Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing is substantially effective in sickle cell disease but may not completely eliminate vaso-occlusive activity, according to a case study published in Case Reports in Hematology

This finding was based on the results of optical coherence tomography angiography (OCT-A), which was capable of detecting and measuring micro-occlusive events within the retinal capillary bed as an indicator of systemic ischemic disease activity. 

When performed following red blood cell exchange transfusion or CRISPR-based gene therapy, OCT-A can determine the efficacy of the treatment. 

“Noninvasive ocular biomarkers . . . have the potential to allow hematologists to be less reliant on blood draws and measures such as number of [vaso-occlusive crises] and hospitalizations over time to grade ischemic disease activity, measure disease progression, prognosticate risk of systemic and ophthalmic complications, and measure treatment response objectively and quantitatively,” the researchers wrote.

It is difficult to estimate the risk of complications in patients with sickle cell disease due to the large variability of the disease. Moreover, existing biomarkers often fail to reliably predict ischemic disease activity and the efficacy of treatments.

Read more about the complications of sickle cell disease

In the present study, a team of researchers from the United States presented the case of a 23-year-old male patient with sickle cell anemia (HbSS) who had a history of many complications. The patient required chronic monthly red blood cell transfusions and multiple red blood cell exchange transfusions. 

He eventually underwent CRISPR-based gene therapy and did not require any repeat blood transfusions thereafter. The patient underwent OCT-A twice while preparing for gene-editing therapy, once 2 months after his first exchange transfusion, which showed a relatively high disease activity, and again 2 weeks after the second exchange transfusion, showing substantial improvements.

The patient underwent OCT-A a third time approximately 6 months after the administration of the gene-editing therapy, the results of which showed that there was a reduction in microvascular occlusive events comparable to that seen with exchange transfusion, but without the need for repeat treatment. This was maintained during the following 3 visits.

“OCT-A may be useful for minimizing time to decision making to maintain or alter therapy, including identifying candidates for adjunctive oral therapy following gene editing, which can decrease patient morbidity and mortality while reducing healthcare expenditures,” the researchers concluded.


Pinhas A, Zhou DB, Otero-Marquez O, et al. Efficacy of CRISPR-based gene editing in a sickle cell disease patient as measured through the eye. Case Rep Hematol. 2022;2022:6079631. doi:10.1155/2022/6079631