1. Acridine orange leukocyte fluorography
We developed a technique to visualize leukocytes in the retinal microcirculation of living monkeys, rats, and mice using acridine orange, a nuclear staining dye, and the scanning laser ophthalmoscope in 1993. Using this technique named acridine orange leukocyte fluorography in monkeys, rats, and mice, we studied the dynamics of leukocytes in various retinal pathologies, including diabetic retinopathy and retinal ischemia, to clarify their pathological significance. We discovered that leukocytes plug the retinal capillaries at the very early stage of diabetes mellitus and that leukocytes play a very important role in the development of retinal ischemia and neovascularization in diabetic retinopathy. The findings of these studies suggest that capillary embolization by leukocytes is the initial step in the pathogenesis of diabetic retinopathy.
2. Ultra-wide field fundus imaging
Ultra-wide field fundus imaging by Optos^Ⓡ covers 80% of the fundus (200°) in one shot and has been used to study the significance of peripheral fundus lesions in various chorioretinal diseases. With this technique, we demonstrated the new findings in the peripheral fundus pertinent to diabetic retinopathy, retinal vein occlusion, age-related macular degeneration, pathological myopia, and central serous chorioretinopathy. Quantitative evaluation of the ultra-wide field indocyanine green infrared angiograms revealed that the density of choroidal vessels was higher not only in the posterior pole but throughout the fundus in eyes with central serous chorioretinopathy.
3. Optical coherence tomography (OCT) and OCT angiography
We used OCT angiography to demonstrate that the foveal avascular zone (FAZ) becomes enlarged before the development of diabetic retinopathy in diabetic patients and that the severity of diabetic retinopathy increases as the FAZ size increases. We also demonstrated that most of the microaneurysms are located at the deep capillary plexus of the retina in the area of diabetic macular edema. Additionally, we reported that OCT angiography is very useful to evaluate the retinal microcirculation in eyes with retinal vein occlusion. We successfully developed an OCT instrument with diagnostic support function using machine learning algorithm.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 124: 125-154, 2020.