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To evaluate the degree of genetic influence on macular choroidal volume.A cross-sectional twin and family study.In total, 353 Korean adults with healthy eyes from 78 households with 2 or more family members were included in the study. Macular choroidal volume was measured using spectral-domain optical coherence tomography with enhanced depth imaging at 9 macular subfields defined by the ETDRS. Demographics and clinical characteristics were investigated, including age, sex, axial length, hypertension, diabetes, drinking habits, and smoking status. The associations of these factors with macular choroidal volume were assessed using univariate and subsequent multivariate regression analyses while accounting for family structure. The heritability estimates of macular choroidal volume in total and at each of the 9 macular subfields were calculated after adjusting the covariates.Patients who were younger, male, and had a shorter axial length showed associations with greater choroidal volume (P.001 for all 3 independent variables). The covariates-adjusted heritability (±standard error) of the total macular choroidal volume was 0.76 ± 0.06, and the heritabilities of choroidal volume at each subfield ranged from 0.55 ± 0.09 (inner temporal subfield) to 0.77 ± 0.08 (inner superior subfield).The macular choroidal volume is highly heritable.

PurposeTo evaluate genetic influence on macular ganglion cell inner plexiform layer (GCIPL) thickness.MethodsMacular GCIPL thickness was measured with optical coherence tomography in nine macular subfields defined by the E TDRS. Intraclass correlation coefficients (ICC) of GCIPL thickness by different types of family relationships were estimated to assess intrafamilial resemblance. Then, heritability of GCIPL thickness was estimated.ResultsThree hundred and sixty-one Korean adults from 89 families with normal healthy eyes were included. GCIPL thickness was highest in inner subfields and lowest in fovea. Monozygotic twin pairs showed significantly higher ICCs of GCIPL thickness in all subfields compared to those in parent–offspring pairs and sibling pairs. GCIPL thickness was highly heritable in the centre (0.71) and outer subfields but moderate to highly heritable in inner subfields. Heritability of GCIPL thickness in outer subfields was 0.69, 0.67, 0.72 and 0.68 for superior, inferior, temporal and nasal fields, respectively. Heritability of GCIPL thickness in inner subfields was 0.55, 0.56, 0.75 and 050 for superior, inferior, temporal and nasal subfields, respectively.ConclusionMacular GCIPL thickness is significantly influenced by genetic factors. It varies according to subfields with moderate to high heritability in all subfields.

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.

Purpose To investigate association between the development of retinal vein occlusion (RVO) and blood high-density lipoprotein cholesterol (HDL-C). Design A retrospective, nationwide, population-based cohort study. Methods This study was set in the Republic of Korea and included 23,149,403 people ≥20 years of age who underwent the Korean National Health Screening Program examination between January 2009 and December 2012. Among them, the RVO group was composed of patients with an initial diagnosis of RVO made between 2009 and 2015 (n = 117,639). The earliest claim with an RVO diagnostic code was considered as the incident time. The predictive value of HDL-C level for RVO was analyzed using hazard ratios. The primary outcome measure was the incident cases of RVO. Results Subjects with RVO were generally older; had high body mass index, waist circumference, fasting blood glucose, blood pressure, total and low-density lipoprotein cholesterol, and triglyceride values, and low glomerular filtration rate and HDL-C values; and were more likely to experience diabetes mellitus and hypertension compared with the non-RVO group. The fully adjusted hazard ratio of RVO was 1.12 (95% confidence interval 1.10-1.14) in the lowest quartile of HDL-C versus in the highest quartile. The association between the development of RVO and HDL-C was higher those with a younger age, male sex, current smoking habit, diabetes mellitus, and hypercholesterolemia. In addition, we observed a significant synergistic effect of low HDL-C level with obesity and hypertension. Conclusion This is the first nationwide population-based epidemiologic study evaluating the association between HDL-C level and the risk of RVO development. A significant association between low HDL-C and RVO development was found.

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.

Background/aimsTo investigate the prevalence of abnormal central and peripheral ultra-wide-field (UWF) angiography findings, and their association with clinical features in acute Vogt-Koyanagi-Harada (VKH) disease.MethodsThis retrospective, observational study included 26 eyes of 13 treatment-naïve patients with acute VKH disease who underwent UWF fluorescein angiography (FA). Sixteen eyes of eight patients also underwent UWF indocyanine green angiography (ICGA). A circle simulating the central 75° field was used to divide the acquired image into the central fundus area (CFA) and peripheral fundus area (PFA), in which the presence of six previously reported abnormal angiographic findings were analysed. Correlations between abnormal angiography findings in FA and clinical features were also investigated.ResultsAll eyes demonstrated more than one abnormal angiographic finding in both the CFA and PFA. UWF FA revealed three abnormal findings in the CFA versus the PFA: focal leakage (92.3% vs 76.9%); pooling with a dark rim (84.6% vs 53.8%); and retinal vascular leakage (0% vs 46.2%). UWF ICGA revealed three abnormal findings in the CFA versus the PFA: hypofluorescent dark dots (100% vs 100%); diffusely leaking fuzzy choroidal vessels (93.8% vs 75.0%); and late hypofluorescent patches (81.3% vs 31.3%). Pooling with a dark rim and retinal vascular leakage in the PFA were significantly associated with low initial visual acuity (p=0.03) and subfoveal choroidal thickness change ratio (p=0.04), respectively.ConclusionAbnormal UWF angiography findings were frequently detected in the CFA and PFA. Such findings may be useful in evaluation and monitoring of VKH disease.

PURPOSE To investigate the anatomical and refractive outcomes in patients with Type 1 retinopathy of prematurity in Zone I. METHODS The medical records of 101 eyes of 51 consecutive infants with Type 1 retinopathy of prematurity in Zone I were analyzed. Infants were treated by conventional laser photocoagulation (Group I), combined intravitreal bevacizumab injection and Zone I sparing laser (Group II), or intravitreal bevacizumab with deferred laser treatment (Group III). The proportion of unfavorable anatomical outcomes including retinal fold, disc dragging, retrolental tissue obscuring the view of the posterior pole, retinal detachment, and early refractive errors were compared among the three groups. RESULTS The mean gestational age at birth and the birth weight of all 51 infants were 24.3 ± 1.1 weeks and 646 ± 143 g, respectively. In Group I, an unfavorable anatomical outcome was observed in 10 of 44 eyes (22.7%). In contrast, in Groups II and III, all eyes showed favorable anatomical outcomes without reactivation or retreatment. The refractive error was less myopic in Group III than in Groups I and II (spherical equivalent of -4.62 ± 4.00 D in Group I, -5.53 ± 2.21 D in Group II, and -1.40 ± 2.19 D in Group III; P < 0.001). CONCLUSION In Type 1 retinopathy of prematurity in Zone I, intravitreal bevacizumab with concomitant or deferred laser therapy yielded a better anatomical outcome than conventional laser therapy alone. Moreover, intravitreal bevacizumab with deferred laser treatment resulted in less myopic refractive error.

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

Background/aimCharacterising genetic effect on macular retinal nerve fibre layer (RNFL) is needed to obtain better understanding of various retinopathies and optic neuropathies. The purpose of this study was to evaluate genetic influence on macular RNFL thickness.MethodsThis is a cross-sectional, twin and family study. Three hundred and sixty-two Korean adults with healthy eyes were included in the study from 79 households with two or more family members. Macular RNFL thickness was measured with optical coherence tomography at nine macular subfields defined by the ETDRS. Intraclass correlation coefficients (ICCs) were estimated to assess intrafamilial resemblance of RNFL thickness by different types of family relationship. Heritability of RNFL thickness was evaluated using variance decomposition model.ResultsRNFL thickness increased from central subfield to outer subfields. Temporal quadrant RNFL was thinner compared with other quadrants. Monozygotic twin pairs showed the highest ICCs of RNFL thickness, although the ICC level varied across different subfields. Heritability of RNFL thickness was the highest at central subfield (0.81). RNFL thicknesses of outer subfields were moderately to highly heritable: 0.53, 0.71, 0.47 and 0.66 for superior, inferior, temporal and nasal fields, respectively. RNFL thicknesses at inner subfields showed the lowest heritability: 0.21, 0.24, 0.27 and 0.27 for superior, inferior, temporal and nasal subfields, respectively.ConclusionMacular RNFL thickness is significantly influenced by genetic factors. It varies largely by subfields with the highest heritability at the central subfield and a relatively lower heritability at inner subfields.

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 To investigate the incidence of late age-related macular degeneration (AMD) over 3 years and risk factors for the development of late AMD in Korean patients having reticular pseudodrusen (RPD). Methods Clinical records of Korean RPD patients with no late AMD at first examination and completion of 3 years of regular follow-up were retrospectively reviewed. All patients underwent complete ocular examinations, including multimodal imaging. Reticular pseudodrusen were classified as a separate lesion different from other early AMD lesions, and RPD were not considered a sign of early AMD. Risk factors for the development of late AMD were assessed. Results One hundred and ninety-two RPD eyes of 104 patients were included in this study. Mean age of patients was 69.4 ± 8.9 years, and other early AMD lesions were accompanied in 152 eyes (79.2%) at baseline. During 3 years, late AMD occurred in 30 eyes (15.6%); geographic atrophy in 24 eyes (12.5%); and neovascular AMD in 6 eyes (3.1%). Eyes having early AMD at baseline revealed significantly higher incidence for late AMD than those eyes having no early AMD at baseline (18.4% vs. 5%, P = 0.048). Late AMD occurred in 5 eyes (38.5%) from 13 fellow RPD eyes of unilateral late AMD at baseline. In logistic regression analysis, thin choroidal thickness, diffuse distribution of RPD, and the presence of late AMD on fellow eye at baseline were significant risk factors for developing late AMD in RPD eyes. Conclusion Reticular pseudodrusen eyes revealed various progression rates to late AMD according to AMD status of both eyes. More frequent monitoring should be considered for patients with RPD at risk of progression to late AMD.

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

Purpose To compare the risk factors and rate of progression of zone I versus zone II type 1 retinopathy of prematurity (ROP). Methods The medical records of consecutive preterm infants with bilateral type 1 ROP in zone I and age-matched control infants with type 1 ROP in zone II were retrospectively analyzed. Fundus findings at each screening examination and systemic parameters were compared between groups. Univariate and conditional multivariate regression analyses were employed to identify variables significantly associated with zone I ROP. Results A total of 30 cases and 30 controls were included. The mean gestational age of included infants was 24.6 weeks in both groups, and the mean birth weights were 685 g in the zone I group and 667 g in the zone II group. The postmenstrual age (PMA) at the time of initial ROP detection did not differ between groups, but the PMA at the time of type 1 ROP detection was significantly earlier in the zone I group (mean, 34.9 vs 37.6 weeks). Conditional multiple logistic regression revealed that mechanical ventilation for 30 days or more was significantly associated with the type 1 ROP in zone I compared with zone II (OR, 3.5; 95% CI, 1.2-10.0). Conclusions Zone I ROP exhibited rapid progression, necessitating close monitoring and prompt treatment. Compromised pulmonary function with associated mechanical ventilation in early life may restrict retinal vascular growth and increase the likelihood of zone I type 1 ROP.

Purpose To characterize a variant type of drusenoid deposit with different imaging features in comparison to reticular pseudodrusen. Methods Retrospective observational consecutive case series. Eyes showing atypical drusenoid lesions were sorted out from 257 eyes of 133 patients previously diagnosed as reticular pseudodrusen. Eyes were evaluated using color fundus photography, confocal scanning laser ophthalmoscopy, and spectral domain optical coherence tomography. Results A variant type of drusenoid deposits showing different imaging features from reticular pseudodrusen was found in 17 eyes of 12 patients (6.6%). The mean age of patients was 62.7 ± 11.6 years, and all patients were women. These deposits were observed as yellowish white, round to oval lesions on color photographs, located under the sensory retina and above the retinal pigment epithelium on spectral domain optical coherence tomography similar to reticular pseudodrusen. However, they were present in a smaller number as discrete lesions and showed increased autofluorescence. None of them were accompanied by late age-related macular degeneration. Conclusion Subretinal drusenoid deposits are not homogeneous and can be classified into two types according to the fundus autofluorescence. Multimodal imaging tests are needed for the differential diagnosis of subretinal drusenoid deposits.

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.

Purpose The purpose of this study was to demonstrate a negative association between intraocular pressure (IOP) and age in 2 Asian populations. In addition, we evaluated genetic and nongenetic factors associated with IOP. Design Family-based cohort study. Participants Study subjects >10 years of age from one Korean ( The Healthy Twin ; n=1431) and 2 Mongolian populations ( The GENDISCAN ; n=859 and 806) with IOP values. Methods The IOP values were measured with a noncontact tonometer. Each participant received a standard health examination and received questionnaires, which include candidate risk factors on IOP. Mixed models were used to identify risk factors for IOP. Variance-component methods were applied to estimate the heritability of IOP. Main Outcome Measures The negative trend of IOP with aging and evaluation of impact of genetic and nongenetic components on IOP. Results The mean ages were 43.6, 34.1, and 36.3 years for the Korean, Orhontuul, and Dashbalbar populations, respectively. The mean IOPs were 14.4 mmHg (95% confidence interval [CI], 14.3–14.6) in the Koreans and 14.1 mmHg (95% CI, 13.9–14.3) and 12.6 mmHg (95% CI, 12.4–12.9) in the Orhontuul and Dashbalbar populations, respectively. In the 3 populations, the IOP decreased as age increased. We replicated an association of systolic blood pressure (SBP) with IOP. In addition, components of the metabolic syndrome (MS), such as plasma glucose, lipid level, and body mass index, showed positive associations with IOP, after adjusting for age and SBP. The IOP also had strong genetic contributions in all populations (heritability, 0.47–0.51). Conclusions Negative associations between age and IOP were observed in all 3 populations, which cannot be explained by the increasing prevalence of myopia in the younger generation. The different age trend in IOP may in part be responsible for differences in the prevalence of glaucoma subtypes. Our findings suggest that associations between IOP and MS components were independent of established risk factors such as SBP or age. In addition, the importance of inherited risks requires further genetic dissection of IOP determinants for biological understandings of underlying pathophysiology. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

Background/aims: To analyse the clinical manifestations and results of treatment for patients with retinoblastoma in Korea. Methods: The medical records of 70 children (92 eyes) diagnosed as having retinoblastoma and treated between 2000 and 2006 were retrospectively analysed. Data on gender, age at diagnosis, laterality, presenting sign, classification of tumour, treatment modality and prognosis were collected. Results: The most common presenting sign was leucocoria (80%). 31.4% developed bilateral retinoblastoma. Using the International Classification of Retinoblastoma, 7.5% were group A, 23.8% were group B, 6.3% were group C, 38.8% were group D, and 23.8% were group E. 26.1% of eyes were treated with chemoreduction and/or focal therapy, namely, they achieved globe preservation, and all other eyes were enucleated. The globe preservation was achieved in 100% of group A, 77.8% of group B, 66.7% of group C, and 26.7% of group D. Conclusions: In Korea, most children with retinoblastoma showed an advanced stage of tumour at the time of diagnosis and although they were treated with an updated therapeutic approach according to the newly introduced classification, the rate of globe preservation did not reach that of developed countries. Increased surveillance should be performed.

To assess the correlation between the features of optical coherence tomography (OCT) and fluorescein angiography in clinically significant diabetic macular edema.Retrospective observational case series.This study involved 145 eyes (91 patients) with clinically significant diabetic macular edema. The fluorescein angiography features were categorized into focal leakage type, diffuse leakage type, and diffuse cystoid leakage type. The OCT features were categorized into four types: type 1, thickening with homogeneous optical reflectivity; type 2, thickening with markedly decreased optical reflectivity in the outer retinal layer; type 3A, foveolar detachment without traction; and type 3B, foveolar detachment with apparent vitreofoveal traction. The correlation between fluorescein angiography types and OCT types were analyzed, and their associations with visual acuity, central foveal thickness. and stages of diabetic retinopathy were evaluated.The prevalence of OCT type 1 was higher in the focal leakage type (73.0%) and in the diffuse leakage type (58.9%) than in the diffuse cystoid leakage type (3.8%) of fluorescein angiography (P.0001). The prevalence of OCT type 2 and 3A was higher in the diffuse cystoid leakage type (57.7% and 34.6%, respectively) than in the focal leakage type (20.6% and 3.2%) or diffuse leakage type(28.6% and 10.7%; P.0001). The stages of retinopathy correlated with fluorescein angiography types (P =.016). Optical coherence tomography type 1 and the focal leakage type of fluorescein angiography showed the least foveal thickness and the best visual acuity (P.05).There was a significant correlation between the features of OCT and fluorescein angiography in clinically significant diabetic macular edema. The combined data from both OCT and fluorescein angiography may provide a clearer understanding of the anatomic and physiologic characteristics of clinically significant diabetic macular edema.

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: To determine whether endolaser photocoagulation to the retinal pigment epithelium at the base of a macular hole increases the anatomic success rate of surgery. METHODS: In a prospective consecutive clinical trial, eight eyes of seven patients with idiopathic macular hole underwent vitrectomy with posterior cortical vitreous removal and peeling of visible epiretinal membrane when present. A single shot of argon endolaser photocoagulation was applied to the retinal pigment epithelium at the center of the macular hole with a duration of 0.05 to 0.2 seconds and an intensity of 50 to 200 mW. After fluid-gas exchange was performed with 14% perfluoropropane gas, patients maintained face-down positioning for 2 weeks. RESULTS: One eye with stage 2 macular hole, six eyes with stage 3 macular hole, and one eye with stage 4 macular hole were included. All eight eyes had a closed macular hole (100% anatomic success rate) at final examination 6 to 12 months after surgery. Best-corrected visual acuity improved 3 or more lines on the Early Treatment Diabetic Retinopathy Study visual acuity chart in all eyes. Four (50%) of the eight eyes had a final visual acuity of 20/40 or better. CONCLUSIONS: Endolaser photocoagulation may be a useful adjunct to macular hole surgery but requires further investigation and long-term evaluation.

Purpose To evaluate the retinal thickness and volume measured with the enhanced depth imaging (EDI) method compared with those measured with the conventional method using spectral-domain optical coherence tomography (OCT). Design Retrospective, observational, case-control study. Methods Clinical records of 20 healthy subjects and those of 35 patients with chorioretinopathy (central serous chorioretinopathy, polypoidal choroidal vasculopathy, Vogt-Koyanagi-Harada disease, and reticular pseudodrusen) were analyzed retrospectively. All subjects underwent spectral-domain OCT using both the conventional and the EDI OCT raster scan protocols. The raster scan was composed of 31 B-scans that were 9.0 mm in length and 240 μm apart. Retinal thickness and volume of 9 Early Treatment Diabetic Retinopathy Study subfields were investigated. Intraclass correlation coefficients, Bland-Altman plots, and Wilcoxon signed-rank test results were used for the analysis. Results Sixty-five eyes of 35 patients with chorioretinal diseases and 40 eyes of 20 normal healthy subjects were evaluated. The automatically measured retinal thickness and volume of 9 Early Treatment Diabetic Retinopathy Study subfields with conventional and EDI raster scan showed an intraclass correlation coefficient of 0.861 to 0.995 and 0.873 to 0.995, respectively. The 95% limits of agreement between the 2 protocols in the measurement of central subfield were −14.52 to 12.88 μm in retinal thickness and −0.014 to 0.013 mm 3 in retinal volume. The differences of segmentation error rate between the 2 protocols were statistically insignificant ( P > .05), except in eyes with reticular pseudodrusen in the subgroup analysis ( P = .006). No significant differences were observed in measured values between healthy eyes and unaffected fellow eyes. Conclusions The EDI OCT raster scan showed high agreement with conventional OCT in the measurement of retinal thickness and volume and could be used to evaluate both the retina and choroid in normal eyes and in eyes with some forms of chorioretinal disorder.

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).

To clarify the clinical characteristics of reticular pseudodrusen in Korean patients.Retrospective, observational, consecutive case series.A total of 255 eyes of 130 patients diagnosed with reticular pseudodrusen were evaluated. Reticular pseudodrusen were diagnosed by characteristic fundus findings using ophthalmoscopy, color fundus photography with blue-channel examination, near-infrared photography, red-free photography, autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography. Age-related macular degeneration (AMD) was determined by the International Classification and Grading System.The mean age was 72.6 ± 9.0 years (range, 43 to 92 years). Most reticular pseudodrusen patients had bilateral disease (97.7%), with a female preponderance (86.2%). All 3 patients who showed unilateral reticular pseudodrusen had neovascular AMD in the eye with no reticular pseudodrusen. AMD was found in 183 eyes (71.8 %), among which early AMD was found in 115 eyes (45.1%), geographic atrophy was found in 41 eyes (16.1%), and neovascular AMD was found in 27 eyes (10.6%). The mean age of patients with AMD and with no AMD was 73.7 ± 9.2 years (range, 58 to 92 years) and 69.9 ± 11.7 years (range, 43 to 90 years), respectively, and there was a statistical difference between these 2 groups (P.05). Classic choroidal neovascularization was found in 13 eyes (48.1%), and occult choroidal neovascularization was found in 14 eyes (51.9%) in the neovascular AMD group.Reticular pseudodrusen occurs in Koreans, and clinical manifestations of reticular pseudodrusen in Koreans did not differ significantly from those described in white persons. However, our study demonstrated a higher rate of bilaterality compared with those previously reported, and geographic atrophy was found to be associated more commonly with reticular pseudodrusen than with neovascular AMD. Ethnical differences may be associated with these findings, and further studies are required.

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.

Purpose To describe a new instrument, the subretinal aspiration and injection device (SR-AID), designed to facilitate the controlled external drainage or injection of fluid in the subretinal space. Methods The SR-AID is formed by an assembly of a probe, handle body, and a driving unit. The curved conduit within the probe segment forms a curved tunnel and acts as a guide along which a needle moves back and forth. The feasibility of fluid injection beneath the attached retina was tested in animal eyes. The efficacy of subretinal fluid drainage with the SR-AID were assessed in six cases of clinical retinal detachment. Results External approach to the subretinal space under ophthalmoscopic monitoring can be achieved by oblique angle penetration of the scleral wall with a needle from the SR-AID. Fluid was injected successfully into the subretinal space in three of six rabbit eyes and in two of two pig eyes. The mean duration required for the drainage of subretinal fluid with the SR-AID was 127 seconds. There was no incidence of significant subretinal hemorrhage or retinal perforation in the animal experiments and in human cases. Conclusion Our case series suggests that the SR-AID provides an efficient and safe means of access to the subretinal space.

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.

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.