Retinal pigment epithelium melanin distribution estimated by polarisation entropy and its association with retinal sensitivity in patients with high myopia.

PURPOSE: To investigate retinal sensitivity of highly myopic eyes without choroidal neovascularisation (CNV) or patchy chorioretinal atrophy (PCA) and investigated its association with anatomical characteristics including melanin distribution at the retinal pigment epithelium (RPE), which was evaluated with polarisation-sensitive optical coherence tomography (PS-OCT). DESIGN: Retrospective consecutive observational cohort study. METHODS: We included highly myopic eyes (refractive error ≤-8.0 dioptres or axial length of ≥26.5 mm) from patients at the University of Tokyo Hospital. Retinal sensitivity was measured by microperimetry at 25 sectors within 6 degrees from the fovea. Depolarisation value, which reflected melanin pigmentation, was measured by a clinical prototype of PS-OCT and was parameterised as polarimetric entropy. Retinal sensitivity or entropy at the RPE in high myopia was compared with emmetropic control subjects. The association of retinal sensitivity with age, axial length, entropy, or choroidal thickness was assessed in per-eye and per-sector analysis. RESULTS: Twenty-three highly myopic eyes (age, 66.6±12.3 years) were included. The average retinal sensitivity was 25.3±3.0 dB, which was significantly decreased compared with the control (p<0.0001). The average entropy at the RPE in the highly myopic eyes was significantly lower than in the control (p<0.0001). Univariate analysis followed by multivariate analysis showed that besides age, axial length or choroidal thickness, RPE entropy was independently associated with retinal sensitivity (ß=4.4; 95% CI 0.5 to 8.3; p=0.03). CONCLUSIONS: Decreased depolarisation at the RPE measured with PS-OCT, which reflected altered melanin pigmentation, was independently associated with reduced retinal sensitivity in patients with early stages of myopic maculopathy without CNV or PCA.

Changes in entropy on polarized-sensitive optical coherence tomography images after therapeutic subthreshold micropulse laser for diabetic macular edema: A pilot study.

PURPOSE: To investigate the dynamics of the healing process after therapeutic subthreshold micropulse laser (SMPL) for diabetic macular edema (DME) using polarization-sensitive optical coherence tomography (PS-OCT). METHODS: Patients with treatment-native or previously-treated DME were prospectively imaged using PS-OCT at baseline, 1, 2, 3, and 6 months. The following outcomes were evaluated: changes in the entropy value per unit area (pixel2) in the retinal pigment epithelium (RPE) on the B-scan image; changes in the entropy value in each stratified layer (retina, RPE, choroid) based on the ETDRS grid circle overlaid with en face entropy mapping, not only the whole ETDRS grid area but also a sector irradiated by the SMPL; and the relationship between edema reduction and entropy changes. RESULTS: A total of 11 eyes of 11 consecutive DME patients were enrolled. No visible signs of SMPL treatment were detected on PS-OCT images. The entropy value per unit area (pixel2) in the RPE tended to decrease at 3 and 6 months from baseline (35.8 ± 17.0 vs 26.1 ± 9.8, P = 0.14; vs 28.2 ± 18.3, P = 0.14). Based on the en face entropy mapping, the overall entropy value did not change in each layer in the whole ETDRS grid; however, decrease of entropy in the RPE was observed at 2, 3, and 6 months post-treatment within the SMPL-irradiated sectors (P < 0.01, each). There was a positive correlation between the change rate of retinal thickness and that of entropy in the RPE within the SMPL-irradiated sector at 6 months (r2 = 0.19, P = 0.039). CONCLUSION: Entropy measured using PS-OCT may be a new parameter that facilitates objective monitoring of SMPL-induced functional changes in the RPE that could not previously be assessed directly. This may contribute to a more promising therapeutic evaluation of DME. CLINICAL TRIAL: This clinical study was registered in UMIN-CTR (ID: UMIN000042420).

Assessment of macular function in patients with non-vascularized pigment epithelial detachment.

Non-vascularized pigment epithelial detachments (PED) are usually associated with dry age-related macular degeneration (AMD). In this study, we aimed to investigate the correlation between visual function and morphologic parameters. Seventeen eyes of eleven patients with non-vascularized AMD were enrolled. In addition to conventional optical coherence tomography (OCT), polarization-sensitive optical coherence tomography (PS-OCT) measurements were performed by evaluating the regularity of retinal pigment epithelium (RPE) entropy within the PED area. Retinal sensitivity was measured with MP-3 microperimetry, and retinal sensitivities within (RSin) and outside (RSout) the PED area were calculated. The relationship between OCT parameters and visual function was analyzed. As a result, there was a significant difference between the RSin and RSout (p < 0.001, Wilcoxon signed rank test). Moreover, RSin was significantly related to logMAR VA (p = 0.033, linear mixed model). The regularity of RPE entropy was significantly related to visual acuity and RSin (p = 0.00038, p = 0.031, linear mixed model), although neither the height nor area of PED correlated with visual function. Our results suggest that retinal sensitivity is significantly deteriorated within the PED area and RPE entropy measured with PS-OCT was closely related to visual function in eyes with non-vascularized PED.

Three-Dimensional Distribution Of Fundus Depolarization and Associating Factors Measured Using Polarization-Sensitive Optical Coherence Tomography.

Purpose: To investigate the three-dimensional distribution and associating demographic factors of depolarization, using polarization-sensitive optical coherence tomography (PS-OCT), to evaluate melanin pigmentation in the retinal pigment epithelium (RPE) and choroid in healthy eyes. Methods: In total, 39 unaffected healthy eyes of 39 subjects were examined using a PS-OCT clinical prototype. The degree of depolarization, expressed as the polarimetric entropy, was assessed in the RPE, the superficial and the total choroid layer, especially in the center, the inner, or the outer areas centered at the fovea. The values and their association with the demographic data were analyzed. Near-infrared fundus autofluorescence (NIRAF) was also used, in the same manner, for the comparison. Twenty-eight of 39 eyes were measured twice to evaluate intrasession repeatability. Results: Both the polarimetric entropy in the RPE and the gray level in NIRAF, decreased from the center to the periphery (P < 0.001). The polarimetric entropy in the RPE was significantly associated with age in each area (P ≤ 0.001). In the RPE and the superficial choroid, the polarimetric entropy was negatively associated with axial length in each area (P ≤ 0.002). The intraclass correlation coefficient of the polarimetric entropy in the same session was excellent in each area of the RPE, superficial choroid, or total choroid layer (0.94-0.98). Conclusions: The distribution of fundus melanin pigment-related depolarization was evaluated using PS-OCT. The depolarization was associated with the subjects' demographic data, such as age or axial length. Translational Relevance: The presented information in healthy eyes provides an essential basis for the investigation into a variety of chorioretinal pathologies.

Imaging of a retinal pigment epithelium aperture using polarization-sensitive optical coherence tomography.

PURPOSE: To evaluate cases with a retinal pigment epithelium (RPE) aperture using polarization-sensitive optical coherence tomography (PS-OCT). STUDY DESIGN: Retrospective consecutive case series. METHODS: A retrospective study that included three eyes (three patients) with RPE aperture and age-related macular degeneration (AMD) evaluated at the Macular Clinic in Tokyo University Hospital. A three-dimensional dataset of depolarization information was obtained with a clinical prototype of PS-OCT. RESULTS: All patients were categorized as intermediate AMD. RPE apertures were identified with PS-OCT as discontinuities of depolarization in the RPE layer of the pigment epithelial detachment (PED). A nonuniform decrease of depolarization in the RPE layer was also observed around the aperture. Two findings were observed above the aperture, intraretinal focal areas with high reflectivity and increased depolarization and subretinal bands with moderate reflectivity and low depolarization. Retinal sensitivity according to fundus microperimetry measured at 25 points was significantly associated with the degree of depolarization at the corresponding area (r-square = 0.60, p = 0.0001). CONCLUSION: The RPE aperture was characterized as a round discontinuity of depolarization. The findings with PS-OCT suggest atrophic changes in the overlying RPE of the PED. The degree of depolarization was associated with retinal sensitivity. The current results indicate that RPE apertures developed within the spectrum of atrophic AMD.

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.

Two-year outcome of treat-and-extend aflibercept after ranibizumab in age-related macular degeneration and polypoidal choroidal vasculopathy patients.

BACKGROUND: The purpose of the study was to evaluate the 2-year outcome and predictive factors of treat-and-extend aflibercept in patients with eyes affected by typical neovascular age-related macula degenelation (t-AMD) or polypoidal choroidal vasculopathy (PCV), who were switched from ranibizumab. PATIENTS AND METHODS: The patients underwent three monthly aflibercept injections and subsequent administration following the treat-and-extend protocol. Sixty-two eyes of 62 patients were reviewed retrospectively. R statistical software was used for statistical analysis. RESULTS: Twenty-two eyes were t-AMD and the remaining 40 eyes were PCV. There was no significant difference in the logarithm of the minimal angle of resolution visual acuity (VA) between baseline and 2 years after switching to aflibercept (0.40 vs 0.40; P=0.99). Multivariate analyses suggested that the following factors were significantly correlated with better VA at 2 years after switching to aflibercept: patients with PCV, the absence of intraretinal fluid at baseline, and better VA at baseline. CONCLUSION: In conclusion, VA was maintained and there was an anatomical improvement at 2 years in patients with t-AMD and PCV who were switched from ranibizumab to treat-and-extend aflibercept. PCV patients showed more favorable visual outcomes and less injections at 2 years compared to t-AMD patients. Intraretinal fluid and VA at baseline were predictors of VA at 2 years.

Unilateral pigmented paravenous retinochoroidal atrophy with retinitis pigmentosa in the contralateral eye: A case report.

PURPOSE: We describe a sporadic case of unilateral pigmented paravenous retinochoroidal atrophy (PPRCA) with retinitis pigmentosa (RP) in the contralateral eye. OBSERVATIONS: a 24-year-old female aware of the narrowing of visual field was examined at our hospital. Funduscopic examination revealed left eye showing retinochroidal atrophy along the retinal veins with pigment accumulation while right eye showing peripheral diffuse retinal pigmented epithelium atrophy with bone spicule pigmentation. Fundus autofluorescence, electroretinogram, visual field test and optic coherent tomography were also performed and obtained results were compatible with funduscopic observation. CONCLUSIONS AND IMPORTANCE: Simultaneous manifestation of PPRCA and RP observed in this case is rare and supports a shared genetic basis between the two diseases. Further genetic investigations are needed to elucidate the etiology and to properly manage PPRCA.

Inner retinal changes in acute-phase Vogt-Koyanagi-Harada disease measured by enhanced spectral domain optical coherence tomography.

PURPOSE: To assess the changes of inner retinal thickness in patients with Vogt-Koyanagi-Harada disease (VKH) using enhanced spectral domain optical coherence tomography (SD-OCT). METHODS: We retrospectively reviewed enhanced SD-OCT images of 12 eyes of seven consecutive patients with VKH in both acute and convalescent phases. Inner retinal thickness, measured from the inner limiting membrane to the inner plexiform layer (ILM-IPL), and nerve fiber layer (NFL) thickness at 1.5 and 2.0 mm along the outer border of the IPL from the central fovea at nasal, temporal, superior, and inferior points were measured. Twelve eyes of 12 patients with central serous chorioretinopathy (CSC) were evaluated as controls. RESULTS: In the VKH patients, ILM-IPL thickness in the acute phase was significantly greater than that in the convalescent phase at each point of the retina; however, an intraretinal cystoid space was not observed. The thickness of the NFL was significantly larger in the nasal quadrant. On fluorescein angiography, no leakage from the retinal vasculature was seen in any of the cases. In the CSC cases, no differences were seen in ILM-IPL thickness between the acute and convalescent phases at any point. CONCLUSIONS: Inner retinal thickness in the acute phase of VKH is larger than in the convalescent phase.

Visualization of cystoid macular oedema using a scanning laser ophthalmoscope in the retro-mode.

PURPOSE: To investigate cystoid macular oedema using a scanning laser ophthalmoscope. METHODS: We retrospectively reviewed the medical records of 101 eyes with cystoid macular oedema because of various aetiologies. All eyes were examined with a new, commercially available scanning laser ophthalmoscope in the retro-mode with an infrared laser. RESULTS: In all eyes, scanning laser ophthalmoscope in the retro-mode showed numerous oval or polygonal cystoid spaces. Most eyes showed a large cystoid space beneath the fovea, with surrounding small cystoid spaces. The area of the foveal cystoid space showed a correlation with its height, as measured with optical coherence tomography (R = 0.60, P < 0.0001). Visual acuity, however, did not show any correlation with either the area of the foveal cystoid space or area of all of the cystoid spaces in the macular area. CONCLUSION: Scanning laser ophthalmoscope in the retro-mode can show each cystoid space located in any layer of the retina and allows us to detect the extent of cystoid macular oedema.

Ultrahigh-resolution versus speckle noise-reduction in spectral-domain optical coherence tomography.

Ultrahigh-resolution (UHR) spectral-domain optical coherence tomography (SD-OCT) and speckle noise-reduced SD-OCT instruments were compared with regard to their ability to visualize retinal microstructures and detect micropathologies in the same series of eyes in this hospital-based study. Both the instruments identically visualized normal retinal structures, except for the retinal ganglion cell layer, which was better delineated by the speckle noise-reduced SD-OCT instrument. Retinal pigment epithelium (RPE) and Bruch's membrane were better delineated by UHR SD-OCT. Retinal and sub-RPE pathologies were also identically visualized by both the instruments. Layer differentiation for locating each pathology was better visualized by speckle noise-reduced SD-OCT.

Cystoid macular edema in polypoidal choroidal vasculopathy viewed by a scanning laser ophthalmoscope: CME in PCV viewed by SLO.

Visual prognosis for polypoidal choroidal vasculopathy (PCV) is reported to be relatively good. However, some eyes in the end-stage of PCV show cystoid macular edema (CME) with severe loss of vision. We examined two eyes with CME in the end-stage of PCV. The fundus of each of these eyes was examined noninvasively with a new commercially available scanning laser ophthalmoscope (SLO) in the retro-mode with an infrared laser. In the retro-mode, scattered light that passed the aperture deviated laterally, giving a shadow to the silhouetted cystoid spaces, enabled visualisation of the CME. In each eye, although no cystoid spaces were detected on fundus photographs, monochromatic images obtained with an SLO in the retro-mode showed numerous cystoid spaces on the disciform scar. SLO in the retro-mode can show each cystoid space located in any layer of the retina, and allows us to detect the extent of the CME.