Effects of Y-27632, a Rho-associated Kinase Inhibitor, on Human Corneal Endothelial Cells Cultured by Isolating Human Corneal Endothelial Progenitor Cells

Purpose@#Human corneal endothelial progenitor cells (HCEPs), which has been selectively isolated and differentiated into human corneal endothelial cells (HCECs), are crucial for repairing corneal endothelial damage. In this study, we evaluated the roles of a Rho-assisted kinase (ROCK) inhibitor, Y-27632, on the isolation and expansion of HCEPs, and assessed the in vitro effects of different concentrations of Y-27632 on the differentiated HCEPs. @*Methods@#HCEPs were isolated and expanded in a medium with and without 10μM Y-27632, and then differentiated into HCECs in a medium with fetal bovine serum. The characteristics of HCEPs and differentiated HCEPs were confirmed by immunofluorescence staining. The proliferation, viability, morphology, and wound-healing ability of differentiated HCEPs were assessed in the presence of different concentrations of Y-27632. @*Results@#Y-27632 enabled the isolation and expansion of HCEPs from the corneal endothelium. The differentiated HCEPs showed an optimal increase in proliferation and survival in the presence of 10μM Y-27632. As the concentration of Y-27632 increased, differentiated HCEPs became elongated, and actin filaments were redistributed to the periphery of cells. Y-27632 also caused a concentration-dependent enhancement in the wound-healing ability of differentiated HCEPs. @*Conclusions@#Y-27632 enabled the isolation and expansion of HCEPs. It also enhanced the proliferation, viability, and migration of differentiated HCEPs.

Prevalence and Risk Factors of Hydroxychloroquine Retinopathy in Rheumatic Patients with Dry Eye Symptoms

Purpose@#Hydroxychloroquine is widely used for long-term treatment of rheumatic diseases, but the drug can trigger irreversible toxic retinopathy. We studied the prevalence of, and the risk factors for, hydroxychloroquine retinopathy in rheumatic patients with dry eye symptoms and we introduce a representative case. @*Methods@#We retrospectively studied a cohort of 133 rheumatological patients who had taken hydroxychloroquine for at least 12 months and who visited our ophthalmology clinic with dry eye symptoms from April 2016 to December 2021. Hydroxychloroquine retinopathy was diagnosed via fundus photography, spectral-domain optical coherence tomography, the Humphrey visual field test, autofluorescence fundus photography, and multifocal electroretinography. The principal outcomes were the prevalence of retinopathy at the first screening and the risk factors. @*Results@#Of the 133 patients, hydroxychloroquine retinopathy was diagnosed in seven (5.2%) at the first screenings. The Mann-Whitney U-test revealed that older age; higher daily doses; longer dosing duration; greater cumulative doses; and higher daily and cumulative doses/kg were statistically significant in terms of retinopathy development. On multivariate logistic regression analysis, the average daily dose (odds ratio [OR] 6.02; 95% confidence interval [CI] 1.64-22.12, 100 mg increments) and duration of dosing (OR 3.39; 95% CI 1.19-9.62, 5 years increments) remained statistically significant (P = 0.021, P = 0.007 respectively) @*Conclusions@#Ophthalmologists should enquire about any history of hydroxychloroquine therapy, and perform a retinal examination, when encountering dry eye in patients with rheumatic disease. Early detection of hydroxychloroquine retinopathy followed by discontinuation of hydroxychloroquine is the only way to prevent visual loss. High daily drug doses and long dosing durations are risk factors for retinopathy.

Clinical Features and Visual Prognosis of Retinal Vein Occlusion in Those under 50 Years Old

Purpose@#To analyze the clinical features and visual prognosis of retinal vein occlusion (RVO) in patients under 50 years of age. @*Methods@#A retrospective analysis of medical records of 36 patients under 50 years of age diagnosed with RVO from January 2016 to October 2021. @*Results@#The mean age was 39.53 ± 9.98 years and 50%, 44.4%, and 5.6% had branch, central, and hemi-central RVO, respectively. Before the RVO diagnosis, systemic disease had been diagnosed in 38.9%. Further, 13.89% of the cases had a new systemic disease diagnosed after the diagnosis of RVO. Hypercholesterolemia was observed in 47.6%. The initial visual acuity (VA), best corrected visual acuity (BCVA), and central subfield thickness (CST) showed significant correlations with the final VA, BCVA, and CST. @*Conclusions@#In patients with RVO under the age of 50 years, the initial VA and CST can be used as indicators to determine whether treatment is necessary by reflecting the final VA and CST. The initial VA and CST can also be used to predict the visual prognosis. Even at a young age, if complications occur, the visual prognosis of RVO may be poor, so an evaluation of the patient’s general condition is essential, especially the blood cholesterol level.

Phakic Intraocular Lenses for Myopia / 항공우주의학회지

Phakic intraocular lenses (PIOLs) are gaining popularity as an alternative to wearing spectacles for correction of myopia in patients who are not appropriate candidates for traditional corneal refractive surgery (CRS). Although the visual outcome of such a procedure is at least equivalent to traditional CRS (i.e., photorefractive keratectomy, laser-assisted in situ keratomileusis), the risks and complications are different. This risk profile must be considered when evaluating an airman with PIOLs for medical clearance. This case involves an otherwise healthy applicant for Class-3 medical certification who has had these lenses implanted for the correction of myopia.

Prediction of the Expected Extent of Surgical Difficulty When Removing an Idiopathic Epiretinal Membrane

Purpose@#We sought to predict how difficult surgical removal of an epiretinal membrane (ERM) might be by analyzing the preoperative characteristics of the ERM. @*Methods@#From 2016 to 2020, 75 patients diagnosed with idiopathic ERMs who underwent ERM removal were evaluated in terms of surgical time (via video analysis); associations between that time and preoperative color fundus photographs and optical coherence tomography findings were sought. @*Results@#The surgical time was associated with the vascular tortuosity grade, the ERM stage, and fibrillary changes (p = 0.024, p = 0.020, and p = 0.018). Dummy regression analysis showed that EMR stage 4, and vascular tortuosity grades of 2 or 3, increased the surgical time (p = 0.036, p = 0.049). @*Conclusions@#Surgery may be difficult if the ERM is of stage 4 or the vascular tortuosity grade 2 or more. A retinal surgery novice should consider these factors when contemplating surgery.

Prediction of the Expected Extent of Surgical Difficulty When Removing an Idiopathic Epiretinal Membrane

Purpose@#We sought to predict how difficult surgical removal of an epiretinal membrane (ERM) might be by analyzing the preoperative characteristics of the ERM. @*Methods@#From 2016 to 2020, 75 patients diagnosed with idiopathic ERMs who underwent ERM removal were evaluated in terms of surgical time (via video analysis); associations between that time and preoperative color fundus photographs and optical coherence tomography findings were sought. @*Results@#The surgical time was associated with the vascular tortuosity grade, the ERM stage, and fibrillary changes (p = 0.024, p = 0.020, and p = 0.018). Dummy regression analysis showed that EMR stage 4, and vascular tortuosity grades of 2 or 3, increased the surgical time (p = 0.036, p = 0.049). @*Conclusions@#Surgery may be difficult if the ERM is of stage 4 or the vascular tortuosity grade 2 or more. A retinal surgery novice should consider these factors when contemplating surgery.

Evaluation of the Cone Contrast Sensitivity Test in Normal Eyes and those with Congenital Color Blindness

Purpose@#We evaluated a new color vision test, thus the ColorDx Cone contrast test HD ([CCT-HD]; Konan Medical, Inc., Irvine, CA, USA) in normal and color vision-deficient (CVD) eyes of Koreans. @*Methods@#The CCT-HD was performed on 66 healthy Koreans (125 normal eyes) and 25 patients (50 eyes) with congenital CVD. The results from normal eyes were compared and analyzed in terms of binocular agreement, patient ages, and spherical equivalents. The CCT-HD results on CVD eyes were compared and analyzed. @*Results@#We found no significant difference in any of the long (L), medium (M), or short wavelength (S) cone cell sensitivity (L-CCT, M-CCT, S-CCT) scores for normal eyes; also, there was no significant effect of age and no significant correlation between the spherical equivalent and the CCT score. In normal eyes, all scores were >75 (normal ≥75). The average protan L-CCT score was significantly reduced (13.0 ± 13.2; p < 0.001) as was the average deutan M-CCT score (31.7 ± 16.6; p < 0.001). The CCT-HD L-CCT and M-CCT exhibited 100% sensitivity and specificity in terms of diagnosing protans and deutans respectively. @*Conclusions@#CCT-HD allows classification and quantitative evaluation of protans and deutans, and is thus useful when examining color vision status.

A Comparison of Nagel Anomaloscope and Farnsworth Munsel 100-hue in Congenital Color Vision Deficiency

PURPOSE: To compare the classification and severity of congenital color vision deficiency using a Nagel anomaloscope and Farnsworth Munsel 100-hue Test (FM 100-hue).METHODS: A total of 394 eyes of 197 patients diagnosed with congenital color vision deficiency were included. Examinations using a Nagel anomaloscope and FM 100-hue were performed, and color vision abnormalities were classified as a protan color defect or deutan color defect by each test, and the degrees of color vision abnormalities were compared.RESULTS: The tests showed 64.3% (p < 0.001) agreement in the classification of color vision deficiencies. The Nagel anomaloscope was able to classify all cases, whereas 143 eyes (36.3%) could not be classified using the FM 100-hue test. In the case of the same type of color vision abnormality in both eyes, 196 cases (99.5%) using the Nagel anomaloscope and 111 cases (56.3%) using the FM 100-hue were observed. Regarding the degree of color defect, there was a moderate positive correlation between the two tests (r = 0.43; p < 0.001). There were no significant differences in the total error scores between mild anomalous trichromacy and severe anomalous trichromacy as assessed using FM 100-hue (p = 0.087).CONCLUSIONS: The Nagel anomaloscope was a more appropriate test for discerning the degree of color defect and binocular classification. In severity assessments, there was a moderate positive correlation between the two test methods. However, there were no significant differences in the total error scores between mild anomalous trichromacy and severe anomalous trichromacy as assessed using FM 100-hue. Therefore, it was difficult to perform severity classification using the Nagel anomaloscope based on the total error score of the FM 100-hue test.

Changes in the Ganglion Cell-inner Plexiform Layer after Consecutive Intravitreal Injections of Anti-vascular Endothelial Growth Factor in Age-related Macular Degeneration Patients

Late Postoperative Opacification of Multifocal Intraocular Lens after Vitrectomy in a Diabetic Patient

PURPOSE@#We report a case of late opacity of an AT LISA intraocular lens after vitrectomy in a diabetic patient.CASE SUMMARY: A 61-year-old man presented with blurring in the left eye. He had undergone bilateral phacoemulsification and intraocular lens implantation 6 years ago, and vitrectomy with SF₆ gas tamponade in the left eye due to rhegmatogenous retinal detachment 3 years ago. The patient was diagnosed with pre-existing diabetes, hypertension, and coronary heart disease. Examination of the left eye showed round and centrally located whitish fine granular deposits on the surface of the intraocular lens, and zonular rupture from the 3 to 6 o'clock position. The intraocular lens in the right eye was clear. The corrected vision was 0.9 in the right eye and 0.5 in the left eye. The intraocular lens was explanted from the left eye together with the capsular bag, and was examined under light microscopy, histochemical analysis, and with scanning electron microscopy equipped with an energy dispersive X-ray spectroscopy detector with light element capabilities.@*CONCLUSIONS@#This study was the first to report late postoperative opacity in the multifocal intraocular lens, AT LISA 809M. The possibility of intraocular lens opacity in patients with underlying disease or in those undergoing vitrectomy should be explained prior to corrective procedures.

Two Cases of Cytomegalovirus Infection Developed in Pediatric Acute Lymphoblastic Leukemia Patients / 임상소아혈액종양

A 14 year-old boy with acute lymphoblastic leukemia (ALL) on maintenance chemotherapy presented with vision-threatening cytomegalovirus (CMV) retinitis. Treatment with intavitreal ganciclovir injection (2 mg/0.1 mL) followed by oral ganciclovir resulted in successful resolution of CMV retinitis. Another 13 year-old boy with ALL on maintenance chemotherapy presented with prolonged fever with no response to antibiotics administration. CMV and real-time PCR revealed positive result and a titer of 2,618,700 copies/mL, respectively. Ganciclovir was used for more than the approved duration of treatment, but viral titer frequently recurred with elevated liver enzymes and fever. In these 2 cases of CMV infection, a high index of suspicion and prompt management is important in children receiving ALL chemotherapy.

Atypical Fundus Manifestation of Ocular Toxocariasis

No abstract available.

Effects of Histone Deacetylase Inhibitor (Valproic Acid) on the Expression of Hypoxia-inducible Factor-1 Alpha in Human Retinal Müller Cells

PURPOSE: To evaluate the effects of valproic acid (VPA), a histone deacetylase inhibitor (HDACI), on the expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in human retinal Müller cells under hypoxic conditions. METHODS: Chemical hypoxia was induced in human retinal Müller cells (MIO-M1) by treatment with increasing concentrations of cobalt(II) chloride (CoCl₂). Müller cells were also treated with a set concentration of CoCl₂, along with various concentrations of VPA. The expression of HIF-1α and VEGF in the treated Müller cells was determined by enzyme-linked immunosorbent assay. RESULTS: Exposure of human retinal Müller cells to increasing concentrations of CoCl₂ produced a dose-dependent increase in HIF-1α expression. The addition of increasing concentrations of VPA lead to a dose-dependent decrease in expression of HIF-1α and VEGF in Müller cells exposed to a set concentration of CoCl₂. CONCLUSIONS: HDACI VPA downregulated the expressions of HIF-1α and VEGF in human retinal Müller cells under hypoxic conditions. Using HDACI to target HIF-1α expression in Müller cells could be a new therapeutic strategy for the treatment of retinal vascular diseases.

Comparison of the Recurrence of RRD in PPV Combined Cataract Surgery with PPV Alone, and Risk Factors in PPV Combined Cataract Surgery

PURPOSE: To compare the recurrence percentage and risk factors of recurrence in rhegmatogenous retinal detachment (RRD) after pars plana vitrectomy (PPV) by in two groups of patients according to combined cataract surgery. METHODS: The recurrence percentage of RRD and risk factors after PPV over 20 years, performed by a single surgeon from January 1997 to September 2016, were retrospectively evaluated by classification into two groups according to combined cataract surgery. The risk factors were the patients' factors (age and sex), duration of disease, preoperative visual analyses, posterior capsular tears (PCR) during cataract surgery, the tamponade used, retinal detachment ranges, macular status, number and position of retinal tears, proliferative vitreoretinopathy (PVR) grade, and vitreous opacity. A total of 158 cases were included in the study. RESULTS: The recurrence percentage of RRD was not associated with combined cataract surgery. In the combined cataract surgery group, PCR (p = 0.020), inferior retinal tears (p = 0.037), and PVR above grade B (p = 0.037) were associated with the recurrence of RRD using univariate logistic regression analyses, but PCR (odds ratio 1.880, p = 0.021) was the only significant risk factor for RRD using multivariate logistic regression analyses. CONCLUSIONS: Cataract surgery can be performed at any time, but there should be consideration of the recurrence of RRD if there was PCR during combined cataract surgery.

Effects of Intravitreal Injection of Bevacizumab or Ranibizumab on Systemic Circulation

PURPOSE: The purpose of this study was to evaluate the systemic effects of ranibizumab and bevacizumab by examining the plasma levels of anti-vascular endothelial growth factor (anti-VEGF) and VEGF before and after a single intravitreal injection. METHODS: Twenty-eight eyes of 28 patients with various retinal diseases were enrolled. Seventeen eyes received an injection of intravitreal bevacizumab, and 11 eyes received an injection of ranibizumab. Blood samples were collected just before and 1 day, 1 week, and 1 month after injection. Concentrations of anti-VEGF and VEGF in plasma were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: In the bevacizumab group, anti-VEGF concentration before the injection was 91.0 ng/mL, while those at 1 day, 1 week, and 1 month post-injection increased to 153.6, 196.3, and 140.3 ng/mL, respectively (p 0.05 for all). VEGF level also showed no significant change. VEGF concentration before the injection was 80.9 pg/mL, while those at 1 day, 1 week and 1 month post-injection were 96.7, 106.3, 106.1 pg/mL, respectively (p > 0.05 for all). CONCLUSIONS: Contrary to ranibizumab, intravitreal bevacizumab significantly lowers plasma VEGF level in patients with various retinal diseases. The study suggests the consideration of the systemic effects of intravitreal bevacizumab injection.

Effects of Vitreomacular Traction on Ranibizumab Treatment Response in Eyes with Neovascular Age-related Macular Degeneration

PURPOSE: To investigate the effects of vitreomacular traction (VMT) on ranibizumab treatment response for neovascular age-related macular degeneration (AMD). METHODS: A retrospective review of 85 eyes of 85 patients newly diagnosed with neovascular AMD was conducted. Patients were eligible if they had received more than three consecutive monthly ranibizumab (0.50 mg) treatments and ophthalmic evaluations. Patients were classified into a VMT (+) group or VMT (-) group according to optical coherence tomography imaging. Best corrected visual acuity and central retinal thickness (CRT) measurements were obtained at three and six months after initial injection. RESULTS: One month after the third injection, mean visual acuity (VA) increases of 6.36 and 9.87 letters were observed in the VMT (+) and VMT (-) groups, respectively. The corresponding mean CRT values decreased by 70.29 microm and 121.68 microm, respectively. A total 41 eyes were identified as eligible for a subsequent fourth injection; 71.1% of patients (27 eyes) in the VMT (+) group but only 29.8% of patients in the VMT (-) group needed a subsequent fourth injection. Follow-up was extended to six months for 42 of the 85 enrolled patients (49.4%). The trends in VA and optical coherence tomography were found to be maintained at six-month follow-up. CONCLUSIONS: VA and CRT appeared to be more improved after ranibizumab treatment in the VMT (-) group compared to the VMT (+) group. VMT might antagonize the effect of ranibizumab treatment in a subpopulation of AMD patients.

Effects of Bevacizumab on Bcl-2 Expression and Apoptosis in Retinal Pigment Epithelial Cells under Oxidative Stress

PURPOSE: To evaluate the effects of bevacizumab on expression of B-cell leukemia/lymphoma (Bcl)-2 and apoptosis in retinal pigment epithelial (RPE) cells under oxidative stress conditions. METHODS: RPE cells were treated with H2O2 (0, 100, 200, 300, and 400 microM) and bevacizumab at or above the doses normally used in clinical practice (0, 0.33, 0.67, 1.33, and 2.67 mg/mL). Cell apoptosis was measured using flow cytometry with annexin V-fluorescein isothiocyanate. The expression of Bcl-2 mRNA was determined using reverse transcription polymerase chain reaction. RESULTS: Under low oxidative stress conditions (H2O2 100 microM), cell apoptosis was not significantly different at any concentration of bevacizumab, but Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL). Under moderate oxidative stress conditions (H2O2 200 microM), Bcl-2 mRNA expression decreased with increasing concentration of bevacizumab (0.33, 0.67, 1.33, and 2.67 mg/mL), but cell apoptosis increased only at 2.67 mg/mL of bevacizumab. Under high oxidative stress (300 microM) conditions, cell apoptosis increased at high concentrations of bevacizumab (1.33 and 2.67 mg/mL), but it did not correlate with Bcl-2 expression. CONCLUSIONS: Withdrawal of vascular endothelial growth factor can lead to RPE cell apoptosis and influences the expression of anti-apoptotic genes such as Bcl-2 under oxidative stress conditions. Since oxidative stress levels of each patient are unknown, repeated injections of intravitreal bevacizumab, as in eyes with age-related macular degeneration, might influence RPE cell survival.

The Effect of Simvastatin on the Expression of Catalase in Human Retinal Pigment Epithelial Cells

PURPOSE: To evaluate the effects of simvastatin on the catalase expression in human retinal pigment epithelium. METHODS: Retinal pigment epithelial (RPE) cells were incubated for 6 hours and 24 hours with various concentrations of simvastatin. In addition, RPE cells were incubated with 200 microM of H2O2 and various concentrations of simvastatin. After incubation, real-time polymerase chain reaction (PCR) was performed to examine the catalase messenger ribonucleic acid (mRNA) expression and a catalase assay was performed to examine the catalase activity in RPE. Intracellular reactive oxygen species (ROS) was measured using a fluorescence activated cell sorter (FACS). RESULTS: Simvastatin increased the amount of catalase mRNA and catalase activity at 10 microM in RPE cells. Under oxidative stress (200 microM of H2O2), 2.5 microM of simvastatin increased the catalase mRNA expression and 5 microM of simvastatin increased catalase activity in RPE cells. In addition, simvastatin reduced free radical formation but this effect was diminished in the presence of an irreversible catalase inhibitor, 3-amino-1,2,4-triazole (3-AT). CONCLUSIONS: Simvastatin exhibits anti-oxidative effects by inducing the catalase expression in human RPE cells. This anti-oxidative effect may be beneficial for preventing age-related macular degeneration induced by oxidative stress.

Effects of Simvastatin on the Expression of VEGF in Human Retinal Pigment Epithelial Cells

PURPOSE: To examine the effect of simvastatin on vascular endothelial growth factor (VEGF) expression in cultured human retinal pigment epithelial (RPE) cells under oxidative stress. METHODS: RPE cell viability was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay after 24 hours of incubation with various concentrations of simvastatin or H2O2. Cultured human RPE cells were pretreated with various concentrations of simvastatin and then incubated with 100 microm H2O2. After 24 hours of incubation, an enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the expression of VEGF. RESULTS: Simvastatin showed no toxicity up to 10 microm, but cell viability gradually decreased with increased concentration of simvastatin. Human RPE cells showed increased VEGF expression when exposed only to H2O2. When RPE cells were preincubated with simvastatin and later exposed to H2O2, VEGF expression was relatively lower. CONCLUSIONS: Simvastatin downregulated the expression of VEGF in human RPE cells under oxidative stress. Simvastatin may have some clinical benefits in preventing retinal diseases associated with VEGF.

Complications after Intravitreal Triamcinolone Acetonide Injection: Incidence and Risk Factors

PURPOSE: To reduce complications and provide proper management for better clinical outcomes in the treatment of macular edema through a large-scale analysis of the incidence and risk factors for complications of intravitreal triamcinolone injection. METHODS: The medical records of 490 eyes that received intravitreal triamcinolone (4.0 mg) injection for treatment of macular edema caused by various diseases were retrospectively reviewed, and relevant parameters were included in a multivariate regression model. RESULTS: Vitrectomized (p < 0.001) and pseudophakic (p = 0.054) eyes were less likely to exhibit an intraocular pressure increase, but glaucoma (p < 0.001) and young age (p = 0.073) were found to be significant risk factors for this complication. Vitrectomized eyes (p = 0.011), diabetic macular edema (p < 0.001), secondary ocular hypertension (p = 0.029) and old age (p = 0.059) were associated with cataract progression. Three consecutive case of sterile endophthalmitis, which differs from bacterial endophthalmitis in clinical course and prognosis, occurred during the same period. CONCLUSIONS: Risk factors and the incidence of complications after intravitreal triamcinolone injection should be evaluated through regular follow-up evaluation to ensure proper management and a better prognosis.