Choroidal infarction following ophthalmic artery chemotherapy

Abstract

BackgroundMethylenetetrahydrofolate reductase (MTHFR) genetic mutations and intra-procedural inhaled nitrous oxide (N2O) independently increase blood levels of homocysteine, a compound associated with thrombosis. Patients with MTHFR mutations who also receive N2O during ophthalmic artery chemotherapy (OAC) for retinoblastoma may have a heightened thrombotic risk.Case presentationsSingle-center retrospective review of pediatric patients with advanced retinoblastoma who received OAC and developed choroidal infarcts. Four retinoblastoma patients with advanced intraocular disease (2 males, 2 females: 13–58 months) experienced choroidal infarcts within the one-month period after OAC, in which procedural N2O induction was used (duration between 21 and 58 min). All 4 patients had MTHFR (chromosome 1p, position 36.22) genetic abnormalities: one was homozygous for the C677T mutation, one was C677T heterozygous, one was A1298C heterozygous, and one was heterozygous for both C677T and A1298C. In all 4 patients, indirect ophthalmoscopy and fundus photography showed marked disturbance of the retinal pigment epithelium and optical coherence tomography (OCT) confirmed thinning of the choroid. Follow-up time ranged from 15 to 46 months (median 21 months).ConclusionsChoroidal infarction in eyes treated with OAC developed in children who were both deficient in at least one working allele of the MTHFR gene (heterozygous or homozygous) and received N2O induction during OAC.

Conservative management of retinoblastoma: Challenging orthodoxy without compromising the state of metastatic grace. “Alive, with good vision and no comorbidity”

“…Finally, genetic predispositions to thromboembolism have been reported in association with choroidal occlusive vasculopathy, including sickle cell trait, prothrombin mutation, plasminogen activator inhibitor-1 polymorphism (Abramson et al, 2012b;Francis et al, 2012), as well as methylenetetrahydrofolate reductase (MTHFR) polymorphic alleles (Bohm et al, 2018). In the latter case, 4 patients were recently reported who inhaled nitrous oxide pre-intra-arterial chemotherapy resulting in an increase of homocysteine in the blood (Bohm et al, 2018). The exact role of these inherited thrombophilic traits among the patients with choroidal occlusive vasculopathy is still unknown.…”

Nitrous oxide inhalation-induced cerebral venous sinus thrombosis in a 20-year-old man: A case report

“…Moreover, nitrous oxide-induced thrombosis may also be attributed to acquired methylenetetrahydrofolate reductase (MTHFR) deficiency [ 1 ]. A patient with genetic MTHFR deficiency was reported to have deep vein thrombosis of the upper extremity and retinal vein without nitrous oxide [ 11 ], and pediatric retinoblastoma patients with MTHFR gene mutation were more likely to suffer choroidal infarction after nitrous oxide induction and subsequent ophthalmic artery chemotherapy [ 12 ]. Notably, one of the previous cases of nitrous oxide-induced intracranial thrombosis also had MTHFR mutations [ 6 ].…”