Ocular toxicity of intravitreal melphalan for retinoblastoma in Chinese patients

Abstract

Background To evaluate the efficacy, complications, and clinical characteristics, including the ocular toxicity, of intravitreal melphalan(IVM) treatment for vitreous seeding in Chinese retinoblastoma patients. Methods This was a retrospective, non-comparative analysis including 30 consecutive eyes of 23 patients with viable persistent or recurrent vitreous seeding following retinoblastoma treatment. All of the eyes received IVM injections (20–33 μg). Vitreous seeding control, determination of the ocular toxicity, and the clinical characteristics of intravitreal melphalan treatments were observed. Results The mean patient age at the time of the injection was 28 months (median = 22 months, range = 12–50 months). In total, 80 injections were administered in 30 eyes, the overall enucleation-free survival rate was 83.3% (25/30). The complications included retinal pigment epithelium (RPE) and choroidal atrophy (19/30, 63.3%), pupillary synechiae (13/30, 43.3%), iris atrophy (12/30, 40%), retinal vascular occlusion (12/30, 40.0%), optic atrophy (6/30, 20%), vitreous hemorrhage (3/30, 10%), persistent hypotonia and phthisis bulbi (4/30 13.3%), and cataracts (8/30, 26.6%). Twelve eyes demonstrated grade 3 or greater IVM-associated retinal or anterior segment toxicity post injection. Mean dosage given showed significant difference between the groups. There were no significant differences in the retinal toxicity grades regarding the seed classification or seed regression patterns. Conclusions Intravitreal melphalan is an effective treatment for refractory vitreous seeding from retinoblastoma, but exhibits both anterior and posterior segment toxicity in Chinese patients.

Successful growth of fresh retinoblastoma cells in chorioallantoic membrane

“…The findings observed using different concentrations of Melphalan point to potential toxicity causing thrombo-hemorrhagic changes when used in higher doses. Despite the conjectural nature of this finding, it correlates to clinical outcomes reported of vascular occlusion and vitreous hemorrhage following intravitreal Melphalan in eyes with RB [ 12 ].…”

Outcomes of Group D Retinoblastoma With Resistant Vitreous Seeds After Integration of Intravitreal Chemotherapy to the Treatment Protocol

“…Based on another theory [ 20 ] that darkly pigmented eyes are more vulnerable to intraocular inflammation. Xue et al also postulated that intravitreal melphalan in the Asian population might incite inflammation more than that of the Caucasian population [ 21 ]. Some studies support the use of topotecan in such eyes as it is thought to induce lesser inflammation [ 22 , 23 ].…”

Intravitreal Melphalan for Retinoblastoma: The Impact of Toxicity on Recurrence and Ultimate Globe Salvage

“…While singular IVM dosages higher than 30 µg may increase the risk of toxicity, neither the cumulative dosage nor the number of injections that an eye received correlates with toxicity grade [17]. It has also been previously suggested that more deeply pigmented eyes may be at increased risk for toxicity due to increased absorption of melphalan by the choroid and retinal pigment epithelium [7,11,24,25]. Regardless, not all deeply pigmented eyes experience IVM toxicity.…”

“…Although severe toxicity was initially thought to be associated with posterior vitreous detachment, thus concentrating the chemotherapy to the retina, a review of a larger cohort of patients failed to find an association between posterior vitreous detachment and toxicity [10]. A recent publication from a Chinese cohort described significant toxicity: 40% of patients with grade 3 or higher toxicity, 40% with vascular occlusion (similar to the acute hemorrhagic presentation), 40% anterior toxicity, and upwards of 20% with optic atrophy [11].…”