Suppressive Role of Pigment Epithelium-derived Factor in a Rat Model of Corneal Allograft Rejection.

BACKGROUND: Immunological rejection is the most common reason for corneal transplantation failure. The importance of T cells in corneal allograft rejection is well demonstrated. Recent studies highlight that pigment epithelium-derived factor (PEDF) plays an immunoregulatory role in ocular diseases by enhancing the suppressive phenotype of regulatory T cells besides its other functions in neurotrophy and antiangiogenesis. METHODS: The effects of PEDF on immune rejection were examined in rat models of corneal transplantation using slit-lamp microscope observation, immunohistochemistry, flow cytometry, and Western blot. In vitro, we demonstrated PEDF reduced alloreactive T-cell activation using real-time polymerase chain reaction, flow cytometry, and Western blot. RESULTS: Topical administration of PEDF provided corneal transplantation rats with an improved graft survival rate of corneal allografts, reduced hemangiogenesis, and infiltration of immune cells in corneas, in particular, type 17 T helper cells while increased regulatory T cells. Moreover, nerve reinnervation within grafts was promoted in PEDF-treated recipient rats. In vitro, PEDF inhibited alloreactive T-cell activation via the c-Jun N-terminal kinase/c-Jun signaling pathway and upregulated the expressions of interleukin-10 and transforming growth factor-ß, emphasizing the suppressive role of PEDF on immune responses. CONCLUSIONS: Our results underscore the feasibility of PEDF in alleviating corneal allograft rejection and further illustrate its potential in managing immune-related diseases.

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.

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.

Functional role of translocator protein and its ligands in ocular diseases (Review).

The 18 kDa translocator protein (TSPO) is an essential outer mitochondrial membrane protein that is responsible for mitochondrial transport, maintenance of mitochondrial homeostasis and normal physiological cell function. The role of TSPO in the pathogenesis of ocular diseases is a growing area of interest. More notably, TSPO exerts positive effects in regulating various pathophysiological processes, such as the inflammatory response, oxidative stress, steroid synthesis and modulation of microglial function, in combination with a variety of specific ligands such as 1­(2­chlorophenyl­N­methylpropyl)­3­isoquinolinecarboxamide, 4'­chlorodiazepam and XBD173. In the present review, the expression of TSPO in ocular tissues and the functional role of TSPO and its ligands in diverse ocular diseases was discussed.

Effects of climate factors and Demodex infestation on meibomian gland dysfunction-associated dry eye diseases.

We examined the effects of climatic factors and Demodex infestations on meibomian gland dysfunction (MGD)-associated dry eye disease (DED) in a cross-sectional study. This study included 123 patients from Tianjin and Chengdu regions, and climate factors and the Air Quality Index (AQI) were recorded for one year. Ocular surface parameters and Demodex infestations were evaluated using various tests. Significant differences in all climatic factors and AQI were observed between Tianjin and Chengdu (P < 0.01), and ocular surface parameters also differed significantly between the two regions (P < 0.05). Temperature, relative humidity, and precipitation positively correlated with tear break-up time (BUT), meibum gland expressibility, and lid margin irregularity but negatively correlated with lissamine green staining scores (P < 0.05). Wind speed and atmospheric pressure positively correlated with corneal fluorescein staining and lissamine green staining but negatively correlated with BUT and lid margin irregularity (P < 0.05). AQI positively correlated with DED symptoms and corneal findings but negatively correlated with tear film stability and meibomian gland characteristics (P < 0.05). Demodex infestation was only positively correlated with meibum quality scores (P < 0.05). Our findings suggest that geographic climates influence ocular surface characteristics in MGD-associated DED, with daily precipitation potentially playing a significant role, and Demodex infestation contributes to meibum gland degeneration.

A comparative study of pupil offset measurement using Pentacam and Keratron Scout in myopic young adults.

CLINICAL RELEVANCE: Assessing the consistency of pupil offset measurements between the Pentacam and Keratron Scout is essential for the refractive surgery design of young myopic patients. BACKGROUND: Accurate preoperative measurement of pupil offset is critical to achieving a better quality of vision after refractive surgery. The Pentacam and Keratron Scout are commonly used in hospitals, and evaluating their consistency is essential for accurate measurement of pupil offset. METHODS: Six hundred eyes (600 subjects) were included in this study. Pupil offset and its X, Y-component were measured by Pentacam and Keratron Scout, respectively. Agreement and repeatability between the two devices were identified by intraclass correlation coefficient and Bland-Altman plots with 95% limits of agreement. Paired t-tests and Pearson analysis were used to compare the differences and correlations between the two devices. RESULTS: The mean age of all subjects was 23 ± 5 years. The mean pupil offset magnitude obtained from Pentacam and Keratron Scout was 0.16 ± 0.08 mm and 0.15 ± 0.07 mm. The 95% limits of agreement (-0.11-0.13, -0.09-0.11, and -0.11-0.12) and intraclass correlation coefficient (0.82, 0.84, and 0.81) demonstrated good agreement and repeatability of the two devices in measuring pupil offset and its X, Y-component. A significant correlation between the two devices was found (r = 0.71, 0.73, and 0.70). The direction of pupil offset measured by the devices was both predominately towards the superonasal quadrant. CONCLUSION: Pentacam and Keratron Scout showed good agreement in measuring pupil offset and its X, Y-component, which can be used interchangeably in clinical practice.

Molecular mechanism of Wilms tumour 1-associated protein in diabetes-related dry eye disease by mediating m6A methylation modification of lncRNA NEAT1.

Background: Dry eye disease (DED) is often secondary to diabetes mellitus (DM).Purpose: This study is to explore the action of Wilms tumor 1-associated protein (WTAP) in DM-DED via lncRNA NEAT1 m6A methylation.Methods: DM-DED mouse models were treated with sh-WTAP/sh-NEAT1, followed by assessment of corneal epithelial damage/histopathological changes. HCE-2 cells were exposed to hyperosmotic conditions to establish in vitro DED models and treated with oe-NEAT1/sh-NEAT1/sh-WTAP/nigericin (an NLRP3 inflammasome inducer). Cell viability/apoptosis were evaluated by CCK-8/TUNEL. Levels of WTAP/NEAT1/inflammatory factors/NLRP3 inflammasome- and apoptosis-related markers were determined. m6A modification was examined by MeRIP-qPCR and NEAT1 stability was also detected.Results: DM-DED mice exhibited up-regulated WTAP/NEAT1 expression and severe corneal damage, whereas WTAP/NEAT1 knockdown alleviated inflammation/corneal damage. In hyperosmolarity-induced HCE-2 cells, NEAT1 aggravated inflammation and apoptosis, while NEAT1 knockdown suppressed NLRP3 inflammasome activation and ameliorated cell injury. Hyperosmolarity-induced WTAP expression increased m6A modification and NEAT1 mRNA stability. WTAP mediated m6A methylation of NEAT1 and NLRP3 inflammasome activation in DM-DED mice.

Identification of key genes modules linking diabetic retinopathy and circadian rhythm.

Background: Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Recent studies highlighted the crucial impact of circadian rhythms (CR) on normal retinopathy in response to the external light cues. However, the role of circadian rhythms in DR pathogenesis and potential investigational drugs remains unclear. Methods: To investigate the weather CR affects DR, differential expression analysis was employed to identify differentially expressed genes (DEGs) from the GEO database (GSE160306). Functional enrichment analysis was conducted to identify relevant signaling pathways. LASSO regression was utilized to screen pivotal genes. Weighted gene co-expression network anlaysis (WGCNA) was applied to identify different modules. Additionally, we use the Comparative Toxicogenomics Database (CTD) database to search key genes related to drugs or molecular compounds. The diabetic mouse model received three consecutive intraperitoneal injections of streptozotocin (STZ) during 3 successive days. Results: We initially identified six key genes associated with circadian rhythm in DR, including COL6A3, IGFBP2, IGHG4, KLHDC7A, RPL26P30, and MYL6P4. Compared to normal tissue, the expression levels of COL6A3 and IGFB2 were significantly increased in DR model. Furthermore, we identified several signaling pathways, including death domain binding, insulin-like growth factor I binding, and proteasome binding. We also observed that COL6A3 was positively correlated with macrophages (cor=0.628296895, p=9.96E-08) and Th17 cells (cor=0.665120835, p=9.14E-09), while IGFBP2 showed a negatively correlated with Tgd (cor=-0.459953045, p=0.000247284) and Th2 cells (cor=-0.442269719, p=0.000452875). Finally, we identified four drugs associated with key genes: Resveratrol, Vitamin E, Streptozocin, and Sulindac. Conclusion: Our findings revealed several key genes related to circadian rhythms and several relevant drugs in DR, providing a novel insight into the mechanism of DR and potential implications for future DR treatment. This study contributes to a better understanding of CR in DR and its implications for future therapeutic interventions.

A PEDF peptide mimetic effectively relieves dry eye in a diabetic murine model by restoring corneal nerve, barrier, and lacrimal gland function.

PURPOSE: The study investigated effectiveness of a novel PEDF peptide mimetic to alleviate dry eye-like pathologies in a Type I diabetic mouse model established using streptozotocin. METHODS: Mice were treated topically for 3-6 weeks with Ppx (a 17-mer PEDF mimetic) 2x/day or vehicle. Corneal sensitivity, tear film, epithelial and endothelial injury were measured using Cochet-Bonnet esthesiometer, phenol red cotton thread wetting, fluorescein sodium staining, and ZO1 expression, respectively. Inflammatory and parasympathetic nerve markers and activation of the MAPK/JNK pathways in the lacrimal glands were measured. RESULTS: Diabetic mice exhibited features of dry eye including reduced corneal sensation and tear secretion and increased corneal epithelium injury, nerve degeneration, and edema. Ppx reversed these pathologies and restored ZO1 expression and morphological integrity of the endothelium. Upregulation of IL-1ß and TNFα, increased activation of P-38, JNK, and ERK, and higher levels of M3ACHR in diabetic lacrimal glands were also reversed by the peptide treatment. CONCLUSION: The study demonstrates that topical application of a synthetic PEDF mimetic effectively alleviates diabetes-induced dry eye by restoring corneal sensitivity, tear secretion, and endothelial barrier and lacrimal gland function. These findings have significant implications for the potential treatment of dry eye using a cost-effective and reproducible approach with minimal invasiveness and no obvious side effects.

A deep learning-based model for automatic segmentation and evaluation of corneal neovascularization using slit-lamp anterior segment images.

Background: Corneal neovascularization (CoNV) is a common sign in anterior segment eye diseases, the level of which can indicate condition changes. Current CoNV evaluation methods are time-consuming and some of them rely on equipment which is not widely available in hospitals. Thus, a fast and efficient evaluation method is now urgently required. In this study, a deep learning (DL)-based model was developed to automatically segment and evaluate CoNV using anterior segment images from a slit-lamp microscope. Methods: A total of 80 cornea slit-lamp photographs (from 80 patients) with clinically manifested CoNV were collected from December 2021 to July 2022 at Tianjin Medical University Eye Hospital. Of these, 60 images were manually labelled by ophthalmologists using ImageJ software to train the vessel segmentation network IterNet. To evaluate the performance of this automated model, evaluation metrics including accuracy, precision, area under the receiver operating characteristic (ROC) curve (AUC), and F1 score were calculated between the manually labelled ground truth and the automatic segmentations of CoNV of 20 anterior segment images. Furthermore, the vessels pixel count was automatically calculated and compared with the manually labelled results to evaluate clinical usability of the automated segmentation network. Results: The IterNet model achieved an AUC of 0.989, accuracy of 0.988, sensitivity of 0.879, specificity of 0.993, area under precision-recall of 0.921, and F1 score of 0.879. The Bland-Altman plot between manually labelled ground truth and automated segmentation results produced a concordance correlation coefficient of 0.989, 95% limits of agreement between 865.4 and -562.4, and the vessels pixel count's Pearson coefficient of correlation was 0.981 (P<0.01). Conclusions: The fully automated network model IterNet provides a time-saving and efficient method to make a quantitative evaluation of CoNV using slit-lamp anterior segment images. This method demonstrates great value and clinical application potential for patient care and future research.

Exploration of efficacy and mechanism of 0.05% cyclosporine eye drops (II) monotherapy in allergic conjunctivitis-associated dry eye.

PURPOSE: To explore the efficacy and relevant mechanism of 0.05% cyclosporine A (CsA) eye drops (II) monotherapy in patients with allergic conjunctivitis-associated dry eye (ACDE). METHODS: Prospective, randomized, controlled study. Fifty-three patients with mild-to-moderate ACDE were randomly assigned to two groups. The CsA group received 0.05% CsA eye drops (II) monotherapy four times daily. The control group received 0.1% olopatadine twice daily combined with 0.1% preservative-free artificial tears four times daily. Clinical symptoms and signs, tear total IgE, and lymphotoxin-α (LT-α) concentrations were assessed at pre- and post-treatment days 7, 30, and 60. And we further measured six tear cytokines levels using a microsphere-based immunoassay. RESULTS: The CsA group showed significant improvement in symptoms (Ocular Surface Disease Index and itching scores) and signs (conjunctival hyperaemia, conjunctival oedema, conjunctival papillae, tear break-up time (TBUT), corneal fluorescein staining, and goblet cell density) at each follow-up period compared to pre-treatment (all P < 0.050). And its improvement in itching scores (P7th < 0.001, P30th = 0.039, and P60th = 0.031) and TBUT (P7th = 0.009, P30th = 0.003, and P60th = 0.005) was more significant than the control group at all follow-up periods. The tear total IgE, interleukin (IL)-5, IL-6, periostin, eotaxin-3, and MMP-9 levels significantly decreased in the CsA group at day 60 after treatment (all P < 0.050). And the changed values in tear total IgE were positively correlated with the change in itching scores. CONCLUSIONS: 0.05% CsA eye drops (II) monotherapy can rapidly improve the symptoms and signs, especially in ocular itching and TBUT, in patients with ACDE. And its efficacy is superior to 0.1% olopatadine combined with artificial tears. Moreover, CsA downregulates the expression levels of tear inflammatory cytokines, including tear total IgE, IL-5, IL-6, periostin, eotaxin-3, and MMP-9. Among that, the reduction in tear total IgE levels may reflect the improvement of ocular itching.

Clinical and in vivo confocal microscopy characteristics of Candida keratitis following keratoplasty.

BACKGROUND: We present six patients who developed Candida keratitis postoperatively. The clinical features, diagnostic testing including in vivo confocal microscopy, and outcomes are presented. METHODS: Six patients who developed Candida keratitis following penetrating and endothelial keratoplasty, were referred to Tianjin Medical University Eye Hospital between 2018 to 2021.The diagnosis was established following cultures of either corneal scraping or biopsy. In vivo confocal microscopy examination was also performed to confirm the diagnosis and characterize the morphology, distribution and the depth of Candida spp. All patients were treated with topical voriconazole (VCZ) 1% and natamycin (NTM) 5%. Patients with mid/deep stromal keratitis or interface infection were treated additionally with intrastromal or interface VCZ irrigation (0.05 mg/0.1mL). RESULTS: The cultures of corneal scrapings (4 cases) or biopsies (2 cases) were all positive for Candida spp. In vivo confocal microscopy examination was positive for fungal elements in five of the six patients. The infection resolved in five of the six patients. The patients' final uncorrected visual acuity (UCVA) ranged from hand movements (HM) to 20/80. CONCLUSION: In vivo confocal microscopy is a useful non-invasive clinical technique for confirming the diagnosis of Candida keratitis. Intrastromal and interface irrigated VCZ injections are effective treatment options.

Safety and Efficacy of the Phototherapeutic Keratectomy for Treatment of Recurrent Corneal Erosions: A Systematic Review and Meta-Analysis.

BACKGROUND: Phototherapeutic keratectomy (PTK) has been increasingly used to treat severe recurrent corneal erosion syndrome (RCES) patients who do not respond to other treatments. However, the efficacy and complication of each study are currently uncertain due to varying rates. OBJECTIVES: The objective of this study was to investigate the safety and efficacy of the PTK for recurrent corneal erosions. METHODS: This article performed a systematic literature research in Cochrane, Embase, PubMed, Scopus, and the Web of Science for the literature on PTK treatment of RCES until December 20, 2022. The extracted data including recurrence rate and the adverse event rate were used for meta-analysis. RESULTS: The recurrence rate was 18% (95% CI, 13%-24%) (129/700 eyes). Subgroup analysis showed that the RCE recurrence was 17% (95% CI, 9%-24%) after trauma and 22% (95% CI, 11%-32%) in the corneal dystrophy group. Treatment-related adverse events included subepithelial haze, hyperopic shift, and decrease of the best spectacle-corrected visual acuity. In this study, the incidence of these events was 13% (95% CI, 6%-21%), 20% (95% CI, 11%-28%), and 11% (95% CI, 5%-16%), respectively. CONCLUSIONS: PTK represented a valuable treatment option for patients with recurrent corneal erosions, especially those with traumatic injuries, which had minimal side effects.

3% diquafosol sodium eye drops in Chinese patients with dry eye: a phase IV study.

Introduction: The efficacy and safety of 3% diquafosol sodium eye drops in Chinese patients with dry eye in the real-world setting remains unclear. Methods: 3099 patients with dry eye symptoms were screened according to Asia Dry Eye Society latest recommendation. Among them, 3000 patients were enrolled for a phase IV study. We followed up with multiple clinical characteristics including corneal fluorescein staining, tear break up time, Schirmer's tests, visual acuity, intraocular pressure, and others. The follow ups were performed at baseline, 2 weeks and 4 weeks after treatment. Results: Based on the results of corneal fluorescein staining and tear break up time, all age and gender subgroups exhibited obvious alleviation of the symptoms among the patients with dry eye, and the data in elderly group showed the most significant alleviation. All the adverse drug reactions (ADRs, 6.17%) were recorded, among which 6% local ocular ADRs were included. Meanwhile, mild ADRs (91.8%) accounted for the most. Most of the ADRs (89.75%) got a quick and full recovery, with an average time at 15.6 days. 1.37% of patients dropped out of the study due to ADRs. Discussion: The use of 3% diquafosol sodium eye drop is effective and safe in the treatment of dry eye, with a low incidence of ADRs showing mild symptoms. This trial was registered at Chinese Clinical Trial Registry ID: ChiCTR1900021999 (Registration Date: 19/03/2019).

Effect of preoperative pupil offset on corneal higher-order aberrations after femtosecond laser-assisted in situ keratomileusis.

BACKGROUND: This study aimed to investigate the relationship between multiple higher-order aberrations (HOAs) subgroups and pupil offset, as well as to analyze the factors affecting postoperative corneal HOAs in patients with different degrees of refractive errors. METHODS: We enrolled 160 patients (316 eyes) aged ≥ 18 years who had undergone femtosecond laser-assisted in situ keratomileusis (FS-LASIK) treatment. Based on the relationship between the preoperative pupil offset and the postoperative ΔHOAs, all patients were divided into two groups: group I (pupil offset ≤ 0.20 mm) and group II (pupil offset > 0.20 mm). All of the eyes had low to high myopia with or without astigmatism (manifest refraction spherical equivalent (MRSE) < -10.00 D). Uncorrected distance visual acuity, corrected distance visual acuity, MRSE, pupil offset, central corneal thickness, corneal HOAs, vertical coma (Z3-1), horizontal coma (Z31), spherical aberration (Z40), trefoil 0° (Z33), and trefoil 30° (Z3-3) over a 6 mm diameter central corneal zone diameter were evaluated preoperatively and at 1 and 3 months postoperatively. RESULTS: Our result revealed significant differences in postoperative corneal total root mean square (RMS) HOAs, RMS vertical coma, RMS horizontal coma, RMS spherical aberration, and RMS trefoil 30° between group I and group II. ΔMRSE was found to be an effective factor for ΔRMS HOAs (R2 = 0.383), ΔRMS horizontal coma (R2 = 0.205), and ΔRMS spherical aberration (R2 = 0.397). In group II, multiple linear regression analysis revealed a significant correlation between preoperative pupillary offset and Δtotal RMS HOAs (R2 = 0.461), ΔRMS horizontal coma (R2 = 0.040), and ΔRMS trefoil 30°(R2 = 0.089). The ΔRMS vertical coma effect factor is the Y-component, and the factor influencing ΔRMS spherical aberration was ΔMRSE (R2 = 0.256). CONCLUSION: A small pupil offset was associated with a lower induction of postoperative corneal HOAs. Efforts to optimize centration are critical for improving surgical outcomes in patients with FS-LASIK.

Effect of PPARγ on oxidative stress in diabetes-related dry eye.

Oxidative stress is closely associated with diabetes and can cause free radical accumulation and eventually lead to ocular surface tissue damage. The purpose of this study was to investigate peroxisome proliferator-activated receptor-γ (PPARγ) expression in the lacrimal gland (LG), meibomian gland, and cornea of diabetes-related dry eye mice and whether the PPARγ agonist rosiglitazone can alleviate the oxidative stress of the ocular surface, thereby improving the condition of diabetes-related dry eye. Quantitative RT-PCR (Q-PCR) showed that the PPARγ, catalase, glutathione peroxidase 3, and heme oxygenase-1 (HO-1) mRNA expression levels in the LG of diabetes-related dry eye mice decreased at 8 and 12 weeks. In addition, the increased levels of oxidative stress were confirmed by western blot. Although the mRNA expression levels of antioxidant enzymes in the cornea and meibomian gland decreased at 8 weeks, some of them recovered by 12 weeks. Rosiglitazone alleviated ocular surface damage and increased corneal sensitivity and tear production in diabetes-related dry eye mice. Moreover, the reactive oxygen species accumulation was reduced and the PPARγ, HO-1, and glutathione peroxidase 3 mRNA expression levels were increased in the LG. The PPARγ, HO-1, translocase of the outer membrane 20, and mitochondrial transcription factor A protein levels were also significantly increased. These results demonstrated that rosiglitazone reduced oxidative stress in the LG of diabetes-related dry eye mice, at least in part, by activating PPARγ to up-regulate antioxidant enzyme expression.

Perfluorohexyloctane Eye Drops for Dry Eye Disease Associated With Meibomian Gland Dysfunction in Chinese Patients: A Randomized Clinical Trial.

Importance: Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye disease (DED). Medical and surgical management for DED is limited; therefore, new treatment options are sought. Objective: To evaluate the efficacy and safety of SHR8058 (perfluorohexyloctane) eye drops in Chinese patients with DED associated with MGD through 57 days. Design, Setting, and Participants: This was a randomized, multicenter, double-masked, saline-controlled, phase 3 clinical trial conducted from February 4, 2021, to September 7, 2022. Patients were recruited from the departments of ophthalmology in 15 hospitals in China. Patients with DED associated with MGD were enrolled between February 4 and July 1, 2021. The diagnosis was based on patient complaint of DED symptoms, an ocular surface disease index of 25 or higher, tear film break-up time of 5 seconds or less, Schirmer I test without anesthesia results of 5 mm or more at 5 minutes, total corneal fluorescein staining (tCFS) score of 4 to 11, and an MGD score of 3 or higher. Interventions: Eligible participants were randomly assigned 1:1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]) 4 times per day. Main Outcomes and Measures: The primary end points were the changes from baseline in tCFS and eye dryness scores at day 57. Results: A total of 312 participants were included in the analysis: 156 (mean [SD] age, 45.4 [15.2] years; 118 female [75.6%]) in the perfluorohexyloctane group and 156 (mean [SD] age, 43.7 [15.1] years; 127 female [81.4%]) in the NaCl group. Both primary end points were achieved, ie, changes from baseline at day 57 of tCFS score (mean [SD], -3.8 [2.7] vs -2.7 [2.8]) and eye dryness score (mean [SD], -38.6 [21.9] vs -28.3 [20.8]) in the perfluorohexyloctane group were superior to the control group, with estimated mean differences of -1.14 (95% CI, -1.70 to -0.57; P < .001) and -12.74 (95% CI, -17.20 to -8.28, P < .001), respectively. Improvements on both end points appeared to be noted on day 29 and day 15, respectively, and maintained through day 57. Compared with the control, perfluorohexyloctane eye drops also alleviated symptoms including pain (mean [SD] tCFS score, 26.7 [23.7] vs -18.7 [22.5]; P = .003), awareness of DED symptoms (mean [SD] tCFS score, -38.1 [25.1] vs -23.7 [27.6]; P < .001), and frequency of dryness (mean [SD] tCFS score, -43.3 [23.8] vs -29.1 [24.8]; P < .001). Treatment-emergent adverse events occurred in 34 participants (21.8%) and 40 participants (25.6%) in the perfluorohexyloctane and control groups, respectively. Conclusions and Relevance: Results of this randomized clinical trial demonstrate that perfluorohexyloctane eye drops significantly ameliorated the signs and symptoms of DED associated with MGD with a rapid efficacy as well as satisfactory tolerability and safety through 57 days. Findings support the use of these eye drops if results can be confirmed independently and over longer time periods. Trial Registration: ClinicalTrials.gov Identifier: NCT05515471.

ICL Postimplantation Decentration and Tilt in Myopic Patients with Primary Iridociliary Cysts.

Purpose: To observe the decentration and tilt of implantable collamer lens (ICL) as well as possible visual effects postimplantation in primary iridociliary cysts. Methods: The present investigation was a retrospective cohort study. All 48 patients (91 eyes) who underwent ICL surgery at the Center of Refraction Surgery of Tianjin Medical University Eye Hospital between July 2018 and May 2020 were split into two groups based on the absence or presence of primary iridociliary cysts established by ultrasonic biological microscopy (UBM) examination. Intraocular pressure (IOP), corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), anterior chamber angle (ACA), anterior chamber volume (ACV), and anterior chamber depth (ACD) were recorded preoperatively and postoperatively at 1, 6, and 12 months. Additionally, we performed an analysis of the ICL vault, decentration, and tilt using a rotating Scheimpflug Oculus Pentacam camera system at 1, 6, and 12 months after surgery. Results: No serious complications were observed. Significant postoperative improvement (P < 0.05) of UDVA was established in the two studied groups; however, we did not observe statistically significant intergroup differences (P > 0.05) throughout the entire research period. In each group, the preoperative ACA, ACV, and ACD were statistically significantly reduced (P < 0.05), but no such decrease was established between their postoperative values (P > 0.05). We observed no statistical differences between both groups with regard to their values of IOP, ACA, ACV, ACD, ICL vault, ICL decentration, and tilt at 1, 6, and 12 months after surgery. Similarly, no statistically significant within-group correlation (P > 0.05) of the decentration of ICL and the tilt and the CDVA values was established. Conclusion: No postimplantation effect of ICL with a central hole on vision was established in myopia patients with primary iridociliary cysts, within certain limits of ICL decentration and tilt values.

Overcoming the Stromal Barrier of the Cornea with a Peptide Conjugate Nano-Assembly to Combat Fungal Keratitis.

Fungal hyphae deeply invade the cornea in fungal keratitis. The corneal stroma hinders the infiltration of antifungal drugs and reduces their bioavailability. Here, this work reports a peptide conjugate nano-assembly that permeates the stroma and kills the pathogen without irritating the ocular cornea. The hydrophilic surface of the nano-assembly ensures deep permeation into the stroma. When encountering a fungal hyphal cell, the nano-assembly disassembles and exposes the α-helical peptide to destroy the fungal membrane, thus inactivating the pathogen. In a rabbit model of fungal keratitis, the nano-assembly exhibits a better therapeutic effect than commercially available natamycin ophthalmic suspension. Peptide conjugates with a nano-assembled structure and assembly-disassembly behavior could serve as the foundation of a new therapy for fungal keratitis.

Characteristics and factors associated with the position of the haptic after ICL V4C implantation.

PURPOSE: To assess the position of implantable collamer lens (ICL) haptic after ICL V4C implantation using standardized panoramic ultrasound bimicroscopy (UBM), to analyze its characteristics, associated factors, and the relationship with the clinical vault quantitatively. SETTING: Hankou Aier Eye Hospital, Wuhan, Hubei, China. DESIGN: Cross-sectional study. METHODS: 167 subjects (323 eyes) implanted with ICL V4C who had a 3-month follow-up with UBM examination were included in this study. The relative position of ICL to the adjacent structure and ICL haptic-related parameters (the final tip point of ICL haptic [ftICL haptic], measured from the scleral spur to the final tip of the ICL haptic, the posterior of the ICL to ICL haptic [ICL arc], measured from the posterior surface of the ICL to the ICL haptic plane, and the height of the crystalline lens from the ICL haptic (lens arc), measured from the anterior surface of the crystalline lens to the ICL haptic plane and other parameters), were estimated on the UBM image. Eyes were divided into 3 subgroups according to the ftICL haptic (Group 1: ≤0.5 mm; Group 2: 0.5 to 1.0 mm; and Group 3:≥1.0 mm, respectively), and the factors associated with the ICL haptic-related parameters and their impact on the clinical vault were evaluated. RESULTS: The haptics could be imaged in the ciliary sulcus, on the ciliary body, and under the ciliary body in 629 (48.7%), 525 (40.6%), and 138 (10.7%) eyes, respectively. The ftICL haptic and the summation of ICL arc and lens arc showed a correlation with the clinical vault ( r = -0.34, P = .00; r = 0.87, P = .00). When the ftICL haptic results were divided into 3 groups, the percentage of eyes that exhibited clinical vault >750 µm were lowest in Group 3. Multivariate regression analysis showed spherical equivalent, white-to-white (WTW), anterior chamber volume (ACV) and iris-ciliary angle (ICA); the difference between the implanted ICL size and horizontal sulcus-to-sulcus (ICL size-STS) were associated with the ftICL haptic. The IOP, WTW, ACV, and the ICL size-STS were significantly associated with ICL arc, while the ICA and lens rise were associated with lens arc. CONCLUSIONS: The position of ICL haptic was associated with the clinical vault. Its quantitative evaluation may provide valuable information to help clinicians to select the best ICL size before surgery and understand the formation of clinical vault after surgery.