Central Retinal Artery Occlusion as a Rare Complication of Trichoderma-Associated Acute Invasive Fungal Sinusitis

Central Retinal Artery Occlusion as a Rare Complication of Trichoderma-Associated Acute Invasive Fungal Sinusitis | 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 Central Retinal Artery Occlusion as a Rare Complication of Trichoderma-Associated Acute Invasive Fungal Sinusitis Chen Mei, Li Xiaodong, Qin Xuewei, Liu Xin This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7170511/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Nov, 2025 Read the published version in BMC Ophthalmology → Version 1 posted 12 You are reading this latest preprint version Abstract Background: Acute invasive fungal sinusitis (AIFRS) is a life-threatening infection characterized by fungal hyphen invading the nasal mucosal, blood vessels, and nerves, leading to tissue necrosis. It often complicates intracranial infection with a high mortality rate. Ocular manifestations can indicate intracranial or systemic infection. This article reports a rare case of AIFRS complicated by central retinal artery occlusion (CRAO) caused by Trichoderma infection to provide a reference for early diagnosis and treatment. Case presentation: A 45-year-old male with undiagnosed diabetes presented with left facial numbness, periodontal pain, and progressive vision loss. Initial misdiagnosis of the patient as having facial neuritis delayed anti-fungal therapy. Despite intensive care unit (ICU) admission and surgical debridement, the patient succumbed to sepsis and intracranial infection. Ophthalmic imaging confirmed CRAO, with fundus fluorescein angiography (FFA) revealing arterial occlusion. Conclusions: This case underscores the need for early recognition of AIFRS in high-risk patients and systematic ophthalmic evaluation in cases of rapid vision loss. Multidisciplinary collaboration and cautious use of corticosteroids are critical. International guidelines recommend prompt anti-fungal therapy, but thrombolysis for CRAO remains controversial in systemic fungal infections. Trichoderma Acute invasive fungal sinusitis Central retinal artery occlusion Cavernous sinus syndrome orbital apical syndrome Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Fungal sinusitis is classified into two categories based on the location of fungal involvement: non-invasive (superficial mucosal involvement) and invasive (submucosal, vascular, or bony invasion). Acute invasive fungal rhinosinusitis (AIFRS) is mainly caused by Aspergillus and Trichoderma, its etiology is complex, and most of them are closely related to the immunocompromise or prolonged immunocompromised states, which may result from long-term use of antibiotics, suffering from diabetes mellitus, tumors, or being infected with human immunodeficiency virus (HIV), and other diseases. The disease follows an acute course with rapid systemic progression, so it is also known as explosive fungal sinusitis [1, 2] .In recent years, the incidence of AIFRS has shown a steady annual increase. While intracranial infection as a complication of AIFRS has been well-documented in domestic and international case reports, the occurrence of AIFRS induced by Trichoderma infection with secondary Central Retinal Artery Occlusion (CRAO) remains exceedingly rare. This paper presents, for the first time from an ophthalmological perspective, a detailed clinical analysis of such a unique case alongside a comprehensive review of relevant literature, aiming to enhance clinical awareness of this uncommon complication. Notably, although various systemic diseases can cause retinal vascular occlusion (e.g., retinal vein occlusion) through inflammatory processes or thrombus formation, the distinctive aspect of this case lies in the integrated diagnostic pathway: AIFRS was confirmed through nasal endoscopy and histopathological examination, while secondary CRAO was definitively diagnosed using ophthalmic imaging modalities including Fundus Fluorescein Angiography (FFA) and Optical Coherence Tomography (OCT). This diagnostic workflow underscores the critical importance of multidisciplinary collaboration in identifying rare clinical entities. Case Presentation A 45-year-old male presented with left facial numbness after cold exposure, accompanied by periodontal pain. After taking oral painkillers at a local oral clinic, the periodontal pain relieved, but the facial numbness worsened, and he developed mouth deviation. He also had progressive left eye vision loss, difficulty opening the eyes, left head swelling and pain, loss of appetite, nausea, and one episode of projectile vomiting. Initial examination in the neurosurgery outpatient clinic showed that the patient was conscious but had generalized weakness (muscle power grade 3/5 in limbs), left facial numbness, nausea, vomiting, unequal pupils (left:right = 5:3 mm), loss of left eye light reflex and vision, facial muscle weakness, and tongue deviation. Cranial computed tomography (CT) showed left maxillary and ethmoid sinusitis, along with slightly thickened bilateral oblique fissures. Cranial Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) showed left optic nerve abnormalities and sinusitis (possibly fungal).Electrocardiogram results showed sinus rhythm with ST - segment depression in some leads. Neurologists initially diagnosed the patient with facial neuritis and administered acyclovir, dexamethasone fosfomycin sodium, triclopyr enanthamycin hydrolysate, and mannitol. Due to the severe left eye condition, ophthalmology consultation was requested. Ophthalmic examination showed Visual acuity of the right eye (VOD): 0.8; visual acuity of the left eye (VOS): no light perception, The remaining ophthalmic examinations are shown in Figure 1. Intraocular pressure was 21 mmHg in the right eye and 11 mmHg in the left eye. Fundus examination, Macular OCT and FFA diagnosed CRAO in the left eye,The detailed examination results are shown in Figure 2 and Figure 3. After lumbar puncture, the intracranial pressure was 250 mmHg. Cerebrospinal fluid analysis revealed elevated glucose levels, normal adenosine deaminase levels, and no bacterial or fungal growth within 72 hours. However, C-reactive protein was 235.14 mg/L. As the condition worsened, with a rising body temperature, the patient was transferred to the ICU. In the ICU, Nasal endoscopy revealed necrotic black mucosa with adherent dry crusts and hyphal colonies, findings consistent with AIFR. The diagnosis was revised, and antifungal treatment with caspofungin, acid suppression with esomeprazole sodium, and correction of acidosis with sodium bicarbonate were initiated. Surgical treatment including nasal endoscopic sinus surgery and tissue debridement was performed. After surgery, the patient was diagnosed with sepsis and septic shock. Despite treatment, the patient died due to family abandonment of resuscitation. Pathology confirmed chronic inflammation of the left middle and upper turbinate mucosa. A small number of fungi (morphologically similar to mucor) were found in the interstitium, and there were some areas of necrosis (Figure 4). Discussion AIFRS represents an aggressive subtype of invasive fungal sinusitis, distinguished by intravascular mucosal inflammation, thrombus formation, granulomatous tissue proliferation, and progressive ulcerative necrosis that may extend to osseous structures. Pathologically, diagnostic hallmarks include the presence of fungal hyphae infiltrating mucosal layers, submucosal tissues, or bone matrices observed in histopathological sections.AIFRS is extremely rare but commonly affects immunosuppressed patients with poorly controlled diabetes mellitus. It is highly lethal, with a mortality rate of up to 50% - 80% [3, 4] . The diagnosis of AIFRS remains non-standardized and necessitates integration of multiple diagnostic modalities:).Radiographic confirmation of sinus involvement,2.Endoscopic verification of sinusitis via nasal endoscopic examination，3.Histopathological evidence demonstrating fungal hyphae invasion into nasal mucosa, submucosal tissues, vascular structures, or osseous components，4.Microbiological identification of the pathogenic organism，5Correlation with clinical history and manifestations.This multi-faceted approach ensures comprehensive evaluation while acknowledging the current lack of standardized diagnostic criteria [2] . AIFRS in patients with diabetes mellitus, especially those with ketoacidosis, is mostly caused by fungi such as Rhizoctonia solani, Rhizopus arrhizus, Trichoderma reesei , and the proportion can be up to 80% [5,6] . AIFRS constitutes an aggressive variant of invasive fungal sinusitis, characterized by intravascular mucosal inflammation, thrombus formation, granulomatous proliferation, and progressive ulcerative necrosis that may extend to osseous structures. Pathologically, its diagnostic hallmark lies in the identification of fungal hyphae infiltrating mucosal layers, submucosal tissues, or bone matrices upon histopathological examination.Accordingly, it was considered that the patient had type 2 diabetes mellitus. Blitzer et al [7] demonstrated that diabetes-associated immune dysfunction leads to diminished phagocytic activity in neutrophils, impairing the clearance of fungal pathogens and exacerbating susceptibility to mycoses. Trichoderma often invades the vascular wall and lumen. After invading tissues, it initially lodges in the elastic lamina of arteries or in veins and lymphatics, triggering an inflammatory reaction and the formation of fungal emboli. This leads to embolism, ischemia, and necrosis of adjacent tissues. Mycelial invasion of blood vessels can cause progressive tissue necrosis of the nasal septum, palate, and orbital or perisinus bones.Patients with AIFRS present clinically with painless, necrotizing nasal septal ulcers (crusts), and sinusitis can lead to death with rapid orbital and intracranial invasion. It often spreads to invade the orbital, intracranial, and maxillofacial regions, causing symptoms such as exophthalmos, visual disturbances, headache, altered mental status, seizures, neurological deficits, coma, and maxillofacial soft tissue swelling [8] . The patient's symptoms in this case aligned with most clinical manifestations documented in existing literature, corresponding to the typical presentation of AIFRS. Septic shock secondary to intracranial infection likely represented the primary cause of death. Case reports of AIFRS caused by Trichoderma infection and complicated by monocular CRAO are rare..Yang Yongqi et al [9] reporteda case of 22-year-old T1DM female with invasive Trichoderma sinusitis developed cavernous sinus syndrome, manifesting as right-eye NLP, complete ophthalmoplegia, and elevated IOP (32 mmHg). MRI confirmed fungal extension to the cavernous sinus, though vascular imaging omissions precluded CRAO confirmation. Despite combined antifungals (voriconazole/amphotericin B) and endoscopic debridement, irreversible vision and motility deficits persisted at 6-month follow-up. Notably, in the context of COVID-19-associated mucormycosis (CAM), CRAO shows accelerated progression, often leading to blindness within days. This may be attributed to the combined effects of viral induced endothelial injury and fungal angioinvasion, indicating that urgent intervention is required even in immunocompetent hosts [10] . Currently, uniform expert consensus and clinical guidelines for the treatment of AIFRS remain lacking. The management approach necessitates nasal endoscopic examination combined with culture and pathological analysis of secretions or necrotic tissues to identify the causative fungal pathogen. Additionally, timely administration of systemic antifungal therapy and thorough surgical debridement of locally infected necrotic tissues are considered essential interventions.The final pathologic diagnosis of this case was Trichoderma infections, and according to the latest global guidelines for the diagnosis and treatment of Trichoderma diseases, it is recommended that: in immunocompromised patients suspected of having Trichoderma, liposomal amphotericin B 5-10 mg/kg/d is preferentially recommended as first-line treatment in all systemic infections [11] . According to the recommendations of the Chinese guidelines for the treatment of severe sepsis/septic shock (2014) [12] , empiric antifungal therapy is recommended for adult patients with sepsis or septic shock who are at high risk of fungal infection, with empiric anti-G- bacillus, G+ cocci, and fungal therapy at the early stage of the disease and timely addition of liposomal amphotericin B 60 mg per day for anti-infective therapy based on pathologic and culture results. Caspofungin targets β(1,3)-D-glucan, a critical component of fungal cell walls. thus exerting an antifungal effect, which is more effective in controlling invasive Pseudomona aeruginosa and Candida infections [13, 14] . A study [15] confirmed that for the treatment of invasive Candida infections, Caspofungin is as effective as amphotericin B. However, this case was an invasive Trichoderma infection, so the patient's inflammatory indexes kept rising after admission, with persistent fever, tachycardia, and ineffective control of the infection. Despite aggressive surgical debridement and antifungal therapy, the survival rate of AIFR patients remains alarmingly low. Given the poor prognosis associated with delayed intervention, extensive surgical resection should be carefully considered to achieve local disease control. However, long-term survivors face significant risks of sinonasal complications, including chronic rhinosinusitis and orbital deformities, necessitating vigilant follow-up [16] . CRAO is an acute ischemic event characterized by obstruction of the central retinal artery, leading to severe visual impairment or irreversible vision loss. The predominant etiology is arterial embolization, with thrombotic emboli (15.5% of cases) typically originating from the internal carotid artery or cardiac sources, calcific emboli (10.5%) associated with valvular heart disease, and cholesterol emboli accounting for the majority (74.5%). In cases where embolic origin remains undetermined after initial evaluation, inflammatory etiologies—particularly giant cell arteritis and hypercoagulable states—should be systematically investigated [17] .While fungal embolism into the ophthalmic artery is the primary hypothesized mechanism of CRAO in this case, alternative pathways such as cavernous sinus thrombosis or inflammatory vasculitis cannot be excluded. Fungal angioinvasion may directly occlude retinal arterioles through hyphal proliferation and emboli formation, whereas thrombosis in the cavernous sinus could indirectly compromise ocular perfusion via venous congestion or arterial compression. Emerging evidence underscores thrombophilia's critical pathophysiological role in CRAO pathogenesis. Comprehensive thrombophilia screening should thus be integrated into preventive strategies, with subsequent initiation of tailored antithrombotic prophylaxis based on identified coagulation abnormalities [18] . Although there are no high-quality studies demonstrating that the visual prognosis of conservative treatment is better than that of the natural course of the disease [19] , it has been observed clinically that patients, who present to the clinic within 4-6 hours of onset of the disease and who are treated promptly with conservative emergency care usually do not have blindness, and retain light-sensitive vision typically. Intravenous or microcatheter intraocular arterial injection of tissue-type plasminogen activator (tPA) for the treatment of acute CRAO has been controversial because of its possible efficacy and concomitant complications. There have been previous case reports [20, 21] that thrombolytic therapy at an early stage is effective for CRAO, but there has been a lack of high-quality randomized controlled trials to validate this. If absolute contraindications are excluded such as coagulation dysfunctions, intravenous or intra-arterial injections of tPA may promptly release the thrombus from the blockage,.Thrombolysis with tPA was considered but deferred due to systemic fungal infection, coagulopathy (D-dimer:18.27 mg/L), and risks of hemorrhagic complications.Current guidelines caution against thrombolysis in sepsis-associated hypercoagulability [22] . Cavernous sinus syndrome leads to ocular muscle paralysis , and an aggressive treatment program is significant for the improvement of visual function in successful salvage, especially in young patients. Conclusions The diagnosis and management of AIFRS in immunocompromised populations present significant challenges. Key hurdles include nonspecific early clinical manifestations, high false-negative rates in imaging studies, and the escalating issue of antifungal resistance, which collectively complicate therapeutic efficacy and patient outcomes.While multidisciplinary collaboration and emerging diagnostic technologies may optimize therapeutic windows, three key limitations persist: 1. Lack of consensus on personalized therapies tailored to fungal subtypes;2. Insufficient clinical validation of predictive early warning systems for pre-symptomatic detection，3.Poorly defined fungus-host immune interactions hindering targeted therapy development. Declarations Consent for Publication Written informed consent was obtained posthumously from the patient’s legal guardian for publication. Ethics statement This case report involves a human subject. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine Author contributions LXD and CM designed the study and drafted the manuscript, LXDand CM as the co-first author. QXW carried out the literature search ,Liu,Xin contributed to data extraction and quality assessment. LXD supervised the study as the corresponding author. All authors contributed to the article and approved the submitted version. Funding This work was supported by Discipline innovation Team of Chengdu University of Traditional Chinese Medicine-Research on the prevention and treatment of fundus diseases with traditional Chinese Medicine (XKTD2022005). The funders had no role in the study design, data collection, data analysis, interpretation, or writing of the report. Competing Interest declaration The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflflict of interest. Data Availability declaration All published data can be obtained from the first author or correspondent by email. Acknowledgments We would like to acknowledge all the authors of the research articles used for the analysis. References Fung M, Babik J, Humphreys I, Davis G. Diagnosis and Treatment of Acute Invasive Fungal Sinusitis in Cancer and Transplant Patients. Curr Infect Dis Rep. 2019;21(12):53. Raz E, Win W, Hagiwara M, Lui Y, Cohen B, Fatterpekar G. Fungal Sinusitis. Neuroimaging Clin N Am. 2015;25(4):569–76. Shamsaei S, Falahati M, Farahyar S, Raiesi O, Haghighi L, Eraghiye Farahani H, Akhavan A, Shamsaie A, Yarahmadi M, Keymaram M. Acute invasive fungal rhinosinusitis: Molecular identification and update in management of frozen section biopsy. Microb Pathog. 2021;159:105125. Hennessy M, McGinn J, White B, Payne S, Warrick J, Crist H. Frozen Section as a Rapid and Accurate Method for Diagnosing Acute Invasive Fungal Rhinosinusitis. Otolaryngology–head neck surgery: official J Am Acad Otolaryngology-Head Neck Surg. 2018;159(3):576–80. Craig J. Updates in management of acute invasive fungal rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. 2019;27(1):29–36. Piromchai P, Thanaviratananich S. Invasive fungal rhinosinusitis versus bacterial rhinosinusitis with orbital complications: a case-control study. TheScientificWorldJournal 2013, 2013:453297. Blitzer A, Lawson W. Fungal infections of the nose and paranasal sinuses. Part I. Otolaryngol Clin North Am. 1993;26(6):1007–35. Deshazo R. Syndromes of invasive fungal sinusitis. Med Mycol 2009:S309–314. Yang YQ, Tu B, Cao QS, Li F. A case of acute invasive fungal sinusitis complicating cavernous sinus syndrome. Hainan Med 2020(22):2987–9. Srivastava Smiti Rani,Sarkar Peyalee,Ganguly Purban. Central Retinal Artery Occlusion in COVID-Associated Mucormycosis.[J].J Glob Infect Dis, 2023, 15: 66–71. Cornely O, Alastruey-Izquierdo A, Arenz D, Chen S, Dannaoui E, Hochhegger B, Hoenigl M, Jensen H, Lagrou K, Lewis R, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. Lancet Infect Dis. 2019;19(12):e405–21. Chinese Society of Critical Care Medicine. Chinese guidelines for the treatment of severe sepsis/septic shock (2014). Chin J Intern Med 2015(6):557–81. Jarque I, Tormo M, Bello J, Rovira M, Batlle M, Julià A, Tabares S, Rivas C, Fernández-Sevilla A, García-Boyero R, et al. Caspofungin for the treatment of invasive fungal disease in hematological patients (ProCAS Study). Med Mycol. 2013;51(2):150–4. Zaas A, Dodds Ashley E, Alexander B, Johnson M, Perfect J. Caspofungin for invasive candidiasis at a tertiary care medical center. Am J Med. 2006;119(11):e993991–996. Mora-Duarte J, Betts R, Rotstein C, Colombo A, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347(25):2020–9. Monroe Marcus M, Nathan, et al. Invasive fungal rhinosinusitis: a 15-year experience with 29 patients.[J]. Laryngoscope. 2013;123:1583–7. Rudkin A, Lee A, Chen C. Vascular risk factors for central retinal artery occlusion. Eye. 2010;24(4):678–81. Dziedzic, Radosław et al. Zaręba Lech,Iwaniec Teresa. High prevalence of thrombophilic risk factors in patients with central retinal artery occlusion.[J].Thromb J, 2023, 21: 81. Olsen T, Pulido J, Folk J, Hyman L, Flaxel C, Adelman R. Retinal and Ophthalmic Artery Occlusions Preferred Practice Pattern®. Ophthalmology. 2017;124(2):P120–43. Mac Grory B, Nackenoff A, Poli S, Spitzer M, Nedelmann M, Guillon B, Preterre C, Chen C, Lee A, Yaghi S, et al. Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis. Stroke. 2020;51(7):2018–25. Schrag M, Youn T, Schindler J, Kirshner H, Greer D. Intravenous Fibrinolytic Therapy in Central Retinal Artery Occlusion: A Patient-Level Meta-analysis. JAMA Neurol. 2015;72(10):1148–54. Katriel E, Lee,Christine, Tschoe,Stephanie A, Coffman et al. Management of Acute Central Retinal Artery Occlusion, a Retinal Stroke: An Institutional Series and Literature Review.[J].J Stroke Cerebrovasc Dis, 2020, 30(2):105531. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 25 Nov, 2025 Read the published version in BMC Ophthalmology → Version 1 posted Editorial decision: Revision requested 21 Oct, 2025 Reviews received at journal 07 Oct, 2025 Reviewers agreed at journal 07 Oct, 2025 Reviewers agreed at journal 06 Oct, 2025 Reviewers agreed at journal 06 Oct, 2025 Reviews received at journal 01 Oct, 2025 Reviewers agreed at journal 01 Oct, 2025 Reviewers invited by journal 24 Sep, 2025 Editor invited by journal 25 Aug, 2025 Editor assigned by journal 28 Jul, 2025 Submission checks completed at journal 25 Jul, 2025 First submitted to journal 25 Jul, 2025 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. 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14:25:36","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":63127,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7170511/v1/6182c0e78ca7bf1f464af381.html"},{"id":92874229,"identity":"e9b2c21c-e0e9-4842-a0b1-9966019d5fd3","added_by":"auto","created_at":"2025-10-06 14:25:35","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":646534,"visible":true,"origin":"","legend":"\u003cp\u003eAnterior segment photography on the first day of admission: A: the anterior segment of the eye of the right eye (-), B-C:the conjunctiva of the left eye is congested, the pupil is dilated, the eyeball is fixed, the light reflex is lost, the crystalline lens is mildly cloudy, and the vitreous body is cloudy, D:the left eye's eyelid ptosis, which completely obscures the pupil.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7170511/v1/937eea1c730f67d37da222c4.png"},{"id":92874230,"identity":"3eb6ed96-485d-4c25-8d7f-473233113f0e","added_by":"auto","created_at":"2025-10-06 14:25:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":439087,"visible":true,"origin":"","legend":"\u003cp\u003eA: Fundus color photograph: normal fundus of the right eye, grayish edema of the retina at the posterior pole of the left eye, and cherry-red changes of the macula; B:Red-free fundus photography: normal fundus of the right eye, hyperfluorescence of the optic disc of the left eye with unclear borders, and hypofluorescent changes of the paravascular choroid of the retina; C-D: OCT photographs of the macula: C shows a normal OCT fundus of the right eye, with a morphologically structured macula that is available, and D shows blurring of the refractive medium of the left eye, with edema of the inner layer of the retina in the macular area, an increase in the thickness, and the existence of a morphology of the central concavity of the macula.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7170511/v1/96624ae51576803af0344088.png"},{"id":92874232,"identity":"ceab1ae3-0c7c-4b75-9bc5-b8279878ae18","added_by":"auto","created_at":"2025-10-06 14:25:35","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":486684,"visible":true,"origin":"","legend":"\u003cp\u003eA-B:A wide-angle fundus color photograph, A:Normal fundus in right eye, B:the optic disc is pale, the border is blurred, the posterior retina is gray and edematous, and the macula is cherry-red, C:FFA photographs:the fluorescence filling time of the right eye is normal, there is no abnormal hyper- and hypofluorescence; the left eye is the main photographic eye, and the left eye had prolonged brachial - retinal circulation, the delayed arterial filling at 1 minute and 11 seconds , the venules begin to fill up in late stage, and the posterior retinal artery and retinal vein show the change of the \"sausage-like segmentation\" in posterior retinal arteries and vena cava.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7170511/v1/0e3fb74060305232b20943a9.png"},{"id":92874234,"identity":"9e21dd92-bcc8-4c65-a086-d7be84298244","added_by":"auto","created_at":"2025-10-06 14:25:36","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":452572,"visible":true,"origin":"","legend":"\u003cp\u003eA-D: the left nasal mucosa was black in color and a large number of dry crusts, white hyphae and necrotic-like tissue were seen adhering to it.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7170511/v1/f035b4b1160889767e779253.png"},{"id":97178876,"identity":"8e043d6d-b04a-440d-872b-39a625291ae5","added_by":"auto","created_at":"2025-12-01 16:13:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3139519,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7170511/v1/54c3311e-c7d3-4b7a-b7f7-e491517ca76f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Central Retinal Artery Occlusion as a Rare Complication of Trichoderma-Associated Acute Invasive Fungal Sinusitis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFungal sinusitis is classified into two categories based on the location of fungal involvement: non-invasive (superficial mucosal involvement) and invasive (submucosal, vascular, or bony invasion). Acute invasive fungal rhinosinusitis (AIFRS) is mainly caused by Aspergillus and Trichoderma, its etiology is complex, and most of them are closely related to the immunocompromise or prolonged immunocompromised states, which may result from long-term use of antibiotics, suffering from diabetes mellitus, tumors, or being infected with human immunodeficiency virus (HIV), and other diseases. The disease follows an acute course with rapid systemic progression, so it is also known as explosive fungal sinusitis \u003csup\u003e[1, 2]\u003c/sup\u003e.In recent years, the incidence of AIFRS has shown a steady annual increase. While intracranial infection as a complication of AIFRS has been well-documented in domestic and international case reports, the occurrence of AIFRS induced by Trichoderma infection with secondary Central Retinal Artery Occlusion (CRAO) remains exceedingly rare. This paper presents, for the first time from an ophthalmological perspective, a detailed clinical analysis of such a unique case alongside a comprehensive review of relevant literature, aiming to enhance clinical awareness of this uncommon complication. Notably, although various systemic diseases can cause retinal vascular occlusion (e.g., retinal vein occlusion) through inflammatory processes or thrombus formation, the distinctive aspect of this case lies in the integrated diagnostic pathway: AIFRS was confirmed through nasal endoscopy and histopathological examination, while secondary CRAO was definitively diagnosed using ophthalmic imaging modalities including Fundus Fluorescein Angiography (FFA) and Optical Coherence Tomography (OCT). This diagnostic workflow underscores the critical importance of multidisciplinary collaboration in identifying rare clinical entities.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 45-year-old male presented with left facial numbness after cold exposure, accompanied by periodontal pain. After taking oral painkillers at a local oral clinic, the periodontal pain relieved, but the facial numbness worsened, and he developed mouth deviation. He also had progressive left eye vision loss, difficulty opening the eyes, left head swelling and pain, loss of appetite, nausea, and one episode of projectile vomiting.\u003c/p\u003e\n\u003cp\u003eInitial examination in the neurosurgery outpatient clinic showed that the patient was conscious but had generalized weakness (muscle power grade 3/5 in limbs), left facial numbness, nausea, vomiting, unequal pupils (left:right = 5:3 mm), loss of left eye light reflex and vision, facial muscle weakness, and tongue deviation. Cranial computed tomography (CT) showed left maxillary and ethmoid sinusitis, along with slightly thickened bilateral oblique fissures. Cranial Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) showed left optic nerve abnormalities and sinusitis (possibly fungal).Electrocardiogram results showed sinus rhythm with ST - segment depression in some leads.\u003c/p\u003e\n\u003cp\u003eNeurologists initially diagnosed the patient with facial neuritis and administered acyclovir, dexamethasone fosfomycin sodium, triclopyr enanthamycin hydrolysate, and mannitol. Due to the severe left eye condition, ophthalmology consultation was requested. Ophthalmic examination showed Visual acuity of the right eye (VOD): 0.8; visual acuity of the left eye (VOS): no light perception, The remaining ophthalmic examinations are shown in Figure 1. Intraocular pressure was 21 mmHg in the right eye and 11 mmHg in the left eye. Fundus examination, Macular OCT \u0026nbsp;and FFA diagnosed CRAO in the left eye,The detailed examination results are shown in Figure 2 and Figure 3.\u003c/p\u003e\n\u003cp\u003eAfter lumbar puncture, the intracranial pressure was 250 mmHg. Cerebrospinal fluid analysis revealed elevated glucose levels, normal adenosine deaminase levels, and no bacterial or fungal growth within 72 hours. However, C-reactive protein was 235.14 mg/L. As the condition worsened, with a rising body temperature, the patient was transferred to the ICU. In the ICU, Nasal endoscopy revealed necrotic black mucosa with adherent dry crusts and hyphal colonies, findings consistent with AIFR. The diagnosis was revised, and antifungal treatment with caspofungin, acid suppression with esomeprazole sodium, and correction of acidosis with sodium bicarbonate were initiated. Surgical treatment including nasal endoscopic sinus surgery and tissue debridement was performed. After surgery, the patient was diagnosed with sepsis and septic shock. Despite treatment, the patient died due to family abandonment of resuscitation. Pathology confirmed chronic inflammation of the left middle and upper turbinate mucosa. A small number of fungi (morphologically similar to mucor) were found in the interstitium, and there were some areas of necrosis (Figure 4).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAIFRS represents an aggressive subtype of invasive fungal sinusitis, distinguished by intravascular mucosal inflammation, thrombus formation, granulomatous tissue proliferation, and progressive ulcerative necrosis that may extend to osseous structures. Pathologically, diagnostic hallmarks include the presence of fungal hyphae infiltrating mucosal layers, submucosal tissues, or bone matrices observed in histopathological sections.AIFRS is extremely rare but commonly affects immunosuppressed patients with poorly controlled diabetes mellitus. It is highly lethal, with a mortality rate of up to 50% - 80%\u003csup\u003e\u0026nbsp;[3, 4]\u003c/sup\u003e. The diagnosis of AIFRS remains non-standardized and necessitates integration of multiple diagnostic modalities:).Radiographic confirmation of sinus involvement,2.Endoscopic verification of sinusitis\u0026nbsp;via nasal endoscopic examination，3.Histopathological evidence\u0026nbsp;demonstrating fungal hyphae invasion into nasal mucosa, submucosal tissues, vascular structures, or osseous components，4.Microbiological identification\u0026nbsp;of the pathogenic organism，5Correlation with clinical history and manifestations.This multi-faceted approach ensures comprehensive evaluation while acknowledging the current lack of standardized diagnostic criteria\u003csup\u003e[2]\u003c/sup\u003e. AIFRS in patients with diabetes mellitus, especially those with ketoacidosis, is mostly caused by fungi such as Rhizoctonia solani, Rhizopus arrhizus, Trichoderma reesei , and the proportion can be up to 80% \u003csup\u003e[5,6]\u003c/sup\u003e. AIFRS constitutes an aggressive variant of invasive fungal sinusitis, characterized by intravascular mucosal inflammation, thrombus formation, granulomatous proliferation, and progressive ulcerative necrosis that may extend to osseous structures. Pathologically, its diagnostic hallmark lies in the identification of fungal hyphae infiltrating mucosal layers, submucosal tissues, or bone matrices upon histopathological examination.Accordingly, it was considered that the patient had type 2 diabetes mellitus. Blitzer et al\u003csup\u003e\u0026nbsp;[7]\u003c/sup\u003e demonstrated that diabetes-associated immune dysfunction leads to diminished phagocytic activity in neutrophils, impairing the clearance of fungal pathogens and exacerbating susceptibility to mycoses. Trichoderma often invades the vascular wall and lumen. After invading tissues, it initially lodges in the elastic lamina of arteries or in veins and lymphatics, triggering an inflammatory reaction and the formation of fungal emboli. This leads to embolism, ischemia, and necrosis of adjacent tissues. Mycelial invasion of blood vessels can cause progressive tissue necrosis of the nasal septum, palate, and orbital or perisinus bones.Patients with AIFRS present clinically with painless, necrotizing nasal septal ulcers (crusts), and sinusitis can lead to death with rapid orbital and intracranial invasion. It often spreads to invade the orbital, intracranial, and maxillofacial regions, causing symptoms such as exophthalmos, visual disturbances, headache, altered mental status, seizures, neurological deficits, coma, and maxillofacial soft tissue swelling\u003csup\u003e[8]\u003c/sup\u003e. The patient's symptoms in this case aligned with most clinical manifestations documented in existing literature, corresponding to the typical presentation of AIFRS. Septic shock secondary to intracranial infection likely represented the primary cause of death.\u003c/p\u003e\n\u003cp\u003eCase reports of AIFRS caused by Trichoderma infection and complicated by monocular CRAO are rare..Yang Yongqi et al\u003csup\u003e\u0026nbsp;[9]\u003c/sup\u003ereporteda case of 22-year-old T1DM female with invasive Trichoderma sinusitis developed cavernous sinus syndrome, manifesting as right-eye NLP, complete ophthalmoplegia, and elevated IOP (32 mmHg). MRI confirmed fungal extension to the cavernous sinus, though vascular imaging omissions precluded CRAO confirmation. Despite combined antifungals (voriconazole/amphotericin B) and endoscopic debridement, irreversible vision and motility deficits persisted at 6-month follow-up. Notably, in the context of COVID-19-associated mucormycosis (CAM), CRAO shows accelerated progression, often leading to blindness within days. This may be attributed to the combined effects of viral induced endothelial injury and fungal angioinvasion, indicating that urgent intervention is required even in immunocompetent hosts\u003csup\u003e[10]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eCurrently, uniform expert consensus and clinical guidelines for the treatment of AIFRS remain lacking. The management approach necessitates nasal endoscopic examination combined with culture and pathological analysis of secretions or necrotic tissues to identify the causative fungal pathogen. Additionally, timely administration of systemic antifungal therapy and thorough surgical debridement of locally infected necrotic tissues are considered essential interventions.The final pathologic diagnosis of this case was Trichoderma \u0026nbsp;infections, and according to the latest global guidelines for the diagnosis and treatment of Trichoderma \u0026nbsp;diseases, it is recommended that: in immunocompromised patients suspected of having Trichoderma, liposomal amphotericin B 5-10 mg/kg/d is preferentially recommended as first-line treatment in all systemic infections\u003csup\u003e[11]\u003c/sup\u003e. According to the recommendations of the Chinese guidelines for the treatment of severe sepsis/septic shock (2014) \u003csup\u003e[12]\u003c/sup\u003e, empiric antifungal therapy is recommended for adult patients with sepsis or septic shock who are at high risk of fungal infection, with empiric anti-G- bacillus, G+ cocci, and fungal therapy at the early stage of the disease and timely addition of liposomal amphotericin B 60 mg per day for anti-infective therapy based on pathologic and culture results. Caspofungin targets β(1,3)-D-glucan, a critical component of fungal cell walls. thus exerting an antifungal effect, which is more effective in controlling invasive Pseudomona aeruginosa and Candida infections\u003csup\u003e\u0026nbsp;[13, 14]\u003c/sup\u003e. A study\u003csup\u003e\u0026nbsp;[15]\u003c/sup\u003econfirmed that for the treatment of invasive Candida infections, Caspofungin is as effective as amphotericin B. However, this case was an invasive Trichoderma infection, so the patient's inflammatory indexes kept rising after admission, with persistent fever, tachycardia, and ineffective control of the infection. Despite aggressive surgical debridement and antifungal therapy, the survival rate of AIFR patients remains alarmingly low. Given the poor prognosis associated with delayed intervention, extensive surgical resection should be carefully considered to achieve local disease control. However, long-term survivors face significant risks of sinonasal complications, including chronic rhinosinusitis and orbital deformities, necessitating vigilant follow-up\u003csup\u003e[16]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eCRAO is an acute ischemic event characterized by obstruction of the central retinal artery, leading to severe visual impairment or irreversible vision loss. The predominant etiology is arterial embolization, with thrombotic emboli (15.5% of cases) typically originating from the internal carotid artery or cardiac sources, calcific emboli (10.5%) associated with valvular heart disease, and cholesterol emboli accounting for the majority (74.5%). In cases where embolic origin remains undetermined after initial evaluation, inflammatory etiologies—particularly giant cell arteritis and hypercoagulable states—should be systematically investigated\u003csup\u003e[17]\u003c/sup\u003e.While fungal embolism into the ophthalmic artery is the primary hypothesized mechanism of CRAO in this case, alternative pathways such as cavernous sinus thrombosis or inflammatory vasculitis cannot be excluded. Fungal angioinvasion may directly occlude retinal arterioles through hyphal proliferation and emboli formation, whereas thrombosis in the cavernous sinus could indirectly compromise ocular perfusion via venous congestion or arterial compression. Emerging evidence underscores thrombophilia's critical pathophysiological role in CRAO pathogenesis. Comprehensive thrombophilia screening should thus be integrated into preventive strategies, with subsequent initiation of tailored antithrombotic prophylaxis based on identified coagulation abnormalities\u003csup\u003e[18]\u003c/sup\u003e. Although there are no high-quality studies demonstrating that the visual prognosis of conservative treatment is better than that of the natural course of the disease \u003csup\u003e[19]\u003c/sup\u003e, it has been observed clinically that patients, who present to the clinic within 4-6 hours of onset of the disease and who are treated promptly with conservative emergency care usually do not have blindness, and retain light-sensitive vision typically. Intravenous or microcatheter intraocular arterial injection of tissue-type plasminogen activator (tPA) for the treatment of acute CRAO has been controversial because of its possible efficacy and concomitant complications. There have been previous case reports \u003csup\u003e[20, 21]\u003c/sup\u003e that thrombolytic therapy at an early stage is effective for CRAO, but there has been a lack of high-quality randomized controlled trials to validate this. If absolute contraindications are excluded such as coagulation dysfunctions, intravenous or intra-arterial injections of tPA may promptly release the thrombus from the blockage,.Thrombolysis with tPA was considered but deferred due to systemic fungal infection, coagulopathy (D-dimer:18.27 mg/L), and risks of hemorrhagic complications.Current guidelines caution against thrombolysis in sepsis-associated hypercoagulability\u003csup\u003e[22]\u003c/sup\u003e. Cavernous sinus syndrome leads to ocular muscle paralysis , and an aggressive treatment program is significant for the improvement of visual function in successful salvage, especially in young patients.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe diagnosis and management of AIFRS in immunocompromised populations present significant challenges. Key hurdles include nonspecific early clinical manifestations, high false-negative rates in imaging studies, and the escalating issue of antifungal resistance, which collectively complicate therapeutic efficacy and patient outcomes.While multidisciplinary collaboration and emerging diagnostic technologies may optimize therapeutic windows, three key limitations persist: 1. Lack of consensus on personalized therapies tailored to fungal subtypes;2. Insufficient clinical validation of predictive early warning systems for pre-symptomatic detection，3.Poorly defined fungus-host immune interactions hindering targeted therapy development.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained posthumously from the patient’s legal guardian for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case report involves a human subject. The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLXD and CM designed the study and drafted the manuscript, LXDand CM as the co-first author. QXW carried out the literature search ,Liu,Xin contributed to data extraction and quality assessment. LXD supervised the study as the corresponding author. All authors contributed to the article and approved the submitted version.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Discipline innovation Team of Chengdu University of Traditional Chinese Medicine-Research on the prevention and treatment of fundus diseases with traditional Chinese Medicine (XKTD2022005). The funders had no role in the study design, data collection, data analysis, interpretation, or writing of the report.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interest declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflflict of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability declaration\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll published data can be obtained from the first author or correspondent by email.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe would like to acknowledge all the authors of the research articles used for the analysis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFung M, Babik J, Humphreys I, Davis G. Diagnosis and Treatment of Acute Invasive Fungal Sinusitis in Cancer and Transplant Patients. Curr Infect Dis Rep. 2019;21(12):53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRaz E, Win W, Hagiwara M, Lui Y, Cohen B, Fatterpekar G. Fungal Sinusitis. Neuroimaging Clin N Am. 2015;25(4):569\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShamsaei S, Falahati M, Farahyar S, Raiesi O, Haghighi L, Eraghiye Farahani H, Akhavan A, Shamsaie A, Yarahmadi M, Keymaram M. Acute invasive fungal rhinosinusitis: Molecular identification and update in management of frozen section biopsy. Microb Pathog. 2021;159:105125.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHennessy M, McGinn J, White B, Payne S, Warrick J, Crist H. Frozen Section as a Rapid and Accurate Method for Diagnosing Acute Invasive Fungal Rhinosinusitis. Otolaryngology\u0026ndash;head neck surgery: official J Am Acad Otolaryngology-Head Neck Surg. 2018;159(3):576\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCraig J. Updates in management of acute invasive fungal rhinosinusitis. Curr Opin Otolaryngol Head Neck Surg. 2019;27(1):29\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePiromchai P, Thanaviratananich S. Invasive fungal rhinosinusitis versus bacterial rhinosinusitis with orbital complications: a case-control study. \u003cem\u003eTheScientificWorldJournal\u003c/em\u003e 2013, 2013:453297.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBlitzer A, Lawson W. Fungal infections of the nose and paranasal sinuses. Part I. Otolaryngol Clin North Am. 1993;26(6):1007\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDeshazo R. Syndromes of invasive fungal sinusitis. Med Mycol 2009:S309\u0026ndash;314.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYang YQ, Tu B, Cao QS, Li F. A case of acute invasive fungal sinusitis complicating cavernous sinus syndrome. Hainan Med 2020(22):2987\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSrivastava Smiti Rani,Sarkar Peyalee,Ganguly Purban. Central Retinal Artery Occlusion in COVID-Associated Mucormycosis.[J].J Glob Infect Dis, 2023, 15: 66\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCornely O, Alastruey-Izquierdo A, Arenz D, Chen S, Dannaoui E, Hochhegger B, Hoenigl M, Jensen H, Lagrou K, Lewis R, et al. Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium. 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Am J Med. 2006;119(11):e993991\u0026ndash;996.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMora-Duarte J, Betts R, Rotstein C, Colombo A, Thompson-Moya L, Smietana J, Lupinacci R, Sable C, Kartsonis N, Perfect J. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002;347(25):2020\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMonroe Marcus M, Nathan, et al. Invasive fungal rhinosinusitis: a 15-year experience with 29 patients.[J]. Laryngoscope. 2013;123:1583\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRudkin A, Lee A, Chen C. Vascular risk factors for central retinal artery occlusion. Eye. 2010;24(4):678\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDziedzic, Radosław et al. Zaręba Lech,Iwaniec Teresa. High prevalence of thrombophilic risk factors in patients with central retinal artery occlusion.[J].Thromb J, 2023, 21: 81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOlsen T, Pulido J, Folk J, Hyman L, Flaxel C, Adelman R. Retinal and Ophthalmic Artery Occlusions Preferred Practice Pattern\u0026reg;. Ophthalmology. 2017;124(2):P120\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMac Grory B, Nackenoff A, Poli S, Spitzer M, Nedelmann M, Guillon B, Preterre C, Chen C, Lee A, Yaghi S, et al. Intravenous Fibrinolysis for Central Retinal Artery Occlusion: A Cohort Study and Updated Patient-Level Meta-Analysis. Stroke. 2020;51(7):2018\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSchrag M, Youn T, Schindler J, Kirshner H, Greer D. Intravenous Fibrinolytic Therapy in Central Retinal Artery Occlusion: A Patient-Level Meta-analysis. JAMA Neurol. 2015;72(10):1148\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKatriel E, Lee,Christine, Tschoe,Stephanie A, Coffman et al. Management of Acute Central Retinal Artery Occlusion, a Retinal Stroke: An Institutional Series and Literature Review.[J].J Stroke Cerebrovasc Dis, 2020, 30(2):105531.\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":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Trichoderma, Acute invasive fungal sinusitis, Central retinal artery occlusion, Cavernous sinus syndrome, orbital apical syndrome","lastPublishedDoi":"10.21203/rs.3.rs-7170511/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7170511/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eAcute invasive fungal sinusitis (AIFRS) is a life-threatening infection characterized by fungal hyphen invading the nasal mucosal, blood vessels, and nerves, leading to tissue necrosis. It often complicates intracranial infection with a high mortality rate. Ocular manifestations can indicate intracranial or systemic infection. This article reports a rare case of AIFRS complicated by central retinal artery occlusion (CRAO) caused by Trichoderma infection to provide a reference for early diagnosis and treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation: \u003c/strong\u003eA 45-year-old male with undiagnosed diabetes presented with left facial numbness, periodontal pain, and progressive vision loss. Initial misdiagnosis of the patient as having facial neuritis delayed anti-fungal therapy. Despite intensive care unit (ICU) admission and surgical debridement, the patient succumbed to sepsis and intracranial infection. Ophthalmic imaging confirmed CRAO, with fundus fluorescein angiography (FFA) revealing arterial occlusion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eThis case underscores the need for early recognition of AIFRS in high-risk patients and systematic ophthalmic evaluation in cases of rapid vision loss. Multidisciplinary collaboration and cautious use of corticosteroids are critical. International guidelines recommend prompt anti-fungal therapy, but thrombolysis for CRAO remains controversial in systemic fungal infections.\u003c/p\u003e","manuscriptTitle":"Central Retinal Artery Occlusion as a Rare Complication of Trichoderma-Associated Acute Invasive Fungal Sinusitis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-06 14:25:31","doi":"10.21203/rs.3.rs-7170511/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-21T11:02:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-07T08:34:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"96684165129428591993944622068095996233","date":"2025-10-07T08:22:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"280156225008810854977317232311324810716","date":"2025-10-06T10:48:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"78935788500125073195773797119776948913","date":"2025-10-06T08:02:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-01T17:57:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"110117577935806594081301615064089065730","date":"2025-10-01T10:12:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-24T07:05:46+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-08-25T08:11:54+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-28T10:21:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-25T17:21:49+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-07-25T12:24:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"87bf5e39-17d7-436b-85e5-5b046a1c4003","owner":[],"postedDate":"October 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:07:50+00:00","versionOfRecord":{"articleIdentity":"rs-7170511","link":"https://doi.org/10.1186/s12886-025-04487-w","journal":{"identity":"bmc-ophthalmology","isVorOnly":false,"title":"BMC Ophthalmology"},"publishedOn":"2025-11-25 15:58:25","publishedOnDateReadable":"November 25th, 2025"},"versionCreatedAt":"2025-10-06 14:25:31","video":"","vorDoi":"10.1186/s12886-025-04487-w","vorDoiUrl":"https://doi.org/10.1186/s12886-025-04487-w","workflowStages":[]},"version":"v1","identity":"rs-7170511","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7170511","identity":"rs-7170511","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}