Inflammation due to ocular surface homeostasis imbalance caused by pterygia: tear lymphotoxin-alpha study and a literature review.

OBJECTIVE: To estimate the pterygium ocular surface state, and compare with healthy eyes and dry eyes. To investigate the inflammation due to pterygia growth by tear Lymphotoxin-alpha (LT α) test. DESIGN: Prospective, single-center study. PARTICIPANTS: 400 patients, divided into 100 pterygium group, 100 mild dry eye group, 100 moderate dry eye group, and 100 age-and sex-matched normal controls. METHODS: The non-invasive break-up time (NIBUT), tear meniscus height (TMH) test, corneal fluorescein staining (CFS), meibomian gland loss score (MGs), and lipid layer thickness (LLT) were evaluated in all patients. Pterygium status and ocular status in the pterygium group were collected. The tear LT α test was conducted in the pterygium patients group. RESULT: Pterygium can affect the ocular surface, leading to decreased tear film stability. The TMH, NIBUT, CFS, MGs, and lipid layer thickness can provide insights into this phenomenon. The presence of pterygium can change the structure and condition of the ocular surface. Tear LT α testing shows an abnormal decrease in LT α levels in pterygium patients. This indicates an immune-inflammation microenvironment that causes tissue repair deficiency. CONCLUSION: The dry eye triggered by the growth of pterygium may originate from the tear film instability due to pterygia. As an inflammatory index, LT α in the development of pterygium and the aggravation of dry eye patients can indicate that the ocular surface is in different inflammatory states. Future tear testing in LT α may be a potential indicator to assess the inflammatory status of the dry eye.

Clinical features and comprehensive treatment of persistent corneal epithelial dysfunction after cataract surgery.

OBJECTIVE: Evaluation of clinical efficacy and safety of tobramycin/dexamethasone eye ointment in treating persistent corneal epithelial dysfunction (PED) after cataract surgery. METHODS: 26 cases diagnosed as PED after cataract surgery accept the tobramycin/dexamethasone ophthalmic ointment and intense pulse light treatment in the Xiamen University of Xiamen eye center between September 2016 and April 2022 were retrospectively analyzed, mainly including clinical manifestations, characteristics of morphological changes imaged by in vivo confocal microscopy, meibomian glands infrared photography, lipid layer thickness (LLT), management and therapeutic effects. RESULTS: There were 26 eyes, include 8(35%) males and 15(65%) females with an average age of 69.6 ± 5.2 years(50 to 78 years). The mean hospitalization time was (18.4 ± 7.5) days after cataract surgery. Twenty patients had meibomian gland dysfunction. Infrared photography revealed varying loss in the meibomian glands, with a mean score of 3.8 ± 1.2 for gland loss. The mean LLT was 61.6 ± 8.4 nm. After treatment, 20 patients were cured, and 3 received amniotic membrane transplantation. After treatment, the uncorrected visual acuity (UCVA) and best-corrected vision activity (BCVA) improved (P < 0.001), and there was no significant difference in intraocular pressure (IOP) before and after treatment (P > 0.05). CONCLUSIONS: The early manifestation of PED after surgery is punctate staining of the corneal epithelium. Tobramycin and dexamethasone eye ointment bandages have a good repair effect. The meibomian gland massage combined with intense pulse light treatment can effectively shorten the course of the disease.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging. Objective: To evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED. Design, Setting, and Participants: This was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis. Interventions: Following a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29. Results: A total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group. Conclusions And Relevance: Results demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT05841043.

Evaluation of lymphotoxin-alpha in pterygium and diagnostic value in active and inactive pterygium states.

To explore the correlation between tear LT-a, pterygium status, and dry eye indicators. We established a diagnostic model to evaluate active pterygium. A retrospective study was conducted between June 2021 and June 2023 on 172 patients, comprising 108 men and 64 women. The study analyzed LT-a and various ocular parameters in all participants. The data was collected using Excel software and analyzed using SPSS 25.0 statistical software and Medcalc. We made a nomogram diagnostic model to different diagnosed the state of pterygium. This study found that pterygium has progressive eye surface damage during the active state. There was no significant difference in dry eye indicators between the two groups. However, the concentration of LT-a in the active group was significantly lower than that in the inactive group (P < 0.001). We observed that increased pterygium grade corresponded to a worse ocular surface condition. In addition, LT-a was significantly positively correlated with disease duration, but negatively correlated with age, pterygium size, active pterygium state, and LLT value. The optimal intercept value for evaluating active pterygium in Lt-a was ≤ 0.49 dg/ml. We screened three variables for evaluating active pterygium through Single and Multiple regression analysis: LT-a grading, pterygium size, and congestion score. Finally, we made a reliable diagnostic nomogram model. Pterygium development triggers immune inflammation. Our model based on LT-a identifies active pterygium for personalized treatment options and new research directions.

Accurate detection and grading of pterygium through smartphone by a fusion training model.

BACKGROUND/AIMS: To improve the accuracy of pterygium screening and detection through smartphones, we established a fusion training model by blending a large number of slit-lamp image data with a small proportion of smartphone data. METHOD: Two datasets were used, a slit-lamp image dataset containing 20 987 images and a smartphone-based image dataset containing 1094 images. The RFRC (Faster RCNN based on ResNet101) model for the detection model. The SRU-Net (U-Net based on SE-ResNeXt50) for the segmentation models. The open-cv algorithm measured the width, length and area of pterygium in the cornea. RESULTS: The detection model (trained by slit-lamp images) obtained the mean accuracy of 95.24%. The fusion segmentation model (trained by smartphone and slit-lamp images) achieved a microaverage F1 score of 0.8981, sensitivity of 0.8709, specificity of 0.9668 and area under the curve (AUC) of 0.9295. Compared with the same group of patients' smartphone and slit-lamp images, the fusion model performance in smartphone-based images (F1 score of 0.9313, sensitivity of 0.9360, specificity of 0.9613, AUC of 0.9426, accuracy of 92.38%) is close to the model (trained by slit-lamp images) in slit-lamp images (F1 score of 0.9448, sensitivity of 0.9165, specificity of 0.9689, AUC of 0.9569 and accuracy of 94.29%). CONCLUSION: Our fusion model method got high pterygium detection and grading accuracy in insufficient smartphone data, and its performance is comparable to experienced ophthalmologists and works well in different smartphone brands.

Clinical and Morphological in Vivo Confocal Microscopy Findings following a Modified Biphasic Higher Fluence Transepithelial Corneal Crosslinking.

Purpose: To compare the refractive efficacy and morphological changes in the cornea following a novel biphasic higher fluence transepithelial corneal crosslinking (BI-TE-CXL) and transepithelial corneal crosslinking (TE-CXL) in adults keratoconus.Methods: Patients with progressive keratoconus who required corneal crosslinking were assigned to the BI-TE-CXL group (32 eyes, phase 1: 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro; phase 2: 3.6 J/cm2 for 6 min and 40 s of continuous light exposure at the front curvature apex with a 6 mm diameter light spot, UVX-2000, IROC) or the TE-CXL group (32 eyes, uniform 7.2 J/cm2 for 5 min and 20 s of pulsed-light exposure, KXL, Glaukos-Avedro). Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), corneal fluorescein staining (CFS), corneal topography, anterior segment optical coherence tomography (AS-OCT), and in vivo corneal confocal microscopy (IVCM) were performed 3, 6, 12 and 24 months after surgery.Results: The CFS scores in the BI-TE-CXL group were significantly higher than those in the TE-CXL group on the first two days after surgery (p < 0.001). The Kmax (at 12 and 24 months) and CDVA (logMAR) were significantly lower in the BI-TE-CXL group than those in the TE-CXL group (p < 0.05). The corneal demarcation line under AS-OCT was visible in 81.3% of patients in the BI-TE-CXL group and 15.6% in the TE-CXL group. The depth of the demarcation line under IVCM was significantly deeper in the BI-TE-CXL group (248.3 ± 25.0 µm) than that of the TE-CXL group (136.5 ± 15.6 µm) in the central cornea (p < 0.001). The cross-linked collagen structures in the central cornea were still present after 12 months in the BI-TE-CXL group. No significant difference in sub-basal nerve density between the two groups (p > 0.05).Conclusions: Following BI-TE-CXL, CDVA was significantly improved, accompanied by deeper demarcation line depth and persistent crosslinked structures in the central corneal stroma.

Relation Between Corneal Dendritic Cell Density and Tear Film Stability in Patients with Epidemic Keratoconjunctivitis Associated Dry Eye.

PURPOSE: To clarify the ocular surface features of patients with recent history of epidemic keratoconjunctivitis (EKC) and the relation between corneal dendritic cells (DCs) and ocular discomfort. METHODS: Normal controls (NC) and dry eye (DE) patients without EKC were recruited. Patients with recent EKC history (onset >4 weeks, but <20 weeks) were recruited as EKC + DE group (with dry eye) or EKC-DE group (without dry eye). Ocular surface disease index (OSDI) questionnaire, tear film parameters including lipid layer thickness, first tear break-up time (fBUT), average tear break-up time (aBUT), tear meniscus height and Schirmer I test, meibomian gland parameters, and in vivo corneal confocal microscopy were evaluated. RESULTS: 50 subjects in the NC group, 83 patients in the DE group, 76 patients in the EKC + DE group, and 38 patients in the EKC-DE group were included. Compared with the NC, DE, and EKC-DE groups, the EKC + DE group represented higher OSDI, lid margin, and meibum score (p < 0.05). In the EKC + DE group, the tear volume (10.5 ± 3.7 mm) was significantly higher than in the DE group (8.1 ± 2.8 mm, p < 0.001). The DC density in the EKC + DE group (29.98 ± 15.38 cells/image) was significantly higher than in NC, DE, and EKC-DE groups (4.68 ± 4.05 cells/image) (p < 0.001). The DC density was positively correlated with OSDI, lid margin, and meibum score (all p < 0.01) while inversely correlated with fBUT, aBUT (all p < 0.001) in the EKC + DE group. CONCLUSIONS: Corneal DC density significantly correlates to ocular discomfort and tear film instability in patients with recent EKC history who suffer from DE without aqueous tear deficiency.

Advances in clinical examination of lacrimal gland.

In humans, the lacrimal gland is located in the socket of the frontal bone above the outer orbital area. As an essential part of the eye surface, the gland is fixed to the orbital periosteum by connective tissue. The lacrimal gland passes through the outer tendon membrane, which divides the gland into larger orbital and minor eyelid glands. The lacrimal glands are the main contributors to tear film. They secrete electrolytes, proteins, and water to help nourish and protect the eye's surface. Furthermore, clinically, lacrimal glands are associated with a variety of inflammatory reactions and immune factors and are also vulnerable sites for tumors. Changes in tear gland morphology or secretory function affect tear film stability and tear secretion quality. Various technological devices have been developed and applied to lacrimal glands. This article systematically reviewed the clinical examination of the lacrimal gland to help inform personalized strategies for the diagnosis of lacrimal gland-related diseases.

Limbal Stem Cell Dysfunction Induced by Severe Dry Eye via Activation of the p38 MAPK Signaling Pathway.

Severe dry eye (SDE) can cause grievous damage to the ocular surface and result in vision impairment and even blindness. To investigate the fate of limbal stem cells in SDE and the underlying mechanism, the current study established an SDE rat model by removing the extraorbital and infraorbital lacrimal glands and maintaining them in a low-humidity environment. One month after the surgery, aqueous tear secretion was reduced dramatically, blood vessels invaded into the central cornea, and inflammatory cells infiltrated into the limbal stroma. The expressions of keratin 12 and paired box gene 6 were down-regulated dramatically, while those of keratin 10, small proline-rich protein 1b, and mucin 5AC were up-regulated in the corneal epithelium of the SDE rats. Cell proliferation in the limbal epithelium was up-regulated, while the stem/progenitor marker adenosine 5'-triphosphate-binding cassette member 2 and the limbal epithelial colony-forming efficiency were decreased in the SDE condition. Furthermore, the p38 mitogen-activated protein kinase signaling pathway was activated in the limbal corneal epithelium of SDE rats. The abnormal differentiation and stemness loss in the corneal epithelium could be reversed upon treatment with a p38 inhibitor in a SDE in vivo model and in vitro hyperosmolar corneal epithelial culture conditions. These data suggest that SDE can lead to limbal stem cell dysfunction, and p38 mitogen-activated protein kinase signaling pathway activation plays an essential role in this process.

The clinicopathological analysis of ocular and orbit tumors in southeast of China.

Purpose: The purpose of this study is to describe the clinicopathologic characteristics of ocular surface and orbit tumors in the Southeast of China and explore the method to differentiate the benign and malignant masses. Materials and methods: 3468 patients undergoing mass resection from January 2015 to December 2020 were selected as observation subjects and were classified into benign and malignant masses according to postoperative pathology. The clinicopathologic characteristics were collected, including gender, age, pathological tissue signs, and pathological signs. Multivariate Logistic regression analysis of independent risk factors of malignant mass was applied to establish a diagnostic model and the efficacy was evaluated by the subject working characteristics (ROC) curve. Results: Benign tumors accounted for 91.5% of all cases, and malignant tumors accounted for 8.5%. The most common ocular benign tumors were nevi (24.2%), granuloma (17.1%), and cysts (16.4%). The most common ocular malignant tumors were malignant lymphoma (32.1%) and Basal cell carcinoma (20.2%). As for the histologic origin, melanocytic origin was on the list with 819 (23.6%), mesenchymal 661 (19.1%), epithelial 568 (16.3%), cystic 521 (15.0%), skin adnexal 110 (3.1%), lymphoid 94 (2.8%), and Neural 25(0.8%). Based on the gender, age, tumor location, and the pathological tissue image feature (including differentiation, structural atypia, covering epithelial, keratosis, nest structure/distribution, nuclear atypia, cytoplasmic change and nuclear division), the diagnostic model had predictive value to differentiate the benign and malignant masses. Conclusion: Most ocular surface and orbit tumors are benign. Tumor diagnosis is relative to the patient's age, gender, tumor location, and pathologic characteristics. We generated a satisfactory diagnostic model to differential diagnosis of benign and malignant masses.

Optimization of method for achieving a single-cell suspension from mouse corneas.

The single-cell RNA-sequencing (scRNA-seq) technique is used to explore the biological characteristics of tissues under pathological and physiological conditions that include certain chronic eye diseases. Harvesting of single-cell suspensions is one challenge inherent to scRNA-seq procedures. This study aimed to use an optimized method to digest a whole mouse cornea to harvest single-cell suspensions. We utilized five different mouse cornea digestion methods to obtain single-cell suspensions: (1) 5 dissected mouse corneas were cut into pieces (∼0.5 mm) and digested in trypsin for 10 min, and this digestion was repeated for 10 cycles; (2) 5 dissected mouse corneas were cut into pieces and incubated with 5 mg/ml collagenase A at 37 °C for 1h and then further digested in trypsin at 37 °C for 10 min; (3) used the same approach as that used in method 2, but the second digestion step was performed in TrypLE for 20 min; (4) used the same approach as that used in method 2, but the concentration of collagenase A was 2 mg/ml and the incubation time was 2h; (5) used the same approach as that used in method 3, but the corneas were incubated in 2 mg/ml collagenase A at 37 °C for 2h. Trypan blue staining was used to calculate the cell viability and agglomeration rate. The cell types and percentages were determined using immunofluorescence staining. RNA integrity number (RIN) was measured by Agilent 2100. Method 1 showed the lowest cell yield (0.375 × 105), epithelial cell percentage, and less than 70% cell viability, thus not a proper protocol. Method 2 showed the highest cell viability (over 90%), percentage of single-cell (89.53%), and high cell quantity (1.05 × 105). Method 3 had a significantly lower cell viability (55.30%). Cell agglomeration rates of method 4 and 5 reached up to 20% and 13%, and with lower cell viability (72.51%, 59.87%, respectively) and decreased epithelial cell rate compared to method 2 and 3. The results suggest that method 2 (5 mg/ml collagenase A and trypsin) is a preferred protocol for digesting mouse cornea to obtain single-cell suspension which achieves the criterion of single-cell RNA sequencing.

Histopathology-based diagnosis of Mooren's ulcer concealed beneath the pterygium on eye.

Mooren's ulcer (MU) is a chronic and painful ulcerative keratitis that is difficult to diagnose, especially when concealed beneath the pterygium, which is a common, benign, wedge-shaped, fleshy tissue growth of the conjunctiva extending onto the cornea. The coexistence of MU and pterygium is extremely rare. A 41-year-old man presented with a 2-month history of unprovoked redness, pain, and blurred vision in the right eye. Corneal epithelial defects around the pterygium head were noted upon slit-lamp examination and fluorescein staining. The patient was initially misdiagnosed with a corneal epithelial defect and pterygium. The initial treatments with anti-inflammatory and corneal epithelial growth promotion tear agents failed. Anterior segment optical coherence tomography (AS-OCT) showed corneal stromal lysis thinning, and in vivo confocal microscopy (IVCM) revealed marked inflammatory cell infiltration and stromal degeneration. We suspected the pathology was an immune-related or tumor-related corneal ulcer. The MU concealed beneath the pterygium was diagnosed by histopathological examination of a biopsy specimen that presented typical localized loss of the corneal epithelium and Bowman's layer, stromal degeneration, and inflammatory cell infiltration. Finally, we performed lamellar keratoplasty (LKP) combined with pterygium excision surgery. The patient recovered with no complications or recurrence during the 1-year follow-up period. Few cases of MU concealed beneath the pterygium have been reported. It is beneficial to rule out the pathological changes concealed beneath the pterygium, combined with multiple means of examination such as slit-lamp examination, AS-OCT, and IVCM. A histopathological examination should be performed to establish a diagnosis.

Corneal Perforation Caused by Eyelid Margin Trichilemmal Carcinoma: A Case Report and Review of Literature.

Background: Trichilemmal carcinoma (TLC) is a rare malignant adnexal tumor most commonly found in the elderly, usually affecting the scalp, eyelids, neck and face. Here, we first reported a rare case of corneal perforation caused by eyelid margin TLC. Case Presentation: A 68-year-old female presented with 2 months history of unprovoked redness, pain and blurred vision in the left eye. On slit-lamp examination, a 1 × 2 mm sized aseptic corneal perforation embedded by iris prolapsed was noted. Upon detailed case investigation, we speculated that the severe meibomian gland dysfunction (MGD) and subsequent Blepharokeratoconjunctivitis (BKC) could have led to corneal perforation. The patient underwent penetrating keratoplasty to prevent ulcer enlargement and infection. However, several tiny nodules gradually developed on the eyelid margin postoperatively, accompaniedby with bleeding, burst and madarosis postoperatiely. Subsequently, biopsy revealed the growth of TLC on the eyelid margin, and lesionectomy was immediately conducted During the 1-year follow-up period, no local recurrence or metastasis was observed. Conclusions: To date, there has not been any report of corneal perforation caused by eyelid margin TLC. Consideration of the clinical presentation, feature and histopathologist will be benefit for the dignoses and treatment of TLC. Ensuring a smooth eyelid margin by total excision of TLC and consistent followup of patient will avoid recurrence.

Ovalbumin-Induced Allergic Inflammation Diminishes Cross-Linked Collagen Structures in an Experimental Rabbit Model of Corneal Cross-Linking.

Background: Allergic conjunctivitis (AC) is one of the reported potential risk factors of progression in keratoconus patients after corneal cross-linking surgery; however, the causal relationship is still inconclusive. Recent studies have indicated that various inflammatory cytokines play a vital role in the development of primary keratoconus. It is still unclear whether these inflammatory mediators also trigger CXL failures. This study aimed to investigate the impact of AC on the rabbit corneas after trans-epithelial corneal cross-linking (TCXL). Methods: A total of six rabbits were kept untreated as the normal control (NC) group. A total of 18 rabbits were treated by TCXL and divided into three groups (six in each group), namely, no treatment (TCXL group); induction of AC (TCXL + AC group); and induction of AC plus topical prednisolone acetate (TCXL + AC + PA group), according to additional treatment. AC was induced by topical application of ovalbumin after intraperitoneal pre-sensitization with ovalbumin. Rabbits were evaluated by slit lamp, in vivo laser scanning confocal microscopy, anterior segment optical coherence tomography, and measurement of corneal biomechanics. The cornea specimens were collected for the transmission electron microscope, the collagenase I digestion test, and PCR assay for TNF-α, IL-6, IL-1ß, matrix metalloproteinase 9 (MMP-9), lysyl oxidase (LOX), and tissue inhibitor of metalloproteinases 1 (TIMP-1) on the day (D) 28. Results: On D28, the TNF-α, IL-6, IL-1ß, MMP-9, and LOX levels were significantly increased while the TIMP-1 was decreased in the TCXL + AC group when compared with the TCXL and TCXL + AC + PA groups. In vivo confocal microscopy revealed that at a depth of 150-210 µm, a trabecular patterned hyperdense structure surrounded by elongated needle-like processes could be observed in the TCXL and TCXL + AC + PA groups, but hardly seen in the TCXL + AC group. The demarcation lines were indistinct and blurred in the TCXL + AC group. An electron microscope demonstrated less interlacing fibril lamellae and higher interfibrillar spacing in the TCXL + AC group. The stability of corneal biomechanics and resistance to collagenase were decreased in the TCXL + AC group. Conclusion: The corneal microstructures induced by TCXL and biomechanical stability were diminished in rabbits with AC but could be maintained by topical anti-inflammatory treatment. Our results supported the causal relationship between altered cytokine profiles and corneal microstructure after primary corneal cross-linking.

Meibomian Glands and Tear Film Findings in Type 2 Diabetic Patients: A Cross-Sectional Study.

Background: The characteristics of the meibomian gland and tear film in patients with type 2 diabetes (T2D) with different glycemic control levels and diabetic durations remain largely unexplored. This study aimed to identify the association of dry eye and meibomian gland dysfunction (MGD) in T2D. Materials and Methods: Ninety-nine patients with type 2 diabetes mellitus (DM group), 33 dry eye patients without diabetes mellitus (DE group), and 40 normal subjects (NC group) were recruited for this study. Participants were evaluated with an Ocular Surface Disease Index (OSDI) questionnaire, tear film breakup time (BUT), the Schirmer I test (SIT), corneal fluorescein staining (FL), lipid layer thickness (LLT), and MGD parameters. Glycosylated hemoglobin (HbA1c ) and duration of diabetes were recorded. Results: The SIT value in the DM group was higher than that of the DE group (p < 0.05). The BUT and LLT were lower, and MGD parameters were higher in the DM group than those of the DE and NC groups (p < 0.05). In the DM group, 47 patients were diagnosed with dry eye (DM + DE group), whereas 40 patients without dry eye were categorized as the DM - DE group. The SIT, BUT, and LLT values in the DM - DE group were higher (p < 0.01), and MGD parameters were lower (p < 0.01) in the DM - DE group than those of the DM + DE group. The MGD parameters were higher in the DM - DE group than those in the NC group (p < 0.05). The HbA1c levels were correlated with OSDI, BUT, LLT, FL, and MGD parameters (p < 0.001) in the DM group. However, in patients with low HbA1c , normal SIT value, and low OSDI, the MGD parameters were higher than those in the NC group (p < 0.05). The duration of diabetes positively correlated with MGD parameters (p < 0.001). Conclusion: Asymptomatic MGD may be an early sign of dry eye and ocular discomfort in T2D. The MGD parameters were associated with the HbA1c level and diabetic duration.

Effects of Sodium Hyaluronate Eye Drops With or Without Preservatives on Ocular Surface Bacterial Microbiota.

PURPOSE: This study aimed to determine the composition and diversity of bacterial communities on the ocular surface before and after the intervention with sodium hyaluronate eye drops (with or without preservatives) using 16S rRNA gene amplicon sequencing. METHODS: Sixteen healthy adults were randomly divided into two groups and treated with sodium hyaluronate eye drops with or without preservatives for 2 weeks. The individuals used the same artificial tears in both eyes. The microbial samples from the conjunctival sac of each participant were collected at baseline and 2 weeks after intervention. The diversity and taxonomic differences among different groups before and after intervention were compared by sequencing the V3-V4 region of the 16S rRNA gene. RESULTS: The similarity in the binocular microbial community was high in 1 of the 16 volunteers (Bray-Curtis dissimilarity score < 0.3). At the genus level, 11 bacteria were detected in all samples with an average relative abundance of more than 1%. The bacterial community changed significantly after the use of sodium hyaluronate eye drops (with or without preservatives), whether within individuals or between individuals in different groups (P < 0.05, PERMANOVA). Different dosage forms of sodium hyaluronate eye drops significantly decreased the relative abundance of Flavobacterium caeni and Deinococcus antarcticus, respectively (P < 0.05). CONCLUSIONS: Healthy people had a rich diversity of the bacterial microbiota on the ocular surface, but the bacterial communities between the eyes were not completely similar. Irrespective of containing benzalkonium chloride (BAC), sodium hyaluronate eye drops can change the bacterial community on the ocular surface.

[Effects of magnesium supply level on growth, nutrient element absorption and distribution, and quality of Panax quinquefolium].

This study aims to investigate the effects of different magnesium supply levels on the growth, nutrient absorption and distribution, and quality of Panax quinquefolium, and to determine the optimum content of exchangeable magnesium in soil. Three-year-old plants of P. quinquefolium were used in this study, and eight magnesium supply gradients(CK, Mg1-Mg7) were designed for indoor pot experiment(cultivation in soil). The plant growth indexes, nutrient element content in soil and plant, and root saponin content were determined at the end of the growth period. The correlation analysis of nutrient element content in aboveground and underground parts of P. quinquefolium showed significantly negative correlations of magnesium-calcium, magnesium-potassium, and magne-sium-manganese. With the increase in magnesium supply level, the biological absorption coefficient of magnesium increased, while that of total nitrogen, potassium, iron, and manganese decreased; the biological transfer coefficient of magnesium decreased, while that of nitrogen, phosphorus, calcium, iron, and manganese increased. The saponin content was analyzed by principal component analysis, which showed the comprehensive score in the order of Mg4(2.537), Mg2(1.001), Mg3(0.600), Mg1(0), Mg7(-0.765), CK(-0.825), Mg6(-0.922), and Mg5(-1.663). The partial least squares-path modeling(PLS-PM) showed that the correlation coefficients of exchangeable magnesium and pH with quality were-0.748 and-0.755, respectively, which were significant. Magnesium-calcium, magnesium-potassium, and magnesium-manganese showed antagonism in the nutritional physiology of P. quinquefolium. Excessive application of magnesium can lead to the imbalance of nutrient elements in P. quinquefolium. The content of exchangeable magnesium in soil suitable for the quality formation of P. quinquefolium was 193.34-293.34 mg·kg~(-1). In addition to exchangeable magnesium, pH was also important to the quality formation of P. quinquefolium. Therefore, exchangeable magnesium and pH could be regarded as monitoring factors for the quality formation of P. quinquefolium.

Cytokine Changes in the Aqueous Humor in Rubella-Related Fuchs Heterochromic Iridocyclitis.

This retrospective study is aimed at determining the correlation between cytokine levels and virus status in the aqueous humor of 38 patients with Fuchs heterochromic iridocyclitis (FHI) with/without a viral presence between May 2017 and January 2020. The levels of cytokines were analyzed in the groups with and without virus-related FHI. Among the patients, 50% had rubella virus, 5.26% had cytomegalovirus, and 2.63% had herpes simplex virus infections. The expression of interleukin-6 (IL-6) and IL-8 was significantly higher, and that of basic fibroblast growth factor (bFGF) was significantly lower in the virus-positive group than in the virus-negative group (P = 0.015, P = 0.001, and P = 0.001, respectively). Although there was no significant difference in the mean expression of vascular cell adhesion protein 1 (VCAM-1), IL-10, and vascular endothelial growth factor (VEGF), that of VCAM-1 and IL-10 was higher (M = 1338 and M = 1390, respectively; M = 6.225 and 10.600, respectively) and that of VEGF was lower (M = 134.5 and M = 38.70, respectively) in the virus-positive group than in the virus-negative group. Similar findings were observed for the expressions of IL-6, IL-8, and bFGF in the rubella-positive and rubella-negative groups. Viral presence was highly related to FHI, especially that of the rubella virus. High levels of inflammatory cytokines and low levels of neovascularization-related factors are involved in rubella-related FHI. These study findings could be helpful in the diagnosis and treatment of FHI.

Crosslinking-Induced Corneal Endothelium Dysfunction and Its Protection by Topical Ripasudil Treatment.

PURPOSE: To investigate the changes of corneal endothelium under different crosslinking conditions and the protective effect of ripasudil. METHODS: Corneal crosslinking groups were infiltrated with riboflavin and subsequently irradiated with 0.54 J/cm2 or 1.08 J/cm2 UVA, while noncrosslinking groups included neither UVA nor riboflavin treatment, only 1.08 J/cm2 UVA and only riboflavin treatment. Corneal opacity, variations in corneal endothelial cells, and corneal thickness of all groups were observed by slit lamp, in vivo confocal microscopy, and optical coherence tomography. Immunofluorescence staining and scanning electron microscopy were performed to evaluate changes in the structure and function of the corneal endothelium. The mice that received a corneal crosslinking dose of 1.08 J/cm2 were instilled with ripasudil to explore its protective effect on the corneal endothelium. RESULTS: Treatment with UVA and riboflavin caused an increase in corneal opacity and corneal thickness and decreased endothelial cell density. Furthermore, treatment with UVA and riboflavin caused endothelial cell DNA damage and destroyed the tight junction and pump function of the endothelium, while riboflavin or the same dose of UVA alone did not affect the endothelium. Ripasudil reduced DNA damage in endothelial cells, increased the density of cells, and protected the endothelium's integrity and function. CONCLUSION: Riboflavin combined with UVA can damage the corneal endothelium's normal functioning. The corneal endothelium's wound healing is dose-dependent, and the ROCK inhibitor ripasudil maintains the endothelium's pump and barrier functions.

Convenient hyaluronidase biosensors based on the target-trigger enhancing of the permeability of a membrane using an electronic balance as a readout.

The change in hyaluronidase (HAase) is related to specific changes in the structure of vitreous, and it is necessary to develop simple but sensitive methods for HAase detection. In this work, a thin film fabricated from a hyaluronic acid (HA)-polyethyleneimine (PEI) hydrogel has been covered on a mixed cellulose microporous membrane (MCEM) to form a HA-PEI-MCEM firstly and it was then applied in a filtration system. The permeability of the filter membrane greatly affects the amount of water passing through within a certain time and the water can be collected and quantitatively measured with a simple electronic balance easily. The low permeability of the HA-PEI-MCEM allows a small amount of water to be drained. But after the addition of HAase, which can hydrolyze HA in the hydrogel, the permeability of the membrane increased. Therefore, the amount of water passing through the HA-PEI-MCEM composite membrane increased accordingly. The composite of the membrane, and the reaction conditions after the addition of HAase were optimized. Under the optimized conditions, the amount of water collected within 5 min showed a linear relationship with the HAase concentration in a range of 1.0-36 U mL-1 with a limit of detection of 0.35 U mL-1.The proposed method has been applied to detect HAase in vitreous samples with satisfactory results.