OBJECTIVES Diabetic macular edema (DME) is a serious condition occurring in patients with diabetic retinopathy (DR) which is a common complication of diabetes. Understanding not only objective measurements such as visual acuity, but also the patients’ perspective is important in gaining a comprehensive understanding of the impact of DME and its treatment on their functioning and well-being. The aim of this study is to understand possible measurements to investigate the impact of DME on health-related quality of life (HRQoL), by identifying currently available measurements, their ability to differentiate between DR and DME, and possible reasons for difficulties in measuring HRQoL specifically for DME. METHODS We performed a literature review on articles describing instruments of patient-reported outcomes (PRO) for DME. We summarized the current evidence on the usefulness of the instruments and whether they differentiate between DR and DME. In addition, we investigated possible hurdles in measuring HRQoL for DME, given the clinical understandings of the systemic aspects of DME. RESULTS We identified seven condition-specific or vision-specific measurements and seven general measurements including generic HRQoL and utilities for possible instruments for DME. However, realistic use for DME appears questionable even for vision-related measurements. The possible reasons could be that: 1) DME is not the primary disease, 2) many of DME patients have comorbidities such as DR, cataracts, and DR-induced glaucoma, and 3) those comorbidities itself may lead to decreased visual acuity with decreased HRQoL. CONCLUSIONS Evidence is limited when measuring the impacts of DME on diabetic patients largely due to the lack of an effective PRO instrument for DME. The major difficulties in developing such instruments is that DME patients have complex health statuses, which provides for multiple reasons in decrease of QoL which may not be directly due to their DME.