1.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
2.Deep Learning-based Prediction of Axial Length Using Ultra-widefield Fundus Photography
Richul OH ; Eun Kyoung LEE ; Kunho BAE ; Un Chul PARK ; Hyeong Gon YU ; Chang Ki YOON
Korean Journal of Ophthalmology 2023;37(2):95-104
Purpose:
To develop a deep learning model that can predict the axial lengths of eyes using ultra-widefield (UWF) fundus photography.
Methods:
We retrospectively enrolled patients who visited the ophthalmology clinic at the Seoul National University Hospital between September 2018 and December 2021. Patients with axial length measurements and UWF images taken within 3 months of axial length measurement were included in the study. The dataset was divided into a development set and a test set at an 8:2 ratio while maintaining an equal distribution of axial lengths (stratified splitting with binning). We used transfer learning-based on EfficientNet B3 to develop the model. We evaluated the model’s performance using mean absolute error (MAE), R-squared (R2), and 95% confidence intervals (CIs). We used vanilla gradient saliency maps to illustrate the regions predominantly used by convolutional neural network.
Results:
In total, 8,657 UWF retinal fundus images from 3,829 patients (mean age, 63.98 ±15.25 years) were included in the study. The deep learning model predicted the axial lengths of the test dataset with MAE and R2 values of 0.744 mm (95% CI, 0.709–0.779 mm) and 0.815 (95% CI, 0.785–0.840), respectively. The model’s accuracy was 73.7%, 95.9%, and 99.2% in prediction, with error margins of ±1.0, ±2.0, and ±3.0 mm, respectively.
Conclusions
We developed a deep learning-based model for predicting the axial length from UWF images with good performance.
3.Autosomal Dominant Drusen Confirmed by Molecular Genetics
Jae Shin SONG ; Baek Lok OH ; Un Chul PARK ; Hyeong Gon YU ; Eun Kyoung LEE
Journal of the Korean Ophthalmological Society 2021;62(1):120-126
Purpose:
To report a case of autosomal dominant drusen confirmed by molecular genetic testing and the clinical features and findings of a multimodal diagnostic imaging study.Case summary: A 32-year-old male presented with decreased visual acuity in his right eye from 1 year prior to his first visit. On the first visit, his visual acuities were 0.3 in the right eye and 1.2 in the left eye. A fundus examination showed numerous drusen of various sizes widely distributed on the posterior pole of both eyes, as well as subretinal fibrotic change with pigmentation in the right eye. Optical coherence tomography showed extensive hyperreflective deposits beneath the retinal pigment epithelium in both eyes and small amounts of cystic intraretinal fluid in the right eye. Fluorescein angiography and fundus autofluorescence showed the drusen as multiple hyperfluorescent spots, while indocyanine green angiography indicated hypofluorescence corresponding to the drusen. Genetic sequence analysis revealed a pathogenic variant of the EFEMP1 gene, heterozygous c.1033C>T (p.Arg345Trp), which accords with the diagnosis of autosomal dominant drusen. Intravitreal bevacizumab injection was given in the right eye; however, there was no improvement in the amount of intraretinal fluid nor visual acuity.
Conclusions
Autosomal dominant drusen is a very rare disease. It is necessary to distinguish it from age-related macular degeneration, as the affected age and clinical features of drusen are different, including the response to anti-vascular endothelial growth factor treatment.
4.Clinical Characteristics of Uveitis in Patients with Psoriasis in Korea: A Retrospective Multicenter Case Series
Yunjin LEE ; Baek-Lok OH ; Hyeong Gon YU ; Sang Woong YOUN ; Se Joon WOO
Korean Journal of Ophthalmology 2021;35(1):64-72
Purpose:
To describe the clinical characteristics and treatment outcomes of uveitis in patients with psoriasis in Korea.
Methods:
The medical records of 20 patients (27 eyes) with psoriatic uveitis in two tertiary hospitals were retrospectively reviewed. We analyzed data about patient demographics, uveitis types, laterality, onset of disease, human leukocyte antigen (HLA) types, intraocular pressure, visual acuity, comorbidities, and medical treatments and outcomes for uveitis and psoriasis.
Results:
The cohort comprised 11 males and nine females (age of onset, 50.1 ± 13.2 years) and the mean follow-up period was 3.9 ± 4.0 years. Types of uveitis included anterior (85%), intermediate (10%), and panuveitis (5%). A total of 13 (65%) cases presented with unilateral involvement and 12 out of 18 patients (66.7%) were positive for HLA-B27. The average intraocular pressure of affected eyes was 11.6 ± 3.6 at the first visit and 13.8 ± 3.6 mmHg at the final visit. The average logarithm of the minimum angle of resolution visual acuity of affected eyes at the initial examination was 0.16 ± 0.52 and 0.27 ± 0.71 at the last examination. Most common comorbidity (13 patients, 65%) was psoriatic arthritis (PsA). All cases underwent topical corticosteroid treatment; however, 11 (55%) required systemic corticosteroid and immunosuppressants for the treatment of uveitis. Notable deterioration in visual outcome was found in two cases (10%) due to severe intraocular inflammation and its complications (uveitic glaucoma and bullous keratopathy). Recurrent uveitis was observed in 57.9% of patients. Patients with PsA tended to have higher positive rate of HLA-B27 (83.3%). However, there was no significant correlation between visual prognosis and location of psoriatic uveitis, presence of PsA, and HLA-B27 positivity.
Conclusions
Psoriatic uveitis in Koreans usually presents with anterior uveitis with unilateral involvement. PsA was the most common comorbidity. In majority of patients, visual outcomes are satisfactory with appropriate topical or systemic immunosuppressive treatment.
5.Evaluation of the Safety and Efficacy of Selective Retina Therapy Laser Treatment in Patients with Central Serous Chorioretinopathy
Jaeryung OH ; Chang Ki YOON ; Bo Hee KIM ; Hyeong Gon YU
Korean Journal of Ophthalmology 2021;35(1):51-63
Purpose:
To assess the safety and efficacy of selective retina therapy (SRT) using a Q-switched neodymium-doped yttrium lithium fluoride laser with feedback systems in patients with idiopathic central serous chorioretinopathy (CSC).
Methods:
This randomized clinical trial enrolled patients having at least 3-month symptom of CSC. From month 3 visit, all subjects in both groups were eligible for SRT retreatment if they showed persistent or recurrent subretinal fluid (SRF). The primary outcome was complete resolution of SRF by optical coherence tomography at 3 months after treatment. The secondary outcomes were changes in SRF, central macular thickness (CMT) and best-corrected visual acuity at the 1-, 3-, and 6-month examinations.
Results:
Sixty-eight CSC patients were included (SRT, 31; control, 37). After 1 and 3 months, complete resolution of SRF was achieved in 25.8% and 54.8% of SRT group and 17.6% and 35.1% of controls. The differences were not statistically significant (p = 0.424 and p = 0.142, respectively). However, mixed model for repeated measures analyses showed that the reduction of SRF and CMT were observed earlier in SRT group than in the sham group (least squares mean difference, -59.7 µm; 95% confidence interval, -98.2 to -21.2; p = 0.0029; least squares mean difference -67.0 µm; 95% confidence interval, -104.8 to -29.2; p = 0.0007, respectively). Significant reduction of SRF (≥50% reduction from baseline) was more frequently observed in SRT group (80.6%) than the sham group (44.1%) at month 1 (p = 0.007). Early reduction of SRF and CMT was more abundant in SRT group with symptom duration less than 6 months. Treatment related serious adverse events were not observed.
Conclusions
SRT using a Q-switched neodymium-doped yttrium lithium fluoride laser with feedback system was safe in this trial and effective for early resolution of SRF in the CSC patients. Early intervention with SRT can be a safe alternative for patients with acute symptomatic CSC.
6.Clinical Manifestations and Risk Factors of Anterior Chamber Migration of a Dexamethasone Implant
Hyuk Jun LEE ; Un Chul PARK ; Hyeong Gon YU ; Eun Kyoung LEE
Journal of the Korean Ophthalmological Society 2020;61(10):1184-1193
Purpose:
To investigate the clinical features, risk factors, and treatment outcomes for anterior chamber migration of an intravitreal dexamethasone implant (Ozurdex®; Allergan Inc., Irvine, CA, USA).
Methods:
We retrospectively reviewed the medical records of patients who were diagnosed with anterior chamber Ozurdex® migration. Prior surgical histories were obtained and comprehensive ophthalmic examinations were conducted for all eyes. Treatment strategies and outcomes were also analyzed.
Results:
Among 1,276 intravitreal Ozurdex® injections, anterior migration occurred in six eyes of six patients (0.47%). All six eyes were pseudophakic, and they had undergone prior vitrectomies. The vitrectomized pseudophakic eyes, in contrast to the nonvitrectomized pseudophakic eyes, were significantly associated with an increased risk of anterior chamber migration (odds ratio [OR] = 19.2, p = 0.009). Moreover, the vitrectomized eyes with reduced zonular/capsular bag complex integrity, in contrast to the vitrectomized eyes with intact zonular/capsular bag complex integrity, were significantly associated with an increased risk of anterior chamber migration (OR = 50.2, p < 0.001). All six eyes underwent surgical intervention: one eye with a repositioning procedure, and the other five eyes with surgical removal of the implant. Corneal edema was resolved within two months after surgery; however, one patient eventually developed corneal endothelial dysfunction.
Conclusions
Prior vitrectomy and a defective lens capsule or weak zonules/zonular dehiscence are risk factors for anterior chamber Ozurdex® migration; thus, caution is recommended in these patients. Urgent removal of the implant should be considered when anterior migration of the implant is diagnosed with corneal edema.
7.Recurrence of Retinal Detachment after Scleral Buckle Removal
Kyung Won KIM ; Un Chul PARK ; Hyeong Gon YU
Korean Journal of Ophthalmology 2020;34(6):454-461
Purpose:
To investigate the indications for scleral buckle removal and the risk factors for the recurrence of rhegmatogenous retinal detachment after scleral buckle removal.
Methods:
In this retrospective study, the medical records of all patients who underwent scleral buckle removal for the treatment of rhegmatogenous retinal detachment were reviewed.
Results:
Forty eyes (40 patients) were included in this study. The indications for scleral buckle removal included exposure without infection in 23 eyes (57.5%), exposure with infection in seven eyes (17.5%), elevated intraocular pressure in six eyes (15.0%), strabismus or diplopia in three eyes (7.5%), and migration of buckle material in one eye (2.5%). After the removal of the scleral buckle, the recurrence of rhegmatogenous retinal detachment was observed in four eyes (10.0%) during follow-up, and the retina was successfully reattached after pars plana vitrectomy in all the eyes. Most clinical and ocular factors of the eyes with and without the recurrence of retinal detachment during follow-up were not different, but the eyes that underwent encircling removal were more likely to have retinal detachment recurrence during follow-up than those that underwent segmental buckle removal (n = 4 / 16 [25.0%] vs. n = 0 / 24 [0.0%]; p = 0.020).
Conclusions
Scleral buckle removal can result in the recurrence of retinal detachment. The benefits and risks of scleral buckle removal should be carefully considered before surgery, and extensive monitoring during follow-up after scleral buckle removal is important, especially for patients who underwent encircling removal.
8.Clinical Manifestations and Risk Factors of Anterior Chamber Migration of a Dexamethasone Implant
Hyuk Jun LEE ; Un Chul PARK ; Hyeong Gon YU ; Eun Kyoung LEE
Journal of the Korean Ophthalmological Society 2020;61(10):1184-1193
Purpose:
To investigate the clinical features, risk factors, and treatment outcomes for anterior chamber migration of an intravitreal dexamethasone implant (Ozurdex®; Allergan Inc., Irvine, CA, USA).
Methods:
We retrospectively reviewed the medical records of patients who were diagnosed with anterior chamber Ozurdex® migration. Prior surgical histories were obtained and comprehensive ophthalmic examinations were conducted for all eyes. Treatment strategies and outcomes were also analyzed.
Results:
Among 1,276 intravitreal Ozurdex® injections, anterior migration occurred in six eyes of six patients (0.47%). All six eyes were pseudophakic, and they had undergone prior vitrectomies. The vitrectomized pseudophakic eyes, in contrast to the nonvitrectomized pseudophakic eyes, were significantly associated with an increased risk of anterior chamber migration (odds ratio [OR] = 19.2, p = 0.009). Moreover, the vitrectomized eyes with reduced zonular/capsular bag complex integrity, in contrast to the vitrectomized eyes with intact zonular/capsular bag complex integrity, were significantly associated with an increased risk of anterior chamber migration (OR = 50.2, p < 0.001). All six eyes underwent surgical intervention: one eye with a repositioning procedure, and the other five eyes with surgical removal of the implant. Corneal edema was resolved within two months after surgery; however, one patient eventually developed corneal endothelial dysfunction.
Conclusions
Prior vitrectomy and a defective lens capsule or weak zonules/zonular dehiscence are risk factors for anterior chamber Ozurdex® migration; thus, caution is recommended in these patients. Urgent removal of the implant should be considered when anterior migration of the implant is diagnosed with corneal edema.
9.Fusion and Suppression in Patients with Unilateral Idiopathic Epiretinal Membrane
In Hwan CHO ; Un Chul PARK ; Seong Joon KIM ; Na-Kyung RYOO ; Hyeong Gon YU
Journal of the Korean Ophthalmological Society 2020;61(7):765-771
Purpose:
To investigate the presence of fusion and suppression in patients with unilateral idiopathic epiretinal membrane (ERM).
Methods:
Thirty-five patients with unilateral idiopathic ERM received a full ophthalmologic exam including best corrected visual acuity (BCVA). Patients were divided into suppression and non-suppression groups according to the results of 4 Prism Dioptre Base-out Test and Worth 4 Dot test. Age, symptoms, duration of ERM, BCVA, average M-chart score, results of Titmus test and optical coherence tomography parameters were compared between the two groups. Factors associated with suppression were also evaluated.
Results:
Eleven (31%) of 35 patients had suppression. The BCVA (0.18 ± 0.12 vs. 0.29 ± 0.12 p = 0.019) and stereopsis (2.25 ± 0.27 vs. 2.66 ± 0.62, p = 0.009) were significantly lower in the suppression group than the non-suppression group. Median age was older (63.21 ± 9.64 vs. 70.82 ± 6.80, p = 0.013) and duration of ERM (7.86 ± 3.69 vs. 18.54 ± 14.92 months, p = 0.004) was longer in the suppression group than the non-suppression group. Average M-chart score was higher in the suppression group. However, not all the patients suffered from metamorphopsia, including the suppression group when using binocular vision.
Conclusions
Unilateral suppression is common in unilateral idiopathic ERM and influences the patient’s stereopsis. Suppression was significantly correlated with age, duration of symptoms and metamorphopsia.
10.Preservative-free Triamcinolone Acetonide-assisted Visualization of the Internal Limiting Membrane
Kyung Tae KANG ; Un Chul PARK ; Hyeong Gon YU
Journal of the Korean Ophthalmological Society 2020;61(5):506-513
Purpose:
To evaluate and compare the degree of visualization of the vitreous and internal limiting membrane (ILM) during pars plana vitrectomy (PPV) using preservative-free triamcinolone acetonide (PF-TA) or triamcinolone acetonide suspension (TAS).
Methods:
We retrospectively analyzed the medical records of 61 eyes of 61 patients who underwent 25-gauge PPV and ILM peeling for various macular diseases. We assigned the patients to PF-TA and TAS groups, i.e., according to the type of triamcinolone acetonide used. The degree of visualization of the vitreous and ILM was classified into four different categories. The number of dye injections during PPV, need for indocyanine green (ICG), time elapsed before ILM peeling, and intraocular pressure (IOP) before surgery, 1 day and 1 month after surgery were determined.
Results:
The degree of visualization of the vitreous and ILM was significantly better in the PF-TA group compared with the TAS group. Although the number of dye injections during PPV was not different between the PF-TA and TAS groups (2.56 ± 0.07 and 2.37 ± 1.08, respectively, p = 0.06), the need for ICG was significantly different (6 and 22 eyes, respectively, p < 0.01). The time elapsed before ILM peeling was 185.68 ± 130.02 s in the PF-TA group and 411.15 ± 267.38 s in the TAS group (p < 0.01). The IOP was not different before or 1 day after surgery between the PF-TA and TAS groups, but was significantly different 1 month after surgery (12.88 ± 3.10 and 14.41 ± 2.91 mmHg, respectively, p = 0.03).
Conclusions
Visualization of the vitreous and ILM was better when using PF-TA compared to TAS. PF-TA-assisted PPV could reduce the usage of ICG and was associated with a reduced latency to ILM peeling. Because this was in turn associated with a lower IOP at postoperative 1 month, PF-TA was safer and more effective than TAS.

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