New advances in medical management of dry eye: optimizing treatment strategies for enhanced relief.

PURPOSE: Dry eye disease (DED) is a prevalent ocular surface disease that is conventionally characterized by tear film hyperosmolarity and instability. This review presents a summarized classification of DED, followed by a comprehensive discussion of the most recent topical and systemic medications and clinical recommendations for selecting the most appropriate option for each patient. METHODS: An extensive literature search was conducted on electronic databases, such as PubMed, Scopus, and Web of Science, using keywords including "dry eye syndrome," "ocular surface disease," "medical management," "artificial tears," "topical immunomodulators," and "meibomian gland dysfunction." RESULTS: The underlying reasons for DED can range from insufficient aqueous tear production to increased tear evaporation. Recent literature has provided a more in-depth understanding of the pathophysiology of DED by examining the tear film's lipid, aqueous, and mucin layers. However, despite these advancements, medical management of patients with symptomatic DED has not fully reflected this modernized knowledge of its pathophysiology. CONCLUSION: To develop a rationalized strategy for treating DED, it is crucial to have updated knowledge of therapeutic options, their mechanisms of actions, and indications based on the DED type and underlying causes.

Rapid Pathogen Purge by Photosensitive Arginine-Riboflavin Carbon Dots without Toxicity.

Photo-activatable antipathogenic carbon dots (CDs) were prepared by carbonization of citric acid and arginine (Arg) via 3 min microwave treatment for use in the eradication of common microorganisms. Nitrogen-doped Arg CDs were spherical in shape with a size range of 0.5 to 5 nm. The Arg CDs were modified with fluorescent dyes, such as fluorescein sodium salt (FSS, as Arg-FSS) and riboflavin (RBF, as Arg-RBF), to improve antimicrobial potency by enhancing their application in photodynamic therapy. The modified Arg CDs afforded fluorescence emission properties at 520 nm in the green region in addition to excellent blue fluorescence intensity at 420 nm under 345 nm excitation upon their FSS and RBF conjugation, respectively. Although the cytotoxicity of Arg CDs was decreased for Arg-RBF CDs to 91.2 ± 0.7% cell viability for fibroblasts, the Arg-based CDs could be safely used for intravenous applications at 1000 µg/mL concentration. The Arg CDs showed broad-spectrum antimicrobial activity against common pathogens and the minimum inhibitory concentration of Arg CDs was almost two-fold decreased for the modified forms without UV light. However, faster and more effective antibacterial activity was determined for photosensitive Arg-RBF CDs, with total bacterial eradication upon UV-A light exposure for 30 min.

Carboxymethyl Chitosan Microgels for Sustained Delivery of Vancomycin and Long-Lasting Antibacterial Effects.

Carboxymethyl chitosan (CMCh) is a unique polysaccharide with functional groups that can develop positive and negative charges due to the abundant numbers of amine and carboxylic acid groups. CMCh is widely used in different areas due to its excellent biocompatibility, biodegradability, water solubility, and chelating ability. CMCh microgels were synthesized in a microemulsion environment using divinyl sulfone (DVS) as a crosslinking agent. CMCh microgel with tailored size and zeta potential values were obtained in a single stem by crosslinking CMCh in a water-in-oil environment. The spherical microgel structure is confirmed by SEM analysis. The sizes of CMCh microgels varied from one micrometer to tens of micrometers. The isoelectric point of CMCh microgels was determined as pH 4.4. Biocompatibility of CMCh microgels was verified on L929 fibroblasts with 96.5 ± 1.5% cell viability at 1 mg/mL concentration. The drug-carrying abilities of CMCh microgels were evaluated by loading Vancomycin (Van) antibiotic as a model drug. Furthermore, the antibacterial activity efficiency of Van-loaded CMCh microgels (Van@CMCh) was investigated. The MIC values of the released drug from Van@CMCh microgels were found to be 68.6 and 7.95 µg/mL against E. coli and S. aureus, respectively, at 24 h contact time. Disk diffusion tests confirmed that Van@CMCh microgels, especially for Gram-positive (S. aureus) bacteria, revealed long-lasting inhibitory effects on bacteria growth up to 72 h.

ESI-IM-MS characterization of cyclodextrin complexes and their chemically cross-linked alpha (α-), beta (ß-) and gamma (γ-) cyclodextrin particles as promising drug delivery materials with improved bioavailability.

Cyclodextrins (CDs) are natural cyclic oligosaccharides with a relatively hydrophobic cavity and a hydrophilic outer surface. In this study, alpha (α-), beta (ß-) and gamma (γ-) CD particles were prepared by directly using α-, ß-, and γ-CDs as monomeric units and divinyl sulfone (DVS) as a crosslinker in a single-step via reverse micelle microemulsion crosslinking technique. Particles of p(α-CD), p(ß-CD), and p(γ-CD) were perfectly spherical in sub- 10 µm size ranges. The prepared p(CD) particles at 1.0 mg/mL concentrations were found biocompatible with > 95 % cell viability against L929 fibroblasts. Furthermore, p(α-CD) and p(ß-CD) particles were found non-hemolytic with < 2 % hemolysis ratios, whereas p(γ-CD) particles were found to be slightly hemolytic with its 2.1 ± 0.4 % hemolysis ratio at 1.0 mg/mL concentration. Furthermore, a toxic compound, Bisphenol A (BPA) and a highly antioxidant polyphenol, curcumin (CUR) complexation with α-, ß-, and γ-CD molecules was investigated via Electrospray-Ion Mobility-Mass Spectrometry (ESI-IM-MS) and tandem mass spectrometry (MS/MS) analysis. It was determined that the most stable noncovalent complex was in the case of ß-CD, but the complex stoichiometry was changed by the hydrophobic nature of the guest molecules. In addition, BPA and CUR were separately loaded into prepared p(CD) particles as active agents. The drug loading and release studies showed that p(CD) particles possess governable loading and releasing profiles.

Biocompatible Glycol Chitosan Microgels as Effective Drug Carriers.

Glycol chitosan (GC) is a chitosan (CH) derivative with improved water solubility with regards to CH which affords significant solubility advantages. In this study, microgels of GC as p(GC) were synthesized by a microemulsion technique at various crosslinking ratios e.g., 5%, 10%, 50%, 75%, and 150% based on the repeating unit of GC using divinyl sulfone (DVS) as a crosslinker. The prepared p(GC) microgels were tested for blood compatibility and it was found that p(GC) microgels at 1.0 mg/mL concentration possessed a 1.15 ± 0.1% hemolysis ratio and 89 ± 5% blood clotting index value confirming their hemocompatibility. In addition, p(GC) microgels were found biocompatible with 75.5 ± 5% cell viability against L929 fibroblasts even at a 2.0 mg/mL concentration. By loading and releasing tannic acid (TA) (a polyphenolic compound with high antioxidant activity) as an active agent, p(GC) microgels' possible drug delivery device application was examined. The TA loading amount of p(GC) microgels was determined as 323.89 mg/g, and TA releases from TA loaded microgels (TA@p(GC)) were found to be linear within 9 h and a total amount of TA released was determined as 42.56 ± 2 mg/g within 57 h. According to the Trolox equivalent antioxidant capacity (TEAC) test, 400 µL of the sample added to the ABTS+ solution inhibited 68.5 ± 1.7% of the radicals. On the other hand, the total phenol content (FC) test revealed that 2000 µg/mL of TA@p(GC) microgels resulted in 27.5 ± 9.5 mg/mL GA eq antioxidant properties.

Physically Crosslinked Chondroitin Sulfate (CS)-Metal Ion (M: Fe(III), Gd(III), Zn(II), and Cu(II)) Particles for Versatile Applications and Their Biosafety.

Chondroitin sulfate (CS), a well-known glycosaminoglycan, was physically crosslinked with Fe(III), Gd(III), Zn(II), and Cu(II) ions to obtain CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) polymeric particles for multipurpose biological applications. The CS-metal ion-containing particles in the micrometer to a few hundred nanometer size range are injectable materials for intravenous administration. The CS-metal ion-containing particles are safe biomaterials for biological applications because of their perfect blood compatibility and no significant cytotoxicity on L929 fibroblast cells up to a 10 mg/mL concentration. Furthermore, CS-Zn(II) and CS-Cu(II) particles show excellent antibacterial susceptibility, with 2.5-5.0 mg/mL minimum inhibition concentration (MIC) values against Escherichia coli and Staphylococcus aureus. Moreover, the in vitro contrast enhancement abilities of aqueous CS-metal ion particle suspensions in magnetic resonance imaging (MRI) were determined by obtaining T1- and T2-weighted MR images using a 0.5 Tesla MRI scanner and by calculating the water proton relaxivities. Therefore, these CS-Fe(III), CS-Gd(III), CS-Zn(II), and CS-Cu(II) particles have significant potential as antibacterial additive materials and MRI contrast enhancement agents with less toxicity.

Poly(Glycerol) Microparticles as Drug Delivery Vehicle for Biomedical Use.

Glycerol (Gly) is a well-known, FDA-approved molecule posing three hydroxyl groups. Since Gly is biocompatible, here, it was aimed to prepare poly(Glycerol) (p(Gly)) particles directly for the first time for the delivery of therapeutic agents. Micrometer-sized particles of p(Gly) were successfully synthesized via the micro-emulsion method with an average size of 14.5 ± 5.6 µm. P(Gly) microparticles up to 1.0 g/mL concentrations were found biocompatible with 85 ± 1% cell viability against L929 fibroblasts. Moreover, p(Gly) microparticles were tested for hemocompatibility, and it was found that up to 1.0 mg/mL concentrations the particles were non-hemolytic with 0.4 ± 0.1% hemolysis ratios. In addition, the blood compatibility index values of the prepared p(Gly) particles were found as 95 ± 2%, indicating that these microparticles are both bio- and hemocompatible. Furthermore, Quercetin (QC) flavonoid, which possessed high antioxidant properties, was loaded into p(Gly) microparticles to demonstrate drug-carrying properties of the particles with improved bioavailability, non-toxicity, and high biocompatibility. The results of this study evidently revealed that p(Gly) particles can be directly prepared from a cost-effective and easily accessible glycerol molecule and the prepared particles exhibited good biocompatibility, hemocompatibility, and non-toxicity. Therefore, p(Gly) particles were found as promising vehicles for drug delivery systems in terms of their higher loading and release capability as well as for sustained long term release profiles.

Nontoxic Natural Polymeric Particle Vehicles Derived from Hyaluronic Acid and Mannitol as Mitomycin C Carriers for Bladder Cancer Treatment.

Hyaluronic acid/mannitol (HA/MN)-based particles were designed as mitomycin c (MMC) delivery vehicles through the crosslinking of 1:0, 3:1, 1:3, and 0:1 mole ratios of HA/MN to investigate their potential use in bladder cancer therapy. The HA/MN-MMC particles prepared by the microemulsion crosslinking method were of 0.5-10 µm size with a zeta potential value of -36.7 mV. The MMC carrier potential of the HA/MN-MMC particles was investigated by changing HA/MN ratios in the particle structure. The MMC loading capacity of neat HA particles was 5.3 ± 1.1 mg/g, whereas HA/MN (1:3) particles could be loaded with about three times more drug, for example, 18.4 ± 0.8 mg/g. The kinetic of MMC drug delivery from the HA/MN-MMC particles were tested in vitro in bladder cancer conditions for example, pH 4.5, 6, and 7.4. The HA-MMC particles released approximately 70% of the loaded drug in 300 h, while 43% of the loaded drug was released from the HA/MN-MMC particles within 600 h under physiological conditions, pH 7.4, 37 °C. The cytotoxicity of HA-based particles on healthy L929 fibroblast cells and HTB-9 human bladder cancer cells was investigated in vitro via MTT tests. Bare MMC inhibited about 90% of L929 fibroblast cells even at 100 µg/mL, but the cell viabilities in the presence of HA-MMC and HA/MN-MMC particles were 85 ± 5 and 109 ± 7% at 1000 µg/mL, respectively. The HA/MN-MMC (1:3) particles at 1000 µg/mL were found capable of destroying half of HTB-9 human bladder cancer cells within 24 h. Interestingly, the same particles at 50 µg/mL destroyed almost all the cancer cells with 8 ± 5% cell viability in 72 h of incubation time. The designed HA/MN-MMC (1:3) particles were found to afford a chemotherapeutic effect on the tumor cancers while reducing the toxicity of MMC against L929 fibroblast cells.

Degradable and Non-Degradable Chondroitin Sulfate Particles with the Controlled Antibiotic Release for Bacterial Infections.

Non-degradable, slightly degradable, and completely degradable micro/nanoparticles derived from chondroitin sulfate (CS) were synthesized through crosslinking reactions at 50%, 40%, and 20% mole ratios, respectively. The CS particles with a 20% crosslinking ratio show total degradation within 48 h, whereas 50% CS particles were highly stable for up to 240 h with only 7.0 ± 2.8% weight loss in physiological conditions (pH 7.4, 37 °C). Tobramycin and amikacin antibiotics were encapsulated into non-degradable CS particles with high loading at 250 g/mg for the treatment of corneal bacterial ulcers. The highest release capacity of 92 ± 2% was obtained for CS-Amikacin particles with sustainable and long-term release profiles. The antibacterial effects of CS particles loaded with 2.5 mg of antibiotic continued to render a prolonged release time of 240 h with 24 ± 2 mm inhibition zones against Pseudomonas aeruginosa. Furthermore, as a carrier, CS particles significantly improved the compatibility of the antibiotics even at high particle concentrations of 1000 g/mL with a minimum of 71 ± 7% fibroblast cell viability. In summary, the sustainable delivery of antibiotics and long-term treatment of bacterial keratitis were shown to be afforded by the design of tunable degradation ability of CS particles with improved biocompatibility for the encapsulated drugs.

Fungal Keratitis Treatment Using Drug-Loaded Hyaluronic Acid Microgels.

Antifungal drug-loaded hyaluronic acid (HA) microgels using conjugation and encapsulation drug-loading techniques were utilized in the treatment of fungal keratitis. Natamycin (NAT) and amphotericin B (AMB) drugs were chemically linked to HA microgels by employing a chemical coupling agent to obtain conjugated (C-) HA:NAT and HA:AMB microgels. Also, these drugs were loaded into the HA microgel network during HA microgel preparation to attain encapsulated (E-) HA:NAT and HA:AMB microgels. The conjugation of drug molecules was confirmed by FT-IR spectra of bare and drug-loaded HA microgels. It was determined that the AMB loading amount was about 4-fold higher for E-HA:AMB in comparison to C-HA:AMB microgels. Furthermore, the antifungal activity of drug conjugated and encapsulated HA:NAT and HA:AMB microgels was tested on Fusarium sp. and compared with the effect of bare drug molecules as control for up to 15 days of incubation time by means of the disc diffusion technique. The antifungal activity of 200 µL at 20 mg/mL concentration of C-HA:NAT and C-HA:AMB microgels was not found to effectively inhibit Fusarium sp. growth after 1 day of incubation, whereas the same concentration of E-HA:NAT and E-HA:AMB microgels totally killed Fusarium sp. for up to 15 days. These E-HA:NAT and E-HA:AMB microgels show no cytotoxicity on the L929 fibroblast cells up to 1000 µg/mL concentration, whereas the free drug molecules destroy the cells even at 100 µg/mL concentration.

Fungal keratitis: Mechanisms of infection and management strategies.

Fungal corneal ulcers are an uncommon, yet challenging, cause of vision loss. In the United States, geographic location appears to dictate not only the incidence of fungal ulcers, but also the fungal genera most encountered. These patterns of infection can be linked to environmental factors and individual characteristics of fungal organisms. Successful management of fungal ulcers is dependent on an early diagnosis. New diagnostic modalities like confocal microscopy and polymerase chain reaction are being increasingly used to detect and identify infectious organisms. Several novel therapies, including crosslinking and light therapy, are currently being tested as alternatives to conventional antifungal medications. We explore the biology of Candida, Fusarium, and Aspergillus, the three most common genera of fungi causing corneal ulcers in the United States and discuss current treatment regimens for the management of fungal keratitis.

Hyaluronic acid (HA)-Gd(III) and HA-Fe(III) microgels as MRI contrast enhancing agents.

Hyaluronic acid (HA) was crosslinked with Gd(III) and Fe(III) ions rendering physically crosslinked HA-metal(III) microgels as magnetic resonance imaging (MRI) enhancing contrast agents. These HA-Gd(III) and HA-Fe(III) microgels are injectable with size range, 50-5000 nm in water. The same isoelectric point, pH 1.2 ± 0.1, was measured for both microgels. HA-Gd(III) and HA-Fe(III) microgels are hemo-compatible biomaterials and can be safely used in intravascular applications up to 1000 µg/mL concentration. Furthermore, no significant toxicity was attained as 95 ± 8 and 81 ± 2% cell viability on L929 fibroblast cells at 100 µg/mL of HA-Gd(III) and HA-Fe(III) microgels were measured. Moreover, HA-Gd(III) microgels were found to afford significant contrast improvement capability in MRI with proton relaxivity, r1 = 2.11 mM-1 s-1, comparable with the values reported for Gd(III) labeled functionalized HA gel systems and commercial Gd based contrast agents.

Versatile Fluorescent Carbon Dots from Citric Acid and Cysteine with Antimicrobial, Anti-biofilm, Antioxidant, and AChE Enzyme Inhibition Capabilities.

Nanostructured fluorescent particles derived from natural molecules were prepared by a green synthesis technique employing a microwave method. The precursors citric acid (CA) and cysteine (Cys) were used in the preparation of S- and N-doped Cys carbon dots (Cys CDs). Synthesis was completed in 3 min. The graphitic structure revealed by XRD analysis of Cys CDs dots had good water dispersity, with diameters in the range of 2-20 nm determined by TEM analysis. The isoelectric point of the S, N-doped CDs was pH value for 5.2. The prepared Cys CDs displayed excellent fluorescence intensity with a high quantum yield of 75.6 ± 2.1%. Strong antimicrobial capability of Cys CDs was observed with 12.5 mg/mL minimum bactericidal concentration (MBC) against gram-positive and gram-negative bacteria with the highest antimicrobial activity obtained against Staphylococcus aureus. Furthermore, Cys CDs provided total biofilm eradication and inhibition abilities against Pseudomonas aeruginosa at 25 mg/mL concentration. Cys CDs are promising antioxidant materials with 1.3 ± 0.1 µmol Trolox equivalent/g antioxidant capacity. Finally, Cys CDs were also shown to inhibit the acetylcholinesterase (AChE) enzyme, which is used in the treatment of Alzheimer's disease, even at the low concentration of 100 µg/mL.

Carbon Dots Fabrication: Ocular Imaging and Therapeutic Potential.

Vision loss is a major complication in common ocular infections and diseases such as bacterial keratitis, age-related macular degeneration (AMD) and diabetic retinopathy (DR). The prevalence of such ophthalmic diseases represents an urgent need to develop safe, effective, and long-term treatments. Current therapies are riddled with drawbacks and limitations which calls for the exploration of alternative drug delivery mechanisms. Toxicity of the inorganic metals and metal oxides used for drug delivery raise safety concerns that are alleviated with the alternate use of, a natural and organic polymer which is both biocompatible and environmentally friendly. Carbon dots (CDs) represent a great potential in novel biomedical applications due to their tunable fluorescence, biocompatibility, and ability to be conjugated with diverse therapeutic materials. There is a growing interest on the exploitation of these properties for drug delivery with enhanced bio-imaging. However, there are limited reports of CD applications for ophthalmic indications. In this review, we focus on the CD potential and the development of translational therapies for ophthalmic diseases. The current review presents better understanding of fabrication of CDs and how it may be useful in delivering anti-bacterial agents, anti-VEGF molecules as well as imaging for ophthalmic applications.

Antimicrobial activity and biocompatibility of slow-release hyaluronic acid-antibiotic conjugated particles.

Here, the aim was to design and use a long-lasting antibiotic release system for prevention of postoperative infections in ophthalmic surgery. Ciprofloxacin and vancomycin-conjugated hyaluronic acid (HA) particles were prepared as drug carriers for sustained release of antibiotics. The antimicrobial effects of the released drugs were determined by disc-diffusion and macro-dilution tests at different times up to 2 weeks. Slow degradable HA particles were obtained with 35.2 wt% degradation within 21 days. The drug loading amount was increased by employing two sequential chemical linking (conjugation, 2C) and one physical absorption loading (A) procedures (2C + A processes) from 148 ± 8 to 355 ± 11 mg/g HA particles for vancomycin. The amounts of vancomycin and ciprofloxacin that were released linearly was estimated as 64.35 ± 7.35 and 25.00 ± 0.68 mg/g, respectively, from drug-conjugated HA particles in 100 h. Antimicrobial studies revealed that antibiotic-conjugated HA particles could inhibit the growth of microorganisms from 1 h to 1 week. The MBC values were measured as 0.25, 4.0, and 0.25 mg/mL against Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis, respectively, after 72 h incubation time. Cytotoxicity studies showed no difference between fibroblast growth or corneal thickness after 5 days with or without HA-antibiotic particles. The drug release studies and antimicrobial activity of antibiotic-loaded HA particles with time against various bacteria further revealed that HA particles are very effective in preventing bacterial infections. Likewise, cytotoxicity studies suggest that these particles pose no toxicity to eukaryotic cells, including corneal endothelium.

Crosslinked poly(Lactose) microgels and nanogels for biomedical applications.

HYPOTHESIS: Lactose (LAC) is a primary carbohydrate and energy source of milk has received intensive attention due to its' unique functional and nutritional properties. Many biological beneficences of LAC make it an appealing molecule to seek for designing functional interfaces. Therefore, crosslinked poly(lactose) (p(LAC)) microgel from lactose disaccharides for potential biomedical applications was pursued as biocolloids for the first time. EXPERIMENT: p(LAC) microgels prepared by chemical crosslinking with DiVinyl Sulfone (DVS) were chemically modified with ethylenediamine (EDA) to obtain amine-modified p(LAC) (p(LAC)-EDA) microgels to induce new functionalities and properties. Blood compatibilities of bare p(LAC)-EDA microgels were tested through hemolysis and blood clotting tests. Rosmarinic acid (RA) used as a model drug was loaded into p(LAC) and p(LAC)-EDA microgels to demonstrate their applicability to be used in drug loading and release applications. FINDINGS: A facile preparation of p(LAC) microgels with high yield, 90 ±â€¯5% and 0.5-50 µm size range was accomplished via water-in-oil (w/o) microemulsion crosslinking method. Upon chemical modification, the isoelectric point (IEP) from pH 1.8 for p(LAC) microgels changed to pH 7.7 for p(LAC)-EDA microgels, and the blood compatibility studies revealed that both microgels can be considered as blood compatible up to 2 mg/mL concentration, and only slight decrease in blood clotting index (BCI) of p(LAC)-EDA microgels was observed. Rosmarinic Acid (RA) was demonstrated to be released up to 4 days in phosphate buffer saline (PBS) with a linear release profile for p(LAC)-EDA microgels.

Surgical Outcomes of Phacoemulsification Followed by iStent Implantation Versus Goniotomy With the Kahook Dual Blade in Patients With Mild Primary Open-angle Glaucoma With a Minimum of 12-Month Follow-up.

PURPOSE: To study surgical outcomes after combined phacoemulsification with either iStent implantation or goniotomy using the Kahook Dual Blade (KDB) with a minimum of 12 months of follow-up. PATIENTS AND METHODS: Patients with mild primary open-angle glaucoma who underwent phacoemulsification in combination with either iStent implantation or goniotomy using the KDB from 2011 to 2017 were included. RESULTS: In total, 48 eyes in the iStent group and 29 eyes in the KDB group were included with at least 12 months of follow-up. There was no difference in patient age, sex, previous surgery, preoperative or postoperative visual acuity or intraocular pressure (IOP) between the 2 groups. Mean preoperative IOP in the iStent group decreased from 17.6±4.8 to 15.9±2.9 mm Hg (P=0.01); mean preoperative IOP in the KDB group decreased from 17.4± 4.3 to 15.0±4.0 mm Hg (P=0.01). The overall percentage of IOP reduction was 14.3% in the iStent group and 12.6% in the KDB group at 12 months of follow-up. Mean topical glaucoma medication use decreased from 2.0±0.9 to 0.7±1.1 in the iStent group and from 2.2±1.0 to 1.6±1.3 in the KDB group. Multivariable linear regression accounting for age, sex, race, baseline IOP, and number of eyes treated as covariates indicated a significant reduction in IOP from baseline with both iStent (Wald χ=3.97, P=0.046) and KDB (Wald χ=4.65, P=0.031). Multivariable logistic regression accounting for age, sex, race, baseline IOP, and number of eyes treated as covariates indicated no significant difference in overall success between iStent and KDB (Z-test=0.92, P=0.359). CONCLUSIONS: Phacoemulsification in combination with either iStent implantation or goniotomy using the KDB both achieved statistical significant reduction in IOP and number of glaucoma medications at 12 months of follow-up in patients with mild primary open-angle glaucoma with no complications.

Cryogel composites based on hyaluronic acid and halloysite nanotubes as scaffold for tissue engineering.

We present here preparation of mechanically strong and biocompatible cryogel composites based on hyaluronic acid (HA) and halloysite nanotubes (HNTs) of various compositions, and their applications as scaffold for different cell growing media. Uniaxial compression tests reveal that the incorporation of HNTs into HA cryogels leads to a ~2.5-fold increase in their Young moduli, e.g., from 38 ±â€¯1 to 99 ±â€¯4 kPa at a HA:HNTs weight ratio of 1:2. Although HA:HNTs based cryogels were found to be blood compatible with 1.37 ±â€¯0.11% hemolysis ratio at a HA:HNTs weight ratio of 1:2, they trigger thrombogenic activity with a blood clotting index of 17.3 ±â€¯4.8. Remarkably, HA:HNTs cryogel composites were found to be excellent scaffold materials in the proliferation of rat mesenchymal stem cells (MSC), human cervical carcinoma cells (HeLa), and human colon cancer cells (HCT116). The cell studies revealed that an increased amount of HNT embedding into HA cryogels leads to an increase of MSC proliferation.

Surgical outcomes of phacoemulsification/goniosynechialysis with and without endocyclophotocoagulation in patients with chronic angle closure glaucoma.

PURPOSE: To compare surgical outcomes of patients after phacoemulsification with goniosynechialysis (phaco/GSL) versus phaco with GSL and endocyclophotocoagulation (phaco/GSL/ECP) in patients with chronic angle closure glaucoma (CACG) through 12-month follow-up. METHODS: A retrospective, nonrandomized, comparative case series was performed. Patients with CACG who underwent phaco in combination with either GSL alone (group 1) or GSL with ECP with intracameral injection of kenalog (group 2) from 2011 to 2018 were included. Group 1 included 6 eyes of 6 patients and group 2 included 11 eyes of 10 patients. All surgeries were performed by a single surgeon (RSA). Primary outcome measures included changes in intraocular pressure (IOP), visual acuity (VA), failure based on IOP (>18 or <6 mmHg at 1 year), and secondary operative procedures and complication rates. Data were analyzed using a paired two-tailed T-test. RESULTS: The mean preoperative IOP decreased from 23.5 ± 11.2 to 14.2 ± 2.4 mmHg (P < 0.0073) in group 1 and 24.4 ± 8.2 to 14.5 ± 2.7 mmHg (P < 0.0001) in group 2. The mean % IOP reduction was 33.7% in group 1 and 34.2% in group 2. The mean improvement in VA (logMAR units) was 0.24 (P = 0.085) in group 1 and 0.13 (P = 0.657) in group 2. The mean number of topical meds decreased from 2.50 ± 1.76 to 1.80 ± 1.64 in group 1 (P = 0.513) and from 2.82 ± 1.25 to 1.17 ± 0.98 in group 2 (P = 0.014). CONCLUSION: Phaco/GSL and phaco/GSL/ECP both achieve a significant reduction in IOP without the complications associated with traditional glaucoma filtration surgeries.

Mesoporous, degradable hyaluronic acid microparticles for sustainable drug delivery application.

Porous and degradable hyaluronic acid (HA) microparticles was synthesized in a single step using different ratio of crosslinker, divinylsulfone (DVS) ranging between 2.5 and 100% mole ratio of HA repeating unit. HA particles less than 25% (≤10%) crosslinker ratio were found to be mesoporous and provided the highest surface area, calculated as 21.54±10.31 m2/g for 2.5% crosslinked HA particles via BET analysis. Hydrolytic degradation of 2.5% crosslinked HA microparticles in PBS (pH 7.4) and at 37.5 ºC revealed a linear weight loss up to 20 days and 94.5±4.5% weight loss for 30 days was attained. A wide spectrum antibiotic, Vancomycin as a model drug was loaded to mesoporous HA particles via directly loading from aqueous corresponding solution and by chemical conjugation method to obtain controllable and sustained release profiles from HA particles. Up to 168 h linear vancomycin release (50.5±4.2 mg/g) was accomplished from 2.5% DVS crosslinked HA particles.