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Vincristine-induced ptosis in pediatric patients: a systematic review and practice recommendations
H Shafeeq Ahmed1, Chinmayee J Thrishulamurthy2
1Department of Ophthalmology, Bangalore Medical College and Research Institute, K.R Road, Bangalore, 560002, Karnataka, India. shafeeqahmed2002@gmail.com.
Insights
Vincristine-induced ptosis, a rare side effect in pediatric cancer patients, is often bilateral and typically emerges after four doses. New grading and treatment protocols aim to standardize management and improve outcomes.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
- Clinical Pharmacology
Background:
- Vincristine is a cornerstone chemotherapy drug for pediatric cancers, but its neurotoxicity, including ocular effects like ptosis, is under-recognized.
- While peripheral neuropathy is a known side effect, specific data on vincristine-induced ptosis in children are limited, necessitating a comprehensive review.
Purpose of the Study:
- To systematically review and analyze pediatric cases of vincristine-induced ptosis.
- To characterize the clinical presentation, management strategies, and outcomes of this rare neurotoxic manifestation.
- To propose standardized assessment and treatment protocols for vincristine-induced ptosis.
Main Methods:
- A systematic review of three databases (PROSPERO: CRD42024617946) identified 379 articles, with 28 articles detailing 31 pediatric cases included.
- Data extraction focused on patient demographics, ptosis characteristics, time to onset, treatment interventions, and recovery patterns.
- Statistical analysis was performed to describe the cohort and identify trends in management and outcomes.
Main Results:
- Vincristine-induced ptosis predominantly affected males (58.06%) with a median age of 3 years, appearing bilaterally in 61.29% of cases.
- Symptom onset occurred a median of 6 days post-last vincristine dose, with varied management including vincristine dose adjustment/discontinuation (74.19%) and pyridoxine-based therapies (70%).
- Most cases showed favorable recovery within 28 days, though 9.67% experienced mild residual ptosis.
Conclusions:
- Vincristine-induced ptosis exhibits specific characteristics, including a left-sided predominance when unilateral, and highlights variability in current management.
- The proposed VICTORIA Grading and VINTOSIS-3 protocol offer standardized tools for ptosis assessment and structured treatment approaches.
- Early detection, vigilant monitoring, and tailored interventions are crucial for balancing neurotoxicity management with effective chemotherapy in pediatric oncology.
Abstract:
Vincristine, a chemotherapy drug primarily used in pediatric cancer treatments like acute lymphoblastic leukemia and Wilms' tumor, is known for neurotoxic side effects, including a rare but under-discussed manifestation-vincristine-induced ptosis. This systematic review (PROSPERO: CRD42024617946) analyzed data from three databases, identifying 379 articles. Of these, 28 articles encompassing 31 unique pediatric cases were included, with Turkey contributing the highest number of cases (9 cases, 29.03%). The median age was 3 years (IQR: 2 - 5.5), with 58.06% male (18 cases) and 41.93% female (13 cases). Ptosis appeared bilaterally in 61.29% (19 cases) and unilaterally in 38.71% (12 cases), showing a left-side predominance in unilateral cases. The median time to symptom onset after the last vincristine dose was 6 days (IQR: 2 - 12). Treatment protocols varied; 74.19% (23 cases) adjusted or discontinued vincristine, with 34.78% (8 cases) restarting after skipping doses. Pyridoxine with or without pyridostigmine was used in 70% (14 of 20 treated cases), and recovery was generally favorable, with symptoms resolving within 28 days (IQR: 22.75 - 42) in most cases. Mild residual ptosis was noted in 9.67% (3 cases). Our review shows the significant variability inherent to management approaches in this patient demographic and highlights the need for standardized documentation and treatment approaches, proposing "VINTOSIS-3" as a practical treatment protocol. Furthermore, the VICTORIA (Vincristine-InduCed pTOsis cRIteriA) Grading is introduced to standardize ptosis severity evaluation. We further emphasize the importance of early detection, vigilant monitoring, and tailored interventions to balance neurotoxicity management with chemotherapy efficacy. What is Known: • Vincristine, a widely used chemotherapeutic agent in pediatric oncology, is associated with toxic side effects, primarily peripheral neuropathy. • Ocular complications of vincristine, including ptosis, have been reported but remain under-recognized. What is New: • Vincristine-induced ptosis is predominantly bilateral, but when unilateral, it shows a left-sided predominance and typically appears after a median of four doses. • The proposed VICTORIA Grading standardizes severity assessment, and the VINTOSIS-3 protocol provides a structured approach to management.
