Na-Kyung Ryoo

Ocular toxocariasis: clinical features, diagnosis, treatment, and prevention

Despite being one of the most common zoonotic infections worldwide, human toxocariasis has been one of the neglected tropical diseases. Although most human infections are asymptomatic, two main syndromes of human toxocariasis are classically recognized: systemic toxocariasis, which encompasses diseases in major organs; and ocular toxocariasis (OT), disease in the eye or optic nerve, caused by the migration of Toxocara larvae into the eye. OT is usually a unilateral disease, which typically presents as retinal granuloma, a yellowish or whitish inflammatory mass, in the posterior pole or peripheral retina. Granuloma itself or other comorbid conditions such as epiretinal membrane, macular edema, and retinal detachment can lead to permanent retinal damage and visual loss in eyes with OT. OT is diagnosed clinically by identification of clinical signs on ophthalmologic examination. Serological tests, such as enzyme-linked immunosorbent assay (ELISA) for detection of serum antibody against the Toxocara larvae, can confirm the diagnosis. In addition, serum immunoglobulin E and detection of ocular fluid antitoxocara antibody by ELISA may give additional aid to the diagnosis. Standard treatment of OT is corticosteroid in patients with active intraocular inflammation. Although the role of anthelmintic therapy is unclear, favorable outcome has been reported by combined corticosteroid and albendazole therapy in eyes with active inflammation. Prevention, by increasing public awareness and reducing the risk of infection, is also important. Recently, the association between ingestion of uncooked meat or liver and toxocariasis was reported, especially in adult patients. Future research on the potential source of infection, diagnosis, and treatment should be performed.

Choroidal Thickness Changes After Photodynamic Therapy and Recurrence of Chronic Central Serous Chorioretinopathy

PURPOSE To investigate long-term changes in subfoveal choroidal thickness (SCT) after photodynamic therapy (PDT) and their relationship with chronic central serous chorioretinopathy (CSC) recurrence. DESIGN Retrospective, observational, comparative case series. METHODS Fifty-seven eyes with chronic CSC (52 patients, ≥2 years follow-up) treated with half-fluence or half-dose PDT were divided into 2 groups: those with incomplete CSC resolution or subretinal fluid (SRF) recurrence (SRF+) and those with complete SRF absorption without disease recurrence (SRF-). The SCT was measured using spectral-domain optical coherence tomography and relative SCT ratios (follow-up SCT: baseline SCT ratio) were compared between the 2 groups. RESULTS Mean follow-up period was 33.9 ± 9.9 months (range: 24-62 months). Four of 57 eyes (7%) had persistent SRF after PDT and 12 of 53 eyes (22.6%) had initial SRF resolution with SRF recurrence. The SRF+ group had a slower reduction in SCT during the first month (P < .001) and a higher relative SCT ratio than the SRF- group throughout follow-up (P < .001). The relative SCT ratio at 1 month was highly predictive of CSC recurrence (area under the curve = 0.902, 95% confidence interval: 0.823-0.982). Using a relative SCT ratio cutoff of 93.1%, sensitivity of this measure was 93.8% and specificity was 78.1%. CONCLUSIONS Those with incomplete SRF absorption or SRF recurrence had a slower SCT decline at 1 month and a higher SCT ratio throughout follow-up compared to those without CSC recurrence. The SCT changes may reflect PDT efficacy and help predict long-term recurrence and early treatment outcomes.

Proteomics-based identification and validation of novel plasma biomarkers phospholipid transfer protein and mannan-binding lectin serine protease-1 in age-related macular degeneration

Age-related macular degeneration (AMD) is a major cause of severe, progressive visual loss among the elderly. There are currently no established serological markers for the diagnosis of AMD. In this study, we carried out a large-scale quantitative proteomics analysis to identify plasma proteins that could serve as potential AMD biomarkers. We found that the plasma levels of phospholipid transfer protein (PLTP) and mannan-binding lectin serine protease (MASP)-1 were increased in AMD patients relative to controls. The receiver operating characteristic curve based on data from an independent set of AMD patients and healthy controls had an area under the curve of 0.936 for PLTP and 0.716 for MASP-1, revealing excellent discrimination between the two groups. A proteogenomic combination model that incorporated PLTP and MASP-1 along with two known risk genotypes of age-related maculopathy susceptibility 2 and complement factor H genes further enhanced discriminatory power. Additionally, PLTP and MASP-1 mRNA and protein expression levels were upregulated in retinal pigment epithelial cells upon exposure to oxidative stress in vitro. These results indicate that PLTP and MASP-1 can serve as plasma biomarkers for the early diagnosis and treatment of AMD, which is critical for preventing AMD-related blindness.

Anti-VEGF PolysiRNA Polyplex for the Treatment of Choroidal Neovascularization

Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration (AMD). Present ocular siRNA delivery technology is limited due to poor delivery through the retina to the choroid, where CNV originates. Our goal was to develop an optimized nanosized polyRNAi-based therapeutic delivery system to the subretinal space. We developed it by siRNA multimerization (polysiRNA) followed by coating with branched polyethylenimine and hyaluronic acid, and then evaluated its efficacy in vitro and in vivo. The polysiRNA polyplex showed a narrow size distribution (260.7 ± 43.27 nm) and negative charge (-4.98 ± 0.47 mV) owing to the hyaluronic acid outer layer. In vitro uptake of the polysiRNA polyplex by human ARPE cells was discovered, and the direct inhibition of VEGF mRNA translation was confirmed in B16F10 cells. The intravitreally administered polysiRNA polyplex overcame both the vitreous and retina barriers in vivo and reached the subretinal space efficiently. Intravitreal injection of the polysiRNA polyplex was not toxic to the retina in histopathology. Furthermore, intravitreal injections of the polysiRNA polyplex at both 1 and 7 days after laser photocoagulation inhibited laser-induced choroidal neovascularization, compared to that of the control (p < 0.05). These results suggest that anti-VEGF polysiRNA polyplexes show great potential in delivering multimeric RNAi-based therapeutics to treat retinal or choroidal disorders.

No-Reflow Phenomenon in Central Retinal Artery Occlusion: Incidence, Risk Factors, and Clinical Implications.

Purpose To investigate the incidence and risk factors of the no-reflow phenomenon in central retinal artery occlusion (CRAO) patients and to determine its effects on visual and anatomic outcomes. Methods In 102 eyes with CRAO in which arterial recanalization was obtained within 1 week from baseline, fluorescein angiography images obtained at baseline and 1 week were retrospectively reviewed. The no-reflow phenomenon in the retina was defined as macular capillary nonperfusion following arterial recanalization on fluorescein angiographs. We investigated the incidence and risk factors for the no-reflow phenomenon and compared the anatomical and visual outcomes between eyes with and without the phenomenon. Results Among the 102 CRAO eyes with arterial recanalization, 39 exhibited the no-reflow phenomenon, resulting in an incidence of 38.2%. The incidence among the eyes with treatment-induced and spontaneous recanalization was 43.4% and 15.8%, respectively, and it increased with the CRAO stage. CRAO stage and increased central macular thickness were risk factors for the phenomenon, with an odds ratio of 4.47 [95% confidence interval (CI), 1.19–16.8; P = 0.027] and 1.69 (95% CI, 1.12–2.55; P = 0.012) per 100-μm increase, respectively. The visual outcome was significantly poorer and retinal atrophy and photoreceptor disruption was greater in eyes with the no-reflow phenomenon than in those without. Conclusions The no-reflow phenomenon may occur after arterial recanalization in approximately one-third of CRAO patients and can affect anatomical and visual outcomes. This phenomenon may provide an additional explanation regarding the permanent retinal damage and vision loss in eyes with CRAO.

Human Papilloma Virus in Retinoblastoma Tissues from Korean Patients

Purpose Recent reports suggest the association of human papilloma virus (HPV) with retinoblastoma. This study was performed to elucidate whether HPV infection is related to retinoblastoma among Koreans. Methods A total of 54 cases diagnosed with retinoblastoma were enrolled from Seoul National University Childrens Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. Presence of human papilloma viral DNA was detected by in situ hybridization in formalin-fixed paraffin-embedded retinoblastoma tissues using both probes against high- and low risk HPV types. Results The mean age at diagnosis was 22.0 months (range, 1.1 to 98.0 months), and the mean age at enucleation was 27.8 months (range, 1.5 to 112.7 months) among the 54 patients with retinoblastoma. HPV was not detected in any of the retinoblastoma samples using either high risk or low risk HPV probes. Conclusions Our study, being the first study in the Korean population, proposes that HPV infection may have no causal relationship with retinoblastoma in Koreans.

Morphologic Characteristics of Choroid in the Major Choroidal Thickening Diseases, Studied by Optical Coherence Tomography.

We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies.

MANAGEMENT OF VITREAL LOSS FROM POSTERIOR CAPSULAR RUPTURE DURING CATARACT OPERATION: Posterior Versus Anterior Vitrectomy.

Purpose: To compare the efficacy between 23-gauge sutureless pars planar vitrectomy (PPV) and anterior vitrectomy in the management of vitreous loss associated with posterior capsular rupture during cataract surgery. Methods: Medical records of 139 eyes which sustained posterior capsular rupture and vitreal prolapse to anterior chamber during cataract surgery were retrospectively reviewed. Thirty-two eyes which underwent 23-gauge sutureless PPV (group PPV) and 107 eyes which underwent anterior vitrectomy (group AntV) were compared in postoperative visual and anatomical outcomes, operation time, and complications. Results: No significant differences were found between the groups in final best-corrected visual acuity of 20/40 or better (AntV vs. PPV = 80.4 vs. 90.6%, P = 0.139). However, the visual recovery rates (20/40 or better) 1 day, 1 week, 1 month postoperatively were significantly higher in group PPV (AntV vs PPV = 22.4 vs. 44%, 32.2 vs 58.6, 51.9 vs. 78.1%). Postoperative intraocular pressure–related complications requiring medication were less evident in group PPV (AntV vs. PPV = 52.3 vs. 6.3%, P < 0.001). Twelve cases (11.2%) of group AntV and 0 cases of group PPV underwent secondary operation during follow-up. Although no postoperative complications occurred in group PPV, complications such as endophthalmitis, retinal detachment, cystoid macular edema, intraocular lens instability were observed in the AntV group (none vs. 14%, P = 0.022). Conclusion: Twenty-three–gauge sutureless PPV is a safe and reliable solution for managing vitreous loss during cataract surgery. Therefore, it is expected to be considered primarily in institutes with vitreoretinal surgeons.

Consequences of Accidental Mitomycin C Intraocular Injection

Images of a patient’s eye after accidental mitomycin C intraocular injection, with no preinjection eye pathology. Note the iris atrophy and pigmentations and temporal corneal edema (A), the prominent cystoid macular edema (B), and the low endothelial count after exposure (C). A Goldmann visual field reveals central scotoma (D), and images taken 6 months after a vitrectomy reveal that the temporal corneal edema has been reduced but that the iris atrophy and cystoid macular edema remain (E and F). Hydroxychloroquine Toxic Effects Original Investigation Research