Virtual reality training improves accommodative facility and accommodative range.

AIM: To evaluate the effects of virtual reality (VR) training on different parameters of vision. METHODS: Sixty individuals ranged 18-60 years old with asthenopia were randomly divided into short-term (n=40) and long-term (n=20) treatment groups. They were given a specially designed VR training device only once for 15min or 3-4 times a day for 15min each time for 1mo. The visual acuity, spherical equivalent, accommodative range, accommodative facility, pupil size, and visual fatigue were evaluated before (control) and after VR training. RESULTS: The visual acuity, accommodative range, and accommodative facility increased in subjects of the short-term treatment group, whereas their pupil size contracted significantly. No significant changes in spherical equivalent and visual fatigue were observed. The changes in distant vision and corrected visual acuity were positively correlated with those in pupil size, but not with spherical equivalent. The accommodative range and accommodative facility improved significantly in subjects of the long-term treatment group. No significant changes in visual acuity, spherical equivalent, pupil size, and visual fatigue were noted. CONCLUSION: VR training can improve the accommodative range and accommodative facility of human eyes. Although short-term VR training can transiently improve vision, which probably due to bright light adaptation, there is no evidence that it can improve myopia.

The relationship between major intrinsic protein genes and cataract.

BACKGROUND: Genetic factors play an essential role in the development of cataracts, and the major intrinsic protein (MIP) gene is a type of causative genes. Our study aims to discuss the current research progress of MIP genes responsible for cataractogenesis in DNA and protein levels, which is essential in achieving a response to the molecular deficiencies and pathophysiologic features of cataract. METHODS: We developed a search strategy using a combination of the words "Cataract", "Mutation", "MIP gene", and "AQP0" to identify all articles from PubMed, Web of Science, Scopus, and Google Scholar up to December 2019. To find more articles and to ensure that databases were thoroughly searched, the reference lists of selected items were also reviewed. RESULTS: A total of 29 MIP gene mutations causing congenital cataract were obtained by searching these databases and analyzing the results of genetic mutation pathogenicity prediction software tools; most of them caused amino acid codon changes in the H4, H5, H6, C-TIDs, and loop C in the structure of the MIP protein. However, there was no clear causality between lens morphology, phenotypes, and genotypes. The genotype TC in polymorphism c.-4T > C and haplotype CCG of rs2269348, c.-4T > C, and rs74641138 in MIP may attach an additional genetic risk factor for age-related cataract. CONCLUSION: These single-base mutations and single nucleotide polymorphisms might be importantly involved in the pathogenesis of congenital cataract and age-related cataract, respectively. This review provides a significant reference for clinical trials and theoretical studies.

The Effects of Consumer-grade Virtual Reality Headsets on Adult Visual Function.

INTRODUCTION: Consumer-grade virtual reality (VR) headset is being used with increasing frequency nowadays, however, the effect on visual function is not clear. OBJECTIVES: We here investigate whether using VR headset changes adults' visual function and take into account the possible factors. METHODS: We compared the uncorrected distant visual acuity (UDVA), uncorrected near visual acuity (UNVA), best corrected visual acuity (BCVA), low contrast visual acuity (LCVA), glare visual acuity (GVA), refractive error (RE), amplitude of accommodation (ACC), and pupil diameter (PD) before and after using VR headset 10 mintues at a time twice per day for 2 successive weeks in 40 volunteers with a mean age of 28.6 years. Differences in these 8 parameters before vs. after VR headset use were analyzed using SPSS 22.0. RESULTS: In our study, we found that the amplitude of accommodation had significantly increased by 0.53 (F = 5.673; P = .006) after using, while visual acuity, refractive error and pupil diameter did not show statistically significant changes (P > .05). Correlation test showed that there was no significant correlation between any two parameters on visual function. CONCLUSION: It is discovered that using a consumer-grade VR headset 10 minutes at a time twice daily for 2 weeks improved the amplitude of accommodation of adults dramatically, while neither visual acuity nor refractive error was affected. ABBREVIATIONS: VR: visual reality; UDVA: uncorrected distant visual acuity; UNVA: uncorrected near visual acuity; BCVA: best corrected visual acuity; LCVA: low contrast visual acuity; GVA: glare visual acuity; RE: refractive error; ACC: amplitude of accommodation; PD: pupil diameter; 3D: three-dimensional; VDTS: visual display terminal syndrome; FOV: field of view; SEQ: spherical equivalent diopter.

Outcomes of 4 surgical adjuvants used for internal limiting membrane peeling in macular hole surgery: a systematic review and network Meta-analysis.

AIM: To compare the outcomes of four adjuvants used for internal limiting membrane (ILM) peeling in macular hole surgery, including indocyanine green (ICG), brilliant blue G (BBG), triamcinolone (TA) and trypan blue (TB), through systematic review and random-effects Bayesian network Meta-analysis. METHODS: PubMed, Cochrane library databases and Web of Science were searched until August 2018 for clinical trials comparing the above four adjuvants. ORs for postoperative best corrected visual acuity (BCVA) improvement and primary macular hole closure rates were compared between the different adjuvants. RESULTS: Twenty-seven eligible articles were included. For postoperative BCVA improvement, results of BBG-assisted peeling were significantly more favorable than those of ICG (WMD 0.08, 95% credible interval 0.01-0.16) and TA ranked highest. No significant differences were found between any other two groups in postoperative BCVA improvement. For postoperative primary macular hole closure rates, BBG ranked highest. However, no significant differences were shown between any two groups. CONCLUSION: TA and BBG are the optimum adjuvants for achieving postoperative BCVA improvement macular hole surgery with adjuvant-assisted ILM peeling. Among all adjuvants, the use of BBG is associated with the highest postoperative macular hole closure rate.

[Clinical practice guidelines for Leber's hereditary optic neuropathy].

Leber's hereditary optic neuropathy (LHON) is a genetic disease featuring maternal inheritance. mtDNA m.11778G>A, m.14484T>C and m.3460G>A mutations are its main molecular basis, but the disease is also affected by nuclear genes, genetic background of mtDNA and environmental factors. By referring to basic and clinical research in the related fields at home and abroad, guidelines and consensus issued by other countries, and combined with data from the Chinese population, this guideline aims to summarize the genetics knowledge and clinical treatment of LHON, with an aim to improve the clinical diagnosis and standardize the clinical management of patients.

Genetic and Functional Analyses of Two Missense Mutations in the Transcription Factor FOXL2 in Two Chinese Families with Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome.

BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare autosomal-dominant inherited disease. This study was carried out to investigate the genetic and functional changes within the FOXL2 gene in two Chinese families with BPES. MATERIALS AND METHODS: DNA was extracted from the peripheral blood of 26 persons from two different Chinese BPES families (13 of which were affected), as well as 200 cataract patients to act as normal controls. FOXL2 gene mutations were detected using polymerase chain reaction (PCR) and DNA sequencing techniques. Bioinformatic analyses were performed to analyze the structures and functions of the mutant proteins. Wild-type and mutant FOXL2 genes were subcloned into pEGFP-N1 and pCDB vectors and then transfected into COS7 and HEK293T cell lines. We observed protein subcellular localization, and used quantitative real-time (qRT)-PCR and western blots to assess regulation of the target OSR2 gene. RESULTS: We detected two novel missense mutations, c.162G>T (p.Lys54Asn) and c.308G>A (p.Arg103His), in the FOXL2 gene; one in each of the study families. Bioinformatic analyses indicated no obvious differences between the wild-type and mutant protein structures. However, they did predict that the two mutations were likely damaging to protein function. We found that the two mutated proteins were both largely distributed within the nucleus and that there was little found in the cytoplasm. The OSR2 mRNA content decreased significantly when the plasmids carrying the c.162G>T and c.308G>A were transfected into COS7 and HEK293 cell lines, when compared to the empty and the wild-type FOXL2 carrier. Western blot analyses indicated, that after transfecting the c.162G>T mutation, the OSR2 protein level was relatively similar to the wild-type, but that the cells transfected with the c.308G>A mutation showed significantly decreased levels of the OSR2 protein. CONCLUSIONS: Our study broadens the BPES gene mutation spectrum and suggests a possible mechanism of action. It also provides reference data for the further studies of BPES.

Phenotype-genotype correlation with Sanger sequencing identified retinol dehydrogenase 12 (RDH12) compound heterozygous variants in a Chinese family with Leber congenital amaurosis.

BACKGROUND: Leber congenital amaurosis (LCA) is a group of clinically and genetically heterogeneous retinal dystrophy. To date, 22 genes are known to be responsible for LCA, and some specific phenotypic features could provide significant prognostic information for a potential genetic etiology. This study is to identify gene variants responsible for LCA in a Chinese family using direct Sanger sequencing, with the help of phenotype-genotype correlations. METHODS: A Chinese family with six members including two individuals affected with LCA was studied. All patients underwent a complete ophthalmic examination. Based on phenotype-genotype correlation, direct Sanger sequencing was performed to identify the candidate gene on all family members and normal controls. Targeted next-generation sequencing was used to exclude other known LCA genes. RESULTS: By Sanger sequencing, we identified two novel missense variants in the retinol dehydrogenase 12 (RDH12) gene: a c.164C>A transversion predicting a p.T55K substitution, and a c.535C>G transversion predicting a p.H179D substitution. The two affected subjects carried both RDH12 variants, while their parents and offspring carried only one of heterozygous variants, showing complete cosegregation of the variants. The compound heterozygous variants were not present in 600 normal controls. Besides, the RDH12 variants were confirmed by targeted next-generation sequencing. CONCLUSIONS: The RDH12 compound heterozygous variants might be the cause of the LCA family. Our study adds to the molecular spectrum of RDH12-related retinopathy and offers an effective example of the power of phenotype-genotype correlations in molecular diagnosis of LCA.

Pediatric Posttraumatic Endophthalmitis in China for Twenty Years.

Pediatric posttraumatic endophthalmitis (PTE) is a rare but serious disease that frequently has a poor visual prognosis. To date, only a few English studies have focused on this disease. We perform a systematic review of the Chinese literature on pediatric PTE and describe the epidemiology, management, causative organisms, and visual acuity outcomes of reported cases in twenty years. We found that Staphylococcus epidermidis was the most common isolated organism and the use of a disposable syringe needle was the most common cause of ocular injuries in pediatric PTE in China. In the last ten years, the time from injury to first presentation for treatment has shortened, the proportion of cases resulting from a disposable syringe needle has decreased, the use of intravitreal antibiotics as the initial treatment has increased, and the use of palliative treatment has decreased. Although these favorable changes have occurred in the last ten years, the visual prognosis of pediatric PTE is still poor.

The role of microRNAs in myopia.

PURPOSE: In recent years, research on microRNAs (miRNAs) has become popular because of the critical role these macromolecules play in post-transcriptional gene regulation. Recent efforts have been made to identify miRNAs and their possible roles in myopia. The aim of this review was to summarize the expression and function of miRNAs during the development of myopia. METHODS: In this article, we reviewed the current research on the mechanisms that regulate miRNA expression, the potential for miRNAs as a diagnostic biomarker for myopia, and the mechanisms by which miRNAs promote the development of myopia. We also discussed the miRNA expression profiles in human fetal sclera. RESULTS: We summarized the miRNA expression profiles in myopia, including miR-328, miR-184, miR-29a, and miR-let-7i, and also the miRNA expression profiles in fetal sclera, including miR-214, miR-let-7, miR-103, miR-107, miR-29b, miR-328, and miR-98. CONCLUSIONS: Such knowledge could lead to more precise diagnosis, prognosis, and response predictions for future treatments for myopia, and the pace of discovery is expected to accelerate dramatically in the near future.

A Meta-analysis of the association between different genotypes (G11778A, T14484C and G3460A) of Leber hereditary optic neuropathy and visual prognosis.

AIM: To analyze the influences of different genotypes (G11778A, T14484C and G3460A) of Leber hereditary optic neuropathy (LHON) on visual prognosis. METHODS: After a systematic literature search, all relevant studies evaluating the association between the three primary mutations of LHON and visual prognosis were included. All statistical tests were calculated with Revman 5.2 and STATA 12.0. RESULTS: Ten independent studies were included finally. A significant association between the three primary mutations and prognostic vision over 0.3 were found in G11778A versus T14484C [odds ratio (OR)=0.10, 95% confidence interval (CI)=0.05-0.17, P<0.001], G11778A versus G3460A (OR=0.18, 95%CI=0.09-0.37, P<0.001) and T14484C versus G3460A (OR=2.45, 95%CI=1.10-5.48, P<0.05). In addition, obtained by pairwise comparison, the vision during onset, age of onset and sex ratio of these three kinds of patients, have no statistical significance (P>0.05). CONCLUSION: From pairwise comparison, we conclude that these three different genotypes of LHON are related to patients' visual prognosis. The T14484C patients might have a best prognostic vision, G3460A second, and G11778A worst. And there is little relation between the three different genotypes and patients' vision, age of onset and sex ratio.

A Head-Mounted Spectacle Frame for the Study of Mouse Lens-Induced Myopia.

The mouse model has been widely employed to explore the mysteries of myopia. For now, existing techniques for induction of experimental myopia in mice can be classified into three types: (1) devices directly glued to the fur; (2) devices attached using a combination of glue and sutures; (3) devices attached using a skull-mounted apparatus. These techniques each have its advantages, disadvantages when considering the devices stability, safety, complexity, effectiveness, and so forth. Thus, techniques for myopia induction in mice have yet to be further refined to popularize the applications. In this pilot study, we introduce a new head fixation device named the head-mounted spectacle frame apparatus for the study of mouse lens-induced myopia. Surgical procedures for device attachment were relatively simple and easy to learn in our study. Effective myopia induction was validated by retinoscopy refraction and axial length measurement using optical coherence tomography. In addition, it showed improved compliance and reliable safety when compared to the published methods. The head-mounted spectacle frame apparatus provides a new choice for the study of lens-induced myopia in mouse. It also allows for the use of form deprivation, making it attractive for future experimental mouse myopia trials.

Comparison of Standard Automated Perimetry, Short-Wavelength Automated Perimetry, and Frequency-Doubling Technology Perimetry to Monitor Glaucoma Progression.

Detection of progression is paramount to the clinical management of glaucoma. Our goal is to compare the performance of standard automated perimetry (SAP), short-wavelength automated perimetry (SWAP), and frequency-doubling technology (FDT) perimetry in monitoring glaucoma progression.Longitudinal data of paired SAP, SWAP, and FDT from 113 eyes with primary open-angle glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study were included. Data from all tests were expressed in comparable units by converting the sensitivity from decibels to unitless contrast sensitivity and by expressing sensitivity values in percent of mean normal based on an independent dataset of 207 healthy eyes with aging deterioration taken into consideration. Pointwise linear regression analysis was performed and 3 criteria (conservative, moderate, and liberal) were used to define progression and improvement. Global mean sensitivity (MS) was fitted with linear mixed models.No statistically significant difference in the proportion of progressing and improving eyes was observed across tests using the conservative criterion. Fewer eyes showed improvement on SAP compared to SWAP and FDT using the moderate criterion; and FDT detected less progressing eyes than SAP and SWAP using the liberal criterion. The agreement between these test types was poor. The linear mixed model showed a progressing trend of global MS overtime for SAP and SWAP, but not for FDT. The baseline estimate of SWAP MS was significantly lower than SAP MS by 21.59% of mean normal. FDT showed comparable estimation of baseline MS with SAP.SWAP and FDT do not appear to have significant benefits over SAP in monitoring glaucoma progression. SAP, SWAP, and FDT may, however, detect progression in different glaucoma eyes.

Illumination from light-emitting diodes (LEDs) disrupts pathological cytokines expression and activates relevant signal pathways in primary human retinal pigment epithelial cells.

Age-related macular degeneration (AMD) is the leading cause of blindness in the aged people. The latest systemic review of epidemiological investigations revealed that excessive light exposure increases the risk of AMD. With the drastically increasing use of high-energy light-emitting diodes (LEDs) light in our domestic environment nowadays, it is supposed to pose a potential oxidative threat to ocular health. Retinal pigment epithelium (RPE) is the major ocular source of pathological cytokines, which regulate local inflammation and angiogenesis. We hypothesized that high-energy LED light might disrupt the pathological cytokine expression of retinal pigment epithelium (RPE), contributing to the pathogenesis of AMD. Primary human RPE cells were isolated from eyecups of normal eye donors and seeded into plate wells for growing to confluence. Two widely used multichromatic white light-emitting diodes (LEDs) with correlated color temperatures (CCTs) of 2954 and 7378 K were used in this experiment. The confluent primary RPE cells were under white LEDs light exposure until 24 h. VEGF-A, IL-6, IL-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Activation of mitogen-activated protein kinases (MAPKs), Akt, Janus kinase (JAK)2 and Nuclear factor (NF)-κB signal pathways after LEDs illumination were evaluated by western blotting analysis. The level of reactive oxygen species (ROS) using chloromethyl- 2',7'-dichlorodihydrofluorescein diacetate. Inhibitors of relevant signal pathways and anti-oxidants were added to the primary RPE cells before LEDs illumination to evaluate their biological functions. We found that 7378 K light, but not 2954 K upregulated the VEGF-A, IL-6, IL-8 and downregulated MCP-1 proteins and mRNAs levels in a time-dependent manner. In parallel, initial activation of MAPKs and NF-κB signal pathways were also observed after 7378 K light exposure. Mechanistically, antioxidants for eliminating reactive oxygen species (ROS) and targeted inhibitors of MAPKs and NF-κB significantly blocked 7378 K light-induced changes of specific cytokines, respectively. Our findings suggest that 7378 K light, not 2954 K induced upregulation of VEGF-A, IL-6, IL-8 and downregulation of MCP-1 via ROS accumulation, activating MAPKs and NF-κB signal pathways.

Topical Use of NaCl Solution with Different Concentration Affects Lens Transparency in Anesthetized Mice.

PURPOSE: To study the influence of NaCl solution with different concentration on lens transparency in anesthetized mice. METHODS: Four kinds of NaCl solution with different concentration were prepared as eye drops to imply graded osmolarity (100, 300, 500 and 1000 mOsmol/kg). Five groups of anesthetized mice were set-up to induce lens opacity, in which four groups were treated with NaCl solution and another group naturally exposed to air. The lens opacity was graded as no opacity, mild, medium and severe opacity at 0, 10, 20, 30, 45 and 60 min after the start of the experiment. A numerical value from 0 to 3 was assigned to each grade for the cataract index (CI) calculation and data analysis. The same procedure was repeated in all groups 48 h later. The reversion process of lens opacity was explored using a hypotonic NaCl solution (100 mOsmol/kg) in another pair of groups, a 500 mOsmol/kg NaCl solution group and natural exposure group. The gross appearance and time course of development and reversion of lens opacity were assessed. RESULTS: Lens opacity primarily developed in a hypertonic NaCl solution-treated and naturally exposed eyes, and the gross anatomical appearance were similar. The speed of lens opacity development and CI changes were osmolarity-dependent, and the higher NaCl concentration solution used, the faster and more severe the formation of opacification. Both hypertonic NaCl-solution-induced lens opacity and natural exposure induced lens opacity could be resolved by hypotonic NaCl solution prior to anesthesia recovery. CONCLUSIONS: This study indicates a crucial effect of NaCl concentration on the development and reversion of lens opacity in the anesthetized mice, and support the osmolarity theory in the reversible lens opacification phenomenon. It is also of practical significance to mouse eye studies that require lens transparency.

Ocular Trauma Score in Siderosis Bulbi With Retained Intraocular Foreign Body.

The purpose of this study was to investigate the clinical characteristic and visual outcome of siderosis bulbi with retained intraocular foreign body (IOFB) and to validate the predictive value of the Ocular Trauma Score (OTS) in siderosis bulbi. Certain numerical values rendered to the OTS variables at present were summated (Table 1) and converted into 5 OTS categories as performed in the OTS study. The prognostic value of OTS was first assessed in cases of siderosis bulbi resulting from a chemical reaction of retained IOFBs. Twenty-four eyes of 24 patients diagnosed with siderosis bulbi who underwent surgery between 2007 and 2013 at our medical centre were reviewed. Due to patients' ignorance in ocular injuries, delayed presentation by the patient (54.17%) and no history of trauma (16.67%) were the most common cause of siderosis bulbi with IOFB retention. The main symptom of all these patients was impaired vision. The most common complications were cataract (23/24, 95.83%), followed by retinal pigmentary degeneration (15/22, 68.18%), iris heterochromia (14/24, 58.33%), pupillary mydriasis (10/21, 47.62%), secondary glaucoma (6/24, 25.00%), relative afferent pupillary defect (6/24, 25.00%), and retinal detachment (3/24, 12.50%). IOFBs were removed in 22 eyes (91.67%), except 2 enucleated eyes with absolute glaucoma (8.33%). Among all the patients (24 eyes), the best-corrected visual acuity improved in 63.64%, unchanged in 18.18% and deteriorated in 18.18% after surgical intervention. No statistically significant difference was found between the categorical distributions of our patients and those in the OTS study group. Further promotion and education on eye protection are needed to minimize visual loss from siderosis bulbi. The OTS, which was designed to predict visual outcomes of general ocular trauma, may also provide reliable information about the prognosis of siderosis bulbi resulting from a chemical reaction of retained IOFBs.

Down-Regulation of miR-146a Expression Induces Allergic Conjunctivitis in Mice by Increasing TSLP Level.

BACKGROUND: Pollen is the most common aeroallergen to cause conjunctivitis. In this study, we established a short ragweed (SRW)-induced mouse model of allergic conjunctivitis (AC) and aimed to explore the potential role of miR-146a and its downstream molecules in the development of ocular allergic inflammation. MATERIAL AND METHODS: The mouse model of challenge pollen was used for in vivo study. The culture model of primary human limbal epithelium (HLE) exposed to lipopolysaccharide (LPS) was performed for in vitro research. The numbers of eosinophils and total inflammatory cells were examined using Giemsa staining. The expression of mRNA and miR-146a was determined by quantitative RT-PCR, and protein production was evaluated by Western blotting. RESULTS: In vivo of mice, pollen challenge induced conjunctiva inflammatory response indicated by increased number of eosinophils and total inflammatory cells. Interestingly, pollen significantly attenuated miR-146a expression while it enhanced expression of thymic stromal lymphopoietin (TSLP) and its downstream molecules, including TSLP receptor (TSLPR)/ OX40 ligand (OX40L) /CD11C. In vitro of HCE, downregulation effect of miR-146a expression induced by LPS was reversed by Bay treatment, an inhibitor for nuclear factor kappa B (NF-κB), and LPS-induced cell inflammation is mediated by miR-146a-TSLP/TSLPR/OX40L/CD11C signaling pathway. This was further demonstrated by overexpression of miR-146a in mouse abrogated pollen-triggered conjunctiva inflammatory reaction as well as pollen-induced activity of TSLP/TSLPR/OX40L/CD11C signaling. CONCLUSIONS: Down-regulation of miR-146a expression induces allergic conjunctivitis in mice by increasing TSLP level.

Long-Term Observation of Coexistence of Posterior Polymorphous Corneal Dystrophy, Resultant High Myopia and Nonkeratoconic Developing Corneal Astigmatism: A Case Report of 7-Year Tracking in a Chinese Boy.

Posterior polymorphous corneal dystrophy (PPCD) is an extremely rare, bilateral, and inherited disorder, which affects the corneal endothelium and Descemet's membrane. Few PPCD cases in Chinese patients have been published so far. As far as we know, there are few studies which focused on the associations between PPCD and high myopia either. Here we report a rare case of coexistence of posterior polymorphous corneal dystrophy, resultant high myopia and with-the-rule developing corneal astigmatism in a young Chinese boy. A 6-year-old boy was first referred to our department 7 years ago, complaining of bilateral poor vision. Examinations of both eyes including ophthalmologic examination, cycloplegic refraction examination, confocal microscopy findings, and corneal topography were performed. Bilateral small aggregates of vesicular lesions and patchy hyperreflectivity were observed at the level of the Descemet's membrane on confocal microscopy, which is consistent with typical PPCD. Optometry and corneal topography examinations showed a resultant high myopia. Ocular examinations were performed annually to follow up with the patient in the past 7 years. The corneal lesions remained stable whereas an axial elongation and a sharp increase in both spherical and cylindrical equivalent power were observed. Close follow-ups including thorough scrutiny of the endothelium and systematic ocular ancillary examinations are essential for patients with PPCD. The pathological coexistence of PPCD and high myopia in our case is possibly due to a shared etiological pathway or genetic background. Advanced genetic analysis on similar cases is expected if more samples can be provided.

A randomised, parallel-group comparison study of diquafosol ophthalmic solution in patients with dry eye in China and Singapore.

AIMS: To compare the efficacy and safety of 3% diquafosol ophthalmic solution with those of 0.1% sodium hyaluronate ophthalmic solution in patients with dry eye in China and Singapore. METHODS: A total of 497 patients with dry eye (Schirmer's test, 5 mm; fluorescein and RB score, 3 points) from China and Singapore were randomised to receive either diquafosol ophthalmic solution (diquafosol) or sodium hyaluronate ophthalmic solution (HA) at 1:1 ratio. The fluorescein staining scores and rose bengal (RB) subjective symptom scores and tear film breakup time were evaluated before treatment and 2 and 4 weeks after start of treatment. RESULTS: In the diquafosol group, changes in fluorescein and RB scores compared with baseline at week 4 or at the time of discontinuation were -2.1±1.5 and -2.5±2.0, respectively. Compared with the HA group, changes in fluorescein score were non-inferior and changes in RB score were superior (p=0.019). In addition, diquafosol and HA improved tear film breakup time by 1.046±1.797 and 0.832±1.775 s, respectively (no significant intergroup difference). Adverse event onset rates were 16.3% (40 of 246 subjects) and 10.0% (25 of 251 subjects) in the diquafosol group and HA group, respectively, with borderline significant intergroup differences (p=0.046), while adverse drug reaction incidence rates were 12.2% (30 of 246 subjects) and 6.0% (15 of 251 subjects), respectively (p=0.019). Only mild adverse drug reactions (>2%) in the form of eye discharge, itching or irritation were observed. CONCLUSIONS: Diquafosol improved fluorescein staining score in a manner similar to HA, and significantly improved RB score compared with HA. TRIAL REGISTRATION NUMBER: NCT01101984.