Comparison of iodine compounds and levofloxacin as postoperative instillation; conjunctival bacterial flora and antimicrobial susceptibility following cataract surgery.

PURPOSE: To compare the cleanliness of the conjunctival sac following the use of iodine compounds (PAI) and levofloxacin as postoperative eye drops. STUDY DESIGN: A prospective open-label study. PATIENTS AND METHODS: Either topical levofloxacin or fourfold-diluted PAI was administered for 1 week postoperatively in 128 eyes of 128 patients who underwent routine cataract surgery. Conjunctival samples were obtained at three time points: pre-surgery, 1 week postoperatively, and 1 month postoperatively. RESULTS: The respective positive bacterial culture rates for postoperative iodine and levofloxacin were 88.1% and 85.2% pre-surgery, 71.6% and 50.8% 1 week postoperatively, and 92.5% and 86.5% 1 month postoperatively. Positive bacterial culture rates in both groups significantly declined at 1 week, and the rates returned to the baseline level 1 month postoperatively. The magnitude of reduction of DNA copy number detected by polymerase chain reaction at 1 week was larger in the levofloxacin group, although no significant differences were seen at pre-surgery or 1 month postoperatively. In the levofloxacin group, only one strain was culture positive at 1 week, however, its minimum inhibitory concentration (MIC) against S. epidermidis was high (128 µg/ml). The MIC value increased from 2.31 ± 2.19 µg/ml pre-surgery to 57.14 ± 22.34 µg/ml 1 month postoperatively, while no significant change was found in the iodine group. CONCLUSION: Postoperative iodine and levofloxacin eye drops both reduced bacterial contamination in the conjunctival sac, with a superior level of disinfection in the levofloxacin group. However, postoperative levofloxacin eye drops enhanced the emergence of highly resistant bacteria, whereas no such development was seen in the iodine group.

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.

Tear fluid cytokine analysis: a non-invasive approach for assessing retinopathy of prematurity severity.

PURPOSE: To determine whether there is a significant association between inflammatory cytokines in the tear fluid and the severity of Retinopathy of Prematurity (ROP). STUDY DESIGN: Retrospective cohort study. METHODS: The cytokine levels in tear fluids were determined in 34 eyes with ROP and 18 eyes without ROP. There were 15 eyes with severe ROP requiring treatment and 19 eyes with mild ROP not requiring treatment. For severe ROP eyes, tear fluids were collected before treatment. RESULTS: Significantly higher levels of CCL2 and vascular endothelial growth factor (VEGF) were detected in eyes with severe ROP compared to eyes with mild ROP and no ROP. When assessed for cytokine levels that discriminate each disease group, CCL2 showed a significant odds ratio of 1.76 for severity change (/quintile, P = 0.032, after adjusting for birth weight). Correlation analysis showed that birth weight correlated with IL-1α levels, and decreased weight gain increased IFN-γ levels. We next determined tear fluid cytokines which discriminate severe ROP using receiver operating characteristics' analysis. We found that combination of higher CCL2 levels, higher VEGF levels, and lower IFN-γ levels in the tear fluid had a stronger predictive value for severe ROP (area under curve, 0.85). CONCLUSION: The levels of CCL2, VEGF, and IFN-γ in tear fluid may serve as useful biomarkers for assessing the severity of ROP.

The relationship between perioperative central venous oxygen saturation and postoperative complications in highly invasive gastroenterological surgery.

Purpose: Operations for malignant diseases of the bile duct, pancreas, and esophagus are the most invasive gastroenterological surgeries. The frequency of complications after these surgeries is high, which affects the postoperative course and mortality. In patients who undergo these types of surgeries, continuous monitoring of the perioperative central venous oxygen saturation (ScvO2) is possible via a central venous catheter. We aimed to investigate the relationship between continuously monitored perioperative ScvO2 values and postoperative complications. Methods: The medical records of 115 patients who underwent highly invasive gastroenterological surgeries and ScvO2 monitoring from April 2012 to March 2014 were analyzed. Sixty patients met the inclusion criteria, and their ScvO2 levels were continuously monitored perioperatively. The relationship between ScvO2 levels and major postoperative complications, defined as Clavien-Dindo grade ≥ III, was examined using uni- and multivariate analysis. Results: Thirty patients developed major postoperative complications. The adequate cut-off value derived from receiver operating curves of the postoperative average ScvO2 levels for predicting major complications was 75%. Multivariate analysis revealed that low average postoperative ScvO2 levels (p = 0.016) and blood loss ≥ 1000 mL (p = 0.039) were significant predictors of major postoperative complications. Conclusions: Low perioperative ScvO2 values were associated with an increased risk of major postoperative complications. Continuous ScvO2 monitoring will help prevent postoperative complications.

Early detection of necrosis in low-enhanced pancreatic parenchyma using contrast-enhanced computed tomography was a better predictor of clinical outcomes than pancreatic inflammation: A multicentric cohort study of severe acute pancreatitis.

OBJECTIVES: We aim to assess the early use of contrast-enhanced computed tomography (CECT) of patients with severe acute pancreatitis (SAP) using the computed tomography severity index (CTSI) in prognosis prediction. The CTSI combines quantification of pancreatic and extrapancreatic inflammation with the extent of pancreatic necrosis. METHODS: Post-hoc retrospective analysis of a large, multicentric database (44 institutions) of SAP patients in Japan. The area under the curve (AUC) of the CTSI for predicting mortality and the odds ratio (OR) of the extent of pancreatic inflammation and necrosis were calculated using multivariable analysis. RESULTS: In total, 1097 patients were included. The AUC of the CTSI for mortality was 0.65 (95 % confidence interval [CI:] [0.59-0.70]; p < 0.001). In multivariable analysis, necrosis 30-50 % and >50 % in low-enhanced pancreatic parenchyma (LEPP) was independently associated with a significant increase in mortality, with OR 2.04 and 95 % CI 1.01-4.12 (P < 0.05) and OR 3.88 and 95 % CI 2.04-7.40 (P < 0.001), respectively. However, the extent of pancreatic inflammation was not associated with mortality, regardless of severity. CONCLUSIONS: The degree of necrosis in LEPP assessed using early CECT of SAP was a better predictor of mortality than the extent of pancreatic inflammation.

Teduglutide-induced acute gastric mucosal necrosis in short bowel syndrome with hepatorenal failure: Case report.

INTRODUCTION: Short bowel syndrome (SBS) resulting from acute aortic dissection (AAD)-induced visceral malperfusions leads to chronic intestinal failure (CIF), necessitating patients to adopt home parenteral nutrition to prevent malabsorption. Teduglutide (TED), a glucagon-like peptide-2 analog, is a promising pharmacotherapy for intestinal rehabilitation that reduces parenteral support and improves the quality of life. Gastric mucosal necrosis, a rare gastrointestinal disorder, had never been observed as an adverse event relevant to this drug. We report a case of mucosal necrosis in the stomach after TED treatment for SBS-CIF with hepatorenal failure. PRESENTATION OF CASE: A 68-year-old Japanese man who underwent massive intestinal resection for AAD experienced malnutrition and diarrhea caused by SBS-CIF. The patient received TED to improve intestinal absorption and entero-hepatic circulation besides controlling infectious diseases. Endoscopy showed mucosal hyperplasia in the stomach and duodenum 1.5 months after TED administration. The patient consented to enteral nutrition via a nasogastric tube because of anorexia. The nutritional status gradually improved after initiating enteral feeding. However, the patient experienced hematemesis 13 days after enteral feeding, and endoscopy revealed acute gastric mucosal necrosis, followed by fatal septic shock. DISCUSSION: For patients with SBS, TED is expected to increase intestinal absorption through epithelial proliferation. When SBS is accompanied by multiple ischemic organ failure, TED therapeutic effects remain unclear as malnutrition-associated infectious diseases are refractory, and many underlying mechanisms can be involved. CONCLUSION: TED administration should be deliberately considered for patients with SBS-CIF and multiple organ failure experiencing uncontrolled systemic infection.

Effect of atopic conditions on development and recurrences of infectious keratitis.

BACKGROUND: Atopic conditions are known to be associated with viral and bacterial infections. The purpose of this study was to determine the relationship between the effects of atopic conditions on the severity and recurrence of ocular infections including herpes simplex virus (HSV). METHODS: This study was performed on 474 consecutive patients with infectious keratitis caused by bacteria, fungus, acanthamoeba, HSV, or varicella-zoster virus. The relationships between the atopic condition and specific infectious pathogens and HSV were determined using real-time PCR. RESULTS: Our findings showed that atopic dermatitis (AD) was significantly associated with the incidence of HSV keratitis (odds ratio (OR), 10.2; P = 0.000). Other associations with AD were observed only with bacteria in an adverse manner. HSV proliferation in the lesions of patients with HSV keratitis whose AD was associated with non-infectious atopic blepharitis were significantly greater by 145-folds (P = 0.000). The presence of asthma or allergic rhinitis also increased the HSV DNA copy numbers. A recurrence of HSV keratitis was observed in 70 patients (43.2 %), and mean time to recurrence was 1647 days. Cox proportional hazard model indicated that the epithelial type of HSV recurrence but not the stromal type was associated with atopic conditions especially with AD. The factors significantly associated with a recurrence was AD associated with non-infectious atopic blepharitis (HR: 6.11, P = 0.000) and asthma (HR: 3.03, P = 0.025). CONCLUSIONS: Atopic conditions, especially AD with atopic blepharitis, are significantly associated with the development, increased proliferation, and shorter time to a recurrence on HSV keratitis.

A fatal septic shock caused by Capnocytophaga gingivalis potentially associated with COVID-19: A case report.

Background: Capnocytophaga spp. is associated with fulminant sepsis, particularly in those with immunosuppression. We here report a rare case of fatal fulminant septic shock caused by C. gingivalis, concurrent with COVID-19. Case Presentation: A Japanese woman developed septic shock, which led to her death. Polymerase chain reaction (PCR) testing of the respiratory specimen was positive for SARS-CoV-2, and a CT scan of the chests revealed bilateral ground glass opacities. The blood cultures identified C. gingivalis. The patient had rheumatoid arthritis and was taking prednisone orally. There were no splenic abnormalities shown on the CT scan. Conclusion: A rare case of fulminant septic shock caused by C. gingivalis, together with COVID-19 was identified. The precise pathogenesis of this combination, together with the best treatment option should be sought by further studies.

Profiling miRNAs in tear extracellular vesicles: a pilot study with implications for diagnosis of ocular diseases.

PURPOSE: To estimate the roles of extracellular vesicles (EVs) in tears and to determine whether their profiles are associated with the type of ocular disease. STUDY DESIGN: Cross-sectional study. METHODS: Tear EVs were extracted from 14 healthy participants and from 21 patients with retinal diseases (age-related macular degeneration [AMD] or diabetic macular edema [DME]). The surface marker expression of tear EVs was examined, and microRNAs (miRNAs) were extracted and profiled by use of real-time PCR array. The stability of the expression of the miRNAs was determined, and their functions were assessed by network analyses. Classification accuracy was evaluated by use of a random forest classifier and k-fold cross-validation. RESULTS: The miRNAs that were highly expressed in tear EVs were miR-323-3p, miR-548a-3p, and miR-516a-5p. The most stably expressed miRNAs independent of diseases were miR-520h and miR-146b-3p. The primary networks of the highly stably expressed endogenous miRNAs were annotated as regulation of organismal injury and abnormalities. The highly expressed miRNAs for severe retinal disease were miR-151-5p for AMD and miR-422a for DME, suggesting potential roles of tear EVs in liquid biopsy. Nine miRNAs (miR-25, miR-30d, miR-125b, miR-132, miR-150, miR-184, miR-342-3p, miR-378, and miR-518b) were identified as distinguishing individuals with AMD from healthy individuals with a classification accuracy of 91.9%. CONCLUSIONS: The finding that tear EVs contain characteristic miRNA species indicates that they may help in maintaining homeostasis and serve as a potential tool for disease diagnosis.

Analyses of Dupilumab-Related Ocular Adverse Drug Reactions Using the WHO's VigiBase.

INTRODUCTION: Dupilumab is a drug that inhibits the action of interleukin (IL)-4 and IL-13 and is a potent therapeutic drug for allergic diseases such as atopic dermatitis. Although its use has been associated with significant ocular adverse drug reactions (ADRs), the IL-4 and IL-13 inhibition may also have favorable therapeutic effects. The aim of this study was to determine the disease spectrum in which the use of dupilumab may have been associated with an increase or decrease of ocular ADRs. METHODS: We searched the World Health Organization's VigiBase for ADRs associated with the use of dupilumab for data up to 12 June 2022. The number of all ADRs that were retrieved was compared with the number of ocular ADRs associated with the use of dupilumab. Disproportionate reporting was assessed by calculating the information component (IC) values and odds ratios. RESULTS: Since the introduction of dupilumab, 100,267 ADRs have been reported. Of all the ADRs associated with dupilumab, 28,522 ADRs were ocular complications, and it ranked fourth in the ocular complications by organ level. By assessments of the IC for age ≤ 44 years, the most significantly associated ADRs were dry eye followed by blepharitis including eyelid crusting and dryness and conjunctivitis. Crusting and dryness of the eyelids were the most significant ADRs for all age groups. Other ocular ADRs reported include meibomian gland dysfunction, keratitis, glaucoma, and retinal disorders. In contrast, periorbital edema, neuro-ophthalmic disorders, optic neuritis, and macular edema were significantly reduced by the use of dupilumab. CONCLUSIONS: Dupilumab-related ADRs included an increase or decrease of various ocular disorders. The results indicate that dupilumab also has potential therapeutic effects.

Effects of the pharmaceutical formulation of topical medications on corneal epithelial healing after phototherapeutic keratectomy.

PURPOSE: To determine the effect of the formulation of topical medications on the healing of corneal epithelial cells after phototherapeutic keratectomy (PTK). STUDY DESIGN: Retrospective cohort study. METHODS: We studied 271 eyes of 189 consecutive patients (aged 67.6 ± 11.8 years) who had undergone PTK for granular corneal dystrophy (n = 140), band keratopathy (n = 47), or lattice corneal dystrophy (n = 2). Postoperatively, generic or brand-named levofloxacin, 0.1% betamethasone, or 0.1% bromfenac sodium hydrate was applied topically. Patients were examined on postoperative days 1, 2, and 5 and weekly thereafter. The time to re-epithelialization was assessed by use of Kaplan-Meier and Cox proportional hazards analyses. RESULTS: The time to re-epithelialization was significantly longer with generic 0.5% levofloxacin, at 8.2 ± 3.5 days, than with 0.5% Cravit (levofloxacin), at 6.7 ± 3.5 days (P = 0.018), or with 1.5% Cravit, at 6.3 ± 2.6 days (P = 0.000). In addition, the time to re-epithelialization was significantly longer with generic 0.1% betamethasone (Sanbetason), at 7.3 ± 3.4 days, than with brand-name 0.1% betamethasone (Rinderon), at 6.1 ± 2.5 days (P = 0.0002). The Cox proportional hazards model indicated that the use of generic formulations for levofloxacin eye drops and 0.1% betamethasone was a significant factor that delayed corneal re-epithelialization (hazard ratio [HR] = 0.72, P = 0.002 and HR = 0.77, P = 0.006, after adjustment for age). Re-epithelialization was significantly shorter in band keratopathy than in corneal dystrophy (HR = 1.56, P = 0.004). No other factors, including age, bandage contact lens, and diabetes mellitus, were significantly associated with time to re-epithelialization. CONCLUSION: Corneal epithelial healing can be significantly affected by different antibacterial or steroid eye drops. Clinicians need to be aware that a generic formulation may affect corneal epithelial healing.

Association of IL-4 with pachychoroid neovasculopathy.

The purpose of this study was to identify the inflammatory cytokines that were associated with pachychoroid neovasculopathy (PNV). Seventy-five eyes of 75 patients with PNV, 145 eyes of 145 patients with neovascular age-related macular degeneration without pachyvessels, and 150 eyes of 150 normal subjects were examined for the levels of intraocular cytokines. In eyes with PNV, the levels of IL-1α, IL-1ß, IL-2, IL-4, IL-10, and VEGF were significantly higher than that of the controls. Logistic regression analysis showed that the highest association with the pachyvessels was found for IL-4, IL-2, and IL-1α. In eyes with PNV, the levels of IL-4, IL-2, IL-5, IL-13, IL-1α, and IL-1ß were significantly higher in eyes with both increased choroidal thickness and choroidal vessel diameter. The strongest correlation with the choroidal thickness and vessel diameter was observed for IL-4. In PNV eyes with polypoidal lesions, the levels of IL-4, IL-17, and TNFß were significantly correlated with the number of polypoidal lesions. Of these cytokines, IL-4 was especially associated with the thickness of the choroidal vessels and the formation of polypoidal lesions. We conclude that IL-4 is most likely involved in establishing the clinical characteristics of PNV and polypoidal vascular remodeling.

Efficacy of Proactive Topical Antihistamine Use in Patients with Seasonal Allergic Conjunctivitis.

INTRODUCTION: Topical antihistamines are often instilled symptomatically to control patients' eye allergy symptoms. The purpose of this study was to evaluate the effectiveness of proactive and as-needed use of antihistamine eye drops in controlling symptoms and to examine whether proactive use may improve quality of life (QOL). METHODS: This was a prospective, multicenter, cohort study in Japan. We classified 418 patients who had developed certain symptoms and used antihistamine eye drops for 2 weeks into two groups: those who used the drops at the required frequency at a fixed time (proactive use) and those who used them as-needed. The Japanese Allergic and Conjunctival Diseases Quality of Life Questionnaire (JACQLQ) and Ten-Item Personality Inventory were used to evaluate QOL and personality. Participants' QOL was evaluated using JACQLQ scores after matching of baseline characteristics using propensity score analysis. RESULTS: After propensity score matching, 115 "proactive" and 115 "as-needed" patients were analyzed. After treatment, in "as-needed" patients, the overall QOL scale was 1.66 (95% CI 1.55-1.78); in "proactive" patients, the overall QOL scale was 1.34 (95% CI 1.23-1.46) and was significantly improved compared with the "as-needed" patients (analysis of covariance, P = 0.002). Furthermore, proactive use significantly alleviated depression (P = 0.03). This improvement of QOL was independent of improvement of the clinical sign scores. CONCLUSION: Proactive use of topical antihistamine may serve as an effective means for improving QOL of patients with seasonal allergic conjunctivitis. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) 000039554.

Executive summary: Japanese guidelines for allergic conjunctival diseases 2021.

Allergic conjunctival disease (ACD) is an inflammatory disease of the conjunctiva that is mainly caused by type I hypersensitivity response to allergens and accompanied by subjective symptoms and other findings induced by antigens. ACD is classified as allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. This article summarizes the third edition of the Japanese guidelines for allergic conjunctival diseases published in 2021 and outlines the diagnosis, pathogenesis, and treatment of ACD. Since the introduction of immunosuppressive eye drops, the treatment strategies for severe ACDs have significantly changed. To clarify the recommended standard treatment protocols for ACD, the advantages and disadvantages of these treatments were assessed using clinical questions, with a focus on the use of steroids and immunosuppressive drugs. This knowledge will assist healthcare providers and patients in taking an active role in medical decision making.

Antiviral cytotoxic T lymphocyte responses for long term prognosis of corneal infection by cytomegalovirus in immunocompetent subjects.

Ocular cytomegalovirus (CMV) infections in immunocompetent individuals are rare, but its activation can cause chronic and relapsing inflammation in anterior segment of the eye resulting in loss of corneal clarity and glaucoma. Fifty five patients with anterior segment CMV infection were assessed for their clinical characteristics, and CMV corneal endotheliitis was found to cause significant loss of corneal endothelial cells. The disease duration with recurrences was significantly correlated with the maximum intraocular level of CMV DNA. To examine why CMV is activated in healthy immunocompetent individuals and causing corneal endothelial cell damage, assays of cytotoxic T cells (CTLs) which directly target infected corneal endothelial cells were performed for 9 HLA-matched CMV corneal endotheliitis patients (HLA-A*2402). When the cell loss was analyzed for associations with CTL responses, CMV-induced endothelial cell damage was mitigated by pp65-specific CTL induction. The recurrence-free time was also prolonged by pp65-specific CTL induction (hazard ratio (HR): 0.93, P = 0.01). In contrast, IE1-specific CTL was associated with endothelial cell damage and reduced the time for corneal transplantation (HR: 1.6, P = 0.003) and glaucoma surgery (HR: 1.5, P = 0.001). Collectively, induction of pp65-specific CTL was associated with improved visual prognosis. However, IE1-specific CTL without proper induction of pp65-specific CTL can cause pathological damage leading to the need of surgical interventions.

Determination of probability of causative pathogen in infectious keratitis using deep learning algorithm of slit-lamp images.

Corneal opacities are important causes of blindness, and their major etiology is infectious keratitis. Slit-lamp examinations are commonly used to determine the causative pathogen; however, their diagnostic accuracy is low even for experienced ophthalmologists. To characterize the "face" of an infected cornea, we have adapted a deep learning architecture used for facial recognition and applied it to determine a probability score for a specific pathogen causing keratitis. To record the diverse features and mitigate the uncertainty, batches of probability scores of 4 serial images taken from many angles or fluorescence staining were learned for score and decision level fusion using a gradient boosting decision tree. A total of 4306 slit-lamp images including 312 images obtained by internet publications on keratitis by bacteria, fungi, acanthamoeba, and herpes simplex virus (HSV) were studied. The created algorithm had a high overall accuracy of diagnosis, e.g., the accuracy/area under the curve for acanthamoeba was 97.9%/0.995, bacteria was 90.7%/0.963, fungi was 95.0%/0.975, and HSV was 92.3%/0.946, by group K-fold validation, and it was robust to even the low resolution web images. We suggest that our hybrid deep learning-based algorithm be used as a simple and accurate method for computer-assisted diagnosis of infectious keratitis.

Role of interferon regulatory factor 7 in corneal endothelial cells after HSV-1 infection.

Viral infections of the cornea including herpes simplex virus 1 (HSV-1) cause visual morbidity, and the corneal endothelial cell damage leads to significant visual impairment. Interferon regulatory factor 7 (IRF7) has been identified as a significant regulator in corneal endothelial cells after an HSV-1 infection. To examine the role played by IRF7, the DNA binding domain (DBD) of IRF7 of human corneal endothelial cells (HCEn) was disrupted. An RNAi inhibition of IRF7 and IRF7 DBD disruption (IRF7 ∆DBD) led to an impairment of IFN-ß production. Impaired IFN-ß production by IRF7 ∆DBD was regained by IRF7 DNA transfection. Transcriptional network analysis indicated that IRF7 plays a role in antigen presentation function of corneal endothelial cells. When the antigen presentation activity of HCEn cells were examined for priming of memory CD8 T cells, IRF7 disruption abolished the anti-viral cytotoxic T lymphocyte (CTL) response which was dependent on the major histocompatibility complex (MHC) class I. To further examine the roles played by IRF7 in CTL induction as acquired immunity, the contribution of IRF7 to MHC class I-mediated antigen presentation was assessed. Analysis of IRF7 ∆DBD cells indicated that IRF7 played an unrecognized role in MHC class I induction, and the viral infection induced-MHC class I induction was abolished by IRF7 disruption. Collectively, the IRF7 in corneal endothelial cells not only contributed to type I IFN response, but also to the mediation of viral infection-induced MHC class I upregulation and priming of CD8 arm of acquired immunity.

Role Played by Receptors for Advanced Glycosylation End Products in Corneal Endothelial Cells after HSV-1 Infection.

Senescence, sterile inflammation, and infection cause dysfunction of corneal endothelial cells, leading to visual morbidity that may require corneal transplantation. With increasing age, the extracellular matrix is modified by non-enzymatic glycation forming advanced glycation end products (AGEs). The modifications are primarily sensed by the receptors for the AGEs (RAGE) and are manifested as a type I interferon response. Interestingly, in our study, human corneal endothelial cells (HCEn) cells did not respond to the typical RAGE ligands, including the AGEs, high mobility group box 1 (HMGB1), and serum amyloid-A (SAA). Instead, HCEn cells responded exclusively to the CpG DNA, which is possessed by typical corneal pathogen, herpes simplex virus-1 (HSV-1). Upon HSV-1 infection, the surface expression of RAGE was increased, and endocytosed HSV-1 was associated with RAGE and CpG DNA receptor, TLR9. RAGE DNA transfection markedly increased interferon-ß secretion by CpG DNA or HSV-1 infection. HSV-1 infection-induced interferon-ß secretion was abolished by TLR9 inhibition and partially by RAGE inhibition. Global transcriptional response analysis confirmed that RAGE and TLR9 were both significantly involved in type I interferon responses. We conclude that RAGE is a sensor of HSV-1 infection and provokes a type I interferon response.

Quantitative Investigation of Viral Load in Acute to Subacute Human Adenovirus Type 54 Conjunctivitis.

To understand the clinical course of human adenoviral (HAdV) conjunctivitis and establish a better treatment regimen, 38 eyes of 19 patients with HAdV-54 conjunctivitis for less than one week from onset were evaluated for clinical signs and symptoms and DNA copy numbers. A viral load of 104-105 is required to develop symptoms of HAdV conjunctivitis, as symptoms were present in eyes with viral loads of ≥104 at least once during the course. Next, it was observed that asymptomatic infections in the contralateral eyes are common, as the virus was detected in most eyes that did not develop conjunctivitis. Furthermore, there was no rapid decrease in the viral load in healed eyes; on the contrary, the viral load in the healed eyes on day 15 was significantly higher than that in the unhealed eyes. This was likely due to corticosteroid instillation, which rapidly alleviated symptoms but prolonged the duration of viral shedding. Recently, combination treatment with iodine and corticosteroids has been recommended for HAdV conjunctivitis. Assessing changes in the viral load and clinical symptoms would be helpful to better understand the clinical course of this disease.