The macula, which is so elaborately "created" for advanced visual function, can be affected by various lesions. Why is the macula prone to lesions? I would like to present the research that has been undertaken to answer the question using macular imaging and discuss the pathogenesis of macular disease and its evolvement to treatment, as well as the prospects for future research.
I. Analyses of choroidal and scleral structures using optical coherence tomography (OCT)
Using OCT, we analyzed the structure of the choroid, which has long been a black box. Photodynamic therapy (PDT) for central serous chorioretinopathy (CSC) was found to normalize pathological choroidal thickness, choroidal vessel diameter, and vascular hyperpermeability and eliminate subretinal fluid. This was the first study to show that choroidal morphology is altered by treatment and is closely related to treatment efficacy. Choroidal status was also involved in disease activity in polypoidal choroidal vasculopathy. Choroidal thickness is also reduced in neovascular age-related macular degeneration (AMD) after PDT or anti-vascular endothelial growth factor drugs, and the degree of reduction is linked to treatment response. With these findings, we suggested a new concept "choroidal findings-based neovascular AMD treatment strategy." The importance of choroidal thickness is now being recognized, as it is measured in clinical trials. In Vogt-Koyanagi-Harada (VKH) disease, the choroidal thickness markedly increases in the acute phase and rapidly decreases with treatment. The same is true of the papillitis type of VKH disease, which is sometimes difficult to distinguish from optic neuritis and other conditions. Choroidal observation using OCT is useful in making the diagnosis and determining the efficacy of treatment.
Analysis of deep scleral images in the highly myopic eyes group and tilted disc syndrome group showed that scleral thickening is confined to the macula and that the morphological abnormalities cause various macular lesions. In highly myopic eyes, scleral elongation accompanied by extension of axial length is not uniform. There is localized scleral thickening at the macula, which suggests there may be a mechanism that preserves ocular morphology to maintain visual function.
II. Development of ultra-widefield OCT and approaches to elucidating pathophysiology
We are now developing ultra-widefield OCT in a collaborative study. It can image the area of 31.5 mm in width and 10.9 mm in depth from the posterior pole to the equator of the fundus. It can observe peripheral retinal lesions such as rhegmatogenous retinal detachment and extensive choroidal structure, volume, and ocular morphology. Using ultra-widefield OCT, we revealed the choroidal thickening in CSC is localized in the posterior pole, and there was no significant difference in the peripheral fundus between CSC and normal eyes. This suggests that CSC has an ocular morphology in which serum retention to the choroid tends to occur at the posterior pole. It provides a clue to the question "why does CSC develop at the macula?"
III. Analysis of foveal structure using OCT angiography (OCTA)
During foveal formation and development, the inner retinal layer moves efferently to form foveal depression and foveal avascular zone (FAZ). OCTA, which can noninvasively evaluate retinal capillaries, performs volume scans of OCT images, allowing detailed observation of morphological changes in the fovea and FAZ evaluation. We found that even in normal eyes, there are cases in which the inner retinal layer remains without FAZ, which is a mild congenital foveal hypoplasia.
Eyes with a history of retinopathy of prematurity (ROP) also had reduced or absent FAZ area and residual inner retinal layer at the fovea, and FAZ area was correlated with gestational age. Underdeveloped fovea persisted into childhood in eyes with a history of ROP. The foveal bulge was located within the FAZ in all eyes, including those with extremely small FAZ, indicating a close relationship between FAZ formation and the development of the photoreceptor layer.
IV. Elucidation of the fovea formation process using mathematical models
Foveal development is not well understood, though it has been studied using a limited number of autopsy eyes from humans and other primates. Therefore, we aim to elucidate the mechanisms of FAZ formation and foveal depression development in the human retina by reproducing the morphogenetic process in silico using mathematical models. The mathematical model of human retinal vascular patterns provided the developmental process of retinal vessels that form the FAZ and reproduced the peripheral avascular zone and curvatures seen in ROP eyes. In the foveal depression formation model, a central elastic area was established, and horizontal and vertical forces were applied to produce a depression similar to the OCT image of the fovea. These models are being applied to disease simulation. The tendency for morphological changes to occur in the macula might be related to the elasticity of the fovea.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 128: 159-196, 2024.