Binarization of enhanced depth imaging optical coherence tomographic images of an eye with Wyburn-Mason syndrome : a case report

Background: To report a thicker choroid and larger choroidal luminal area in an eye with Wyburn-Mason syndrome. To the best of our knowledge, this is the first report demonstrating an increase in the choroidal thickness and the luminal area in a case of Wyburn-Mason syndrome. In addition, we report the changing appearance of retinal arteriovenous malformations over a 16-year period. Case presentation: A 27-year-old woman, who was diagnosed with Wyburn-Mason syndrome at age 11 years, visited our clinic. Her best-corrected visual acuity was 20/12.5 in the right eye and light perception in the left eye. Severely dilated, tortuous vascular loops were distributed from the optic disc over all four quadrants of the left fundus. The vascular loops in some areas were more dilated and tortuous than 16 years earlier. Optical coherence tomography (OCT) showed retinal edema with cystic changes and enlarged choroidal vessel lumens in the left eye. The subfoveal choroidal thickness was manually measured by the caliper function in the enhanced depth imaging OCT (EDI-OCT) images. Binarization of the EDI-OCT images was performed with publicly accessible ImageJ software. The examined area of the subfoveal choroid was 1,500 μm wide, and the dark areas representing the luminal areas were traced by the Niblack method. After determining the distance of each pixel, the luminal area was automatically calculated. The subfoveal choroidal thickness was 250 μm in the right eye and 462 μm in the left eye. The luminal area of the 1,500-μm-wide subfoveal choroid was computed to be 307,165.6 μm2 in the right eye and 545,780.7 μm2 in the left eye. Conclusions: The EDI-OCT images showed a thicker choroid, and binarization of the EDI-OCT images showed that the luminal areas were significantly larger in the affected eye, suggesting a dilatation of the choroidal vessels. The results demonstrated that conversion of EDI-OCT images to binary images was a useful method to quantify the choroidal structure

Changes in choroidal structure following intravitreal aflibercept therapy for retinal vein occlusion

Aims To examine the choroidal change accompanying retinal vein occlusion (RVO) in detail, we measured changes in choroidal structure after intravitreal aflibercept (IVA) injections for RVO using binarisation of enhanced depth imaging optical coherence tomographic (EDI-OCT) images and assessed associations with clinical outcome. Methods Retrospective, observational case series. Forty treatment-naïve patients (10 central, 18 major branch and 12 macular branch RVO) were examined by EDI-OCT before and 1, 3 and 6 months after IVA injections. EDI-OCT images were binarised using ImageJ. Subfoveal cross-sectional areas of the luminal, stromal and total choroid over a 1500 µm span were measured and the stromal area to total choroidal area (S/C) ratio was calculated. Results Compared to normal contralateral eyes, afflicted eyes at baseline exhibited significantly greater stromal area (p<0.001), total choroidal area (p=0.001) and S/C ratio (p<0.001), but no difference in luminal area (p=0.083). The stromal area, S/C ratio and total choroidal area were significantly reduced in afflicted eyes at 1, 3 and 6 months after IVA (all p<0.006). Baseline S/C ratio was significantly correlated with baseline visual acuity (VA), baseline central retinal thickness (CRT) and VA and CRT improvement at 1, 3 and 6 months post-treatment even after adjusting for the axial length, age and sex (all p<0.012). Conclusion RVO induces substantial oedema of the choroidal stromal area that is detectable by binarisation of EDI-OCT images. This stromal oedema likely stems from high intraocular vascular endothelial growth factor levels. Changes in choroidal structure may be used to assess severity and prognosis of RVO

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

CHOROIDAL STRUCTURE IN RP

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

Choroidal Changes After Coffee Intake

PURPOSE. The effects of coffee intake on the ratio of stromal and luminal components in the choroid and the underlying mechanism remain unclear. This prospective cross-sectional study aimed to explore how coffee intake affects the choroidal component ratio and circulation. METHODS. Forty-nine right eyes of healthy adult volunteers were evaluated as the coffee intake group. Thirty-two right eyes of healthy volunteers served as the control group. The participants consumed 185 mL of coffee or water, respectively, and the systemic hemodynamics, enhanced-depth imaging optical coherence tomographic (EDI-OCT) images, and foveal mean blur rate (MBR), an indicator of blood flow velocity, were recorded at baseline and after coffee or water intake. The EDI-OCT images were binarized using ImageJ software, and subfoveal choroidal thickness (SCT) and whole, luminal, and stromal choroidal areas were calculated. RESULTS. In the coffee intake group, significant decreases in SCT and luminal area peaked at 60 minutes after intake (both P < 0.001), whereas a significant increase in MBR peaked at 30 minutes (P < 0.001). No significant stromal area fluctuations were observed. SCT and luminal area fluctuations exhibited a significant positive correlation (r = 0.978, P < 0.001). Significant negative correlations of luminal area fluctuations with MBR fluctuations were observed by stepwise regression analysis (r = –0.220, P < 0.001). The control group exhibited no significant fluctuations. CONCLUSIONS. Coffee-induced choroidal thinning may result mainly from a reduction in the choroidal vessel lumen, and this vessel lumen reduction correlated with an increased choroidal blood flow velocity after coffee intake. These coffee-induced changes in choroidal component ratio and circulation should be considered when evaluating choroids

Quantitative evaluations of vortex vein ampullae by adjusted 3D reverse projection model of ultra-widefield fundus images

The purpose of this study was to determine the number and location of vortex vein ampullae (VVA) in normal eyes. This was an observational retrospective study. Montage images of one on-axis and two off-axis ultra-widefield images of 74 healthy eyes were enhanced, and reverse projected onto a 3D model eye. The number and distance between the optic disc to each VVA in the four sectors were compared. The significance of correlations between these values and age, sex, visual acuity, refractive error, and axial length was determined. The mean number of VVA was 8.10/eye with 1.84, 2.12, 2.19 and 1.95 in upper lateral, lower lateral, upper nasal, and lower nasal sectors, respectively. The mean number of VVA/eye was significantly greater in men at 8.43 than women at 7.76 (P = 0.025). The mean distance between the optic disc and VVA was 14.15 mm, and it was 14.04, 15.55, 13.29 and 13.66 mm in the upper lateral, lower lateral, upper nasal and lower nasal sectors, respectively (all P < 0.05). The number and location of VVA can be obtained non-invasively, and the number was significantly higher in men than women. This technique can be used to determine whether these values are altered in a retinochoroidal disease

Iduronate-2-sulfatase fused with anti-hTfR antibody, pabinafusp alfa, for MPS-II : a phase 2 trial in Brazil

In Hunter syndrome (mucopolysaccharidosis II [MPS-II]),systemic accumulation of glycosaminoglycans (GAGs) dueto a deficiency of iduronate-2-sulfatase (IDS), caused by mu-tations in theIDSgene, leads to multiple somatic manifesta-tions and in patients with the severe (neuronopathic)phenotype, also to central nervous system (CNS) involve-ment. These symptoms cannot be effectively treated withcurrent enzyme-replacement therapies, as they are unableto cross the blood-brain barrier (BBB). Pabinafusp alfa, anovel IDS fused with an anti-human transferrin receptorantibody, was shown to penetrate the BBB and to addressneurodegeneration in preclinical studies. Subsequent phase1/2 and 2/3 clinical studies in Japan have shown markedreduction of GAG accumulation in the cerebrospinalfluid(CSF), along with favorable clinical responses. A 26-week,open-label, randomized, parallel-group phase 2 study wasconducted in Brazil to further evaluate the safety and efficacyof intravenously administered pabinafusp alfa at 1.0, 2.0,and 4.0 mg/kg/week in MPS-II patients. The safety profilesin the three dosage groups were similar. Neurodevelopmentalevaluation suggested positive neurocognitive signals despite arelatively short study period. The 2.0-mg/kg group, whichdemonstrated marked reductions in substrate concentrationsin the CSF, serum, and urine, was considered to provide thebest combination regarding safety and efficacy signals

ターミナルケアの授業における学生の死生観に関する検討

本学看護学科3年次生に開講されているターミナルケアの授業を通して学生の死生観の変化を明らかにし今後の教育の方向性を模索することを目的に授業前後で質問紙による調査をした。対象は,本学看護学科3年次生,50名であり,期間は平成18年4月,7月の2回である。その結果,以下のことが明らかになった。1)死別体験,葬儀参列の体験が8～9割があり体験率は高いと言えた。2)死に対する態度の尺度,死生観尺度,死のイメージ尺度(SD法)の授業前後の比較では授業後が有意に高かった。このことから,授業は学生の死生観が肯定的に変化することに大きな意義を持っていたと考えられた。3)死別体験・葬儀参列の体験・看取り体験と各尺度との関連は一部を除いて有意差はなかった。このことから看護学生の死生観を形成する上でこれらの体験は大きな影響を及ぼしていないと考えられた。4)授業は,専門の講師からの講義や学生が自ら死について考えられるような教材であったが,授業後においても死を否定的に考える学生もいるので今後の授業内容の検討が必要であると考えられた。今回の調査より,ターミナルケアの授業は,学生の肯定的な死生観育成に大きな影響を及ぼしていた。しかし,授業後においても死を否定的に捉える学生はいるので,授業のあり方の継続的な検討が示唆された。This study was conducted to determine changes in students\u27 view of death after they have completed the course on terminal care for third year nursing students, so as to help us decide on how the course should be taught in the future. Fifty students were surveyed before and after the course in April and July of 2006. The study revealed the followings. 1) As high as between 80 and 90% of the students have had death in their family or attended a funeral. 2) The semantic differential scales on attitude toward death, view of death, and image of death were significantly higher after students completed the course, suggesting the lectures played an important role in the positive change on students\u27 view of life-and-death. 3) The relevance of the experience of bereavement, funeral attendance, or seeing someone die on these scales was largely insignificant, indicating these experiences do not have any great influence on how a nursing student developed his or her view on death. 4) The course consisted of lectures by instructors specialized in this field and discussions among students about their own thoughts on death. The fact that some students still thought about death negatively after completing the course suggests that the contents of the course work should be reevaluated. The surveys revealed that the course on terminal care had a great impact on helping the students to develop a positive view on death. Nevertheless, the fact that some students continued to think of death negatively suggested there is still a need to reevaluate how the course has been taught

Changes in Choroidal Structures in Eyes with CSC after Photodynamic Therapy

Purpose To determine the structural changes in the choroid after half-dose photodynamic therapy (hPDT) in eyes with chronic central serous chorioretinopathy (CSC). Methods This was a retrospective interventional study of 29 eyes of 29 patients who underwent hPDT for chronic CSC with serous retinal detachment (SRD) and were followed for ≥3 months. Enhanced depth imaging optical coherence tomographic (EDI-OCT) images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), the cross sectional subfoveal choroidal area, the hyporeflective and hyperreflective areas of the inner, outer, and whole choroid were determined at the baseline, and at 1, 3, and 12 months after the hPDT. Results The SRDs were resolved in 26 (89.7%) eyes at 3 months after the hPDT. The mean CCT (P = 0.001), the total choroidal area (P = 0.001), and the hypo-reflective area (P = 0.003) of the whole choroid were significantly decreased from the baseline at 3 months. The hyperreflective area of whole choroid was not significantly changed during the study period (P = 0.083). The hyperreflective but not the hyporeflective area of the inner choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). The hyporeflective but not the hyperreflective area of the outer choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). Conclusions The hyperreflective area of the inner choroid and hyporeflective area of the outer choroid were significantly decreased after hPDT for chronic CSC. Because the hyperreflective and hyporeflective area correspond to the choroidal stroma and vessels, respectively, the decreased CCT and subfoveal choroidal area after hPDT may be attributed to a decrease in the exudative changes in the inner choroidal stroma and the reduction of the dilation of the outer choroidal vessels

Enzyme replacement therapy with pabinafusp alfa for neuronopathic mucopolysaccharidosis II : an integrated analysis of preclinical and clinical data

Enzyme replacement therapy (ERT) improves somatic manifestations in mucopolysaccharidoses (MPS). However, because intravenously administered enzymes cannot cross the blood–brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT in order to achieve CNS effects, but the burdens on patients are inimical to long-term administrations. However, since pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in a mouse model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT that is effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the previously obtained preclinical and clinical evidence related to the use of this drug, presents latest data, and discusses the preclinical, translational, and clinical challenges of evaluating, ameliorating, and preventing neurodegeneration in patients with MPS-II