Neovascular Glaucoma Associated with Chronic Rhegmatogenous Retinal Detachment

Purpose@#To demonstrate the clinical features and natural course of chronic retinal detachment-associated neovascular glaucoma. @*Methods@#Ten patients, diagnosed with chronic retinal detachment-associated neovascular glaucoma during 2007-2016 were retrospectively investigated. Besides chronic retinal detachment, no patients had any neovascular glaucoma-predisposing conditions, such as carotid artery disease. Retinal perfusion status was evaluated from the fundus fluorescein angiography images. @*Results@#The mean age of patients was 57.5 years (range, 22-78 years). Complete retinal reattachment was achieved in three eyes, while partial or total chronic retinal detachment persisted in seven eyes. Wide-angle fundus fluorescein angiography revealed peripheral retinal capillary obstruction and severe nonperfusion. Neovascular glaucoma developed 213.4 months (range, 17-634 months) after retinal detachment. Three eyes received Ahmed valve implantation, while five eyes received intravitreal bevacizumab injection. Intraocular pressure was controlled in 10 eyes. Two eyes developed phthisis bulbi during follow-up. @*Conclusions@#In eyes with a chronic retinal detachment history, iris neovascularization and neovascular glaucoma can develop due to retinal capillary obstruction and chronic retinal ischemia, even after achieving retinal reattachment. We suggest regular follow-up examinations for patients with chronic retinal detachment, particularly for eyes with retinal nonperfusion, as detected on fundus fluorescein angiography.

Voretigene Neparvovec for the Treatment of RPE65-associated Retinal Dystrophy: Consensus and Recommendations from the Korea RPE65-IRD Consensus Paper Committee

Mutations in the RPE65 gene, associated with Leber congenital amaurosis, early-onset severe retinal dystrophy, and retinitis pigmentosa, gained growing attention since gene therapy for patients with RPE65-associated retinal dystrophy is available in clinical practice. RPE65 gene accounts for a very small proportion of patients with inherited retinal degeneration, especially Asian patients. Because RPE65-associated retinal dystrophy shares common clinical characteristics, such as early-onset severe nyctalopia, nystagmus, low vision, and progressive visual field constriction, with retinitis pigmentosa by other genetic mutations, appropriate genetic testing is essential to make a correct diagnosis. Also, fundus abnormalities can be minimal in early childhood, and the phenotype is highly variable depending on the type of mutations in RPE65-associated retinal dystrophy, which makes a diagnostic difficulty. The aim of this paper is to review the epidemiology of RPE65-associated retinal dystrophy, mutation spectrum, genetic diagnosis, clinical characteristics, and voretigene neparvovec, a gene therapy product for the treatment of RPE65-related retinal dystrophy.

Therapeutic Extracellular Vesicles from Tonsil-Derived Mesenchymal Stem Cells for the Treatment of Retinal Degenerative Disease

BACKGROUND@#Retinal degenerative disease (RDD), one of the most common causes of blindness, is predominantly caused by the gradual death of retinal pigment epithelial cells (RPEs) and photoreceptors due to various causes. Cell-based therapies, such as stem cell implantation, have been developed for the treatment of RDD, but potential risks, including teratogenicity and immune reactions, have hampered their clinical application. Stem cell-derived extracellular vesicles (EVs) have recently emerged as a cell-free alternative therapeutic strategy; however, additional invasiveness and low yield of the stem cell extraction process is problematic. @*METHODS@#To overcome these limitations, we developed therapeutic EVs for the treatment of RDD which were extracted from tonsil-derived mesenchymal stem cells obtained from human tonsil tissue discarded as medical waste following tonsillectomy (T-MSC EVs). To verify the biocompatibility and cytoprotective effect of T-MSC EVs, we measured cell viability by co-culture with human RPE without or with toxic all-trans-retinal. To elucidate the cytoprotective mechanism of T-MSC EVs, we performed transcriptome sequencing using RNA extracted from RPEs. The in vivo protective effect of T-MSC EVs was evaluated using Pde6b gene knockout rats as an animal model of retinitis pigmentosa. @*RESULTS@#T-MSC EVs showed high biocompatibility and the human pigment epithelial cells were significantly protected in the presence of T-MSC EVs from the toxic effect of all-trans-retinal. In addition, T-MSC EVs showed a dosedependent cell death-delaying effect in real-time quantification of cell death. Transcriptome sequencing analysis revealed that the efficient ability of T-MSC EVs to regulate intracellular oxidative stress may be one of the reasons explaining their excellent cytoprotective effect. Additionally, intravitreally injected T-MSC EVs had an inhibitory effect on the destruction of the outer nuclear layer in the Pde6b gene knockout rat. @*CONCLUSIONS@#Together, the results of this study indicate the preventive and therapeutic effects of T-MSC EVs during the initiation and development of retinal degeneration, which may be a beneficial alternative for the treatment of RDD.

Clinical Characteristics of Uveitis in Patients with Psoriasis in Korea: A Retrospective Multicenter Case Series

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.

Severe or Profound Sensorineural Hearing Loss Caused by Novel USH2A Variants in Korea: Potential Genotype-Phenotype Correlation

Objectives@#. We, herein, report two novel USH2A variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL). @*Methods@#. Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. We conducted the whole exome sequencing and subsequent pathogenicity prediction analysis. @*Results@#. We identified the following variants of USH2A from the two probands manifesting more than severe SNHL and retinitis pigmentosa (RP): compound heterozygosity for a nonsense (c.8176C>T: p.R2723X) and a missense variant (c.1823G>A: p.C608Y) in SB237, and compound heterozygosity for two frameshift variants (c.14835delT: p.S4945fs & c.13112_13115delAAAT: p.G4371fs) in SB354. Based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, two novel variants, c.1823G>A: p.C608Y and c.14835delT: p.Ser4945fs, can be classified as “uncertain significance” and “pathogenic,” respectively. The audiogram exhibited more than severe SNHL and a down-sloping configuration, necessitating cochlear implantation. The ophthalmic examinations revealed typical features of RP. Interestingly, one proband (SB 354-692) carrying two truncating compound heterozygous variants exhibited more severe hearing loss than the other proband (SB 237-461), carrying one truncation with one missense variant. @*Conclusion@#. Our results provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring USH2A variants, suggesting that USH2A should also be included in the candidate gene of cochlear implantation. A specific combination of USH2A variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of USH2A variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with USH2A will be helpful for genetic counseling and treatment starategy.

Clinical Manifestations and Visual Prognosis of Cilioretinal Artery Sparing Central Retinal Artery Occlusion

Prognostic Factors Related with Surgical Outcome of Vitrectomy in Myopic Traction Maculopathy

A Case of Recurrent Vogt-Koyanagi-Harada Disease Successfully Treated with Adalimumab in Young Female Adult Patient

No abstract available.

Retinitis Pigmentosa Associated with Bardet-Biedl Syndrome with BBS9 Gene Mutation in a Korean Patient

No abstract available.

Association of Retinal Artery Occlusion with Subclinical Coronary Artery Disease

BACKGROUND: To evaluate the association between retinal artery occlusion (RAO) and subclinical coronary artery disease (CAD). METHODS: We studied 41 patients with non-arteritic RAO without any history or symptoms of CAD, who had undergone coronary computed tomographic angiography (CCTA) for systemic atherosclerotic evaluation between 2007 and 2012. The age- and gender-matched control group comprised 4-fold subjects who were randomly selected from asymptomatic subjects who underwent CCTA during general health evaluation. Medical records and CCTA findings were compared between RAO patients and control groups. Multiple logistic regression analysis was carried out to assess the risk factors associated with CAD. RESULTS: Cardiovascular risk factors were not significantly different between RAO patients and control groups. RAO patients showed higher coronary artery calcium score than did control subjects (267.9 ± 674.9 vs. 120.2 ± 289.5). On CCTA, the prevalence of obstructive CAD (diameter stenosis ≥ 50%) in RAO patients was significantly higher than that in controls (29% vs. 15%; odds ratio [OR], 3.0). RAO patients demonstrated a significantly higher segment-involvement score (SIS) (2.6 ± 3.0 vs. 1.6 ± 2.4) and segment-stenosis score (SSS) (3.6 ± 4.8 vs. 2.0 ± 3.3) than did controls. After adjustment of associated factors, RAO showed significant association (OR, 3.0) with obstructive CAD and extensive CAD (SIS > 4: OR, 2.8; SSS > 8: OR, 3.4). CONCLUSION: Patients with RAO had a higher prevalence of subclinical obstructive CAD with a more extensive and heavier burden of coronary artery plaques than did age- and gender-matched controls. Physicians should understand the potential risk of CAD in RAO patients.

Erratum: Correction of Table: Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases

The authors regret that there were errors in Table 2 and Supplementary Table.

Genetic Mutation Profiles in Korean Patients with Inherited Retinal Diseases

BACKGROUND: Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea. METHODS: Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD. RESULTS: Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. ABCA4 was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n = 1), and cone dystrophy (n = 1). In particular, mutations in EYS were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the ABCA4 gene with an autosomal recessive trait. CONCLUSION: This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients.

Short-term Efficacy and Safety of Ranibizumab for Neovascular Age-related Macular Degeneration in the Real World: A Post-marketing Surveillance Study

PURPOSE: To investigate the short-term efficacy and safety of ranibizumab in the routine clinical setting in patients with neovascular age-related macular degeneration and to analyze the associated factors for visual outcome. METHODS: This was a post-hoc analysis of a ranibizumab regulatory post-marketing surveillance study in which 4,136 patients were enrolled and followed for 12 weeks. Change in best-corrected visual acuity (BCVA), size of choroidal neovascularization, and the presence of hemorrhage and exudate were analyzed and the association between BCVA change and baseline characteristics were investigated. Data on ocular and systemic adverse events were collected. RESULTS: Mean BCVA improved significantly and mean BCVA change was the logarithm of the minimal angle of resolution 0.13 ± 0.01 (p < 0.001). A lower baseline BCVA and younger age were significant predictive factors for visual improvement or maintenance (≥0 lines). For greater visual acuity gain (≥3 lines), no treatment history, lower baseline BCVA, younger age, and classic-type choroidal neovascularization were significant predictive factors. No new safety signals were found. CONCLUSIONS: In this study, conducted in real-world clinical practice with a large number of neovascular age-related macular degeneration patients, visual and anatomical outcomes improved significantly after three monthly ranibizumab treatments. Treatment-naive patients had a higher chance of greater visual gain (≥3 lines) than non-naive patients.

Intravitreal Dexamethasone Implant with Plasma Autoantibody Monitoring for Cancer-associated Retinopathy

No abstract available.

Association of Central Serous Chorioretinopathy with Psychosocial Factors is Dependent on Its Phase and Subtype

PURPOSE: To analyze the psychosocial factors associated with central serous chorioretinopathy (CSC) according to its phases and subtypes and to correlate the factors with the extent of choroidal hyperpermeability. METHODS: Age- and sex-matched CSC patients and controls (n = 37 in each group) were enrolled, and their psychosocial factors were compared. CSC was divided into two phases (active and inactive), and active CSC was further divided into two subtypes (acute and chronic). The correlations between the size of the hyperpermeable choroidal lesion identified on indocyanine green angiography and psychosocial factors were examined. RESULTS: Active CSC patients experienced more stressful events (p = 0.030), were more depressive (p = 0.037), and felt less emotional (p = 0.014) and informational (p = 0.014) support than the matched controls, whereas inactive CSC patients were comparable to the matched controls in all psychosocial factors. Among the active CSC patients, acute patients were more depressive (p = 0.029), while chronic patients experienced more stressful events (p = 0.024) than their matched controls. The size of the hyperpermeable choroidal lesion was correlated with the severity of depression in acute patients. CONCLUSIONS: Association of CSC with psychosocial factors was dependent on the phase and subtype of CSC. Psychosocial factors were associated with CSC in the active phase, and severity of depression was correlated with the size of the choroidal pathology in acute active CSC. Further prospective studies to investigate if psychosocial factors can trigger CSC are warranted.

Bevacizumab versus Dexamethasone Implant Followed by Bevacizumab for the Treatment of Macula Edema Associated with Branch Retinal Vein Occlusion

PURPOSE: To compare visual and anatomical outcomes of intravitreal injections of bevacizumab and dexamethasone implant (Ozurdex) treatment for macular edema associated with branch retinal vein occlusion (BRVO). METHODS: We retrospectively reviewed patients who underwent intravitreal bevacizumab administered monthly on a pro re nata (PRN) basis (26 eyes, IVB group) or an initial 700-µg dexamethasone implant followed by a bevacizumab PRN injection (20 eyes, IVD group) for treatment of macular edema associated with BRVO. We compared best-corrected visual acuity (BCVA) and central macular thickness (CMT). We also measured ellipsoid zone recovery rate and ganglion cell-inner plexiform layer volume within the center 6 mm zone. A linear mixed model analysis was performed to compare serial changes in BCVA and CMT. RESULTS: Both groups showed significant improvement in BCVA and significant reduction in CMT. However, BCVA in the first month was significantly better in the IVD group (logarithm of the minimum angle of resolution, IVD group 0.21 ± 0.26 vs. IVB group 0.39 ± 0.30, p = 0.038) and the 1-month CMT was thinner in the IVD group (IVD group 270.0 ± 62.0 µm vs. IVB group 338.9 ± 122.6 µm, p = 0.028), and these trends were maintained during the 6-month follow-up. The IVD group showed more rapid macular edema resolution (p = 0.049); however, there were no significant differences in ellipsoid zone recovery rate (p = 0.268) or ganglion cell-inner plexiform layer volume between the two groups (p = 0.459). CONCLUSIONS: There were no significant differences in final visual or anatomical outcomes between the two groups; however, initial dexamethasone implant injection followed by bevacizumab PRN injection initially showed more rapid improvement in vision and BRVO-associated macular edema resolution compared to intravitreal bevacizumab administered monthly on a PRN basis.

Clinical Features of Pregnancy-associated Retinal and Choroidal Diseases Causing Acute Visual Disturbance

PURPOSE: To report clinical features of patients with retinal and choroidal diseases presenting with acute visual disturbance during pregnancy. METHODS: In this retrospective case series, patients who developed acute visual loss during pregnancy (including puerperium) and visited a tertiary hospital from July 2007 to June 2015, were recruited by searching electronic medical records. Patients were categorized according to the cause of visual loss. Clinical features and required diagnostic modalities were analyzed in the retinal and choroidal disease group. RESULTS: Acute visual loss occurred in 147 patients; 49 (38.9%) were classified into the retinal and choroidal group. The diagnoses included central serous chorioretinopathy (22.4%), hypertensive retinopathy with or without pre-eclampsia (22.4%), retinal tear with or without retinal detachment (18.4%), diabetic retinopathy progression (10.2%), Vogt-Koyanagi-Harada disease (4.1%), retinal artery occlusion (4.1%), multiple evanescent white dot syndrome (4.1%), and others (14.3%). Visual symptoms first appeared at gestational age 25.9 ± 10.3 weeks. The initial best-corrected visual acuity (BCVA) was 0.27 ± 0.39 logarithm of the minimum angle of resolution (logMAR); the final BCVA after delivery improved to 0.13 ± 0.35 logMAR. Serious visual deterioration (BCVA worth than 20 / 200) developed in two patients. Differential diagnoses were established with characteristic fundus and spectral-domain optical coherence tomography findings in all cases. CONCLUSIONS: In pregnant women with acute visual loss, retinal and choroidal diseases are common and could be vision threatening. Physicians should be aware of pregnancy-associated retinal and choroidal diseases and their clinical features. The differential diagnosis can be established with non-invasive techniques.

Central Retinal Artery Occlusion after Trauma: Report of Two Cases

PURPOSE: To report two patients who developed central retinal artery occlusion (CRAO) after trauma. CASE SUMMARY: A 26-year-old man complained of severe loss of vision in his left eye after falling and bumping his forehead on a staircase. His visual acuity was light perception in the left eye. Fundus examination revealed edematous white retina and a cherry red spot on the macula. Angiography showed severe stenosis in the initial segment of the ophthalmic artery with ophthalmic arterial embolus. He underwent intra-arterial thrombolysis with a clinical diagnosis of CRAO with ophthalmic artery stenosis. A 57-year-old woman presented with vision loss after falling and striking her face below her right lower eyelid on a wooden stick. Her visual acuity was hand motions in the right eye. Fundus examinations showed white retina with opacity and a cherry red spot on the macula. Fluorescein angiography and optical coherence tomography was performed, and a clinical diagnosis of CRAO was made. CONCLUSIONS: CRAO must be considered when clinically differentiating visual loss after a trauma.

Diagnostic Value of the Serum Anti-Toxocara IgG Titer for Ocular Toxocariasis in Patients with Uveitis at a Tertiary Hospital in Korea

PURPOSE: This study evaluated the prevalence of ocular toxocariasis (OT) in patients with uveitis of unknown etiology who visited a tertiary hospital in South Korea and assessed the success of serum anti-Toxocara immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) as a diagnostic test for OT. METHODS: The records of consecutive patients with intraocular inflammation of unknown etiology were reviewed. All participants underwent clinical and laboratory investigations, including ELISA for serum anti-Toxocara IgG. OT was diagnosed based on typical clinical findings. Clinical characteristics, seropositivity, and IgG titers were compared between patients diagnosed with OT and non-OT uveitis. The seropositivity and the diagnostic value of anti-Toxocara IgG was investigated among patients with different types of uveitis. RESULTS: Of 238 patients with uveitis of unknown etiology, 71 (29.8%) were diagnosed with OT, and 80 (33.6%) had positive ELISA results for serum anti-Toxocara IgG. The sensitivity and specificity of the ELISA test were 91.5% (65 / 71) and 91.0% (152 / 167), respectively. The positive predictive value of the serum anti-Toxocara IgG assay was 81.3%. Among patients with anterior, intermediate, posterior, and panuveitis, the prevalence rates of OT were 8.3%, 47.1%, 44.8%, and 7.1%, respectively; the seropositivity percentages were 18.1%, 47.1%, 43.7%, and 17.9%; and the positive predictive values were 38.5%, 95.8%, 92.1%, and 40.0%. The serum anti-Toxocara IgG titer also significantly decreased following albendazole treatment. CONCLUSIONS: OT is a common cause of intraocular inflammation in the tertiary hospital setting. Considering that OT is more prevalent in intermediate and posterior uveitis, and that the positive predictive value of the anti-Toxocara IgG assay is high, a routine test for anti-Toxocara IgG might be necessary for Korean patients with intermediate and posterior uveitis.

Incidence and Clinical Features of Neovascularization of the Iris following Acute Central Retinal Artery Occlusion

PURPOSE: To investigate the incidence of neovascularization of the iris (NVI) and clinical features of patients with NVI following acute central retinal artery occlusion (CRAO). METHODS: A retrospective review of 214 consecutive CRAO patients who visited one tertiary hospital between January 2009 and January 2015 was conducted. In total, 110 patients were eligible for this study after excluding patients with arteritic CRAO, a lack of follow-up, iatrogenic CRAO secondary to cosmetic filler injection, or NVI detected before CRAO attack. Fluorescein angiography (FA) was applied until retinal arterial reperfusion was achieved, typically within 1 to 3 months. RESULTS: The incidence of NVI was 10.9% (12 out of 110 patients). Neovascular glaucoma was found in seven patients (6.4%). The mean time to NVI diagnosis after CRAO events was 3.0 months (range, 1 week to 15 months). The cumulative incidence was 5.5% at 3 months, 7.3% at 6 months, and 10.9% at 15 months. Severely narrowed ipsilateral carotid arteries were observed in only three patients (27.3%). The other nine patients (75.0%) showed no predisposing conditions for NVI, such as proliferative diabetic retinopathy or central retinal vein occlusion. Reperfusion rate and prevalence of diabetes were significantly different between patients with NVI and patients without NVI (reperfusion: 0% [NVI] vs. 94.7% [no NVI], p < 0.001; diabetes: 50.0% [NVI] vs. 17.3% [no NVI], p = 0.017). CONCLUSIONS: CRAO may lead to NVI and neovascular glaucoma caused by chronic retinal ischemia from reperfusion failure. Our results indicate that follow-up fluorescein angiography is important to evaluate retinal artery reperfusion after acute CRAO events, and that prophylactic treatment such as panretinal photocoagulation should be considered if retinal arterial perfusion is not recovered.