Dengue fever case report: a red flag for retinal vein occlusion

Introduction

Dengue is one of the leading arthropod-borne viral illnesses in terms of global morbidity and mortality (1). The incidence of dengue virus infections in Brazil is notably high and continues to rise, with health authorities reporting over 1 million suspected cases in the first 2 months of 2024 alone four times more than in the same period in 2023 (1). This alarming increase highlights the urgent need for better understanding and management of dengue-related complications, both systemic and ocular.

Dengue fever (DF) is caused by the dengue virus, transmitted primarily by the Aedes aegypti mosquito. The disease manifests in a spectrum of clinical presentations, ranging from mild febrile illness to severe and potentially fatal forms, such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (2). Severe dengue is characterized by systemic manifestations, including increased vascular permeability, plasma leakage, and significant hemorrhage due to thrombocytopenia. These systemic changes can lead to hypovolemic shock, organ failure, and, in some cases, death (2). The increased vascular permeability observed in severe dengue is a systemic phenomenon, often resulting in pleural effusion, ascites, and hemoconcentration. However, the same pathophysiological mechanisms can also manifest in ocular tissues, leading to complications such as retinal hemorrhage, macular edema, retinal vasculitis, and uveitis (3).

The underlying mechanisms for these complications involve cytokine release, endothelial dysfunction, and coagulation abnormalities. For instance, the downregulation of the cytoprotective protein C pathway during dengue infection contributes to endothelial damage and a prothrombotic state, increasing the risk of vascular events (4). Additionally, dehydration from plasma leakage can further exacerbate blood viscosity, predisposing patients to thrombotic complications (2).

Systemic manifestations of DF typically begin with a high fever, headache, retro-orbital pain, myalgia, and arthralgia. In more severe cases, patients may develop hemorrhagic manifestations, such as petechiae, epistaxis, gingival bleeding, and gastrointestinal bleeding. The progression to DHF is marked by plasma leakage, thrombocytopenia, and hemoconcentration, while DSS is characterized by circulatory collapse and shock (5). The lethal nature of these severe forms underscores the importance of early recognition and management.

Ocular complications, though less common, are significant and can lead to visual impairment or blindness if not promptly addressed. Retinal vascular occlusions, such as hemiretinal vein occlusion (HRVO) and central retinal vein occlusion (CRVO), have been reported in association with DF, often occurring within days to weeks after the onset of systemic symptoms (6). This report presents a case of bilateral retinal ischemic events, presenting as HRVO in the right eye and cotton wool spots in the left eye, associated with a serology-confirmed diagnosis of DF. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-90/rc).

Case presentation

A 67-year-old male without any known comorbidities presented with a complaint of sudden, painless vision loss in the right eye (OD). At presentation, his blood pressure was 130/90 mmHg, and he denied smoking or prior cardiovascular conditions. Three days before the onset of ocular symptoms, the patient experienced a fever and was subsequently diagnosed with mild DF, confirmed by serology through immunofluorescence showing reactive IgM and IgG levels. Laboratory evaluation for syphilis, coronavirus disease 2019 (COVID-19) and tuberculosis was negative. A clinical ocular examination was performed, and his best corrected visual acuity was 20/200 in the right eye (OD) and 20/20 in the left eye (OS). Intraocular pressure was 12 mmHg in both eyes. Anterior segment examination was normal in both eyes. Fundus examination of OD disclosed a macular edema, venous tortuosity, cotton wool spot, and a hemispheric flame-shaped retinal hemorrhage along the superior arcades. In OS, a cotton wool spot was observed (Figure 1).

Figure 1 Retinography showing macular edema and a hemispheric flame-shaped retinal hemorrhage along the superior arcades in the right eye, as depicted in the image on the right. The image on the right highlights a cotton wool spot, indicated by the black arrow.

Optical coherence tomography (OCT) performed ten days after the initial painless vision loss showed macular edema in OD and no edema in OS (Figure 2). Furthermore, the OCT presented an area of inner retinal hyperreflectivity in the OS (Figure 3).

Figure 2 Macular optical coherence tomography demonstrates macular edema in the right eye, as shown in the right image, and no evidence of edema in the left eye, as shown in the left image.

Figure 3 Optical coherence tomography demonstrates an area of ischemia in the retinal nerve fiber layer of the left eye.

Optical coherence tomography angiography (OCTA) imaging revealed significant non-perfusion areas in both superficial [internal limiting membrane (ILM)-inner plexiform layer (IPL)] and deep [IPL-outer plexiform layer (OPL)] capillary networks in the right eye, indicative of HRVO. En-face OCTA maps showed retinal thickening due to edema in the inner thickness (ILM-IPL) and full thickness [ILM-retinal pigment epithelium (RPE)] maps (Figure 4). In contrast, the left eye presented with reduced vessel density in superficial capillary plexuses and areas of parafoveal ischemia on OCTA (Figure 4).

Figure 4 Optical coherence tomography angiography imaging of the right eye revealed significant non-perfusion areas and dilation in both superficial and deep capillary networks, consistent with hemiretinal vein occlusion. En-face maps demonstrated a marked reduction in vessel density, with inner thickness and full-thickness maps highlighting retinal thickening due to edema. In contrast, the left eye exhibited reduced vessel density in superficial and deep capillary plexuses, consistent with ischemic retinal nerve fiber layer damage. The en-face maps showed decreased vessel density and inner retinal thinning, while full-thickness maps indicated normal retinal thickness. BRM, Bruch’s membrane; ILM, internal limiting membrane; IPL, inner plexiform layer; OPL, outer plexiform layer; RPE, retinal pigment epithelium; SLO, scanning laser ophthalmoscope.

In the right eye, late-phase fluorescein angiography revealed extensive capillary non-perfusion and significant vascular leakage, typical of HRVO. There was notable venous dilation, accompanied by extensive retinal hemorrhaging and macular edema, indicating severe vascular compromise. The hemorrhages caused a blockage in the angiographic imaging, obscuring underlying vascular details and contributing to areas of apparent non-perfusion (Figure 5).

Figure 5 Late-phase fluorescein angiography of the right eye, shown in the right image, revealed areas of hypofluorescence that may be attributed to blockage from flame-shaped hemorrhages rather than true capillary non-perfusion. These areas were limited in extent, measuring less than 5 disc areas. The image also showed marked venous dilation and macular edema, consistent with hemiretinal vein occlusion. In the left eye, shown in the left image, the angiogram demonstrated reduced perfusion and mild vascular leakage in the retinal nerve fiber layer, indicating localized ischemic injury.

The eight-minute phase fluorescein angiography of the left eye showed areas of ischemia in the retinal nerve fiber layer, indicative of ischemic damage. There were also mild vascular leakage and signs of macular ischemia, reflecting localized ischemic injury (Figure 5).

The patient was diagnosed with HRVO in the right eye and ischemia of the retinal nerve fiber layer, consistent with a cotton wool spot, in the left eye. Given the presence of macular edema in OD, intravitreal anti-vascular endothelial growth factor (anti-VEGF) was administered. Although there was no macular edema or neovascularization in OS, fluorescein angiography revealed localized vascular leakage and parafoveal ischemia. Therefore, the patient also received anti-VEGF therapy in OS, aiming to reduce the risk of ischemia-related neovascular complications.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Discussion

We present here a case of a patient with no comorbidities who experienced a mild case of DF, subsequently developing ophthalmologic complaints three days after the onset of systemic symptoms. Ophthalmologic evaluation with multimodal imaging confirmed the diagnosis of HRVO associated with a cotton wool spot in the contralateral eye. DF is a viral infectious disease transmitted to humans via the bite of female Aedes aegypti mosquitoes. Clinical presentations range from mild febrile illness to severe DHF and potentially lethal DSS (2). Retinal involvement in DF is not unusual and has been repeatedly reported in the literature, including manifestations such as retinal vasculitis, maculopathy, and vascular occlusions (6). Additional ophthalmic features comprise subconjunctival bleeding, macular edema, retinal vascular occlusion, foveal inflammation, and optic nerve involvement (6).

The underlying mechanism for retinal vascular occlusions in DF may involve the release of cytokines with vasoactive and procoagulant properties in response to immunological activation (7). Mechanisms for thrombosis include the downregulation of the cytoprotective protein C pathway in human endothelial vascular cells during dengue infection. Profound endothelial damage caused by anti-NS1 antibody cross-reaction with vascular endothelium results in the reduction of thrombomodulin on the endothelial surface (4). This leads to decreased activated protein C, increasing the risk of thrombosis. Additionally, the primary plasminogen activator inhibitor type 1 prevents fibrinolysis, leading to a thrombotic state (2). There is also an increased risk of vascular events in patients with dehydration due to the increased blood viscosity (2).

Retinal vascular occlusions are a less common ophthalmological complication of DF. Velaitham et al. described a patient who presented with retinal vein occlusion 1 week following DF onset, without additional systemic vascular risk factors. This patient later developed proliferative retinopathy and underwent laser photocoagulation therapy (8). Preechawat et al. described a patient with non-ischemic retinal vein occlusion, initially misdiagnosed as inflammatory papillitis, who experienced full visual recovery despite persistent visual field defects and mild optic disc pallor (9). Kanungo et al. reported a retinal artery occlusion in the right eye of a 28-year-old female, who experienced unilateral blurring of the inferior visual field without a decrease in visual acuity (10). Sanjay et al. described a case of unilateral branch retinal artery and vein occlusion associated with panuveitis (11).

Conclusions

In conclusion, we present a case of retinal vascular complication with a temporal association to a systemic DF episode. This case highlights the potential link between dengue infection and retinal vascular events. Multimodal imaging techniques such as OCT, fluorescein angiography, and OCTA can be valuable tools in the evaluation of ischemic events in these patients. Prompt recognition and management of these ocular complications are crucial for improving visual outcomes and preventing further visual impairment. We also highlight the need for further studies and the expansion of prevention programs and vaccination efforts in high-risk areas to mitigate the impact of dengue and other viral diseases on ocular health.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-90/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-90/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-90/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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