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Infectious uveitis is a vision-threatening condition that requires prompt clinical diagnosis and proper treatment. However, rapid and proper diagnosis in infectious uveitis remains challenging. Several examination tests, including polymerase chain reaction (PCR) tests, are transitioning from laboratory-based basic research-level tests to bedside clinical tests, and recently tests have changed to where they can be performed right next to clinicians. In this review, we introduce an updated overview of recent studies that are representative of the current trends in clinical microbiological techniques including PCR tests for infectious uveitis.

Background Polymerase chain reaction (PCR) can be used to confirm or deny infectious ocular inflammation such as uveitis . The purpose of this article is to review the current practical use of PCR examination in ophthalmology, especially multiplex and broad-range PCR, and a novel PCR, termed Strip PCR. Summary of contents At first, in the Introduction, we show the development of the PCR examination in ophthalmology. We next show the clinical applications of multiplex PCR and broad-range PCR. These advances in PCR continue to contribute greatly to the ophthalmology field. We also show how the sample for PCR is collected. Recently, we established a novel examination, a multiplex real-time PCR (Strip PCR) prototype for detecting 24 pathogens responsible for ocular infectious diseases. Moreover, we developed the Direct Strip PCR method, which skips the DNA extraction step in the procedure. This PCR is anticipated to ease etiologic evaluation, increasing pathogen detection in the intraocular fluids of uveitis patients even by general ophthalmologists. We also describe the following: (1) representative cases in which PCR is useful, (2) representative cases in which PCR can exclude a diagnosis, (3) the current status of PCR in the diagnosis of infectious uveitis and advanced medical service, and (4) the prospects for clinical PCR in ophthalmology. Conclusion We have established and developed the multiplex PCR, broad-range PCR, Strip PCR, and Direct Strip PCR methods and have reported the efficacy of such tests in multicenter studies. Our goal is “rapid and simple comprehensive PCR diagnosis anywhere and by anyone” for ocular infections.

Acute retinal necrosis (ARN) is a rare but vision-threatening viral retinitis that can lead to severe visual impairment or blindness if not diagnosed and treated promptly. However, due to its rarity, there are limited large-scale data on the clinical characteristics, treatment approaches, and outcomes of ARN in Japan. A nationwide registry is needed to systematically collect data on ARN cases across Japan to improve understanding of this condition and optimize patient care. We have designed a national registry that collects data of patient characteristics, diagnosis, treatment, and visual outcome to generate evidence for the management of ARN. This research is a combined retrospective and prospective, multicenter cohort study of ARN in Japan from 1 April 2014-31 March 2029 (UMIN000056246). The registry has received Japan-wide approval from a national human research ethics committee. The following data will be collected: patient demographics, visual function at the initial visit and 6, 12, 24, and 36 months later, image data, diagnostic methods, virus analysis, indications and timing of vitrectomy, and complications. Customized software and platforms have been designed to permit data collection for a single baseline and multiple follow-up forms. By analyzing the accumulated patient information, the results of this study will generate real-world evidence that will contribute to solve various important clinical issues in ARN. The results will be presented after data collection and analysis are completed.

Alveolar type 2 (AT2) pneumocytes are a cell type critical for repair of the distal lung after an injury, such as a viral infection. After epithelial damage, AT2 pneumocytes proliferate for both self-renewal and differentiation into type I pneumocytes to repopulate the epithelium. Theoretically, some of the long-term lung sequelae associated with viral infections could be the result of inappropriate AT2 behavior. Here, the authors report that during an influenza B virus infection, some of the actively infected AT2 pneumocytes can ultimately eliminate all traces of the viral RNA and persist in the host long term. As a consequence of having been infected, however, the cells display an altered transcriptional profile and decreased proliferative capacity. These data together suggest a mechanism for how an acute viral infection can have long-term impacts on the pulmonary system.

PurposeHerpes simplex diffuse endotheliitis with accompanying feathery infiltration is difficult to diagnose due to corneal findings that are similar to fungal keratitis. This case series reports on the effectiveness of using real-time polymerase chain reaction (PCR) to diagnose herpes simplex diffuse endotheliitis that is similar in appearance to fungal keratitis.MethodsAfter extracting corneal smear sample DNA, samples were then applied to two independent PCR assays, a qualitative multiplex 24-pathogen strip PCR assay, and a quantitative real-time PCR assay of herpes simplex virus type 1 (HSV-1).ResultsAll 3 cases showed ciliary injection, feathery infiltration in the corneal stroma and hypopyon, which are corneal findings similar to that observed for fungal keratitis. Retrocorneal plaques, which showed clear boundaries between the corneal endothelial surfaces and retrocorneal plaques in anterior segment optical coherence tomography, were observed in 2 out of 3 cases. Corneal scraping was performed in all cases, followed by initiation of antifungal treatment. However, real-time PCR of the corneal scraping detected 6.0 × 106, 1.0 × 105 and 5.0 × 105 copies/μg glyceraldehyde 3-phosphate dehydrogenase (GAPDH) of HSV-1 DNA per each microgram of the samples. Fungi were not cultured in any of the cases. After switching the medication from antifungal to antiviral, the feathery corneal infiltration was cured with only mild scarring.ConclusionsReal-time PCR was an effective tool in diagnosing HSV diffuse endotheliitis with feathery infiltration. Topical corticosteroids in conjunction with oral and topical antivirals were an effective treatment.

Key summary points Aim This study investigated the association between plantar cutaneous sensation and physical function, including postural balance. Findings The plantar sensation threshold was significantly associated with one-leg standing and sit-to-stand time, but not with normal walking speed. Message Assessing plantar sensation could offer valuable insights into factors contributing to poor postural balance and lower limb motor function. Purpose A relationship between decreased plantar cutaneous sensation and impaired balance function has been reported in patients with peripheral neuropathy and diabetes. This cross-sectional study aimed to investigate the relationship between plantar sensation and postural balance, as well as the association between plantar sensation and sarcopenia-related motor function in community-dwelling older adults. Methods The participants included 1659 community-dwelling older adults with a mean age of 74 ± 5 years, of which 43% were male patients. Plantar cutaneous sensation thresholds were assessed using an automatic plantar sensation testing device. Postural balance was measured using one-leg standing (OLS) time. Grip strength, five-time sit-to-stand (STS) time, and normal gait speed were measured as components of muscle strength and physical function related to sarcopenia. The skeletal muscle mass index (SMI) and leg phase angle were obtained using bioelectrical impedance analysis. Results Age, sex, body mass index, and leg phase angle, but not SMI and grip strength, were independently associated with the plantar sensation threshold. Plantar sensation threshold was independently associated with the OLS time ( P  = 0.001) and STS time ( P  = 0.001) after adjusting for potential confounders. No significant association was found between plantar sensation threshold and normal gait speed ( P  = 0.741). Conclusion Plantar sensation was independently associated with postural balance and lower limb function in community-dwelling older adults. The assessment of plantar sensation could be useful for identifying factors contributing to poor postural balance and lower limb motor function.

Although lysyl oxidase-like 1 ( LOXL1 ) is known as the principal genetic risk factor for pseudoexfoliation (PEX) syndrome, a major cause of glaucoma and cardiovascular complications, no functional variants have been identified to date. Here, we conduct a genome-wide association scan on 771 German PEX patients and 1,350 controls, followed by independent testing of associated variants in Italian and Japanese data sets. We focus on a 3.5-kb four-component polymorphic locus positioned spanning introns 1 and 2 of LOXL1 with enhancer-like chromatin features. We find that the rs11638944:C>G transversion exerts a cis -acting effect on the expression levels of LOXL1 , mediated by differential binding of the transcription factor RXRα (retinoid X receptor alpha) and by modulating alternative splicing of LOXL1 , eventually leading to reduced levels of LOXL1 mRNA in cells and tissues of risk allele carriers. These findings uncover a functional mechanism by which common noncoding variants influence LOXL1 expression. LOXL1 is a genetic risk factor for pseudoexfoliation syndrome of the eye but a causal variant has not been identified. Here, Pasutto et al ., find intronic LOXL1 risk variants influence transcription factor binding and alternative splicing of LOXL1 in affected tissues reducing levels of LOXL1 mRNA.

AimsTo investigate the association between corneal hysteresis and the presence of glaucoma and its subtypes in a general Japanese population.MethodsWe analysed the data of 2338 Japanese community-dwellers aged ≥40 years (1059 men, 1279 women) who underwent an eye examination in 2018 as part of the population-based, cross-sectional Hisayama Study. Participants were divided into quartile levels of corneal hysteresis, which had been measured with an ocular response analyzer. Glaucoma was defined based on the International Society of Geographical and Epidemiological Ophthalmology criteria. We conducted a logistic regression analysis to determine the ORs and their 95% CIs for the presence of outcomes according to the corneal hysteresis quartiles.ResultsGlaucoma was diagnosed in 154 participants: primary open-angle glaucoma (POAG), n=115; primary angle-closure glaucoma, n=17; exfoliation glaucoma, n=21 and secondary glaucoma without exfoliation glaucoma, n=1. After adjustment for confounders, the OR for prevalent glaucoma was significantly increased in the participants in the first corneal-hysteresis quartile compared with those in the fourth quartile (OR: 1.80; 95% CI: 1.03 to 3.17). Regarding glaucoma subtypes, the first-quartile participants had significantly greater likelihoods of the presence of POAG (OR: 1.63; 95% CI: 1.02 to 2.61) and exfoliation glaucoma (OR: 6.49; 95% CI: 1.44 to 29.30) compared with those in the third and fourth quartiles after adjustment for potential confounders.ConclusionsThese results demonstrated a significant inverse association between corneal hysteresis and the likelihood of glaucoma, suggesting that the measurement of corneal hysteresis would provide useful information for elucidating the aetiology of glaucoma.

Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections. Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration. Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP. Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP.

Mapping the spatial distribution and molecular identity of constituent cells is essential for understanding tissue dynamics in health and disease. We lack a comprehensive map of human distal airways, including the terminal and respiratory bronchioles (TRBs), which are implicated in respiratory diseases 1 – 4 . Here, using spatial transcriptomics and single-cell profiling of microdissected distal airways, we identify molecularly distinct TRB cell types that have not—to our knowledge—been previously characterized. These include airway-associated LGR5 + fibroblasts and TRB-specific alveolar type-0 (AT0) cells and TRB secretory cells (TRB-SCs). Connectome maps and organoid-based co-cultures reveal that LGR5 + fibroblasts form a signalling hub in the airway niche. AT0 cells and TRB-SCs are conserved in primates and emerge dynamically during human lung development. Using a non-human primate model of lung injury, together with human organoids and tissue specimens, we show that alveolar type-2 cells in regenerating lungs transiently acquire an AT0 state from which they can differentiate into either alveolar type-1 cells or TRB-SCs. This differentiation programme is distinct from that identified in the mouse lung 5 – 7 . Our study also reveals mechanisms that drive the differentiation of the bipotent AT0 cell state into normal or pathological states. In sum, our findings revise human lung cell maps and lineage trajectories, and implicate an epithelial transitional state in primate lung regeneration and disease. Spatial transcriptomics and single-cell profiling identify previously uncharacterized cell types of human terminal and respiratory bronchioles, and show that cell differentiation and lineage trajectories are distinct from those in the mouse lung.