Blepharoconjunctivitis mimicking conjunctival tumor associated with Streptococcus intermedius sinusitis: case report and literature review

Blepharoconjunctivitis mimicking conjunctival tumor associated with Streptococcus intermedius sinusitis: case report and literature review | 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 Case Report Blepharoconjunctivitis mimicking conjunctival tumor associated with Streptococcus intermedius sinusitis: case report and literature review Daiki Ishio, Hiroshi Eguchi, Fumika Hotta, Tatsuro Miyamoto This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7487786/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Streptococcus intermedius , a commensal bacterium in the human oral cavity, can occasionally cause severe infections in deep tissues. Here, we report the first known case of infectious blepharoconjunctivitis associated with S. intermedius sinusitis mimicking a conjunctival tumor. Smear microscopy of the eye and nasal discharge was useful for the differential diagnosis. Metagenomic analysis using MinION as adjunctive diagnostic tool has contributed to rigorous species identification of the pathogenic strain. Streptococcus intermedius blepahroconjunctivitis sinusitis smear microscopy MinION Figures Figure 1 Figure 2 Figure 3 Figure 4 Case presentation An 84-year-old woman presented with chronic epiphora and discharge in her right eye that persisted for several years. Three weeks prior to referral to our hospital, she visited a local ophthalmic practitioner and was suspected to have a conjunctival tumor due to redness, swelling, and mass formation in the right palpebral conjunctiva. During her initial visit, her right upper eyelid appeared deformed and contracted, resulting in lagophthalmos. The palpebral conjunctiva was hyperemic with an associated mass. Microscopic examination of the right eye using slit lamp revealed conjunctival hyperemia, vascularization, and inflammatory cell infiltration in the cornea (Fig. 1 ). The upper eyelid appears deformed by upward traction, a large amount of eye discharge, conjunctival hyperemia, and palpebral conjunctival mass formation. The cornea is opaque due to inflammatory cell infiltration and vascularization. A large amount of mucopurulent discharge was present in the right eye, accompanied by a significant amount of purulent nasal discharge. During the examination, the patient constantly sniffled and spoke in a nasal voice. Both eyes had advanced cataracts which rendered the fundus invisible. Smear microscopy of the eye and nasal discharge revealed Gram-positive cocci in the chain, which appeared reddish in color due to excessive depigmentation (Fig. 2 ). Multiple polynuclear leukocytes and Gram-positive cocci in chains, appearing reddish due to excessive depigmentation, are present in eye discharge. The mass in the right palpebral conjunctiva was diagnosed as inflammatory granuloma secondary to streptococcal infection, which extended from the nasal cavity to the ocular surface. Topical cephem and systemic penicillin administration was initiated. Specifically, the patient received frequent administration of cefmenoxime hydrochloride eye drops (Bestron® for ophthalmic 0.5%, Senju Pharmaceutical Co., Ltd., Japan) and 750 g amoxicillin hydrate (amoxicillin capsules, Nich-Iko Pharmaceutical Co., Ltd., Japan). The definitive diagnosis of sinusitis was made by the otolaryngology department based on the CT imaging of the sinus cavities. Bacterial cultures from both eye and nasal discharge yielded α- Streptococcus . Furthermore, 16S meta-analysis using MinION revealed that 96.1% of the 53,378 bacterial reads corresponded to S. intermedius (Fig. 3 and Supplementary file). The overwhelming majority (96.1%) of reads are for Streptococcus intermedius . The isolate was susceptible to all tested antibiotics except aminoglycosides, to which Streptococcus is naturally resistant. (Table 1 ). One month after treatment, infections of the ocular surface, eyelids, and sinusitis were successfully eradicated, and conjunctival granuloma resolved. Subsequently, the patient underwent penetrating keratoplasty concurrent with cataract extraction and intraocular lens implantation in the right eye, blepharoplasty of the right upper eyelid, and cataract extraction with intraocular lens implantation in the left eye to address the corneal opacity and bilateral cataracts. Nine months after the surgery, the patient’s lagophthalmos improved, visual acuity was restored in both eyes, and no recurrence of sinusitis or blepharoconjunctivitis was observed (Fig. 4 ). Currently, the patient is scheduled to undergo oculoplastic surgery for cosmetic purposes. Table 1 Minimum inhibitory concentration values measured by E-test Drugs MIC(µg/ml) Susceptibility benzylpenicillin 2.0 S ceftazidime 0.5 S ceftriaxone 0.032 S erythromycin 0.032 S azithromycin 0.25 S norfloxacin 4.0 S levofloxacin 0.5 S tobramycin 32 R chloramphenicol 2.0 S teicoplanin 0.032 S vancomycin 1.0 S daptomycin 0.5 S tigecycline 0.032 S linezolid 0.5 S meropenem 0.016 S S: susceptible, R: resistance, Although the upper eyelid remains slightly constricted, the infectious symptoms on the ocular surface have disappeared, the cornea has healed, and eyelid granulomas have disappeared. Discussion Currently, seven cases of S. intermedius infection in the human eye [ 1 – 7 ]. Five cases involved endophthalmitis, one involved dacryocystitis with an orbital abscess, and one involved superior orbital fissure syndrome (Table 2 ). To the best of our knowledge, there are no previous reports of S. intermedius blepharoconjunctivitis associated with sinusitis. In the present case, S. intermedius sinusitis was left untreated, and the inflammation spread to periorbital tissues, such as the maxillary sinus, frontal sinus, and lacrimal sac, resulting in blepharoconjunctivitis and corneal opacity. S. intermedius sinusitis likely preceded and complicated the blepharoconjunctivitis. As S. intermedius sinusitis has been reported more frequently than ocular infections, there may have been prior cases of blepharoconjunctivitis due to S. intermedius sinusitis, similar to the current case, which has not been reported. However, the patient in this case first visited an ophthalmic practitioner and was then referred to our hospital for treatment. Sinusitis was suspected as the cause of blepharoconjunctivitis and the patient was referred to an otolaryngologist who made a definitive diagnosis of sinusitis. This is the first known case report in which an ophthalmologist considered that S. intermedius blepharoconjunctivitis may have originated from an infection of other organs. Table 2 Streptococcus intermedius infections in human ocular tissue Authors Year Age/ Gender Tentative diagnosis Drugs administered* Response to initial therapy Definitive diagnosis Microorganism identification Therapeutic intervention Outcome Mochizuki K, et al 1 2009 33/F blebitis topical LVFX and SBPC subconjunctival GM, iv CPR poor bleb-related endophthalmitis vitreous culture DNA sequencing vitrectomy i-vit VCM and CAZ healed Sun S, et al 2 2010 50/M mycotic endophthalmitis i-vit AMP-B, FLCZ, and GFLX poor endophthalmitis vitreous culture i-vit CPFX, TOB healed Mali OJ, et al 3 2015 50s/F acute anterior uveitis topical corticosteroids cycloplegics poor endophthalmitis iris abscess smear AH † culture AH † irrigation, i-vit VCM and CLDM, ST ‡ healed Martel A 4 2018 86/M superior orbital fissure syndrome iv CVA/AMPC good superior orbital fissure syndrome blood culture not done healed Lee T, et al 5 2022 62/M endophthalmitis i-vit VCM and CAZ good endophthalmitis vitreous culture vitreous tap KPro § replacement healed Takahashi Y, et al 6 2022 48/F orbital abscess dacryocystitis iv TAZ/PIPC good orbital abscess dacryocystitis pus culture dacryocystorhinostomy sinus surgery healed Mercer GD, et al 7 2022 91/F vitreous hemorrhage i-vit VCM and CAZ poor endophthalmitis vitreous culture vitrectomy healed The current report 2025 84/F conjunctival tumor AMPC capsules topical CMX good blepharoconjunctivitis sinusitis smear, culture 16S meta-analysis keratoplasty, cataract surgery, and blepharoplasty healed The abbreviations iv and i-vit denote intravenous and intravitreal, respectively. Abbreviations of antimicrobial agents are as follows: LVFX, levofloxacin; SBPC, sulbenicillin; AMPH-B, amphotericin B; FLCZ, fluconazole; GFLX, gatifloxacin; CPR, cefpirome; VMC, vancomycin; CAZ, ceftazidime; CPFX, ciprofloxacin; TOB, tobramycin; CLDM, clindamycin; ST, sulfamethoxazole-trimethoprim; CVA/AMPC, clavulanic acid/amoxicillin; TAZ/PIPC, tazobactam/piperacillin; CTRX, ceftriaxone; CMX, cefmenoxime †AH denotes aqueous humor. ‡Details of the administration method are not stated; it is assumed to be oral. § KPro denotes keratoprosthesis implantation The patients in the seven cases reported to date ranged in age from 33 to 91 years, with a wide age distribution. There were three males and four females. No clear evidence has been found to explain the sex differences. Four patients [ 1 – 3 , 7 ] showed a poor response to initial treatment, two patients [ 3 , 7 ] were suspected to have non-infectious diseases and received empirical treatment. Two [ 1 , 2 ] patients were diagnosed with infection but were treated empirically with antimicrobial agents to which the S. intermedius isolates were not susceptible. In all cases, S. intermedius was detected in specimens obtained during subsequent therapeutic interventions and infections were treated with antibiotics to which the isolates were susceptible. Conjunctival tumor was initially suspected in the present case. If the palpebral conjunctiva had been excised for early diagnosis without suspicion of infection, the tumor would not have healed, and the patient could have developed bacteraemia [ 8 – 9 ]. We identified the infection through detailed slit-lamp microscopic examination and smear microscopy of both the eye and nasal discharge, which allowed us to appropriately prioritize medical treatment over surgery in a very elderly patient with active sinusitis and infection of the anterior and external ocular tissues. Although the culture of specimens is useful, it is usually time-consuming, and some S. intermedius strains are difficult to culture. This case demonstrates the importance of not ruling out infection based on clinical findings and the importance of performing smear microscopy of clinical specimens when infection is suspected. Streptococcus spp. can be easily identified using smear microscopy. Most Streptococcus spp. are susceptible to cephems, penicillin, or glycopeptides, making them the first line of empiric therapy. Consequently, this is often consistent with definitive therapy. In the case of an iris abscess [ 3 ] initially diagnosed as non-infectious uveitis, surgical removal of the abscess and Gram staining identified an infection caused by Gram-positive cocci in chains, leading to a change in treatment with good outcomes. The visual prognosis of seven patients reported in previous studies describing S. intermedius ocular infections was relatively good. However, to improve prognosis, infection should be suspected when the patient is first seen, and specimens should be collected for smear microscopy and culture. If S. intermedius is detected, administration of first-line drugs, such as penicillin, cephem, and glycopeptides, is crucial. In samples with high and complex biomass, such as the gut and oral cavity, a comparison of the relative abundance of bacterial reads in the sample is meaningful. However, in samples with low biomass, such as the ocular surface, differences in sample collection methods, research protocols, and contamination during experiments may have a disproportionate effect and significant impact on the analysis results [ 10 ]. Therefore, there are fewer reports on microbiome analyses in ophthalmology than in other fields. However, metagenomic analysis using MinION is applicable for acute keratoconjunctivitis and is useful for identifying pathogenic bacteria when combined with smear microscopy and culture [ 11 ]. In addition, rigorous species identification could not be performed using sample culture, but reliable results were obtained with MinION. This study had several limitations. S. intermedius ocular infections have a relatively good prognosis, and many cases are likely managed empirically, leading to a lack of rigorous species identification. Thus, there may have been previously unreported cases of Streptococcous spp. infection in the external and anterior ocular areas of patients with sinusitis, as in the current case. Additional diagnoses of S. intermedius ocular infections based on rigorous species identification should be considered in the future. In conclusion, infectious blepharoconjunctivitis associated with S. intermedius sinusitis can present conjunctival tumor. In such cases, smear microscopy of the eye and nasal discharge is crucial for differential diagnosis. Cephem eye drops and intravenous infusions are also useful treatment options. To the best of our knowledge, this is the first known case of S. intermedius blepahroconjunctivitis associated with sinusitis confirmed by metagenomic analysis using a nanopore sequencer (MinION). Declarations Ethics approval and consent to participate: The present study followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of the Kindai University Faculty of Medicine (approval no. 28–137). The patient in this case provided consent to participate and allowed us to use her health data in this study. There were no name tags or identification of the information disclosed in this study. Consent for publication: Written informed consent was obtained from the patient for publication of this case and the accompanying images. Competing interests: The authors declare no competing interest. Funding: The authors declare no funding was received for this case report. Author Contribution DI and HE treated the patient and wrote the draft; FH and HE performed 16S meta-analysis using MinION; TM measured the minimum inhibitory concentrations; HE performed the literature review and supervised this case report. All the authors have read and approved the manuscript. Acknowledgement We would like to thank Professor Shigeru Yoshida, Kurume University, and Professor Shunji Kusaka, Kindai University, for creating the environment in which the first author's DI treated this patient. We would like to thank Editage (www.editage.jp) for the English language editing. Data Availability Research data supporting this publication are available from corresponding author. References Mochizuki K, Kumada M, Suemori S, Kawakami H, Sawada A, Yamamot T, Mikamo H. Streptococcus intermedius -associated late-onset endophthalmitis after trabeculectomy with adjunctive mitomycin C. J Glaucoma. 2009;18(1):79–80. Sun S, Yuan G, Zhao G, Chen H, Yu B. Endophthalmitis caused by Phialophora verrucose and Streptococcus intermedius : a case report. Med Mycol. 2010;48(8):1108–11. 10.1097/IJG.0b013e318170a732 . Mali JO, Falk NS, Mali YP, Mencias L. Endogenous endophthalmitis with iris abscess after routine dental cleaning. JAMA Ophthalmol. 2015;133(5):616–7. Martel A. Septic thrombosis of cavernous sinus extended to the ipsilateral internal jugular vein and transversal sinus with favorable outcome: Clinical and radiological features of Lemierre syndrome. Orbit. 2018;37(2):94–6. Lee T, Robbins CB, Wisely CE, Grewal DS, Daluvoy MB, Fekrat S. Clinical characteristics and visual outcomes in endophthalmitis after keratoprosthesis implantation. Retina. 2022;42(2):321–7. Takahashi Y, Kono S, Yokoyama T, Kuruma T, Vaidya A, Kakizaki H. Orbital abscess developed apart from paranasal sinusitis and dacryocystitis in fibrous dyspasia. Cureus. 2022;14(6):e26061. 10.7759/cureus.26061 . Mecer GD, Politis M, Campagnoli TR, Galic IJ, Chen JC. Delayed-onset Streptococcus intermedius endophthalmitis following ant-vascular endothelial growth factor intravitreal injection. Retina Cases Brief Rep. 2022;16(6):688–90. Morrow M, Ogino M, Shah A, Ning J. Extensive invasive sinusitis secondary to Streptococcus intermedius infection. Clin Med Res. 2024;22(3):160–4. Livingston LV, Perez-Colon E. Streptococcus intermedius bacteremia and liver abscess following a routine dental cleaning. Case Rep Infect Dis. 2014;2014:954046. Eguchi H, Ozkan J, Holland MJ, Editorial. Next-generation sequencing in ophthalmology: The microbiome in ocular health and disease. Front Cell Infect Microbiol. 2022;12:1080932. Eguchi H, Hotta F, Kusaka S. Applying metagenomic analysis using nanopore sequencer (MinION) for precision medicine in bacterial keratoconjunctivitis: comprehensive validation if molecular biological and conventional examinations. Int J Mol Sci. 2023;30(3):2611. Additional Declarations No competing interests reported. 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2","display":"","copyAsset":false,"role":"figure","size":110561,"visible":true,"origin":"","legend":"\u003cp\u003eGram-stained images of the eye discharge\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7487786/v1/aa8b4deac499e0925de4aee0.jpeg"},{"id":93013893,"identity":"f4fe9f0a-dae5-4d99-a0ce-0711afb971e4","added_by":"auto","created_at":"2025-10-08 07:32:11","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":260004,"visible":true,"origin":"","legend":"\u003cp\u003eRelative abundance of 16S rDNA reads in eye discharge\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7487786/v1/e83106dc54ad9d66aeb9d2d1.jpeg"},{"id":93013207,"identity":"8f1e20ff-7393-48aa-b661-ed8f04223335","added_by":"auto","created_at":"2025-10-08 07:24:11","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":218107,"visible":true,"origin":"","legend":"\u003cp\u003ePost-surgical anterior segment picture of the right eye\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7487786/v1/d7b6624b50f91e7284a923d8.png"},{"id":93014695,"identity":"8f0775d0-bc89-410e-972a-c20f91018ed3","added_by":"auto","created_at":"2025-10-08 07:40:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1283241,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7487786/v1/12247991-39cc-4d65-8cb0-80629e822bc8.pdf"},{"id":93013210,"identity":"57d9e839-6ec3-4690-ac5d-f8b07ff61e64","added_by":"auto","created_at":"2025-10-08 07:24:11","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":11802,"visible":true,"origin":"","legend":"","description":"","filename":"SupplefileStr.intermediusforBMCInfectDis.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7487786/v1/bc020715fea72915e264412d.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eBlepharoconjunctivitis mimicking conjunctival tumor associated with\u003cem\u003e Streptococcus intermedius\u003c/em\u003e sinusitis: case report and literature review\u003c/p\u003e","fulltext":[{"header":"Case presentation","content":"\u003cp\u003eAn 84-year-old woman presented with chronic epiphora and discharge in her right eye that persisted for several years. Three weeks prior to referral to our hospital, she visited a local ophthalmic practitioner and was suspected to have a conjunctival tumor due to redness, swelling, and mass formation in the right palpebral conjunctiva. During her initial visit, her right upper eyelid appeared deformed and contracted, resulting in lagophthalmos. The palpebral conjunctiva was hyperemic with an associated mass. Microscopic examination of the right eye using slit lamp revealed conjunctival hyperemia, vascularization, and inflammatory cell infiltration in the cornea (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe upper eyelid appears deformed by upward traction, a large amount of eye discharge, conjunctival hyperemia, and palpebral conjunctival mass formation. The cornea is opaque due to inflammatory cell infiltration and vascularization.\u003c/p\u003e\u003cp\u003eA large amount of mucopurulent discharge was present in the right eye, accompanied by a significant amount of purulent nasal discharge. During the examination, the patient constantly sniffled and spoke in a nasal voice. Both eyes had advanced cataracts which rendered the fundus invisible. Smear microscopy of the eye and nasal discharge revealed Gram-positive cocci in the chain, which appeared reddish in color due to excessive depigmentation (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eMultiple polynuclear leukocytes and Gram-positive cocci in chains, appearing reddish due to excessive depigmentation, are present in eye discharge.\u003c/p\u003e\u003cp\u003eThe mass in the right palpebral conjunctiva was diagnosed as inflammatory granuloma secondary to streptococcal infection, which extended from the nasal cavity to the ocular surface. Topical cephem and systemic penicillin administration was initiated. Specifically, the patient received frequent administration of cefmenoxime hydrochloride eye drops (Bestron\u0026reg; for ophthalmic 0.5%, Senju Pharmaceutical Co., Ltd., Japan) and 750 g amoxicillin hydrate (amoxicillin capsules, Nich-Iko Pharmaceutical Co., Ltd., Japan). The definitive diagnosis of sinusitis was made by the otolaryngology department based on the CT imaging of the sinus cavities. Bacterial cultures from both eye and nasal discharge yielded α-\u003cem\u003eStreptococcus\u003c/em\u003e. Furthermore, 16S meta-analysis using MinION revealed that 96.1% of the 53,378 bacterial reads corresponded to \u003cem\u003eS. intermedius\u003c/em\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Supplementary file).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe overwhelming majority (96.1%) of reads are for \u003cem\u003eStreptococcus intermedius\u003c/em\u003e.\u003c/p\u003e\u003cp\u003eThe isolate was susceptible to all tested antibiotics except aminoglycosides, to which \u003cem\u003eStreptococcus\u003c/em\u003e is naturally resistant. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). One month after treatment, infections of the ocular surface, eyelids, and sinusitis were successfully eradicated, and conjunctival granuloma resolved. Subsequently, the patient underwent penetrating keratoplasty concurrent with cataract extraction and intraocular lens implantation in the right eye, blepharoplasty of the right upper eyelid, and cataract extraction with intraocular lens implantation in the left eye to address the corneal opacity and bilateral cataracts. Nine months after the surgery, the patient\u0026rsquo;s lagophthalmos improved, visual acuity was restored in both eyes, and no recurrence of sinusitis or blepharoconjunctivitis was observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Currently, the patient is scheduled to undergo oculoplastic surgery for cosmetic purposes.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMinimum inhibitory concentration values measured by E-test\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDrugs\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMIC(\u0026micro;g/ml)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSusceptibility\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ebenzylpenicillin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eceftazidime\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eceftriaxone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eerythromycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eazithromycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003enorfloxacin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003elevofloxacin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003etobramycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eR\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003echloramphenicol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eteicoplanin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003evancomycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003edaptomycin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003etigecycline\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003elinezolid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emeropenem\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eS\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eS: susceptible, R: resistance,\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAlthough the upper eyelid remains slightly constricted, the infectious symptoms on the ocular surface have disappeared, the cornea has healed, and eyelid granulomas have disappeared.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCurrently, seven cases of \u003cem\u003eS. intermedius\u003c/em\u003e infection in the human eye [\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Five cases involved endophthalmitis, one involved dacryocystitis with an orbital abscess, and one involved superior orbital fissure syndrome (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). To the best of our knowledge, there are no previous reports of \u003cem\u003eS. intermedius\u003c/em\u003e blepharoconjunctivitis associated with sinusitis. In the present case, \u003cem\u003eS. intermedius\u003c/em\u003e sinusitis was left untreated, and the inflammation spread to periorbital tissues, such as the maxillary sinus, frontal sinus, and lacrimal sac, resulting in blepharoconjunctivitis and corneal opacity. \u003cem\u003eS. intermedius\u003c/em\u003e sinusitis likely preceded and complicated the blepharoconjunctivitis. As \u003cem\u003eS. intermedius\u003c/em\u003e sinusitis has been reported more frequently than ocular infections, there may have been prior cases of blepharoconjunctivitis due to \u003cem\u003eS. intermedius\u003c/em\u003e sinusitis, similar to the current case, which has not been reported. However, the patient in this case first visited an ophthalmic practitioner and was then referred to our hospital for treatment. Sinusitis was suspected as the cause of blepharoconjunctivitis and the patient was referred to an otolaryngologist who made a definitive diagnosis of sinusitis. This is the first known case report in which an ophthalmologist considered that \u003cem\u003eS. intermedius\u003c/em\u003e blepharoconjunctivitis may have originated from an infection of other organs.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cem\u003eStreptococcus intermedius\u003c/em\u003e infections in human ocular tissue\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthors\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYear\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAge/\u003c/p\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTentative diagnosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eDrugs administered*\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eResponse to initial therapy\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eDefinitive diagnosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eMicroorganism identification\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eTherapeutic intervention\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c10\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMochizuki K, et al\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33/F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eblebitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003etopical LVFX and SBPC\u003c/p\u003e\u003cp\u003esubconjunctival GM, iv CPR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003epoor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ebleb-related endophthalmitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003evitreous culture\u003c/p\u003e\u003cp\u003eDNA sequencing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003evitrectomy\u003c/p\u003e\u003cp\u003ei-vit VCM and CAZ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ehealed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSun S, et al\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50/M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003emycotic endophthalmitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ei-vit AMP-B, FLCZ, and GFLX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003epoor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eendophthalmitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003evitreous culture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ei-vit CPFX, TOB\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ehealed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMali OJ, et al\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2015\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50s/F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eacute anterior\u003c/p\u003e\u003cp\u003euveitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003etopical corticosteroids\u003c/p\u003e\u003cp\u003ecycloplegics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003epoor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eendophthalmitis\u003c/p\u003e\u003cp\u003eiris abscess\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003esmear\u003c/p\u003e\u003cp\u003eAH\u003csup\u003e\u0026dagger;\u003c/sup\u003e culture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003eAH\u003csup\u003e\u0026dagger;\u003c/sup\u003e irrigation,\u003c/p\u003e\u003cp\u003ei-vit VCM and CLDM, ST\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ehealed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMartel A\u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86/M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003esuperior orbital\u003c/p\u003e\u003cp\u003efissure syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eiv CVA/AMPC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003egood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003esuperior orbital\u003c/p\u003e\u003cp\u003efissure syndrome\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eblood culture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003enot done\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ehealed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLee T, et al\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62/M\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eendophthalmitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ei-vit VCM and CAZ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003egood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eendophthalmitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003evitreous culture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003evitreous tap\u003c/p\u003e\u003cp\u003eKPro\u003csup\u003e\u0026sect;\u003c/sup\u003e replacement\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ehealed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTakahashi Y, et al\u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48/F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eorbital abscess\u003c/p\u003e\u003cp\u003edacryocystitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eiv TAZ/PIPC\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003egood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eorbital abscess\u003c/p\u003e\u003cp\u003edacryocystitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003epus culture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003edacryocystorhinostomy sinus surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ehealed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMercer GD, et al\u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91/F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003evitreous hemorrhage\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ei-vit VCM and CAZ\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003epoor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eendophthalmitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003evitreous culture\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003evitrectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ehealed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThe current report\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e84/F\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003econjunctival tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eAMPC capsules\u003c/p\u003e\u003cp\u003etopical CMX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003egood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003eblepharoconjunctivitis\u003c/p\u003e\u003cp\u003esinusitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003esmear, culture\u003c/p\u003e\u003cp\u003e16S meta-analysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003ekeratoplasty, cataract surgery, and blepharoplasty\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c10\"\u003e\u003cp\u003ehealed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003eThe abbreviations iv and i-vit denote intravenous and intravitreal, respectively. Abbreviations of antimicrobial agents are as follows: LVFX, levofloxacin; SBPC, sulbenicillin; AMPH-B, amphotericin B; FLCZ, fluconazole; GFLX, gatifloxacin; CPR, cefpirome; VMC, vancomycin; CAZ, ceftazidime; CPFX, ciprofloxacin; TOB, tobramycin; CLDM, clindamycin; ST, sulfamethoxazole-trimethoprim; CVA/AMPC, clavulanic acid/amoxicillin; TAZ/PIPC, tazobactam/piperacillin; CTRX, ceftriaxone; CMX, cefmenoxime\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003e\u0026dagger;AH denotes aqueous humor. \u0026Dagger;Details of the administration method are not stated; it is assumed to be oral. \u0026sect; KPro denotes keratoprosthesis implantation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe patients in the seven cases reported to date ranged in age from 33 to 91 years, with a wide age distribution. There were three males and four females. No clear evidence has been found to explain the sex differences. Four patients [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] showed a poor response to initial treatment, two patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] were suspected to have non-infectious diseases and received empirical treatment. Two [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] patients were diagnosed with infection but were treated empirically with antimicrobial agents to which the \u003cem\u003eS. intermedius\u003c/em\u003e isolates were not susceptible. In all cases, \u003cem\u003eS. intermedius\u003c/em\u003e was detected in specimens obtained during subsequent therapeutic interventions and infections were treated with antibiotics to which the isolates were susceptible.\u003c/p\u003e\u003cp\u003eConjunctival tumor was initially suspected in the present case. If the palpebral conjunctiva had been excised for early diagnosis without suspicion of infection, the tumor would not have healed, and the patient could have developed bacteraemia [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. We identified the infection through detailed slit-lamp microscopic examination and smear microscopy of both the eye and nasal discharge, which allowed us to appropriately prioritize medical treatment over surgery in a very elderly patient with active sinusitis and infection of the anterior and external ocular tissues. Although the culture of specimens is useful, it is usually time-consuming, and some \u003cem\u003eS. intermedius\u003c/em\u003e strains are difficult to culture. This case demonstrates the importance of not ruling out infection based on clinical findings and the importance of performing smear microscopy of clinical specimens when infection is suspected. \u003cem\u003eStreptococcus\u003c/em\u003e spp. can be easily identified using smear microscopy. Most \u003cem\u003eStreptococcus\u003c/em\u003e spp. are susceptible to cephems, penicillin, or glycopeptides, making them the first line of empiric therapy. Consequently, this is often consistent with definitive therapy. In the case of an iris abscess [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] initially diagnosed as non-infectious uveitis, surgical removal of the abscess and Gram staining identified an infection caused by Gram-positive cocci in chains, leading to a change in treatment with good outcomes. The visual prognosis of seven patients reported in previous studies describing \u003cem\u003eS. intermedius\u003c/em\u003e ocular infections was relatively good. However, to improve prognosis, infection should be suspected when the patient is first seen, and specimens should be collected for smear microscopy and culture. If \u003cem\u003eS. intermedius\u003c/em\u003e is detected, administration of first-line drugs, such as penicillin, cephem, and glycopeptides, is crucial.\u003c/p\u003e\u003cp\u003eIn samples with high and complex biomass, such as the gut and oral cavity, a comparison of the relative abundance of bacterial reads in the sample is meaningful. However, in samples with low biomass, such as the ocular surface, differences in sample collection methods, research protocols, and contamination during experiments may have a disproportionate effect and significant impact on the analysis results [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Therefore, there are fewer reports on microbiome analyses in ophthalmology than in other fields. However, metagenomic analysis using MinION is applicable for acute keratoconjunctivitis and is useful for identifying pathogenic bacteria when combined with smear microscopy and culture [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In addition, rigorous species identification could not be performed using sample culture, but reliable results were obtained with MinION.\u003c/p\u003e\u003cp\u003eThis study had several limitations. \u003cem\u003eS. intermedius\u003c/em\u003e ocular infections have a relatively good prognosis, and many cases are likely managed empirically, leading to a lack of rigorous species identification. Thus, there may have been previously unreported cases of \u003cem\u003eStreptococcous\u003c/em\u003e spp. infection in the external and anterior ocular areas of patients with sinusitis, as in the current case. Additional diagnoses of \u003cem\u003eS. intermedius\u003c/em\u003e ocular infections based on rigorous species identification should be considered in the future.\u003c/p\u003e\u003cp\u003eIn conclusion, infectious blepharoconjunctivitis associated with \u003cem\u003eS. intermedius\u003c/em\u003e sinusitis can present conjunctival tumor. In such cases, smear microscopy of the eye and nasal discharge is crucial for differential diagnosis. Cephem eye drops and intravenous infusions are also useful treatment options. To the best of our knowledge, this is the first known case of \u003cem\u003eS. intermedius\u003c/em\u003e blepahroconjunctivitis associated with sinusitis confirmed by metagenomic analysis using a nanopore sequencer (MinION).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003cp\u003eThe present study followed the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of the Kindai University Faculty of Medicine (approval no. 28\u0026ndash;137). The patient in this case provided consent to participate and allowed us to use her health data in this study. There were no name tags or identification of the information disclosed in this study.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e\u003cp\u003e Written informed consent was obtained from the patient for publication of this case and the accompanying images.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003cp\u003eThe authors declare no competing interest.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThe authors declare no funding was received for this case report.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eDI and HE treated the patient and wrote the draft; FH and HE performed 16S meta-analysis using MinION; TM measured the minimum inhibitory concentrations; HE performed the literature review and supervised this case report. All the authors have read and approved the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to thank Professor Shigeru Yoshida, Kurume University, and Professor Shunji Kusaka, Kindai University, for creating the environment in which the first author's DI treated this patient. We would like to thank Editage (www.editage.jp) for the English language editing.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eResearch data supporting this publication are available from corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMochizuki K, Kumada M, Suemori S, Kawakami H, Sawada A, Yamamot T, Mikamo H. \u003cem\u003eStreptococcus intermedius\u003c/em\u003e-associated late-onset endophthalmitis after trabeculectomy with adjunctive mitomycin C. 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Int J Mol Sci. 2023;30(3):2611.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Streptococcus intermedius, blepahroconjunctivitis, sinusitis, smear microscopy, MinION","lastPublishedDoi":"10.21203/rs.3.rs-7487786/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7487786/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eStreptococcus intermedius\u003c/em\u003e, a commensal bacterium in the human oral cavity, can occasionally cause severe infections in deep tissues. Here, we report the first known case of infectious blepharoconjunctivitis associated with \u003cem\u003eS. intermedius \u003c/em\u003esinusitis mimicking a conjunctival tumor. Smear microscopy of the eye and nasal discharge was useful for the differential diagnosis. Metagenomic analysis using MinION as adjunctive diagnostic tool has contributed to rigorous species identification of the pathogenic strain.\u003c/p\u003e","manuscriptTitle":"Blepharoconjunctivitis mimicking conjunctival tumor associated with Streptococcus intermedius sinusitis: case report and literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 07:24:03","doi":"10.21203/rs.3.rs-7487786/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-21T11:44:37+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-11T08:06:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-02T14:24:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-29T06:42:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"248472475229055591700338900554479601345","date":"2025-09-27T04:54:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"184274809044185451291040104860421233674","date":"2025-09-27T03:33:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"193896303523514353881728053251694400740","date":"2025-09-25T20:10:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303427298788418274663455024055670091079","date":"2025-09-25T13:19:34+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-25T00:33:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-22T11:12:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-02T14:10:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-02T13:29:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2025-09-02T13:26:56+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"40d509c2-15c7-4d88-af05-60946a09c1c4","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-20T10:38:23+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-08 07:24:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7487786","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7487786","identity":"rs-7487786","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}