Research progress in ocular manifestations of hemophagocytic lymphohistiocytosis: Clinical features, mechanisms and therapeutic perspectives (Review).
- 1Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China.
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.
Related
- Commentary: Hemophagocytic lymphohistiocytosis induced by immune checkpoint inhibitors: observations and proposed clinical management
- Hemophagocytic Lymphohistiocytosis in a Patient With Alcohol‐Associated Liver Disease: A Case Report Highlighting Diagnostic Challenges
- Hemophagocytic Lymphohistiocytosis as a Clinical Harbinger of Rapid Disease Progression in Multiple Myeloma During Daratumumab-Based Therapy
- An Active Cytomegalovirus Infection and Epstein-Barr Virus Reactivation Complicated by Cytomegalovirus Meningitis and Virus-Associated Hemophagocytic Lymphohistiocytosis during Methotrexate and Upadacitinib Therapy in a Patient with Rheumatoid Arthritis
- Hepatic Sarcoidosis as a Rare Cause of Secondary Hemophagocytic Lymphohistiocytosis
BibTeX
@article{wu2026research,
title = {{Research progress in ocular manifestations of hemophagocytic lymphohistiocytosis: Clinical features, mechanisms and therapeutic perspectives (Review).}},
author = {Weizhen Wu and Yifan Zhou and Ruofei Wu and Ming Yang and Yanling Wang and Kang Wang},
journal = {Biomedical reports},
year = {2026},
month = sep,
doi = {10.3892/br.2026.2208},
url = {https://europepmc.org/article/MED/42923866},
note = {CC BY},
}
RIS
TY - JOUR
TI - Research progress in ocular manifestations of hemophagocytic lymphohistiocytosis: Clinical features, mechanisms and therapeutic perspectives (Review).
AU - Weizhen Wu
AU - Yifan Zhou
AU - Ruofei Wu
AU - Ming Yang
AU - Yanling Wang
AU - Kang Wang
PY - 2026
DA - 2026/09/30
JO - Biomedical reports
DO - 10.3892/br.2026.2208
UR - https://europepmc.org/article/MED/42923866
AB - 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.
SN - 2049-9434
SN - 2049-9442
ER -