Blood-Brain Barrier Disruption Associated With Maculopathy

Investigators advocate for ophthalmic examination before and annually following the tumor treatment.

In a case series of blood-brain barrier disruption-associated maculopathy, researchers found an association between it and the number of blood-brain barrier disruption therapy sessions, which could suggest a dose-dependent effect, according to a study, published in JAMA Ophthalmology.

“In some cases, maculopathy progression, including enlargement of geographic atrophy, occurred years after completion of systemic therapy,” according to investigators. “These findings may have important implications for patient education and ophthalmic monitoring.”

The study, a retrospective case series, examined how blood-brain barrier disruption is a systemic therapy used to treat malignant central nervous system tumors that “has been linked to poorly understood pigmentary maculopathy.” Researchers examined  data collected between February 1, 2006 and December 31, 2019 from 283 patients who were treated at a single center with osmotic blood-brain barrier disruption and chemotherapy for malignant central nervous system tumors. A total of 68 (mean [SD] age, 46.0 [17.9] years; 25 [38.5%] female) patients had a follow-up ophthalmic evaluation.

They found, following the removal of 3 patients for bilateral media opacities, pigmentary maculopathy in 32 of 65 (49.2%) who had blood-brain barrier disruption treatment. “The number of [blood-brain barrier disruption] treatment sessions, but not age, [central nervous system] malignant cancer type, or systemic chemotherapy agent, was associated with maculopathy development (odds ratio, 1.30; 95% CI, 1.12-1.50; P =.001),” the research shows.

Researchers noted progressive enlargement of geographic atrophy in 5 eyes of 3 patients, and neovascularization in 1 eye, following the end of blood-brain barrier disruption therapy.

“Of importance, [blood-brain barrier disruption] can be a life- and function-saving therapy, and therefore we are not advocating changes to systemic treatment,” researchers report. “Rather, these findings may have implications for patient education and ophthalmic monitoring. We propose that patients undergo a baseline ophthalmic examination before the start of [blood-brain barrier disruption] therapy, as well as yearly ophthalmic examinations during and after systemic treatment with retinal imaging if a pigmentary maculopathy or [retinal pigment epithelium] atrophy is detected.”

Study limitations included its retrospective design and, the researchers say, the fact it did not have “uniform follow-up.” Additionally,  the relatively high mortality rate also limited follow-up.


Simonett J, Skalet A, Lujanet B, et al. Risk factors and disease course for blood-brain barrier disruption–associated maculopathy. JAMA Ophthalmol. Published online December 3, 2020. doi: 10.1001/jamaophthalmol.2020.5329