Choroidal morphologic features in central serous chorioretinopathy using ultra-widefield optical coherence tomography.

PURPOSE: To analyze the choroidal morphological changes in central serous chorioretinopathy (CSC) using ultra-widefield (UWF)-optical coherence tomography (OCT). METHODS: This single-center, case-control study included 65 CSC eyes (52 males; age, 55.6 ± 13.0 years) and 65 healthy eyes (50 males; age, 57.1 ± 17.9 years). UWF-OCT (viewing angle, 200°) with real-shape correction was used to create an automated choroidal thickness (CT) map. The CT map had three sub-areas: the central (0-30°), middle (30-60°), and peripheral areas (60-100°), and was divided by vertical and horizontal lines. Differences in the CT and the CT change rate (CTCR) from the central to peripheral areas were examined between the CSC and control groups after adjusting for subjects' demographic and clinical factors. Furthermore, we assessed the vortex veins dilation patterns (VVDP) in the macula and examined the CT and the CTCR differences between CSC patients and controls for each VVDP. RESULTS: CSC patients had greater CT than those of the controls in all sectors (CSC vs. controls, the peripheral area: supratemporal 284.4 ± 71.2 µm vs. 220.4 ± 71.2 µm, infratemporal 263.3 ± 69.2 µm vs. 195.3 ± 52.3 µm, supranasal 251.9 ± 70.3 µm vs. 189.5 ± 58.1 µm, infranasal 193.6 ± 71.2 µm vs. 146.3 ± 48.9 µm, P < 0.0001 for all sectors). The CTCR was apparently larger in CSC eyes than controls only for the upper-dominant type of VVDP (CSC patients vs. controls, supratemporal 32.1 ± 9.9% vs. 4.6 ± 23.1%, infratemporal 44.0 ± 11.2% vs. 25.6 ± 16.8%, supranasal 42.6 ± 9.8% vs. 22.2 ± 19.4%, infranasal 57.6 ± 41.2% vs. 41.2 ± 13.9%, P < 0.0001 for all sectors). CONCLUSIONS: CSC has a thicker choroid, even in the peripheral areas, and the macular choroidal thickening was more severe in the upper-dominant type of VVDP. VVDP may affect the location of excessive fluid.

Changes in choriocapillaris structure occurring in idiopathic macular hole before and after vitrectomy.

PURPOSE: The aim of this study was to analyze the anatomical choroidal vascular layers and the changes in idiopathic macular hole (IMH) eyes over time after vitrectomy. METHODS: This is a retrospective observational case-control study. Fifteen eyes from 15 patients who received vitrectomy for IMH and age-matched 15 eyes from 15 healthy controls were enrolled in this study. Retinal and choroidal structures were quantitatively analyzed before vitrectomy and 1 and 2 months after surgery using spectral domain-optical coherence tomography. Each choroidal vascular layer was divided into the choriocapillaris, Sattler's layer, and Haller's layer, and then, the choroidal area (CA), luminal area (LA), stromal area (SA), and central choroidal thickness (CCT) were calculated using binarization techniques. The ratio of LA to CA was defined as the L/C ratio. RESULTS: The CA, LA, and L/C ratios were 36.9 ± 6.2, 23.4 ± 5.0, and 63.1 ± 7.2 in the choriocapillaris of IMH and were 47.3 ± 6.6, 38.3 ± 5.6, and 80.9 ± 4.1 in that of control eyes, respectively. Those values were significantly lower in IMH eyes than in control eyes (each P < 0.01), whereas there was no significant difference in total choroid, Sattler's layer, and Haller's layer or CCT. The ellipsoid zone defect length showed a significant negative correlation with the L/C ratio in total choroid and with CA and LA in the choriocapillaris of IMH (R = - 0.61, P < 0.05, R = - 0.77, P < 0.01, and R = - 0.71, P < 0.01, respectively). In the choriocapillaris, the LA were 23.4 ± 5.0, 27.7 ± 3.8, and 30.9 ± 4.4, and the L/C ratios were 63.1 ± 7.2, 74.3 ± 6.4, and 76.6 ± 5.4 at baseline, 1 month, and 2 months after vitrectomy, respectively. Those values showed a significant increase over time after surgery (each P < 0.05), whereas the other choroidal layers did not alter consistently with respect to changes in choroidal structure. CONCLUSIONS: The current OCT-based study demonstrated that the choriocapillaris was exclusively disrupted between choroidal vascular structures in IMH, which may correlate with the ellipsoid zone defect. Furthermore, the L/C ratio of choriocapillaris recovered after IMH repair, suggesting an improved balance between supply and demand of oxygen that has collapsed due to temporary loss of central retinal function by IMH.

NORMAL PERIPHERAL CHOROIDAL THICKNESS MEASURED BY WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: Choroidal stasis plays an important role in the pathogenesis of many conditions and leads to choroidal thickening. However, the normal peripheral choroidal thickness (PCT) pattern remains unknown. This study investigated PCT and associated factors using ultrawidefield optical coherence tomography in healthy eyes. METHODS: This cross-sectional study included 120 healthy eyes (57 males; age, 52.0 ± 20.5 years). We used choroidal thickness maps created by ultrawidefield optical coherence tomography (viewing angle, 200°) with real-shape correction. The peripheral area was defined from 60° to 100° and further separated vertically and horizontally. The PCT and the correlations between PCT and subjects' characteristics were examined. RESULTS: The PCT were 227.1 ± 57.0 µ m, 199.6 ± 53.9 µ m, 196.6 ± 57.1 µ m, and 148.0 ± 38.2 µ m in supratemporal, infratemporal, supranasal, and infranasal areas, respectively. The thickest peripheral sector was most frequently observed in supratemporal (69.2%). The PCT negatively correlated with age in all regions ( P -values < 0.001) and axial length in supratemporal, supranasal, and infranasal areas ( P -values ≤ 0.003). The temporal PCT was thicker on the side contiguous with the posterior pole Haller's vessels ( P -values ≤ 0.020). CONCLUSION: The PCT is associated with age, axial length, and the running pattern of Haller's vessels.

Genetic LAMP2 deficiency accelerates the age-associated formation of basal laminar deposits in the retina.

The early stages of age-related macular degeneration (AMD) are characterized by the accumulation of basal laminar deposits (BLamDs). The mechanism for BLamDs accumulating between the retinal pigment epithelium (RPE) and its basal lamina remains elusive. Here we examined the role in AMD of lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes/phagosomes. LAMP2 was preferentially expressed by RPE cells, and its expression declined with age. Deletion of the Lamp2 gene in mice resulted in age-dependent autofluorescence abnormalities of the fundus, thickening of Bruch's membrane, and the formation of BLamDs, resembling histopathological changes occurring in AMD. Moreover, LAMP2-deficient mice developed molecular signatures similar to those found in human AMD-namely, the accumulation of APOE, APOA1, clusterin, and vitronectin-adjacent to BLamDs. In contrast, collagen 4, laminin, and fibronectin, which are extracellular matrix proteins constituting RPE basal lamina and Bruch's membrane were reduced in Lamp2 knockout (KO) mice. Mechanistically, retarded phagocytic degradation of photoreceptor outer segments compromised lysosomal degradation and increased exocytosis in LAMP2-deficient RPE cells. The accumulation of BLamDs observed in LAMP2-deficient mice was eventually followed by loss of the RPE and photoreceptors. Finally, we observed loss of LAMP2 expression along with ultramicroscopic features of abnormal phagocytosis and exocytosis in eyes from AMD patients but not from control individuals. Taken together, these results indicate an important role for LAMP2 in RPE function in health and disease, suggesting that LAMP2 reduction may contribute to the formation of BLamDs in AMD.

QUANTIFICATION OF VESSELS OF HALLER'S LAYER BASED ON EN-FACE OPTICAL COHERENCE TOMOGRAPHY IMAGES.

PURPOSE: To quantify the vessels of Haller's layer of normal subjects in en-face optical coherence tomographic images. METHODS: One hundred and seventy-two normal eyes were studied. En-face images of the top 25% slab of Haller's layer was analyzed. The vessel area, vessel length, and mean vessel diameter were calculated. The vessel running pattern was quantified for the degree of symmetry and designated as the "symmetry index." The coefficient of correlation between each choroidal parameter and the age, sex, axial length, and central choroidal thickness was determined. RESULTS: The vessel area was 23.4 ± 3.6 mm2, vessel length was 164.6 ± 24.1 mm, mean vessel diameter was 0.143 ± 0.019 mm, and the symmetry index was 58.6 ± 6.1%. Multiple regression analysis showed that the vessel area was significantly correlated with the age (R = -0.421, P < 0.001) and central choroidal thickness (R = 0.315, P < 0.001). The vessel length was significantly correlated with the age (R = -0.391, P = 0.024) and central choroidal thickness (R = -0.410, P < 0.001). The mean vessel diameter was significantly correlated with the age (R = -0.107, P = 0.024) and central choroidal thickness (R = 0.775, P < 0.001). The correlation between the symmetry index and any clinical findings was not significant. CONCLUSION: Quantification of en-face images of Haller's layer provide new biomarkers of the choroid.

Alteration of choroidal vascular structure in diabetic macular edema.

PURPOSE: The aim of this study was to analyze choroidal structures in healthy subjects and patients with/without diabetic macular edema (DME). METHODS: This was a retrospective observation case control study. Four hundred and two eyes of patients with diabetes mellitus (DM), and 124 age-matched eyes of healthy subjects were enrolled in this study. DM patients were divided into 3 groups: presence of central-involved (CI) DME (n = 81) and nonCI-DME/non-DME (n = 321), based on OCT findings. Central choroidal thickness (CCT) and total choroidal, luminal, and stromal areas were determined using EDI-OCT and a binarization method, respectively. The luminal area expressed as a ratio of the total choroidal area was defined as the L/C ratio. RESULTS: DM eyes showed a significantly lower L/C ratio than control eyes, whereas there was no significant difference in CCT or total choroidal, luminal, or stromal areas. There was no significant difference between CI-DME and non-DME groups in HbA1c, blood pressure, dyslipidemia, or renal function. CCT and total choroidal, luminal, and stromal areas were significantly greater in the CI-DME group than non-DME group (each P < 0.05). CONCLUSIONS: These results suggest that CCT was thickened in the presence of DME, associated with both increased luminal and stromal areas, which might be related to the pathology of DME.

MORE EFFECTIVE SCREENING FOR EPIRETINAL MEMBRANES WITH MULTICOLOR SCANNING LASER OPHTHALMOSCOPE THAN WITH COLOR FUNDUS PHOTOGRAPHS.

PURPOSE: To assess the ability of the multicolor scanning laser ophthalmoscope (MC-SLO) to screen for epiretinal membranes (ERMs). METHODS: A retrospective cross-sectional study of 35 eyes of 32 patients with an ERM detected by optical coherence tomography and 46 eyes of 23 healthy volunteers. The detection of the ERM was graded into three visibility scores-1, not visible, 2, barely visible, and 3, clearly visible-by retina specialists or by ophthalmology residents. The sensitivity and specificity of the detection with the merged image of the MC-SLO or color fundus photographs (CFPs) were calculated. RESULTS: The sensitivity for ERM detection in the MC-SLO and CFP were 91.4% and 65.7% by specialists and 97.1% and 60.0% by residents. The specificity for both devices was 100% by specialists and residents. The visibility score for the MC-SLO images were significantly higher than that for the CFP by both specialists and residents. In addition, the visibility score for the MC-SLO determined by residents was significantly higher than that for the CFP by specialists. CONCLUSION: The detection of an ERM is better with the MC-SLO images than with CFP. Furthermore, the ERM detection in the MC-SLO images by residents was comparable to that by specialists.

Running pattern of choroidal vessel in en face OCT images determined by machine learning-based quantitative method.

PURPOSE: To evaluate the new method to quantitate the running pattern of the vessels in Haller's layer in en face optical coherence tomographic (OCT) images using the new algorithm. METHODS: A retrospective and cross-sectional study. The en face image of top 25% slab of Haller's layer was analyzed. The vascular area in these images was calculated after binarization. Then, the vessels were thinned, and the total length of the vessels and the mean vessel diameter were calculated. Based on the angle of vessel running, "natural oblique vessel" was defined. The ratio of the natural oblique vessel to the whole vessels was defined as the "symmetry index". To examine the reproducibility of the software, the images obtained on two different examination dates of the same subject (25 eyes of 25 healthy subjects) were analyzed. Also, to compare the symmetry index and subjective evaluations, 180 eyes and 180 healthy subjects were analyzed. The subjective evaluations classified the images into 3 groups, the Symmetrical, Semi-symmetrical, and Asymmetrical types. Symmetry index was compared in each group. RESULTS: The inter-measurement correlation coefficient (ICC) of the vessel area, vessel length, and vessel diameter were 0.955, 0.934, and 0.954, respectively. The ICC of the symmetry index was 0.926. The symmetry index of the Symmetrical type was 60.4 ± 7.2%, that of the Semi-symmetry type was 56.2 ± 4.6%, and that of the Asymmetry type was 52.6 ± 5.2%. CONCLUSIONS: The present algorithm can analyze vessels in Haller's layer of the en face images of choroid in an objective manner with good repeatability.

Changes of choroidal structure and circulation after water drinking test in normal eyes.

PURPOSE: To determine whether water drinking test (WDT) alters choroidal structure using binarization of enhanced depth imaging optical coherence tomographic (EDI-OCT) images. METHODS: We performed a prospective study of 57 eyes of 57 normal subjects. The intraocular pressure (IOP), EDI-OCT images, and laser speckle flowgraphic images were recorded at baseline, and at 15, 30, 45, and 120 min after the WDT. The EDI-OCT images were converted to binary images using ImageJ software, and we examined luminal area, interstitial area, whole choroidal area, the ratio of luminal area to whole choroidal area (L/W ratio), subfoveal choroidal thickness (SCT), and central retinal thickness (CRT). RESULTS: The luminal area, L/W ratio, whole choroidal area, and IOP were significantly increased 30 min after water drinking; levels returned to the baseline at 120 min. No significant changes were found in the CRT and interstitial area. The fluctuations in the SCT after water intake were significantly correlated with those in the L/W ratio and luminal area but not with those of the interstitial area. The choroidal blood flow velocity was significantly decreased at 30 min. Fluctuations in the luminal area, L/W ratio, and whole choroidal area were significantly correlated with IOP fluctuations. CONCLUSIONS: The changes in the SCT after water drinking were mainly due to the changes in the choroidal vascular space. Dilatations of the choroidal vessels after water drinking may lead to choroidal thickening and subsequent IOP elevation. These findings should be considered in the evaluation of choroidal structure in patients with retinal disease.

Relationship between choroidal structure and duration of diabetes.

BACKGROUND: The aim of this study was to evaluate the relationship between the choroidal structure of diabetic patients without diabetic retinopathy (DR) and duration of diabetes. METHODS: This study is a retrospective observational study in diabetic patients without DR. Eyes with diabetes mellitus (DM) (n = 105) were divided into two groups based on the duration: long duration group (over 10 years, n = 31) and short duration group (less than 10 years, n = 74). One hundred seventeen eyes of non-diabetic patients were used as control group. All patients underwent enhanced depth imaging optical coherence tomography, and the choroidal structure was analyzed using a binarization method. RESULTS: There was no significant difference in areas of total choroid and lumina/stroma or central choroidal thickness (CCT) between control and DM groups. In contrast, lumina/total choroidal (L/C) ratio was significantly lower in diabetic eyes than in control eyes (P = 0.02). Although there was no significant difference in the areas or CCT between short and long duration groups, L/C ratio was significantly lower in the long duration group than in the short duration group (P = 0.03). CONCLUSIONS: The current study suggests that choroidal vasculature is involved in the diabetic eyes and that the choroidal structure has changed with duration of diabetes. Our study points out that L/C ratio is a new potential biomarker in monitoring choroidal vascular disorders in diabetic eyes without DR.

CORRELATIONS BETWEEN CHOROIDAL STRUCTURES AND VISUAL FUNCTIONS IN EYES WITH RETINITIS PIGMENTOSA.

PURPOSE: To investigate the choroidal structures in the enhanced depth imaging optical coherence tomographic images in eyes with retinitis pigmentosa (RP) and to determine correlations between the choroidal structures and visual functions. METHODS: The enhanced depth imaging optical coherence tomographic images of 100 eyes with typical RP and 60 age-, sex-, and axial length-matched normal eyes were binarized using ImageJ. The cross-sectional luminal and stromal areas of the inner and outer subfoveal choroid of 1,500-µm width were measured. The inner choroid included the choriocapillaris and medium vessel layer, and the outer choroid included the larger vessel layer. RESULTS: In the inner choroid, the luminal area and the ratio of luminal/total choroidal area (L/C ratio) were significantly smaller in RP than in controls (P = 0.010, P < 0.001, respectively), whereas the stromal area was not significantly different (P = 0.114). The inner choroidal L/C ratio was significantly correlated with the best-corrected visual acuity, mean deviation, foveal sensitivity, width of the ellipsoid zone, and central foveal thickness in RP after adjusting for the axial length, age, and sex (all P < 0.005). CONCLUSION: The significant correlations between the inner choroidal structures and the visual functions and retinal structures indicate that the choroidal structures are altered in association with the progression of RP.

Ability of MultiColor scanning laser ophthalmoscope to detect non-glaucomatous retinal nerve fiber layer defects in eyes with retinal diseases.

PURPOSE: To compare the ability of ocular fundus images obtained by Spectralis MultiColor scanning laser ophthalmoscope (MC-SLO) to that obtained by conventional color fundus images (CF) in detecting non-glaucomatous nerve fiber layer defects (NFLDs). METHODS: A cross-sectional, retrospective study. Patients with retinal diseases who had ocular examination with both the MC-SLO and CF instruments at the Kagoshima University from December 2016 to February 2017 were studied. Eyes that had NFLDs with non-glaucomatous optic discs were analyzed. The visibility of the NFLDs was classified into three grades: grade 0, not visible; grade 1, barely visible; and grade 2, clearly visible. The NFLD grade for blue, green, and red scanning lights of the MC-SLO, merged images with three wavelengths and the color and red-free images were determined by two ophthalmologists. These scores were compared by Steel-Dwass tests. RESULTS: Thirty-one eyes of 26 patients with a mean age of 63.1 ± 11.2 years were studied. There were 14 eyes with diabetic retinopathy, 11 eyes with age-related macular degeneration, 3 eyes with a branch retinal vein occlusion, and 3 eyes with an epiretinal membrane/macular hole. Both the intra-rater (0.631-0.790) and inter-rater (0.637-0.733) agreements were good. NFLDs were detected by the blue wavelength in all cases and by green wavelength and merged wavelengths in 90.3% of the images. The mean NFLD grade was 1.58 ± 0.49 for blue light images, 1.13 ± 0.54 for green light images, 0.07 ± 0.24 for red light images, and 1.16 ± 0.56 for merged images. The NFLD score for blue wavelength was significantly higher than that for green and red wavelength images (P < 0.05 and P < 0.01) but not significantly higher than that for the merged images. NFLDs were detected in 12 eyes (38.7%) in the color images and 16 eyes (51.6%) in the red-free images. The NFLD score for the CF and the red-free image was 0.41 ± 0.55 and 0.70 ± 0.67 which is significantly lower than that of blue MC-SLO images. CONCLUSION: The images obtained by MC-SLO are superior to that obtained by CF in detecting NFLDs in eyes with retinal diseases. We recommend MC-SLO imaging to screen for NFLDs in eyes with retinal diseases.

Effect of fluid-air exchange on reducing residual silicone oil after silicone oil removal.

PURPOSE: Our purpose was to determine the effect of fluid-air exchange on the amount of silicone oil (SO) droplets remaining in the vitreous cavity after removal of the main body of the SO. METHODS: This was a retrospective comparative study of 56 eyes of 56 patients that had undergone vitrectomy with SO tamponade. Fluid-air exchange was performed during surgery in 30 eyes [Air Ex(+) group] and was not done in 26 eyes [Air Ex(-) group]. All of the eyes were examined by ultrasonography, and the images were converted to binarized image. The amount of residual SO droplets/vitreal area in the images was expressed as the, "silicone oil index (SOI)". The correlations between SOI and clinical findings were determined. RESULTS: The SOI was significantly correlated with the axial length (AL, R = 0.444, P = 0.023). The SOI in the Air Ex(+) group was significantly higher (7.4 ± 2.6%) than in the Air Ex(-) group (4.9 ± 3.4%; P = 0.004). Multiple linear regression analyses showed that the SOI was independently and significantly correlated with the AL and the Air Ex(+) group (P = 0.003, P = 0.006, respectively). CONCLUSIONS: Fluid-air exchange during vitrectomy to remove residual SO is not effective. Our findings indicate that it may increase the amount of residual SO droplets.

CHOROIDAL STRUCTURE ALTERED BY DEGENERATION OF RETINA IN EYES WITH RETINITIS PIGMENTOSA.

PURPOSE: To compare the structural characteristics of the choroid in the areas with greater retinal degeneration to the areas with less retinal degeneration in eyes with retinitis pigmentosa (RP). METHODS: Patients with RP who had a hyperautofluorescent ring were studied. The choroidal images obtained by enhanced depth imaging optical coherence tomography located 7,500 µm from the optic disk in the horizontal plane were analyzed. The cross-sectional areas of the total, luminal, and stromal choroid were measured. The area within the hyperautofluorescent ring was defined as the "central choroid" with less retinal degeneration. RESULTS: Thirty-seven eyes of 24 patients with RP were studied. The cross-sectional area of the total choroid was significantly smaller in the RP eyes than that in the control eyes (P < 0.01). The stromal areas of the choroid were not significantly different from the stromal areas of the controls. However, the luminal areas of the nasal and temporal choroid in the RP eyes were significantly smaller than that of the corresponding areas of the controls. The ratio of the luminal area to the total choroidal area in the central choroid was 68.0 ± 3.3% which was significantly larger than that of the nasal or the temporal choroid (P < 0.01). CONCLUSION: The choroidal structure is differentially altered in eyes with RP. The changes in the choroid were dependent on whether they were located within the hyperautofluorescent or outside the hyperautofluorescent ring.

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.

One-Year Outcomes following Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in Japanese Patients: The APOLLO Study.

PURPOSE: To evaluate 1-year outcomes of intravitreal injections of aflibercept (IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients. METHODS: In this prospective, open-label, single-arm multicenter clinical trial, treatment-naïve PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly doses. The primary endpoint assessed was the proportion of patients maintaining baseline best-corrected visual acuity (BCVA) at 1 year. RESULTS: Fifty eyes with PCV were included in the study. BCVA was maintained or improved in 97.6% of the patients. Mean logMAR BCVA at baseline was 0.33, and had improved to 0.12 logMAR 1 year after the initiation of aflibercept treatment (p < 0.001). Mean central foveal thickness decreased from 356 to 239 µm (p < 0.001). Complete regression of polypoidal lesions was seen in 72.5% after 1 year of treatment. CONCLUSIONS: One year of IVA resulted in stabilization of BCVA and anatomical improvement in Japanese PCV patients.

Relative changes in luminal and stromal areas of choroid determined by binarization of EDI-OCT images in eyes with Vogt-Koyanagi-Harada disease after treatment.

PURPOSE: The aim of this study was to determine the changes in the luminal and stromal areas of the choroid in eyes with Vogt-Koyanagi-Harada disease by optical coherence tomography (OCT). METHODS: A retrospective observational study. Choroidal images were recorded by enhanced depth imaging (EDI-OCT) at the baseline, and at 1 week and 1 month after initiating steroid therapy. The EDI-OCT images were converted to binarized images, and the luminal areas and the stromal areas were measured separately. RESULTS: Thirty-two eyes of 16 patients were enrolled, and 16 eyes of 10 patients had suitable images for the binarization analyses. The ratio of the luminal areas to the choroidal areas was 0.60 ± 0.03 at the baseline, 0.67 ± 0.04 at 1 week, and 0.66 ± 0.04 at 1 month. There was a significant increase from the baseline at 1 week (P < 0.01) but not from 1 week to 1 month. Although both the stromal and luminal areas were reduced, the percent reduction of the stromal areas (56.5 ± 7.2 %) was significantly greater than that of the luminal areas (42.5 ± 12.6 %) at 1 week (P < 0.01). CONCLUSIONS: A significant decrease of the choroidal area was detected in eyes with Vogt-Koyanagi-Harada disease at 1 week after beginning steroid therapy. The decrease was more evident in the stromal area than in the luminal area.

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.

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.

Changes of choroidal structure after treatment for primary intraocular lymphoma: retrospective, observational case series.

BACKGROUND: We report changes of choroidal structure determined by binarization of enhanced depth imaging optical coherence tomographic (EDI-OCT) images after treatment for primary intraocular lymphoma (PIOL). METHODS: Five eyes of four patients with PIOL were examined by EDI-OCT before and 6 months after intravitreal methotrexate injections. In addition, 15 eyes of 15 normal individuals controlled by age and refractive error were examined by EDI-OCT. Binarization of the EDI-OCT images was performed using publicly accessible software (ImageJ). The examined area of the subfoveal choroid was 1,500 µm wide, and the dark areas that represented the luminal areas were traced by the Niblack method. Wilcoxon signed rank test was used to determine the significance of changes in the subfoveal choroidal thickness, interstitial area, and luminal area. Mann-Whitney U test was used to compare the parameters in the eyes with pretreatment PIOL and normal control eyes. RESULTS: The subfoveal choroidal thickness was significantly decreased after treatment (P = 0.0431). In the binarized images, the interstitial area was significantly decreased after treatment (P = 0.0431), while the luminal area was not significantly changed (P = 0.8927). After delayed onset of PIOL, increased interstitial area, thickened choroid and unchanged luminal area were observed in one eye. The interstitial area and choroidal thickness were significantly increased in the eyes with pretreatment PIOL compared with the normal control eyes (P = 0.0207, P = 0.0495, respectively), while the luminal area was not significantly different (P = 0.2752). CONCLUSIONS: After treatment for PIOL, the EDI-OCT images showed a thinner choroid, and binarization of the EDI-OCT images showed significantly decreased interstitial areas compared with the luminal areas. The binarized EDI-OCT images can provide useful information on choroidal structure in eyes with PIOL, and combining these images with intraocular interleukin levels or fundus autofluorescence images should provide valuable information for determining the PIOL activity.