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Corneal injuries from chemical burns, mechanical trauma, infections, immunological rejections, surgical complications, and some diseases are commonly associated with persistent epithelial defects (PED), neurotrophic epitheliopathy, scarring fibrosis, corneal neovascularization (CNV), and/or corneal endothelial damage that lead to vision loss. Several Food and Drug Administration (FDA) approved medications have recently become available, are currently in clinical trials, or are likely to enter clinical trials in the near future. For example, a 2-week course of topical human recombinant nerve growth factor is frequently an effective treatment for corneal neurotrophic epitheliopathy associated with PEDs. Topical losartan, an angiotensin converting enzyme II receptor antagonist that also inhibits TGF beta signaling, has been shown to effectively decrease myofibroblast generation and scarring fibrosis in alkali burn injury and Descemetorhexis rabbit models. Small molecule topical tyrosine kinase inhibitors, such as sunitinib and axitinib, FDA approved as chemotherapeutic agents to treat specific cancers, have also been found to be effective topical inhibitors of CNV in animal and human trials. Rho-kinase inhibitors, such as ripasudil and netarsudil, that are currently approved agents for the treatment of glaucoma in some countries, have been shown to stimulate corneal endothelial proliferation in animal studies and human trials, and may accelerate the regeneration of Descemet's membrane. These agents, as well as other drugs in development, will be used in targeted combinations to treat corneal pathophysiology associated with epithelial healing disorders, stromal scarring fibrosis, CNV, and corneal endothelial injury during the next decade.
To compare the performance and safety of 2 tear substitutes containing sodium hyaluronate (SH); one containing 0.15% SH and polyethylene glycol (PEG) 8000, and the other containing 0.18% SH.
Both groups improved significantly in terms of signs and symptoms. Among the 78 patients without major protocol deviations (the PP population), the OSFS score decreased by 2.9 ± 2.0 on day 28 from 5.4 ± 1.3 at baseline in the SH plus PEG group and by 2.3 ± 2.2 from 5.2 ± 1.4 in the comparator group (95% confidence interval of the difference: −1.2 to 0.3), demonstrating noninferiority. On day 90, the improvement in OSFS scores was significantly greater in the SH plus PEG group (
SH plus PEG tear substitute was noninferior to SH tear substitute in the studied population and may provide additional benefits in the long term. ClinicalTrials.gov ID: NCT02975102.
Bilastine is a second-generation antihistamine that has been shown to be effective for treatment of allergic conjunctivitis. The objective of this study was to evaluate the pharmacokinetics (PKs) and biodistribution of 0.6% bilastine preservative-free eye drops.
Bilastine was quantified in the conjunctiva, cornea, aqueous humor, vitreous humor, iris/ciliary body, retina/choroid, crystalline lens, and plasma, following a single topical administration to male Dutch-belted rabbits.
Concentrations of bilastine were highest in the conjunctiva [Cmax: 2,545.04 ng/g, at 6 h postadministration; area under the concentration–time curve (AUCt): 11,382.40 ng·h/g] and cornea (Cmax: 609.11 ng/g, at 1 h postadministration; AUCt: 1,993.88 ng·h/g), followed by the iris/ciliary body, retina/choroid, aqueous humor, plasma, vitreous humor, and crystalline lens. Quantifiable bilastine concentrations were observed up to 24 h after instillation in the conjunctiva (388.45 ng/g), cornea (28.68 ng/g), iris/ciliary body (12.42 ng/g), retina/choroid (1.91 ng/g), and crystalline lens (0.12 ng/g). In plasma, aqueous humor, and vitreous humor, bilastine was detected up to 12 h postadministration (0.18 ng/mL, 0.40 ng/mL, and 0.32 ng/g, respectively).
PKs and biodistribution of 0.6% bilastine eye drops in rabbits revealed a marked preferential distribution in the conjunctiva (target tissue), with sustained levels up to 24 h. These findings are consistent with clinical efficacy trials supporting once-daily administration of topical bilastine for treatment of allergic conjunctivitis.
The purpose of this prospective study was to compare the tear film pattern, meibomian gland (MG) losses in patients with polycystic ovary syndrome (PCOS) and healthy individuals in the control group, and to examine the correlation between peripheral blood values and findings in patients with PCOS.
Eighty-one eyes of 81 patients with PCOS and 78 eyes of 78 healthy individuals were included in this study. Mean noninvasive first tear film break-up time (NIF-BUT) values and the mean noninvasive average tear film break-up time (NIAvg-BUT) values of all breaking-up occurring in the test were compared. MG losses were compared between the groups. In the second step of this study, we examined the correlation between NIF-BUT and NIAvg-BUT values and MG losses with inflammatory parameters.
NIF-BUT values were 7.21 ± 5.75 and 10.18 ± 5.90 s, respectively, in PCOS and control groups (
Increased tear film instability and increased MG loss rates were detected in PCOS patients. In addition, we found a positive correlation between MG losses and inflammatory indices of patients with PCOS. We think that inflammatory processes also provide an additive effect, in addition to hormonal changes on the physiopathological process on the ocular surface in patients with PCOS.
This study aimed to investigate the simultaneous neuroprotective and proangiogenic effects of 7,8-dihydroxyflavone (7,8-DHF) and explore the potential underlying molecular mechanisms.
A coculture system of rat retinal explants and human umbilical vein endothelial cells (HUVECs) was established to determine the optimal concentration of 7,8-DHF, promoting neurite regeneration and HUVEC proliferation. Subsequently, the neuroprotective effect, proangiogenesis properties, and action mechanism of 7,8-DHF at an optimal concentration were investigated.
The cell proliferation, survival, migration, tube formation and p-tropomyosin-related kinase receptor B (TrkB)/TrkB levels in HUVECs were significantly promoted by 5 μM 7,8-DHF. The ganglion cell layer neuron survival, neurite regeneration, and p-TrkB/TrkB levels in retinal explants were also significantly promoted by 5 μM 7,8-DHF. All of these pharmacological actions of 7,8-DHF were blocked by N-[2-[(2-oxoazepan-3-yl)carbamoyl]phenyl]-1-benzothiophene-2-carboxamide.
7,8-DHF yields neuroprotection of retinal explants and proangiogenesis of HUVECs through the TrkB signaling pathway
We systematically retrospected and analyzed the general characteristics of ophthalmic drug clinical trials (CTs) registered in China from January 2014 to December 2021.
Data were retrieved from the Drug Trial Registration and Information Publication Platform and then standardized and statistically classified using bibliometric analysis.
We identified 201 drug CTs for eye diseases, including 24 international multicenter trials. The number of drug CTs for eye diseases has considerably increased since 2017 in parallel with new policies to encourage innovation in drugs and medical devices in China. The drug types consist of biologicals (48.26%), chemicals (45.77%), and traditional Chinese medicine/natural medicines (5.97%). The main indications were age-related macular degeneration (AMD;
Research and development of ophthalmic drugs have substantially increased in recent years and are influenced by regulatory policies. Among these drugs, biologicals for AMD are the most prevalent, followed by biologicals for macular edema. Randomized double-masked research designs are often used and represent high-quality evidence.