[Noninvasive analysis of retinal microstructure and function: challenges and a promising future]

Challenges in the evaluation of the retinal microstructure. To facilitate evaluation of the retinal microstructure we participated in the development of a scanning laser ophthalmoscope (SLO) for 32 years. The 'retro-mode' is the latest developed lateral aperture SLO made in Japan. This instrument enables us to observe the cystoid spaces and retinal microfolds underlying the epiretinal membrane. We investigated the pathogenesis and the mechanism of early development of idiopathic macular holes (MHs) and the vitreomacular interface in idiopathic full-thickness MHs using spectral-domain optical coherence tomography (SD-OCT). We studied the anatomic morphology of stage 1-A impending MHs, characterized by a foveolar yellow spot, using SD-OCT in the fellow eyes of patients diagnosed with a full-thickness MH. SD-OCT showed the reflectivity of the perifoveal posterior vitreous detachment (PVD) with vitreofoveal adhesion in the eyes with a yellow spot; the foveal microstructure had a triangular foveolar detachment of the cone outer segment tip line. The foveolar detachment of the cone outer segment tip line might be responsible for the yellow spot seen in stage 1-A MHs. Using SD-OCT, we also analyzed the vitreomacular interface in idiopathic full-thickness MHs and identified four configurations of the vitreomacular interface in MHs without a complete PVD. The majority, i.e., 92%, of eyes with a MH without a complete PVD are likely due to the anteroposterior vitreofoveal traction exerted by a perifoveal PVD. About 55% of cases with an open roof in the eyes without a complete PVD might be at risk of progression to operculum formation (loss of retinal tissue). 2. Challenges in the evaluation of retinal function SLO microperimetry is used to evaluate the retinal function during observation of the retinal microstructure. We evaluated the retinal sensitivity and the focal visual acuity using our original microperimetry program and clarified the characteristics of the preferred retinal locus (PRL) in macular diseases and the importance of the PRL evaluation. Further refinement of the SLO as an all-in-one instrument with the addition of a treatment feature is planned. We evaluated the retinal blood flow (RBF) using a laser Doppler velocimetry instrument that we developed. In clinical studies, we found that the RBF decreased in patients with type 2 diabetes mellitus with no or mild retinopathy compared with healthy subjects. In in vivo animal studies performed in anesthetized cats, we elucidated the mechanism of RBF regulation in response to physiologic stimuli, i.e., systemic hypoxia, hypercapnia, hyperoxia, hyperglycemia and hypertension. We showed that the retinal vascular endothelium plays an important role in regulating the RBF. In in vitro studies, we examined the effects of laminar shear stress on gene expression in human retinal microvascular endothelial cells (HRMECs) and found that long-term exposure to physiologic shear stress in the retinal arterioles upregulated eNOS and thrombomodulin mRNA expression and down-regulated ET-1 mRNA expression in the HRMECs. In ex vivo studies, we found that simvastatin, pioglitazone, resveratrol and fenofibrate dilated isolated porcine retinal arterioles, suggesting that systemic administration of these drugs may have the therapeutic potential to improve the impaired RBF in patients with type 2 diabetes mellitus. 3. Challenges to the development of a telemedicine support system We established a real-time telemedicine system that can transmit precise retinal images of patients between Asahikawa Medical University Hospital and our branch hospitals. We also developed a method of 3-dimensional high-definition transmission and stereoscopic display for ophthalmology. Moreover, we established a system to share medical information using Peer to Peer technology and network control technology that can transmit urgent information during a disaster. In response to a request from the Chinese Government, which has limited medical facilities in rural areas, we donated our system to four hospitals in Beijing, Shanghai, Sichuan and Shaanxi Provinces. As a result of the development of our unique telemedicine home medical care system, patients can be followed at home even after discharge from a hospital. 4. Conclusions. We believe that ophthalmologists can obtain important information about not only ocular but also systemic diseases by analyzing the retinal microstructure and functions simultaneously and can share this information worldwide via the telemedicine technology that we established, which can be a promising advance in patient care.