Choroidal manifestations of non-ocular sarcoidosis: an enhanced depth imaging OCT study.

BACKGROUND: Although choroidal thickening was reported as a sign of active inflammation in ocular sarcoidosis, there has been no research on the choroidal changes in non-ocular sarcoidosis (defined as systemic sarcoidosis without overt clinical signs of ocular involvement). Therefore, this study aimed to investigate choroidal structural changes in patients with non-ocular sarcoidosis. METHODS: This retrospective case-control study was conducted at Asan Medical Center, a tertiary referral center. We evaluated 30 eyes with non-ocular sarcoidosis and their age- and spherical equivalent-matched healthy control eyes. The subfoveal choroidal thickness, area ratio (Sattler layer-choriocapillaris complex [SLCC] area to Haller layer [HL] area), and choroidal vascularity index (CVI, luminal area to choroidal area) were analyzed using enhanced depth imaging in optical coherence tomography. Systemic and ocular factors associated with the choroidal thickness were investigated. RESULTS: Compared with the healthy control group, the non-ocular sarcoidosis group had significantly thicker subfoveal choroid (total and all sublayers [SLCC and HL]) and lower area ratio. There were no significant differences in the CVIs at all sublayers between groups. In the non-ocular sarcoidosis group, eyes under oral steroid treatment had thinner choroid than eyes under observation. In the control group, eyes with older age and more myopic spherical equivalent had thinner choroidal thickness. CONCLUSION: Total and all sublayers of the subfoveal choroid were significantly thicker without significant vascularity changes in non-ocular sarcoidosis eyes than in healthy control eyes. The degree of choroidal thickening was disproportionally greater at HL than at SLCC. These characteristic choroidal changes may be the subclinical manifestations in non-ocular sarcoidosis.

Clinical manifestations and associated factors of uveitis in patients with pulmonary sarcoidosis: a case control study.

Sarcoidosis, an idiopathic and inflammatory disease, affects various organs and can manifest as uveitis. Due to limited evidence, researchers investigated the risk factors associated with uveitis in patients with pulmonary sarcoidosis. A retrospective study was conducted on 71 pulmonary sarcoidosis patients, including 19 with uveitis and 52 without. Data on involved organs, imaging findings, spirometry, and analyses from blood and bronchoalveolar lavage fluid were collected. Logistic regression models were used for multivariate analysis. Among the 71 newly diagnosed pulmonary sarcoidosis patients, uveitis was observed in 19 patients (26.8%). No significant differences were found in clinical characteristics between patients with and without uveitis. Fewer patients with uveitis presented lung parenchymal lesions (P = 0.043). In multivariate analysis, skin lesions (aOR 7.619, 95% CI 1.277-45.472, P = 0.026) and ophthalmic symptoms (aOR 4.065, 95% CI 1.192-13.863, P = 0.025) were associated with uveitis. Absence of uveitis was related to lung parenchymal lesions (aOR 0.233, 95% CI 0.062-0.883, P = 0.032). Approximately one-quarter of patients with an initial diagnosis of pulmonary sarcoidosis were diagnosed with uveitis. Presence of skin lesions, ophthalmic symptoms, and absence of lung parenchymal lesions were related to uveitis. These results need to be clarified by further studies to confirm the clinical role of early ophthalmologic screening for pulmonary sarcoidosis patients with these factors.

Factors Affecting Intensive Aflibercept Treatment Response in Diabetic Macular Edema: A Real-World Study.

Objective: To investigate the systemic and ocular factors that affect the response to intensive aflibercept treatment in diabetic macular edema (DME) in a real-world setting. Methods: This retrospective cohort study evaluated 30 eyes of 23 patients with DME who underwent intensive intravitreal aflibercept injections (five monthly loading doses). Treatment response was assessed by central retinal thickness (CRT) and best-corrected visual acuity (BCVA) at each monthly visit. The patients were categorized as good (<300 µm) and suboptimal (≥300 µm) responders based on CRT after the loading phase. Baseline systemic and ocular factors associated with treatment response were investigated. Results: The mean CRT and BCVA significantly improved after five loading injections (486.87 ± 95.46 to 334.90 ± 69.47 µm and 0.51 ± 0.30 to 0.35 ± 0.25 LogMAR, respectively, all p < 0.05). During 12 months of follow-up, 16 eyes (53.33%) maintained CRT without additional treatment. Eyes with diabetes mellitus (DM) for ≥15 years, estimated glomerular filtration rate (eGFR) < 80 mL/min/1.73 m2, serum creatinine ≥ 0.95 mg/dL and potassium ≥ 4.7 mmol/L, and presence of epiretinal membrane (ERM) were more likely to have a suboptimal response to the treatment. Conclusions: Five monthly loading doses of intravitreal aflibercept injection provided significant anatomical and visual improvements in patients with DME. Patients with longer DM duration, lower eGFR, higher serum creatinine or potassium levels, or ERM were predisposed to a suboptimal treatment response. Individual response to intensive aflibercept treatment for DME can be predicted by these systemic and ocular risk factors.

Effectiveness of An Intraoperative Lagophthalmos Formula for Levator Resection in Patients With Congenital Ptosis.

PURPOSE: To evaluate the effectiveness of an intraoperative lagophthalmos formula (IOLF) for levator resection in congenital ptosis and investigate the optimal preoperative conditions for IOLF application. METHODS: This retrospective interventional cohort study evaluated 30 eyelids of 22 patients with congenital ptosis who underwent levator resection using the IOLF to calculate the extent of surgical correction under general anesthesia. Surgical success was defined as margin reflex distance-1 (MRD1)≥3 mm in each eye and a difference of MRD1 1 mm between the eyes at 6 months postoperatively. Logistic regression was performed to investigate the preoperative conditions associated with surgical success. RESULTS: Among 30 eyelids, 19 had good-to-fair levator function (LF) (≥5 mm) and 11 had poor LF ( 4 mm). The overall success rate was 90.0% (n=27/30), whereas the under-correction rate was 10.0% (n=3/30). The surgical success rate was 100% (n=19/19) in eyelids with LF ≥5 mm and 72.7% (n=8/11) in eyelids with LF 4 mm. Patients with preoperative MRD1≥0 mm (versus MRD1<0 mm, odds ratio=34.5, P =0.0098) or a combination of preoperative MRD1≥0 mm and LF≥5 mm (versus MRD1<0 mm and LF 4 mm, odds ratio=48.0, P =0.0124) more likely had successful surgical outcomes. CONCLUSIONS: Levator resection using the IOLF can provide satisfactory results for congenital ptosis regardless of LF. Preoperative MRD1≥0 mm may be suitable for IOLF application, and the combination of preoperative MRD≥0 mm and LF≥5 mm may be the optimal preoperative condition for IOLF application.

Intense pulsed light treatment of the upper and lower eyelids in patients with moderate-to-severe meibomian gland dysfunction.

PURPOSE: We investigated the subjective and objective outcome after intense pulsed light (IPL) treatment and meibomian gland expression on the upper and lower eyelids compared with those after IPL treatment on the lower eyelid alone in patients with moderate-to-severe meibomian gland dysfunction (MGD). METHODS: Patients who underwent four IPL treatment sessions with meibomian gland expression were divided into upper and lower treatment group and conventional treatment group treated with lower eyelid alone. All patients underwent an ophthalmologic examination and answered a symptom questionnaire before the first treatment and 1 month after the last treatment. An ophthalmologic examination included tear break-up time (TBUT), fluorescein staining score, Schirmer's test, matrix metalloproteinase-9 (MMP-9), meibum grade, color, consistency, and lid margin telangiectasia. Additionally, visual acuity and adverse effects were checked on every visit. RESULTS: Of 115 patients, 75 in the upper and lower treatment group and 40 in the conventional treatment group were included. TBUT, fluorescein staining score, subjective symptom, and meibum grade were significantly improved in both groups. Additionally, meibum color and consistency of upper and lower eyelids significantly decreased post-treatment in both groups. The lid margin telangiectasia of the upper and lower eyelids significantly decreased post-treatment in the upper and lower treatment group. MMP-9 positivity and grading scores significantly decreased post-treatment in both groups, and no severe adverse effects occurred during the follow-up period. CONCLUSION: Additional IPL treatment on the upper eyelid using a protective device was proven safe and provided an additive improvement in treating moderate-to-severe MGD.

Prognostic value of myopic disk deformation in myopic choroidal neovascularization: A 6-year follow-up study.

Purpose: To evaluate the clinical characteristics of myopic choroidal neovascularization (mCNV) according to peripapillary atrophy (PPA) and optic disk tilt and to explore whether those myopic disk deformations are associated with the prognosis of mCNV. Methods: Patients with subfoveal mCNV who received intravitreal bevacizumab injection and followed for ≥3 years were included. PPA was quantified as area of the ß-zone PPA/disk area ratio (PDR) and optic disk tilt as the tilt ratio (the longest/shortest disk diameter). We compared the clinical characteristics in terms of PDR and tilt ratio and identified the poor prognostic factors using Logistic regression and Cox proportional hazard model. Results: Among 80 eyes of 80 patients, 29 (36.30%) eyes developed macular atrophy during 80.71 ± 34.76 months. PDR and tilt ratio are strongly correlated with each other (P = 0.004). Higher PDR showed significant correlations with longer axial length (P = 0.013), worse baseline and final VA (P = 0.007 and P = 0.047), and thinner subfoveal choroidal thickness (P = 0.039), while higher tilt ratio showed significant correlations only with longer axial length (P = 0.036). High PDR was also an independent risk factor for both macular atrophy (OR = 2.257, P < 0.001) and poor visual outcome (HR = 1.174, P = 0.007), while high disk tilt ratio was not. Conclusion: Subfoveal mCNV with higher ß-zone PPA area/disk area ratio had worse functional and structural outcomes.

Effect of Optic Disc Tilt on the Measurement of Peripapillary Vessel Density Using Optical Coherence Tomography Angiography.

PRCIS: Eyes with tilted disc (TD) had significantly lower peripapillary vessel density (pVD) and lower long-term measurement reproducibility in optical coherence tomography angiography (OCTA). After adjusting for confounding factors, disc tilt still contributed to the reduction of pVD in most sectors. PURPOSE: The purpose of this study was to investigate the effect of optic disc tilt on the measurement of sectoral pVD by OCTA and on the long-term measurement reproducibility. MATERIALS AND METHODS: This retrospective observational case-control study included 70 healthy eyes. Average and 8-sector pVDs and peripapillary retinal nerve fiber layer (pRNFL) thicknesses were obtained from OCTA at 2 visits at 1-year intervals. The disc tilt was quantified by ovality ratio (the longest/shortest disc diameter) on fundus photography, with a TD defined as an ovality ratio ≥1.3. pVD and pRNFL thickness of each sector were compared in the TD and nontilted disc (NTD) groups. Long-term reproducibility was assessed by the intraclass correlation coefficients (ICCs) for both groups. Factors associated with pVD were evaluated by univariable and multivariable linear regression analyses. RESULTS: Thirty-five eyes each had TD and NTD. Average pVD was lower in the TD than in the NTD group (47.0%±3.5% vs. 51.7%±2.8%, P <0.001), as were pVDs in all 8 sectors. The long-term reproducibilities of average and sectoral pVD measurements were lower in the TD (ICC: 0.46-0.83) than in the NTD (ICC: 0.67-0.96) group. Disc tilt was significantly associated with pVD in average and all sectors except for nasal inferior sector after adjusting for axial length, pRNFL thickness, and signal strength index of OCTA image. CONCLUSION: OCTA-measured pVD and the long-term reproducibility were lower in eyes with TD than NTD. These findings should be considered when interpreting OCTA-measured pVD.

Clinical Outcomes of Nanothin Descemet Stripping Automated Endothelial Keratoplasty in Korean Patients with Corneal Endothelial Dysfunction.

PURPOSE: To evaluate the clinical outcomes of nanothin Descemet stripping automated endothelial keratoplasty (DSAEK) in Korean patients with corneal endothelial dysfunction. METHODS: We retrospectively reviewed medical records of the patients who underwent nanothin DSAEK (graft thickness ≤50 µm) due to corneal endothelial dysfunction and followed up more than 1 year. We evaluated best-corrected visual acuity (BCVA), central corneal thickness, and corneal endothelial cell density at preoperative and 1, 3, 6, and 12 months postoperatively. RESULTS: Sixteen eyes of 16 patients with the mean follow-up period of 13.00 ± 0.96 months were included. The mean graft thickness after deswelling was 45.25 ± 4.59 µm (range, 38.0-50.0 µm). The mean logarithm of the minimum angle of resolution BCVA improved from 1.37 ± 0.53 preoperatively to 0.68 ± 0.46, 0.55 ± 0.35, 0.40 ± 0.25, and 0.39 ± 0.25 at 1, 3, 6, and 12 months postoperatively (p = 0.005, p < 0.001, p < 0.001, and p < 0.001), respectively. The mean central corneal thickness improved from 752.00 ± 129.11 to 555.75 ± 54.66 µm at 12 months postoperatively (p = 0.006). The mean graft endothelial cell density decreased from 2,859.62 ± 228.34 to 1,542.25 ± 627.34 cells/mm2 at 12 months postoperatively (p = 0.012). The postoperative complications included increased intraocular pressure (n = 3, 18.75%) and graft dislocation (n = 1, 6.25%), all of which were successfully managed by anterior chamber paracentesis or rebubbling. No other serious complications were encountered. CONCLUSIONS: Nanothin DSAEK produced significant and stable visual improvements without severe postoperative complications in Korean patients with corneal endothelial dysfunction.

Metformin use in cancer survivors with diabetes reduces all-cause mortality, based on the Korean National Health Insurance Service between 2002 and 2015.

ABSTRACT: Malignant neoplasms are the leading cause of death in Korea. We aimed to examine if metformin use in cancer survivors reduces all-cause mortality. This study was retrospectively designed based on data from the Korean National Health Insurance Service-National Health Screening Cohort (HEALS) between 2002 and 2015. The Kaplan-Meier estimator and log-rank test was performed to estimate the survival function according to metformin usage (3721 metformin non-users with diabetes, 5580 metformin users with diabetes, and 24,483 non-diabetic individuals). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were calculated using Cox proportional hazards regression models.The median follow-up duration was 4.2 years. The HRs (95% CIs) for all-cause mortality of metformin users and the non-diabetic group were 0.762 (0.683-0.850) and 1.055 (0.966-1.152) in men and 0.805 (0.649-0.999), and 1.049 (0.873-1.260) in women, respectively, compared with metformin non-users among diabetic cancer survivors, in a fully adjusted model. After stratifying metformin users into pre- and post-diagnosis of cancers, adjusted HRs (95% CIs) of pre- and post-diagnosis metformin users for all-cause mortality were 0.948 (0.839-1.071) and 0.530 (0.452-0.621) in men and 1.163 (0.921-1.469) and 0.439 (0.323-0.596) in women, respectively.Metformin use in cancer survivors with diabetes reduced overall mortality rates. In particular, metformin use after cancer diagnosis, not before cancer diagnosis, was inversely associated with overall mortality.Active treatment with metformin for diabetic cancer survivors after cancer diagnosis can improve their survival rates.

Changes in the expression of matrix metalloproteinase-9 after intense pulsed light therapy combined with meibomian gland expression in moderate and severe meibomian gland dysfunction.

PURPOSE: To evaluate the combined effect of intense pulsed light (IPL) therapy and meibomian gland expression on extracellular matrix metalloproteinase-9 (MMP-9) levels and clinical outcomes of moderate and severe meibomian gland dysfunction (MGD) treatment. METHODS: This retrospective study was conducted on 45 eyes of 23 patients with moderate and severe MGD. Each eye underwent three IPL sessions and meibomian gland expression at 2-week intervals. In this study the evaluated parameters included tear film break-up time (TBUT), corneal and conjunctival fluorescein staining scores, biomicroscopic examination of lid margins and meibomian glands, ocular surface disease index (OSDI) questionnaire score, and extracellular MMP-9 levels using the immunoassay device before and two weeks after the last treatment session. Linear mixed model and generalized estimating equations model were used to evaluate possible differences. RESULTS: There were significant improvements in TBUT (P < 0.001), SICCA ocular staining score (P = 0.008), Oxford staining score (P = 0.023), lid margin irregularity (P < 0.001 for upper and lower eyelids), lid thickness (P < 0.001 for upper and lower eyelids), meibomian gland plugging (P = 0.010 and P = 0.012 for upper and lower eyelids), meibum color (P = 0.044 and P < 0.001 for upper and lower eyelids), meibum consistency (P < 0.001 for upper and lower eyelids), MGD grade (P < 0.001), and OSDI questionnaire score (P < 0.001). Incidence of positive results for MMP-9 immunoassay significantly decreased from 84.0% to 56.0% (P = 0.031) after treatment. CONCLUSION: In patients with moderate to severe MGD, three sessions of IPL combined with meibomian gland expression improved objective findings, subjective symptoms, meibomian gland function, and MMP-9 immunoassay results. The results support the combination of IPL and meibomian gland expression for treating moderate to severe MGD.

Metformin usage and the risk of colorectal cancer: a national cohort study.

PURPOSE: This study aimed to investigate the association between metformin usage and the risk of colorectal cancer (CRC) using data from the Korean National Health Insurance Service-National Health Screening Cohort database. METHODS: Data from the NHIS-HEALS cohort between 2002 and 2015 were longitudinally analyzed. Subjects were divided into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and no DM group. CRC was defined using the ICD-10 code (C18.0-C20.0) at the time of admission. Cox proportional hazard regression models were adopted after stepwise adjustment for confounders to investigate the association between metformin usage and colorectal cancer risk. RESULTS: During the follow-up period, of the total 323,430 participants, 2341 (1.33%) of the 175,495 males and 1204 (0.81%) of the 147,935 females were newly diagnosed with CRC. The estimated cumulative incidence of CRC was significantly different among the three groups based on Kaplan-Meier's survival curve (p values < 0.05 in both sexes). Compared with metformin non-users, hazard ratios (95% CIs) of metformin users and the no DM group were 0.66 (0.51-0.85) and 0.72 (0.61-0.85) in males and 0.59 (0.37-0.92) and 0.93 (0.66-1.29) in females, respectively, after being fully adjusted. CONCLUSIONS: Metformin users with diabetes appear to have a significantly lower risk of CRC compared with metformin non-users.

Metformin use in elderly population with diabetes reduced the risk of dementia in a dose-dependent manner, based on the Korean NHIS-HEALS cohort.

AIMS: The aim of this study is to investigate the association between metformin usage and dementia in an elderly Korean population. METHODS: Participants were divided into five groups: metformin non-users with diabetes mellitus (DM), metformin users with DM (low-, mid-, and high-users), and non-diabetic Individuals. Dementia was defined with primary diagnostic dementia codes according to the 10th edition of the International Classification of Diseases. To compare the incidence rate of dementia among the five groups, Kaplan-Meier estimates and log-rank test were employed. Also, to control the confounding factors, Cox proportional hazards regression models were fitted in a sequential adjustment. RESULTS: The median follow-up was 12.4 years. The overall incidence rate of dementia was 11.3% (8.4% in men and 13.9% in women). Compared with metformin non-users, hazard ratios (95% confidence intervals) of low-, mid-, and high-users and non-diabetic individuals for dementia were 0.97 (0.73-1.28), 0.77 (0.58-1.01), 0.48 (0.35-0.67), and 0.98 (0.84-1.15), respectively, in men, respectively, and 0.90 (0.65-0.98), 0.61 (0.50-0.76), 0.46 (0.36-0.58), and 0.92 (0.81-1.04), respectively, in women, after full adjustment of confounding variables. CONCLUSIONS: Metformin use in an elderly population with DM reduced dementia risk in a dose-response manner.

Metformin use reduced the overall risk of cancer in diabetic patients: A study based on the Korean NHIS-HEALS cohort.

BACKGROUND AND AIM: Several studies have reported the preventive effect of metformin on cancer development. This study aimed to investigate the relationship between use of metformin and risk of cancer in Koreans. METHODS AND RESULTS: This study was designed retrospectively using the National Health Insurance Service-National Health Screening Cohort conducted between 2002 and 2015. 40 to 69-year-old subjects who received a health screening examination from 2002 to 2003 were enrolled. Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer were estimated in a multivariate Cox proportional regression analysis. A total of 323,430 subjects was enrolled (301,905 individuals without diabetes [No DM], 8643 diabetic patients with metformin treatment [metformin users], and 12,882 diabetic patients without metformin treatment [metformin non-users]). The median follow-up period was 12.7 years. Cumulative incidence of overall cancer was 7.9% (7.7, 10.3, and 11.1% in No DM, metformin users and non-users, respectively). Compared to metformin non-users, the fully adjusted HRs (95% CIs) of metformin users and No DM for overall cancer incidence were 0.73 (0.66-0.81) and 0.75 (0.64-0.88), respectively, in men and 0.83 (0.78-0.89) and 0.81 (0.72-0.92) in women. CONCLUSIONS: Diabetic patients receiving metformin treatment, and individuals without diabetes were at lower risk for cancer incidence than diabetic patients without metformin treatment.

Statin use increased new-onset diabetes in hypercholesterolemic individuals: Data from the Korean National Health Insurance Service-National Health Screening Cohort database (NHIS-HEALS).

AIM: We investigated the association between statin use and new-onset diabetes (NODM) in Korean adults with hypercholesterolemia. METHODS: This study performed based on data from the National Health Insurance Service-National Health Screening Cohort for the years from 2002 to 2015. Statin users classified as high- or low- users according to medication possession ratio. Statin non-users consisted of hypercholesterolemic participants who never used statin over the entire follow-up period. 21,469 participants (10,880 statin users, 10,589 statin non-users) with a median follow-up period of 12.5 years were included. We estimated the NODM risk based on the survival analyses. In particular, to adjust for confounding effects, we considered Cox proportional hazards regression models over three stages. RESULTS: Compared to non-users, statin users had a significantly higher risk for NODM. The fully adjusted hazard ratios (aHRs) (95% confidential intervals [95% CIs]) of statin users for NODM were 1.43 (1.31-1.57) in men, and 1.86 (1.66-2.10) in women, respectively after adjusted confounding factors including age and lifestyle factors. Compared to high-users, aHRs (95% CIs) of low-users for NODM were 1.16 (1.03-1.30) and 1.28 (1.16-1.43) in men and women, respectively. CONCLUSIONS: In hypercholesterolemic patients, statin users have a higher risk of NODM than non-users.

Association between statin use and all-cause mortality in cancer survivors, based on the Korean health insurance service between 2002 and 2015.

BACKGROUND AND AIMS: Cancer is the number one cause of death in Korea. This study aimed to investigate if statin use in cancer survivors was inversely associated with all-cause mortality. METHODS AND RESULTS: Data from the 2002 to 2015 National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) were used. The Kaplan-Meier estimator was used to estimate the survival function according to statin usage. Cox proportional hazards regression models were adopted after stepwise adjustment for potential confounders to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. The median follow-up duration was 10.0 years. Statin users had a higher percentage of diabetes and hypertension in both sexes. Survival rates of statin users were higher than non-users (p-values <0.001 in men and 0.021 in women). Compared to non-users, the HRs (95% CIs) of statin users for all-cause mortality were 0.327 (0.194-0.553) in men and 0.287 (0.148-0.560) in women after adjustment for potential confounding factors. CONCLUSIONS: Statin users in cancer survivors had higher survival rate than non-users in both sexes.