Relationship between dry eye disease and myopia: A systematic review and meta-analysis.

Background/objectives: Dry eye disease (DED) and myopia are common ocular disorders. This systematic review and meta-analysis investigated the association between DED and myopia. Methods: PubMed and EMBASE were searched for articles published between 1984 and 2022. Study quality was assessed using the Joanna Briggs Institute Critical Appraisal Checklist, and analysis was conducted using the DerSimonian-Laird random-effects model. Results: Of the 1,313 studies identified, 15 studies on DED and myopia were included. The meta-analysis revealed that the overall prevalence of subjective DED symptoms in the myopia population was 45.1 % (95 % confidence interval: 0.287-0.616). There was a significant association between DED and myopia. The myopia population had higher Ocular Surface Disease Index scores and shorter tear film breakup times than the non-myopia population. Additionally, the meta-regression analysis showed that spherical equivalent was significantly associated with the prevalence of DED symptoms in adults with myopia. Conclusion: Interventions to prevent DED are required in the myopia population. Enhancing patient awareness and self-management for DED, in addition to early screening and detection, is especially critical for younger populations who are at a higher risk of developing myopia.

The impact of COVID-19 on hay fever treatment in Japan: A retrospective cohort study based on the Japanese claims database.

BACKGROUND: Hay fever (HF) presents with various symptoms, including allergic conjunctivitis and rhinitis, and requires cross-organ treatment. This study assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HF treatment trends. METHODS: This retrospective cohort study utilized data from the JMDC database collected between January 2018 and May 2021. Patients with HF were identified based on the relevant International Classification of Diseases 10th Revision diagnosis codes and the prescription of HF-related medications. The treatment approaches were compared during the cedar and cypress pollen allergy season (January to May in Japan) before and during the COVID-19 pandemic (2018 and 2019, and 2020 and 2021, respectively). RESULTS: This study included 2,598,178 patients with HF. The numbers of prescribed HF-related claims in 2018, 2019, 2020, and 2021 were 3,332,854, 3,534,198, 2,774,380, and 2,786,681 times, respectively. Oral second-generation antihistamine prescriptions decreased by >10% from 2019 to 2020, with a <10% change in the subsequent year. Anti-allergic eye drop prescriptions also decreased by >10% from 2019 to 2020 but increased by >10% from 2020 to 2021. Compared with 2018, 2019, and 2020, the number of claims in the rhinitis symptoms dominant group was significantly decreased in 2021 (p < 0.001, all). In contrast, the number of claims in the eye symptoms dominant group and the rhinitis and eye symptoms dominant group increased in 2021 compared with that in 2018, 2019, and 2020 (p < 0.001, all). CONCLUSION: Changes in HF treatment and related outcomes could be attributed to lifestyle modifications resulting from the COVID-19 pandemic. Measures, such as limiting outdoor activities and adopting mask-wearing practices may have influenced HF symptoms, preventive behaviors, and the overall approach to treating HF.

Impact of the Coronavirus Disease 2019 Pandemic on Outpatient Visits for Diabetic Retinopathy in Japan: A Retrospective Cohort Study.

Purpose: Long-term ramifications of the coronavirus disease 2019 pandemic on various care-seeking characteristics of patients with diabetic retinopathy remain unclear. This study aimed to identify risk factors for dropout from regular fundus examinations (RFEs) in patients with diabetic retinopathy in Japan. Methods: We extracted demographic and health checkup data (April 2018 to March 2021) from the JMDC database. Patients with diabetes identified using diagnosis-related and medication codes were included. The dropout and continuation groups included patients who discontinued and continued to undergo RFEs during the coronavirus disease 2019 pandemic, respectively. Results: The number of RFEs was significantly lower during the mild lockdown period (April and May 2020) than during the prepandemic period. Of the 14,845 patients with diabetes, 2333 (15.7%) dropped out of RFEs during the pandemic, whereas before the pandemic, of the 11,536 patients with diabetes, 1666 (14.4%) dropped out of RFEs (P = 0.004). Factors associated with dropout in the multivariate logistic regression analysis included younger age, male sex, high triglyceride levels, high γ-glutamyl transpeptidase levels, smoking habit, alcohol consumption, weight gain of more than 10 kg since the age of 20 years, and certain stages of lifestyle improvement. Factors associated with continuation included low body mass index and high glycosylated hemoglobin levels. Conclusions: Our findings can assist in identifying patients with diabetes at risk of dropout. Translational Relevance: These results have implications for public health and identifying patients with diabetes at risk of dropout. Education and tailored monitoring regimens could be pivotal role in fostering adherence.

Use of explainable AI on slit-lamp images of anterior surface of eyes to diagnose allergic conjunctival diseases.

BACKGROUND: Artificial intelligence (AI) is a promising new technology that has the potential of diagnosing allergic conjunctival diseases (ACDs). However, its development is slowed by the absence of a tailored image database and explainable AI models. Thus, the purpose of this study was to develop an explainable AI model that can not only diagnose ACDs but also present the basis for the diagnosis. METHODS: A dataset of 4942 slit-lamp images from 10 ophthalmological institutions across Japan were used as the image database. A sequential pipeline of segmentation AI was constructed to identify 12 clinical findings in 1038 images of seasonal and perennial allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC), and normal subjects. The performance of the pipeline was evaluated by determining its ability to obtain explainable results through the extraction of the findings. Its diagnostic accuracy was determined for 4 severity-based diagnosis classification of AC, AKC/VKC, GPC, and normal. RESULTS: Segmentation AI pipeline efficiently extracted crucial ACD indicators including conjunctival hyperemia, giant papillae, and shield ulcer, and offered interpretable insights. The AI pipeline diagnosis had a high diagnostic accuracy of 86.2%, and that of the board-certified ophthalmologists was 60.0%. The pipeline had a high classification performance, and the area under the curve (AUC) was 0.959 for AC, 0.905 for normal subjects, 0.847 for GPC, 0.829 for VKC, and 0.790 for AKC. CONCLUSIONS: An explainable AI model created by a comprehensive image database can be used for diagnosing ACDs with high degree of accuracy.

Effect of antihistamine-releasing contact lenses on ocular symptoms and treatment behavior in patients with seasonal allergic conjunctivitis: A retrospective study.

Purpose: This study aimed to compare subjective allergic conjunctivitis symptoms and anti-allergic eye drop use patterns between antihistamine-releasing contact lens users and daily disposable soft contact lens users during Japan's hay fever season. Methods: This web-based retrospective cohort study included daily disposable soft contact lens or antihistamine-releasing contact lens users with a history of seasonal allergic conjunctivitis who regularly used daily disposable soft contact lenses since the previous year. The total ocular symptom score (range 0-20) based on 5-item questionnaire scores and time from the start of the hay fever season to the initiation of anti-allergic eye drop treatment were compared between antihistamine-releasing contact lens users and daily disposable soft contact lens users. Results: The study included 24 participants: 17 using daily disposable soft contact lenses and 7 using antihistamine-releasing contact lenses. Antihistamine-releasing contact lens users experienced a greater reduction in total ocular symptom score from 2021 to 2022 compared with daily disposable soft contact lens users (mean total ocular symptom score [standard deviation]: daily disposable soft contact lens: -0.65 [1.4], antihistamine-releasing contact lens: -4.7 [3.6]; n = 24; Mann-Whitney U test, P = 0.010). Fourteen daily disposable soft contact lens users and five antihistamine-releasing contact lens users eventually required anti-allergic eye drops. Kaplan-Meier analysis revealed a significant delay in the initiation of anti-allergic eye drop treatment among those using antihistamine-releasing contact lenses compared with those using daily disposable soft contact lenses (median days, daily disposable soft contact lenses: 19 days, antihistamine-releasing contact lens: 57 days; n = 24; log-rank test, P = 0.045). Conclusions: Antihistamine-releasing contact lenses can potentially mitigate worsening ocular allergic responses during the hay fever season when used appropriately as a preventive measure.

Human ocular thelaziasis with genetic analysis in Niigata Prefecture, Japan: A case report on an emerging zoonosis.

Purpose: We report the clinical findings and molecular identification of ocular Thelazia callipaeda from Niigata Prefecture in the Hokuriku area of Japan during winter. Observations: A 77-year-old male visited an ophthalmology clinic in Niigata Prefecture in January 2022 after a 2-week-duration of a conjunctival injection in the left eye and foreign body sensation. Slit-lamp microscopy revealed 11 active nematodes in the left conjunctival sac. Morphological characteristics included longer female body length than male, buccal cavity lacking teeth and lips, and serrated striations along the body surface. The specimens were determined to be T. callipaeda. Genetic analysis of the mitochondrial cytochrome c oxidase subunit 1 (cox1) gene revealed an h9 haplotype. Conclusions and Importance: T. callipaeda infection, especially the h9 haplotype, commonly occurs in western Japan owing to its higher incidence in warmer climates, suggesting the origin of the case. Here, we report a human case of Thelaziasis diagnosed in a cold region of Japan (the Hokuriku area) during winter. This human case of T. callipaeda infection from a cold, previously unassociated region, raises concerns about the potential geographical widening of its distribution, and further investigation may be warranted to prevent its spread.

Optimal cutoff value of the dry eye-related quality-of-life score for diagnosing dry eye disease.

This retrospective study aimed to determine the optimal cutoff values of the Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire for diagnosing dry eye disease (DED) and classifying DED severities. Participants completed the DEQS questionnaire, the Japanese version of the Ocular Surface Disease Index (J-OSDI) questionnaire, and DED examinations. DED was diagnosed according to the 2016 Asia Dry Eye Society diagnostic criteria based on DED symptoms (J-OSDI ≥ 13 points) and tear film breakup time ≤ 5 s. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the DEQS summary score for detecting DED and grading its severity. Among 427 patients, 296 (69.3%) and 131 (30.7%) were diagnosed with DED and non-DED, respectively. ROC analysis determined an optimal cutoff value of 15.0 points for DED diagnosis, with 83.5% sensitivity, 87.0% specificity, and an area under the curve of 0.915. The positive and negative predictive values for DEQS ≥ 15.0 points were 93.6% and 69.9%, respectively. DEQS cutoff values of 15.0, 20.0, and 26.8 points could be accepted for severity classification of DED subjective symptoms in clinical use and represent mild, moderate, and severe DED, respectively. Conclusively, the optimal cutoff values of DEQS enable DED detection and subjective symptom severity classification.

Using the AllerSearch Smartphone App to Assess the Association Between Dry Eye and Hay Fever: mHealth-Based Cross-Sectional Study.

BACKGROUND: Dry eye (DE) and hay fever (HF) show synergistic exacerbation of each other's pathology through inflammatory pathways. OBJECTIVE: This study aimed to investigate the association between DE and HF comorbidity and the related risk factors. METHODS: A cross-sectional observational study was conducted using crowdsourced multidimensional data from individuals who downloaded the AllerSearch smartphone app in Japan between February 2018 and May 2020. AllerSearch collected the demographics, medical history, lifestyle and residential information, HF status, DE symptoms, and HF-related quality of life. HF symptoms were evaluated using the nasal symptom score (0-15 points) and nonnasal symptom score (0-12 points). HF was defined by the participants' responses to the questionnaire as HF, non-HF, or unknown. Symptomatic DE was defined as an Ocular Surface Disease Index total score (0-100 points), with a threshold score of 13 points. HF-related quality of life was assessed using the Japanese Allergic Conjunctival Disease Standard Quality of Life Questionnaire (0-68 points). We conducted a multivariable linear regression analysis to examine the association between the severity of DE and HF symptoms. We subsequently conducted a multivariable logistic regression analysis to identify the factors associated with symptomatic DE (vs nonsymptomatic DE) among individuals with HF. Dimension reduction via Uniform Manifold Approximation and Projection stratified the comorbid DE and HF symptoms. The symptom profiles in each cluster were identified using hierarchical heat maps. RESULTS: This study included 11,284 participants, classified into experiencing HF (9041 participants), non-HF (720 participants), and unknown (1523 participants) groups. The prevalence of symptomatic DE among individuals with HF was 49.99% (4429/9041). Severe DE symptoms were significantly associated with severe HF symptoms: coefficient 1.33 (95% CI 1.10-1.57; P<.001) for mild DE, coefficient 2.16 (95% CI 1.84-2.48; P<.001) for moderate DE, and coefficient 3.80 (95% CI 3.50-4.11; P<.001) for severe DE. The risk factors for comorbid symptomatic DE among individuals with HF were identified as female sex; lower BMI; medicated hypertension; history of hematologic, collagen, heart, liver, respiratory, or atopic disease; tomato allergy; current and previous mental illness; pet ownership; living room and bedrooms furnished with materials other than hardwood, carpet, tatami, and vinyl; discontinuation of contact lens use during the HF season; current contact lens use; smoking habits; and sleep duration of <6 hours per day. Uniform Manifold Approximation and Projection stratified the heterogeneous comorbid DE and HF symptoms into 14 clusters. In the hierarchical heat map, cluster 9 was comorbid with the most severe HF and DE symptoms, and cluster 1 showed severe HF symptoms with minimal DE-related symptoms. CONCLUSIONS: This crowdsourced study suggested a significant association between severe DE and HF symptoms. Detecting DE among individuals with HF could allow effective prevention and interventions through concurrent treatment for ocular surface management along with HF treatment.

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.

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.

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.

Biological effects of stored platelet-rich plasma eye-drops in corneal wound healing.

BACKGROUND/AIMS: This study aimed to assess the efficacy and sterility of stored platelet-rich plasma (PRP) eye-drops for corneal epithelial wound healing compared with those of autologous serum (AS) eye-drops. METHODS: At our single institution, PRP and AS eye-drops were prepared using peripheral blood obtained from six healthy volunteers and stored at 4°C. Platelet and leucocyte counts and transforming growth factor (TGF)-ß1, epidermal growth factor (EGF), and fibronectin levels were assessed during storage for up to 4 weeks. Sterility was assessed by culturing 4-week poststorage samples. PRP, AS, and phosphate-buffered saline (PBS) eye-drop efficacies were compared using corneal epithelial wound healing assays in vitro and in vivo and monitoring wound areas under a microscope every 3 hours. RESULTS: Higher platelet and lower leucocyte counts were seen in PRP than in whole blood on the day of preparation. After storage, TGF-ß1, EGF, and fibronectin levels were significantly higher in PRP than in AS eye-drops. In vitro and in vivo, PRP eye-drops used on the day of preparation significantly promoted corneal epithelial wound healing compared with PBS. Moreover, PRP eye-drops stored for 4 weeks significantly promoted corneal wound healing compared with PBS and AS eye-drops. CONCLUSION: PRP eye-drops stored at 4°C for 4 weeks promoted corneal epithelial wound healing with higher levels of growth factors than those observed in AS eye-drops, while maintaining sterility, suggesting that this preparation satisfies the unmet medical needs in the treatment of refractory keratoconjunctival epithelial disorders.

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.