The relationship between corneal calcareous degeneration and various ophthalmic diseases in dogs: A retrospective study.

OBJECTIVE: To investigate ocular factors that influence the development of corneal calcareous degeneration (CCD) in dogs. ANIMALS AND PROCEDURES: The medical records of 96 eyes of dogs with CCD and 288 eyes without CCD were retrospectively reviewed. Dogs with evidence of causative systemic illness associated with CCD were excluded from the study. Logistic regression analysis was used to identify the ocular factors associated with the development of CCD. To identify the effect of phosphate-containing eyedrops on CCD, the application periods of phosphate-containing antiglaucoma eyedrops were compared between the glaucomatous eyes in the CCD and non-CCD groups. RESULTS: Increased age, brachycephalic breed, keratoconjunctivitis sicca, advanced cataract, history of phacoemulsification, and topical corticosteroid application were significantly associated with CCD development. Glaucoma was significantly overrepresented in the non-CCD group, and the application period of phosphate-containing antiglaucoma eyedrops was significantly longer in eyes with CCD than in those without CCD. CONCLUSIONS: Ophthalmic diseases requiring long-term management of ocular inflammation and long-term application of phosphate-containing eyedrops may contribute to the development of CCD. Glaucoma is overrepresented in dogs without CCD, which is thought to be due to the differences in predisposed age and breeds between dogs with glaucoma and CCD.

Evaluation of the Clinical Characteristics of Dry Eye Secondary to Different Types of Liver Diseases.

INTRODUCTION: This study compares the clinical characteristics of dry eye secondary to primary biliary cholangitis (PBC), drug-induced liver injury (DILI), and viral hepatitis B(HBV) to evaluate the ocular surface damage caused by different types of liver diseases. METHODS: Thirty healthy people were included as control group. Sixty patients with dry eye secondary to different types of liver disease were included, including 19 cases of PBC, 18 cases of DILI, and 23 cases of HBV. All patients were evaluated by the SPEED questionnaire, corneal fluorescein staining (CFS), noninvasive tear breakup time (NIBUT), Schirmer I test (SIt), tear meniscus height test (TMH), the area of meibomian glands dropout (MG dropout), partial blinking rate (PBR), lipid layer thickness (LLT), meibum expressibility, and meibum quality. RESULTS: There are statistical differences in ophthalmic examination results between different types of liver diseases and normal people (P < 0.05). Compared with DILI and HBV groups, the CFS score of PBC group score was higher (P < 0.05), the PBR was higher (P < 0.05), and the SIt was lower (P < 0.01). The TMH of PBC and DILI groups were significantly lower than the HBV group, and the difference was statistically significant (P < 0.05). Compared with the PBC group, the LLT of the DILI group decreased (P < 0.01). The area of meibomian glands dropout of the three groups had mild-to-moderate defects, but there was no significant statistical difference between groups (P > 0.05).The Meibum quality score in the DILI group was significantly higher than the HBV group (P < 0.05). CONCLUSIONS: The PBC group was more prone to aqueous-deficient dry eye. The DILI group was more prone to obstructive meibomian gland dysfunction (MGD).The HBV group was more prone to nonobstructive MGD. The symptoms of dry eye in the PBC group are mild-to-moderate discomfort, but the degree of corneal damage is higher, indicating that the corneal sensitivity is reduced, which may be related to the high rate of partial blinking.

3-month post-procedural evaluation of a combined intense pulsed light and photo-biomodulation system in the treatment of meibomian gland dysfunction.

PURPOSE: Meibomian gland dysfunction (MGD) is the leading cause of dry eye syndrome. It is a frequent and underdiagnosed condition with a significant socioeconomic impact. We propose here the evaluation of a platform combining intense pulsed light and photo-biomodulation in the treatment of Meibomian gland dysfunction. METHODS: We conducted a retrospective study at Brest University Hospital analyzing a cohort of 74 eyes (37 patients) at 1 month and 3 months after a protocol of 3 Eye-Light® (Espansione Group, Italy) sessions 14 days apart between January 2019 and April 2020. The primary outcome was the change in OSDI quality of life score. Secondary outcomes were the SPEED questionnaire score; tear break-up time (BUT), Oxford score, non-invasive break-up time (NIBUT), lipid layer thickness, lacrimal meniscus height and Meibomian gland atrophy rate. Tolerance of the treatment was also evaluated. RESULTS: We found a significant improvement in OSDI scores at 1 month (-17.32; 95% CI (-25.84; -8.79), P<0.0001) and 3 months (-16.95; 95% CI (-25.26; -8.64), P<0.0001). The SPEED score, BUT, Oxford score, Meibomian gland atrophy and NIBUT were also statistically significantly improved. Tolerance to treatment was very good despite two cases of herpetic keratitis, which resolved on treatment. CONCLUSION: Treatment with the Eye-Light® in three sessions every two weeks significantly reduced symptoms and ocular surface damage in patients with MGD. This data suggests that the use of Eye-Light® may represent a good option for patients with MGD.

Effects of long-term oral administration of antipsychotic clozapine on the ocular surface / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the effects of long-term use of clozapine on tear film stability and ocular surface tissue structure.METHODS: Case-control study was conducted on 45 patients(group 1)who were diagnosed with schizophrenia and treated with clozapine for 3.45±0.72a between March 2021 and December 2021. Another 45 healthy subjects(group 2)served as controls, whose demographic characteristics were similar to those of group 1. Patients' dry eye symptoms were investigated using OSDI questionnaire, tear secretion was detected by the Schirmer I test, ocular surface damage was assessed by the ocular surface staining score, and comprehensive ophthalmic examination was performed on all patients through LipiView ocular surface interferometer, ocular surface integrated analyzer, corneal confocal microscope and slit lamp photographic system.RESULTS: Slit-lamp photography showed diffuse grayish-white spot-like opacification in the corneal stroma of group 1, accompanied by brown star-like opacification in the center of the anterior capsule of the lens. OSDI scores were 38.00(31.50, 48.50)and 15.00(9.00, 19.50)in the two groups respectively. Schirmer test showed that the group 1 was 5.27±2.18mm/5min, while group 2 was 15.62±3.05mm/5min. Corneal fluorescein staining score: 4.00(2.50, 5.00)for group 1 and 1.00(0.00, 1.50)for group 2. The lissamine green staining score for the conjunctiva was 9.00(6.50, 10.00)and 3.00(2.00, 3.50)for the two groups, respectively. LipiView detected lipid layer thickness(LLT), suggesting that the results of group 1 and group 2 were similar, respectively 75.91±15.51 and 77.24±12.11nm; and the results were similar for the lid gland deficiency score, with 1.37±0.26 and 1.29±0.31 points, respectively. The mean tear meniscus height in group 1 was 0.13±0.06mm, which was lower than 0.23±0.04mm of group 2. Non-invasive breakup time(NIBUT)was 6.04±2.62 and 11.4±2.74s in group 1 and group 2 respectively. OSDI score, Schirmer Ⅰ test, ocular surface staining score, tear meniscus height and NIBUT were significantly different between the two groups(P&#x003C;0.05). Confocal corneal microscopy suggested decreased corneal nerve fiber density with stromal layer inflammatory cell infiltration and pigmentation in group 1.CONCLUSION: The antipsychotic drug clozapine can induce dry eye with a range of ocular surface injuries such as corneal pigmentation, and patients who taking such drugs should be routinely examined by an ophthalmologist.

Phenotypic and Transcriptomics Analyses Reveal Underlying Mechanisms in a Mouse Model of Corneal Bee Sting.

Corneal bee sting (CBS) is one of the most common ocular traumas and can lead to blindness. The ophthalmic manifestations are caused by direct mechanical effects of bee stings, toxic effects, and host immune responses to bee venom (BV); however, the underlying pathogenesis remains unclear. Clinically, topical steroids and antibiotics are routinely used to treat CBS patients but the specific drug targets are unknown; therefore, it is imperative to study the pathological characteristics, injury mechanisms, and therapeutic targets involved in CBS. In the present study, a CBS injury model was successfully established by injecting BV into the corneal stroma of healthy C57BL/6 mice. F-actin staining revealed corneal endothelial cell damage, decreased density, skeletal disorder, and thickened corneal stromal. The terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay showed apoptosis of both epithelial and endothelial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that cytokine-cytokine interactions were the most relevant pathway for pathogenesis. Protein-protein interaction (PPI) network analysis showed that IL-1, TNF, and IL-6 were the most relevant nodes. RNA-seq after the application of Tobradex® (0.3% tobramycin and 0.1% dexamethasone) eye ointment showed that Tobradex® not only downregulated relevant inflammatory factors but also reduced corneal pain as well as promoted nerve regeneration by repairing axons. Here, a stable and reliable model of CBS injury was successfully established for the first time, and the pathogenesis of CBS and the therapeutic targets of Tobradex® are discussed. These hub genes are expected to be biomarkers and therapeutic targets for the diagnosis and treatment of CBS.

Role of Caspase-1 as a Biomarker of Ocular Surface Damage.

PURPOSE: To examine the potential of caspase-1 as a biomarker for ocular surface damage. DESIGN: Cross-sectional study. METHODS: A total of 113 tear samples (64 subjects) were analyzed. Sixty-one samples were from individuals with dry eye disease (DED), defined as Ocular Surface Disease Index (OSDI) ≥13 and/or corneal staining (CS) ≥3; 32 were from individuals who used glaucoma medication, irrespective of DED metrics; and 20 were from controls (CS <3 and OSDI <13). All individuals completed a medical history form and underwent an ocular surface assessment. Protein levels of caspase-1 were determined by enzyme-linked immunosorbent assay off Schirmer's strips. The primary analysis compared caspase-1 levels in individuals with signs of ocular surface damage (CS ≥3) in both case groups and controls. Secondary correlational analyses were conducted to examine relationships between caspase-1 levels and ocular signs and symptoms. Finally, area under the curve (AUC) analyses were performed to examine relationships between inflammatory markers and CS. RESULTS: The mean age of the population was 58±18 years; 70% were female. Tear samples from individuals with ocular surface damage presented higher caspase-1 levels than the control group. Caspase-1 levels showed a moderate positive correlation with CS (Spearman r = 0.31; P = .001) and eye redness (Spearman r = 0.39; P = .004), and a negative correlation with Schirmer's (Spearman r = -0.46; P < .001) and tear break-up time (Spearman r = -0.33; P = .0006). Caspase-1 showed higher sensitivity and AUC for detecting ocular surface damage than InflammaDry, and its expression was not affected by anti-inflammatory agents. CONCLUSION: Caspase-1 levels were higher in the tears of individuals with ocular surface damage, suggesting its potential to be used as a biomarker and/or therapeutic target.

Comparative analysis of 0.1% cyclosporin A cationic emulsion and 0.05% cyclosporin A emulsion in murine dry eye cases with different severities.

Dry eye (DE), especially severe DE (SDE), can cause ocular surface defects and reduce the patient's quality of life. Several clinical studies have shown that 0.1% cyclosporin A cationic emulsion (CsA CE) could decrease corneal damage. However, no experimental study has reported the effect of 0.1% CsA CE on SDE. The present study aimed to compare the efficacy of 0.1% CsA CE with that of 0.05% CsA emulsion for ocular surface damage and inflammation in the cases of murine DE with different severities. Following exposure to desiccating stress and subcutaneous injection of scopolamine for 5 days, C57BL/6 female mice were divided into SDE and non-SDE (NSDE) groups based on corneal fluorescein staining scores (CFSs). Mice from both groups were topically treated with 0.05% CsA emulsion or 0.1% CsA CE for 10 days. The results demonstrated that 0.1% CsA CE-treated mice in the SDE and NSDE groups exhibited significant improvements in all the clinical and experimental parameters. Furthermore, the CFS of 0.1% CsA CE-treated mice in the SDE group was lower compared with that of the 0.05% CsA-treated mice. In addition, in the SDE group, 0.1% CsA CE-treated mice had significantly lower levels of nuclear factor-κB activation, inflammatory infiltrations and apoptosis on the ocular surface, and they also exhibited higher conjunctival goblet cell density compared with the 0.05% CsA-treated mice. In summary, these findings indicated that 0.1% CsA CE was more effective than topical 0.05% CsA emulsion at improving corneal epithelial injury and decreasing the levels of inflammatory cytokines and T cells in mice with SDE.

N-acetylcysteine alleviates ocular surface damage in STZ-induced diabetic mice by inhibiting the ROS/NLRP3/Caspase-1/IL-1ß signaling pathway.

Diabetes mellitus (DM) induces damage to the ocular surface, which leads to vision decline. In the current study, we investigated whether N-acetylcysteine (NAC) plays a protective role in diabetes-induced ocular surface damage. The diabetic mice model was treated with 0.3% NAC topically. Corneal epithelial integrity, tear volume and corneal sensitivity were examined by sodium fluorescein staining, phenol red cotton thread and esthesiometer respectively. The level of reactive oxygen species (ROS) was measured with 2',7-dichlorofluorescein diacetate. The expression of NLRP3, IL-1ß and caspase-1 were evaluated by RT-PCR, western blot and immunostaining. The level of SOD1 was assessed by RT-PCR. We found that the expression of NLRP3, IL-1ß and caspase-1 were elevated in diabetic cornea and conjunctiva. Treatment with NAC improved corneal epithelial integrity, increased tear production and corneal sensitivity in diabetic mice. Moreover, NAC markedly attenuated ROS accumulation and decreased NLRP3, IL-1ß and caspase-1 levels in diabetic cornea and conjunctiva. These results suggest that NAC improves ocular surface damage in STZ-induced diabetic mice, which may be related to the inhibition of the ROS/NLRP3/Caspase-1/IL-1ß signaling pathway.

Assessment of ocular surface disease in glaucoma patients with benzalkonium chloride-preserved latanoprost eye drops: a short-term longitudinal study.

PURPOSE: To prospectively evaluate the effect of benzalkonium chloride (BAK)-preserved latanoprost on ocular surface damage and identify the associated risk factors among treatment-naive glaucoma patients. METHODS: The basal Schirmer's test results, corneal Oxford staining score, non-invasive keratograph tear-breakup time, oculus hyperemia index score (objective metrics), and ocular surface disease index (OSDI) questionnaire (subjective metric) were evaluated at baseline, 1 month, and 4 months after receiving latanoprost eye drops. Associated risk factors were assessed by multivariate linear regression. RESULTS: Seventy-four eyes (44 patients) were enrolled. Basal Schirmer's test tear-flow and Oxford scores gradually deteriorated (ß = -0.14, P = 0.001 and ß = 0.1, P < 0.001, respectively). The percentage of unstable tear-film (breakup time < 10 s) increased significantly at 4 months (6.21% vs 9.11%, P = 0.042). Hyperemic scores increased significantly at 1 month and normalized at 4 months (P = 0.01 and P = 0.16, respectively); total OSDI scores tended to improve (ß = -0.76, P = 0.06). Older age was associated with additional corneal Oxford staining (P = 0.005); female sex was associated with increased unstable tear-film scores (P = 0.01). Artificial tear use was associated with a smaller decrease in basal Schirmer's test values (P = 0.01) and a smaller increase in unstable tear-film scores (P = 0.02). CONCLUSIONS: Preserved latanoprost eye drops affected ocular surface changes in glaucoma patients through decreased basal tear secretion. Artificial tears represent an early intervention in vulnerable glaucoma patients with reduced tear secretion and impaired tear-film stability.

PEDF Attenuates Ocular Surface Damage in Diabetic Mice Model Through Its Antioxidant Properties.

PURPOSE: To investigate the antioxidative effect and mechanism of pigment epithelium-derived factor (PEDF) on the ocular surface damage in diabetic mice. METHODS: C57BL/6 mice were injected intraperitoneally with streptozocin to generate diabetic models and then 50 nM PEDF or artificial tears were used to treat the diabetic mice. Treatment was given three times a day for eight weeks. Corneal epithelial damage, corneal sensitivity, and tear volume were quantified by fluorescein staining, esthesiometer, and phenol red cotton thread, respectively. Animals were sacrificed at 16 weeks after diabetes and the whole globe specimens were subjected to histochemical staining. Reactive oxygen species (ROS) generation was detected by 2',7-dichlorodihydrofluorescein probe. The levels of receptor for advanced glycation end products (RAGE) and superoxide dismutase 1 (SOD1) were examined by quantitative real-time PCR and western blotting. RESULTS: Topical application of PEDF improved corneal epithelial damage, increased corneal sensitivity, and tear volume in diabetic mice. ROS levels in the cornea were significantly higher in the diabetic mice than in the normal mice. Moreover, PEDF attenuated the accumulation of ROS, decreased the expression of RAGE, and elevated SOD1 expression in the cornea. CONCLUSIONS: Topical application of PEDF can alleviate diabetes-related ocular surface damage and increase tear volume, along with the improvement of oxidative stress status.

Ocular surface damage in dry eye patients with seborrheic dermatitis / 中华实验眼科杂志

Objective@#To observe the ocular surface function changes of dry eye patients with seborrheic dermatitis and discuss the significance of seborrheic dermatitis in ocular surface damage.@*Methods@#A cohort study was performed.Forty-nine patients (49 eyes) who were initial diagnosed with dry eye enrolled in General Hospital of Tianjin Medical University from October 2015 to March 2016 were divided into 2 groups, including 21 patients with seborrheic dermatitis and 28 patients without seborrheic dermatitis.Gender, age, meibomian gland dysfunction (MGD), eyelid margin scores, eyelid secretions scores, meibomian gland imaging scores, conjunctival congestion scores, ocular surface disease index (OSDI), Schirmer Ⅰtest (SⅠt), break-up time of tear film (BUT), fluorescent integral score were examined and compared.The study was followed the Declaration of Helsinki and was approved by General Hospital of Tianjin Medical University (No.IRB2015-YX-069). Written informed consent was obtained from all subjects before entering the study.@*Results@#There were not significant differences in gender and ages (χ2=1.536, P=0.215; t=0.642, P=0.524). The rate of MGD in seborrheic dermatitis group was 57.15%, which was significantly higher than that in the non-seborheic dermatitis group (25.00%), with significan difference between the two groups (χ2=5.222, P=0.022). There were significant differences in eyelid margin scores, eyelid secretions scores, meibomian gland imaging scores, fluorescent integral scores between the two groups (Z=2.105, 3.303, 3.368, 3.036, all at P<0.05). The OSDI in the seborheic dermatitis group was 26.43±8.05, which was significantly larger than that in the non-seborheic dermatitis group (16.75±5.74); the BUT in the seborheic dermatitis group was (6.14±1.98)s, which was significantly shorter than that in the non-seborheic (8.75±1.38)s (t=4.918, 5.434; both at P<0.05).@*Conclusions@#Seborrheic dermatitis may aggravate ocular surface dysfunction in dry eye patients.

Ocular surface damage in dry eye patients with seborrheic dermatitis / 中华实验眼科杂志

Objective To observe the ocular surface function changes of dry eye patients with seborrheic dermatitis and discuss the significance of seborrheic dermatitis in ocular surface damage. Methods A cohort study was performed. Forty-nine patients (49 eyes) who were initial diagnosed with dry eye enrolled in General Hospital of Tianjin Medical University from October 2015 to March 2016 were divided into 2 groups,including 21 patients with seborrheic dermatitis and 28 patients without seborrheic dermatitis. Gender, age, meibomian gland dysfunction (MGD), eyelid margin scores, eyelid secretions scores, meibomian gland imaging scores, conjunctival congestion scores,ocular surface disease index ( OSDI) ,Schirmer Ⅰtest ( SⅠt) ,break-up time of tear film ( BUT) ,fluorescent integral score were examined and compared. The study was followed the Declaration of Helsinki and was approved by General Hospital of Tianjin Medical University (No. IRB2015-YX-069). Written informed consent was obtained from all subjects before entering the study. Results There were not significant differences in gender and ages (χ2=1. 536,P=0. 215;t=0. 642,P=0. 524). The rate of MGD in seborrheic dermatitis group was 57. 15％,which was significantly higher than that in the non-seborheic dermatitis group (25. 00％),with significan difference between the two groups (χ2 =5. 222,P=0. 022). There were significant differences in eyelid margin scores,eyelid secretions scores,meibomian gland imaging scores,fluorescent integral scores between the two groups (Z=2. 105,3. 303,3. 368, 3. 036,all at P<0. 05). The OSDI in the seborheic dermatitis group was 26. 43±8. 05,which was significantly larger than that in the non-seborheic dermatitis group (16. 75±5. 74);the BUT in the seborheic dermatitis group was (6. 14± 1. 98)s,which was significantly shorter than that in the non-seborheic (8. 75±1. 38)s (t=4. 918,5. 434;both at P<0. 05). Conclusions Seborrheic dermatitis may aggravate ocular surface dysfunction in dry eye patients.