Eye-Saving Chemotherapy With Melphalan Increases Pediatric Cataract Risk

An eye-saving chemotherapy approach to treating retinoblastoma increases pediatric patients’ risk for cataracts, according to results of a study published in the British Journal of Ophthalmology. Cataract risk in children was associated with repeated intra-arterial chemotherapy (IAC) and intravitreous chemotherapy (IvitC) with melphalan.

The treatment landscape for intraocular tumors among children has shifted from radiotherapy to in situ chemotherapy. This shift has improved survival outcomes, however, reports of adverse outcomes, including cataracts, have increased.

This retrospective analysis evaluated cataract risk among 184 eyes of 151 children (median age, 18.0 (range, 0.2-81.6) months, 51.0% boys) who underwent the eye-saving chemotherapy treatment in one or both eyes between 2017 and 2021 at the Shanghai Ninth People’s Hospital in China.

Cases of unilateral disease treated comprised 56.5% of participants who underwent the repeated IAC and intravitreous chemotherapy treatment. Patients had a median intraocular pressure (IOP) of 12 (range, 5-41) mm Hg, 58.2% had an International Intraocular Retinoblastoma Classification (IIRC) of group E, and 42.4% had a mixed growth pattern.

During an average 27.6 months of follow-up, 31 eyes developed cataracts. The cataract group were more likely to have endophytic growth (32.3% vs 13.1%; P =.02) and have higher IOP (mean, 16.8 vs 13.5 mm Hg; P =.02) than the noncataract group, respectively.

In addition, eyes that developed cataract received more cycles of IAC (mean, 4.0 vs 3.0 cycles; P =.02), a higher dose of melphalan (mean, 6.2 vs 5.1 mg; P <.001), and more cycles of intravitreous chemotherapy (mean, 3 vs 2 cycles; P =.02) compared with cataract-free eyes, respectively.

In the multivariate analysis, risk for cataracts associated with melphalan dose in IAC (hazard ratio [HR], 3.50; 95% CI, 1.65-7.42; P =.001), the number of intravitreous chemotherapy cycles (HR, 1.38; 95% CI, 1.02-1.85; P =.04), and IOP (HR, 1.06; 95% CI, 1.02-1.10; P =.003).

Despite ocular toxicities, the eye-saving chemotherapy approach remains a primary treatment for unilateral or bilateral retinoblastoma, and as a secondary treatment following failure of other treatments, according to the report.

“[T]his report demonstrated that cataract seen in retinoblastoma patients might be related to the growth pattern, intraocular pressure, the number of IAC cycles, melphalan dose per IAC cycle and the number of IvitC cycles,” the researchers report. “The toxic effect of melphalan is an essential factor in cataract development, as indicated by the association of cataract occurrence with the melphalan dose.”

The limitations of this study included the single center, retrospective design.