A novel fixed-combination timolol-netarsudillatanoprost ophthalmic solution for the treatment of glaucoma and ocular hypertension

Currently commercial fixed-concomitant three agents have multiple problems such as multiple dosing administration,poor efficacy and side effects.Once-daily fixed-combination timolol-netarsudil-latanoprost ophthalmic solution(FC-TNL)has the ability to treat glaucoma by lowering the intraocular pressure(IOP)with great efficacy and improving patient compliance.However,the commercialized netarsudil dimesylate precipitated when the p H of the solution was above 5.4,or when maleic acid,the salt of commercial timolol maleate,was mixed with netarsudil dimesylate.Consequently,the homologous salt engineering strategy was used to make netarsudil dimesylate soluble in p H 4.8–5.2 solution by synthesizing timolol mesylate.Next,the morphology of timolol mesylate was observed by scanning electron microscopy,differential scanning calorimetry,thermogravimetric analysis,and powder X-ray diffraction.The prepared FC-TNL showed good stability during refrigeration storage.Additionally,FC-TNL exerted no influence on the intraocular penetration of each active compounds in the pharmacokinetic study.Importantly,oncedaily FC-TNL exerted potent IOP-lowering effect and protective effect on retinal ganglion cells.The FC-TNL was stable,safe and effective,being a promising glaucoma therapeutic.

Clinical effectiveness of diquafosol ophthalmic solution 3%in Korean patients with dry eye disease:a multicenter prospective observational study

AIM:To investigate the effectiveness of diquafosol ophthalmic solution 3%administered in Korean patients with dry eye disease in real-world clinical settings.METHODS:Diquafosol was administered for 8 wk to 3 patient groups who received diquafosol as add-on therapy to existing medication(Add group,n=150);received diquafosol only(Monotherapy group,n=196);or discontinued part of their existing medication in favor of diquafosol(Switch group,n=11).Tear break-up time(TBUT),cornea and conjunctival staining based on National Eye Institute/Industry scoring scheme,subjective symptoms using the Ocular Surface Disease Index(OSDI)questionnaire,and meibum quality and expressibility were evaluated at baseline,week 4,and week 8.RESULTS:The mean TBUT increased(from 3.46,3.92,and 5.84 s,respectively,to 5.15,5.53,and 8.59 s,respectively)and corneal staining score decreased(from 2.23,2.24,and 3.09,respectively,to 0.85,0.97,and 1.64,respectively)in a time-dependent manner from baseline to week 8 in all three groups.Conjunctival staining score,OSDI questionnaire,and meibum quality and expressibility improved over time from baseline to week 8 in the Add and Monotherapy groups,but differences were not statistically significant in the Switch group.CONCLUSION:Diquafosol improves subjective symptoms and objective signs in patients treated with existing medicines combined with diquafosol and treated solely with diquafosol.Diquafosol can be used as an effective therapeutic agent for dry eye disease or additionally applied in patients who have insufficient response to existing medicines.

Effects of pirenzepine ophthalmic solution on form-deprivation myopia in the guinea pigs

Background Nonselective muscarinic receptor antagonist, atropine, was believed to inhibit myopic progression. The purpose of this study was to determine the efficacy, through topical administration, of the M1-selective muscarinic antagonist pirenzepine in preventing experimentally induced form-deprivation myopia in guinea pigs.Methods Fifty-three guinea pigs, which underwent monocular deprivation with their eyelids sutured, were divided into 6 groups. Three groups were treated with 1%, 2% or 4% pirenzepine ophthalmic solutions; the fourth group with atropine; the fifth with saline and the last group left untreated. Ocular refraction, in vivo biometric measurements and wet eye weight were collected before and after the experiment. All the eyes were finally enucleated for histopathological examination to evaluate the possible toxic effects on ocular structures.Results Animals untreated or treated with saline produced (-2.31±1.47) D and (-2.25±0.88) D of axial myopia respectively. Those treated with 1% pirenzepine ophthalmic solution produced relative myopia of (-1.63±0.48) D, and those under the treatment of 2% and 4% pirenzepine ophthalmic solution only developed a relative myopia of (-0.89±0.42) D and (-0.70±0.41) D (F=9.56, P<0.05). The significant reduction in myopia in 2% and 4% pirenzepine treated animals was caused by significantly less vitreous chamber elongation and axial elongation of the deprived eyes [2% group: (0.009±0.052) mm, 4% group: (0.006±0.078) mm] when compared with untreated, saline treated or 1% pirenzepine treated guinea pigs [(0.057±0.056) mm, (0.064±0.053) mm and (0.033±0.035) mm, respectively]. Histological examinations revealed no obviously toxic effects on the eyes treated with pirenzepine.Conclusion Topical administration of the M1-selective muscarinic antagonist, pirenzepine, can prevent induced form-deprivation myopia in guinea pigs by inhibiting axial elongation without obvious damage to ocular tissues.

Technical Evaluation of Eye Drops Instillation： A Systematic Review

Objective： Assess the profile of eye drops in patients with eye diseases. Methods： Studies available in the scientific literature were identified without any time limits using the databases Embase-Medline, Scielo, Scopus and Web of Knowledge. The selected studies were compared with the following inclusion criteria： （i） if the study evaluated the eye drop instillation, （ii） if the study involved participation of patients with eye diseases. Results： Twelve studies met the inclusion criteria. Of them, 83.33% evaluated the technique of eye drop instillation in patients with glaucoma, 8.33% in patients with eye diseases and 8.33% in patients with cataract after undergoing surgery to correct. 41.66% of studies have chosen to record a video of patients to analyze the technique of instilling eye drops and 41.66% did not describe the/esearch location. Regarding the type of study, 75% had the design as prospective cross-sectional, 8.33% prospective open label study, 8.33% intervention study and 8.33% study called masked trial. Although studies evaluate the technique of eye drop instillation, only 8.33% describe in the article the reference in the literature used to evaluate patients. 50% of articles acknowledged some sort of bias or limitation. Conclusion： The limitations inherent in these types of studies should guide future research.

Effect of plum-blossom needling versus tropicamide eye drops on adolescent myopia: protocol for a randomized crossover trial

OBJECTIVE: Myopia is the most common eye problem and affects an estimated 28.3% of the global population. Its incidence is increasing annually. Myopia treatment is limited to correcting visual acuity.Acupuncture is one of the main therapies in traditional Chinese medicine and includes plum-blossom needling, which has been widely used forboth the prevention and treatment of adolescent myopia. We hypothesized that plum-blossom needling would be effective in treating myopia compared with a tropicamide eye drops control.METHODS: This is a crossover randomized controlled trial involving adolescents with myopia. Participants will be randomized 1∶1 to plum-blossom needle or tropicamide eye drops arms. Subjects in each arm will be treated for 20 d, followed by a 1-month washout period and treatment change for another 20 d. The primary outcome is uncorrected distance and cycloplegic refractive errors. The secondary outcomes comprise corneal curvature, lens thickness, axial length, ciliary body thickness, accommodation amplitude, the NRA/PRA(negative/positive relative accommodation), flexible adjustment, and near point of convergence. The outcome measures will be assessed at baseline, after the first treatment course(the first month), at the end of the washout period(the second month), after the second treatment course(the third month), and at follow-up(the sixth month).DISCUSSION: The results of the trial will help to provide evidence for the efficacy of plum-blossom needling for myopia in China.

Higher incidence of steroid-induced ocular hypertension in keratoconus

Background:To compare intraocular pressure(IOP)changes following topical dexamethasone administration for 1 month in keratoconic versus normal eyes.Methods:This is a retrospective,single-center,non-randomized case series evaluation of 350 eyes.Two groups were formed:normal/control Group A(n_(A)=73),eyes that underwent excimer laser photorefractive keratectomy;and keratoconic(KCN)Group B(n_(B)=277),eyes that were subjected to partial laser photorefractive keratectomy combined with collagen cross-linking(The Athens Protocol).All eyes received the same post-operative regimen of topical dexamethasone 0.1%for at least 1 month.Goldmann applanation tonometry IOP readings and central corneal thickness(CCT)measurements were monitored.Cases with induced ocular hypertension(OHT,defined as post-operative IOP higher than 21 mmHg),were identified and correlated to refractive procedure,gender,and corneal thickness.Results:At 4 weeks postoperatively,OHT was noted on 27.4%(20/73 eyes)in Group A,and 43.7%(121/277 eyes)in KCN Group B,(p<0.01).Six months post-operatively(following 5-months of discontinuing topical dexamethasone treatment and commencing treatment of IOP-lowering medications),OHT rate was 1.8%in Group A and 3.9%in the KCN Group B.Conclusion:This study demonstrates a potentially significant pre-disposition of keratoconic eyes to the development of steroid-induced OHT.