In silico evaluation of corneal patch eluting anti-VEGF agents concept.

This study introduces a novel approach utilizing a temporary drug-eluting hydrogel corneal patch to prevent neovascularization, alongside a numerical predictive tool for assessing the release and transport kinetics of bevacizumab (BVZ) after the keratoplasty. A key focus was investigating the impact of tear film clearance on the release kinetics and drug transport from the designed corneal patch. The proposed tear drug clearance model incorporates the physiological mechanism of lacrimal flow (tear turnover), distinguishing itself from previous models. Validation against experimental data confirms the model's robustness, despite limitations such as a 2D axisymmetrical framework and omission of blink frequency and saccadic eye movements potential effects. Analysis highlights the significant influence of lacrimal flow on ocular drug transport, with the corneal patch extending BVZ residence time compared to topical administration. This research sets the stage for exploring multi-layer drug-eluting corneal patches as a promising therapeutic strategy in ocular health.

The effect of different potency glucocorticosteroids treatments on tear inflammatory factors and corneal optical density after femtosecond-assisted laser in situ keratomileusis.

To assess the impact of glucocorticosteroids with varying potencies on inflammatory mediators in tears and corneal optical density after femtosecond-assisted laser in situ keratomileusis (FS-LASIK). In a prospective study, 110 patients (220 eyes) who underwent FS-LASIK were divided into 2 groups: 55 patients (110 eyes) received dexamethasone, and another 55 patients (110 eyes) received fluorometholone. Visual acuity, intraocular pressure, and corneal optical density were measured before, 1 week, and 1 month after surgery. Tear fluid samples were also collected to assess expression levels of TNF-α, IL-1α, IL-6, and TGF-ß1. One week after the procedure, the dexamethasone group exhibited elevated intraocular pressure (IOP) levels (P > .05) and a decreased expression of TNF-α in tears (P < .001) compared to the fluorometholone group. Within the 0 to 2 mm range from the corneal apex, the anterior corneal layer's optical density in the fluorometholone group surpassed that of the dexamethasone group (P < .05). At 1 month post-surgery, the IOP in the fluorometholone group was higher than that in the dexamethasone group (P < .05). In both the 0 to 2 mm and 2 to 6 mm intervals from the corneal apex, the optical density of the anterior corneal layer was significantly higher in the fluorometholone group compared to the dexamethasone group (P < .05). There was no statistically significant difference in visual acuity between the 2 groups at any postoperative time point. Short-term use of potent corticosteroids after FS-LASIK can swiftly address ocular surface inflammation, enhance corneal wound healing, reduce corneal edema, and accelerate the restoration of corneal transparency, in contrast to prolonged use of milder corticosteroids post-surgery.

Sodium hyaluronate and pranoprofen improve visual function and reduce inflammation in patients with dry eye.

OBJECTIVE: The aim of this study was to investigate the clinical use of sodium hyaluronate (SH) combined with pranoprofen in treating patients with dry eye. METHODS: A total of 117 patients with dry eye who were treated in the Traditional Chinese Medicine Hospital of Kunshan from March 2020 and May 2022 were included. According to the therapy approaches, they were treated with SH (SH group), pranoprofen (pranoprofen group), and SH combined with pranoprofen (joint group) (n = 39). RESULTS: The effective rates of dry eye were 79.49%, 74.36% and 94.87% in the SH group, the pranoprofen group and the joint group, respectively (p < 0.05). After treatment, the tear BUT and SIT in the joint group were all prominently increased than those in the other two groups (p < 0.05). The corneal fluorescein staining and dry eye symptom scores in the joint group after treatment were dramatically lower than those in the other two groups (p < 0.001). After treatment, the visual contrast sensitivity (12 c/d, 18 c/d and 24 c/d) in the joint group was markedly higher than those in the other two groups (p < 0.001). The CPR, TNF-α, IFN-γ and IL-1ß levels in the joint group were notably decreased than those in other two groups (p < 0.001). After treatment, the VRQOL quality-of-life scores in the joint group were significantly higher than those in the other two groups (p < 0.05). CONCLUSION: SH combined with pranoprofen showed clear therapeutic benefit in treating dry eye, and the curative effect was more favorable than with either medication alone.

Effects of combined intense pulsed light and cyclosporine 0.05% eyedrops in ocular surface matrix metalloproteinase-9 levels in patients with moderate-to-severe MGD.

To investigate the changes in meibomian gland dysfunction (MGD) and tear matrix metalloproteinase-9 (MMP-9) levels in patients with moderate-to-severe MGD after combined treatment with intense pulsed light (IPL) therapy and cyclosporine 0.05%. Thirty-six patients concurrently treated with IPL and cyclosporine 0.05% ophthalmic drops were retrospectively enrolled. Tear break up time (TBUT), corneal and conjunctival staining scores, Schirmer test, and ocular surface disease index (OSDI) questionnaire responses were recorded. Meibum quality, consistency, and eyelid margin telangiectasia were evaluated. MMP-9 levels were examined by the positivity and signal intensity of red lines (scored 0-4). IPL was performed four times with a vascular filter at 2-week intervals, followed by a 1-month follow-up after treatment cessation. Immediately after each IPL treatment, gentle meibomian gland expression was performed in both the upper and lower eyelids using meibomian gland expressor forceps. TBUT (1.88 ± 1.02 s to 3.12 ± 1.08 s, p < 0.001), corneal and conjunctival staining (6.19 ± 2.11 to 3.12 ± 1.89, p < 0.001), Oxford staining grade (2.66 ± 0.89 to 1.35 ± 0.76, p < 0.001), and OSDI (52.97 ± 21.86 to 36.36 ± 22.45, p < 0.001) scores significantly improved after the combined treatment. Meibum quality, consistency and lid margin telangiectasia showed significant post-treatment improvement in both the upper and lower eyelids. MMP-9 positivity showed a significant decrease (97-69%, p = 0.026) with a reduction in signal intensity (2.72 ± 0.87 to 2.09 ± 0.95, p = 0.011). The combination of IPL therapy and 0.05% cyclosporine eye drops effectively treats moderate-to-severe MGD by reducing symptoms and signs of MGD and by decreasing ocular surface MMP-9-associated inflammation.

Wearable, Biocompatible, and Dual-Emission Ocular Multisensor Patch for Continuous Profiling of Fluoroquinolone Antibiotics in Tears.

The abuse or misuse of antibiotics in clinical and agricultural settings severely endangers human health and ecosystems, which has raised profound concerns for public health worldwide. Trace detection and reliable discrimination of commonly used fluoroquinolone (FQ) antibiotics and their analogues have consequently become urgent to guide the rational use of antibiotic medicines and deliver efficient treatments for associated diseases. Herein, we report a wearable eye patch integrated with a quadruplex nanosensor chip for noninvasive detection and discrimination of primary FQ antibiotics in tears during routine eyedrop treatment. A set of dual-mode fluorescent nanoprobes of red- or green-emitting CdTe quantum dots integrated with lanthanide ions and a sensitizer, adenosine monophosphate, were constructed to provide an enhanced fluorescence up to 45-fold and nanomolar sensitivity toward major FQs owing to the aggregation-regulated antenna effect. The aggregation-driven, CdTe-Ln(III)-based microfluidic sensor chip is highly specific to FQ antibiotics against other non-FQ counterparts or biomolecular interfering species and is able to accurately discriminate nine types of FQ or non-FQ eyedrop suspensions using linear discriminant analysis. The prototyped wearable sensing detector has proven to be biocompatible and nontoxic to human tissues, which integrates the entire optical imaging modules into a miniaturized, smartphone-based platform for field use and reduces the overall assay time to ∼5 min. The practicability of the wearable eye patch was demonstrated through accurate quantification of antibiotics in a bactericidal event and the continuous profiling of FQ residues in tears after using a typical prescription antibiotic eyedrop. This technology provides a useful supplement to the toolbox for on-site and real-time examination and regulation of inappropriate daily drug use that might potentially lead to long-term antibiotic abuse and has great implications in advancing personal healthcare techniques for the regulation of daily medication therapy.

Comparison of the effects of intranasal and intramuscular midazolam-butorphanol-ketamine on intraocular pressure, tear production and sedation in New Zealand White rabbits.

OBJECTIVE: To compare the effects of intranasal (IN) and intramuscular (IM) midazolam-butorphanol-ketamine on intraocular pressure (IOP), tear production (TP) and sedation in rabbits. STUDY DESIGN: Prospective, randomized, crossover experimental study. ANIMALS: Fourteen male New Zealand White rabbits, aged 1-2 years, body mass 3.1 ± 0.8 kg (mean ± standard deviation). METHODS: Rabbits were administered midazolam (1 mg kg-1), butorphanol (1.5 mg kg-1) and ketamine (5 mg kg-1) via IN and IM routes. IOP, TP and sedation scores were assessed at 0 (before drug administration), 5, 15, 30, 45 and 60 minutes after drug administration. Heart rate (HR), respiratory rate (fR), rectal temperature (RT), noninvasive mean arterial blood pressure (MAP) and peripheral hemoglobin oxygen saturation (SpO2) were simultaneously recorded until 45 minutes after drug administration. The onset and duration of sedation and sedation scores were recorded. RESULTS: Drug delivery route had no significant impact on mean IOP (p = 0.271) or TP (p = 0.062), and there were no significant changes over time for IOP (p = 0.711) or TP (p = 0.372). Similarly, delivery route had no significant impact on HR (p = 0.747), fR (p = 0.872), RT (p = 0.379), MAP (p = 0.217) and SpO2 (p = 0.254). Sedation onset was faster with IN (3.0 ± 1.0 minutes) than with IM administration (4.9 ± 0.7 minutes) (p = 0.011), but sedation duration was significantly longer with IM (52.6 ± 7.2 minutes) than with IN delivery (30.7 ± 6.8 minutes) (p = 0.004). There was no significant difference in sedation scores between the two delivery routes at any of the recorded time points. CONCLUSIONS AND CLINICAL RELEVANCE: The combination of midazolam-butorphanol-ketamine had minimal impact on physiological and ocular variables regardless of the route of administration, whereas IN drug administration led to a shorter onset and duration of action than IM administration.

Evaluation methods using tear volume in a conjunctivitis mice model.

Allergic conjunctival disease is an immune-mediated inflammatory disease of the conjunctiva. To develop clinically useful drugs, it is necessary to develop quantitative evaluation methods that reflect the clinical symptoms in experimental animal models. Allergic conjunctivitis model mice were systemically sensitised with ovalbumin (OVA) administered intraperitoneally and locally sensitised with OVA eye drops between day 14-28. Next, conjunctivitis induced by ocular administration of OVA solution to sensitised mice was evaluated based on tear volume. Additionally, we evaluated increase in tear volume induced by direct ocular instillation of histamine, compound 48/80, and carrageenan. An increase in antigen-induced tear volume was observed in the mice model. Additionally, direct instillation of histamine, compound 48/80, and carrageenan increased tear volume. Furthermore, levocabastine inhibited the increase in tear volume in antigen-induced allergic conjunctivitis and histamine- and compound 48/80-induced conjunctivitis models. In contrast, betamethasone suppressed carrageenan-induced tear volume but not histamine- or compound 48/80-induced tear volume. Histamine may be involved in increased tear volume in allergic conjunctivitis. Betamethasone is not directly involved in the action of histamine and is thought to suppress increase in tear volume. Evaluation of tear volume in a conjunctivitis mice model is highly quantitative; therefore, it is possible to evaluate drug efficacy. This is considered a useful index compared with conventional methods.

ROS-responsive celastrol-nanomedicine alleviates inflammation for dry eye disease.

Dry eye disease (DED) is a major global eye disease leading to severe eye discomfort and even vision impairment. The incidence of DED has been gradually increasing with the high frequency of use of electronic devices. It has been demonstrated that celastrol (Cel) has excellent therapeutic efficacy in ocular disorders. However, the poor water solubility and short half-life of Cel limit its further therapeutic applications. In this work, a reactive oxygen species (ROS) sensitive polymeric micelle was fabricated for Cel delivery. The micelles improve the solubility of Cel, and the resulting Cel loaded micelles exhibit an enhanced intervention effect for DED. Thein vitroresults demonstrated that Cel-nanomedicine had a marked ROS responsive release behavior. The results ofin vitroandin vivoexperiments demonstrated that Cel has excellent biological activities to alleviate inflammation in DED by inhibiting TLR4 signaling activation and reducing pro-inflammatory cytokine expression. Therefore, the Cel nanomedicine can effectively eliminate ocular inflammation, promote corneal epithelial repair, and restore the number of goblet cells and tear secretion, providing a new option for the treatment of DED.

The impact of systemic isotretinoin treatment on the tear film, meibomian glands, and corneal endothelium.

PURPOSE: The study aims to investigate changes in tear function, meibomian glands and corneal endothelium in patients receiving systemic isotretinoin therapy. MATERIALS AND METHODS: This prospective study included 38 eyes from 38 patients (23 females and 15 males) treated with systemic isotretinoin (0.5-1 mg/kg/day) following the diagnosis of acne vulgaris. All patients underwent a comprehensive ophthalmologic examination at baseline, 1st month, and third month of treatment. Subjective complaints were assessed using the Ocular Surface Disease Index (OSDI). Tear functions were evaluated through non-invasive tear break up time (NIBUT) and Schirmer I test. Meibomian gland (MG) changes were examined using meibography. Corneal parameters, including endothelial cell density (ECD), coefficient of variation (CV), the number of cells with a hexagonal shape (6A), average cell area (AVG), and central corneal thickness (CCT) were assessed using non-contact specular microscopy. RESULTS: The mean age of the patients was 19.29 ± 2.83 years. Ocular surface-related discomfort, measured with OSDI scores, significantly worsened at the third month measurements compared to the pre-treatment values (p < 0.001). In the 1st month of treatment, there was a significant decrease in NIBUT (p < 0.05). No statistically significant difference was found in the Schirmer test results at each visit. According to the 1st and third-month analysis, there was a significant increase in MG loss compared to the pre-treatment period (p < 0.001). ECD, CV, 6 A, AVG measurements at the first and third months showed a significant change compared to the pre-treatment values (p < 0.001). No significant difference was observed in the CCT measurements during the treatment. CONCLUSION: Systemic isotretinoin disrupted tear stability, caused MG loss, deterioration in corneal endothelium, and led to symptomatic complaints in patients.

Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats.

Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.

Effects of a Long-Acting Diquafosol Ophthalmic Solution on the Ocular Surface, Tolerability, and Usability in Dry Eye Disease.

INTRODUCTION: This study aimed to investigate the tolerability of high-viscosity diquafosol tetrasodium (DQS) ophthalmic solution (DIQUAS LX; DQSLX) and examine its usability and effect on clinical findings in patients with dry eye disease (DED). METHODS: This interventional retrospective study included 66 eyes of 66 patients with DED who switched from conventional DQS to DQSLX ophthalmic solution. Tear function assessments (tear film breakup time [BUT], keratoconjunctival vital staining [VS] score), evaluations of DED symptom relief, and a four-item usability questionnaire ("comfort upon instillation," "irritation upon instillation," "eye mucus discharge," "convenience of instillation frequency") assessed using a visual analog scale from 0 (worst) to 10 (best) were administered 4 weeks after switching to DQSLX. Factors associated with drug tolerability were assessed using multiple regression analysis. RESULTS: The symptoms improved by 64.2% after switching to DQSLX. The BUT value, VS score, and the questionnaire items "comfort upon instillation" and "convenience of instillation frequency" were significantly improved after switching to DQSLX. DQSLX tolerability was reported as acceptable in 56 (84.8%) and unacceptable in 10 (15.2%) patients. Overall, DQSLX tolerability was significantly associated with "comfort upon instillation" and "convenience of instillation frequency" and tended to be associated with a VS score ≥ 1. DQSLX tolerability depended on symptom and VS score improvements and absence of excessive "eye mucus discharge" in patients with a VS score ≥ 1 (39 patients), but on "comfort upon instillation" and absence of excessive "eye mucus discharge" in patients with a VS score = 0 (27 patients). CONCLUSION: The high-viscosity DQSLX ophthalmic solution was generally considered acceptable in the study population. However, drug tolerability seemingly differed between patients with DED with and without epithelial damage. The former were affected by improvements in symptoms and clinical findings, whereas the latter were affected by comfort upon instillation. TRIAL REGISTRATION: University Hospital Medical Information Network identifier, UMIN000051390.

Antioxidant Carbon Dots Nanozyme Loaded in Thermosensitive in situ Hydrogel System for Efficient Dry Eye Disease Treatment.

Purpose: Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment. Methods: In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED. Results: This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells. Conclusion: Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.

Impact of pH modification of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus).

BACKGROUND: Commercial tobramycin ophthalmic solution is frequently used empirically to treat ocular disorders in equines, despite being primarily formulated for use in humans. It has been noted that tobramycin MIC90 concentration (minimal inhibitory concentration to 90% of microbial growth) rapidly declined following topical administration. It is hypothesized that adjustment of the pH of the empirically used tobramycin ophthalmic solution -prepared for human use- with the pH of the tears of donkeys, could increase the bioavailability of the drug and subsequently improve its penetration to the aqueous humor. Therefore, this study aimed to evaluate the impact of pH adjustment of the empirically used tobramycin ophthalmic solution on MIC90 concentration in tears and aqueous humor of donkeys (Equus asinus). The study was conducted on six (n = 6) clinically healthy donkeys. In each donkey, one eye was randomly selected to receive 210 µg tobramycin of the commercial tobramycin (CT) and used as a positive control (C group, n = 6). The other eye (treated eye) received 210 µg of the modified tobramycin ophthalmic solution (MT) (T group, n = 6). Tears and aqueous humor samples were collected 5-, 10-, 15-, 30- min, and 1-, 2-, 4-, and 6 h post-instillation. RESULTS: Modifying the pH of the empirically used commercial tobramycin ophthalmic solution in donkeys at a pH of 8.26 enhanced the drug's bioavailability. The MIC90 of the most hazardous bacteria isolated from equines' eyes such as Pseudomonas aeruginosa (MIC90 = 128 µg/ml) and Staphylococcus aureus (MIC90 = 256 µg/ml) was covered early (5 min post-instillation) and over a longer period in donkey tears (239-342 min) and aqueous humor (238-330 min) with the modified tobramycin solution. CONCLUSIONS: Adjustment of the pH of the commercial tobramycin ophthalmic solution, empirically used by veterinarians to treat donkeys' ophthalmic infections at a pH of 8.26, isotonic with the donkeys' tears pH, resulting in higher concentrations of tobramycin in tears and aqueous humor for a longer time.

A Novel Ex Vivo Blinking Method for Comparing the Corneal Residence Time of New Shampoo Formulations.

In the cosmetics sector, many products such as shampoos have a probability of accidental ocular exposure during their routine use. One very specific safety parameter is the residence time of the substance on the corneal surface, as prolonged exposure may cause injury. In this study, we developed a system that simulates corneal exposure to blinking and tear flow, for comparing the corneal clearance times of viscous detergent formulations. The Ex Vivo Eye Irritation Test (EVEIT), which uses corneal explants from discarded rabbit eyes from an abattoir, was used as the basis for the new system. To simulate blinking, we developed a silicone wiping membrane to regularly move across the corneal surface, under conditions of constant addition and aspiration of fluid, to mimic tear flow. Six shampoo formulations were tested and were shown to differ widely in their corneal clearance time. Three groups could be identified according to the observed clearance times (fast, intermediate and slow); the reference shampoo had the shortest clearance time of all tested formulations. With this new system, it is now possible to investigate an important physicochemical parameter, i.e. corneal clearance time, for the consideration of ocular safety during the development of novel cosmetic formulations.

Effectiveness and safety of Jiejing Runmu decoction in treatment of dry eye disease.

OBJECTIVE: To investigate the effectiveness and safety of Jiejing Runmu decoction in relieving the clinical manifestations of dry eye disease (DED). DESIGN AND INTERVENTIONS: This single-arm prospective intervention study was conducted at the Peking University Third Hospital and People's Hospital of Yongqing. Of the 211 patients recruited, 200 completing the follow-up were included in the analysis. Patients received Jiejing Runmu decoction once a day for 4 weeks continuously, without any change in eye care habits. Individuals were evaluated at four time points: pretreatment (baseline), 2 weeks, 1 month, and 3 months (2 months after completion of treatment), using the Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), corneal fluorescein staining, Schirmer test I and meibomian gland assessments. Adverse effects were evaluated at each follow-up visit and systematic examinations were performed during the first and last visits. RESULTS: OSDI, TBUT, corneal fluorescein staining, Schirmer test I, meibomian gland expressibility, and quality of secretions improved at 2 weeks, 1 month and 3 months compared to baseline (P < 0.0001). No significant differences were found between the sexes. Patients above 45 years showed worse subjective symptoms and objective signs, and greater improvements in corneal fluorescein staining, meibomian gland expressibility, and quality of secretions were observed in this group. No obvious adverse effects were detected during any follow-up visit. CONCLUSION: Jiejing Runmu decoction significantly improved both the subjective symptoms and objective signs of DED, with favorable tolerance.

Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs.

OBJECTIVES: The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs. PROCEDURES: Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 µL of BACKT, while the other received 40 µL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination. RESULTS: Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05). CONCLUSIONS: Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding.

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.

Autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution: a clinical comparative study.

PURPOSE: This clinical study compared autologous serum eye drops diluted with 0.5% methylcellulose and 0.9% saline solution. The subjective criteria for symptom improvement and the objective clinical criteria for response to therapy were evaluated. METHODS: This longitudinal prospective study enrolled 23 patients (42 eyes) with persistent epithelial defects or severe dry eye disease refractory to conventional therapy who had been using autologous serum 20% prepared with methylcellulose for > 6 months and started on autologous serum diluted in 0.9% saline solution. The control and intervention groups consisted of the same patients under alternate treatments. The subjective criteria for symptom relief were evaluated using the Salisbury Eye Evaluation Questionnaire. The objective clinical criteria were evaluated through a slit-lamp examination of the ocular surface, tear breakup time, corneal fluorescein staining, Schirmer's test, rose Bengal test, and tear meniscus height. These criteria were evaluated before the diluent was changed and after 30, 90, and 180 days. RESULTS: In total, 42 eyes were analyzed before and after 6 months using autologous serum diluted with 0.9% saline. No significant differences were found in the subjective criteria, tear breakup time, tear meniscus, corneal fluorescein staining, or rose Bengal test. Schirmer's test scores significantly worsened at 30 and 90 days (p=0.008). No complications or adverse effects were observed. CONCLUSIONS: This study reinforces the use of autologous serum 20% as a successful treatment for severe dry eye disease resistant to conventional therapy. Autologous serum in 0.9% saline was not inferior to the methylcellulose formulation and is much more cost-effective.

Therapeutic effects of orthokeratology lens combined with 0.01% atropine eye drops on juvenile myopia.

PURPOSE: To explore the therapeutic effects of orthokeratology lens combined with 0.01% atropine eye drops on juvenile myopia. METHODS: A total of 340 patients with juvenile myopia (340 eyes) treated from 2018 to December 2020 were divided into the control group (170 cases with 170 eyes, orthokeratology lens) and observation group (170 cases with 170 eyes, orthokeratology lens combined with 0.01% atropine eye drops). The best-corrected distance visual acuity, best-corrected near visual acuity, diopter, axial length, amplitude of accommodation, bright pupil diameter, dark pupil diameter, tear-film lipid layer thickness, and tear break-up time were measured before treatment and after 1 year of treatment. The incidence of adverse reactions was observed. RESULTS: Compared with the values before treatment, the spherical equivalent degree was significantly improved by 0.22 (0.06, 0.55) D and 0.40 (0.15, 0.72) D in the observation and control groups after the treatment, respectively (p<0.01). After the treatment, the axial length was significantly increased by (0.15 ± 0.12) mm and (0.24 ± 0.11) mm in the observation and control groups, respectively, (p<0.01). After the treatment, the amplitude of accommodation significantly declined in the observation group and was lower than that in the control group, whereas both bright and dark pupil diameters significantly increase and were larger than those in the control group (p<0.01). After the treatment, the tear-film lipid layer thickness and tear break-up time significantly declined in the two groups (p<0.01). CONCLUSIONS: Orthokeratology lens combined with 0.01% atropine eye drops can synergistically enhance the control effect on juvenile myopia with high safety.

Cyclosporine A (0.05%) Ophthalmic Gel in the Treatment of Dry Eye Disease: A Multicenter, Randomized, Double-Masked, Phase III, COSMO Trial.

Purpose: To confirm the efficacy and safety of a novel ophthalmic cyclosporine A gel (CyclAGel, 0.05% CsA) in treating patients with moderate-to-severe dry eye disease (DED). Patients and Methods: The COSMO trial was a randomized, multicenter, double-masked, vehicle-controlled, phase III trial. Patients with moderate-to-severe DED were enrolled in 37 hospitals in China between November 2020 and April 2021. Eligible patients were randomized 1:1 to receive CyclAGel 0.05% or vehicle eye drops once nightly (QD). The primary endpoint was the proportion of subjects with at least a 1-point improvement in ICSS at day 84. Treatment-emergent adverse events (TEAEs) were recorded. Results: The full analysis set (FAS) included 315 and 312 participants in the CyclAGel and vehicle groups, respectively. The primary efficacy endpoint was achieved. The proportion of subjects with at least a 1-point improvement in ICSS from baseline to day 84 was significantly higher in the CyclAGel group than in the vehicle group (73.7% [232/315] vs 53.2% [166/312], P<0.0001). Significant improvements relative to the vehicle were also observed in the ICSS and Oxford scale scoring of corneal and conjunctival fluorescein staining at day 14, 42, and 84. The Schirmer tear test results were significantly higher in the CyclAGel group than in the vehicle group on days 14 and 84 (all P<0.05). The CyclAGel 0.05% was well tolerated, and the TEAEs were mostly mild. The most frequent treatment-related TEAE was eye pain (6.9% vs 1.6% in the CyclAGel and vehicle groups, respectively). No serious treatment-related TEAEs were reported. Conclusion: Clinically and statistically significant improvements in ICSS, tear production, and symptoms were observed in participants administered CyclAGel 0.05% QD for moderate-to-severe DED. CyclAGel 0.05% QD is a new effective, safe, and well-tolerated therapeutic option that might bring additional benefits of convenience and compliance as a once-A-day treatment for DED.