Recurrence-Independent Progressive Inner-Retinal Thinning After Optic Neuritis: A Longitudinal Study.

BACKGROUND: Longitudinal changes in the inner retina in patients with optic neuritis (ON) may be helpful in monitoring patients and determining maintenance treatment. The aim of this study was to investigate longitudinal changes in the inner retina after subsiding of acute demyelinating ON and to identify the factors associated with such changes. METHODS: In this multicenter retrospective observational study, we reviewed the medical records of 77 patients with ON, including 23 with neuromyelitis optica spectrum disorder with aquaporin 4 (AQP4)-immunoglobulin G (IgG) (AQP4 group), 23 with myelin oligodendrocyte glycoprotein (MOG)-antibody-associated disease (MOG group), 18 with multiple sclerosis (MS group), and 13 with idiopathic ON (iON group). We measured the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell-inner plexiform layer (mGCIPL) using optical coherence tomography (OCT) at baseline and at follow-up examinations (mean follow-up duration, 29.6 ± 8.6 months; mean number of OCT, 4.2 ± 1.2) in the absence of ON recurrence. RESULTS: The estimated rate of pRNFL thinning in the AQP4, MOG, MS, and iON groups was 0.66 (95% confidence interval, 0.35-0.97), 0.35 (0.04-0.66), 0.53 (0.16-0.90), and 0.25 (-0.18 to 0.68) µm/year, respectively, indicating that, in the iON group in contrast to the other groups, there was no significant decrease of pRNFL thickness. Among the AQP4, MOG, and MS groups, there was no significant difference in the rate of pRNFL thinning (P = 0.560). The rate of mGCIPL thinning in the AQP4 and MOG groups was 0.25 (0.04-0.46) µm/year and 0.38 (0.23-0.53) µm/year, respectively. Meanwhile, the rate of mGCIPL change in the MS and iON groups was 0.04 (-0.12 to 0.19) and 0.00 (-0.17 to 0.16) µm/year, respectively, which indicates that there was no significant mGCIPL thinning in the latter 2 groups. Between the AQP4 and MOG groups, meanwhile, the rate of mGCIPL change did not significantly differ (P = 0.295). Age older than 40 years was associated with significant progression of mGCIPL thinning (P = 0.005). CONCLUSIONS: We noted inner retina thinning progression independent of relapse activity in AQP4-ON, MOG-ON, and MS-ON. Because subclinical neuroaxonal damage continues to be incurred after an acute attack of ON subsides despite suppression of new attacks, long-term follow-up and neuroprotection should be considered to be integral to the treatment of patients with ON.

Novel Variant of FDXR as a Molecular Etiology of Postlingual Post-synaptic Auditory Neuropathy Spectrum Disorder via Mitochondrial Dysfunction: Reiteration of the Correlation between Genotype and Cochlear Implantation Outcomes.

OBJECTIVES: FDXR encodes mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. To date, only two studies have described FDXR-related hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiological mechanisms remain incompletely understood. Here we report a hearing-impaired individual with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiological mechanism of adult-onset ANSD involving mitochondrial dysfunction. METHODS: A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and a functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically evoked compound action potential (ECAP) responses were measured, and the mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. RESULTS: In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP levels, reduced mitochondrial membrane potential, and increased reactive oxygen species levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is post-synaptic. As a result of increasing the pulse width during mapping, the patient's CI outcomes showed significant improvement over 1-year post-CI. CONCLUSION: A novel FDXR variant associated with mitochondrial dysfunction and post-synaptic ANSD was first identified in a Korean individual. Additionally, 1-year post-CI outcomes were reported for the first time in the literature. Excellent audiologic. RESULTS: were obtained, and our. RESULTS: reiterate the correlation between genotype and CI outcomes in ANSD.

Poor visual prognosis of Asian patients with 3460 mitochondrial DNA mutation in Leber's hereditary optic neuropathy.

BACKGROUND: Among the 3 primary mutations of Leber's hereditary optic neuropathy (LHON), the incidence of LHON with a mutation at nucleotide position 3460 is the lowest in Asians. Therefore, information about the clinical manifestations of LHON mutations in Asians with the 3460 mutation is limited. OBJECTIVE: To determine the clinical manifestations including visual prognosis of Asians with the LHON 3460 mutation. METHODS: We performed a retrospective study of 5 Korean LHON patients with the 3460 mutation. RESULTS: All patients were male, and the age of onset for visual impairment varied from 17 to 35 years, with an average of 25.4 ± 7.16 years. Among the 10 affected eyes, only 1 eye of 1 patient showed visual improvement to 20/50 at 2 years after onset. The remaining patients had a visual acuity of worse than 20/200. CONCLUSION: The visual prognosis of Korean patients with the LHON 3460 mutation was generally poor. Further studies regarding Asian patients with the LHON 3460 mutation are necessary.

Self-Reported Findings of the Korean Intermittent Exotropia Multicenter Study Questionnaire.

PURPOSE: To determine subjective symptoms and medical history of patients with intermittent exotropia in a large study population. METHODS: The Korean Intermittent Exotropia Multicenter Study (KIEMS) is a nationwide, observational, cross-sectional, multicenter study conducted by the Korean Association for Pediatric Ophthalmology and Strabismus including 5,385 patients with intermittent exotropia. Subjective symptoms and medical history of patients with intermittent exotropia were extracted by a comprehensive survey based on a self-administered questionnaire according to the study protocol of the KIEMS. RESULTS: The mean age of symptom onset was 5.5 years. The most common symptom reported in patients with intermittent exotropia was photophobia (52.1%), followed by diplopia at near fixation (7.3%) and distance fixation (6.2%). Preterm birth was found in 8.8%, and 4.1% had perinatal complications. A family history of strabismus was present in 14.9%, and 5.5% of patients had a family member who underwent strabismus surgery. CONCLUSIONS: The KIEMS is one of the largest clinical studies on intermittent exotropia. Intermittent exotropia frequently caused photophobia and diplopia, and patients with a family history was not uncommon.

Mitochondrial DNA mutations in Korean patients with Leber's hereditary optic neuropathy.

In order to explore the spectrum of mitochondrial DNA (mtDNA) mutations in Korean patients with Leber's hereditary optic neuropathy (LHON), we investigated the spectrum of mtDNA mutations in 145 Korean probands confirmed with the diagnosis of LHON. Total genomic DNA was isolated from the peripheral blood leukocytes of the patients with suspected LHON, and mtDNA mutations were identified by direct sequencing. Analysis of mtDNA mutations revealed seven primary LHON mutations including the nucleotide positions (nps) 11778A (101 probands, 69.2%), 14484C (31 probands, 21.2%), 3460A (5 probands, 3.4%), and G3635A, G3733A, C4171A, and G13051A mutations in one proband each. In addition, two provisional mtDNA mutations at nps T3472C, and G13259A were each found in one proband, respectively. Another provisional mtDNA mutation at np T3394C was found in two probands. In conclusion, the spectrum of mtDNA mutations in Korean patients with LHON may differ from other ethnicities, which is characterized by high prevalence of 11778A and 14484C mutations, and a low prevalence of the 3460A mutation.

Etiological distribution of isolated oculomotor nerve palsy: analysis of 633 patients and literature review.

BACKGROUND AND PURPOSE: The etiological distribution of oculomotor nerve palsy has varied amongst the studies. This study aimed to define the clinical features and underlying etiologies of isolated oculomotor nerve palsy by recruiting patients from all departments in a referral-based university hospital. METHODS: The medical records of 672 patients who had a confirmed diagnosis of isolated oculomotor nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020 were reviewed. A proportion of the etiology of isolated oculomotor nerve palsy was also compared with that of patients pooled from the previous studies that were searched on PubMed in May 2022. RESULTS: The most common etiology was microvascular (n = 168, 26.5%), followed by vascular anomalies (n = 110, 17.4%), neoplastic (n = 86, 13.6%), inflammatory (n = 79, 12.5%), idiopathic (n = 60, 9.5%) and traumatic (n = 53, 8.4%). Neurologists were mainly involved in the management of microvascular and inflammatory oculomotor nerve palsies whilst ophthalmologists mainly participated in the care of idiopathic, neoplastic and traumatic palsies. Neurosurgeons mostly took care of oculomotor nerve palsy due to vascular anomalies. CONCLUSIONS: The proportion of etiologies of isolated oculomotor nerve palsy may differ according to the specialties involved in the management. The results of previous studies on the etiological distribution of isolated oculomotor nerve palsy should be interpreted with this consideration.

Efficacy of 3D-printed eye model to enhance retinoscopy skills.

We conducted a prospective study to evaluate the efficacy of simulation-based education using a three-dimensional (3D)-printed schematic eye model in improving the retinoscopy refraction skills of medical students. A schematic eye model was printed using a fused deposition modeling-based 3D printer. Twenty medical students randomized into 3D (n = 10) and control (n = 10) groups received a 1-h lecture on the principles and methods of manifest refraction and were shown how to use the retinoscope and sciascope bars. The 3D group additionally attended a tutorial on the schematic eye. Both groups performed refractive examinations on four eyes of volunteer patients, and the results were recorded as a baseline. Instructor feedback and refraction practice was provided with the 3D group or with control group. To account for subject fatigue, patients spent no more than 8 min on the examination. After a 1-h break to allow for fatigue and familiarity, refraction tests were repeated on four randomly selected eyes of patients. Students' refraction readings were compared with the autorefractor values using a spherical equivalent value and blur strength. All participants measured the time required to complete the refraction test and reported their subjective confidence in the results of each refraction test. Refractive errors before and after training did not differ between the control and 3D groups, with a significant improvement in errors observed in both groups (p = 0.005 and 0.008, respectively). The time to complete refraction before and after training did not differ between the two groups, both of which showed a significant reduction in time (p = 0.005 and 0.028, respectively). Pre- and post-training confidence scores for the accuracy of each refraction on a 10-point Likert scale were not significantly different. However, when comparing score changes between pre- and post-training, only the control group showed a significant increase in confidence (p = 0.005). Tests for the non-inferiority of refractive errors after training indicated that the 3D group was non-inferior to the control group. In conclusion, training in retinoscopy refraction skills using a 3D-printed eye model resulted in significant improvement in accuracy and speed compared to practice with real patients. Except for better confidence in the control group, schematic eye model training was not inferior to practice with real patients.

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.

Etiologic distribution of isolated abducens nerve palsy: Analysis of 807 patients and literature review.

BACKGROUND AND PURPOSE: The etiologies of abducens nerve palsy have shown a large variability among studies. This study aimed to establish the clinical features and underlying etiologies of isolated abducens nerve palsy by recruiting patients from all departments in a referral-based university hospital. METHODS: We reviewed the medical records of 807 patients with a confirmed diagnosis of isolated abducens nerve palsy at all departments of Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. We also compared the proportion of etiology with that of the patients pooled from the previous studies. RESULTS: The most common etiology was microvascular (n = 296, 36.7%), followed by idiopathic (n = 143, 17.7%), neoplastic (n = 115, 14.3%), vascular anomalies (n = 82, 10.2%), inflammatory (n = 76, 9.4%), and traumatic (n = 35, 4.3%). Patients were mostly managed by ophthalmologists (n = 576, 71.4%), followed by neurologists (n = 479, 59.4%), emergency physicians (n = 278, 34.4%), neurosurgeons (n = 191, 23.7%), and others (n = 72, 8.9%). The proportion of etiology significantly differed according to the age and sex of the patients and the specialties involved in the management (p < 0.001). Compared to the pooled data from the previous reports, the current study showed a higher prevalence of microvascular cause but a lower occurrence of traumatic and neoplastic causes. CONCLUSIONS: The results of previous studies on etiologic distribution of isolated abducens nerve palsy should be interpreted with consideration of the demographic features of patients recruited and the specialties involved.

Long-Term Efficacy of Inferior Oblique Myectomy Accompanied with Tenon's Capsule Closure: Objective Analysis Using Nine-Gaze Photographs.

Background: The aim is to evaluate the long-term efficacy of inferior oblique (IO) myectomy combined with Tenon's capsule closure to prevent muscle reattachment to the sclera. Methods: We retrospectively reviewed the medical records of 18 patients with primary and secondary IO overaction who underwent IO myectomy accompanied by Tenon's capsule closure. Patients were followed up for at least 1 year after the surgery. The main outcome measures included oblique muscle dysfunction, which was objectively graded through computerized analysis of nine-gaze photographs, and the amount of vertical deviation in the primary position using alternate prism cover testing. Results: After a mean follow up of 2.5 years, the grade of IO overaction decreased from +2.2 ± 1.0 to -0.8 ± 1.0 (p < 0.001). In patients with secondary IO overaction with superior oblique (SO) palsy, SO underaction improved from -2.2 ± 1.5 to -0.2 ± 1.8 (p = 0.006). Successful vertical deviation in the primary position of seven prism diopters or less was achieved in 83.3% of the patients. Underaction of the IO was observed in 11.1% of patients, whereas none of the patients showed antielevation syndrome. Conclusion: IO myectomy combined with Tenon's capsule closure might be safe and effective for the treatment of primary and secondary IO overaction in the long term.

Diplopia: characteristics and etiologic distribution in a referral-based university hospital.

BACKGROUND AND OBJECTIVES: The etiologic distribution and clinical features of diplopia may differ according to the specialties involved in the management. This study aimed to establish the clinical features and underlying etiologies of diplopia by recruiting patients from all departments. METHODS: We reviewed the medical records of 4127 patients with diplopia as the chief complaint, who had been recruited from all departments at Seoul National University Bundang Hospital, Seongnam, Republic of Korea, from 2003 to 2020. RESULTS: Diplopia was binocular in 3557 (94.2%) and monocular in 219 (5.8%) patients. The common causes of binocular diplopia included microvascular (n = 516, 14.5%), strokes (n = 412, 11.6%), neoplastic (n = 304, 8.5%), myasthenia gravis (n = 253, 7.1%), traumatic (n = 240, 6.7%), and decompensated phoria (n = 232, 6.5%), and comprised more than a half of the causes. Patients with binocular diplopia were usually managed by neurologists (2549/3557, 71.7%), followed by ophthalmologists (2247/3557, 63.2%), emergency physicians (1528/3557, 43.0%), neurosurgeons (361/3557, 10.1%), and others (271/3557, 7.6%). The etiologies of binocular diplopia differed markedly according to the patients' age and the specialties involved in the management (p < 0.001). CONCLUSIONS: Given the differences in the etiologic distribution of diplopia according to the patients' age and the specialties involved in the management, the results of previous reports on the characteristics and etiology of diplopia, primarily performed in a single specialty department, should be interpreted with a possible selection bias.

Integration of Artificial Intelligence into the Approach for Diagnosis and Monitoring of Dry Eye Disease.

Dry eye disease (DED) is one of the most common diseases worldwide that can lead to a significant impairment of quality of life. The diagnosis and treatment of the disease are often challenging because of the lack of correlation between the signs and symptoms, limited reliability of diagnostic tests, and absence of established consensus on the diagnostic criteria. The advancement of machine learning, particularly deep learning technology, has enabled the application of artificial intelligence (AI) in various anterior segment disorders, including DED. Currently, many studies have reported promising results of AI-based algorithms for the accurate diagnosis of DED and precise and reliable assessment of data obtained by imaging devices for DED. Thus, the integration of AI into clinical approaches for DED can enhance diagnostic and therapeutic performance. In this review, in addition to a brief summary of the application of AI in anterior segment diseases, we will provide an overview of studies regarding the application of AI in DED and discuss the recent advances in the integration of AI into the clinical approach for DED.

Characteristics of Optic Neuritis in South Korean Children and Adolescents: A Retrospective Multicenter Study.

Purpose: To analyze the clinical characteristics and prognosis of optic neuritis (ON) in pediatric patients aged <19 years in South Korea. Methods: This multicenter retrospective cohort study included 127 pediatric patients (median age: 10.3 (IQR: 7.3-14.2) years; female, 62.2%) who experienced ON for the first time between January 2004 and January 2018, with data obtained from five tertiary university-based hospitals in Korea. When ON was bilateral, the worse eye was selected for analysis. The baseline clinical characteristics and prognoses of patients, as well as the associations between these parameters, were analyzed. Results: The baseline clinical characteristics of the patients were as follows: best-corrected visual acuity (BCVA) < 20/200, 65.9%; pain on eye movement, 47.2%; optic disc swelling, 66.9%; and bilateral involvement, 41.7%. Among 101 patients who were followed up for ≥6 months, 48 (47.5%), 12 (11.9%), 19 (18.8%), 13 (12.9%), and 9 (8.9%) had been diagnosed with isolated ON, recurrent ON, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and acute disseminated encephalomyelitis (ADEM)-related ON, respectively. At the latest visit, 81.9% and 71.1% had achieved BCVA of ≥20/40 and ≥ 20/25, respectively. Only disc swelling at presentation was associated with poor baseline BCVA (coefficient: 0.31, P=0.004) and greater improvement in BCVA (coefficient: 0.49, P = 0.001P=0.001); there were no significant associations between the baseline factors and final BCVA. Conclusions: This study demonstrated pediatric ON-related clinical characteristics and visual outcomes in South Korea. Within this cohort, in about 40.6% of patients, ON was associated with other demyelinating diseases, namely, MS, NMOSD, and ADEM.

Etiologic distribution of isolated trochlear palsy: Analysis of 1020 patients and literature review.

BACKGROUND AND PURPOSE: Trochlear palsy is the most common cause of vertical diplopia. The etiologies of trochlear palsy have shown a large discrepancy among studies. This study aimed to establish the clinical features and underlying etiologies of isolated trochlear palsy by recruiting the patients from all departments in a referral-based university hospital. METHODS: We reviewed the medical records of 1258 patients who had a confirmed diagnosis of isolated trochlear palsy at all departments of Seoul National University Bundang Hospital, Seongnam, South Korea, from 2003 to 2020. We also compared the proportion of etiologies with that of the patients pooled from previous studies. RESULTS: The most common etiology was congenital (n = 330, 32.4%), followed by idiopathic (n = 256, 25.1%), microvascular (n = 212, 20.8%), and traumatic (n = 145, 14.2%). These four etiologies explained 92.5% of isolated trochlear palsy. Patients were mostly managed by ophthalmologists (n = 841, 82.5%), followed by neurologists (n = 380, 37.3%), emergency physicians (n = 197, 19.3%), neurosurgeons (n = 75, 7.4%), and others (n = 18, 1.8%). The etiologic distribution of isolated trochlear palsy in the current study did not differ from that of 2664 patients pooled from the previous studies. CONCLUSIONS: The proportion of etiologies of isolated trochlear palsy differs according to the age ranges of the patients and specialties involved in the management. The etiologic distribution of isolated trochlear palsy in the current study was comparable to the pooled result of previous reports.

Automated Mathematical Algorithm for Quantitative Measurement of Strabismus Based on Photographs of Nine Cardinal Gaze Positions.

This study presents an automated algorithm that measures ocular deviation quantitatively using photographs of the nine cardinal points of gaze by means of deep learning (DL) and image processing techniques. Photographs were collected from patients with strabismus. The images were used as inputs for the DL segmentation models that segmented the sclerae and limbi. Subsequently, the images were registered for the mathematical algorithm. Two-dimensional sclera and limbus were modeled, and the corneal light reflex points of the primary gaze images were determined. Limbus recognition was performed to measure the pixel-wise distance between the corneal reflex point and limbus center. The segmentation models exhibited high performance, with 96.88% dice similarity coefficient (DSC) for the sclera segmentation and 95.71% DSC for the limbus segmentation. The mathematical algorithm was tested on two cranial nerve palsy patients to evaluate its ability to measure and compare ocular deviation in different directions. These results were consistent with the symptoms of such disorders. This algorithm successfully measured the distance of ocular deviation in patients with strabismus. With complementation in the dimension calculations, we expect that this algorithm can be used further in clinical settings to diagnose and measure strabismus at a low cost.