Measurement of Anions in Tear Fluid Using Ion Chromatography.

PURPOSE: Tear fluid (TF) contains a variety of electrolytes that exhibit a strong correlation with its osmotic pressure. These electrolytes are also related to the etiology of diseases on ocular surfaces such as dry eye syndromes and keratopathy. Although positive ions (cations) in TF have been investigated to understand their roles, negative ions (anions) have hardly been studied because applicable analytical methods are restricted to a few kinds. In this study, we established a method to analyze the anions involved in a sufficiently small amount of TF for in situ diagnosis of a single subject. METHODS: Twenty healthy volunteers (10 men and 10 women) were recruited. Anions in their TF were measured on a commercial ion chromatograph (IC-2010, Tosoh, Japan). Tear fluid (5 µL or more) was collected from each subject with a glass capillary, diluted with 300 µL of pure water, and conveyed to the chromatograph. We successfully monitored the concentrations of bromide, nitrate, phosphate, and sulfate anions (Br - , NO 3- , HPO 42- , and SO 42- , respectively) in TF. RESULTS: Br - and SO 42- were universally detected in all samples, whereas NO 3- was found in 35.0% and HPO 42- in 30.0% of them. The mean concentrations (mg/L) of each anion were Br - , 4.69 ± 0.96; NO 3- , 0.80 ± 0.68; HPO 42- , 17.48 ± 7.60; and SO 42- , 3.34 ± 2.54. As for SO 42- , no sex differences or diurnal variations were observed. CONCLUSIONS: We established an efficient protocol to quantitate various inorganic anions involved in a small amount of TF using a commercially available instrument. This is the first step to elucidate the role of anions in TF.

Diagnostic Ability of a Smartphone App for Dry Eye Disease: Protocol for a Multicenter, Open-Label, Prospective, and Cross-sectional Study.

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.

Evaluation of In Vitro Wettability of Soft Contact Lenses Using Tear Supplements.

OBJECTIVE: To evaluate the interaction between tear supplements and soft contact lenses (SCLs), we measured the contact angles (CAs) on the SCLs using commercially available tear supplements. METHODS: We used four daily disposable conventional hydrogel lenses (etafilcon A, etafilcon A+ polyvinylpyrrolidone, nelfilcon A, and omafilcon A containing 2-methacryloyloxyethyl phosphorylcholine [MPC]) and four silicone hydrogel lenses (narafilcon A, senofilcon A, delefilcon A, and stenfilcon A). The CAs on the SCLs were measured using a sessile drop technique and four different types of sessile drops, including saline, artificial tears, lubricants containing 2-MPC (MPC solution), and 0.1% hyaluronate acid (HA). RESULTS: The CA values associated with the silicone hydrogel lenses were significantly (P<0.001) lower than those associated with the conventional hydrogel lenses with all four solutions. The mean CA of 0.1% HA was significantly (P<0.01) higher than that of saline. The mean CA of the MPC solution was significantly (P<0.01) lower than that of saline with the conventional hydrogel lenses but significantly (P<0.05) higher than that of saline with the silicone hydrogel lenses. CONCLUSIONS: The CAs associated with the silicone hydrogel SCLs were higher with the use of the MPC solutions and HA in vitro. The measured CAs may depend on ingredient agents, surface treatment of the CLs, and components of the tear supplements.

Correlation between Blood Flow and Temperature of the Ocular Anterior Segment in Normal Subjects.

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.

Bacterial keratoconjunctivitis caused by Staphylococcus argenteus belonging to sequence type 1223 isolated in Japan.

Staphylococcus argenteus, characterized by the formation of non-pigmented (white) colonies, was recently identified as a new lineage separated from Staphylococcus aureus. However, correct identification of this lineage is difficult because of the similar characteristics to S. aureus. Here, we describe the first known case of keratoconjunctivitis due to S. argenteus in a 64-year-old man with diabetes. The symptoms of the patient were not improved by antibiotic therapy using levofloxacin eye drops (15 mg/mL). The conjunctival scraping was cultured, and coagulase-positive staphylococci forming white colonies were detected. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry confirmed the species as S. argenteus with a spectral score of 1.97. After the antibiotic was changed to vancomycin eye drops (10 mg/mL), the patient's symptom clearly improved. Multi-locus sequence typing showed that this isolate belonged to sequence type 1223, which has been predominantly isolated worldwide. Furthermore, this isolate harbored various virulence genes associated with S. aureus, such as staphylococcal enterotoxins and leukocidin. Since only limited information is available for this organism, further studies are needed to establish the epidemiology of S. argenteus.

Influence of temperature change in donor corneas on postoperative endothelium cell density following endothelial transplantation.

To examine the influence on postoperative endothelial cell density (ECD) caused by preoperative temperature change from 4 °C to room temperature in donor corneas for Descemet stripping automated endothelial keratoplasty (DSAEK). This retrospective, case-controlled comparison of 100 eyes that underwent DSAEK using imported donor corneas transferred from an overseas eye bank (SightLife, Seattle, WA, USA). Fifty donor corneas experienced temperature reversal for ECD measurement (TR group), and postoperative outcomes were compared with 50 disease-matched cases that did not experience temperature changes before DSAEK (NTR group). The main outcome measure was endothelial cell loss and reduction rate of ECD at 1, 3, and 6 months following DSAEK. ECD at 3 months following DSAEK was significantly less in the TR group (1458 ± 494/mm2) than in the NTR group (1696 ± 374/mm2; P = 0.014), though ECD at 6 months was not significantly less in the TR group. The reduction rate of ECD at 3 months was greater in the TR group (42.3% ± 17.2%) than in the NTR group (35.7% ± 14.2%; P = 0.044), though reduction rate of ECD at 6 months was not significantly less in the TR group. We found that preoperative temperature change in donor corneas may adversely affect ECD following DSAEK.

Association among Blink Rate, Changes in Ocular Surface Temperature, Tear Film Stability, and Functional Visual Acuity in Patients after Cataract Surgery.

PURPOSE: To investigate the association among the ocular surface temperature (OST), tear film stability, functional visual acuity (FVA), and blink rate in patients after cataract surgery. METHODS: We recruited 98 eyes of 69 patients (mean age, 73.7 ± 5.2 years) 1 month after phacoemulsification with implantation of acrylic intraocular lenses and assessed slit-lamp microscopy, corrected distance VA, FVA, noninvasive tear breakup time (NIBUT), and OST. We defined the changes in the OST from 0 to 10 seconds after eye opening as the ΔOST. We measured the FVA and blink rate using the FVA measurement system. We divided the patients into two groups based on tear film stability: stable tear film (NIBUT, >5.0 seconds) and unstable tear film (NIBUT, ≤5.0 seconds). We evaluated the differences between the two groups and the association between the blink rate and other clinical parameters. RESULTS: The unstable tear film group (56 eyes) had significantly (p < 0.0001, unpaired t-test) shorter NIBUTs than the stable tear film group (42 eyes). The ΔOSTs and blink rates were significantly (p < 0.0001) higher in the unstable tear film group than in the stable group. Linear single regression analysis showed that the ΔOST (r = -0.430, p < 0.0001), NIBUT (r = -0.392, p < 0.0001), and gender (r = -0.370, p=0.0002) were correlated significantly with the blink rate. Multiple regression analysis showed that the ΔOST independently contributed to the blink rate. CONCLUSIONS: The frequency of blinks is associated with tear film stability in patients after cataract surgery. The blink rate may be useful for evaluating the tear film stability in clinical practice. The ΔOST should be an important contributing factor to the blink rate. [This trial is registered with UMIN000026970].

Association of Iris Damage With Reduction in Corneal Endothelial Cell Density After Penetrating Keratoplasty.

PURPOSE: To evaluate the effect of iris damage on endothelial cell loss in the early phase after penetrating keratoplasty (PKP). METHODS: This prospective consecutive study included 74 patients who underwent PKP without graft rejection during the follow-up period. Endothelial cell density (ECD) was measured using specular microscopy at 1, 3, 6, and 12 months after PKP. Iris damage scores (IDSs) were determined on the basis of slit-lamp microscopy or anterior segment optical coherence tomography imaging. Graft survival rates were compared among the different IDSs. Using multivariate analysis, the factors influencing postoperative ECD were assessed, taking into consideration the presence of glaucoma, history of graft failure, donor age, and graft ECD as independent variables. RESULTS: Graft ECD decreased from 2674 ± 329 cells/mm to 2114 ± 570 at 1 month, 1907 ± 629 at 3 months, 1669 ± 738 at 6 months, and 1404 ± 792 at 12 months (all, P < 0.0001). ECD at 12 months was associated with the IDS (ß = -0.444, P < 0.0001), graft ECD (ß = 0.309, P = 0.003), and history of graft failure (ß = -0.251, P = 0.016). The IDS was significantly correlated with %ECD loss at 1 month (r = 0.427, P = 0.003), at 3 months (r = 0.376, P = 0.002), at 6 months (r = 0.301, P = 0.013), and at 12 months (r = 0.517, P < 0.0001). The graft survival rates in eyes with severe iris damage were significantly lower than those in eyes with either no or mild iris damage (P < 0.0001). CONCLUSIONS: Severe iris damage is associated with rapid reduction in ECD and graft endothelial failure after PKP.

Association Between Ocular Surface Temperature and Tear Film Stability in Soft Contact Lens Wearers.

Purpose: To investigate the correlation between the changes in the ocular surface temperature (OST) and tear film stability over soft contact lenses (SCLs). Methods: We enrolled 20 eyes of 20 normal SCL wearers (20 men; 24.4 ± 4.1 years). We used four different daily disposable SCLs: one silicone hydrogel lens (delefilcon A) and three hydrogel lenses (etafilcon A with polyvinylpyrrolidone [PVP], etafilcon A, and polymacon). OST was measured every second during 10 seconds without blinking. We defined the difference in the OST from 0 to 10 seconds as ΔOST. To evaluate tear film stability, we measured noninvasive tear break-up time (NIBUT) and tear interference patterns on the contact lenses (TIPCL) using tear film interferometry. The parameters were measured before and 15 minutes after wearing each SCL. Results: ΔOST was correlated significantly with NIBUT without (r = 0.411, P < 0.01) and with SCL (r = 0.642, P < 0.01). TIPCL grade was correlated significantly with ΔOST over SCLs (r = -0.636, P < 0.01). ΔOST was significantly smaller with silicone hydrogel delefilcon A than hydrogel etafilcon A and polymacon lenses (P < 0.05 and P < 0.01, respectively). Delefilcon A and etafilcon A with PVP lenses had significantly smaller NIBUT than etafilcon A (P < 0.05 for both comparisons). TIPCL grade of delefilcon A lens was significantly smaller than those of etafilcon A and polymacon (P < 0.01 for both comparisons). Conclusions: The changes in OST over SCLs are related to tear film stability. Measurements of OST can be used to evaluate tear film stability for SCL wearers.

Development and efficacy of a drug-releasing soft contact lens.

PURPOSE: The purpose of this study was to investigate the uptake and the release of antibiotics from a newly synthesized drug delivery hydrogel soft contact lens (SCL) using an ion ligand mechanism. METHODS: The antibiotics used were Gatifloxacin (GFLX) and Moxifloxacin (MFLX). The uptake amount and the sustained-release kinetics of antibiotics were investigated in vitro, and were also compared with newly synthesized SCLs, etafilcon A and polymacon. The antibiotic concentrations in the cornea, aqueous humor, and crystalline lens, and the effect against bacterial proliferation were investigated in vivo using rabbit subjects. Additionally the drug release efficacy of the new SCL was compared with that of eye drop administrations. RESULTS: In vitro, antibiotic uptake was increased with the weight percent (wt%) of the anionic group, and the released amount of antibiotics was highest during the initial 1 hour period, which then decreased over the next 72 hours. The released antibiotics volume of the new SCLs was significantly higher throughout 72 hours than that of the other two materials, etafilcon A and polymacon (P < 0.01). Whereas in vivo, the concentrations found in the cornea and aqueous humor were higher than those for the eye drop groups (P < 0.05 or P < 0.01). Antibiotic release at those sites decreased over 72 hours. No bacterial populations were detectable in the group treated with the new SCL presoaked in antibiotics throughout the experimental periods. CONCLUSIONS: The new SCLs released the antibiotics over several days, and showed improved penetration into the eye, along with prevention of bacterial proliferation.

Calcification and membrane formation on the surface of intraocular lenses in a rabbit model.

PURPOSE: The aim of this study is to evaluate the calcification and membrane formation in different intraocular lenses (IOLs) models by implanting the IOLs in the subcutaneous plane of a Rabbit model. DESIGN: Experimental study. METHODS: IOLs were implanted subcutaneously in 13 Japanese albino rabbits for 1 month (n = 6), 3 months (n = 4) and 6 months (n = 3). Five kinds of IOLs were used, including three hydrophobic acrylic IOLs, the MA60AC (Alcon), ZA9003 (AMO) and X-60 (Santen), and two hydrophilic acrylic IOLs, the HP60M and MI60 (Bausch & Lomb). Scanning electron microscopy was used to observe the IOL optics. Energy dispersive x-ray spectroscopy and infrared spectroscopy were used to analyse any surface depositions on the optics, and the modulation transfer function was applied to evaluate the optical performance. RESULTS: Membrane formation was noted to have occurred on the surfaces of the two hydrophobic acrylic IOLs (MA60AC and ZA9003) during the investigation period. The membrane components originated from a serum protein that most likely would be serum albumin. Calcification was noted to have occurred on the surfaces of the two hydrophilic IOLs. However, no calcification was observed on the hydrophobic IOLs, nor was there any membrane formation on the hydrophilic IOLs. The values for the MI60 were not measurable at all at 3 or 6 months. The values of the three hydrophobic IOLs were significantly better than the value for the HP60M at three and six months (p < 0.01). CONCLUSION: Calcification to the hydrophilic IOLs severely affected optical performance, whereas, membrane formation on the hydrophobic IOLs did not affect optical performance. The X-60 had the optics that best maintained long-term transparency.