4. Discussion
PDR, visual loss, blindness, tractional retinal detachment, Diabetes mellitus, retinal ischemia, retinal damage, TEAEs, NPDR, Diabetes, vitreous hemorrhage, diabetes
ADVERSE EFFECTS, PROLIFERATIVE, RETINAL ISCHEMIA, VITREOUS HEMORRHAGE, TYPE 2 DIABETES, PATHOGENESIS, DISEASES, DIABETES, TRACTIONAL RETINAL DETACHMENT, DISEASE STILL, DIABETES MELLITUS, RETINAL DAMAGE, MALIGNANCIES, LEAKAGE, GENOTOXICITY, COMPLICATIONS, BLINDNESS, DISEASE, DIABETES
Diabetes mellitus is one of the most persistent diseases in human history. Despite the tremendous achievements in diabetes research, this disease still negatively affects patients’ well-being with numerous complications in varying loci and severity grades [Recent DR treatment trends have two main therapeutic goals: (i) prevention of progression from NPDR to PDR, which has a high risk of visual loss due to vitreous hemorrhage or tractional retinal detachment, and (ii) prevention of loss of central vision due to DME [Diabetes is a disease in which high levels of circulating blood sugar damage blood vessels [EG-Mirotin was developed to prevent retinal damage and blindness by restoring capillaries before their damage progresses to an irreversible stage. Existing anti-VEGF antibodies for intraocular injection reduce damage to new blood vessels in the irreversible stage [In the present study, progression to proliferative DR did not occur in any of the participants. Moreover, both ischemic and leakage index values determined in UWFA images of lesions related to fundus microvascularization were significantly reduced compared with baseline values. Of note, a greater degree of change was observed in patients who had a larger ischemic index value at baseline. The participants were further categorized into two groups based on the cutoff of 1.59% in the baseline ischemic index. There was a significant interaction between group assignment and therapeutic effect over time, of which statistical significance was only observed in the >1.59 group in the post hoc comparison. It is expected that the ≤1.59 group showed no difference in the ischemic index over time because there was little room for change, as the initial ischemic value was ≤1.59%, with a few patients having an ischemic index of zero. The lack of index change can also be interpreted as the absence of disease deterioration. As retinal ischemia is a major factor in the pathogenesis of PDR [We found no serious adverse effects or safety concerns following EG-Mirotin administration. None of the participants reported TEAEs that resulted in drug discontinuation. In preclinical studies, EG-Mirotin had no acute or genotoxicity. EG-Mirotin alone did not induce angiogenesis and had no growth-promoting effects on malignancies [Despite showing promising results, this study has a few limitations. Based on our preclinical experience, we chose to use 3 mg of EG-Mirotin, which may not be a sufficient dose to cause substantial changes in retinal blood vessels. Theoretically, the dose could be increased to 10 mg per administration. However, we need to collect more safety data to justify a dose increase. The small number of subjects in this trial limits our ability to precisely define safety and efficacy. In the IIb clinical trial that we are planning for the future, we believe that between 100 and 300 participants should be enrolled, which is a generally accepted number of participants. Because type 1 and type 2 diabetes play different mechanisms, this study should be considered separately with sufficient samples. Hormonal changes in studies of gender differences should be considered in future trials. In the present study, the participants visited the clinic during the treatment period (i.e., a total of 5 days: V2–V6). A daily clinic visit is a nuisance for many patients. Therefore, our future goal is to prepare EG-Mirotin for self-injection, as established for insulin administration, so patients will not have to visit the clinic daily for their drug treatment.