Results of a retrospective case series revealed an association between blood-brain barrier disruption (BBBD)–related maculopathy and the number of BBBD treatment sessions patients underwent, suggesting a dose-dependent effect of the treatment.
Results of a retrospective case series published in JAMA Ophthalmology revealed an association between blood-brain barrier disruption (BBBD)–related maculopathy and the number of BBBD treatment sessions patients underwent, suggesting a dose-dependent effect of the treatment.
BBBD, first introduced in the early 1980s, is a systemic therapy for malignant central nervous system (CNS) tumors. Specifically, the treatment aims to increase the penetration of chemotherapeutics into the CNS and “involves intra-arterial injection of a warmed, hypertonic mannitol solution to disrupt the tight junctions of vascular endothelial cells that form the blood-brain barrier followed by intra-arterial or intravenous chemotherapy,” researchers wrote.
However, BBBD has been linked to poorly understood pigmentary maculopathy unique to patients who undergo the therapy. This condition was first reported in 1986 in patients with primary CNS lymphoma.
To evaluate the rate of and potential risk factors for maculopathy development in patients with a variety of malignant CNS tumors treated with BBBD therapy, researchers conducted a case series study of patients presenting to the Oregon Health & Science University between February 2006 and December 2019. Functional and structural changes in eyes with BBBD-associated maculopathy were also evaluated after the completion of systemic therapy.
Using electronic health records, researchers collected and reviewed data of 238 patients treated with osmotic BBBD and chemotherapy for a CNS tumor. Of these patients, 68 individuals underwent an ophthalmoscopic examination and/or retinal imaging after their therapy start date. The mean (SD) patient age was 46 (17.9) years, and the majority (n = 43) of patients were male. However, 3 patients were excluded from final analyses “because the presence of maculopathy was unable to be determined because of dense bilateral vitritis or retinal disease attributable to intraocular lymphoma.”
Of the 65 individuals included, patients underwent a mean (SD) of 19.8 (10.9) BBBD treatment sessions. Thirty-three patients were diagnosed with primary CNS lymphoma, 21 had glioma, 6 had pineal tumor, and the remaining 5 had other types of tumors.
Analyses revealed:
- Pigmentary maculopathy was present in 32 of 65 patients (49.2%) treated with BBBD.
- The number of BBBD treatment sessions was associated with maculopathy development (odds ratio [OR], 1.30; 95% CI, 1.12-1.50; P = .001).
- Age, CNS malignant cancer type, and systemic chemotherapy agent were not associated with development of maculopathy.
- After completion of BBBD therapy, progressive enlargement of geographic atrophy occurred in 5 eyes of 3 patients, and choroidal neovascularization developed in 1 eye.
Notably, the study documented the first observation of BBBD-associated maculopathy in patients treated for malignant tumors other than primary CNS lymphoma, researchers wrote. They also concluded that their results suggest the treatment can be associated with late-onset and progressive retinal pigment epithelium (RPE) and outer retinal atrophy.
The absence of uniform follow-up among patients marks a limitation to the study, as researchers were unable to draw definite conclusion about the timeline of structural changes. Patients may also have alternative causes of the maculopathy, such as atypical age-related macular degeneration.
Future studies ought to include standardized imaging and follow-up intervals, in addition to OCT angiography and histopathologic correlation to help address the underlying mechanism of maculopathy.
“These findings may have implications for patient education and ophthalmic monitoring,” the authors concluded. “We propose that patients undergo a baseline ophthalmic examination before the start of BBBD therapy, as well as yearly ophthalmic examinations during and after systemic treatment with retinal imaging if a pigmentary maculopathy or RPE atrophy is detected.”
Reference
Simonett JM, Skalet AH, Lujan BJ, Neuwelt EA, Ambady P, Lin P. 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
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