Jinu Han

Ophthalmological manifestations in patients with Leigh syndrome

Background To describe the ophthalmological manifestations in patients with childhood onset Leigh syndrome (LS) and investigate the correlation between genotypes and phenotypes in patients with LS. Methods Childhood onset LS was clinically and enzymatically confirmed in a total of 63 patients. Among them, 44 patients who underwent ophthalmologic consultation were included in this study. Patients with LS underwent genotyping for the whole genome of mitochondrial DNA and SURF1 mutations. The clinical demographic and ophthalmologic phenotypes were compared between the good prognosis group and the poor prognosis group. Results Strabismus (40.9%) was the most frequently observed ophthalmologic manifestation, followed by pigmentary retinopathy (22.5%), optic atrophy (22.5%), ptosis (15.9%), and nystagmus (13.6%). Thirteen patients were exotropes and five patients were esotropes. The mean exodeviation was 29.6±12.5 prism dioptres (PD) and the mean esodeviation was 24.0±8.9u2005PD. All patients with esotropia reported disease onset at <1u2005year old. Among 26 patients older than 4u2005years, eight (30.8%) patients had better than 0.4 in the best eye was noted. Eyelid ptosis was a main presenting sign in four patients (9.1%). Among these patients, two patients had m.13513G>A mutation in the MT-ND5 gene. Age at onset was 2.47±2.06u2005years in the good prognosis group and 0.92±0.98u2005years in the poor prognosis group (p=0.002). Serum lactate peak concentration was 3.23±1.36u2005mmol/L in the good prognosis group and 4.54±2.31u2005mmol/L in the poor prognosis group (p=0.051). Conclusions LS is a group of mitochondrial disorders with variable ophthalmologic manifestations, the most frequent being strabismus in this study. Ptosis could be an initial sign in patients with LS and these patients can be easily misdiagnosed as having juvenile myasthenia gravis.

Longitudinal analysis of retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness in ethambutol-induced optic neuropathy.

PurposeThe aim of the study was to evaluate longitudinal analysis of peripapillary retinal nerve fiber layer (RNFL) and perifoveal ganglion cell–inner plexiform layer (GCIPL) thickness in patients being treated with ethambutol (EMB).MethodsThis prospective longitudinal cohort study enrolled 37 patients who were treated with EMB for pulmonary tuberculosis. Best-corrected visual acuity, color vision test, automated perimetry, fundus photography, and RNFL and GCIPL thickness were measured at baseline and at 4xa0and 6xa0months after the start of EMB treatment, using Cirrus optical coherence tomography.ResultsAmong 37 patients, EMB-induced optic neuropathy occurred in one patient (2.7xa0%). In this patient, thickening of the RFNL and thinning of the GCIPL were noted at the onset of symptoms. After discontinuation of EMB, RNFL and GCIPL thickness progressively normalized. Changes in RNFL and GCIPL thickness were not statistically significant in the 36 patients who did not exhibit EMB-induced optic neuropathy-related symptoms during follow-up (all P valuesu2009>u20090.05).ConclusionsThickening of the peripapillary RNFL and thinning of the perifoveal GCIPL is an effective quantitative and early marker for diagnosis of EMB-induced optic neuropathy.

Linezolid-associated optic neuropathy in a patient with drug-resistant tuberculosis.

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Risk factors for consecutive exotropia after esotropia surgery.

PurposeTo evaluate the risk factors in development of postoperative exotropia following bilateral medial rectus (BMR) recession for esotropia.Methods108 patients who underwent BMR recession for esotropia between November 1996 and July 2010 were enrolled. 54 patients who required surgery for consecutive exotropia were compared to 54 controls whose angle of deviation showed less than five prism diopters of esotropia at all periods after BMR recession. Amblyopia, dissociated vertical deviation (DVD), refractive error, inferior oblique overaction, and multiple surgery history were evaluated as risk factors for the development of consecutive exotropia. The postoperative changes of angle of deviation were calculated.ResultsAmblyopia was found in 27 patients (50.5xa0%) in the exotropia group, and in six patients (11.1xa0%) in the control group (Pxa0<xa00.001) before esotropia surgery. DVD was detected in 16 (29.06xa0%) patients in the exotropia group as compared to 4 (7.4xa0%) in the control group (Pxa0=xa00.003). With logistic regression analysis, the odds ratio of DVD was 5.27 (95xa0% CI 1.63–17.03; Pxa0=xa00.006) and of amblyopia, 8.00 (95xa0% CI 2.94–21.80; Pxa0<xa00.001). There were no significant differences between the two groups with regards to the pre-operative deviation, follow up periods, degree of hyperopia, presence of anisometropia or inferior oblique overaction, and history of multiple surgery. Using linear mixed model analysis, the exotropic shift across time was higher in the consecutive exotropia group relative to the controls (Pxa0<xa00.001).ConclusionsThe presence of amblyopia before esotropia surgery and DVD correlated with risk of consecutive exotropia.

Real Stereopsis Test Using a Three-Dimensional Display with Tridef Software

Purpose To investigate horizontal image disparity in three-dimensional (3-D) perception using 3-D animations in normal control patients and patients with intermittent exotropia, anisometropic amblyopia, and partially accommodative esotropia. Materials and Methods A total of 133 subjects were included. Stereopsis was measured using the Titmus Stereo test (Stereo Optical Inc., Chicago, IL, USA) and a 3-D stereopsis test with a 15 inch 3-D display laptop, adjusting 3-D parameters of 0 mm horizontal disparity to 15 mm horizontal disparity. Results When compared with normal controls, the average threshold of the 3-D stereopsis test was significantly reduced for esotropia patients (p<0.001) and for anisometric amblyopia patients (p<0.001), compared to normal controls. No significant difference was observed between normal controls and intermittent exotropia patients (p=0.082). The 3-D stereopsis test was correlated with the Titmus Stereo test (Spearmans rho=0.690, p<0.001). Mean difference in stereoacuity was 1.323 log seconds of arc (95% limits of agreement: 0.486 to 2.112), and 125 (92.5%) patients were within the limits of agreement. Conclusion This study demonstrated that a 3-D stereopsis test with animation is highly correlated with the Titmus Stereo test; nevertheless, 3-D stereopsis with animations generates more image disparities than the conventional Titmus Stereo test. The 3-D stereopsis test is highly predictive for estimating real stereopsis in a 3-D movie theater.

Recurrent Bilateral Retinal Vasculitis as a Manifestation of Post-streptococcal Uveitis Syndrome

We report a case of post-streptococcal uveitis mainly presenting with bilateral recurrent retinal vasculitis in Korea. A 14-year-old Asian female presented with decreased visual acuity of 20 / 30 in the right eye and 20 / 25 in the left eye. The patient had a history of glomerulonephritis nine months before onset of uveitis. The manifestation of uveitis was predominantly retinal vasculitis. We presumed post-streptococcal uveitis because probable streptococcal infection was confirmed by anti-streptolysin O titer elevation. With topical and oral steroid treatments, the patient experienced complete vision recovery. Post-streptococcal uveitis occurs rarely and mostly involves young patients in the form of non-granulomatous anterior uveitis. However, as this case shows, it may primarily involve the posterior uvea without anterior inflammation and may recur.

Transient neonatal myasthenia gravis due to a mother with ocular onset of anti-muscle specific kinase myasthenia gravis

We describe a 27-year-old pregnant female with new onset of conjugate gaze deficit during the third trimester of pregnancy. Repetitive nerve stimulation tests, neostigmine tests, and acetylcholine receptor antibody assays were all negative. The patient delivered a normal healthy baby at a local clinic via cesarean section. The baby became hypotonic and had respiratory failure several minutes after birth. The result of acetylcholine receptor antibody was negative in the neonate. The neonate became healthy spontaneously and was extubated after 21 days of ventilation care. Two months after delivery, the mother developed ptosis and generalized symptoms and subsequent workup revealed she was muscle specific kinase (MuSK) antibody positive. The neonate was presumed to have an anti-MuSK-mediated transient neonatal myasthenia gravis. Although MuSK antibody testing is rarely indicated in ocular myasthenia gravis, MuSK antibody testing is necessary in pregnant women who are presumed ocular myasthenia gravis to warn occurrence of transient neonatal myasthenia gravis.

Accuracy of Next-Generation Sequencing for Molecular Diagnosis in Patients With Infantile Nystagmus Syndrome

Importance Infantile nystagmus syndrome (INS) is a group of disorders presenting with genetic and clinical heterogeneities that have challenged the genetic and clinical diagnoses of INS. Precise molecular diagnosis in early infancy may result in more accurate genetic counseling and improved patient management. Objective To assess the accuracy of genomic data from next-generation sequencing (NGS) and phenotypic data to enhance the definitive diagnosis of INS. Design, Setting, and Participants A single-center retrospective case series was conducted in 48 unrelated, consecutive patients with INS, with or without associated ocular or systemic conditions, who underwent genetic testing between June 1, 2015, and January 31, 2017. Next-generation sequencing analysis was performed using a target panel that included 113 genes associated with INS (nu2009=u200947) or a TruSight One sequencing panel that included 4813 genes associated with known human phenotypes (nu2009=u20091). Variants were filtered and prioritized by in-depth clinical review, and finally classified according to the American College of Medical Genetics and Genomics guidelines. Patients underwent a detailed ophthalmic examination, including electroretinography and optical coherence tomography, if feasible. Main Outcomes and Measures Diagnostic yield of targeted NGS testing. Results Among the 48 patients (21 female and 27 male; mean [SD] age at genetic testing, 9.2 [10.3] years), 8 had a family history of nystagmus and 40 were simplex. All patients were of a single ethnicity (Korean). Genetic variants that were highly likely to be causative were identified in 28 of the 48 patients, corresponding to a molecular diagnostic yield of 58.3% (95% CI, 44.4%-72.2%). FRMD7, GPR143, and PAX6 mutations appeared to be the major genetic causes of familial INS. A total of 10 patients (21%) were reclassified to a different diagnosis based on results of NGS testing, enabling accurate clinical management. Conclusions and Relevance These findings suggest that NGS is an accurate diagnostic tool to differentiate causes of INS because diagnostic tests, such as electroretinography and optical coherence tomography, are not easily applicable in young infants. Accurate application of NGS using a standardized, stepwise, team-based approach in early childhood not only facilitated early molecular diagnosis but also led to improved personalized management in patients with INS.

Obstructive Sleep Apnea in Patients with Branch Retinal Vein Occlusion: A Preliminary Study.

Purpose Our study aimed to determine whether obstructive sleep apnea (OSA) is common among branch retinal vein occlusion (BRVO) patients without systemic risk factors using a Watch PAT-100 portable monitoring device. Methods The study participants included consecutive patients with BRVO of less than 3 months duration without any risk factors known to be associated with OSA (diabetes, coronary artery disease, stroke, hematologic diseases, autoimmune disease, etc.) except for hypertension. All patients underwent full-night unattended polysomnography by means of a portable monitor Watch PAT-100 device. The apnea-hypopnea index (AHI) was calculated as the average number of apnea and hypopnea events per hour of sleep, and an AHI score of five or more events was diagnosed as OSA. Results Among 19 patients (6 males and 13 females), 42.1% (8 of 19) had an AHI reflective of OSA. In the 13 patients who had no concurrent illness, including hypertension, 30.8% (4 of 13) had positive test results for OSA; three of these patients were ranked as mild OSA, while one had moderate OSA. The OSA group had an average AHI of 12.3 ± 7.8, and the average AHI was 2.0 ± 0.9 in the non-OSA group. Although it was not statistically proven, we found that OSA patients experienced a more severe form of BRVO. Conclusions We found a higher than expected rate of OSA in BRVO patients lacking concomitant diseases typically associated with OSA. Our findings suggest that OSA could be an additional risk factor in the pathogenesis of BRVO or at least a frequently associated condition that could function as a triggering factor.

Changes in fusional vergence amplitudes after laser refractive surgery for moderate myopia

Purpose To analyze the effect of bilateral laser refractive surgery on fusional vergence amplitude and near point convergence in normal orthotropic myopic patients. Setting Cornea and refractive private practice, Seoul, South Korea. Design Prospective observational study. Methods Moderately myopic patients (2.0 to 6.0 diopters [D]) had bilateral laser refractive surgery with postoperative follow‐ups at 1 week and 1 and 3 months. Patients with manifest strabismus, previous strabismus surgery, amblyopia, absent or impaired binocularity, or planned monovision were excluded. The preoperative and postoperative examinations included uncorrected and corrected visual acuities; a prism cover test; evaluation of the convergence, divergence, and vertical fusion amplitude using a rotary prism; and near point convergence. Results The mean age of the 30 patients was 29 years ± 4 (SD). The mean preoperative refractive error was −4.10 ± 1.32 D in right eyes and −4.14 ± 1.37 D in left eyes. The convergence amplitude at near decreased 1 week and 1 month postoperatively, after which it progressively stabilized to near preoperative values. The convergence amplitude at far (break point) was not changed postoperatively; however, the convergence amplitude at far (recovery point) was increased at 1 month and 3 months (P=.008 and P=.003, respectively). There was a slight increase in near point convergence at 3 months (P<.001). Conclusions Although fusional vergence amplitudes at near and near point convergence changed after laser refractive surgery, the changes observed were small or transient. However, patients with latent phoria or strabismus should be warned before having refractive surgery. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.