Clinical utility of maximum blink interval measured by smartphone application DryEyeRhythm to support dry eye disease diagnosis.

The coronavirus disease (COVID-19) pandemic has emphasized the paucity of non-contact and non-invasive methods for the objective evaluation of dry eye disease (DED). However, robust evidence to support the implementation of mHealth- and app-based biometrics for clinical use is lacking. This study aimed to evaluate the reliability and validity of app-based maximum blink interval (MBI) measurements using DryEyeRhythm and equivalent traditional techniques in providing an accessible and convenient diagnosis. In this single-center, prospective, cross-sectional, observational study, 83 participants, including 57 with DED, had measurements recorded including slit-lamp-based, app-based, and visually confirmed MBI. Internal consistency and reliability were assessed using Cronbach's alpha and intraclass correlation coefficients. Discriminant and concurrent validity were assessed by comparing the MBIs from the DED and non-DED groups and Pearson's tests for each platform pair. Bland-Altman analysis was performed to assess the agreement between platforms. App-based MBI showed good Cronbach's alpha coefficient, intraclass correlation coefficient, and Pearson correlation coefficient values, compared with visually confirmed MBI. The DED group had significantly shorter app-based MBIs, compared with the non-DED group. Bland-Altman analysis revealed minimal biases between the app-based and visually confirmed MBIs. Our findings indicate that DryEyeRhythm is a reliable and valid tool that can be used for non-invasive and non-contact collection of MBI measurements, which can assist in accessible DED detection and management.

Smartphone App-Based and Paper-Based Patient-Reported Outcomes Using a Disease-Specific Questionnaire for Dry Eye Disease: Randomized Crossover Equivalence Study.

BACKGROUND: Using traditional patient-reported outcomes (PROs), such as paper-based questionnaires, is cumbersome in the era of web-based medical consultation and telemedicine. Electronic PROs may reduce the burden on patients if implemented widely. Considering promising reports of DryEyeRhythm, our in-house mHealth smartphone app for investigating dry eye disease (DED) and the electronic and paper-based Ocular Surface Disease Index (OSDI) should be evaluated and compared to determine their equivalency. OBJECTIVE: The purpose of this study is to assess the equivalence between smartphone app-based and paper-based questionnaires for DED. METHODS: This prospective, nonblinded, randomized crossover study enrolled 34 participants between April 2022 and June 2022 at a university hospital in Japan. The participants were allocated randomly into 2 groups in a 1:1 ratio. The paper-app group initially responded to the paper-based Japanese version of the OSDI (J-OSDI), followed by the app-based J-OSDI. The app-paper group responded to similar questionnaires but in reverse order. We performed an equivalence test based on minimal clinically important differences to assess the equivalence of the J-OSDI total scores between the 2 platforms (paper-based vs app-based). A 95% CI of the mean difference between the J-OSDI total scores within the ±7.0 range between the 2 platforms indicated equivalence. The internal consistency and agreement of the app-based J-OSDI were assessed with Cronbach α coefficients and intraclass correlation coefficient values. RESULTS: A total of 33 participants were included in this study. The total scores for the app- and paper-based J-OSDI indicated satisfactory equivalence per our study definition (mean difference 1.8, 95% CI -1.4 to 5.0). Moreover, the app-based J-OSDI total score demonstrated good internal consistency and agreement (Cronbach α=.958; intraclass correlation=0.919; 95% CI 0.842 to 0.959) and was significantly correlated with its paper-based counterpart (Pearson correlation=0.932, P<.001). CONCLUSIONS: This study demonstrated the equivalence of PROs between the app- and paper-based J-OSDI. Implementing the app-based J-OSDI in various scenarios, including telehealth, may have implications for the early diagnosis of DED and longitudinal monitoring of PROs.

The minimal clinically important difference of app-based electronic patient-reported outcomes for hay fever.

BACKGROUND: Hay fever is a common allergic disease, with an estimated worldwide prevalence of 14.4% and a variety of symptoms. This study assessed the minimal clinically important difference (MCID) of nasal symptom score (NSS), non-nasal symptom score (NNSS), and total symptoms score (TSS) for app-based hay-fever monitoring. METHODS: MCIDs were calculated based on the data from a previous large-scale, crowdsourced, cross-sectional study using AllerSearch, an in-house smartphone application. MCIDs were determined with anchor-based and distribution-based methods. The face scale score of the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire Domain III and the daily stress level due to hay fever were used as anchors for determining MCIDs. The MCID estimates were summarized as MCID ranges. RESULTS: A total of 7590 participants were included in the analysis (mean age: 35.3 years, 57.1% women). The anchor-based method produced a range of MCID values (median, interquartile range) for NSS (2.0, 1.5-2.1), NNSS (1.0, 0.9-1.2), and TSS (2.9, 2.4-3.3). The distribution-based method produced two MCIDs (based on half a standard deviation, based on a standard error of measurement) for NSS (2.0, 1.8), NNSS (1.3, 1.2), and TSS (3.0, 2.3). The final suggested MCID ranges for NSS, NNSS, and TSS were 1.8-2.1, 1.2-1.3, and 2.4-3.3, respectively. CONCLUSIONS: MCID ranges for app-based hay-fever symptom assessment were obtained from the data collected through a smartphone application, AllerSearch. These estimates may be useful for monitoring the subjective symptoms of Japanese patients with hay fever through mobile platforms.

Symptom-based stratification algorithm for heterogeneous symptoms of dry eye disease: a feasibility study.

BACKGROUND/OBJECTIVE: To test the feasibility of a dry eye disease (DED) symptom stratification algorithm previously established for the general population among patients visiting ophthalmologists. SUBJECT/METHODS: This retrospective cross-sectional study was conducted between December 2015 and October 2021 at a university hospital in Japan; participants who underwent a comprehensive DED examination and completed the Japanese version of the Ocular Surface Disease Index (J-OSDI) were included. Patients diagnosed with DED were stratified into seven clusters using a previously established symptom-based stratification algorithm for DED. Characteristics of the patients in stratified clusters were compared. RESULTS: In total, 426 participants were included (median age [interquartile range]; 63 [48-72] years; 357 (83.8%) women). Among them, 291 (68.3%) participants were diagnosed with DED and successfully stratified into seven clusters. The J-OSDI total score was highest in cluster 1 (61.4 [52.2-75.0]), followed by cluster 5 (44.1 [38.8-47.9]). The tear film breakup time was the shortest in cluster 1 (1.5 [1.1-2.1]), followed by cluster 3 (1.6 [1.0-2.5]). The J-OSDI total scores from the stratified clusters in this study and those from the clusters identified in the previous study showed a significant correlation (r = 0.991, P < 0.001). CONCLUSIONS: The patients with DED who visited ophthalmologists were successfully stratified by the previously established algorithm for the general population, uncovering patterns for their seemingly heterogeneous and variable clinical characteristics of DED. The results have important implications for promoting treatment interventions tailored to individual patients and implementing smartphone-based clinical data collection in the future.

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.

Individual multidisciplinary clinical phenotypes of nasal and ocular symptoms in hay fever: Crowdsourced cross-sectional study using AllerSearch.

BACKGROUND: Multidisciplinary efforts to prospectively collect and analyze symptoms of hay fever are limited. We aimed to identify the characteristics of nasal and ocular symptoms of hay fever, using the AllerSearch smartphone application. METHODS: This mobile health-based prospective observational study using the AllerSearch smartphone application was conducted between February 1, 2018, and May 1, 2020. Individuals who downloaded AllerSearch from Japan and provided comprehensive self-assessments (including 17 items related to quality of life [QoL]-related items) were included. The characteristics and risk factors for allergic rhinitis (AR) and allergic conjunctivitis (AC) were identified using hierarchical heat maps and multivariate logistic regression. RESULTS: Of the 9041 participants with hay fever, 58.8% had AR and AC, 22.2% had AR, and 5.7% had AC. The AR-AC comorbid cohort showed worse symptoms of hay fever and QoL scores than the other cohorts. Factors (odds ratio, 95% confidence interval) associated with AR-AC included a lower age (0.98, 0.97-0.98), female sex (1.31, 1.19-1.45), liver disease (1.58, 1.26-2.35), dry eye disease (1.45, 1.30-1.63), unknown dry eye disease status (1.46, 1.31-1.62), contact lens use discontinuation during the hay fever season (1.69, 1.28-2.23), and bedroom flooring material other than hardwood, carpet, tatami, or vinyl (1.91, 1.16-3.14). CONCLUSIONS: Analysis of medical big data for hay fever performed using a mobile health app helped identify risk factors and characteristics of AC, AR, and AR-AC. Phenotyping of highly variable symptoms of hay fever, such as nasal and ocular symptoms, can facilitate better-quality clinical care.

P4 Medicine for Heterogeneity of Dry Eye: A Mobile Health-based Digital Cohort Study.

During the 5th Science, Technology, and Innovation Basic Plan, the Japanese government proposed a novel societal concept -Society 5.0- that promoted a healthcare system characterized by its capability to provide unintrusive, predictive, longitudinal care through the integration of cyber and physical space. The role of Society 5.0 in managing our quality of vision will become more important in the modern digitalized and aging society, both of which are known risk factors for developing dry eye. Dry eye is the most common ocular surface disease encountered in Japan with symptoms including increased dryness, eye discomfort, and decreased visual acuity. Owing to its complexity, implementation of P4 (predictive, preventive, personalized, participatory) medicine in managing dry eye requires a comprehensive understanding of its pathology, as well as a strategy to visualize and stratify its risk factors. Using DryEyeRhythm®, a mobile health (mHealth) smartphone software (app), we established a route to collect holistic medical big data on dry eye, such as the subjective symptoms and lifestyle data for each individual. The studies to date aided in determining the risk factors for severe dry eye, the association between major depressive disorder and dry eye exacerbation, eye drop treatment adherence, app-based stratification algorithms based on symptomology, blink detection biosensoring as a dry eye-related digital phenotype, and effectiveness of app-based dry eye diagnosis support compared to traditional methods. These results contribute to elucidating disease pathophysiology and promoting preventive and effective measures to counteract dry eye through mHealth.

Prevalence and characteristics of dry eye disease in Parkinson's disease: a systematic review and meta-analysis.

We investigated and characterized the prevalence of dry eye disease (DED) in Parkinson's disease (PD). PubMed and EMBASE databases were searched for relevant studies between January 1, 1979 and March 10, 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist. Study-specific estimates were combined using the DerSimonian-Laird random-effects model. Prevalence of subjective DED symptoms in patients with PD and mean differences in blink rate, corneal thickness, tear film breakup time, and tear secretion volume on Schirmer test I were compared to those in controls. Of 383 studies, 13 (1519 patients with PD) and 12 were included in qualitative and quantitative syntheses, respectively. Meta-analysis revealed a 61.1% prevalence of subjective DED symptoms in PD and that, compared with controls, patients with PD had significantly lower blink rate, thinner corneal thickness, shorter tear film breakup time, and lower tear secretion volumes on Schirmer test I, without and with anesthesia.

Characteristics and Clinical Ocular Manifestations in Patients with Acute Corneal Graft Rejection after Receiving the COVID-19 Vaccine: A Systematic Review.

This study aimed to determine the characteristics and clinical ocular manifestations of acute corneal graft rejection after coronavirus disease 2019 (COVID-19) vaccination. We conducted an online search of the PubMed and EMBASE databases. Data on recipients' characteristics, corneal transplantation types, interval between vaccination and allograft rejection, clinical manifestations, and graft rejection medication were extracted. Thirteen articles on 21 patients (23 eyes) with acute corneal graft rejection after COVID-19 vaccination, published between April and December 2021, were included. The median (interquartile range) age at the onset of rejection was 68 (27-83) years. Types of transplantation included penetrating keratoplasty (12 eyes), Descemet membrane endothelial keratoplasty (six eyes), Descemet stripping automated endothelial keratoplasty (four eyes), and living-related conjunctival-limbal allograft (one eye). The interval between vaccination and rejection ranged from 1 day to 6 weeks. Corneal edema was the leading clinical manifestation (20 eyes), followed by keratic precipitates (14 eyes) and conjunctival or ciliary injection (14 eyes). Medications included frequently applied topical corticosteroids (12 eyes), followed by a combination of topical and oral corticosteroids (four eyes). In addition, the clinical characteristics of corneal allograft rejection after COVID-19 vaccination were identified. Corneal transplant recipients may require further vaccination, necessitating appropriate management and treatment.

Prevalence of Comorbidity between Dry Eye and Allergic Conjunctivitis: A Systematic Review and Meta-Analysis.

This systematic review aimed to determine the comorbid dry eye (DE) and allergic conjunctivitis (AC) prevalence. We searched PubMed and EMBASE for articles published until 22 March 2022, combining the terms "(dry eye OR keratoconjunctivitis sicca) AND allergic conjunctivitis." Study-specific estimates (DE and AC incidence rates among patients with AC and DE, respectively) were combined using the one-group meta-analysis in a random-effects model. The initial search yielded 700 studies. Five articles reporting AC incidence among individuals with DE and six articles reporting DE incidence among individuals with AC were included in the qualitative synthesis. In these nine articles, the total sample size was 7254 patients. The DE incidence among individuals with AC was 0.9-97.5%; the AC incidence among individuals with DE was 6.2-38.0%. One-group meta-analysis using a random-effects model showed that 47.2% (95% confidence interval: 0.165-0.779; 320/1932 cases) of patients with AC had comorbid DE and 17.8% (95% confidence interval: 0.120-0.236; 793/4855 cases) of patients with DE had comorbid AC, as defined by each article. Complimentary screening and treatment for patients with DE and AC may improve long-term outcomes and prevent chronic ocular damage in highly susceptible populations.

Application of Animal Models in Interpreting Dry Eye Disease.

Different pathophysiologic mechanisms are involved in the initiation, development, and outcome of dry eye disease (DED). Animal models have proven valuable and efficient in establishing ocular surface microenvironments that mimic humans, thus enabling better understanding of the pathogenesis. Several dry eye animal models, including lacrimal secretion insufficiency, evaporation, neuronal dysfunction, and environmental stress models, are related to different etiological factors. Other models may be categorized as having a multifactorial DED. In addition, there are variations in the methodological classification, including surgical lacrimal gland removal, drug-induced models, irradiation impairment, autoimmune antibody-induced models, and transgenic animals. The aforementioned models may manifest varying degrees of severity or specific pathophysiological mechanisms that contribute to the complexity of DED. This review aimed to summarize various dry eye animal models and evaluate their respective characteristics to improve our understanding of the underlying mechanism and identify therapeutic prospects for clinical purposes.

Fatty liver disease in living liver donors: a single-institute experience of 220 donors.

We retrospectively reviewed 220 living liver donors, with a focus on the development of postoperative fatty liver. Data regarding demographics, comorbidities, imaging tests, operations and biopsies were obtained from medical records. We used unenhanced CT and USG to diagnose fatty liver. Donor candidates with fatty liver underwent weight loss intervention until imaging tests no longer demonstrated any features of fatty liver. Among 220 donors, 61 were diagnosed with preoperative fatty liver. The mean BMI of these 61 donors significantly decreased from 24.9 at the first visit to 23.6 kg/m2 immediately before surgery (P = 0.0386). A multivariate analysis revealed the following significant risk factors for postoperative fatty liver: male sex (P = 0.0033), BMI immediately before surgery (P = 0.0028) and a history of treatment for preoperative fatty liver (P = 0.0231). Postoperative fatty liver was often refractory to weight loss intervention. No improvement was observed in 14 of the 32 donors who had been diagnosed with fatty liver postoperatively, and one of the 14 donors even developed NASH. In conclusion, special attention should be paid to prevent fatty liver after surgery in male donors who show a high BMI immediately before surgery and with a history of treatment for preoperative fatty liver, and lifelong follow-up is recommended.

Long-term donor quality of life after living donor liver transplantation in Japan.

AIMS: This study examined the long-term quality of life (QOL) of living liver donors (LLDs) in Japan using both generic and LLD-specific instruments. METHODS: The sample comprised 374 LLDs from five university hospitals in Japan who underwent surgery more than a year previously. QOL was evaluated using the Short Form-36 health survey (SF-36) and LLD-QOL scale. RESULTS: SF-36 results indicated that the overall long-term QOL of LLDs was significantly better than the Japanese standard. When comparing by donor factors, LLDs whose recipients were children scored higher for "satisfaction" than those whose recipients were adults on the LLD-QOL scale. LLDs with complications had lower QOL for "scars" and "burden" on the LLD-QOL scale but no differences in SF-36 scores. LLDs with longer hospital stay had lower physical QOL on SF-36 and lower QOL for "scars" and "after-effects" on the LLD-QOL scale. LLDs whose recipients have died showed lower mental QOL on SF-36 and lower "satisfaction" and greater "lack of understanding of donor health" on the LLD-QOL scale. CONCLUSIONS: Our multicenter study clarified the long-term QOL of LLDs and suggested that donors' QOL was related to the donors' and recipients' ages, donor's complications and hospital stay length, and recipient's prognosis.

Perceptions of transplant surgery among living liver donors in Japan.

CONTEXT: To minimize impaired psychosocial outcomes among living liver donors, it may be useful to obtain their views about being a donor with respect to their specific backgrounds. OBJECTIVE: To describe the perceptions of living liver donors with respect to transplant surgery and to determine whether any differences in perceptions were related to the recipient's age or prognosis. DESIGN, SETTING, AND PATIENTS: In total, 240 living liver donors (mean age, 44.4 years) openly and freely described their views on transplant. RESULTS: Content analysis of the descriptions revealed 4 categories: grateful for the benefits of living donor liver transplant (n = 143, 59.6%), facing the limitations of living liver transplant (n = 125, 52.1%), donor stress (n = 105, 43.8%), and crucial preoperative period (n = 75, 31.2%). The frequency of descriptions of gratitude for the benefits of transplant differed significantly between adult-to-adult and adult-to-child transplants: donors to children (ie, recipients <18 years old) were more grateful than were donors to adults (ie, recipients ≥18 years old). In addition, descriptions of gratitude differed significantly depending on the recipient's prognosis: donors with recipients who survived were more grateful and experienced fewer difficulties than did donors with recipients who died. CONCLUSIONS: In general, living liver donors were satisfied with transplant surgery but experienced living donor liver transplant as a burden, which was affected by the transplant outcome and the age of the recipient.

Reliability and validity of a new living liver donor quality of life scale.

PURPOSE: To develop a living liver donor (LLD) quality of life (QOL) scale and test its reliability and validity. METHODS: We sent a draft questionnaire comprising 38 questions to 965 LLDs from five hospitals. To evaluate test-retest reliability, the questionnaire was re-sent 2 weeks later to some of the donors from one hospital. RESULTS: Of the 447 (54.5 %) donors who responded, 15 were excluded. Factor analysis of 26 items extracted 7 subscales; namely, damage from the operation, scarring, satisfaction, burden, after-effects, digestive symptoms, and lack of understanding of donor health. We analyzed construct validity on the basis of factor analysis and observed significant correlations among the seven subscales. Criterion-related validity was confirmed by significant correlation with the 36-item Short-Form Health Survey scores. None of the subscales showed unreasonable values. We evaluated the subscale reliability for internal consistency (α = 0.670-0.868, except for "digestive symptoms", α = 0.431) and test-retest reliability (r = 0.749-0.918). The factor "digestive symptoms" needs careful consideration because of low internal consistency. CONCLUSION: The findings of this study confirmed the reliability and validity of the LLD QOL scale, which can be used for quantitatively evaluating the QOL of LLDs.

Extent of gastric resection impacts patient quality of life: the Dysfunction After Upper Gastrointestinal Surgery for Cancer (DAUGS32) scoring system.

BACKGROUND: Quality of life is an important outcome measure in the care of patients with cancer. We developed a new scoring system specifically for the evaluation of patients with upper gastrointestinal cancer and postoperative gastrointestinal dysfunction. This study was undertaken to evaluate the scoring system's validity in comparing outcomes after gastric resection. MATERIALS AND METHODS: Patients with gastric cancer, 3 months to 3 years postoperatively, were surveyed using the survey instrument. Postoperative dysfunction scores and the status of resuming activities of daily living were compared with the surgical procedure performed by analysis of variance and multiple-comparison techniques. RESULTS: Of 211 patients surveyed, 165 (119 men, 46 women; mean age, 65.1 ± 10.5 years) responded. Procedures included distal gastrectomy in 100, total gastrectomy in 57, and pylorus-preserving gastrectomy in 8. The overall dysfunction score was 61.8 ± 15.5. The dysfunction score was 58.9 ± 15.0 after distal gastrectomy, 66.8 ± 14.1 after total gastrectomy, and 62.4 ± 21.6 after pylorus-preserving gastrectomy. These values differed significantly among the groups (P = .007). Dysfunction scores according to postoperative activity status were 49.1 ± 15.6 in 71 patients who resumed their activities, 56.9 ± 15.7 in 39 patients with reduced activities, 57.3 ± 8.8 in 15 patients with minimal activities, and 63.3 ± 11.8 (P < .05) in 16 patients who did not resume activities because of poor physical condition. CONCLUSIONS: This scoring system for postoperative gastrointestinal dysfunction provides an objective measure of dysfunction related to specific surgical procedures and correlates with activities of daily living in the postoperative period.