Work

Research progress in ocular manifestations of hemophagocytic lymphohistiocytosis: Clinical features, mechanisms and therapeutic perspectives (Review)

Year: 2026

Type: review

Abstract: Hemophagocytic lymphohistiocytosis (HLH) is a cytokine storm-driven immune dysregulation syndrome in which ocular involvement remains critically underreported. Although isolated case reports have documented ocular findings since 1968, no prior work has systematically mapped the full phenotypic spectrum across all ocular structures, to the best of our knowledge. This gap spans both ophthalmology and hematology, where such manifestations are routinely misattributed to primary infection, autoimmunity or neoplasia. Addressing this lack of information, the present scoping review consolidates 40 peer-reviewed sources via a structured PubMed scoping search, providing the first dedicated synthesis of HLH ocular disease, to the best of our knowledge. Among the published case reports, uveitis, particularly intermediate uveitis or panuveitis, was frequently reported, and retinal pathology encompassed hemorrhage, vascular occlusive changes, serous detachment and distinct acute macular neuroretinopathy-like outer retinal atrophy. Optic nerve involvement may present as disc edema or optic neuritis, occasionally antedating systemic diagnosis, and orbital inflammation frequently mimics cellulitis. Multimodal imaging, including optical coherence tomography, optical coherence tomography angiography and fluorescein fundus angiography, delineates microstructural and microvascular alterations, contextualizing infectious etiologies, such as cytomegalovirus, human herpesvirus 8 and fungal retinitis, alongside primary HLH phenotypes. Consistent with the heterogeneous nature of the current evidence, the present scoping review maps these phenotypes without differentiating between direct HLH-mediated injury and sequelae related to immunosuppression or therapy. Despite the absence of standardized classifications, these findings underscore that ocular assessment may be informative for the early recognition and interdisciplinary management of atypical HLH presentations.

Source: Biomedical Reports

DOI: 10.3892/br.2026.2208

Authors: Weizhen Wu, Yifan Zhou, Ruofei Wu, Ming Yang, Yanling Wang, Kang Wang

Institutions: Capital Medical University, Beijing Friendship Hospital

Language: English

Topic: Autoimmune and Inflammatory Disorders Research

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: Natural Science Foundation for Young Scientists of Shanxi Province