Chikako Hara

En-face high-penetration optical coherence tomography imaging in polypoidal choroidal vasculopathy.

Aim To observe the choroidal microstructure in polypoidal choroidal vasculopathy (PCV) using high-penetration optical coherence tomography (HP-OCT) with a long-wavelength light source that visualises tissue beneath the retinal pigment epithelium (RPE) and deep choroid, and to compare the findings with those of indocyanine green angiography (ICGA). Methods In this retrospective, non-invasive, observational case series, 19 eyes (18 patients) with PCV were observed using HP-OCT (swept source, 100 000 A-scans/s, 1060 nm wavelength) and ICGA. The HP-OCT scan protocol was a 3×3-mm or 6×6-mm square containing 256×256 or 512×128 A-scans. The choroidal thickness (CT) was measured using HP-OCT. Results ICGA showed 43 polypoidal lesions in 14 eyes and a vascular network in 17 eyes. HP-OCT showed 41 of the 43 polypoidal lesions visualised by ICGA as RPE rings with inner reflectivity and 15 eyes with a vascular network. Six eyes with RPE rings with inner reflectivity on HP-OCT were not visualised on ICGA images. The choroidal vascular network was dilated in 14 (33%) of 43 polypoidal lesions and 22 (47%) of 47 polypoidal lesions on ICGA and HP-OCT images, respectively. The mean CT at the fovea was 250 μm. The CT at the dilated choroidal vessels beneath the polypoidal lesions was significantly (p = 0.0095) thicker than that of the undilated choroidal vessels beneath the polypoidal lesions. Conclusions HP-OCT can visualise choroidal vascular abnormalities in eyes with PCV and should be useful for understanding the pathogenesis of these abnormalities.

Characteristics Of Central Serous Chorioretinopathy Complicated By Focal Choroidal Excavation

Purpose: To investigate the characteristics of central serous chorioretinopathy complicated by focal choroidal excavation (FCE) using fundus angiography and optical coherence tomography (OCT). Methods: A retrospective single-institution study. We reviewed the charts of 7 eyes of 7 patients (5 men, 2 women; mean age, 56.9 ± 9.8 years) with central serous chorioretinopathy complicated by FCE using fundus angiography and OCT. Results: In six of the seven eyes, the points of leakage were at the edge of FCE on OCT. All FCE lesions were hypofluorescent from early to late phase on indocyanine green angiography. All eyes had late-phase hyperfluorescence on indocyanine green angiography secondary to choroidal vascular hyperpermeability around the FCE lesion. Five fellow eyes also had choroidal vascular hyperpermeability. The mean subfoveal choroidal thicknesses by swept source high-penetration OCT were 377 &mgr;m and 333 &mgr;m in the fellow eyes, a difference that did not reach significance (P = 0.21). Conclusion: Fundus angiography and OCT showed that choroidal circulatory disruption and atrophic retinal pigment epithelium at the FCE lesion might be related to central serous chorioretinopathy complicated by FCE.

Laser-Induced Choroidal Neovascularization in Mice Attenuated by Deficiency in the Apelin-APJ System

PURPOSE To investigate the role of the apelin-APJ system in the development of choroidal neovascularization (CNV). METHODS Experimental CNV was induced by laser photocoagulation in wild-type (WT), apelin-deficient (apelin-KO), and apelin receptor (APJ)-deficient (APJ-KO) mice. The gene expression levels of angiogenic or inflammatory factors were determined by quantitative real-time reverse transcription-polymerase chain reaction. APJ expression in CNV lesions was examined by immunohistochemistry. The sizes of the CNV lesions in the three mouse models were measured and compared histologically using isolectin B4 staining. Macrophage recruitment was measured by flow cytometric analysis. Proliferation of endothelial cells was determined using the alamar Blue assay. RESULTS Laser photocoagulation significantly increased expression of apelin and APJ in the retina-retinal pigment epithelium (RPE) complex. APJ immunoreactive cells were found in the CNV lesions and colocalized with platelet endothelial cell adhesion molecule-1, an endothelial cell marker. The sizes of the CNV lesions in apelin-KO or APJ-KO mice decreased significantly compared with those in the WT mice. Macrophages in the RPE complex of the apelin-KO mice, in which gene expression of the inflammatory factors was almost equal to that in WT mice, were recruited as a result of laser photocoagulation to the same degree as in WT mice. In addition, apelin small and interfering RNA (siRNA) suppressed proliferation of endothelial cells independently of vascular endothelial growth factor (VEGF) receptor 2 signaling, while VEGF increased expression of apelin and APJ in human umbilical vein endothelial cells. CONCLUSIONS The results suggested that the apelin-APJ system contributes to CNV development partially independent of the VEGF pathway.

ONE-YEAR RESULTS OF INTRAVITREAL AFLIBERCEPT FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.

Purpose: To evaluate the 1-year results of intravitreal aflibercept injections for polypoidal choroidal vasculopathy based on indocyanine green angiography findings. Methods: Twenty-nine eyes with treatment-naive polypoidal choroidal vasculopathy treated with intravitreal aflibercept injections and followed longer than 1 year were retrospectively reviewed. The best-corrected visual acuity, optical coherence tomography findings, and polypoidal lesions in indocyanine green angiography were evaluated. Results: The mean number of injections through 1 year was 3.9 ± 1.9 (range: 1–8). Fourteen eyes (48%) were received no additional injections because of no recurrence of exudative change after the first loading dose. The mean best-corrected visual acuity levels at 6 months and 1 year significantly improved, and the mean central retinal thickness significantly decreased at all observation points from the baseline. At 3 months, the polypoidal lesions completely resolved in 19 (66%) eyes. At 1 year, the complete resolution of polypoidal lesions was seen in 4 of 10 eyes with persistent polypoidal lesions at 3 months. However, polypoidal lesions recurred at 1 year in 5 of 19 eyes (26%) with complete resolution of polypoidal lesions at 3 months. Conclusion: Aflibercept is effective for the eyes with treatment-naive polypoidal choroidal vasculopathy to achieve the resolution of polypoidal lesions. The athors need to carefully observe the eyes after confirming complete resolution of polypoidal lesion because of recurrent polyps seen in one-quarter of the study eyes.

A prospective multicenter study on genome wide associations to ranibizumab treatment outcome for age-related macular degeneration

We conducted a genome-wide association study (GWAS) on the outcome of anti-VEGF treatment for exudative age-related macular degeneration (AMD) in a prospective cohort. Four hundred and sixty-one treatment-naïve AMD patients were recruited at 13 clinical centers and all patients were treated with 3 monthly injections of ranibizumab followed by pro re nata regimen treatment for one year. Genomic DNA was collected from all patients for a 2-stage GWAS on achieving dry macula after the initial treatment, the requirement for an additional treatment, and visual acuity changes during the 12-month observation period. In addition, we evaluated 9 single-nucleotide polymorphisms (SNPs) in 8 previously reported AMD-related genes for their associations with treatment outcome. The discovery stage with 256 patients evaluated 8,480,849 SNPs, but no SNPs showed genome-wide level significance in association with treatment outcomes. Although SNPs with P-values of <5 × 10−6 were evaluated in replication samples of 205 patients, no SNP was significantly associated with treatment outcomes. Among AMD-susceptibility genes, rs10490924 in ARMS2/HTRA1 was significantly associated with additional treatment requirement in the discovery stage (P = 0.0023), and pooled analysis with the replication stage further confirmed this association (P = 0.0013). ARMS2/HTRA1 polymorphism might be able to predict the frequency of injection after initial ranibizumab treatment.

Effects of a Lutein Supplement on the Plasma Lutein Concentration and Macular Pigment in Patients With Central Serous Chorioretinopathy

PURPOSE To investigate the effects of lutein supplementation on plasma lutein concentrations and the macular pigment optical density (MPOD) in central serous chorioretinopathy (CSC). METHODS In this double-masked placebo-controlled study, 20 patients received lutein 20 mg/d and 19 received placebo. The plasma lutein concentration and MPOD using autofluorescence spectrometry (density unit, DU) were measured at baseline and 1 and 4 months. RESULTS The mean plasma lutein concentrations and MPOD values in the lutein and control groups, respectively, were 91.5 and 78.2 ng/mL and 0.444 and 0.437 DU at baseline; 204.9 and 79.3 ng/mL and 0.460 and 0.442 DU at 1 month; and 228.0 and 78.4 ng/mL and 0.441 and 0.421 DU at 4 months. The plasma concentration in the lutein group was significantly higher than in controls at 1 and 4 months (P < 0.0001 for both comparisons); however, the MPOD values did not differ significantly between groups at 1 (P = 0.479) or 4 months (P = 0.883). In patients with a plasma lutein concentration below the mean level in 20 age-matched healthy subjects (mean 105.3 ng/mL; n = 13 in lutein group, n = 15 in control group), the control MPOD values significantly (P = 0.0430) decreased at 4 months (mean baseline, 0.437 DU; 4 months, 0.404 DU). The MPOD in the lutein group remained at the baseline level (mean baseline, 0.426 DU; 4 months, 0.438 DU) (P = 0.6542). CONCLUSIONS The MPOD did not increase in patients with CSC with short-term lutein supplementation; however, among patients with low plasma lutein, supplemental lutein prevented a decline in MPOD that was observed in control subjects (www.umin.ac.jp/ctr number, UMIN000005849).

A Multicenter Randomized Controlled Study of Antioxidant Supplementation with Lutein for Chronic Central Serous Chorioretinopathy

Purpose: To investigate functional and morphological changes in patients with chronic central serous chorioretinopathy after supplementation with antioxidants containing lutein or a placebo. Procedures: One hundred eyes of 100 patients were randomly divided into 2 groups, one taking tablets with lutein plus other antioxidants and the other taking a placebo for 6 months. Best-corrected visual acuity (BCVA) and the subfoveal fluid height on optical coherence tomography were measured. Results: Seventy-nine patients (37 in the supplementation and 42 in the placebo group) completed the 6-month follow-up. In the supplementation group, mean BCVA showed significant improvement (p = 0.003), while there was no significant change in the placebo group (p = 0.589). The mean subfoveal fluid height was significantly reduced, by 28.6%, in the supplementation group (p = 0.028), in contrast to 3.3% in the placebo group (p = 0.898). Conclusions: Antioxidant supplementation significantly reduced subfoveal fluid height. The impacts of antioxidant supplementation on BCVA remain to be elucidated in future studies.

Factors Associated With Corneal Deformation Responses Measured With a Dynamic Scheimpflug Analyzer

Purpose The purpose of this study was to clarify correlations between corneal deformation parameters measured with a dynamic Scheimpflug analyzer and baseline factors such as axial length, intraocular pressure (IOP), age, central corneal thickness (CCT), and corneal curvature. Methods Ninety-six eyes of 96 healthy subjects (mean 55.2 ± 16.1 years of age) were examined using a dynamic Scheimpflug analyzer. Eighteen of 35 deformation parameters were selected for analyses based on measurement reliability and clinical relevance. The associations between corneal deformation parameters and axial length, IOP, age, CCT, and average corneal power were evaluated using multivariate regression analyses. Results Deformation parameters were correlated significantly with axial length (n = 13), IOP (n = 13), age (n = 8), and CCT (n = 6) in the multivariate models. Longer axial length corresponded with greater corneal deformability, less viscous damping, and less movement of the entire eye. Higher IOP was associated with greater corneal resistance and less movement of the entire eye. Older age was associated with less corneal deformability and greater movement of the entire eye. Corneal curvature was correlated significantly with only three deformation parameters. Conclusions This study clarified the substantial impact of axial length, age, and IOP on the biomechanical responses of the cornea and the entire eye. In contrast, corneal curvature did not affect most of the deformation parameters. The current results confirmed the importance of corneal biomechanics, especially in eyes with longer axial length and in older subjects.

Simulation of panretinal laser photocoagulation using geometric methods for calculating the photocoagulation index

Purpose To establish geometrically based methods for simulating panretinal laser photocoagulation (PRP) for the photocoagulation index. Methods A formula for calculating the curved surface area of a spherical dome was used for the simulation. If the radius of the dome is c and the height of the dome is h, then the curved surface area (S) of the dome is S = π (c2 + h2). We calculated the area of the whole retina using this formula and the anatomical dimensions of the standard eyeball. To simulate PRP with a 400-μm spot on the retina with 1-spot spacing, we drew 400-μm-diameter circles, separated by 400 μm, on a retinal map. We calculated the ratio of the total retinal photocoagulated area to the whole retina, termed the photocoagulation index, in order to investigate the impact of the extent of the photocoagulated area and the pulse duration on PRP. Results The whole retinal area was 1,092 mm2. The numbers of spots in the scattered and full-scattered PRP were 1,222 and 1,814, respectively. The photocoagulation index was 14.1% and 20.9% for scattered and full-scattered PRP, respectively. These values changed to 14.3% (5.6%) and 21.3% (8.3%), respectively, for PRP with a 100-ms pulse or a 20-ms pulse. Conclusions This method will be useful for investigating the impact of various PRP parameters (duration, spacing, intensity of burns, extent of photocoagulated area, etc.) on the photocoagulation index.

Characteristics of patients with neovascular age-related macular degeneration who are non-responders to intravitreal aflibercept

Purpose To investigate the frequency and patient characteristics that influence anatomic response of intravitreal aflibercept in treatment-naïve neovascular age-related macular degeneration (AMD). Design Retrospective, interventional, consecutive case series. Methods Three hundred and sixty-five eyes of 365 patients with AMD who underwent 3 monthly intravitreal aflibercept treatments with follow-up for at least 12 months were investigated. Treatment response was evaluated as follows. Responders were defined as those with complete resolution of exudation, including intraretinal oedema, subretinal fluid and pigment epithelial detachment, or more than a 100 µm decrease of central retinal thickness at 3 months compared with baseline. Non-responders were defined as patients exhibiting an increase in exudation or a decreased central retinal thickness of less than 100 µm. Results Nineteen (5.2%) of 365 eyes were identified as non-responders. The remaining were responders to intravitreal aflibercept. The non-responders group was significantly associated with choroidal vascular hyperpermeability on indocyanine green angiography and lower frequency of subretinal hyper-reflective materials on optical coherence tomography. The central choroidal thickness at baseline and after 3 monthly injections tended to be thicker in the non-responder group than the responder group, although the differences did not meet statistical significance (p=0.066 and p=0.051, respectively). Additional treatments with either intravitreal ranibizumab or PDT in combination with aflibercept were effective in 15 (79%) of 19 non-responders. Conclusion Intravitreal aflibercept is effective for treating eye pathology in most naïve AMD cases. However, non-responsiveness may occur in small subgroup of patients with choroidal vascular hyperpermeability.