Diabetic macular edema is the primary cause of vision loss in the working-age population in Japan. In 1995, the authors were the first to globally report that vascular endothelial growth factor (VEGF) is the causative agent of diabetic macular edema. Over the past 30 years since this discovery, intravitreal injections of anti-VEGF drugs have become the primary choice for treating diabetic macular edema. When vision loss occurs because of macular edema, it is recommended to initiate anti-VEGF drugs early to absorb an edema for preventing damage to photo-receptor cells (induction-phase treatment). Subsequently, intravitreal injections of anti-VEGF drugs are periodically administered to prevent recurrence of edema (maintenance-phase treatment). Reports suggest that successful implementation of this approach (i.e., preventing damage to photo-receptor cells and recurrence of edema) can lead to the restoration of corrected visual acuity (1.0).
However, the recommended protocols from these clinical studies involve frequent intravitreal injections of anti-VEGF drugs over several years, posing challenges in terms of high drug costs and the burden of clinic visits; thus, implementing the protocols in clinical practice is difficult. To address this issue, we have refined the treatment approach by reducing the number of anti-VEGF intravitreal injections to save the vision of patients with diabetic macular edema.
Specifically, a combination of methods, such as direct laser coagulation (50 µm, 0.03 s, 150-250 mW), a method preventing leakage from microaneurysms, was employed to absorb an edema while minimizing the number of anti-VEGF intravitreal injections as much as possible. Under this approach, it is crucial to consistently confirm the presence of clinically significant macular edema (CSME), which threatens visual acuity, using optical coherence tomography (OCT) macular thickness maps. Even in cases with good visual acuity, CSME often approaches the fovea. Performing panretinal photocoagulation directly in such cases can induce visual impairment because of macular edema. Monitoring with OCT macular thickness maps, along with the concurrent use of anti-VEGF intravitreal injections and direct laser coagulation on microaneurysms, is essential to complete panretinal photocoagulation without expanding CSME into the fovea.
Finally, we reported on the ongoing research involving artificial intelligence-inferred fluorescein angiography (AI-FA), which is based on OCT angiography (OCTA), for the detection of leakage without the use of contrast agents, thus eliminating the risk of anaphylactic shocks.
This review serves as a guidebook for young ophthalmologists, broadening their perspectives to the global level by learning from the past struggles and failures and establishing long-term research plans. Moreover, the clinical cases and treatment protocols described herein will contribute to the management of diabetic macular edema by ophthalmologists in Japan in their daily clinical practices. Finally, heartfelt gratitude is extended to all the collaborators who contributed to this research.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 128: 197-215, 2024.