the second test (with stress) on the sixth day. The stress stimulus consisted of recordings of barking dogs, cats fighting and the murmuring of people. For both tests, the heart rate was assessed with a stethoscope before, during and after the tests, and the environmental stress level was also evaluated. Results are presented as mean ± SD and 95% confidence interval (CI). RESULTS: The study found that STT-1 values were significantly higher (P = 0.009) with stress (22.2 ± 6.0 mm/min [95% CI 19.9-24.6]) than without stress (17.5 ± 6.9 mm/min [95% CI 14.8-20.2]). Similarly, the heart rate was significantly higher (P = 0.028) in stress vs non-stress conditions (213.4 ± 37.5 beats per minute [bpm] [95% CI 198.7-228.1] vs 171.5 ± 28.6 bpm [95% CI 160.3-182.7], respectively), and the environmental stress score was significantly higher (P <0.001) in stress vs non-stress conditions (3.3 ± 0.5 [95% CI 3.1-3.5] vs 1.2 ± 0.4 [95% CI 1.1-1.4], respectively). CONCLUSIONS AND RELEVANCE: Stress increased tear production in cats. Although the mean STT-1 value obtained under stress conditions was within the normal range, stress can influence the test results. The use of cat friendly handling techniques facilitates execution of the STT-1.

Effects of intranasal and intramuscular administration of butorphanol and zolazepam-tiletamine combination on intraocular pressure and tear secretion in New Zealand White rabbits.

This study aimed to compare the effect of intranasal (IN) and intramuscular (IM) administration of butorphanol and zolazepam-tiletamine (ZT) combination on intraocular pressure (IOP) and tear secretion (TS) in rabbits. Fourteen healthy male New Zealand White rabbits weighing 3.05 ± 0.72 kg, aged between 1 and 2 years old, were included in the study. Animals randomly received 0.5 mg/kg butorphanol and 15 mg/kg ZT combination either with IN or IM administration. IOP and TS were measured at baseline (T0), and followed by 5, 15, 30, 45, and 60 min after drug administration. The sedation variables, the time to onset of sedation, duration of sedation, and sedation scores were also recorded. The route of administration for the butorphanol and ZT combination had no significant effect on the mean IOP (p = .301) and TS (p = .445). Furthermore, there were no significant changes observed in the IOP (p = .472) and TS (p = .348) over time. The time to onset of sedation was earlier in the IN group (4.57 ± 0.79 min) than in the IM group (5.86 ± 0.9 min; p = .0004). The duration of sedation was significantly longer for IM (57.43 ± 3.41 min) compared with IN (45.0 ± 1.91 min; p < .0001). No significant difference in the sedation score was observed between groups at all time points. In conclusion, both IN and IM administration of the butorphanol and ZT combination in rabbits had similar effects on IOP and TS.

Subjective Dry Eye Symptoms and Objective Ocular Surface Signs in a Civil Air Crew Population: A Cross-Sectional Study.

Background Aviation professionals are often exposed to conditions such as low cabin air pressure, reduced humidity, and prolonged artificial lighting, which may predispose them to dry eye disease (DED). We therefore designed a cross-sectional study with three primary objectives. Our first aim was to determine the prevalence of subjective dry eye symptoms among civil flight personnel. To achieve this, we administered the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Second, we performed ocular examinations to assess objective DED indicators, such as the Schirmer's-1 (SCH-1) test and tear film break-up time (TBUT). We then correlated the results of these objective tests with the subjective symptoms reported by the participants. Last, we aimed to identify the independent risk factors for positive SCH-1 and TBUT results among aircrew personnel who did not report subjective dry eye symptoms. Methods The study sample consisted of 189 aircrew personnel (94 men and 95 women; mean age: 35.8 ± 10.4 years). They completed the SPEED questionnaire, a tool for assessing ocular surface symptoms. Participants' symptoms were classified as normal (SPEED scores 0-6), moderate (SPEED scores 7-15), or severe (SPEED scores 16-28). The objective assessment included the SCH-1 test for tear production and the TBUT test for tear film quality. Results A significant majority of participants (n = 165; 87.3%) did not report any subjective symptoms of DED. However, 12.2% (n = 23) and 0.5% (n = 1) of the study subjects experienced moderate and severe symptoms, respectively. The SCH-1 test and TBUT test were positive in 25.4% (n = 48) and 24.9% (n = 47) of the participants, respectively. Interestingly, among the aircrew personnel who did not report any subjective dry eye symptoms (SPEED scores 0-6), 18.8% (n = 31) and 17.6% (n = 29) showed abnormal results on the SCH-1 test and TBUT, respectively. Age was identified as the only independent predictor of a positive TBUT (odds ratio = 1.05, 95% confidence interval (CI) = 1.01-1.08, p = 0.01), with a borderline significant association with a positive SCH-1 test (odds ratio = 1.03, 95% CI = 0.99-1.07, p = 0.06). Conclusions The disparity between subjective symptoms and objective tests emphasizes the significance of incorporating objective measures for screening and diagnosing DED in civil flight personnel. If independently confirmed by future research, our findings could potentially lead to the routine implementation of surveillance protocols that incorporate objective DED indicators. Moreover, as age emerged as an independent predictor of positive results on objective tests, it is crucial to consider age-specific screening strategies.

The impact of prolonged face mask use on ocular surface health during COVID-19 pandemic: a clinical, and conjunctiva impression cytology study.

PURPOSE: To investigate the relationship between prolonged face mask use and ocular surface health utilizing conjunctival impression cytology, the Schirmer test, the tear break-up time (TBUT) test, and the ocular surface disease index (OSDI) questionnaire. METHODS: In this cross-sectional prospective study, individuals who used face masks for at least eight hours per day for at least six months were compared to healthy volunteers who used face masks for no more than one hour per day. Each participant completed an OSDI questionnaire. The Schirmer test (under anesthesia), the TBUT test, and conjunctiva impression cytology analysis according to the Nelson classification method were performed on each participant. RESULTS: This study included 102 (49 male, 53 female) face mask users with an average age of 33.29 ± 7.71 years and 110 (60 male, 50 female) healthy controls with an average age of 32.96 ± 7.10 years (p = 0.746). The total OSDI score was significantly higher in face mask users than the control group (25.18 ± 3.54 vs 9.46 ± 2.13, p < 0.001). The mean Schirmer test value and TBUT were significantly lower in the study group than the control group (p < 0.001, p < 0.001). There was a statistically significant difference between the two groups in total score and stage of the Nelson classification system (p < 0.001, and p = 0.024, respectively). All conjunctiva impression cytology assessments, including cellularity, cell-cell contact, nucleus/cytoplasma ratio, goblet cell amount, and metaplasia, revealed statistically significant deterioration in the study group compared to the control group (p < 0.001, p = 0.025, p < 0.001, p < 0.001, and p < 0.001, respectively). CONCLUSION: The prolonged use of face masks leads to dry eyes. The findings of conjunctiva impression cytology indicate the role of inflammation in the pathogenesis of mask associated dry eye.

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.

Comparing the effects of intraocular pressure and tear production measurements in horses in two different environments: Horse stable and medical barn.

BACKGROUND: To date, there are no studies on the impact of two distinct environments-one familiar to the horse and another unfamiliar-on intraocular pressure (IOP) and tear production. OBJECTIVES: To compare the measured IOP and tear production values in horses between a horse stable and a medical barn. STUDY DESIGN: Cross-over. METHODS: Thirty healthy male Arabian horses, aged 6.88 ± 3.34 years were used. IOP and tear production measurements were assessed in both the horse stable and the medical barn, with a paired Student's t-test and Bland-Altman analysis conducted for comparison and agreement, respectively. RESULTS: A significant increase in IOP was observed in the medical barn (34.2 ± 6.8 mmHg) compared with the horse stable (29.5 ± 7.2 mmHg, p = 0.02). However, no statistically significant difference in tear production was found between horse stable (22.1 ± 2.8 mm/min) and medical barn (23.6 ± 3.4 mm/min) (p = 0.09). The standard error of the slope was 0.36 for the IOP measured in the medical barn, indicating a difference of -4.7 mmHg compared with the IOP measured in the horse stable (p = 0.02). The bias was fitted to y = -7.9350 + 0.1003x. The standard error of the slope was 0.39 for the tear production measured in the medical barn, indicating a difference of -1.5 mm/min compared with the tear production measured in the horse stable (p = 0.09). The bias was fitted to y = 6.1530 + -0.3367x. MAIN LIMITATIONS: The absence of horses with ocular disorders and an assessment of the potential impact of transportation. CONCLUSIONS: A notable increase in IOP was observed in the medical barn compared with the horse stable, while tear production exhibited no significant variance between the two environments. The Bland-Altman analysis highlighted a discrepancy in IOP measurements in the horse stable, emphasising the potential influence of the environment on ocular parameters in horses.

Ocular examination findings and selected ophthalmic diagnostic tests in African green monkeys (Chlorocebus aethiops sabaeus).

OBJECTIVE: To document ocular lesions and establish ophthalmic diagnostic test reference values in a colony of African green monkeys (Chlorocebus aethiops sabaeus). ANIMALS STUDIED: Fifty one geriatric (GAGM, 19-30 years old), 10 adult (AAGM, 5-9 years old) and 10 juvenile (JAGM, <2 years old) African green monkeys housed in a single Caribbean research colony. PROCEDURES: Ocular biomicroscopy, indirect fundoscopy, Schirmer tear test (STT), rebound tonometry (TonoVet®) and corneal fluorescein staining were performed. Mixed ANCOVA tests were performed to compare STT and IOP between groups. RESULTS: Common ocular lesions in GAGM included vitreal degeneration (27/51, 51/102 eyes) and cataracts (21/51, 32/102 eyes). Vitreal degeneration was also common in AAGM (8/10, 16/20 eyes) and infrequent in JAGM (3/10, 6/20 eyes). Cataracts were not present in any JAGM or AAGM. All eyes in all three groups had perilimbal corneal pigmentation and faint lace-like anterior corneal stromal opacification. Median (range) STT values were 16.0 (18) mm/min in GAGM. Mean (SD) STT values were 14.2 (4.6) mm/min in AAGM, and 8.9 (3.4) mm/min in JAGM. Median (range) IOP values were 16.5 (27) mmHg in GAGM. Mean (SD) IOP values were 18.0 (2.8) mmHg in AAGM, and 14.1 (2.2) mmHg in JAGM. JAGM had significantly lower STT and IOP values compared to AAGM (p = .0449, .0057, respectively) and GAGM (p = .0002, .0130, respectively). CONCLUSIONS: Spontaneous ocular lesions were common in geriatric monkeys in this research colony. IOP and STT values were lower in juvenile African green monkeys relative to adult or geriatric animals.

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.

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.

Tear clearance rate in dogs: Measurement using anterior segment optical coherence tomography.

OBJECTIVE: The tear clearance rate (TCR), determined using anterior segment optical coherence tomography (AS-OCT) images, and its correlation with ocular surface parameters, including blink rate, Schirmer tear test-1 (STT-1) and tear film breakup time (TFBUT), were evaluated. ANIMALS STUDIED: Left eyes of 20 client-owned dogs with no ocular disease symptoms. PROCEDURES: The tear meniscus height (TMH) was evaluated using AS-OCT images before the instillation of 5 µL saline (TMHbase ), immediately post-instillation (TMH0 ), 30-s post-instillation (TMH0.5 ) and at 1 min intervals for 5 min post-instillation (TMH1 , TMH2 , TMH3 , TMH4 and TMH5 ). The TCR was calculated using the formula [(TMH0  - TMH0.5 )/TMH0 ]×100 (%). The eyes were classified into two groups with the median: 'High TMHbase ' (n = 10) and 'Low TMHbase ' (n = 10). Eyes with STT-1 values ≥15 mm/min and TFBUT ≥ 12 s were assigned to the 'Satisfied' subgroup, whereas eyes not satisfying these criteria were assigned to the 'Not satisfied' subgroup. RESULTS: TMH0 was higher than TMH0.5 (p = 0.02), wherein TMH0.5 to TMH5 did not differ significantly. The TCR and blink rate were negatively correlated (p = 0.02). The 'Not satisfied' subgroup in the low TMHbase group had a lower TCR (p = 0.02) and higher blink rate (p = 0.04) than the 'Satisfied' subgroup. CONCLUSIONS: TCR can be evaluated using AS-OCT in dogs. Eyes with a lower TCR blink more frequently. TMH merits studying to understand ocular surface health.

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.

Development and validation of a diagnostic model for the identification of chronic ocular graft-versus-host disease (oGVHD).

Purpose: To verify the International Chronic Ocular Graft-Versus-Host Disease (ICCGVHD) Group diagnostic criteria and establish an easy-to-use and reliable diagnosis model for quick identification of chronic oGVHD. Methods: This study included 180 patients (355 eyes) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and visited the Peking University Third Hospital Cornea and Ocular Surface Disease Specialist Clinic from July 2020 to February 2021. The proportion of chronic oGVHD was 76.06% (279/355). Results: Five complaints, including eye dryness, photophobia, foreign body sensation, eye redness, and burning sensation; six ophthalmic examinations, including Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer's test score without anesthesia, conjunctival score, tear meniscus height, and non-ocular GVHD-involved organs were significantly different between patients with chronic oGVHD and control group (p < 0.05). Binary logistic regression (backward LR algorithm) selection demonstrated that three variables retained diagnostic significance for chronic oGVHD: CFS (OR = 2.71 (1.92-3.81), p < 0.001), Schirmer's test score without anesthesia (OR = 0.83 (0.76-0.91), p < 0.001), and conjunctival score (OR = 1.96 (1.13-3.42), p = 0.031). A nomogram for the identification of chronic oGVHD was developed, and its performance was examined using an internal validation cohort (118 eyes). The areas under the curve (AUCs) for the three-variable-based nomogram were 0.976 (95% CI (0.959-0.992), p < 0.01) and 0.945 (95% CI (0.904-0.986), p < 0.01) in the development and internal validation cohorts, respectively. Conclusion: This concise three-variable-based nomogram based on ICCGVHD criteria could serve as an easy-to-use and reliable tool for rapid screening of chronic oGVHD.

Determination of reference values for tear production and intraocular pressure in Pygoscelis penguins of the Antarctic Peninsula.

BACKGROUND: According to the literature review, this is the first study investigating tear production (TP) and intraocular pressure (IOP) in the Pygoscelis penguins living in their natural habitat. The study aimed to establish normal values for standard ocular tests in the genus Pygoscelis, namely, the Adélie (Pygoscelis adeliae), gentoo (Pygoscelis papua), and chinstrap (Pygoscelis antarctica) penguins, in four different islands of Antarctica. Sampling was made by specifically using the left eye of the penguins. The Schirmer's tear test type I (STT-I) and the Tonovet® (rebound tonometer) were used to measure the TP and the IOP, respectively. RESULTS: The mean TP and IOP values of 129 Adélie, chinstrap, gentoo, and 120 adult Adélie, gentoo penguins were determined as 10.2 ± 4.0 mm/min and 38.9 ± 13.2 mmHg, respectively. No statistical difference was detected between the penguin species for the mean IOP values, while the difference was determined in all the locations. However, statistical differences in the mean TP values were determined between all locations. CONCLUSION: The results of this study provide a reference range of Schirmer's tear test (STT) and IOP values in Pygoscelis penguins and show that the IOP is significantly affected by locations. This result can be attributed to the harsh climatic conditions of the Antarctic Peninsula that change very quickly. The described data may help diagnose clinical pathological findings in Pygoscelis penguins. The STT and rebound tonometry appears to be safe and reproducible methods in Pygoscelis penguins, as the results were obtained quickly and were well tolerated by the birds. Based on our results, we propose that similar studies can be initiated in crowded colonies of three penguin species of this genus on the Antarctic Peninsula, the southern Shetland Islands, and other frequently visited islands in Antarctica.

Long-term effect of oral cannabidiol administration to healthy adult dogs on tear production, intraocular pressure, and tear concentrations.

OBJECTIVE: To determine the chronic effects of oral cannabidiol (CBD) use on tear production, intraocular pressure (IOP), and concentration of CBD in tears of healthy dogs. ANIMALS STUDIED: Eighteen healthy research Beagles. PROCEDURES: This was a masked, placebo-controlled, randomized prospective study. Eighteen dogs were randomly assigned to three groups (six dogs per group) based on daily dosage of oral MCT oil (placebo), CBD 5 mg/kg, and CBD 10 mg/kg. Schirmer tear test (STT-1) and IOP were measured twice daily (7 am and 7 pm) every 4 weeks for 36 weeks. Week 36 tears were collected and analyzed for CBD concentrations (ng/mL) using liquid chromatography/mass spectrometry. A mixed linear model was used as the statistical method and p-value <.05 was considered significant. RESULTS: No significant differences were found between placebo vs. 5 mg/kg vs. 10 mg/kg for STT-1 or IOP (AM and PM). CBD was detected in 10 out of 11 (91%) viable tear samples receiving 5 mg/kg or 10 mg/kg dosages. One sample in the 5 mg/kg group had inadequate tear volume for analysis. The CBD concentration in tears was at or below the lower limit of quantification in placebo group, 4.12-11.2 ng/mL for the 5 mg/kg group, and 6.22-152 ng/mL for the 10 mg/kg group. CONCLUSIONS: Long-term administration of oral CBD in healthy research beagles demonstrates a favorable safety profile regarding ocular tolerability. Oral CBD administration does not appear to affect tear production or IOP over a 36-week period. This is the first canine study positively identifying concentrations of CBD in tears following oral administration.