Naoya Yoshihara

Objective Analyses of Tessellated Fundi and Significant Correlation between Degree of Tessellation and Choroidal Thickness in Healthy Eyes

A tessellated fundus is a common characteristic of myopic eyes and is an important clinical marker for the development of retinochoroidal changes. However, the exact cause and significance of tessellated fundi have not been definitively determined. We determined the degree of tessellation in fundi objectively in normal, non-pathological myopic eyes, and correlated the degree of tessellation and the choroidal thickness (CT) and axial length (AL). This was a prospective observational cross sectional study. The eyes were classified subjectively into three groups based on the degree of tessellation observed ophthalmoscopically. Digital color fundus photographs were assessed for the degree of tessellation by ImageJ, an image processing program. Three tessellated fundus indices (TFIs) were calculated and were compared to the three subjectively-determined groups. The subfoveal and nasal CTs were measured in the optical coherence tomographic images. The correlations between the TFIs and the CT were calculated. Additionally, the correlation between the TFIs and the AL was calculated. One hundred right eyes of 100 healthy volunteers (mean age 25.8±3.9 years) were studied. Ophthalmoscopically, 57 eyes were placed in the non-tessellated group, 27 eyes into the weakly tessellated group, and 16 eyes into the strongly tessellated group. There was a significant correlation between the subjective classifications and the TFI values (P<0.05, Kruskal-Wallis test). All of the TFIs were significantly associated with the subfoveal and nasal CT (R = −0.20 to −0.24, P<0.05). The TFIs were not significantly correlated with the ALs. In conclusion, the significant correlation between the subjective and objective classifications of the degree of tessellation indicates that TFIs can be used to classify the degree of tessellation. The results indicate that the differences in the CT account for the degree of tessellation.

Structural Changes of Inner and Outer Choroid in Central Serous Chorioretinopathy Determined by Optical Coherence Tomography

Purpose To determine the structural changes of the choroid in eyes with central serous chorioretinopathy (CSC) by enhanced depth imaging optical coherence tomography (EDI-OCT). Methods A retrospective comparative study was performed at two academic institutions. Forty eyes with CSC, their fellow eyes, and 40 eyes of age-matched controls were studied. Subfoveal cross sectional EDI-OCT images were recorded, and the hypo reflective and hyperreflective areas of the inner and outer choroid in the EDI-OCT images were separately measured. The images were analyzed by a binarization method to determine the sizes of the hyporeflective and hyperreflective areas. Results In the inner choroid, the hyperreflective area was significantly larger in the CSC eyes (35,640±10,229 μm2) than the fellow eyes (22,908±8,522 μm2) and the control eyes (20,630±8,128 μm2; P<0.01 vs control for both, Wilcoxon signed-rank test). In the outer choroid, the hyporeflective area was significantly larger in the CSC eyes (446,549±121,214 μm2) than the control eyes (235,680±97,352 μm2, P<0.01). The average ratio of the hyporeflective area to the total choroidal area was smaller in the CSC eyes (67.0%) than the fellow eyes (76.5%) and the control eyes (76.7%) in the inner choroid (P<0.01, both). However, the ratio was larger in the CSC eyes (75.2%) and fellow eyes (71.7%) than in the control eyes (64.7%) in the outer choroid (P<0.01, both). Conclusions The larger hyperreflective area in the inner choroid is related to the inflammation and edema of the stroma of the choroid in the acute stage of CSC. The larger hyporeflective areas in the outer choroid is due to a dilatation of the vascular lumens of the larger blood vessels. These are the essential characteristics of eyes with CSC regardless of the onset.

Penetration of bevacizumab and ranibizumab through retinal pigment epithelial layer in vitro.

Purpose: To determine the permeability of bevacizumab and ranibizumab through highly-polarized retinal pigment epithelial (RPE) cells in vitro. Methods: Highly-polarized RPE cells were cultured in the upper chamber of a Transwell culture system. Bevacizumab or ranibizumab was added to the upper chamber. After 3 hours, the concentrations of bevacizumab or ranibizumab were determined in the upper and lower chambers. The cytotoxicities of the two anti-vascular endothelial growth factor agents were determined histologically. The effects of inhibiting endocytosis by pharmacologic inhibitors were also evaluated. Results: The concentration of ranibizumab was higher than that of bevacizumab in the lower chamber (P < 0.05). Vascular endothelial growth factor was found mainly in the lower chamber under normal conditions. However, the concentration of vascular endothelial growth factor in the lower chamber was significantly less when ranibizumab was added to the upper chamber than when bevacizumab was added. Histology showed no obvious changes in bevacizumab-exposed or ranibizumab-exposed RPE cells. Pretreatment with protein kinase C inhibitor staurosporine had significant negative effects on the permeability of bevacizumab and ranibizumab (P < 0.05). Conclusion: Ranibizumab is more permeable than bevacizumab through the highly-polarized RPE layer at clinically equivalent concentrations, and their permeability was partially protein kinase C–dependent. Ranibizumab might be more therapeutically effective than bevacizumab on choroidal neovascularization beneath the RPE layer.

Circumpapillary course of retinal pigment epithelium can be fit to sine wave and amplitude of sine wave is significantly correlated with ovality ratio of optic disc.

The purpose of this study was to develop a method of quantifying the degree of optic disc tilt in normal eyes. This was a prospective, observational cross sectional study of 126 right eyes of 126 healthy volunteers. The optic disc tilt was determined from the circular peripapillary optical coherence tomographic (OCT) scan images. The course of the retinal pigment epithelium (RPE) layer in the peripapillary cross sectional scan images was fit to a sine wave curve, and the amplitude of the sine curve was used to reflect the degree of the optic disc tilt in the optical axis. The repeatability of the amplitude determinations was calculated. The correlation between the amplitude and the ovality ratio of the optic disc was determined. The correlation between the amplitude and the body height was also calculated. The mean amplitudewas 36.6 ± 17.5 pixels, which was significantly and inversely correlated with the ovality ratio of the optic disc (R = -0.59, P<0.001). The intra-rater and inter-rater correlation coefficients of the amplitude were significant high (P<0.001, both). The amplitude was significantly and inversely correlated with the body height (R = -0.38, P<0.001), but not with the axial length. In conclusion, a sine wave function can be used to describe the course of the RPE in the circumpapillary OCT images. The results indicate that the amplitude of the sine wave can be used to represent the degree of optic disc tilt. Thus, the sine wave analyses can be used as a quantifiable and repeatable method to determine the optic disc tilt.

Location of Tessellations in Ocular Fundus and Their Associations with Optic Disc Tilt, Optic Disc Area, and Axial Length in Young Healthy Eyes.

Tessellated fundus is found as common and early-phase characteristic of myopic eyes and their locations are varied among patients. However, the relationship between their locations and morphological parameters of the eyes is still unknown. The purpose is this study is to determine the locations of the tessellations in the ocular fundus of young healthy eyes, and to determine relationships between their locations and morphological parameters of the eyes. This is a prospective observational cross sectional study of 126 eyes of 126 healthy volunteers (mean age 26.0±4.1 years). The eyes were classified into eight groups based on the location of the tessellations; no tessellation, temporal, infra-temporal, inferior, nasal, peripapillary, whole retina, and unclassified tessellations. The degree of optic disc tilt was quantified using a sine curve fitting program on the optical coherence tomographic circle scan images. The correlations between each tessellation location and the axial length, area of the optic disc plus conus (AOC), and optic disc tilt were determined. Forty-four eyes were place in the no tessellation group, 12 eyes in the temporal, 21 eyes in the infra-temporal, 9 eyes in the inferior, 8 eyes in the nasal, 15 eyes in the peripapillary, 11 eyes in the whole, and 6 eyes in the unclassified groups. The differences in the axial lengths between the no tessellation group and the infra-temporal groups were significant. A significant difference was found in the AOC between the no tessellation and the inferior, infra-temporal, and peripapilalry groups. A significant difference was found in the optic disc tilt between the no tessellation and infra-temporal groups (P<0.05). The tessellations are located at specific sites in the fundus of young healthy eyes with the infra-temporal location most frequent. It was correlated with some parameters associated with myopia.

Correlations Between Retinal Nerve Fiber Layer Thickness and Axial Length, Peripapillary Retinal Tilt, Optic Disc Size, and Retinal Artery Position in Healthy Eyes.

Purpose: To determine the correlations between the retinal nerve fiber layer thickness (RNFLT) and the axial length, peripapillary retinal tilt (PRT), and optic disc size, and retinal artery position. Methods: A prospective, observational cross-sectional study of 119 healthy right eyes of 119 volunteers. All participants underwent comprehensive ophthalmologic examinations including peripapillary RNFLT imaging and measurements of the axial length. The RNFLT was determined by the TOPCON 3D OCT-1000, MARK II. The RNFLT in a 3.4 mm circular scan was divided into 12 clock-hour sectors and 4 quadrant sectors around the optic disc. The PRT was assessed using the RNFLT B-scan images. The angle between the supra-temporal and infra-temporal retinal arteries was determined in the color fundus photographs. The correlations between the sectorial RNFLTs and the axial length, PRT, optic disc size, and artery angles were determined by simple and multiple regression analyses. Results: Multiple regression analyses showed that the nasal and inferior quadrants and the whole RNFLT were significantly and negatively correlated with the axial length (standardized coefficient (SC)=−0.39 to −0.30, P<0.05). The PRT was significantly and positively associated with all of the quadrants and the whole RNFLT (SC=0.22 to 0.45, P<0.05). The retinal artery angle was significantly and negatively associated with the temporal RNFLT and positively associated with inferior RNFLT (SC=−0.49 to 0.31, P<0.05). The optic disc size was significantly and positively associated with the superior and nasal quadrants, and the whole RNFLT (SC=0.20 to 0.27, P<0.05). Conclusions: The axial length, PRT, optic disc size, retinal artery angle can affect the peripapillary RNFLT. These variables should be considered when assessing the peripapillary RNFLT.

PERMEABILITY AND ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR EFFECTS OF BEVACIZUMAB, RANIBIZUMAB, AND AFLIBERCEPT IN POLARIZED RETINAL PIGMENT EPITHELIAL LAYER IN VITRO.

Purpose: To determine the effects of bevacizumab, ranibizumab, and aflibercept on the permeability and the effects of anti–vascular endothelial growth factor (VEGF) on highly polarized retinal pigment epithelial cells (RPECs) in vitro. Methods: Highly polarized RPECs were cultured in the upper chamber of a Transwell system. Anti-VEGF antibodies were added to the upper chamber, and the concentrations of the drugs in the lower chambers were measured. The permeability rates of the three anti-VEGF drugs through the RPEC layer and the concentration of VEGF in each chamber were determined. Results: The permeability of aflibercept was significantly lower by about 40% than that of bevacizumab through the RPEC layer (P < 0.05). Ranibizumab was significantly more permeable through the RPECs than bevacizumab (180% of bevacizumab, P < 0.05). Although VEGF was almost absent in the upper chamber after exposure to the 3 antibodies, it was decreased more significantly with aflibercept than with bevacizumab in the lower chamber (2.8% vs. 65.8% of control; P < 0.01). Ranibizumab also decreased the VEGF level compared with bevacizumab (31.7% vs. 65.8% of control; P < 0.01). Conclusion: The greater reduction of the amount of VEGF in the lower chamber by aflibercept and ranibizumab than bevacizumab may explain why aflibercept and ranibizumab are more effective than bevacizumab against type 1 choroidal neovascularization.

AMOUNT OF RESIDUAL SILICONE OIL IN VITREOUS CAVITY IS SIGNIFICANTLY CORRELATED WITH AXIAL LENGTH.

Purpose: To determine the parameters of the eye that are significantly correlated with the amount of residual silicone oil remaining after most of it is removed by vitrectomy. Methods: Nineteen eyes of 19 patients who had silicone oil removed were studied. The day after the surgery for silicone oil removal, B-scan ultrasonography was performed, and the residual silicone oil droplets were observed as hyperechoic particles in the ultrasonographic images. The images of the vitreous cavity were binarized, and the ratio of area of hyperechoic particles to the total vitreous area was quantified and named the silicone oil index (SOI). The correlations between SOI and clinical findings were determined. Results: The SOI was significantly and positively correlated with the axial length (AL) and the preoperative intraocular pressure (AL, R = 0.676, P = 0.002; preoperative intraocular pressure, R = 0.771, P < 0.001). Partial correlation analysis showed that the AL remained significantly correlated with the SOI but the preoperative intraocular pressure was not (AL, R = 0.734, P = 0.001; preoperative intraocular pressure, R = 0.417, P = 0.096). None of the other clinical factors was significantly correlated with the SOI. Conclusion: Considering the significant correlation between the amount of residual silicone oil and the AL of the eye, myopic eyes should be carefully scrutinized for residual silicone oil.

Peripapillary Nerve Fiber Elevation in Young Healthy Eyes

PURPOSE Eyes with a peripapillary nerve fiber elevation (pNFE) are those with a discrepancy between the optic disc margin in a color fundus photograph and the Bruchs membrane opening in an optical coherent tomographic (OCT) cross-sectional image. The purpose of this study was to determine the prevalence of pNFE in young healthy eyes, and to compare the axial length and optic disc tilt between pNFE and non-pNFE groups. METHODS This was a prospective, observational, cross-sectional study of 117 right eyes. All participants (mean age 25.8 ± 4.0 years) underwent a comprehensive ophthalmologic examination. The pNFE was determined from the color fundus photographs, scanning laser ophthalmoscopic images, and optic disc cross-sectional OCT images. The degree of optic disc tilt was determined by the sine curve technique. Mann-Whitney U tests were used to determine the significance of the differences in the axial length and optic disc tilt between the pNFE and non-pNFE groups. RESULTS Fifty-nine eyes were placed in the pNFE group and 58 eyes in the non-pNFE group. The axial length of the pNFE group (26.0 ± 1.4 mm) was significantly longer than that of the non-pNFE group (24.9 ± 1.2 mm; P < 0.001). The optic disc tilt of the pNFE group (42.1 ± 16.5 pixels) was significantly greater than that of the non-pNFE group (33.2 ± 16.8 pixels; P = 0.003). CONCLUSIONS The presence of pNFE is not rare in young healthy eyes. The eyes with pNFE have longer axial lengths and greater optic disc tilt. The pNFE should be considered when the disc margin is assessed.

Relationship between retinal artery trajectory and axial length in Japanese school students

PurposeThe trajectories of the supratemporal and infratemporal retinal arteries are associated with the position of the nerve fiber layer defects of glaucomatous eyes. However, no reports have thus far been published on changes in the retinal artery trajectory (RA trajectory) along with growth. Thus, the purpose of this study was to investigate the differences in the RA trajectories of elementary and junior high school students and the associations with axial length (AL).Study designProspective cross-sectional observational study.MethodsIn total, 122 right eyes of healthy elementary school students (61 boys, 61 girls) and 170 right eyes of healthy junior high school students (83 boys, 87 girls) were studied. The AL was measured and color fundus photographs were taken, and used for the analysis. The RA trajectory was plotted in the color fundus photographs and fitted to a second-degree polynomial equation,