Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study

Background@#Epidemiological data have shown that vitamin D deficiency is highly prevalent in Korea. Genetic factors influencing vitamin D deficiency in humans have been studied in Europe but are less known in East Asian countries, including Korea. We aimed to investigate the genetic factors related to vitamin D levels in Korean people using a genome-wide association study (GWAS). @*Methods@#We included 12,642 subjects from three different genetic cohorts consisting of Korean participants. The GWAS was performed on 7,590 individuals using linear or logistic regression meta- and mega-analyses. After identifying significant single nucleotide polymorphisms (SNPs), we calculated heritability and performed replication and rare variant analyses. In addition, expression quantitative trait locus (eQTL) analysis for significant SNPs was performed. @*Results@#rs12803256, in the actin epsilon 1, pseudogene (ACTE1P) gene, was identified as a novel polymorphism associated with vitamin D deficiency. SNPs, such as rs11723621 and rs7041, in the group-specific component gene (GC) and rs11023332 in the phosphodiesterase 3B (PDE3B) gene were significantly associated with vitamin D deficiency in both meta- and mega-analyses. The SNP heritability of the vitamin D concentration was estimated to be 7.23%. eQTL analysis for rs12803256 for the genes related to vitamin D metabolism, including glutamine-dependent NAD(+) synthetase (NADSYN1) and 7-dehydrocholesterol reductase (DHCR7), showed significantly different expression according to alleles. @*Conclusion@#The genetic factors underlying vitamin D deficiency in Korea included polymorphisms in the GC, PDE3B, NADSYN1, and ACTE1P genes. The biological mechanism of a non-coding SNP (rs12803256) for DHCR7/NADSYN1 on vitamin D concentrations is unclear, warranting further investigations.

Changes in High-order Aberrations after Phacotrabeculectomy Surgery

PURPOSE: To investigate changes in ocular high-order aberrations (HOAs) resulting from phacotrabeculectomy and phacoemulsification. METHODS: We retrospectively reviewed 38 eyes of 38 glaucoma and cataract patients who underwent mitomycin C (MMC) augmented trabeculectomy with phacoemulsification and 34 eyes of 34 cataract patients who underwent phacoemulsifiction. For all patients, we measured the best corrected visual acuity (BCVA), intraocular pressure (IOP), keratometry, and HOAs (iTrace, Tracey Technologies, Houston, TX, USA) both preoperatively and postoperatively. RESULTS: IOP was significantly decreased after surgery in the combined group (p < 0.001). Entire eye, coma-like, and spherical-like high-order aberrations from each entire eye, corneal aberrations, and internal-optics aberration were increased until after 2 weeks, which then decreased until 3 months after phacotrabeculectomy. In the phacoemulsification group, entire eye (each p = 0.006, p =0.006), coma-like (each p = 0.006 and p = 0.005), and spherical-like high-order aberrations (each p = 0.008, p = 0.005) from entire eye and internal-optics aberrations were decreased. CONCLUSIONS: After cataract surgery, entire eye, coma-like, and spherical-like high-order aberrations were significantly decreased while aberrations did not change after combined operation. These results suggest that a change in high-order aberrations of internal optics results in a decrease in postoperative HOAs. In addition, the baseline HOAs of the cataract group were higher than those of the combined surgery group, and the effect of trabeculectomy on HOAs may offset the impact of cataract surgery in the combined surgery group.

A Case of Pigmentary Glaucoma Due to Multidrug-Resistant Tuberculosis Treatment

PURPOSE: To report a case of secondary pigmentary glaucoma due to clofazimine treatment for extensive drug-resistant tuberculosis. CASE SUMMARY: A 23-year-old man presented with blurred vision in both eyes. The patient started to take clofazimine for extensive drug-resistant tuberculosis six months prior, after which his facial skin color changed to a dark-brown. Intraocular pressure (IOP) was 50 mm Hg in the right eye and 48 mm Hg in the left eye. Slit lamp examination revealed corneal edema, opacity, and flare in the anterior chamber in both eyes. A color vision test revealed a mild color defect in both eyes. Visual field (VF) test revealed superior temporal VF loss in the left eye. Gonioscopy revealed open angles with high pigmentation in the trabecular meshwork in both eyes. The patient was diagnosed with pigmentary glaucoma, and maximum tolerated medical therapy was performed. However, the IOP was uncontrolled. Trabeculectomy was performed in both eyes. Postoperative IOP was measured to be 12 mm Hg in both eyes without medication, and visual acuity measured 20/22 in the right eye and 20/17 in the left eye. CONCLUSIONS: To the best of our knowledge, this report is the first case of clofazimine being a possible cause of pigmentary glaucoma in a patient with extensive drug-resistant tuberculosis.

Characterization of Incidentally Detected Adrenal Pheochromocytoma

BACKGROUND: In approach to an adrenal incidentaloma, early exclusion of pheochromocytoma is clinically important, due to the risk of catecholamine crisis. The aims of this study are to investigate the characteristics of incidentally detected pheochromocytomas, compared with that of the other adrenal incidentalomas, and to compare these characteristics with those of symptomatic pheochromocytomas. METHODS: In this retrospective study, we reviewed the medical records of 198 patients with adrenal incidentaloma from 2001 to 2010. We analyzed the clinical, laboratory and radiological data of pheochromocytomas, in comparison with those of the other adrenal incidentalomas. We also compared the characteristics of these incidentally detected pheochromocytomas with the medical records of 28 pathologically proven pheochromocytomas, diagnosed based on typical symptoms. RESULTS: Among the 198 patients with adrenal incidentaloma, nineteen patients were diagnosed with pheochromocytoma. Pheochromocytomas showed larger size and higher Hounsfield unit at precontrast computed tomography (CT) than did non-pheochromocytomas. All pheochromocytomas were larger than 2.0 cm, and the Hounsfield units were 19 or higher in precontrast CT. When both criteria of size > 2.0 cm and Hounsfield unit > 19 were met, the sensitivity and specificity for the diagnosis of pheochromocytoma were 100% and 79.3%, respectively. Compared with patients with pheochromocytoma, diagnosed based on typical symptoms, patients with incidentally detected pheochromocytoma were older, presented less often with hypertension, and showed lower levels of 24-hour urine metanephrine. CONCLUSION: Adrenal incidentaloma with < 2.0 cm in size or < or = 19 Hounsfield units in precontrast CT imaging was less likely to be a pheochromocytoma. Patients with incidentally discovered pheochromocytoma showed lower catecholamine metabolites, compared with those patients with symptomatic pheochromocytoma.

The Experience and Competence of Physicians Who Provide Emergency Health Care at Public Health Sub-Centers on Remote Islands in Korea / 農村醫學 地域保健

OBJECTIVES: To investigate the experience and competence of physicians providing emergency medical services at public health sub-centers on remote Korean islands. METHODS: This study enrolled 79 doctors who work at public health sub-centers on remote Korean islands. Data were collected in December 2009 via self-administered e-mail questionnaires. The response rate was 44.3%. RESULTS: Emergent situations occurred at most (58.68%) of the public health sub-centers that were surveyed in December 2009. An average of 1.92 cases required treatment by public health physicians. Only 20.25% of the physicians were specialists in emergency medicine, while the remainder were general practitioners (GPs) without clinical experience as emergency doctors. We also found that the physicians we surveyed had insufficient knowledge of emergency medical care. At some health centers only one doctor was available, and there was no medical team in holiday, although most of the physicians indicated that the ideal number of doctors per center was two or three. In cases of emergency, patients were often sent to the mainland by ship without receiving first-aid treatment. The public health sub-centers lacked the necessary medical equipment to save lives in emergencies and lacked escort systems for emergency patients. CONCLUSIONS: The Korean government should address the importance of providing emergency care in remote areas. Health administrators should provide suitable manpower, medical equipment, guidelines for emergency medicine, and education for public health physicians on remote islands.

A Case of Carotid Aneurysm in Familial Retinal Arterial Tortuosity

A 44-year-old woman who showed recurrent vitreous hemorrhages with vascular tortuosity received CT angiography which revealed an internal carotid artery aneurysm. A case of internal carotid aneurysm was associated with a pattern of retinal arteriolar tortuosity pathognomic for familial retinal arterial tortuosity (fRAT), suggesting possible involvement of the cerebral circulation. We present a case of internal carotid aneurysm associated with a pattern of retinal arteriolar tortuosity pathognomic for fRAT.

Assessment of Functional Vision Score and Vision-Specific Quality of Life in Individuals With Retinitis Pigmentosa

PURPOSE: To determine the relationship between the American Medical Association's (AMA) functional vision score (FVS) and vision-specific quality of life in retinitis pigmentosa (RP) patients using the National Eye Institute's Visual Functioning Questionnaire (NEI-VFQ 25). METHODS: One hundred eight patients with RP participated in the study. We measured best-corrected visual acuity, conducted Goldmann perimetry, and collected the self-reported NEI-VFQ 25. The FVS was calculated using the functional field score (FFS) and the functional acuity score (FAS). The correlations of the VFQ composite scores to the FVS, FFS, and FAS were determined using correlation and regression analyses. RESULTS: FVS was highly correlated to the BCVA (r=0.69, p<0.001), the FFS (r=0.86, p<0.001) and the FAS (r=0.73, p<0.001). Significant correlations of the VFQ composite score to the BCVA (r=0.60, p<0.001), FFS (r=0.44, p<0.001), FAS (r=0.60, p<0.001), FVS (r=0.58, p<0.001) were also found. However, the correlation strengths of BCVA, FVS, FAS, and FFS to NEI-FVQ were not different. CONCLUSIONS: In RP patients, the vision-specific quality of life was correlated with the AMA guidelines' FVS, FFS, and FAS. Their correlation degrees to NEI-FVQ were not different. This result suggests that vision-specific quality of life can be explained by both visual acuity and visual field in RP patients.

A Case of Vogt-Koyanagi-Harada Disease in a Patient With Graves Disease

A case of Vogt-Koyanagi-Harada disease (VKH) that developed in a 36-year-old woman with Graves' disease was described. The patient was treated with Lugol's solution and presented with bilateral serous retinal detachment. She had also suffered from methimazole-induced hypersensitivity and steroid-induced myopathy. Fluorescein angiography showed multiple leakage points and a lumbar puncture revealed pleocytosis, which was compatible with VKH. High dose steroid pulse therapy was successful. Altered immune regulation associated with drug-induced hypersensitivity may contribute to the development of VKH in patients with Graves' disease.

Differences in the Histopathology and Matrix Metalloproteinase Expression in Tenon's Tissue of Primary Open-Angle Glaucoma and Primary Angle-Closure Glaucoma

PURPOSE: To investigate the differences in the histopathology and matrix metalloproteinase (MMP) expression in the Tenon's tissue of primary open-angle glaucoma (POAG) patients, primary angle-closure glaucoma (PACG) patients, and non-glaucomatous patients. METHODS: POAG and PACG patients, who underwent a trabeculectomy and had no history of ocular disease except glaucoma, were enrolled. The number and instillation period of topical eye drops were reviewed. For the controls, which were patients without glaucoma or a history of ocular surgery, the Tenon's tissue was obtained in the course of retinal detachment surgery. For glaucoma patients, the Tenon's tissue was obtained during the trabeculectomy. H&E and Masson's trichrome staining and immunohistochemistry for MMP-1, MMP-2, and MMP-9 were performed. A total of six eyes of POAG, six eyes of PACG, and four control eyes were evaluated. RESULTS: The duration of topical anti-glaucoma medication and the mean number of anti-glaucoma medications were similar in the POAG and PACG groups. The levels of MMP-1 and 2 were elevated in the POAG and PACG groups compared to the control group (p=0.03, 0.01, respectively). Compared with the control group, the MMP-2 level was higher in the POAG patients (p=0.01), whereas the MMP-1 was higher in the PACG patients (p=0.04). The levels of MMP-9 in the POAG and PACG patients were not significantly different from that of the control patients (p=0.48, 0.26). The levels of MMP-2 were significantly lower in the PACG patients than in the POAG patients (p=0.02). CONCLUSIONS: The MMP expression was altered in the Tenon's tissue of glaucoma patients compared to the control group. The levels of MMP-2 were lower in the PACG patients than in the POAG patients. These results suggest that there may be histopathological differences in the Tenon's tissue of POAG and PACG patients.

Differences in the Histopathology and Matrix Metalloproteinase Expression in Tenon's Tissue of Primary Open-Angle Glaucoma and Primary Angle-Closure Glaucoma

PURPOSE: To investigate the differences in the histopathology and matrix metalloproteinase (MMP) expression in the Tenon's tissue of primary open-angle glaucoma (POAG) patients, primary angle-closure glaucoma (PACG) patients, and non-glaucomatous patients. METHODS: POAG and PACG patients, who underwent a trabeculectomy and had no history of ocular disease except glaucoma, were enrolled. The number and instillation period of topical eye drops were reviewed. For the controls, which were patients without glaucoma or a history of ocular surgery, the Tenon's tissue was obtained in the course of retinal detachment surgery. For glaucoma patients, the Tenon's tissue was obtained during the trabeculectomy. H&E and Masson's trichrome staining and immunohistochemistry for MMP-1, MMP-2, and MMP-9 were performed. A total of six eyes of POAG, six eyes of PACG, and four control eyes were evaluated. RESULTS: The duration of topical anti-glaucoma medication and the mean number of anti-glaucoma medications were similar in the POAG and PACG groups. The levels of MMP-1 and 2 were elevated in the POAG and PACG groups compared to the control group (p=0.03, 0.01, respectively). Compared with the control group, the MMP-2 level was higher in the POAG patients (p=0.01), whereas the MMP-1 was higher in the PACG patients (p=0.04). The levels of MMP-9 in the POAG and PACG patients were not significantly different from that of the control patients (p=0.48, 0.26). The levels of MMP-2 were significantly lower in the PACG patients than in the POAG patients (p=0.02). CONCLUSIONS: The MMP expression was altered in the Tenon's tissue of glaucoma patients compared to the control group. The levels of MMP-2 were lower in the PACG patients than in the POAG patients. These results suggest that there may be histopathological differences in the Tenon's tissue of POAG and PACG patients.

Risk Factors Affecting Efficacy of Intracameral Amphotericin Injection in Deep Keratomycosis

PURPOSE: To investigate the clinical efficacy of intracameral amphotericin injection and to evaluate risk factors affecting primary treatment success in fungal infection invading the anterior segment of the eye. METHODS: Twenty-six eyes of 26 patients diagnosed with fungal infection in the anterior segment were studied. The initial treatment regimen was a topical 0.15% amphotericin application and itraconazole oral administration after culture. Amphotericin (5 ug/0.1 ml, 0.1 cc) was repeatedly injected intracamerally when the infection intensified. Penetrating keratoplasty was conducted for eyes unresponsive to intracameral amphotericin injection. The relative risk ratios of ulcer size, infiltration depth, culture positivity, and hypopyon were compared in each treatment group to evaluate the treatment response. RESULTS: Of patients with fungal infection, 30.7% were cured with intracameral amphotericin injection, while 30.7% needed penetrating keratoplasty. Intracameral amphotericin injection was needed in the presence of large corneal ulcers (>14 mm2), hypopyon, positive fungal culture, use of steroid eye drops, and deep infiltration at initial examination. Large ulcer size (>14 mm2) was the main risk factor for needing penetrating keratoplasty. Of the eyes Candida infection, 66.5% needed evisceration. CONCLUSIONS: Large ulcer size and the isolation of Candida were poor prognostic factors related to the efficacy of intracameral amphotericin injection.

Effect of Base Curve Radius of Therapeutic Lenses on Epithelial Healing after Laser-Assisted Subepithelial Keratectomy

PURPOSE: To determine the effect of the base curve radius (BCR) of therapeutic soft contact lens (T-lens) on epithelial healing after laser-assisted subepithelial keratectomy (LASEK). METHODS: Ninety-two eyes in 47 patients with myopia were prospectively evaluated after LASEK. All the patients wore T-lenses with the BCR (R1) randomly chosen after LASEK. The T-lenses were removed after complete healing of the epithelial wounds. We calculated an estimated BCR (R2) from postoperative topography using a diopter conversion table. The patients were divided into two groups according to the differences between the BCR (R1) and the estimated BCR (R2). The flat fitting group was R1 > R2 (Group A), and the steep fitting group was R1R2) had 53 eyes, and Group B (R1

Effect of Base Curve Radius of Therapeutic Lenses on Epithelial Healing after Laser-Assisted Subepithelial Keratectomy

PURPOSE: To determine the effect of the base curve radius (BCR) of therapeutic soft contact lens (T-lens) on epithelial healing after laser-assisted subepithelial keratectomy (LASEK). METHODS: Ninety-two eyes in 47 patients with myopia were prospectively evaluated after LASEK. All the patients wore T-lenses with the BCR (R1) randomly chosen after LASEK. The T-lenses were removed after complete healing of the epithelial wounds. We calculated an estimated BCR (R2) from postoperative topography using a diopter conversion table. The patients were divided into two groups according to the differences between the BCR (R1) and the estimated BCR (R2). The flat fitting group was R1 > R2 (Group A), and the steep fitting group was R1R2) had 53 eyes, and Group B (R1

Early versus Late Intravitreal Triamcinolone Acetonide for Macular Edema associated with Branch Retinal Vein Occlusion

PURPOSE: To compare the effect of early versus late intravitreal injection of triamcinolone in patients with macular edema due to branch retinal vein occlusion (BRVO). METHODS: Twenty eyes of 20 patients with macular edema from BRVO, including 10 with duration after onset of 3 months, were treated using a single intravitreal triamcinolone injection (4 mg/0.1 ml). Best-corrected visual acuity and foveal thickness by optical coherence tomography were measured 1, 3, and 6 months post-injection. RESULTS: In patients that received treatment after a disease duration of 3 months, improvements in visual acuity and foveal thickness, though apparent at 1 month, were not maintained at 3 and 6 months post-triamcinolone. CONCLUSIONS: Intravitreal triamcinolone is more effective in patients with BRVO who are treated earlier.

Onset of Retinal Detachment in Eyes with Phacoemulsification and Posterior Chamber Lens Implantaton

PURPOSE: To evaluate the onset of retinal detachment (RD) in eyes with phacoemulsification and post chamber lens (PE & PCL) implantation. METHODS: We retrospectively analyzed 3023 eyes that had undergone clear cornea incision and PE and PCL implantation and 116 eyes that had undergone scleral incision and PE and PCL implantation. They had been operated from January 1995 to December 2000 by one surgeon and followed up for 4 years or more. RESULTS: Eighteen eyes (0.57%) of the 3139 eyes developed pseudophakic RD within a mean period of 663 days. In the scleral incision group, there were 4 cases of pseudophakic RD (3.4%) of 116 eyes developed in a mean period of 185.2 days. In the clear cornea group, there were 14 pseudophakic RD eyes (0.46%) of the 3023 eyes and the mean period was 799 days. Of these, 3 eyes made up the intraoperative complication group with a mean period 205.6 days. But in the group of cases with no intraoperative complications, the mean period was 962 days. CONCLUSIONS: In high myopic eyes, retinal detachment developed in the earlier postoperative period and at a higher rate than those of non-high myopic eyes after PE and PCL implantation.