Injectable cross-linked hyaluronic acid hydrogels with epigallocatechin gallate loading as vitreous substitutes.

Hyaluronic acid (HA) serves as a vitreous substitute owing to its ability to mimic the physical functions of native vitreous humor. However, pure HA hydrogels alone do not provide sufficient protection against potential inflammatory risks following vitrectomy. In this study, HA was crosslinked with 1,4-butanediol diglycidyl ether (BDDE) to form HA hydrogels (HB). Subsequently, the anti-inflammatory agent epigallocatechin gallate (EGCG) was added to the hydrogel (HBE) for ophthalmic applications as a vitreous substitute. The characterization results indicated the successful preparation of HB with transparency, refractive index, and osmolality similar to those of native vitreous humor, and with good injectability. The anti-inflammatory ability of HBE was also confirmed by the reduced expression of inflammatory genes in retinal pigment epithelial cells treated with HBE compared with those treated with HB. In a New Zealand white rabbit model undergoing vitreous substitution treatment, HBE 50 (EGCG 50 µM addition) exhibited positive results at 28 days post-surgery. These outcomes included restored intraocular pressure, improved electroretinogram responses, minimal increase in corneal thickness, and no inflammation during histological examination. This study demonstrated the potential of an injectable HA-BDDE cross-linked hydrogel containing EGCG as a vitreous substitute for vitrectomy applications, offering prolonged degradation time and anti-inflammatory effects postoperatively.

Impact of dry eye disease treatment on patient quality of life.

Dry eye disease (DED) is a common multifactorial disease affecting a substantial proportion of the population worldwide. Objective tests and subjective symptoms evaluation are necessary to assess DED. Although various treatments have been introduced, accurately evaluating the efficacy of those treatments is difficult because of the disparity between diagnostic tests and patient-reported symptoms. We reviewed the questionnaires used to evaluate DED and the improvements of quality of life with various treatments. In addition, we highlighted the importance of patient-reported outcomes (PRO) assessments for evaluating the effect of DED treatments. Given that the assessment of DED treatment effectiveness substantially relies on individual ocular experiences, acquiring qualitative PRO data is essential for comprehensive evaluation and optimal treatment management. Clinicians should not only focus on improving objective symptoms but also prioritize the well-being of patients in clinical management.

Relationship between Dry Eye Disease and Dyslipidemia: A Systematic Review.

BACKGROUND: Dyslipidemia has been suggested to be associated with the occurrence of dry eye disease (DED). However, whether dyslipidemia is responsible for the development of DED remains unclear. In this systematic review, we explored the relationship between DED and dyslipidemia by using quantitative data. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a comprehensive literature search in several databases, including PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar, and obtained six relevant studies. RESULTS: Our findings indicated that the majority of the selected studies reported a statistically significant association between dyslipidemia and DED, particularly in women. However, our quantitative analysis revealed that only two studies reported statistically significant differences in total cholesterol and high-density lipoprotein cholesterol values. CONCLUSION: No statistically significant differences exist in the majority of lipid profile parameters between individuals with and without DED, but there is a statistically significant association between dyslipidemia and DED.

Dry eye syndrome model established in rabbits via mitomycin C injection in the lacrimal gland.

PURPOSE: To develop a new dry eye syndrome (DES) animal model by injecting mitomycin C (MMC) into the lacrimal glands (LGs) of rabbits evaluated by clinical examinations. MATERIALS AND METHODS: A volume of 0.1 mL of MMC solution was injected in the LG and the infraorbital lobe of the accessory LG of rabbits for DES induction. Twenty male rabbits were separated into three groups, the control group, and different concentration of MMC, (MMC 0.25: 0.25 mg/mL or MMC 0.50: 0.5 mg/mL) were tested. Both MMC-treated groups received MMC twice injection on day 0 and day 7. Assessment of DES included changes in tear production (Schirmer's test), fluorescein staining pattern, conjunctival impression cytology, and corneal histological examination. RESULTS: After MMC injection, no obvious changes in the rabbit's eyes were noted by slit-lamp examination. Both the MMC 0.25 and the MMC 0.5 groups revealed decreased tear secretion after injection, and the MMC 0.25 group showed a continuous decrease in tear secretion up to 14 days. Fluorescent staining showed punctate keratopathy in both MMC-treated groups. In addition, both MMC-treated groups demonstrated decreased numbers of conjunctival goblet cells after injection. CONCLUSION: This model induced decreased tear production, punctate keratopathy, and decreased numbers of goblet cells, which are consistent with the current understanding of DES. Therefore, injecting MMC (0.25 mg/mL) into the LGs is an easy and reliable method to establish a rabbit DES model which can apply in new drug screening.

Risk analysis for patients with arterial thromboembolic events after intravitreal ranibizumab or aflibercept injections.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been increasingly applied in the treatment of retinal neovascular diseases. Concerns have arisen that these intravitreal agents may be associated with a potential risk of arterial thromboembolic (ATE) events. We conducted a retrospective, nationwide population-based cohort study to analyze the risks for ATE events in patients receiving intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA). Data (2011-2018) were obtained from Taiwan's National Health Insurance Research Database. Cox proportional-hazards model was used to identify the risk factors for ATEs. Of the total 3,469 patients, 1393 and 2076 patients received IVR and IVA, respectively. In our result, 38 ATEs occurred within 6 months after IVR or IVA. The risk of ATEs was lower in patients receiving IVR than in those receiving IVA (adjusted hazard ratio [aHR], 0.27; 95% confidence interval [CI], 0.11-0.66). Patients with coronary artery disease (CAD) exhibited a higher risk of ATEs than did those without CAD (aHR, 3.47; 95% CI, 1.41-8.53). The risk of ATEs was higher in patients with an event of acute myocardial infarction (AMI) or ischemic stroke (IS) within 6 months prior to index IVI than in those without recent AMI/IS events (aHR, 23.8; 95% CI, 7.35-77.2 and IS: aHR, 290.2; 95% CI, 103.1-816.4). In conclusion, compared with IVA, IVR was associated with a lower risk of ATEs. When strategies for anti-VEGF agents are devised, risk factors, such as CAD and a history of AMI or IS within 6 months should be considered. Further large-scale studies are warranted to elucidate the safety of anti-VEGF injections.

Functional Peptide-Loaded Gelatin Nanoparticles as Eyedrops for Cornea Neovascularization Treatment.

Background: Corneal neovascularization (NV) is a process of abnormal vessel growth into the transparent cornea from the limbus and can disturb the light passing through the cornea, resulting in vision loss or even blindness. The use of nanomedicine as an effective therapeutic formulation in ophthalmology has led to higher drug bioavailability and a slow drug release rate. In this research, we designed and explored the feasibility of a new nanomedicine, gp91 ds-tat (gp91) peptide-encapsulated gelatin nanoparticles (GNP-gp91), for inhibiting corneal angiogenesis. Methods: GNP-gp91 were prepared by a two-step desolvation method. The characterization and cytocompatibility of GNP-gp91 were analyzed. The inhibition effect of GNP-gp91 on HUVEC cell migration and tube formation was observed by an inverted microscope. The drug retention test in mouse cornea was observed by in vivo imaging system, fluorescence microscope, and DAPI/TAMRA staining. Finally, the therapeutic efficacy and evaluation of neovascularization-related factors were conducted through the in vivo corneal NV mice model via topical delivery. Results: The prepared GNP-gp91 had a nano-scale diameter (550.6 nm) with positive charge (21.7 mV) slow-release behavior (25%, 240hr). In vitro test revealed that GNP-gp91 enhanced the inhibition of cell migration and tube formation capacity via higher internalization of HUVEC. Topical administration (eyedrops) of the GNP-gp91 significantly prolongs the retention time (46%, 20 min) in the mouse cornea. In chemically burned corneal neovascularization models, corneal vessel area with a significant reduction in GNP-gp91 group (7.89%) was revealed when compared with PBS (33.99%) and gp91 (19.67%) treated groups via every two days dosing. Moreover, GNP-gp91 significantly reduced the concentration of Nox2, VEGF and MMP9 in NV's cornea. Conclusion: The nanomedicine, GNP-gp91, was successfully synthesized for ophthalmological application. These data suggest that GNP-gp91 contained eyedrops that not only have a longer retention time on the cornea but also can treat mice corneal NV effectively delivered in a low dosing frequency, GNP-gp91 eyedrops provides an alternative strategy for clinical ocular disease treatment in the culture.

Association of lipid-lowering agent use and dry eye disease: A nationwide matched case-control study in Taiwan, 2002-2016.

PURPOSE: The purpose of this study is to evaluate the association between lipid-lowering agent use and the risks of diagnosed dry eye disease (DED). METHODS: This retrospective, case-control study included 780 786 patients who received lipid-lowering agents in 2002-2016, of which 17 409 were newly diagnosed with DED during a ≥2-year follow-up period. These patients were matched 1:4 with control participants for age, sex, and comorbidities. Separate odds ratios (OR) were calculated for DED and each of statin and fibrate use. RESULTS: Statin users had significantly higher odds of DED (adjusted OR = 1.12; 95% confidence interval (CI) = 1.08-1.16, p < 0.0001) than nonusers. Fibrate users did not show higher odds of DED than nonusers (adjusted OR = 1.04; 95% CI = 0.99-1.10, p = 0.125). The lipophilic statin users did not show higher odds of DED compared with the hydrophilic statin users (adjusted OR = 0.99, 95% CI = 0.93-1.06, p = 0.729). Among statin users, the odds of DED did not differ significantly between patients receiving statin therapy for >180 days vs. ≤90 days or patients receiving statin therapy for 91-180 days vs. ≤90 days (adjusted OR = 1.00, p = 0.922; adjusted OR = 0.94, p = 0.541, respectively). The odds of DED were not statistically different among patients receiving low-intensity, moderate-intensity, and high-intensity of statin therapy. CONCLUSIONS: Patients receiving statin therapy had a higher DED risk than patients not receiving statin therapy. The type of statin, the duration, and the intensity of statin use were not significantly associated with DED risks. Further studies are required to identify the relevant factors related to DED risks with statin.

Trends in Diagnosed Dry Eye Disease Incidence, 2001 to 2015: A Nationwide Population-Based Study in Taiwan.

PURPOSE: The purpose of this study was to estimate the longitudinal trend in the incidence of diagnosed dry eye disease (DED) from 2001 to 2015 in Taiwan. METHODS: We obtained data from the Taiwan National Health Insurance Research Database that covers 99.9% of Taiwanese residents. The incident DED cases were identified according to diagnoses, drug codes, and procedure codes. We estimated age-specific and sex-specific incidence rates (IRs) between 2001 and 2015. RESULTS: The annual age-adjusted IRs of DED increased from 0.97 per 1000 in 2001 to 2.52 per 1000 in 2015 among male population and from 2.06 in 2001 per 1000 to 4.91 in 2015 per 1000 among female population. From 2001 to 2015, the annual IRs increased starting from age 20 to 39 years to age 70 to 79 years in both the male and female population. The men in both 20 to 39 and 50 to 59 age groups showed 3-fold higher IRs in 2015 than in 2001. However, the IRs were consistently lower in men than in women from 2001 to 2015. Overall, the IR was highest, between 10.3 (95% confidence interval, 10.1-10.5) and 13.8 (13.5-14.1) per 1000 population, in the population with the highest socioeconomic status. CONCLUSIONS: The IRs of DED increased from 2001 to 2015 for all demographics, particularly in the 20 to 39 and 50 to 59 years aged male population. These findings highlight the disease burden of DED and are expected to grow substantially.

Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye.

Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an effective and non-invasive method is required. Self-assembling nanoparticles (NPs) made from gelatin-epigallocatechin gallate (EGCG) were synthesized (GE) and surface-decorated with hyaluronic acid (HA) for drug delivery to the retinal/choroidal area. Different HA concentrations were used to prepare NPs with negative (GEH-) or positive (GEH+) surface charges. The size/zeta potential and morphology of the NPs were characterized by a dynamic light scattering (DLS) system and transmission electron microscope (TEM). The size/zeta potential of GEH+ NPs was 253.4 nm and 9.2 mV. The GEH- NPs were 390.0 nm and -35.9 mV, respectively. The cytotoxicity was tested by adult human retinal pigment epithelial cells (ARPE-19), with the results revealing that variant NPs were non-toxicity at 0.2-50 µg/mL of EGCG, and that the highest amount of GEH+ NPs was accumulated in cells examined by flowcytometry. Topical delivery (eye drops) and subconjunctival injection (SCI) methods were used to evaluate the efficiency of NP delivery to the posterior eyes in a mouse model. Whole eyeball cryosections were used to trace the location of fluorescent NPs in the eyes. The area of fluorescent signal obtained in the posterior eyes treated with GEH+ NPs in both methods (eye drops: 6.89% and SCI: 14.55%) was the greatest when compared with other groups, especially higher than free dye solution (2.79%). In summary, GEH+ NPs can be transported to the retina by eye drops and SCI; in particular, eye drops are a noninvasive method. Furthermore, GEH+ NPs, characterized by a positive surface and HA decoration, could facilitate drug delivery to the posterior eye as a useful drug carrier.

Comparison of risks of arterial thromboembolic events and glaucoma with ranibizumab and aflibercept intravitreous injection: A nationwide population-based cohort study.

BACKGROUND: To compare intravitreal aflibercept injection with intravitreal ranibizumab injection for the risk of major arterial thromboembolic events (ATEs) and glaucoma. METHODS: This retrospective, nationwide cohort study investigated 15 611 and 3867 patients aged >50 years with at least one pharmacy claim for intravitreal ranibizumab injection and aflibercept injection between 2011 and 2016, respectively. The inverse probability of treatment weighting method was performed to adjust the baseline difference between the two groups and the hazard risk of adverse events was estimated using the Cox proportional regression model. RESULTS: No significant difference was noted between intravitreal ranibizumab and aflibercept injection for arterial thromboembolic risk, including ischemic stroke and acute myocardial infarction, during a 2-year follow-up (adjusted hazard ratio (HR): 0.87, 95% confidence interval (CI): 0.53-1.42; P = .583). Subgroup analyses revealed that patients age >65 years (adjusted HR: 0.64, 95% CI: 0.45-0.92) and those without coronary artery disease (adjusted HR: 0.59, 95% CI: 0.37-0.95) had significantly lower arterial thromboembolic risk in the aflibercept group than in the ranibizumab group. Additionally, the risk of glaucoma development after intravitreal injection did not significantly differ between the two groups (adjusted HR: 0.63, 95% CI: 0.37-1.06; P = .084). CONCLUSIONS: No significant differences in the risk of major ATEs and glaucoma were found between ranibizumab and aflibercept, and aflibercept might be safe for use in elderly patients.

Refractive outcomes of femtosecond laser-assisted cataract surgery with arcuate keratotomy and standard phacoemulsification with toric intraocular lens implantation.

PURPOSE: Femtosecond laser arcuate keratotomy (FS-AK) and toric intraocular lens (IOL) implantation are effective for the correction of eyes with corneal astigmatism. In this study, the postoperative refractive outcomes of patients receiving femtosecond laser-assisted cataract surgery (FLACS) with FS-AK and patients receiving standard phacoemulsification with toric IOL implantation were evaluated. METHODS: This retrospective study reviewed the postoperative outcomes of patients undergoing FLACS with FS-AK (the FS-AK group) and patients undergoing standard phacoemulsification with toric IOL implantation (the toric IOL group). The main outcome measures were uncorrected and corrected visual acuities, keratometric and refractive astigmatism, and vector analysis. RESULTS: The FS-AK group included 41 eyes with preoperative keratometric astigmatism of - 1.64 ± 0.42 diopters (D), and the toric IOL group included 53 eyes with preoperative keratometric astigmatism of - 2.29 ± 0.91 D (P < 0.001). Postoperative refractive astigmatism was comparable between the two groups. Compared with the FS-AK group, postoperative uncorrected visual acuity was significantly better (P = 0.005) and corrected visual acuity was marginally better in the toric IOL group (P = 0.051). The absolute angles of error were 9.95° ± 9.57° and 5.08° ± 4.94° (P = 0.02) in the FS-AK and the toric IOL groups, respectively. CONCLUSION: Both FLACS with FS-AK and standard phacoemulsification with toric IOL implantation are safe and effective methods for astigmatism correction during cataract surgery. Standard phacoemulsification with toric IOL implantation achieves better visual acuity than FLACS with FS-AK at the 6-month follow-up.

Development of Lutein-Containing Eye Drops for the Treatment of Dry Eye Syndrome.

Dry eye syndrome (DES) is a common ophthalmological disease that decreases tear secretion and causes dryness, photophobia, pain, severe corneal rupture, and even blindness. Ocular and lacrimal gland inflammation is one of the pathological mechanisms underlying DES. Therefore, effective suppression of inflammation is a crucial strategy for the treatment of DES. Lutein, commonly found in healthy foods, has anti-inflammatory effects in corneal or retina-related cells and may be a potential therapy for DES. The addition of lutein to artificial tears (AT) as an eye-drop formulation for DES treatment in a mouse model was studied in the present work. Polyvinyl alcohol (PVA) was used as a thickener to increase the viscosity of eye drops to prolong drug retention on the ocular surface. A WST-8 assay in human corneal epithelial cells (HCE-2) showed that a concentration of <5 µM lutein (L5) and <1% PVA (P1) maintained the cell viability at 80%. A real-time PCR showed that the inflamed human corneal epithelial cells (HCECs) cocultured with L5P1 had downregulated expression of inflammatory genes such as IL-1ß, IL-6, and TNF-α. In a benzalkonium chloride- (BAC) induced DES mouse model, AT/L5P1 could repair damaged corneas, elevate tear secretion, increase the number of goblet cells, and inhibit the production of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in the cornea. In conclusion, we demonstrate that lutein/PVA as eye drops could prolong the drug ocular retention time and effectively to decrease inflammation in DES mice. Therefore, lutein, obtained from eye drops, has a potential therapeutic role for DES.

Association of interleukin-6 gene polymorphisms and glaucoma: Systematic review and meta-analysis.

AIM: To conduct a systematic review and meta-analysis to explore the association between IL-6 gene polymorphisms (rs1800795 and rs1524107) and glaucoma. METHODS: A comprehensive search was performed to select eligible studies regarding IL-6 polymorphisms and glaucoma. The effect sizes in the fixed-effects model were calculated using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Four eligible studies comprising 762 cases and 799 controls were selected for meta-analysis. Regarding the association between the IL-6 rs1800795 polymorphism and glaucoma, those who carried the G/G+G/C genotypes had a non-significant higher risk of glaucoma (OR = 1.29, 95% CI = 0.76-2.19) in the dominant model. However, no obvious association (OR = 0.97, 95% CI = 0.68-1.37) was found for the recessive model (G/G vs G/C+C/C). In the subgroup analysis stratified by ethnicity, no significant associations were observed in populations of Asian or European heritage. Significantly higher glaucoma risks of 15.9 and 99.0 were observed for the dominant (C/C+C/T vs T/T) and recessive (C/C vs C/T+T/T) models, respectively. CONCLUSION: No statistically significant glaucoma risks were observed for the rs1800795 except rs1524107 polymorphism of IL-6. Further studies with a larger sample size are required to validate the effects of IL-6 polymorphisms on glaucoma risk.

Chitosan-cartilage extracellular matrix hybrid scaffold induces chondrogenic differentiation to adipose-derived stem cells.

INTRODUCTION: Adipose-derived stem cells (ASCs) are potential cell sources for cartilage tissue engineering. Chitosan has been shown to enhance the stemness and differentiation capability of ASCs, and the native extracellular matrix (ECM) derived from articular cartilage has been also reported to induce chondrogenic differentiation of ASCs. Here we tested the hypothesis that a porous three-dimensional (3D) hybrid scaffold composed of chitosan and cartilage ECM can provide a better environment to induce ASC chondrogenesis. METHODS: Mixed solution composed of chitosan and cartilage ECM was frozen and lyophilized to form a composite construct. The porous 3D scaffolds were further crosslinked by genipin and used for ASC culture. RESULTS: Cultivation of ASCs in the chitosan/cartilage ECM composite 3D scaffolds induced the formation of cell spheroids with profound glycosaminoglycan production after 14 and 28 days culture. Chondrogenesis of ASCs seeded in the 3D scaffolds was also evident by mRNA expressions of cartilage-specific gene COL2A1 and ACAN on day 14. Histology and immunohistochemistry on day 28 also showed abundant cartilage-specific macromolecules, namely collagen type II and proteoglycan, deposited in a surface layer of the composite scaffold with tangential layer, transitional layer, and lacunae-like structures. Otherwise, hypertrophic markers collagen type I and X were concentrated in the area beneath the surface. CONCLUSION: Our findings demonstrated spatial chondrogenic differentiation of ASCs in the chitosan-cartilage ECM composite scaffolds. This 3D hybrid scaffold exhibits great potentials for ASC-based cartilage tissue engineering.

Dry Eye Disease: A Review of Epidemiology in Taiwan, and its Clinical Treatment and Merits.

Dry eye disease (DED) has become common on a global scale in recent years. There is a wide prevalence of DED in different countries based on various ethnicities and environment. DED is a multifactorial ocular disorder. In addition to advanced age and gender, such factors as living at high altitude, smoking, pterygium, prolonged use of consumer electronics or overingesting of caffeine or multivitamins are considered to be the major risk factors of DED. We report the DED epidemiology in Taiwan firstly in this article. According to the pathophysiological factors and changes inthe composition of the tear film in DED, it can be categorized into several subtypes, including lipid anomaly dry eye, aqueous tear deficiency, allergic and toxic dry eye among others. Each subtype has its own cause and disease management; therefore, it is important for ophthalmologists to identify the type through literature review and investigation. The management of DED, relies not only on traditional medications such as artificial tears, gels and ointments, but also newer treatment options such as acupuncture, SYL1001, and nanomedicine therapy. We also conducted a comprehensive literature review including common subtypes and treatment of DED. Clearly, more clinical trials are needed to assess the efficacy and safety of the various treatments and common subtypes of DED.

Efficacy of Vectored Thermal Pulsation and Warm Compress Treatments in Meibomian Gland Dysfunction: A Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Meibomian gland dysfunction is the main cause of dry eye disease (DED) and is traditionally managed using warm compress treatment (WCT). Vectored thermal pulsation treatment (VTPT) is a novel method for treating DED. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that compared the efficacy of VTPT and WCT in treating DED. The primary outcome was the gland function. The secondary outcomes were the tear breakup time, Schirmer test, tear osmolarity, lipid layer thickness, Standard Patient Evaluation for Eye Dryness, and the improvement of subjective symptoms as assessed by using the Ocular Surface Disease Index. PubMed, Embase, Cochrane Library, and ClinicalTrials.gov registries were searched for studies published before July 2018. RESULTS: This study consisted of 4 trials with 385 patients. Significantly greater improvement was observed in meibomian gland function [mean difference (MD): 2.19 (95% confidence interval (CI), 0.95, 3.43)], tear breakup time [MD: 1.08 (95% CI, 0.06, 2.10)], and Standard Patient Evaluation for Eye Dryness [MD: -2.76 (95% CI, -4.22, -1.30)] at 2 to 4 weeks in the VTPT group than in the WCT group. A significantly greater decrease in Ocular Surface Disease Index was observed at 2 to 4 weeks [MD: -8.61 (95% CI, -13.62, -3.61)] and 3 months [MD: -6.92 (95% CI, -11.95, -1.89)] in the VTPT group than in the WCT group. CONCLUSIONS: A single 12-minute VTPT was more efficacious than traditional WCT in treating DED either in objective or subjective measurements. We recommended choosing an appropriate treatment after shared decision-making.

Gelatin-epigallocatechin gallate nanoparticles with hyaluronic acid decoration as eye drops can treat rabbit dry-eye syndrome effectively via inflammatory relief.

INTRODUCTION: Dry-eye syndrome (DES) is a general eye disease. Eye drops are the common ophthalmological medication. However, the ocular barrier makes it difficult to attain high drug bioavailability. Nanomedicine is a promising alternative treatment for ocular diseases and may increase drug content in the affected eye. METHODS: To explore this potential, we constructed nanoparticles (NPs) containing an anti-inflammatory agent for DES treatment. The NPs were made of gelatin-epigallocatechin gallate (EGCG) with surface decoration by hyaluronic acid (HA) and designated "GEH". The particle size, surface charge, and morphology were evaluated. The in vitro biocompatibility and anti-inflammation effect of nanoparticles were assayed via culturing with human corneal epithelium cells (HCECs) and in vivo therapeutic effect was examined in a DES rabbit's model. RESULTS: The synthesized GEH NPs had a diameter of approximately 250 nm and were positively charged. A coculture experiment revealed that 20 µg/mL GEH was not cytotoxic to HCECs and that an EGCG concentration of 0.2 µg/mL downregulated the gene expression of IL1B and IL6 in inflamed HCECs. Large amounts of GEH NPs accumulated in the cytoplasm of HCECs and the ocular surfaces of rats and rabbits, indicating the advantage of GEH NPs for ocular delivery of medication. Twice-daily topical treatment with GEH NPs was performed in a rabbit model of DES. The ocular surface of GEH-treated rabbits displayed normal corneal architecture with no notable changes in inflammatory cytokine levels in the cornea lysate. The treatment improved associated clinical signs, such as tear secretion, and fluorescein staining recovered. CONCLUSION: We successfully produced GEH NPs with high affinity for HCECs and animal eyes. The treatment can be delivered as eye drops, which retain the drug on the ocular surface for a longer time. Ocular inflammation was effectively inhibited in DES rabbits. Therefore, GEH NPs are potentially valuable as a new therapeutic agent delivered in eye drops for treating DES.

Ocular Drug Delivery: Role of Degradable Polymeric Nanocarriers for Ophthalmic Application.

Ocular drug delivery has been a major challenge for clinical pharmacologists and biomaterial scientists due to intricate and unique anatomical and physiological barriers in the eye. The critical requirement varies from anterior and posterior ocular segments from a drug delivery perspective. Recently, many new drugs with special formulations have been introduced for targeted delivery with modified methods and routes of drug administration to improve drug delivery efficacy. Current developments in nanoformulations of drug carrier systems have become a promising attribute to enhance drug retention/permeation and prolong drug release in ocular tissue. Biodegradable polymers have been explored as the base polymers to prepare nanocarriers for encasing existing drugs to enhance the therapeutic effect with better tissue adherence, prolonged drug action, improved bioavailability, decreased toxicity, and targeted delivery in eye. In this review, we summarized recent studies on sustained ocular drug/gene delivery and emphasized on the nanocarriers made by biodegradable polymers such as liposome, poly lactic-co-glycolic acid (PLGA), chitosan, and gelatin. Moreover, we discussed the bio-distribution of these nanocarriers in the ocular tissue and their therapeutic applications in various ocular diseases.

Influence of visual impairment and hearing impairment on functional dependence status among people in Taiwan-An evaluation using the WHODAS 2.0 score.

BACKGROUND: Visual impairment (VI) and hearing impairment (HI) are the two most common types of sensory disability encountered clinically. However, VI and HI result in different limitations in daily life. We assessed the level of functioning in patients with VI or HI based on the International Classification of Functioning, Disability, and Health. METHODS: This nationwide, cross-sectional study included 312 people with VI and 540 people with HI. Each participant's degree of functioning and disability was evaluated using the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). The standardized WHODAS 2.0 scores ranged from 0 (least difficulty) to 100 (most difficulty). RESULTS: Patients with VI and those with HI had a mean (±standard error) 32-item WHODAS 2.0 score of 42.4 ± 2.9 and 27.1 ± 1.6, respectively. The degree of restriction was positively related to the level of VI. Specifically, the patients with VI and a WHODAS 2.0 score of 33.7-35.3 or higher were likely to experience barriers to accessing mobility products, communication products, and education products. Furthermore, patients with a score of 42.9 or higher might experience barriers to accessing ingestion products and living products. CONCLUSION: WHODAS 2.0 scores are strongly correlated with the severity of VI. Mild VI should be targeted for treatment and referral as early as possible. Compared with the patients with HI, the patients with VI more frequently experience barriers to accessing environmental factors.