Comparison of macular changes according to the etiology of optic neuritis: a cross-sectional study.

AIM: To compare the macular structure including foveal thickness among patients with optic neuritis (ON) according to the etiology and to investigate the possible correlation between structural and visual outcomes. METHODS: In this retrospective cross-sectional study, the clinical data of patients with aquaporin-4 immunoglobulin G-related ON (AQP4 group, 40 eyes), myelin oligodendrocyte glycoprotein IgG-related ON (MOG group, 31 eyes), and multiple sclerosis-related ON (MS group, 24 eyes) were obtained. The retinal thickness of the foveal, parafoveal and perifoveal regions were measured. Visual acuity (VA), visual field index and mean deviation were measured as visual outcomes. RESULTS: The AQP4 group showed a significantly thinner fovea (226.4±13.4 µm) relative to the MOG (236.8±14.0 µm, P=0.015) and MS (238.9±14.3 µm, P=0.007) groups. The thickness in the parafoveal area also was thinner in the AQP4 group, though the difference in perifoveal retinal thickness was not significant. Foveal thickness was correlated with VA in the AQP4 group (coefficient ρ=-0.418, P=0.014), but not in the MOG and MS groups (P=0.218 and P=0.138, respectively). There was no significant correlation between foveal thickness and visual field test in all three groups. CONCLUSION: The significant thinning in the fovea and parafoveal areas in the AQP4 group compared to the MOG and MS groups are found. Additionally, macular changes in AQP4-ON show a significant correlation with VA. The results provide the possibility that retinal structural damage could reflect functional damage in AQP4-ON, distinct from MOG-ON and MS-ON.

Redescription and molecular phylogeny of Trochilia sigmoides Dujardin, 1841 (Ciliophora, Cyrtophoria) collected from South Korea.

During a survey of Korean marine ciliates, Trochilia sigmoides, the type species of the genus Trochilia, was collected and examined using in vivo observation and protargol impregnation. Moreover, scanning electron microscopy and 18S rRNA gene sequencing have been applied for the first time to study this species. Morphologically, T. sigmoides is characterized by the small body size, the oval body outline, and the spiral dorsal ridges. The Korean population of T. sigmoides shows only minute differences to other populations reported in the literature, mainly in body size and the number of dorsal ridges. Phylogenetic analyses based on 18S rRNA gene sequences show that T. sigmoides and T. petrani are placed together with two members of the family Kyaroikeidae, causing the family Dysteriidae to be non-monophyletic. The present new data increase the knowledge about the morphology and phylogeny of the genus Trochilia and would assist in understanding the phylogenetic relationship between the free-living Dysteriidae and the parasitic Kyaroikeidae.

Prediction of neovascular age-related macular degeneration recurrence using optical coherence tomography images with a deep neural network.

Neovascular age-related macular degeneration (nAMD) can result in blindness if left untreated, and patients often require repeated anti-vascular endothelial growth factor injections. Although, the treat-and-extend method is becoming popular to reduce vision loss attributed to recurrence, it may pose a risk of overtreatment. This study aimed to develop a deep learning model based on DenseNet201 to predict nAMD recurrence within 3 months after confirming dry-up 1 month following three loading injections in treatment-naïve patients. A dataset of 1076 spectral domain optical coherence tomography (OCT) images from 269 patients diagnosed with nAMD was used. The performance of the model was compared with that of 6 ophthalmologists, using 100 randomly selected samples. The DenseNet201-based model achieved 53.0% accuracy in predicting nAMD recurrence using a single pre-injection image and 60.2% accuracy after viewing all the images immediately after the 1st, 2nd, and 3rd injections. The model outperformed experienced ophthalmologists, with an average accuracy of 52.17% using a single pre-injection image and 53.3% after examining four images before and after three loading injections. In conclusion, the artificial intelligence model demonstrated a promising ability to predict nAMD recurrence using OCT images and outperformed experienced ophthalmologists. These findings suggest that deep learning models can assist in nAMD recurrence prediction, thus improving patient outcomes and optimizing treatment strategies.

Prognostic factors of first-onset optic neuritis based on diagnostic criteria and antibody status: a multicentre analysis of 427 eyes.

BACKGROUND: Optic neuritis (ON) prognosis is influenced by various factors including attack severity, underlying aetiologies, treatments and consequences of previous episodes. This study, conducted on a large cohort of first ON episodes, aimed to identify unique prognostic factors for each ON subtype, while excluding any potential influence from pre-existing sequelae. METHODS: Patients experiencing their first ON episodes, with complete aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) antibody testing, and clinical data for applying multiple sclerosis (MS) diagnostic criteria, were enrolled. 427 eyes from 355 patients from 10 hospitals were categorised into four subgroups: neuromyelitis optica with AQP4 IgG (NMOSD-ON), MOG antibody-associated disease (MOGAD-ON), ON in MS (MS-ON) or idiopathic ON (ION). Prognostic factors linked to complete recovery (regaining 20/20 visual acuity (VA)) or moderate recovery (regaining 20/40 VA) were assessed through multivariable Cox regression analysis. RESULTS: VA at nadir emerged as a robust prognostic factor for both complete and moderate recovery, spanning all ON subtypes. Early intravenous methylprednisolone (IVMP) was associated with enhanced complete recovery in NMOSD-ON and MOGAD-ON, but not in MS-ON or ION. Interestingly, in NMOSD-ON, even a slight IVMP delay in IVMP by >3 days had a significant negative impact, whereas a moderate delay up to 7-9 days was permissible in MOGAD-ON. Female sex predicted poor recovery in MOGAD-ON, while older age hindered moderate recovery in NMOSD-ON and ION. CONCLUSION: This comprehensive multicentre analysis on first-onset ON unveils subtype-specific prognostic factors. These insights will assist tailored treatment strategies and patient counselling for ON.

Risk of central nervous system demyelinating attack or optic neuritis recurrence after pediatric optic neuritis in Korea.

PURPOSE: To investigate the rate of development of symptomatic central nervous system (CNS) demyelinating attacks or recurrent optic neuritis (ON) after the first episode of ON and its risk factors for Korean pediatric patients. METHODS: This multicenter retrospective cohort study included the patients under 18 years of age (n=132) diagnosed with ON without previous or simultaneous CNS demyelinating diseases. We obtained the clinical data including the results of neuro-ophthalmological examinations, magnetic resonance images (MRIs), antibody assays, and laboratory tests. We investigated the chronological course of demyelinating disease with respect to the occurrence of neurological symptoms and/or signs, and calculated the 5-year cumulative probability of CNS demyelinating disease or ON recurrence.  RESULTS: During the follow-up period (63.1±46.7 months), 18 patients had experienced other CNS demyelinating attacks, and the 5-year cumulative probability was 14.0±3.6%. Involvement of the extraorbital optic nerve or optic chiasm and asymptomatic lesions on the brain or spinal MRI at initial presentation were significant predictors for CNS demyelinating attack after the first ON. The 5-year cumulative probability of CNS demyelinating attack was 44.4 ± 24.8% in the AQP4-IgG group, 26.2±11.4% in the MOG-IgG group, and 8.7±5.9% in the double-negative group (P=0.416). Thirty-two patients had experienced a recurrence of ON, and the 5-year cumulative probability was 24.6±4.0%. In the AQP4-IgG group, the 5-year cumulative probability was 83.3±15.2%, which was significantly higher than in the other groups (P<0.001). CONCLUSIONS: A careful and multidisciplinary approach including brain/spinal imaging and antibody assay can help predict further demyelinating attacks in pediatric ON patients.

Morphology and molecular phylogeny of two hypotrichous ciliates (Ciliophora, Spirotrichea) from South Korea, including Hemiurosomoida koreana n. sp.

The living morphology, infraciliature, and molecular phylogeny of a new soil ciliate, Hemiurosomoida koreana n. sp., discovered in a sample collected from a mountain in the northeast of South Korea, were investigated. The new species possesses the characteristics of the genus Hemiurosomoida, i.e., a reduced number of frontal-ventral-transverse cirri, three dorsal kineties of which kineties 1 and 2 each bears a caudal cirrus, and a single dorsomarginal kinety. It is distinguishable from congeners and other similar species by at least one distinct qualitative or quantitative character including the body size, the presence and arrangement of cortical granules, the number of adoral membranelles, marginal cirri, and dorsal dikinetids, or by the arrangement of transverse cirri. Phylogenetic analyses based on 18S rRNA gene sequences also support the assignment of the new species to the non-monophyletic genus Hemiurosomoida. In addition, the living morphology, infraciliature, and the 18S rRNA gene sequence of a Korean population of Nothoholosticha flava were studied.

Morphology, morphogenesis, and molecular phylogeny of Aspidisca koreana n. sp. (Ciliophora, Euplotida) from South Korea.

The morphology, morphogenesis, and molecular phylogeny of a new ciliate, Aspidisca koreana n. sp., discovered in the eastern coast of South Korea, were investigated. The morphological description is based on the observation of living cells, 4'-6-diamidino-2-phenylindole (DAPI) and silver-stained specimens (e.g., protargol, silver nitrate), and scanning electron micrographs. The new species is characterized by having a small body size (17-25 × 15-18 µm in vivo), a distinct peristomial spur on the posterior portion of left margin, seven frontoventral cirri in "polystyla-arrangement", and the arrangement of the anterior portion of adoral zone of membranelles, i.e., anteriormost membranelle is distinctly separated from the other three membranelles. The morphogenesis follows the typical pattern of this genus. Phylogenetic analyses, using the 18S rDNA sequence, also support the establishment of a new species.

Report on the seventh meeting of national control laboratories for vaccines and biologicals of the WHO Western Pacific and South-East Asia member states.

The Biregional Network of National Control Laboratories (NCLs) of the WHO Western Pacific and South-East Asia Regions has been meeting annually since 2018 to enhance NCLs' voluntary participation capacity. Its seventh meeting was hosted by the Korea National Institute of Food and Drug Safety Evaluation (NIFDS) of the Ministry of Food and Drug Safety (MFDS), in conjunction with the Global Bio Conference, in Seoul on September 6, 2022. Over 60 participants from seven countries, (India, Indonesia, Japan, Korea, Malaysia, the Philippines, and Vietnam) attended the meeting on-site and online. The theme of this meeting was 'Quality Control Issues and International Trends for Biologicals including Vaccines and Plasma-Derived Medicinal Products.' Three special speeches were presented on sharing the quality control system for biologicals, including NCLs' considerations in preparing the WHO Listed Authorities and sharing MFDS experiences. Furthermore, the participating NCLs shared country-specific issues related to national lot releases during the COVID-19 pandemic and acknowledged the meeting's crucial role in response preparedness for pandemic emergencies and enhancing regulatory capacity through coalitions and information exchange among NCLs. The NIFDS will cooperate closely with other Asian NCLs to enhance biological product quality control, aiming to establish regional standards and standardize test methods through collaboration.

Extraocular muscle enlargement of indeterminate cause in pediatric patients: case series and literature review.

PURPOSE: To specify the clinical characteristics of enlarged extraocular muscles of indeterminate cause in pediatric patients based on a case series and literature review. METHODS: The medical records of pediatric patients who presented between January 2019 and January 2022 with enlarged extraocular muscles, where the underlying cause could not be determined, were retrospectively reviewed. RESULTS: Four patients were included. The main reason for presentation was evaluation of abnormal head posture. Head tilt or turn with duction deficit was observed in all patients. The age of onset ranged from 6 months to 1 year. Two patients presented with esotropia and hypotropia; the other 2 patients, with large-angle esotropia. Orbital imaging was performed in all cases and revealed unilateral rectus muscle enlargement sparing the muscle tendon. All 4 patients were found to have an enlarged medial rectus muscle. In the 2 patients with hypotropia, the inferior rectus muscle was also involved. No underlying systemic or orbital disease was found. There were no changes in the orbit or extraocular muscles on follow-up imaging test. The intraoperative forced duction test revealed severe restriction in the direction of gaze opposite to the primary field of action of the enlarged muscles. CONCLUSIONS: Enlargement of extraocular muscles should be considered in the differential diagnosis when large-angle incomitant vertical or horizontal misalignment and abnormal head posture are observed in infancy.

Brain natriuretic peptide as a clinical screening tool for the diagnosis of Kawasaki disease.

N-terminal pro-brain natriuretic peptide (NT-proBNP) has been studied as a diagnostic screening tool for Kawasaki disease (KD). However, brain natriuretic peptide (BNP) has been less studied while has less variability among age groups. We aimed to find out if BNP can be used as a diagnostic screening tool for KD in Korea. This was a retrospective cohort study performed in a single pediatric emergency department. Patients younger than 19 years of age who presented with fever and underwent BNP examination for suspected KD was included. The primary outcome was the diagnostic performance of BNP for KD, and the secondary outcome was the diagnostic performance of BNP for coronary artery aneurysm (CAA). We also derived a scoring system for predicting KD and CAA. Of the 778 patients who were finally included, 400 were not diagnosed with KD and 378 were diagnosed with KD. The odds ratio of BNP at the cutoff of 30 pg/mL for KD was 7.80 (95% CI, 5.67-10.73) in the univariate analysis and 3.62 (95% CI, 2.33-5.88) in the multivariable analysis. The odds ratio of BNP at the cutoff of 270 pg/mL for CAA was 3.67 (95% CI, 2.18-6.19) in the univariate analysis and 2.37 (95% CI, 1.16-8.74) in the multivariable analysis. The AUC of KD and CAA were 0.884 and 0.726, respectively, which was the highest AUCs among all variables. Additionally, we proposed a scoring system for KD and CAA. It is important to clinically suspect KD and CAA in children with high BNP levels.

Polymorphism, gigantism, and cannibalism, one stylonychid ciliate (Ciliophora, Hypotricha) to rule them all.

The morphology, ontogenesis, and molecular phylogeny of the polymorphic and cannibalistic giant forming Tetmemena polymorpha n. sp., found in a brackish water sample in South Korea, were investigated. The present species has long been misidentified as "Oxytricha bifaria." The new investigation shows that the species produces three morphologically different morphs. The small morph is bacterivorous and characterized by its small body size and slim body and it is found only in the stationary and decline phases of the culture. The large morph has a wide body, larger oral apparatus, and feeds on small eukaryotes such as yeast cells and small ciliates. It divides very quickly and produces the other two morphs and found in the exponential phase of the cultures. The giant morph is characterized by its huge body and oral apparatus. It feeds on the small morph cells of the same species and other ciliates, and occurs together with the small morph. Phylogenetic analyses based on the 18S rRNA gene sequences show that the new species is placed in a sister subclade to that containing other Tetmemena sequences. Moreover, Tetmemena indica Bharti et al., 2019 nov. stat. is raised to species level based on the differences in the cyst morphology and the dorsal ciliature to the authoritative Tetmemena pustulata population.

Quality of life in intermittent exotropia for Korean children and their parents.

BACKGROUND: Patients with strabismus are more likely to have mental health problems, including high rates of depressive symptoms and social phobia. Intermittent exotropia (IXT) typically occurs in early childhood and is more common in Asian populations. We aim to assess the health-related quality of life (HRQOL) concerns in children with intermittent exotropia (IXT) using the Intermittent Exotropia Questionaire (IXTQ), and their associations with the clinical severity of IXT and the parents' HRQOL concerns. METHODS: IXT, defined as both distance and near exodeviation ≥ 10 prism diopters were eligible for inclusion. The final IXTQ score is calculated using the mean score for all items, and ranges from 0 (worst HRQOL) to 100 (best HRQOL). The correlations of child IXTQ scores with their deviation angle and stereoacuity were measured, as were those with their parent's IXTQ scores. RESULTS: One hundred twenty-two children with IXT (aged 5-17 years) and one parent for each child completed the child and parent IXTQ, respectively. The greatest HRQOL concern for each child with IXT and their parent was "Worry about eyes" (frequency 88%, score 35.0 ± 27.8). Lower child IXTQ scores were associated with a larger distance (r = 0.24, p = 0.007) and near deviation angle (r = 0.2, p = 0.026). "It bothers me because I have to wait for my eyes to clear up" and "Waiting for their eyes to clear up" were more common in children with a larger deviation angle (both p < 0.05). The parent IXTQ scores (52.1 ± 25.3) were lower than the child ones (79.7 ± 15.8) and showed a positive correlation with child IXTQ scores (r = 0.26, p = 0.004). Lower parent IXTQ scores were associated with poor distance stereoacuity (r = 0.23, p = 0.01). CONCLUSION: The HRQOL of IXT children was positively related to that of their parents. A larger deviation angle and worse distance stereoacuity function may predict more-negative impacts on children and their parents, respectively.

Synthesis, In Silico and In Vitro Characterization of Novel N,N-Substituted Pyrazolopyrimidine Acetamide Derivatives for the 18KDa Translocator Protein (TSPO).

The translocator protein (TSPO) is an interesting biological target for molecular imaging and therapy because the overexpression of TSPO is associated with microglial activation caused by neuronal damage or neuroinflammation, and these activated microglia are involved in various central nervous system (CNS) diseases. The TSPO is a target for neuroprotective treatment, which is used with the aim of reducing microglial cell activation. The novel N,N-disubstituted pyrazolopyrimidine acetamides scaffold (GMA 7-17), which bears a fluorine atom and is directly linked to the phenyl moiety, was synthesized, and each of the novel ligands was characterized in vitro. All of the newly synthesized ligands displayed picomolar to nanomolar affinity for the TSPO. Particularly, an in vitro affinity study led to the discovery of 2-(5,7-diethyl-2-(4-fluorophenyl)pyrazolo [1,5-a]pyrimidin-3-yl)-N-ethyl-N-phenylacetamide GMA 15 (Ki = 60 pM), a novel TSPO ligand that exhibits a 61-fold enhancement in affinity compared to the reference standard DPA-714 (Ki = 3.66 nM). Molecular dynamic (MD) studies of the highest affinity binder, GMA 15, were carried out to check its time-dependent stability with the receptor compared to DPA-714 and PK11195. The hydrogen bond plot also indicated that GMA 15 formed higher hydrogen bonds compared to DPA-714 and PK11195. We anticipate that further optimization to enhance the potency in a cellular assay needs to be followed, but our strategy of identifying potential TSPO binding novel scaffolds may open up a new avenue to develop novel TSPO ligands suited for potential molecular imaging and a wide range of therapeutic applications.

Non-Arteritic Ischemic Optic Neuropathy Following COVID-19 Vaccination in Korea: A Case Series.

BACKGROUND: To report the clinical manifestations of non-arteritic anterior ischemic optic neuropathy (NAION) cases after coronavirus disease 2019 (COVID-19) vaccination in Korea. METHODS: This multicenter retrospective study included patients diagnosed with NAION within 42 days of COVID-19 vaccination. We collected data on vaccinations, demographic features, presence of vascular risk factors, ocular findings, and visual outcomes of patients with NAION. RESULTS: The study included 16 eyes of 14 patients (6 men, 8 women) with a mean age of 63.5 ± 9.1 (range, 43-77) years. The most common underlying disease was hypertension, accounting for 28.6% of patients with NAION. Seven patients (50.0%) had no vascular risk factors for NAION. The mean time from vaccination to onset was 13.8 ± 14.2 (range, 1-41) days. All 16 eyes had disc swelling at initial presentation, and 3 of them (18.8%) had peripapillary intraretinal and/or subretinal fluid with severe disc swelling. Peripapillary hemorrhage was found in 50% of the patients, and one (6.3%) patient had peripapillary cotton-wool spots. In eight fellow eyes for which we were able to review the fundus photographs, the horizontal cup/disc ratio was less than 0.25 in four eyes (50.0%). The mean visual acuity was logMAR 0.6 ± 0.7 at the initial presentation and logMAR 0.7 ± 0.8 at the final visit. CONCLUSION: Only 64% of patients with NAION after COVID-19 vaccination have known vascular and ocular risk factors relevant to ischemic optic neuropathy. This suggests that COVID-19 vaccination may increase the risk of NAION. However, overall clinical features and visual outcomes of the NAION patients after COVID-19 vaccination were similar to those of typical NAION.

A cross-sectional study of ophthalmologic examination findings in 5385 Koreans presenting with intermittent exotropia.

The Korean Intermittent Exotropia Multicenter Study (KIEMS) was a retrospective, cross-sectional and multicenter study for the investigation of intermittent exotropia involved 65 strabismus specialists from 53 institutions in Korea. Purpose of this study was to present ophthalmologic findings of intermittent exotropia from the KIEMS. Consecutive patients with intermittent exotropia of ≥ 8 prism diopters (PD) at distance or near fixation were included. Best-corrected visual acuity, cycloplegic refraction data, angles of deviation at several cardinal positions, ocular dominance, fusion control, oblique muscle function, and binocular sensory outcomes were collected. A total of 5385 participants (2793 females; age 8.2 years) were included. Non-dominant eye was more myopic than the dominant eye (- 0.60 vs. - 0.47 diopters, P < 0.001). Mean exodeviation angles were 23.5 PD at distance and 25.0 PD at near fixation. Basic type (86.2%) was the most, followed by convergence insufficiency (9.4%) and divergence excess (4.4%) types. Alternating ocular dominance and good fusion control were more common at near than at distance fixation. Good stereopsis at 40 cm was observed in 49.3% in Titmus stereo test (≤ 60 arcsec) and in 71.0% in Randot stereo test (≤ 63 arcsec). Intermittent exotropia was mostly diagnosed in childhood and patients with the condition showed relatively good binocular functions. This study may provide objective findings of intermittent exotropia in a most reliable way, given that the study included a large study population and investigated comprehensive ophthalmology examinations.