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We aimed to assess the clinical and epidemiological impacts of the coronavirus disease 2019 pandemic on the number of ophthalmology outpatient department (oOPD) visits. PubMed and EMBASE were searched for literature published between January 1, 2020, and December 5, 2022. The extracted data were pooled using a random-effects model. The primary outcome was the number of oOPD visits. Of the 335 screened articles, 21 and 16 were included in the qualitative and quantitative syntheses, respectively. Among the 16 studies included in the meta-analysis, 7 involving 4,204,209 individuals reported the number of oOPD visits during the pandemic. Compared with the number of pre-pandemic visits, the numbers of oOPD visits declined to 58.1% (95% confidence interval [CI], 0.378–0.784) and 29.8% (95% CI 0.130–0.465) during the pandemic and lockdown, respectively. The proportions of female patient visits decreased from 50.9 to 47.8% and from 48.3 to 42.3% during the pandemic and lockdown, respectively. The proportions of adult visits increased from 86.3 to 89.6% and decreased from 90.6 to 80.1% during the pandemic and lockdown, respectively. The decrease in oOPD visits during the pandemic may have caused delays in diagnosis and treatment, potentially exacerbating the existing ocular diseases. [ABSTRACT FROM AUTHOR]

CorneAI, a deep learning model designed for diagnosing cataracts and corneal diseases, was assessed for its impact on ophthalmologists' diagnostic accuracy. In the study, 40 ophthalmologists (20 specialists and 20 residents) classified 100 images, including iPhone 13 Pro photos (50 images) and diffuser slit-lamp photos (50 images), into nine categories (normal condition, infectious keratitis, immunological keratitis, corneal scar, corneal deposit, bullous keratopathy, ocular surface tumor, cataract/intraocular lens opacity, and primary angle-closure glaucoma). The iPhone and slit-lamp images represented the same cases. After initially answering without CorneAI, the same ophthalmologists responded to the same cases with CorneAI 2–4 weeks later. With CorneAI's support, the overall accuracy of ophthalmologists increased significantly from 79.2 to 88.8% (P < 0.001). Specialists' accuracy rose from 82.8 to 90.0%, and residents' from 75.6 to 86.2% (P < 0.001). Smartphone image accuracy improved from 78.7 to 85.5% and slit-lamp image accuracy from 81.2 to 90.6% (both, P < 0.001). In this study, CorneAI's own accuracy was 86%, but its support enhanced ophthalmologists' accuracy beyond the CorneAI's baseline. This study demonstrated that CorneAI, despite being trained on diffuser slit-lamp images, effectively improved diagnostic accuracy, even with smartphone images. [ABSTRACT FROM AUTHOR]

We developed an AI system capable of automatically classifying anterior eye images as either normal or indicative of corneal diseases. This study aims to investigate the influence of AI's misleading guidance on ophthalmologists' responses. This cross-sectional study included 30 cases each of infectious and immunological keratitis. Responses regarding the presence of infection were collected from 7 corneal specialists and 16 non-corneal-specialist ophthalmologists, first based on the images alone and then after presenting the AI's classification results. The AI's diagnoses were deliberately altered to present a correct classification in 70% of the cases and incorrect in 30%. The overall accuracy of the ophthalmologists did not significantly change after AI assistance was introduced [75.2 ± 8.1%, 75.9 ± 7.2%, respectively (P = 0.59)]. In cases where the AI presented incorrect diagnoses, the accuracy of corneal specialists before and after AI assistance was showing no significant change [60.3 ± 35.2% and 53.2 ± 30.9%, respectively (P = 0.11)]. In contrast, the accuracy for non-corneal specialists dropped significantly from 54.5 ± 27.8% to 31.6 ± 29.3% (P < 0.001), especially in cases where the AI presented incorrect options. Less experienced ophthalmologists were misled due to incorrect AI guidance, but corneal specialists were not. Even with the introduction of AI diagnostic support systems, the importance of ophthalmologist's experience remains crucial. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) after cataract surgery is associated with various risk factors, while causing a wide range of heterogeneous symptoms including decreased quality of vision. This systematic review and meta-analysis aimed to determine the prevalence and characteristics of DED after cataract surgery. We searched PubMed and EMBASE and included studies on patients with DED after cataract surgery, between January 2011 and June 2020. Study-specific estimates (DED prevalence rates after cataract surgery in patients without preexisting DED) were combined using one-group meta-analysis in a random-effects model. We included 36 studies published between 2013 and 2020. We included nine of these in the meta-analysis of DED prevalence after cataract surgery. Overall 37.4% (95% CI 22.6–52.3; 206/775) of patients without preexisting DED developed DED after cataract surgery. The risk factors for DED after cataract surgery included age, female sex, systemic diseases, systemic medications, psychiatric conditions, preexisting DED, meibomian gland dysfunction, preservatives in eye drops, surgery techniques, and lifestyle. DED severity peak occurred 1 day postoperatively and persisted for at least 1–12 months following cataract surgery; therefore, consistent follow-up for DED is warranted for at least 1 month after cataract surgery. Topical administration of preservative-free diquafosol tetrasodium solution and preoperative meibomian gland treatment were effective in preventing and treating DED following cataract surgery. As more than one-third of patients develop DED after cataract surgery, careful DED management and treatment is needed after cataract surgery to improve satisfaction and vision quality. [ABSTRACT FROM AUTHOR]

We investigated the effects of anti-CD80/86 antibodies in a murine high-risk corneal transplantation rejection model. A mixed lymphocyte reaction (MLR) assay was conducted with anti-CD80/86 antibodies. Inflammatory cytokine levels in the culture supernatant were measured using an enzyme-linked immunosorbent assay. Interferon (IFN)-γ-producing CD4+ T cell frequencies in the MLR were assessed using flow cytometry. In vivo, high-risk corneal allograft survival and IFN-γ-producing CD4+ T cell frequencies in corneal grafts were assessed with intraperitoneal injection of anti-CD80/86 antibodies compared to phosphate-buffered saline (PBS). RNA-sequencing was performed on corneal grafts 2 weeks post-transplantation. Anti-CD80/86 antibodies significantly decreased T-cell proliferation, IFN-γ+-producing CD4+ T cell frequencies, and IFN-γ, interleukin (IL)-1β, IL-2, IL-10, and tumor necrosis factor-α production in the MLR compared to PBS injection. Intraperitoneal injection of anti-CD80/86 antibodies significantly prolonged corneal graft survival and decreased IFN-γ+-producing CD4+ T cell frequencies compared to PBS injection. Gene set enrichment analysis showed that the gene sets mainly enriched in the control group were related to allograft rejection and inflammatory response compared to PBS injection. Anti-CD80/86 antibodies significantly prolonged corneal graft survival by inhibiting T-cell proliferation and inflammatory response. [ABSTRACT FROM AUTHOR]

Multidimensional integrative data analysis of digital phenotyping is crucial for elucidating the pathologies of multifactorial and heterogeneous diseases, such as the dry eye (DE). This crowdsourced cross-sectional study explored a novel smartphone-based digital phenotyping strategy to stratify and visualize the heterogenous DE symptoms into distinct subgroups. Multidimensional integrative data were collected from 3,593 participants between November 2016 and September 2019. Dimension reduction via Uniform Manifold Approximation and Projection stratified the collected data into seven clusters of symptomatic DE. Symptom profiles and risk factors in each cluster were identified by hierarchical heatmaps and multivariate logistic regressions. Stratified DE subgroups were visualized by chord diagrams, co-occurrence networks, and Circos plot analyses to improve interpretability. Maximum blink interval was reduced in clusters 1, 2, and 5 compared to non-symptomatic DE. Clusters 1 and 5 had severe DE symptoms. A data-driven multidimensional analysis with digital phenotyping may establish predictive, preventive, personalized, and participatory medicine. [ABSTRACT FROM AUTHOR]

Corneal neovascularization (CNV) causes higher-order aberrations, corneal edema, ocular inflammation, and corneal transplant rejection, thereby decreasing visual acuity. In this study, we investigated the effects of topical administration of the kappa opioid receptor agonist nalfurafine (TRK-820) on CNV. To induce CNV, intrastromal corneal sutures were placed on the corneal stroma of BALB/c mice for 2 weeks. Nalfurafine (0.1 µg/2 μL/eye) was topically administered to the cornea once or twice daily after CNV induction. The CNV score, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in neovascularized corneas were evaluated using slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. The mRNA expression of the kappa opioid receptor gene Oprk1 was significantly upregulated following CNV induction. Topical administration of nalfurafine twice daily significantly suppressed CNV and lymphangiogenesis, as well as reduced the mRNA levels of angiogenic and pro-inflammatory factors in the neovascularized corneas. Moreover, nalfurafine administration twice daily reduced the numbers of infiltrating leukocytes, neutrophils, macrophages, and interferon-γ-producing CD4+ T cells in the neovascularized corneas. In this study, we demonstrated that topical administration of nalfurafine suppressed local CNV in a mouse model along with the activation of KOR, suggesting that nalfurafine may prevent and control CNV in humans. [ABSTRACT FROM AUTHOR]

Purpose: To determine eye drop type and usage frequency and investigate risk factors for no eye drop use in individuals with symptomatic dry eye (DE) in Japan. Study design: Crowdsourced observational study. Methods: This study was conducted using the DryEyeRhythm smartphone application between November 2016 and September 2019. Data collected included the type and frequency of eye drop use, demographics, medical history, lifestyle, and self-reported symptoms. Symptomatic DE was defined as an Ocular Surface Disease Index total score of ≥ 13. Risk factors for no eye drop use were identified using multivariate logistic regression analyses. Results: Among 2619 individuals with symptomatic DE, 1876 did not use eye drops. The most common eye drop type was artificial tears (53.4%), followed by hyaluronic acid 0.1% (33.1%) and diquafosol sodium 3% (18.7%). Risk factors (odds ratio [95% confidence interval]) for no eye drop use were age (0.97 [0.97–0.98]), body mass index (1.04 [1.01–1.07]), brain disease (0.38 [0.15–0.98]), collagen disease (0.30 [0.13–0.68]), mental illness other than depression and schizophrenia (0.65 [0.45–0.93]), cataract surgery (0.12 [0.02–0.59]), ophthalmic surgery other than cataract and laser-assisted in situ keratomileusis (0.55 [0.34–0.88]), current (0.47 [0.38–0.57]) or past (0.58 [0.43–0.77]) contact lens use, >8 h screen exposure time (1.38 [1.05–1.81]), <6 h (1.24 [1.01–1.52]) and >9 h (1.34 [1.04–1.72]) sleep time, and water intake (0.97 [0.94–0.98]). Conclusion: Many participants with symptomatic DE did not use optimized eye drop treatment and identified risk factors for no eye drop use. The DryEyeRhythm application may help improve DE treatment. [ABSTRACT FROM AUTHOR]

Corneal allograft survival is mediated by the variety of immunological reactions and wound healing process. Our aim was to explore the effects of topical administration of ripasudil, a selective Rho-associated coiled-coil protein kinase inhibitor, on corneal allograft survival. Ripasudil was administered to mice thrice a day after allogeneic corneal transplantation. Corneal graft survival, opacity, neovascularization, re-epithelization, immune cell infiltration, and mRNA levels of angiogenic and pro-inflammatory factors in the grafted cornea and draining lymph nodes (dLNs) were evaluated with slit-lamp microscopy, immunohistochemistry, flow cytometry, and polymerase chain reaction. Graft survival was significantly prolonged with lower graft opacity and neovascularization scores in 0.4% and 2.0% ripasudil-treated groups, and mRNA levels of angiogenic and pro-inflammatory factors in ripasudil-treated grafted corneas were reduced. Moreover, 0.4% and 2.0% ripasudil reduced CD45+-infiltrated leukocyte frequency, Cd11b and Cd11c mRNA levels, and the frequencies of mature dendritic cells, IFNγ-, and IL-17- producing CD4+T cells in the dLNs of recipients. Re-epithelization rate of the grafted cornea was significantly higher in the 0.4% and 2.0% ripasudil groups than in the control. Topically applied ripasudil prolonged graft survival by downregulating neovascularization and inflammation factors, while promoting corneal re-epithelization, suggesting that ripasudil may be useful for suppressing immunological rejection in corneal transplantation. [ABSTRACT FROM AUTHOR]

Purpose: The aims of this study were to investigate the incidence of positive donor tissue cultures before transfer to preservation medium (Optisol™-GS) for penetrating keratoplasty, to verify the efficacy of antibiotics contained in Optisol™-GS by examining the drug susceptibility and to assess the relationship between the results of our microbial assessments as well as donor factors and the incidence of contamination. Methods: We conducted a retrospective, cross-sectional study using Juntendo Eye Bank records for all corneal transplantations. Two hundred donor conjunctiva harvestings and storage medium (EP-II) cultures were performed between July 2008 and June 2011. We analyzed the associations between donor factors (age, gender, history of cataract surgery, death-to-preservation interval, cause of death) and contamination rates using multivariate analysis by the generalized estimating equation model. Results: We obtained positive bacterial cultures from 154 of the 200 eyes (77.0%). The isolated bacteria were indigenous, such as coagulase-negative Staphylococci, Corynebacterium sp., and methicillin-resistant Staphylococcus aureus (MRSA). There was significant resistance to levofloxacin (18 eyes, 9.0%) and gentamicin (12 eyes, 6.0%), and no vancomycin-resistant bacteria were detected. The donor factors did not correlate with the prevalence of bacterial contamination in our criteria. Conclusions: Pre-banking microbial assessment allows for microbial detection, bacterial susceptibility and resistance testing. This is useful for developing preservation mediums containing effective spectrum antibiotic agents for high quality control of corneal banking. [ABSTRACT FROM AUTHOR]

Regulatory T cells (Tregs) are crucial for allograft survival. Tregs can be divided into thymus-derived natural Tregs (tTregs) and peripherally-derived induced Tregs (pTregs). Here, we determine whether the suppressive function of Treg subsets is hampered in hosts who are at high risk for rejecting their graft. To induce graft beds that promote high risk of transplant rejection, intrastromal corneal sutures were placed two weeks prior to the transplant procedure in mice. We demonstrate that in high-risk recipients the frequencies and function of pTregs (but not tTregs) are suppressed. Reduced function of pTregs correlated with decreased expression of CTLA-4, interleukin-10, and transforming growth factor-β. Adoptive transfer of pTregs from mice at low risk of subsequent graft rejection is able to rescue graft survival in recipients that are at high risk of rejecting their grafts. Our data suggest that impaired function of pTregs, but not tTregs, mediates the loss of immune tolerance and promotes allograft rejection. [ABSTRACT FROM AUTHOR]