Background: Dry eye disease (DED) is one of the most common ocular surface diseases. Numerous patients with DED remain undiagnosed and inadequately treated, experiencing various subjective symptoms and a decrease in quality of life and work productivity. A mobile health smartphone app, namely, the DEA01, has been developed as a noninvasive, noncontact, and remote screening device, in the context of an ongoing paradigm shift in the health care system, to facilitate a diagnosis of DED. Objective: This study aimed to evaluate the capabilities of the DEA01 smartphone app to facilitate a DED diagnosis. Methods: In this multicenter, open-label, prospective, and cross-sectional study, the test method will involve using the DEA01 smartphone app to collect and evaluate DED symptoms, based on the Japanese version of the Ocular Surface Disease Index (J-OSDI), and to measure the maximum blink interval (MBI). The standard method will then involve a paper-based J-OSDI evaluation of subjective symptoms of DED and tear film breakup time (TFBUT) measurement in an in-person encounter. We will allocate 220 patients to DED and non-DED groups, based on the standard method. The primary outcome will be the sensitivity and specificity of the DED diagnosis according to the test method. Secondary outcomes will be the validity and reliability of the test method. The concordance rate, positive and negative predictive values, and the likelihood ratio between the test and standard methods will be assessed. The area under the curve of the test method will be evaluated using a receiver operating characteristic curve. The internal consistency of the app-based J-OSDI and the correlation between the app-based J-OSDI and paper-based J-OSDI will be assessed. A DED diagnosis cutoff value for the app-based MBI will be determined using a receiver operating characteristic curve. The app-based MBI will be assessed to determine a correlation between a slit lamp–based MBI and TFBUT. Adverse events and DEA01 failure data will be collected. Operability and usability will be assessed using a 5-point Likert scale questionnaire. Results: Patient enrollment will start in February 2023 and end in July 2023. The findings will be analyzed in August 2023, and the results will be reported from March 2024 onward. Conclusions: This study may have implications in identifying a noninvasive, noncontact route to facilitate a diagnosis of DED. The DEA01 may enable a comprehensive diagnostic evaluation within a telemedicine setting and facilitate early intervention for undiagnosed patients with DED confronting health care access barriers. Trial Registration: Japan Registry of Clinical Trials jRCTs032220524; https://jrct.niph.go.jp/latest-detail/jRCTs032220524 International Registered Report Identifier (IRRID): PRR1-10.2196/45218

Purpose: To determine a correlation between temperature and blood flow in the ocular anterior segment, and their effects on corneal temperature. Methods: In experiment 1, we recruited 40 eyes and measured the temperature and blood flow in the ocular anterior-segment (upper/lower eyelid skin, palpebral and bulbar conjunctiva, and cornea) before and after application of warm compresses. In experiment 2, we recruited 20 eyes and measured the same tissues before and during stimulation using water and capsaicin solution in the oral cavity. Results: In experiment 1, the temperatures of the upper/lower eyelid skin and cornea increased significantly until 15 min after the application of the warm compress; the temperatures of the palpebral and bulbar conjunctiva increased significantly until 10 min. The blood flow in the upper/lower eyelid skin and bulbar conjunctiva increased significantly until 10 min, and that of the palpebral conjunctiva increased significantly until 15 min. In experiment 2, the temperatures were correlated significantly with the blood flow in the upper and lower eyelid skin and palpebral and bulbar conjunctiva. The temperature of all locations and palpebral conjunctival blood flow contributed independently to the corneal temperature. Conclusions: In the ocular anterior segment, the temperature and blood flow were correlated significantly, and contributed to the corneal temperature.

Objective: To evaluate the lubricating effect of hyaluronic acid (HA) on soft contact lenses (SCLs) measured using a pendulum-type friction tester. Methods: We measured the coefficient of friction (CoF) of narafilcon A, delefilcon A, and etafilcon A with polyvinylpyrrolidone (PVP), daily disposable SCL material, using a modified pendulum-type friction tester. Sample SCLs were set on an acrylic plastic half-ball and placed into the polyethylene terephthalate hemisphere cup filled with 0.4 mL of test lubricants that included saline and 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, and 0.5% (wt/vol) HA (molecular weight, 850 kDa). The viscosities of saline and HA were measured using an Ubbelohde viscometer. Results: The CoF of the SCL under a low concentration (0.05%) of HA was the lowest and significantly lower than saline in narafilcon A and delefilcon A (P<0.05, Steel multiple comparison test). Under higher HA concentrations (0.3%, 0.4%, and 0.5%), the CoF was significantly higher than that of saline (P<0.01, Steel' multiple comparison test) in all three SCLs. There were no significant differences of CoF among three SCLs in saline and all concentrations of HA. The HA viscosities increased exponentially with the concentration (Y=1.2829e^9.286X). Conclusion: The viscosity of a high concentration of HA may increase the friction of SCLs, which may have a deleterious effect on the ocular surface.

Lacrimal canaliculitis is a rare infection of the lacrimal canaliculi with canalicular concretions formed by aggregation of organisms. Metagenomic shotgun sequencing analysis using next-generation sequencing has been used to detect pathogens directly from clinical samples. Using this technology, we report cases of successful pathogen detection of canalicular concretions in lacrimal canaliculitis cases. We investigated patients with primary lacrimal canaliculitis examined in the eye clinics of four hospitals from February 2015 to July 2017. Eighteen canalicular concretion specimens collected from 18 eyes of 17 patients were analyzed by shotgun metagenomics sequencing using the MiSeq platform (Illumina). Taxonomic classification was performed using the GenBank NT database. The canalicular concretion diversity was characterized using the Shannon diversity index. This study included 18 eyes (17 patients, 77.1 ± 6.1 years): 82.4% were women with lacrimal canaliculitis; canalicular concretions were obtained from 12 eyes using lacrimal endoscopy and six eyes using canaliculotomy with curettage. Sequencing analysis detected bacteria in all samples (Shannon diversity index, 0.05–1.47). The following genera of anaerobic bacteria (>1% abundance) were identified: Actinomyces spp. in 15 eyes, Propionibacterium spp., Parvimonas spp. in 11 eyes, Prevotella spp. in 9 eyes, Fusobacterium spp. in 6 eyes, Selenomonas spp. in 5 eyes, Aggregatibacter spp. in 3 eyes, facultative and aerobic bacteria such as Streptococcus spp. in 13 eyes, Campylobacter spp. in 6 eyes, and Haemophilus spp. in 3 eyes. The most common combinations were Actinomyces spp. and Streptococcus spp. and Parvinomonas spp. and Streptococcus spp., found in 10 cases. Pathogens were identified successfully using metagenomic shotgun sequencing analysis in patients with canalicular concretions. Canalicular concretions are polymicrobial with anaerobic and facultative, aerobic bacteria.

Metagenomic analysis is the comprehensive study of DNA using clinical specimens of organisms including bacteria, fungi, and viruses. In this study, we investigated the efficacy of metagenomic analysis for diagnosing ocular infections, including 11 keratitis cases, four iridocyclitis cases, and one endophthalmitis case. Corneal scraping, aqueous humor, and vitreous humor, were collected respectively. Ocular specimens were used for bacterial and fungal culture, and PCR for detecting viral DNA. Shotgun metagenomic sequencing for 150 bases of single end was performed by Illumina MiSeq^® System. Sequence was retrieved from the database at NCBI using a MegaBLAST search. Since Propionibacterium spp. are commensal bacteria found at the ocular surface, they were excluded from analysis. Six cases (37.5%) were positive for culture or PCR. Metagenome techniques revealed that 9 cases (56.3%) included genomes of organisms that were considered pathogenic in specimens. Five cases (31.3%) possessed genomes of organisms like themselves that were detected by culture and PCR. Six cases (37.5%) were negative for culture, PCR, and metagenome analysis. Moreover, viral pathogens (HSV-1, 2 cases; and VZV, 1 case) were detected by only metagenome analysis. Metagenome analysis using an ocular sample can detect microbial genome comprehensively, and viral pathogens, which were not detected by conventional examination.

Background: Thermal pulsation (LipiFlow) warms the eyelids from the palpebral conjunctival surface. However, temperature and blood flow responses across multiple ocular-surface locations have not been systematically evaluated in a clinical cohort of patients with meibomian gland dysfunction (MGD). We examined changes in ocular surface temperature, blood flow and non-invasive tear break-up time (NIBUT) after LipiFlow in patients with MGD. Methods: Thirteen patients (3 men, 10 women; mean age, 64.9 ± 18.1 years) with MGD were included. The temperature and blood flow of the upper and lower eyelid skin and the palpebral and bulbar conjunctiva, along with the NIBUT, were measured before, 5 min after and 1 month after LipiFlow. The change from baseline was analyzed with Steel’s test. Results: All locations changed significantly 5 min after the treatment: the temperature rose by 1.13–1.21 °C, the blood flow increased to 1.24–1.45 times the baseline value, and NIBUT increased by 3.1 ± 2.7 s. At 1 month, temperature had returned to baseline at all locations, and blood flow had largely returned toward baseline, although bulbar conjunctival blood flow remained significantly elevated; NIBUT remained significantly longer than before treatment. Conclusions: Thermal pulsation warmed the ocular surface, including the palpebral conjunctiva where the meibomian glands are located. The improvement in tear film stability persisted for 1 month despite the largely transient temperature and blood flow responses.