Immune checkpoint inhibitor induced Triple-M syndrome: A case series detailing what every ophthalmologist should know.
5 affiliations
- 1Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
- 2Department of Ophthalmology, The MetroHealth System, Cleveland, OH, USA.
- 3Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
- 4Uveitis Center of Excellence, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
- 5Center for Ophthalmic Bioinformatics, Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Abstract
Immunotherapy has revolutionized cancer treatment but has also been associated with various immune-related adverse events. Triple M syndrome is a particularly rare and life-threatening adverse effect, which encompasses the overlap of immune checkpoint inhibitor-induced myasthenia gravis, myositis, and myocarditis. In this case series, we highlight the ocular manifestations of Triple M Syndrome, which, when recognized in conjunction with other systemic symptoms, can crucially lead to early diagnosis and intervention that may help to improve patient outcomes. Patient 1, a 69 year-old woman, presented with a 1-week history of bilateral ptosis and near complete ophthalmoplegia in both eyes 2 weeks after her second dose of combination therapy of Nivolumab and Ipilimumab for renal cell carcinoma. Patient 2, an 81 year old female, presented with a 3-day history of diplopia, right-sided ptosis, and bilateral partial ophthalmoplegia 2 weeks after completing her second dose of Nivolumab for cecal adenocarcinoma. Patient 3, a 69 year-old male, presented with a 2-week history of bilateral ptosis and poor peripheral vision 4 weeks following his first dose of Durvalumab for squamous cell lung carcinoma. All 3 patients progressed to Triple M Syndrome. Ophthalmologists may play an important role in identifying Triple M Syndrome, a rare but increasingly noted side effect of immune-checkpoint inhibitors. This case series highlights presenting symptoms that should prompt early recognition of Triple M Syndrome and also emphasizes the need for urgent referral to a multi-disciplinary care center for appropriate workup and inpatient management.
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- Immune checkpoint inhibitor-induced multi-organ immune damage complicated by severe pneumonia: case report
BibTeX
@article{moir2026immune,
title = {{Immune checkpoint inhibitor induced Triple-M syndrome: A case series detailing what every ophthalmologist should know.}},
author = {John Moir and Meghana Chalasani and Sunil K Srivastava and Amy S Babiuch},
journal = {American journal of ophthalmology case reports},
year = {2026},
month = oct,
doi = {10.1016/j.ajoc.2026.102699},
url = {https://europepmc.org/article/MED/42997656},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Immune checkpoint inhibitor induced Triple-M syndrome: A case series detailing what every ophthalmologist should know.
AU - John Moir
AU - Meghana Chalasani
AU - Sunil K Srivastava
AU - Amy S Babiuch
PY - 2026
DA - 2026/10/26
JO - American journal of ophthalmology case reports
DO - 10.1016/j.ajoc.2026.102699
UR - https://europepmc.org/article/MED/42997656
AB - Immunotherapy has revolutionized cancer treatment but has also been associated with various immune-related adverse events. Triple M syndrome is a particularly rare and life-threatening adverse effect, which encompasses the overlap of immune checkpoint inhibitor-induced myasthenia gravis, myositis, and myocarditis. In this case series, we highlight the ocular manifestations of Triple M Syndrome, which, when recognized in conjunction with other systemic symptoms, can crucially lead to early diagnosis and intervention that may help to improve patient outcomes. Patient 1, a 69 year-old woman, presented with a 1-week history of bilateral ptosis and near complete ophthalmoplegia in both eyes 2 weeks after her second dose of combination therapy of Nivolumab and Ipilimumab for renal cell carcinoma. Patient 2, an 81 year old female, presented with a 3-day history of diplopia, right-sided ptosis, and bilateral partial ophthalmoplegia 2 weeks after completing her second dose of Nivolumab for cecal adenocarcinoma. Patient 3, a 69 year-old male, presented with a 2-week history of bilateral ptosis and poor peripheral vision 4 weeks following his first dose of Durvalumab for squamous cell lung carcinoma. All 3 patients progressed to Triple M Syndrome. Ophthalmologists may play an important role in identifying Triple M Syndrome, a rare but increasingly noted side effect of immune-checkpoint inhibitors. This case series highlights presenting symptoms that should prompt early recognition of Triple M Syndrome and also emphasizes the need for urgent referral to a multi-disciplinary care center for appropriate workup and inpatient management.
SN - 2451-9936
ER -