Retinal pigment epithelium melanin imaging using polarization-sensitive optical coherence tomography for patients with retinitis pigmentosa.

This study aimed to evaluate the distribution of retinal pigment epithelium (RPE) melanin in patients with retinitis pigmentosa (RP) using entropy measurements by custom-made polarization-sensitive optical coherence tomography (PS-OCT) images, and compare entropy with the intensity of short-wavelength (SW) and near-infrared (NIR) autofluorescence (AF). We retrospectively reviewed the retinal images, including PS-OCT, SW-AF, and NIR-AF of patients with RP who had a hyperautofluorescent ring on AF. A total of 12 eyes of 12 patients (8 women and 4 men; mean age: 37.9 years) were included. There was a strong positive correlation between entropy value and NIR-AF intensity (r = 0.626, p < 0.001), and there was a very weak negative correlation between entropy value and SW-AF (r = - 0.197, p = 0.001). The mean values of the entropy in the foveal, temporal (2 mm from the fovea), and nasal (2 mm from the fovea) sections were 0.41 (± 0.09), 0.29 (± 0.08), and 0.26 (± 0.08), respectively. The entropy was significantly higher in the foveal section than in the temporal and nasal sections (p = 0.002 and p = 0.003, respectively). There was no significant difference between the entropies values for the temporal and nasal sections (p = 0.157). Age, logMAR best-corrected visual acuity, ellipsoid zone width, and central retinal thickness were not correlated with foveal entropy. We presented RPE melanin imaging in patients with RP using PS-OCT for the first time. PS-OCT can be a useful tool for monitoring patients with RP.

Melanin concentration and depolarization metrics measurement by polarization-sensitive optical coherence tomography.

Imaging of melanin in the eye is important as the melanin is structurally associated with some ocular diseases, such as age-related macular degeneration. Although optical coherence tomography (OCT) cannot distinguish tissues containing the melanin from other tissues intrinsically, polarization-sensitive OCT (PS-OCT) can detect the melanin through spatial depolarization of the backscattered light from the melanin granules. Entropy is one of the depolarization metrics that can be used to detect malanin granules in PS-OCT and valuable quantitative information on ocular tissue abnormalities can be retrived by correlating entropy with the melanin concentration. In this study, we investigate a relationship between the melanin concentration and some depolarization metrics including the entropy, and show that the entropy is linearly proportional to the melanin concentration in double logarithmic scale when noise bias is corrected for the entropy. In addition, we also confirm that the entropy does not depend on the incident state of polarization using the experimental data, which is one of important attributes that depolarization metrics should have. The dependence on the incident state of polarization is also analyzed for other depolarization metrics.

HLA-Matched Allogeneic iPS Cells-Derived RPE Transplantation for Macular Degeneration.

Immune attacks are key issues for cell transplantation. To assess the safety and the immune reactions after iPS cells-derived retinal pigment epithelium (iPS-RPE) transplantation, we transplanted HLA homozygote iPS-RPE cells established at an iPS bank in HLA-matched patients with exudative age-related macular degeneration. In addition, local steroids without immunosuppressive medications were administered. We monitored immune rejections by routine ocular examinations as well as by lymphocytes-graft cells immune reaction (LGIR) tests using graft RPE and the patient's blood cells. In all five of the cases that underwent iPS-RPE transplantation, the presence of graft cells was indicated by clumps or an area of increased pigmentation at 6 months, which became stable with no further abnormal growth in the graft during the 1-year observation period. Adverse events observed included corneal erosion, epiretinal membrane, retinal edema due to epiretinal membrane, elevated intraocular pressure, endophthalmitis, and mild immune rejection in the eye. In the one case exhibiting positive LGIR tests along with a slight fluid recurrence, we administrated local steroid therapy that subsequently resolved the suspected immune attacks. Although the cell delivery strategy must be further optimized, the present results suggest that it is possible to achieve stable survival and safety of iPS-RPE cell transplantation for a year.

Polarization-sensitive optical coherence tomography for estimating relative melanin content of autologous induced stem-cell derived retinal pigment epithelium.

Transplantation of autologous human induced pluripotent stem cell-derived retinal pigment epithelial (hiPSC-RPE) sheets is a promising therapy for age-related macular degeneration (AMD). As melanin content is a representative feature of healthy RPE, we used polarization-sensitive optical coherence tomography (PS-OCT) to estimate the relative melanin content of RPE in diseased and non-diseased area, and in human iPSC-RPE sheets in vitro and in vivo by evaluating the randomness of polarization (entropy). Two aged Japanese women, one with neovascular AMD that underwent transplantation of an autologous hiPSC-RPE cell sheet and another with binocular dry AMD, were selected for this study. Entropy value was minimal in cells containing no melanin, whereas that of human RPE and hiPSC-RPE sheets was high. En face entropy of the cultured hiPSC-RPE sheet was compared with its grey-scale photo and its values were found to be inversely correlated with the extent of absence of pigmentation in vitro. En face entropy maps were compared to colour fundus photographs, fundus autofluorescence images, and fluorescein angiography images from patients. Entropy values of intact and defective RPEs and of iPSC-RPE transplant areas were determined in vivo using PS-OCT B-scan images. PS-OCT was found to be applicable in the estimation of relative melanin content of cultured and transplanted RPEs in regenerative medicine.