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This study aimed to investigate the heritability of genetic influence on macular choroidal vascularity index (CVI). This was a cross-sectional healthy twin study. We included 373 Korean adults with healthy eyes from 79 families. CVI, Total choroidal area (TCA) and luminal area (LA) were measured using horizontal scan of spectral-domain optical coherence tomography with enhanced depth imaging. Characteristics of the participants were investigated (age, gender, drinking habits, smoking status, axial length, hypertension, and diabetes). The correlations of these characteristics with CVI were assessed using univariate and subsequently multivariate regression models. Participants who were older and had a higher intraocular pressure, higher diastolic blood pressure, and lower pulse pressure showed associations with lower CVI (p < 0.001, p = 0.014, p = 0.005, and p = 0.015, respectively). The covariate-adjusted heritability (±standard error) of the CVI was 0.716 ± 0.091, and the heritabilities of the TCA and LA were 0.691 ± 0.089 and 0.634 ± 0.100, respectively. The CVI, TCA, and LA are highly heritable.

This study aimed to investigate the change of choroidal venous overload in Vogt‒Koyanagi‒Harada (VKH) disease. Clinical records of 52 patients with VKH disease (52 eyes) and 24 control subjects (24 eyes) who underwent multimodal imaging, including fluorescein angiography (FA) and indocyanine green angiography (ICGA), were retrospectively reviewed. Imaging data were assessed for signs associated with choroidal venous overload, e.g., choroidal perfusion delay, choroidal vascular hyperpermeability, dilated choroidal veins, and intervortex venous anastomosis (IVA). Dual FA and ICGA scoring for active posterior segment inflammation was performed. Clinical and imaging features associated with choroidal venous overload were compared between early- and late-stage VKH disease. Choroidal perfusion delay, choroidal vascular hyperpermeability, dilated choroidal veins, and IVA were more prevalent in eyes with VKH disease (69.2%, 67.3%, 61.5%, and 65.4%, respectively) than in control eyes (25.0%, 20.8%, 25.0%, and 37.5%, respectively) (p < 0.05). All eyes with IVA in the early-stage of VKH disease had got other 3 signs. All choroidal venous overload signs were more prevalent in patients with early-stage (20 eyes) than in those with late-stage VKH disease (32 eyes) (p < 0.05). The number of choroidal venous overload signs were inversely related to disease duration (p < 0.001) and proportionally related to the total ICGA score (p < 0.001). IVA was significantly associated with the total ICGA score in logistic regression (p = 0.014). Choroidal venous overload occurs early in VKH disease. Angiographic signs of choroidal venous overload may be useful markers to assess the status of VKH disease.

This study aimed to investigate the longitudinal change in the reticular pseudodrusen (RPD) area in the fundus and its association with late age-related macular degeneration (AMD). 91 RPD eyes (55 patients; age 67.9 ± 7.3 years) with > 5 years’ follow-up (6.8 ± 0.9 years) from a single medical center were enrolled. Ultrawide-field photography images were analyzed using the concentric rings method, and the RPD area was semi-quantitatively classified according to the affected segment number into central, intermediate, and extensive types. Correlations of longitudinal changes in the RPD area and late AMD risk were investigated. RPD area increased significantly during the follow-up (p .048), RPD area at first visit (r = − 0.222; p = 0.035), and the decrease rate of subfoveal choroidal thickness (SFCT) (r = 0.217; p = 0.039). Many central (18/49, 36.7%) and intermediate (15/23, 65.2%) types switched to the more advanced type during the follow-up. Macular neovascularization and geographic atrophy developed in 12.3% and 18.7% of patients by 7 years. Late AMD incidence was significantly higher in eyes with large than in those with small RPD areas (p = 0.002). Larger RPD area at baseline, faster increase in RPD area, thinner SFCT, rapid decrease in SFCT, and the presence of late AMD on fellow eye were associated with late AMD. All RPD areas progressively increase over time. The regular assessment of RPD area may help to predict late AMD risk in RPD eyes.

We aimed to evaluate the association between obesity and the incidence of retinal vein occlusion (RVO) with and without diabetes mellitus (DM).This is a retrospective cohort study using Korean National Health Insurance System data. The participants were 23,061,531 adults older than 20 years who received a health examination at least once between 2009 and 2012, and all patients were observed for RVO development until 2015. We used a multivariate adjusted Cox regression analysis to evaluate the association between RVO and body mass index (BMI) with and without DM. The analysis were evaluated via a hazard ratio (HR) and 95% confidence interval (CI). The age-, sex-, and multivariable-adjusted HRs for RVO were stratified by BMI. This population-based study revealed evidence that obesity has a different effect on the incidence of RVO in the presence and absence of DM.In people with DM, a lower BMI was associated with an increased risk of RVO, and a higher BMI was associated with a lower risk for RVO. In people without DM, the correlation was reversed: a lower BMI was associated with a lower risk for RVO and vice versa.

The purpose of the study is to evaluate the heritability of inner retinal layer (IRL) and outer retinal layer (ORL) thicknesses in the healthy Korean population. This was a cross-sectional, twin and family study. We included 374 Korean adults with healthy eyes from 89 families. IRL thickness (from the internal limiting membrane to the external limiting membrane) and ORL thickness (from the external limiting membrane to the outer border of the retinal pigment epithelium layer) were measured in the nine macular subfields as defined by the Early Treatment of Diabetic Retinopathy Study using optical coherence tomography. The heritability on IRL and ORL thicknesses were investigated using a variance decomposition model. The heritability of IRL thickness was 0.87, 0.58, 0.85, 0.89, and 0.74 for the central, inner superior, inner inferior, inner temporal, inner nasal subfields, respectively; and 0.62, 0.83, 0.62, and 0.60 for the outer superior, outer inferior, outer temporal, outer nasal subfields, respectively. The heritability of ORL thickness was 0.56, 0.75, 0.66, 0.72, and 0.56 for the central, inner superior, inner inferior, inner temporal, inner nasal subfields, respectively; and 0.64, 0.63, 0.73, 0.54 for the outer superior, outer inferior, outer temporal, and outer nasal subfields, respectively. The heritability estimates of IRL thickness and ORL thickness ranged from moderate to high. The IRL thickness at the central, inner temporal, and inner inferior subfields had particularly high heritability.

This study aimed to describe the clinical characteristics of age-related macular degeneration (AMD) eyes with both cuticular drusen (CD) and reticular pseudodrusen (RPD). Clinical records of patients diagnosed with CD or RPD with multimodal imaging was reviewed for patients diagnosed with both CD and RPD. The distribution patterns of CD (macular and diffuse type) and RPD (localized, intermediate, and diffuse type), presence of soft drusen, large drusen (> 200 µm), variant subretinal drusenoid deposits, and macular complications were investigated. Of the 220 eyes of 110 patients diagnosed with CD and 926 eyes of 463 patients diagnosed with RPD, 13 eyes of seven patients met the diagnostic criteria for both CD and RPD. The mean age at initial presentation was 71.4 ± 8.8 years and six patients were female. The mean subfoveal choroidal thickness was 143.8 ± 25.1 µm. The distribution of CD was of the macular type in all eyes. Distribution of RPD was localized in 11 eyes (84.6%) and intermediate in two eyes (15.4%). Soft drusen, large drusen, and variant subretinal drusenoid deposits were present in 13 (100%), 12 (92.3%) and, seven (53.8%) eyes, respectively. Macular neovascularization was observed in two eyes (15.4%). CD and RPD can coexist in eyes with AMD. Multimodal imaging should be used for AMD eyes with features suggestive of CD and RPD, considering the high likelihood of developing late AMD.

Cuticular drusen show some similarities to and differences from soft drusen in age-related macular degeneration (AMD) and might thus be a unique AMD subtype. Previous studies on cuticular drusen were performed mainly in white ethnic groups, but AMD shows ethnic differences. We investigated clinical manifestations of cuticular drusen in Korean patients to evaluate possible ethnic differences. Clinical records of Korean patients with cuticular drusen were retrospectively reviewed. Fundus distribution pattern, imaging features, and presence of large drusen, drusenoid pigment epithelial detachment (PED), and macular complications, including geographic atrophy (GA), choroidal neovascularization (CNV), and acquired vitelliform lesion (AVL), were assessed via multimodal imaging in 162 eyes with cuticular drusen (n = 81 patients; 67 females; mean age: 66.6 ± 9.1 years). Diffuse distribution was found in 61.7% and peripapillary involvement in 75.3% of eyes. Large drusen, drusenoid PED, GA, CNV, and AVL were observed in 59.3%, 26.5%, 18.5%, 3.7%, and 1.2% of eyes, respectively. The macular complication prevalence was similar between patients ≤ 60 and those > 60 years old. In Korean patients, cuticular drusen were less frequently associated with macular complications than in white patients, and the proportion of macular complications differed significantly, with AVL representing an uncommon complication.

PURPOSE To evaluate changes in the peripapillary retinal nerve fiber layer (RNFL) thicknesses using spectral-domain optical coherence tomography (SD-OCT) in hydroxychloroquine (HCQ) users. METHODS The medical records of HCQ users were retrospectively reviewed. In these HCQ users, an automated perimetry, fundus autofluorescence photography, and SD-OCT with peripapillary RNFL thickness measurements were performed. The peripapillary RNFL thicknesses were compared between the HCQ users and the control groups. The relationships between the RNFL thicknesses and the duration or cumulative dosage of HCQ use were analyzed. RESULTS This study included 77 HCQ users and 20 normal controls. The mean duration of HCQ usage was 63.6 ± 38.4 months, and the cumulative dose of HCQ was 528.1 ± 3.44 g. Six patients developed HCQ retinopathy. Global and six sectoral RNFL thicknesses of the HCQ users did not significantly decrease compared to those of the normal controls. No significant correlation was found between the RNFL thickness and the duration of use or cumulative dose. The eyes of those with HCQ retinopathy had temporal peripapillary RNFL thicknesses significantly greater than that of normal controls. CONCLUSIONS The peripapillary RNFL thicknesses did not change in the HCQ users and did not correlate with the duration of HCQ use or cumulative doses of HCQ. RNFL thickness is not a useful biomarker for the early detection of HCQ retinal toxicity.

This study aimed to evaluate the frequency and clinical characteristics of hydroxychloroquine (HCQ) retinopathy in Korean patients with rheumatologic diseases. We retrospectively reviewed medical records of 310 patients taking HCQ. Ophthalmic examinations included spectral-domain optical coherence tomography (SD-OCT), automated visual field test, and fundus autofluorescence. The severity of retinopathy was categorized as early, moderate, or severe, and the location was categorized as parafoveal, pericentral, or mixed pattern. Among 310 patients, 9 patients (2.9%) were diagnosed as HCQ retinopathy. Among the patients with HCQ use ≥ 5 years (n = 174), the frequency was 5.2%. Only 1 (11.1%) of the 9 patients was symptomatic. The mean daily dose per kilogram of real body weight of the 9 patients was 5.6 mg, and only 3 had used 6.5 mg or more. Four of the 9 patients had severe HCQ retinopathy. Six of the 9 patients showed pericentral or mixed pattern of retinal damage. Consequently, the frequency of HCQ retinopathy in Korean patients was not low, especially when administered at a high cumulative dose and for a long duration. Screening of HCQ retinopathy by the recommended guidelines that include SD-OCT seems useful and should be done to detect retinal damage earlier in patients with chronic exposure to HCQ., Graphical Abstract

The purpose of the study is to propose choroidal spatial distribution indexes (CSDIs) to represent choroidal topographic features, establish a normative database for CSDIs, and identify factors associated with CSDIs in healthy eyes. Retrospective data analysis of 363 healthy eyes from a single-center, prospective, cross-sectional, non-interventional study. Subjects were evaluated using spectral domain OCT with enhanced depth imaging. Choroidal volume and average thickness were measured with OCT in nine macular subfields defined by the Early Treatment Diabetic Retinopathy Study. Vertical CSDI was defined as the natural logarithm of superior choroidal volume divided by inferior choroidal volume. Horizontal CSDI was defined as the natural logarithm of temporal choroidal volume divided by nasal choroidal volume. The overall distributions of vertical and horizontal CSDIs was analyzed. Linear regression analyses were used to identify ocular and systemic factors associated with vertical and horizontal CSDIs. The average vertical CSDI was 0.062 ± 0.206, and average horizontal CSDI was 0.138 ± 0.226. Both vertical and horizontal CSDIs followed normal distribution. Increasing age was significantly associated with greater vertical CSDI (choroidal volume distribution tilted toward the superior region), and longer axial length and thinner subfoveal choroidal thickness were significantly associated with greater horizontal CSDI (choroidal volume distribution tilted toward the temporal region).

To investigate the error rate of automated choroidal segmentation and the effect of frame averaging on error rate.A horizontal B scan at the fovea was performed in patients having various retinochoroidal disorders using swept-source optical coherence tomography (OCT) with frame-averaging technique. Scanned images were classified into four morphological groups: normal from fellow eyes (NF ), normal from pathologic eyes (NP ), retinal abnormality (R) and retinochoroidal abnormality (RC) group. Choroidal segmentation was automatically performed using built-in software of a swept-source OCT device, and the error rate of choroidal segmentation was analysed.Qualified images for all four averaging types with different number of averaged frames were acquired in 89 eyes of 77 patients. Images of 12, 20, 24 and 33 eyes were classified as NF , NP , R and RC group, respectively. The choroidal segmentation error was detected in 1-2 images (8.3-16.7%) in the NF group, 3-6 images (15.0-30.0%) in the NP group, 4-8 images (16.7-33.3%) in the R group and 17-19 images (51.5-57.6%) in the RC group. The error rate was significantly higher in RC group than other groups (p 0.05). Increasing the number of frames for averaging showed no significant effect on the error rate in all groups (p 0.05).Automated choroidal segmentation showed a high error rate in images with choroidal abnormalities, and the averaging effect could not reduce the error rate significantly. Thus, further technological improvement is needed to increase the accuracy of the automated choroidal segmentation.

Purpose To investigate the impact of the metabolic syndrome (METS) on the incidence of retinal vein occlusion (RVO). Methods This is a retrospective cohort study using Korean National Health Insurance System data. 23,153,600 subjects without previous history of RVO underwent a National Health Screening Program examination between 2009 and 2012. They were monitored for RVO development (registration of diagnostic code for RVO) until 2015. Presence of METS was defined using the data from the National Health Screening Program examination according to the revised criteria of the National Cholesterol Education Program Adult Treatment Panel III. A multivariate adjusted Cox regression analysis was used to reveal hazard ratios and 95% confidence interval for RVO development in the presence of METS. Results The age of the subjects was 47.64 ± 13.51 years. In this cohort, 11,747,439 (50.7%) were male, 11,406,161 (49.3%) were female, and 6,398,071 subjects (27.6%) were diagnosed with METS. The overall incidence of RVO was 0.947 per 1000 person-years. The adjusted hazard ratio of RVO in the presence of METS was 1.458 (95% confidence interval, 1.440–1.475; P < 0.001) after adjusting for age, sex, smoking status, alcohol consumption, physical activity, and income. Among all of the criteria for METS diagnosis, elevated blood pressure was the greatest risk for RVO development (adjusted hazard ratio, 1.610; 95% confidence interval, 1.589–1.631; P < 0.001). Conclusions METS and each of diagnostic criteria was associated with an increased risk of RVO development. Elevated blood pressure seems to be especially important factors for RVO development. Translational Relevance Our results provide information about the link between METS and RVO.

Purpose We investigate the measurable range of subfoveal choroidal thickness (SFCT) with conventional spectral domain optical coherence tomography (SD-OCT) in normal healthy eyes. Methods All subjects underwent an SD-OCT horizontal line scan centered at the fovea with standard and enhanced depth imaging (EDI) techniques. Two independent observers manually measured SFCT on standard and EDI-OCT images, if two choroidal borders were identified. The rate of successful measurement with standard OCT was evaluated. Inter- and intraclass correlation coefficients and Bland-Altman plots were used for analysis. Results OCT images of 724 normal healthy eyes from 374 subjects were evaluated. Although the inner choroidal border was identified on all OCT images, the outer choroidal border was identified on 378 of 724 (52.2%) conventional OCT images. Mean SFCT of all study eyes measured by EDI-OCT images was 292.6 ± 94.0. The number of successful measurements with conventional OCT was 100%, 87.5%, 48.1%, 33.0%, and 0%, in the SFCT ranges of 360 μm, respectively. The accumulated rate of successful measurement with conventional OCT was 100%, 96.4%, and 82.2% in the SFCT ranges of ≤240, ≤280, and ≤320 μm, respectively. Two protocols showed good inter-correlation of SFCT, when SFCT were measurable in both scans. Conclusions SFCT can be measured by conventional OCT in eyes with thin choroid, and the measured value shows high agreement with those measured by EDI-OCT. In such eyes, conventional OCT can be used potentially to evaluate the retina and choroid. Translational Relevance In eyes with a thin choroid, conventional OCT can be used potentially to evaluate the retina and choroid with high agreement with EDI-OCT.

Reticular pseudodrusen (RPD) could be present not only in the posterior pole but extramacular area also as a confluent morphological pattern. Thus RPD can be classified by the fundus distribution for the assessment of visual prognosis. The electrophysiological function in eyes with reticular pseudodrusen (RPD), showing various fundus distribution were evaluated using full-field electroretinogram (ERG). Retinal distribution of RPD was divided into three types (localized, intermediate, and diffuse) according to the extent of involvement of retinal areas by fundus photograph montages. RPD were present with the diffuse type in 21 eyes (25.6%), with the intermediate type in 30 eyes (36.6%), and with the localized type in 31 eyes (37.8%). The average age was 74.76 ± 4.52 (range, 65-81) years in the diffuse type, 72.47 ± 9.13 (range, 55-91) years in the intermediate type, and 70.26 ± 7.77 (range, 61-89) years in the localized type. The mean amplitudes of the scotopic rod response, scotopic maximal combined response, oscillatory potentials (OP), photopic cone response, and 30Hz cone flicker response were more decreased in the diffuse, intermediate, and localized types in order, except for the photopic cone a-wave response. The diffuse type showed reduced amplitudes of ERG responses than the normal control group under all testing conditions except for the photopic a-wave response, and differences were statistically significant with the age restriction and adjustment methods (Bonferroni-corrected P < 0.05). The mean implicit times of ERG responses were significantly delayed in the diffuse type in the photopic b-wave. (Bonferroni-corrected P < 0.05). Extensive retinal involvement of RPD correlates with severely reduced electrophysiological retinal function. This acquired form of decreased electrophysiological function should be regarded as different from those of hereditary retinal degeneration.

Eyes with polypoidal choroidal vasculopathy (PCV) were recently reported to have various choroidal thickness, and choroidal thickness might be associated with visual outcome in the treatment of many retinal disorders. The range of subfoveal choroidal thickness (SFCT), clinical features, and 3-month treatment response among three groups having different range of SFCT were investigated in PCV eyes. In 78 treatment-naïve eyes with PCV, SFCT was measured using optical coherence tomography. Eyes were classified into thin, medium, and thick groups, using mean and one standard deviation of SFCT. Clinical features and imaging findings were compared among the three groups. Some eyes were treated with three consecutive monthly injection of anti-vascular endothelial growth factor (VEGF) as an initial treatment. They were also classified into three thickness groups, and the short-term post-treatment improvement in visual acuity and central retinal thickness were compared among groups. The mean SFCT was 271.9 ± 135.6 μm. Twelve, 53, and 13 eyes were classified into thin (407.5 μm) groups, respectively. The thin group showed older age, lower visual acuity, and a higher prevalence of fundus tessellation than the other two groups (P

As younger preterm infants are able to survive, more extremely preterm infants are at risk of developing retinopathy of prematurity (ROP). To investigate the incidence, progression and risk factors of ROP in extremely preterm infants in Korea, the medical records of infants born before 25 weeks gestation were retrospectively reviewed. The criteria for laser treatment agreed with type 1 ROP as defined by the Early Treatment for Retinopathy of Prematurity study. Of the 121 infants included in the analysis, 119 (98.4%) infants developed any stage ROP, including 78 infants (64.5%) with type 1 ROP. The mean postmenstrual age (PMA) at the onset of any ROP and type 1 ROP were 33.5 and 36.1 weeks, respectively. All but one infant developed type 1 ROP after 31 weeks PMA. Univariate analysis showed that duration of total parenteral nutrition and onset of any ROP (PMA) were associated with the development of type 1 ROP. In conclusion, this study shows high incidence of ROP in extremely preterm infants and suggests that, although current screening protocols are feasible for most preterm infants born before 25 weeks gestation, earlier screening before 31 weeks PMA may be necessary in infants with an unstable clinical course.

We evaluated macular ganglion cell-inner plexiform layer (GC-IPL) thickness using spectral-domain optical coherence tomography (SD-OCT) in patients with chronic exposure to hydroxychloroquine (HCQ).This study included 130 subjects, who were divided into three groups: Group 1A, 55 patients with HCQ use ≥5 years; Group 1B, 46 patients with HCQ use5 years; and Group 2, 29 normal controls. In all patients with exposure to HCQ, fundus examination, automated threshold perimetry, fundus autofluorescence photography, SD-OCT, and GC-IPL thickness measurement using the Cirrus HD-OCT ganglion cell analysis algorithm were performed. Average and minimum macular GC-IPL thickness were compared between subjects groups, and correlations between GC-IPL thickness and duration or total dose of HCQ use were analyzed.Among the 101 patients of Group 1, six patients who showed clinically evident HCQ retinopathy also showed markedly thin macular GC-IPL. In addition, weak but significant negative correlations were observed between the average and minimum GC-IPL thickness of Group 1 patients and cumulative dose of HCQ, even when analyzing without the six patients with HCQ retinopathy. However, when analyzing after exclusion of patients with high cumulative doses (1000 g), significant correlations were not observed.This study revealed that macular GC-IPL thickness did not show definite correlations with HCQ use. However, some patients, especially with HCQ retinopathy or high cumulative doses, showed thin GC-IPL.

PURPOSE We evaluated the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a noninvasive biomarker of choroidal neovascularization (CNV) and its utility as a tool for monitoring therapeutic response in laser-induced rat CNV models. METHODS CNV was induced in the right eyes of 14 rats using a laser. Rats (n = 7) were treated daily for 14 days with a candidate drug (KR-31831, 50 mg/kg of body weight) having antiangiogenic effects, whereas control rats (n = 7) were treated with the vehicle alone (10% cremophor, 10% absolute ethyl alcohol, and 80% saline). DCE-MRI examinations were performed on the day before surgery (D - 1), and 3, 7, and 14 days after surgery (D + 3, D + 7, and D + 14), from which pharmacokinetic parameters (K(trans), v(e), v(p)) were calculated. Angiography was performed to visualize CNV using FITC-labeled high molecular weight dextran after MRI on D + 14. The paired Wilcoxon test and Mann-Whitney U test were performed for statistical analysis. RESULTS The K(trans) and v(e) values of the CNV-induced right eyes were significantly higher than those of the intact eyes in control rats at D + 14 (P < 0.05). In the CNV-induced eyes, the relative K(trans) and v(e) values of the KR-31831-treated group were significantly lower than those of the nontreated group at D + 14 (P < 0.05). The angiography showed that decreased CNV was observed in rats treated with KR-31831. CONCLUSIONS Quantitative DCE-MRI produces noninvasive biomarker of CNV, thus allowing monitoring of therapeutic response of antiangiogenic drugs in neovascular age-related macular degeneration (AMD).

PURPOSE: To estimate genetic influences accounting for macular thickness in the Korean population. METHODS: Study subjects were 830 healthy Korean adults (117 monozygotic twin pairs and 523 family members) from the Healthy Twin study. Macular thickness was measured with optical coherence tomography for nine subfields including the fovea, four inner quadrants (within 1 to 3 mm of the center), and four outer quadrants (within 3 to 6 mm of the center). Quantitative genetic analyses were performed to estimate the heritability of macular thickness with respect to familial correlations. RESULTS: Macular thickness varied by subfield and was thinnest at the fovea and thickest at the inner superior area. Heritability of macular thickness at each subfield was 0.76, 0.73, 0.70, 0.56, 0.67, 0.70, 0.73, 0.29, and 0.36 at the fovea, inner superior area, inner inferior area, inner nasal area, inner temporal area, outer superior area, outer inferior area, outer nasal area, and outer temporal area, respectively. CONCLUSIONS: Genetic factors play a significant role in determining macular thickness in the Korean population.

Although external-beam radiation therapy (EBRT) has been an effective treatment modality in patients with bilateral advanced retinoblastoma, it significantly increases the risk of second malignancies and facial deformities. This study aimed to evaluate the efficacy of tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) for treatment, instead of EBRT, in children with bilateral advanced retinoblastoma. Fourteen patients with bilateral retinoblastoma received chemotherapy, and local therapy was provided whenever possible. When at least one functional eye could not be saved by chemoreduction and local therapy, tandem HDCT/ASCR was provided to avoid EBRT. As a result, nine patients received tandem HDCT/ASCR. The toxicities were tolerable and there was no TRM. All nine patients who received tandem HDCT/ASCR had at least one functional eye without EBRT, and in two patients, both eyes were saved. No second malignancy has developed to date. HDCT/ASCR might be an effective treatment for bilateral advanced retinoblastoma, especially in cases in which at least one functional eye could not be preserved with chemoreduction and local therapy alone, and where EBRT was unavoidable. Long-term follow-up and further studies are needed to evaluate the efficacy and toxicity of HDCT/ASCR as an alternative treatment to EBRT.

Clinical features and prognosis of HLA-B27 positive anterior uveitis (AU) were assessed compared with HLA-B27 negative AU in a Korean population, based on the medical records of AU patients seen at a university hospital. Twenty-seven HLA-B27 negative, idiopathic AU patients (group I) and 55 HLA-B27 positive AU patients (group II) were studied. HLA-B27 positive group was further divided into 29 with associated systemic disease (seronegative spondyloarthropathy) (group IIA) and 26 without associated systemic disease (group IIB). Significantly more severe anterior chamber inflammation in terms of anterior chamber cells (P=0.006) and hypopyon formation (P=0.034) was observed with higher frequency of AU attacks (P=0.007) in the HLA-B27 positive group than in the HLA-B27 negative group. Systemic/periocular steroids were required in significantly more patients in the HLA-B27 positive group than in the HLA-B27 negative group (P=0.015). However, no significant differences were observed for final ocular and visual outcomes between these two groups. Associated systemic disease made no significant difference in the clinical features and prognosis in the HLA-B27 positive AU patients. In conclusion, despite more severe inflammation and a higher recurrence rate, HLA-B27 positive AU shows similar good final ocular and visual outcomes compared to HLA-B27 negative, idiopathic AU in a Korean population.

Purpose This study aimed to evaluate an association between hypertension and macular thickness. Methods A total of 827 Korean adults composed of 163 pairs of twins and their family members were included in this population-based cross-sectional study. Macular thickness was measured with optical coherence tomography at nine macular subfields defined by the Early Treatment of Diabetic Retinopathy Study. Cardiometabolic risk factors, including body mass index (BMI), hypertension, diabetes, lipid profiles, and smoking status, were assessed. Linear mixed regression analysis was conducted with consideration of familial correlations and adjustment for covariates. Results Age-, sex-, and axial length-adjusted analysis showed that systemic hypertension was associated with a significant change in macular thickness in most subfields except for the fovea. Compared with normotensive subjects, macular thickness was lower in subjects with systemic hypertension (P ≤ 0.05), with the highest difference (2.52%) in the outer temporal region and the lowest difference (1.44%) in the inner temporal region. This association persisted even after adjusting for other cardiometabolic risk factors. Other cardiometabolic risk factors were not independently associated with macular thickness in any subfields. Stratified analysis showed that the inverse association between macular thickness and hypertension was stronger in the group with elevated fasting glucose compared with the group with normal fasting glucose (P for interaction ≤ 0.05). Conclusions Systemic hypertension was inversely associated with macular thickness in most macular subfields, particularly in subjects with an elevated fasting glucose level. This finding suggests that it may be necessary to consider the presence of hypertension when macular thickness and pericentral macular area volume are evaluated.

Immune cell-mediated inflammatory responses are triggered by TCR engagement with the target antigen, the initial event that brings about the complex sequence of events of the inflammatory process. Another form of inflammation is induced by local expression of certain cytokines. Unlike the former form of inflammation, little is known about the basic features of the cytokine-induced responses. Here, we analyzed tissue morphology, the infiltrating cells, and up-regulated, inflammation-related genes in mouse eyes in which inflammation is triggered by local transgenic (Tg) expression of cytokines and compared these features with those in eyes with experimental autoimmune uveitis (EAU), in which inflammation is initiated by engagement of TCR on sensitized T cells with their target antigen, followed by the well-defined, subsequent cytokine production. Eyes of IFN-γ Tg mice exhibited severe, morphological changes but essentially no inflammation, and intense inflammation was found in eyes of interleukin (IL)-1 or IL-7 Tg mice. The cellular infiltration in eyes of these latter two lines of Tg mice resembled that in eyes with EAU by including many CD4 cells, but unlike in EAU, the infiltration in Tg eyes contained large proportions of B cells and only small numbers of macrophages. Real-time PCR analysis of eye RNA revealed differences among the disease models in the expression profiles of various inflammation-related genes. It is interesting that a bias toward T helper cell type 1 immunity (high IFN-γ, RANTES/CCL5, MIG/CXCL9, and T-bet but low IL-4, IL-5, and GATA-3 transcripts) was found in EAU eyes but not in eyes of IL-1 and IL-7 Tg mice. The results thus show that similar to TCR engagement, local expression of certain cytokines triggers a complex, subsequent production of numerous inflammation-related molecules, but features of the ensued inflammatory process are determined by the triggering mechanism.

PURPOSE. Different conclusions have been reached in recent studies concerning the immune response or tolerance of transgenic (Tg) mice expressing foreign antigens under control of retinal antigen promoters. The present study was aimed at analyzing the state of tolerance in Tg mice expressing hen egg lysozyme (HEL) under control of the rhodopsin promoter. METHODS. Tg mice expressing HEL under control of the rhodopsin promoter (RhHEL-Tg) were generated and tested by conventional methods for immune responses against HEL. These Tg mice were also mated with Tg mice expressing HEL-specific receptor on their T lymphocytes and the double-Tg mice were examined for increased apoptosis in their thymi by the TUNEL assay, as well as for loss of HEL-specific T cells, by flow cytometry and proliferative response. The presence of HEL mRNA in mouse thymi was determined by RTPCR. RESULTS. RhHEL-Tg mice developed tolerance to HEL, shown by reduced cellular and humoral responses to HEL, as well as by the failure of ocular inflammation to develop after immunization with HEL. RhHEL-Tg mice expressed HEL mRNA in their thymus, and the tolerogenic mechanism in these mice was shown to be thymic deletion of HEL-specific T cells by the following observations in the double-Tg mice: (1) increased apoptosis in their thymi, (2) remarkable reduction in the proportion of the HEL-specific T cells, and (3) loss of lymphocyte response to low concentrations of HEL. CONCLUSIONS. Tg mice expressing HEL under control of the rhodopsin promoter develop a tolerance for the foreign antigen, apparently as a result of thymic expression of HEL and deletion of T cells specific to this antigen. (Invest Ophthalmol

Little is known about the natural history and management of choroidal neovascularization (CNV) which developed as a complication of laser photocoagulation for central serous chorioretinopathy (CSC). We experienced two patients with CNV which developed after laser treatment for CSC. Submacular membranectomy was performed on both cases after the confirmation of subretinal CNV with optical coherence tomography. One patient received photodynamic therapy for recurrent CNV. The vision of both patients has been improved over 6 months of follow up. These cases suggest that active intervention, including submacular surgery, improves the visual prognosis of this condition.

To examine the hypothesis that RPE65, a protein specific to the retinal pigment epithelium, is uveitogenic in rats.Rats of four inbred strains (Lewis, Brown Norway, Fischer, and SHR) were immunized with native or recombinant bovine RPE65, or with S-antigen (S-Ag), emulsified with complete Freund adjuvant, and treated simultaneously with killed Bordetella pertussis bacteria, as indicated. Development of ocular changes was examined and scored both clinically and histologically.Lewis rats immunized with RPE65 showed development of acute and severe inflammatory eye disease that affected most ocular tissues. The minimum uveitogenic dose of RPE65 was similar to that of S-Ag (1 microg per rat), but the changes induced by RPE65 at higher dose ranges were less severe than those induced by S-Ag. Concurrent treatment of the RPE65-immunized rats with B. pertussis bacteria was not critical for disease induction, but enhanced dramatically the pathogenic reaction. Unlike the results with several other retinal proteins, no pinealitis was detected in rats immunized with RPE65. Fischer (F344) rats resembled Lewis rats in being similarly affected by RPE65 or S-Ag. In contrast, Brown Norway (BN) rats developed severe disease when immunized with RPE65, but showed minimal changes in response to S-Ag. SHR rats responded poorly to disease induced by RPE65, and S-Ag-induced disease failed to develop.RPE65 is highly uveitogenic in rats, thus suggesting that this molecule could be involved in pathogenic autoimmunity in the human eye.

Purpose: To investigate the advantages of ultrawide-field fluorescein angiography (FA) over the standard fundus examination in the evaluation of diabetic retinopathy (DR). Methods: Ultrawide-field FAs were obtained in 118 eyes of 59 diabetic patients; 11 eyes with no DR, 71 eyes with nonproliferative diabetic retinopathy (NPDR), and 36 eyes with proliferative diabetic retinopathy (PDR), diagnosed by the standard method. The presence of peripheral abnormal lesions beyond the standard seven fields was examined. Results: Ultrawide-field FA images demonstrated peripheral microaneurysms in six (54.5%) of 11 eyes with no DR and all eyes with moderate to severe NPDR and PDR. Peripheral retinal neovascularizations were detected in three (4.2%) of 71 eyes with NPDR and in 13 (36.1%) of 36 eyes with PDR. Peripheral vascular nonperfusion and vascular leakage were found in two-thirds of eyes with severe NPDR and PDR. Conclusions: Ultrawide-field FA demonstrates peripheral lesions beyond standard fields, which can allow early detection and a close evaluation of DR.

Purpose: Cytomegalovirus (CMV) retinitis is common in patients with immunodeficient conditions caused by acquired immunodeficiency syndrome (AIDS), cytotoxic chemotherapy and immunosuppresive treatment. The purpose of this study was to assess the clinical manifestations and prognosis of CMV retinitis cases. Methords: Thirty-one eyes of 21 patients who were diagnosed with CMV retinitis were retrospectively reviewed. The clinical manifestations and prognosis of all patients were analyzed. Results: The average age of patients was 24.419.8 years. Eight patients were female and 13 patients were male. The predisposing conditions of patients were leukemia (nine patients), immunosuppressed conditions due to organ transplantation (three patients), AIDS (two patients) and other (seven patients). Eleven patients exhibited bilateral disease. The mean follow-up period was 31.3 months, and there were no differences between mean initial visual acuity (0.700.31) and mean visual acuity (0.770.20) at final visit. The major causes of visual loss were retinitis and atrophic changes involving the macula. Although retinitis was successfully treated with anti-viral agents in all cases, cataract (10 eyes, 31.3%), cystoid macular edema (four eyes, 12.5%), retinal detachment (two eyes, 6.3%), epiretinal membrane (two eyes, 6.3%) and immune recovery uveitis (two eyes, 6.3%) developed after the initial treatment. Conclusions: Although the visual prognosis of CMV retinitis was relatively good after administration of appropriate antiviral therapy, clinicians should remain alert for the development of late complications, including retinal detachment, cystoid macular edema and immune recovery uveitis.

Purpose: To investigate the clinical characteristics and treatment of intermediate uveitis under new diagnostic standards. Methods: Medical records of patients diagnosed with pars planitis or intermediate uveitis were followed for more than 6 months, and retrospectively reviewed. Results: A total of 90 patients and 117 eyes were enrolled in the study. The mean age was 40.1 years, and the mean follow-up period was 43.0 months. Thirty percent of cases were bilateral. The most common initial symptom was decreased visual acuity. Snowbank was detected in 39.3%, snowballs in 15.4%, vitritis in 96.6%, and vasculitis in 56.4%. Common complications includedcystoid macular edema (57.3%), cataracts (43.6%), and epiretinal membrane (36.8%). Therapies included topical steroids (82.9% of cases), posterior sub-Tenon steroid injection (45.3% of cases), systemic steroid administration (67.8% of cases), and immunosuppressants (28.7% of cases). Vitrectomy was performed in 11.1% of patients due to complications such as epiretinal membrane and traction retinal detachment. The mean initial and final visual acuities were 0.67 and 0.74, respectively. Conclusions: The patients in this study experienced various courses of symptoms that required different treatment plans. Future investigations may corroborate these results.

Retinal ischemia and neovascularization have been demonstrated in several animal models. To determine 1) whether the retinal or preretinal neovascularization can be induced in albino rats by retinal vein occlusion and 2) the type and rate of occurrence on neovascularization, we occluded retinal veins in albino rats by photodynamic thrombosis. After anesthesia, each of 36 rats received an injection of rose bengal photosensitive dye, and their veins underwent argon green laser treatment. Half or all the major retinal veins were occluded in 12 eyes and in 24 eyes, respectively. Ten control rats underwent the same procedures but the laser beam was directed between major retinal vessels. In 46 control eyes, rose bengal dye was seen to have perfused without laser treatment. Retinal detachment developed in most vein occluded eyes within one day of venous occlusion, which was confirmed by fluorescein angiography. On follow-up at two weeks, only four of 24 eyes (16.7%) had undergone occlusion of all retinal veins showed new preretinal vessels on the optic disc. In these four eyes, severe disturbance of both retinal arterial and venous blood flow was observed, but no other eyes showed such severe combined disturbance. These data suggest that preretinal neovascularization in albino rats can be induced by this minimally traumatic method and that venous occlusion is severe enough to compromise arterial blood flow for a certain threshold period, thus inducing the development of preretinal neovascularization.