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Recent concerns regarding the clinical utilization of clustered regularly interspaced short palindromic repeats (CRISPR) involve uncertainties about the potential detrimental effects that many arise due to unintended genetic changes, as in off-target mutagenesis, during CRISPR genome surgery. This review gives an overview of off-targeting detection methods and CRISPR's place in the clinical setting, specifically in the field of ophthalmology.As CRISPR utilization in the laboratory setting has increased, knowledge regarding CRISPR mechanisms including its off-target effects has also increased. Although a perfect method for achieving 100% specificity is yet to be determined, the past few years have seen many developments in off-targeting detection and in increasing efficacy of CRISPR tools.The CRISPR system has high potential to be an invaluable therapeutic tool as it has the ability to modify and repair pathogenic retinal lesions. Although it is not yet a perfect system, with further efforts to improve its specificity and efficacy along with careful screening of off-target mutations, CRISPR-mediated genome surgery potential can become maximized and applied to patients.