Investigating the seasonality of infectious keratitis by pathogen: A retrospective study

Investigating the seasonality of infectious keratitis by pathogen: A retrospective study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Investigating the seasonality of infectious keratitis by pathogen: A retrospective study Naoyuki Yamada, Nanako Iwamoto, Ayano Sakuma, Junki Sunada, Ren Aoki, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4169506/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This study aimed to investigate the seasonal trends in infectious keratitis by assessing the month of onset and causative microorganisms. Five hundred consecutive cases of infectious keratitis that were diagnosed and treated by a corneal specialist at the Department of Ophthalmology, Yamaguchi University Hospital between January 2009 and January 2021 in whom micro-organisms could be identified formed the study population. The month of onset of infectious keratitis was retrospectively examined based on the medical records. The causative microorganisms were bacteria in 249 eyes, fungi in 51 eyes, Acanthamoeba in 27 eyes, and viruses in 173 eyes. The top 10 causative microorganisms accounted for 402 of 500 eyes (80.4% of the total). The incidence of infectious keratitis was highest from January to March and lowest in June. The total number of bacterial-induced infections was high between October and March. Pseudomonas aeruginosa commonly caused infectious keratitis from August to September. Acanthamoeba-induced infection was common in summer from June to August. HSV infections were common between January and May. A seasonal trend was observed in the occurrence of infectious keratitis by examining the months of onset. We contemplate that these results will assist ophthalmologists in diagnosing infectious keratitis. Health sciences/Diseases/Eye diseases Health sciences/Diseases/Infectious diseases Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction The cornea is a transparent avascular tissue located at the surface of the eyeball. It acts as a structural barrier and protects the eye. The cornea is constantly exposed to external stresses, such as trauma and infection. Since the cornea is located along the optical axis, corneal opacity directly leads to loss of vision. Infections caused by pathogenic micro-organisms in the cornea can be defined as infectious keratitis [1]. In general, when pathogenic microorganisms establish an infection in the cornea, corneal epithelial defects occur, which progress to corneal ulceration. Corneal perforation may occur in some cases if the corneal stroma melts. Corneal perforation makes it difficult to maintain the shape of the eye shape. Endophthalmitis can occur if the corneal infection spreads to the anterior chamber, vitreous, and retina. Consequently, the risk of blindness is high in such cases. If severe inflammation or prolonged healing occurs, the cornea may get scarred and develop abnormal shape, resulting in reduced transparency and visual impairment [2, 3]. Thus, infective keratitis is a serious ocular disease that can lead to corneal melting and perforation in severe cases, resulting in blindness. Diverse microorganisms, including bacteria, fungi, viruses, and amoebas, can cause infectious keratitis. For example, in Japan, the "Guidelines for Clinical Management of Infectious Keratitis (2nd edition)," formulated by the Japanese Ophthalmological Society, lists 28 causative micro-organisms for infectious keratitis [4]. Identification of the exact micro-organism that causes infectious keratitis among the 28 species is an arduous task. Several of these 28 species are the common causative microorganisms of infectious keratitis in countries other than Japan. Accurate identification of the causative microorganism is required for selecting the drug to be administered for the treatment of infectious diseases [5]. However, infectious keratitis is an infection of the cornea, a relatively small organ measuring approximately 11 mm in diameter. The amount of sample collected by abrasion of infected foci in the cornea for identification of the causative microorganisms is very small; therefore, the identification rate is never satisfactory [6]. Furthermore, different causative microorganisms may present with similar corneal findings, whereas the same causative microorganism may present with different corneal findings in different cases. In particular, differentiating between bacterial and fungal keratitis on the basis of corneal findings alone is an arduous task. We previously reported that the micro-organism causing infectious keratitis was identified in only 72% cases using culture tests or microscopy [6]. Even with the latest artificial intelligence (AI) technology, the diagnosis of infectious keratitis is limited to differentiating between bacteria, fungi, herpes, and amoebae [7]. Therefore, in the context of infectious diseases, it is advantageous to narrow down the candidate causative microorganisms to select the drug to be administered. Seasonality can be defined as the presence of variations that occur at specific regular intervals of less than a year, such as weekly, monthly, or quarterly. The Japanese Islands extend 3,000 km from north to south, and belong to the subarctic, temperate, and subtropical zones, in that order from north to south. In addition, Japan is surrounded by sea on all sides and is influenced by ocean currents and monsoons, which results in marked seasonal changes in temperature and humidity. Therefore, it can be expected that the microbial world in Japan also varies greatly with seasons. Pathogenic microorganisms are those that cause disease in humans. Previous studies have reported that pathogenic microorganisms vary in frequency and exhibit seasonality [8] [9]. For example, influenza viruses that cause respiratory infections are prevalent worldwide, mainly during the winter season [10]. In Japan, noroviruses, which causes infectious gastroenteritis, are most common during winter [11]. Seasonality is influenced by climatic, social, behavioral, agricultural, environmental, and immune factors. Several studies from other countries have reported about infectious keratitis and its seasonality [12] [13] [14] [15] [16] [17] [18]. Although there have been reports of a few cases of other ocular infections in Japan, to the best of our knowledge, there have been no reports of numerous cases of infectious keratitis. In order for infection to be established, the three factors namely "pathogen," "route of infection" and "host" need to be present. The development of infectious keratitis is also influenced by the virulence of the pathogen, host immunity, and climatic factors such as temperature and humidity. Therefore, we investigated the seasonality of infectious keratitis by pathogen. Results The causative microorganisms included 249 bacteria, 51 fungi, 27 Acanthamoeba, and 173 viruses. A total of 78 causative microorganisms were detected using microbiological culture test, Micro Trak or anterior chamber aqueous polymerase chain reaction (PCR). The number of cases of infectious keratitis caused by bacteria, fungi, Acanthamoeba, and viruses is shown in Figure 1. The number of cases of infectious keratitis was higher in January (46), February (47), and March (52), and lower in June (33). The number of bacterial infections was highest in October (22), November (22), December (27), January (23), February (24), and March (27). Fungal infections ranged from one to six cases per month with no clear seasonality. The number of cases caused by Acanthamoeba were higher during the summer months of June (4), July (12), and August (4). The number of viral infections was highest in January (18), February (20), March (21), April (17), and May (20). This was based on the data for the top 10 causative organisms, including 80.4% (402/500) of all cases (Table 1). Causative microorganisms ranked ≤11 were classified as others. The top 10 species causing infectious keratitis are listed in Table 1. Of these, the number of cases caused by bacterial species, such as methicillin sensitive Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), Propionibacterium acnes, Corynebacterium spp. and Pseudomonas aeruginosa are shown in Figure 2; those caused by fungal species, such as Candida spp. is shown in Figure 3; those by Acanthamoeba are shown in Figure 1; and those by viruses, such as herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) are shown in Figure 4. All these 10 causatives microorganisms were among the 28 causative agents listed in the Guidelines for Clinical Management of Infectious Keratitis. MSSA was multimodal and showed no clear seasonality in causing infectious keratitis. The prevalence of MRSA-induced infectious keratitis was higher in January (4), February (4), March (5), April (4), and September (4). Propionibacterium acnes being the cause of infection was higher in March (8), and Corynebacterium spp. was prevalent from January (7) to February (10). Pseudomonas aeruginosa-induced infectious keratitis was higher from August (5) to September (6) (Figure 2). Candida spp. was multimodal and showed no clear seasonality (Figure 3) in causing infection. HSV-induced infectious keratitis was more common in January (14), February (14), and March (14); whereas VZV and CMV were multimodal and showed no clear seasonality (Figure 4). Based on the results of this study, we found monthly incidence patterns of the microorganisms causing infectious keratitis (absolute values displayed in Figure 5, monthly relative values displayed in Figure 6). Discussion In this study, we identified the causative microorganisms of infectious keratitis in Japan on a monthly basis. It was evident that the causative microorganisms of infectious keratitis can either be seasonal or non-seasonal. The incidence of infectious keratitis was highest from January to March and lowest in June. The total number of bacteria-induced infectious keratitis cases were high between October and March. Infection caused by Pseudomonas aeruginosa was common from August to September. The fungi were multimodal with no clear seasonality in causing infections. Acanthamoeba infections were common in summer from June to August. Viruses were detected commonly from the samples between January and May. HSV infection was common between January and March. These results indicate a seasonal trend in the incidence of infectious keratitis. Several studies from outside Japan have discussed seasonality, and few have evaluated the incidence of infectious keratitis on a monthly basis, as in the present study [12] [13]. A study from Nottingham, England indicated that Gram-positive rods more commonly caused infectious keratitis during the summer season [14]. On the contrary, in this study, Propionibacterium acnes-induced infection was found to be more common in March and Corynebacterium spp.-induced infection in January and February. The aforementioned study also reported that Pseudomonas aeruginosa more commonly caused the infection in summer, which is in line with the present study. A study from Manchester, England reported that Gram-negative bacteria-induced infections were more common during summer and fall seasons [15]. A report from Toronto, Canada showed that Acanthamoeba-induced infectious keratitis were common during the summer season, which is consistent with the present study [16]. Studies from Brisbane and Sydney, Australia demonstrated that Pseudomonas aeruginosa more commonly caused infections during summer, which is consistent with the results of the present study [17] [18]. A report from Southeast India showed that Pseudomonas aeruginosa-induced infectious keratitis was common from July to December, which is partially consistent with the results of the present study [12]. A study from Brazil showed that bacterial infections were common from fall to winter, which is consistent with the results of the present study [13]. However, no reports were found on the seasonality of infectious keratitis in Japan. Although one of the studies focused on bacterial eye infections, which was different from the subject of this study, the bimodality in March and October was partly consistent with the results of this study [19]. Yamaguchi Prefecture, where this study was conducted, is located at 34°N, 131°E and is the westernmost point of Japan's Honshu Island. Yamaguchi Prefecture is surrounded by sea in three directions, and the four seasons are rich in variation. It is difficult to make comparisons with tropical countries such as India and Brazil because, unlike in Japan, there is little distinction among the four seasons. However, reports from the United Kingdom in the Northern Hemisphere and Australia in the Southern Hemisphere, both of which belong to temperate zones like Yamaguchi, are worth comparing. Therefore, it can be elicited that the increased incidence of infectious keratitis caused by Pseudomonas aeruginosa and Acanthamoeba, as demonstrated in this study, also occurs worldwide during summer. To the best of our knowledge, there are no previous reports on seasonality of viral keratitis. A very high proportion of infectious keratitis cases were caused by viruses; therefore, they were included in this study. We found that HSV-induced keratitis was common between January and May. Furthermore, this study is the first to have determined the monthly frequencies of the 10 most frequent causative microorganisms of infectious keratitis (Figures 5, 6). Since this study was conducted at a university hospital, the severity and timing of disease onset may differ slightly from those in the clinic. It has been observed that mild cases are cured completely in the clinics, while severe cases are transferred to the university hospitals. Therefore, data included in this study may have shifted to the slightly more severe side of infectious keratitis. In addition, the time of onset of keratitis may have been delayed by a few days because this study was conducted at a university hospital rather than at clinics. Since this study involved monthly evaluations, it was considered that there was no significant effect. The monthly incidence patterns of causative micro-organisms of infectious keratitis (absolute value display) in Figure 5 reflects the true frequency due to display of absolute values. Moreover, comparison between different months could also be performed. However, the difference was difficult to recognize because the scale became smaller each month, which was a disadvantage. The information actually required is the monthly incidence pattern to determine what can be suspected about patients with infectious keratitis who visit the clinic or hospital on any day in a particular month. A relative monthly display is shown in Figure 6. For example, if a patient with infectious keratitis is examined in the month of July, then the vertical column in Figure 6 would reveal that Acanthamoeba has the darkest color and probably caused the infection. Certainly, the corneal findings along with other background and microscopic results are to be considered; but the possibility of Acanthamoeba causing the infection should also be taken into account. Unlike other studies, inclusion of viral data is required. It is necessary to be able to accurately distinguish between the disease state of infection and non-infection (immunogenicity and wound healing delay) in the cornea as a premise in which these monthly incidence patterns can be used. At the beginning of this study, we envisioned a pollen calendar. Although it is difficult to identify the causative microorganisms in infectious keratitis, we conjectured whether a new tool could be created, which led us to the idea for this study. We contemplate that these monthly incidence patterns will be a useful tool for ophthalmologists in diagnosing infectious keratitis. This study is limited by the experience of a single corneal specialist at a single institution. Future national and international studies are required to prove the generalizability of our results at domestic and universal levels. Methods Data were retrospectively collected from the medical records of the study participants and examined. This study was approved by the Institutional Review Board of the Yamaguchi University. The School of Medicine complied with the tenets of Declaration of Helsinki while performing this study. The institutional review board approved the use of opt-out consent method. An Informed consent was waived by an institutional review board of the Yamaguchi University Hospital. This study was approved by the Ethical Review Board of the Yamaguchi University Hospital for Research Ethics Committee (REC) (2020-215). This retrospective study included 500 consecutive patients diagnosed with infectious keratitis by a single corneal specialist between January 2009 and January 2021 at the Department of Ophthalmology, Yamaguchi University Hospital, Yamaguchi, Japan. Since some cases were bilateral or caused repeated infections in the same eye, there were a total of 500 treatment episodes in 379 patients with 391 eyes. The mean age (± standard deviation) of the study population was 63 ± 22 years, 270:230 for males and females, and 242:258 for the right and left eye, respectively. In principle, the causative microorganisms of infectious keratitis were detected at the time of the first visit using microbiological culture tests of samples obtained from corneal abrasion, discharge, and Contact Lens Preservation Solution, or by Micro Trak (virus-specific antigen test) or anterior chamber aqueous PCR, if viral infection was suspected. However, HSV was defined when clear dendritic or geographic keratitis was confirmed using photographs from a previous physician, whereas pseudodendritic keratitis during or immediately after the onset of herpes zoster was defined as VZV. HSV and VZV cases included not only the epithelial type but also the stromal and endothelial types, which are mainly caused by immune reactions, as well as cases in which these types occurred simultaneously. Once keratitis caused by HSV, VZV, or CMV was diagnosed, subsequent recurrences were considered to be caused by the same virus if the corneal findings were consistent. The month of onset of infectious keratitis (mainly the date of examination when the causative microorganisms were identified) was retrospectively examined. If several causative microorganisms were detected in the same eye on the same day, one was chosen based on the corneal findings. For example, when Pseudomonas aeruginosa and Enterobacter cloacae complex were detected, infection by Pseudomonas aeruginosa was assumed if corneal findings such as ring-shaped abscesses were evident. The monthly incidence patterns of the causative microorganisms of infectious keratitis were created using PowerPoint (Microsoft). For monthly incidence patterns of causative micro-organisms of infectious keratitis (absolute value display), the color of cells in December of Others with the highest number of cases (15) by month for each causative micro-organisms is shown as "black, 0% transparency" (i.e., black), and the color of the cells in months with zero cases is shown as "black, 100% transparency" (i.e., white). For monthly incidence patterns of causative micro-organisms of infectious keratitis (monthly relative value display), the cells of causative micro-organisms with the highest number of cases in each month are colored "black, 0% transparency" (i.e., black), and the cells of months with zero cases are colored "black, 100% transparency" (i.e., white). Declarations Acknowledgements (optional): We would like to thank Editage (www.editage.jp) for English language editing. Author contributions: N.Y. conceived and designed the study. N.Y., N.I., A.S., J.S., R.A., F.H., T.Y., T.N., and Y.M. performed data collection. N.Y. performed analysis. N.Y. drafted the manuscript, and K.K edited it. All authors reviewed the manuscript. Data availability statement: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Additional Information (including a Competing Interests Statement): The authors declare no competing interests. References Sean, L., Edelstein, P. W., Andrew, J. W. & Huang. Bacterial Keratitis. In: Jay H Krachmer MJM, Edward J Holland, editor. CORNEA. 1. THIRD ed: MOSBY ELSEVIER; 2011. p. 919-44. Khor, W. B., et al. The Asia Cornea Society Infectious Keratitis Study: A Prospective Multicenter Study of Infectious Keratitis in Asia. Am. J. Ophthalmol. 195, 161-170 (2018). Menda, S. A., et al. Association of Postfungal Keratitis Corneal Scar Features With Visual Acuity. JAMA Ophthalmol . 138 , 113-118 (2020). Nihon Ganka Gakkai. [Guidelines for the clinical management of infectious keratitis (2nd edition)]. Nippon Ganka Gakkai Zasshi . 117 , 467-509 (2013). Intra, J., Sala, M. R., Falbo, R., Cappellini, F. & Brambilla, P. Reducing time to identification of aerobic bacteria and fastidious micro-organisms in positive blood cultures. Lett Appl Microbiol. 63 , 400-405 (2016). Harada, D., Chikama, T. -I., Yamada, N., Nomi, N., Kawamoto, K. & Nishida, T. Value of microscopic examination of smear in corneal infections. Rinsho Ganka . 63 , 231-235 (2009). Koyama, A., et al. Determination of probability of causative pathogen in infectious keratitis using deep learning algorithm of slit-lamp images. Sci Rep . 11, 22642 (2021). Sung, J., Cheong, H. K., Kwon, H. J. & Kim, J. H. Pathogen-specific response of infectious gastroenteritis to ambient temperature: National surveillance data in the Republic of Korea, 2015-2019. Int J Hyg Environ Health. 240, 113924 (2022). Moriyama, M., Hugentobler, W. J. & Iwasaki, A. Seasonality of Respiratory Viral Infections. Annu Rev Virol . 7 , 83-101 (2020). Neumann, G. & Kawaoka, Y. Seasonality of influenza and other respiratory viruses. EMBO Mol Med . 14 , e15352 (2022). Misumi, M. & Nishiura, H. Long-term dynamics of Norovirus transmission in Japan, 2005-2019. PeerJ . 9 , e11769 (2021). Lin, C. C., et al. Seasonal trends of microbial keratitis in South India. Cornea . 31 , 1123-1127 (2012). Marujo, F. I., Hirai, F. E., Yu, M. C., Hofling-Lima, A. L., Freitas, D., Sato, E. H. [Distribution of infectious keratitis in a tertiary hospital in Brazil]. Arq Bras Oftalmol. 76 , 370-373 (2013). Ting, D. S. J., et al. Seasonal patterns of incidence, demographic factors and microbiological profiles of infectious keratitis: the Nottingham Infectious Keratitis Study. Eye (Lond) . 35, 2543-2549 (2021). Walkden, A., et al. Association Between Season, Temperature and Causative Organism in Microbial Keratitis in the UK. Cornea . 37 , 1555-1560 (2018). McAllum, P., Bahar, I., Kaiserman, I., Srinivasan, S., Slomovic, A. & Rootman, D. Temporal and seasonal trends in Acanthamoeba keratitis. Cornea . 28 , 7-10 (2009). Green, M., Apel, A. & Stapleton, F. A longitudinal study of trends in keratitis in Australia. Cornea . 27 , 33-39 (2008). Khoo, P., Cabrera-Aguas, M. P., Nguyen, V., Lahra, M. M. & Watson, S. L. Microbial keratitis in Sydney, Australia: risk factors, patient outcomes, and seasonal variation. Graefes Arch Clin Exp Ophthalmol . 258 , 1745-1755 (2020). Kubota, T., Hayashi, S., Niimi, H. & Kitajima, I. Trend Survey of Ocular Infections with Bacteria at Toyama University Hospital Over the Past Six Years. Rinsho Byouri. 60 , 605-611 (2012). Tables Table1. Top Ten Causative Microorganisms Causative organisms Number of cases HSV 104 Corynebacterium spp. 46 CMV 43 MRSA 36 Candida spp. 36 Propionibacterium acnes 32 Acanthamoeba 27 MSSA 26 Pseudomonas aeruginosa 26 VZV 26 Total 402 (80.4%) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4169506","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":289037856,"identity":"4bc5ee38-1edd-456f-90f7-1f736f384d27","order_by":0,"name":"Naoyuki 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21:14:34","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":367942,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of cases of bacterial keratitis by month\u003c/p\u003e\n\u003cp\u003eNumber of infectious keratitis cases per month for MSSA, MRSA, Propionibacterium acnes, Corynebacterium spp., and Pseudomonas aeruginosa. These microbes were among the top 10 causative microorganisms.\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4169506/v1/466235701c1584df56725826.jpg"},{"id":54394984,"identity":"e46aedd2-027a-4889-8de9-d840fbaf83d9","added_by":"auto","created_at":"2024-04-09 21:14:32","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":231721,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of cases of Candida keratitis by month\u003c/p\u003e\n\u003cp\u003eNumber of cases of infectious keratitis per month caused by Candida spp.. Candida was included in the top 10 causative micro-organisms.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4169506/v1/d058b9514b4ec2344d52db13.jpg"},{"id":54394981,"identity":"62ee9e59-1079-42af-a74e-5880765a14f6","added_by":"auto","created_at":"2024-04-09 21:14:32","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":293178,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of cases of viral keratitis by month\u003c/p\u003e\n\u003cp\u003eThe number of infectious keratitis cases per month caused by HSV, VZV, and CMV. These viruses were among the top 10 causative microorganisms.\u003c/p\u003e","description":"","filename":"Figure4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4169506/v1/74dac01d087d752a0802645e.jpg"},{"id":54395004,"identity":"080e634c-8714-4ba8-8904-afdd2551e904","added_by":"auto","created_at":"2024-04-09 21:14:33","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":488446,"visible":true,"origin":"","legend":"\u003cp\u003eMonthly incidence patterns of causative micro-organisms of infectious keratitis (absolute value display).\u003c/p\u003e","description":"","filename":"Figure5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4169506/v1/9a59dd11468172c17e2163cf.jpg"},{"id":54394985,"identity":"0e0ca22f-00d5-4920-b941-76ed63aff84e","added_by":"auto","created_at":"2024-04-09 21:14:33","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":484525,"visible":true,"origin":"","legend":"\u003cp\u003eMonthly incidence patterns of causative micro-organisms of infectious keratitis (monthly relative value display).\u003c/p\u003e","description":"","filename":"Figure6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4169506/v1/d4c4587c9e93a84c2dcb7d0a.jpg"},{"id":57667157,"identity":"29f3962e-2d8a-4b9e-a11c-5cd4f8f44cb5","added_by":"auto","created_at":"2024-06-04 05:24:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2529178,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4169506/v1/813cfa93-7ca6-4f34-aea2-cfb493125517.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Investigating the seasonality of infectious keratitis by pathogen: A retrospective study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe cornea is a transparent avascular tissue located at the surface of the eyeball. It acts as a structural barrier and protects the eye. The cornea is constantly exposed to external stresses, such as trauma and infection.\u0026nbsp;Since the cornea is located along the optical axis, corneal opacity directly leads to loss of vision.\u003c/p\u003e\n\u003cp\u003eInfections caused by pathogenic micro-organisms in the cornea can be defined as infectious keratitis [1].\u0026nbsp;In general, when pathogenic microorganisms establish an infection in the cornea, corneal epithelial defects occur,\u0026nbsp;which progress to corneal ulceration. Corneal perforation may occur in some cases if the corneal stroma melts. Corneal perforation makes it difficult to maintain the shape of the eye shape. Endophthalmitis can occur if the corneal infection spreads to the anterior chamber, vitreous, and retina. Consequently, the risk of blindness is high in such cases. If severe inflammation or prolonged healing occurs, the cornea may get scarred and develop abnormal shape, resulting in reduced transparency and visual impairment\u0026nbsp;[2, 3].\u0026nbsp;Thus, infective keratitis is a serious ocular disease that can lead to corneal melting and perforation in severe cases, resulting in blindness.\u003c/p\u003e\n\u003cp\u003eDiverse microorganisms, including bacteria, fungi, viruses, and amoebas, can cause infectious keratitis. For example, in Japan,\u0026nbsp;the \u0026quot;Guidelines for Clinical Management of Infectious Keratitis (2nd edition),\u0026quot; formulated by the Japanese Ophthalmological Society, lists 28 causative micro-organisms\u0026nbsp;for infectious keratitis\u0026nbsp;[4].\u0026nbsp;Identification of the exact micro-organism that causes infectious keratitis among the 28 species is an arduous task. Several of these 28 species are\u0026nbsp;the common causative microorganisms of infectious keratitis in countries other than Japan.\u003c/p\u003e\n\u003cp\u003eAccurate identification of the causative microorganism is required for selecting the drug to be administered for the treatment of infectious diseases\u0026nbsp;[5]. However, infectious keratitis is an infection of the cornea, a relatively small organ measuring approximately 11 mm in diameter. The amount of sample\u0026nbsp;collected by abrasion of infected foci in the cornea for identification of the\u0026nbsp;causative microorganisms is very small; therefore, the identification rate is never satisfactory\u0026nbsp;[6]. Furthermore, different causative microorganisms may present with similar corneal findings, whereas the same causative microorganism may present with different corneal findings in different cases. In particular, differentiating between bacterial and fungal keratitis on the basis of corneal findings alone is an arduous task. We previously reported that the micro-organism causing infectious keratitis was identified in only 72% cases using culture tests or microscopy\u0026nbsp;[6]. Even with the latest artificial intelligence (AI) technology, the diagnosis of infectious keratitis is limited to differentiating between bacteria, fungi, herpes, and amoebae\u0026nbsp;[7]. Therefore, in the context of infectious diseases, it is advantageous to narrow down the candidate causative microorganisms to select the drug to be administered.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeasonality can be defined as\u0026nbsp;the presence of variations that occur at specific regular intervals\u0026nbsp;of less than a year, such as weekly, monthly, or quarterly.\u0026nbsp;The Japanese Islands extend 3,000 km from north to south, and belong to the\u0026nbsp;subarctic,\u0026nbsp;temperate, and\u0026nbsp;subtropical zones, in that order from north to south. In addition, Japan is surrounded by sea on all sides and is influenced by ocean currents and monsoons, which results in marked seasonal changes in temperature and humidity. Therefore, it can be expected that the microbial world in Japan also varies greatly with seasons.\u003c/p\u003e\n\u003cp\u003ePathogenic microorganisms are those that cause disease in humans. Previous studies have reported that pathogenic microorganisms vary in frequency and exhibit seasonality\u0026nbsp;[8]\u0026nbsp;[9].\u0026nbsp;For example, influenza viruses that cause respiratory infections are prevalent worldwide, mainly during\u0026nbsp;the winter season\u0026nbsp;[10]. In Japan, noroviruses, which causes infectious gastroenteritis, are most common during winter\u0026nbsp;[11]. Seasonality is influenced by climatic, social, behavioral, agricultural, environmental, and immune factors. Several studies from other countries have reported about infectious keratitis and its seasonality\u0026nbsp;[12]\u0026nbsp;[13]\u0026nbsp;[14]\u0026nbsp;[15]\u0026nbsp;[16]\u0026nbsp;[17]\u0026nbsp;[18]. Although there have been reports of a few cases of other ocular infections in Japan, to the best of our knowledge, there have been no reports of numerous cases of infectious keratitis.\u003c/p\u003e\n\u003cp\u003eIn order for infection to be established, the three factors namely \u0026quot;pathogen,\u0026quot; \u0026quot;route of infection\u0026quot; and \u0026quot;host\u0026quot; need to be present.\u003c/p\u003e\n\u003cp\u003eThe development of infectious keratitis is also influenced by the virulence of the pathogen, host immunity, and climatic factors such as temperature and humidity.\u003c/p\u003e\n\u003cp\u003eTherefore, we investigated the seasonality of infectious keratitis by pathogen.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe causative microorganisms included 249 bacteria, 51 fungi, 27 Acanthamoeba, and 173 viruses. A total of 78 causative microorganisms were detected using microbiological culture test, Micro Trak or anterior chamber aqueous\u0026nbsp;polymerase chain reaction (PCR).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe number of cases of infectious keratitis caused by bacteria, fungi, Acanthamoeba, and viruses is shown in Figure 1. The number of cases of infectious keratitis was higher in January (46), February (47), and March (52), and lower in June (33). The number of bacterial infections was highest in October (22), November (22), December (27), January (23), February (24), and March (27). Fungal infections ranged from one to six cases per month with no clear seasonality. The number of cases caused by Acanthamoeba were higher during the summer months of June (4), July (12), and August (4). The number of viral infections was highest in January (18), February (20), March (21), April (17), and May (20). This was based on the data for the top 10 causative organisms, including 80.4% (402/500) of all cases (Table 1). Causative microorganisms ranked \u0026le;11 were classified as others. The top 10 species causing infectious keratitis are listed in Table 1. Of these, the number of cases caused by bacterial species, such as \u0026nbsp;methicillin sensitive Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), Propionibacterium acnes, Corynebacterium spp. and Pseudomonas aeruginosa are shown in Figure 2; those caused by fungal species, such as Candida spp. is shown in Figure 3; those by Acanthamoeba are shown in Figure 1; and those by viruses, such as herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV) are shown in Figure 4. All these 10 causatives microorganisms were among the 28 causative agents listed in the Guidelines for Clinical Management of Infectious Keratitis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMSSA was multimodal and showed no clear seasonality in causing infectious keratitis. The prevalence of MRSA-induced infectious keratitis was higher in January (4), February (4), March (5), April (4), and September (4). Propionibacterium acnes being the cause of infection was higher in March (8), and Corynebacterium spp. was prevalent from January (7) to February (10). Pseudomonas aeruginosa-induced infectious keratitis was higher from August (5) to September (6) (Figure 2). Candida spp. was multimodal and showed no clear seasonality (Figure 3) in causing infection. HSV-induced infectious keratitis was more common in January (14), February (14), and March (14); whereas VZV and CMV were multimodal and showed no clear seasonality (Figure 4). Based on the results of this study, we found monthly incidence patterns of the microorganisms causing infectious keratitis (absolute values displayed in Figure 5, monthly relative values displayed in Figure 6).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we\u0026nbsp;identified the causative\u0026nbsp;microorganisms of infectious keratitis in Japan on a monthly basis. It was evident that the causative microorganisms of infectious keratitis can either be seasonal or non-seasonal. The incidence of infectious keratitis was highest\u0026nbsp;from January to March and lowest in June. The total\u0026nbsp;number of bacteria-induced infectious keratitis cases were high\u0026nbsp;between October and March. Infection caused by Pseudomonas aeruginosa was common from August to September. The fungi were multimodal\u0026nbsp;with no clear seasonality in causing infections. Acanthamoeba infections were common in\u0026nbsp;summer from June to August. Viruses were detected commonly from the samples between January and May. HSV\u0026nbsp;infection was common between January and March. These results indicate a seasonal trend in\u0026nbsp;the incidence of infectious keratitis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSeveral studies from outside Japan have discussed seasonality, and few have evaluated the incidence of infectious keratitis on a monthly basis, as in the present study\u0026nbsp;[12]\u0026nbsp;[13]. A study from Nottingham, England indicated that Gram-positive rods more commonly caused infectious keratitis during the summer season\u0026nbsp;[14]. On the contrary, in this study, Propionibacterium acnes-induced infection was found to be more common in March and Corynebacterium spp.-induced infection in January and February. The aforementioned study also reported that Pseudomonas aeruginosa more commonly caused the infection in summer, which is in line with the present study.\u0026nbsp;A study from Manchester, England reported that Gram-negative bacteria-induced infections were more common during summer and fall seasons\u0026nbsp;[15]. A report from Toronto, Canada showed that Acanthamoeba-induced infectious keratitis were common during the summer season, which is consistent with the present study\u0026nbsp;[16]. Studies from Brisbane and Sydney, Australia demonstrated that Pseudomonas aeruginosa more commonly caused infections during summer, which is consistent with\u0026nbsp;the results of the present study\u0026nbsp;[17]\u0026nbsp;[18]. A report from Southeast India showed that Pseudomonas aeruginosa-induced infectious keratitis was common from July to December, which is partially consistent with\u0026nbsp;the results of the present study\u0026nbsp;[12]. A study from Brazil showed that bacterial infections were common from fall to winter, which is consistent with\u0026nbsp;the results of the present study\u0026nbsp;[13]. However, no reports were found on the seasonality of infectious keratitis in Japan. Although one of the studies focused on bacterial eye infections, which was different from the subject of this study, the bimodality in March and October was partly consistent with the results of this study\u0026nbsp;[19]. Yamaguchi Prefecture, where this study was conducted, is located at 34\u0026deg;N, 131\u0026deg;E\u0026nbsp;and is the westernmost point of Japan\u0026apos;s Honshu Island. Yamaguchi Prefecture is surrounded by\u0026nbsp;sea in three directions, and the four seasons are rich in variation.\u0026nbsp;It is difficult to make comparisons with tropical countries such as India and Brazil because, unlike\u0026nbsp;in Japan, there is little distinction among the four seasons.\u0026nbsp;However, reports from the United Kingdom in the Northern Hemisphere and Australia in the Southern Hemisphere,\u0026nbsp;both of which belong to\u0026nbsp;temperate zones\u0026nbsp;like Yamaguchi, are worth comparing. Therefore, it can be elicited that\u0026nbsp;the increased incidence of infectious keratitis caused by Pseudomonas aeruginosa and Acanthamoeba, as demonstrated in this study, also occurs worldwide\u0026nbsp;during\u0026nbsp;summer. To\u0026nbsp;the best of our knowledge, there\u0026nbsp;are no\u0026nbsp;previous reports on seasonality of viral keratitis.\u0026nbsp;A very high proportion of infectious keratitis\u0026nbsp;cases were caused by viruses; therefore, they were included in this study. We found that HSV-induced keratitis was common between January and May. Furthermore, this study is the first to have determined the monthly frequencies of the 10 most frequent causative microorganisms of infectious keratitis (Figures 5, 6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSince this study was conducted at a university hospital, the severity and timing of disease onset may differ slightly from those in the clinic. It has been observed that mild cases are cured completely in the clinics, while severe cases are transferred to the university hospitals. Therefore, data included in this study may have shifted to the slightly more severe side of infectious keratitis. In addition, the time of onset of keratitis may have been delayed by a few days because this study was conducted at a university hospital rather than at clinics. Since this study involved monthly evaluations, it was considered that there was no significant effect.\u003c/p\u003e\n\u003cp\u003eThe monthly incidence patterns of\u0026nbsp;causative micro-organisms of infectious keratitis (absolute value display) in Figure 5 reflects the true frequency due to display of absolute values. Moreover, comparison between different months could also be performed. However, the difference was difficult to recognize because the scale became smaller\u0026nbsp;each month, which was a disadvantage. The information actually required is the monthly incidence pattern to determine what can be suspected about patients with infectious keratitis who visit the clinic or hospital on any day in a particular month. A relative monthly display\u0026nbsp;is shown in Figure 6.\u0026nbsp;For example, if a patient with infectious keratitis is examined in the month of July, then the vertical column in Figure 6 would reveal that Acanthamoeba has the darkest color and probably caused the infection. Certainly, the corneal findings along with other background and microscopic results are to be considered; but the possibility of Acanthamoeba\u0026nbsp;causing the infection should also be taken into account.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUnlike other studies, inclusion of viral data is required. It is necessary to be able to accurately distinguish\u0026nbsp;between the disease state of infection and non-infection (immunogenicity and\u0026nbsp;wound healing delay) in the cornea as a premise in which these monthly incidence patterns\u0026nbsp;can be used. At the beginning of this study, we envisioned a pollen calendar. Although it is difficult to identify the causative microorganisms in infectious keratitis, we conjectured whether a new tool could be created, which led us to the idea for this study. We contemplate that these monthly incidence patterns\u0026nbsp;will be a useful tool\u0026nbsp;for ophthalmologists in diagnosing infectious keratitis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study is limited by the experience of a single corneal specialist at a single institution. Future national and international studies are required to prove the generalizability of our results at domestic and universal levels.\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eData were retrospectively\u0026nbsp;collected\u0026nbsp;from the medical records of the study participants and examined. This study was approved by the Institutional Review Board of the Yamaguchi University.\u0026nbsp;The\u0026nbsp;School of Medicine complied with the tenets\u0026nbsp;of Declaration of Helsinki while performing this study.\u0026nbsp;The institutional review board\u0026nbsp;approved the use of opt-out consent method.\u0026nbsp;An Informed consent was waived by an institutional review board\u0026nbsp;of the Yamaguchi University Hospital.\u0026nbsp;This study was approved by the Ethical Review Board of the Yamaguchi University Hospital for Research Ethics Committee (REC) (2020-215).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis retrospective study included\u0026nbsp;500 consecutive patients\u0026nbsp;diagnosed with infectious keratitis\u0026nbsp;by a single corneal specialist\u0026nbsp;between\u0026nbsp;January 2009 and January 2021\u0026nbsp;at the\u0026nbsp;Department of Ophthalmology, Yamaguchi University Hospital, Yamaguchi, Japan.\u003c/p\u003e\n\u003cp\u003eSince some cases were bilateral or caused repeated infections in the same eye, there were a total of 500 treatment episodes in 379 patients with 391 eyes. The mean age (\u0026plusmn; standard deviation) of the study population was 63 \u0026plusmn; 22 years, 270:230 for males and females, and 242:258 for the right and left eye, respectively. In principle, the causative microorganisms of infectious keratitis were detected at the time of the first visit using microbiological culture tests of samples obtained from corneal abrasion, discharge, and Contact Lens Preservation Solution, or by Micro Trak (virus-specific antigen test) or anterior chamber aqueous PCR, if viral infection\u0026nbsp;was suspected. However, HSV was defined when clear dendritic or geographic keratitis was confirmed using photographs from a previous physician, whereas pseudodendritic keratitis during or immediately after the onset of herpes zoster was defined as VZV. HSV and VZV cases included not only the epithelial type but also the stromal and endothelial types, which are mainly caused by immune reactions, as well as cases in which these types occurred simultaneously. Once keratitis caused by HSV, VZV, or CMV was diagnosed, subsequent recurrences were considered to be caused by the same virus if the corneal findings were consistent.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe month of onset of infectious keratitis (mainly the date of examination when the causative microorganisms were identified) was retrospectively examined.\u003c/p\u003e\n\u003cp\u003eIf several causative microorganisms were detected in the same eye on the same day, one was chosen based on the corneal findings. For example, when Pseudomonas aeruginosa and\u0026nbsp;Enterobacter cloacae complex were detected, infection by Pseudomonas aeruginosa was assumed if corneal findings such as ring-shaped abscesses were evident.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe monthly incidence patterns\u0026nbsp;of\u0026nbsp;the\u0026nbsp;causative microorganisms of infectious keratitis\u0026nbsp;were created using PowerPoint (Microsoft). For monthly incidence patterns of\u0026nbsp;causative micro-organisms of infectious keratitis (absolute value display), the color of cells in December of Others with the highest number of cases (15) by month for each causative micro-organisms is shown as \u0026quot;black, 0% transparency\u0026quot; (i.e., black), and the color of the cells in months with zero cases is shown as \u0026quot;black, 100% transparency\u0026quot; (i.e., white). For monthly incidence patterns of\u0026nbsp;causative micro-organisms of infectious keratitis (monthly relative value display), the cells of causative micro-organisms with the highest number of cases in each month are colored \u0026quot;black, 0% transparency\u0026quot; (i.e., black), and the cells of months with zero cases are colored \u0026quot;black, 100% transparency\u0026quot; (i.e., white).\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements (optional):\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Editage (www.editage.jp) for English language editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eN.Y. conceived and designed the study. N.Y., N.I., A.S., J.S., R.A., F.H., T.Y., T.N., and Y.M. performed data collection. N.Y. performed analysis. N.Y. drafted the manuscript, and K.K edited it.\u003c/p\u003e\n\u003cp\u003eAll authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Information (including a Competing Interests Statement):\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSean, L., Edelstein, P. W., Andrew, J. W. \u0026amp; Huang. Bacterial Keratitis. In: Jay H Krachmer MJM, Edward J Holland, editor. CORNEA. 1. THIRD ed: MOSBY ELSEVIER; 2011. p. 919-44.\u003c/li\u003e\n\u003cli\u003eKhor, W. B., et al. 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Seasonal trends of microbial keratitis in South India. \u003cem\u003eCornea\u003c/em\u003e. \u003cstrong\u003e31\u003c/strong\u003e, 1123-1127 (2012).\u003c/li\u003e\n\u003cli\u003eMarujo, F. I., Hirai, F. E., Yu, M. C., Hofling-Lima, A. L., Freitas, D., Sato, E. H. [Distribution of infectious keratitis in a tertiary hospital in Brazil]. \u003cem\u003eArq Bras Oftalmol.\u003c/em\u003e\u003cstrong\u003e76\u003c/strong\u003e, 370-373 (2013).\u003c/li\u003e\n\u003cli\u003eTing, D. S. J., et al. Seasonal patterns of incidence, demographic factors and microbiological profiles of infectious keratitis: the Nottingham Infectious Keratitis Study. \u003cem\u003eEye (Lond)\u003c/em\u003e. \u003cstrong\u003e35,\u003c/strong\u003e 2543-2549 (2021).\u003c/li\u003e\n\u003cli\u003eWalkden, A., et al. Association Between Season, Temperature and Causative Organism in Microbial Keratitis in the UK. \u003cem\u003eCornea\u003c/em\u003e. \u003cstrong\u003e37\u003c/strong\u003e, 1555-1560 (2018).\u003c/li\u003e\n\u003cli\u003eMcAllum, P., Bahar, I., Kaiserman, I., Srinivasan, S., Slomovic, A. \u0026amp; Rootman, D. Temporal and seasonal trends in Acanthamoeba keratitis. \u003cem\u003eCornea\u003c/em\u003e. \u003cstrong\u003e28\u003c/strong\u003e, 7-10 (2009).\u003c/li\u003e\n\u003cli\u003eGreen, M., Apel, A. \u0026amp; Stapleton, F. A longitudinal study of trends in keratitis in Australia. \u003cem\u003eCornea\u003c/em\u003e. \u003cstrong\u003e27\u003c/strong\u003e, 33-39 (2008).\u003c/li\u003e\n\u003cli\u003eKhoo, P., Cabrera-Aguas, M. P., Nguyen, V., Lahra, M. M. \u0026amp; Watson, S. L. Microbial keratitis in Sydney, Australia: risk factors, patient outcomes, and seasonal variation. \u003cem\u003eGraefes Arch Clin Exp Ophthalmol\u003c/em\u003e. \u003cstrong\u003e258\u003c/strong\u003e, 1745-1755 (2020).\u003c/li\u003e\n\u003cli\u003eKubota, T., Hayashi, S., Niimi, H. \u0026amp; Kitajima, I. Trend Survey of Ocular Infections with Bacteria at Toyama University Hospital Over the Past Six Years. \u003cem\u003eRinsho Byouri.\u003c/em\u003e\u003cstrong\u003e60\u003c/strong\u003e, 605-611 (2012).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable1. Top Ten Causative Microorganisms\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"331\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003eCausative organisms\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003eNumber of cases\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003eHSV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003eCorynebacterium spp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\"\u003e\n \u003cp\u003eCMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003eMRSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003eCandida spp.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003ePropionibacterium acnes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003eAcanthamoeba\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003eMSSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\" valign=\"bottom\"\u003e\n \u003cp\u003ePseudomonas aeruginosa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\"\u003e\n \u003cp\u003eVZV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"57.70392749244713%\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.29607250755287%\" valign=\"bottom\"\u003e\n \u003cp\u003e402 (80.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4169506/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4169506/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"This study aimed to investigate the seasonal trends in infectious keratitis by assessing the month of onset and causative microorganisms. Five hundred consecutive cases of infectious keratitis that were diagnosed and treated by a corneal specialist at the Department of Ophthalmology, Yamaguchi University Hospital between January 2009 and January 2021 in whom micro-organisms could be identified formed the study population. The month of onset of infectious keratitis was retrospectively examined based on the medical records. The causative microorganisms were bacteria in 249 eyes, fungi in 51 eyes, Acanthamoeba in 27 eyes, and viruses in 173 eyes. The top 10 causative microorganisms accounted for 402 of 500 eyes (80.4% of the total). The incidence of infectious keratitis was highest from January to March and lowest in June. The total number of bacterial-induced infections was high between October and March. Pseudomonas aeruginosa commonly caused infectious keratitis from August to September. Acanthamoeba-induced infection was common in summer from June to August. HSV infections were common between January and May. A seasonal trend was observed in the occurrence of infectious keratitis by examining the months of onset. We contemplate that these results will assist ophthalmologists in diagnosing infectious keratitis.","manuscriptTitle":"Investigating the seasonality of infectious keratitis by pathogen: A retrospective study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-09 21:14:22","doi":"10.21203/rs.3.rs-4169506/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3a2ab619-66fd-481f-ad3c-788eeda5a580","owner":[],"postedDate":"April 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":30433767,"name":"Health sciences/Diseases/Eye diseases"},{"id":30433768,"name":"Health sciences/Diseases/Infectious diseases"}],"tags":[],"updatedAt":"2024-06-04T05:08:27+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-09 21:14:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4169506","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4169506","identity":"rs-4169506","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}