Interobserver and Intra-Observer Reliability of Eyelid Tests for Ocular Myasthenia Gravis.

BACKGROUND: Lid fatigability test (LFT), Cogan lid twitch (CLT), and forced eyelids closure test (FECT) are simple clinical screening tests for ocular myasthenia gravis (OMG). However, these tests are subjectively interpreted. We thus evaluated the interobserver and intra-observer reliability of each test. METHODS: The 3 eyelid tests were performed in ptotic patients associated with various conditions, including OMG and others. Video clips of all tests were recorded using smartphone with built-in camera in the following order; LFT, CLT, and FECT. All video clips were distributed to 3 neuro-ophthalmologists and 3 general ophthalmologists, who were trained to evaluate the tests using a single standard instruction. After 3 months, all video clips were re-organized for the second evaluation. Interobserver and intra-observer reliability were calculated using Cohens' Kappa coefficient and Fleiss Kappa statistic. RESULTS: The 3 eyelid tests were performed and recorded in 35 patients, which included the diagnosis of OMG, levator muscle dehiscence, partial oculomotor nerve palsy, and Horner syndrome. CLT received moderate-to-substantial interobserver reliability in neuro-ophthalmologist group (Fleiss Kappa 0.77 [95% CI 0.60-0.94] and 0.66 [95% CI 0.46-0.85] in first and second evaluation respectively), but the results varied in general ophthalmologist group (Fleiss Kappa 0.58 [95% CI 0.37-0.79] and 0.54 [95% CI 0.33-0.76] in first and second evaluation respectively). FECT and LFT received lower interobserver reliability in both groups. CLT also received moderate-to-almost perfect intra-observer reliability in neuro-ophthalmologist group (Cohen Kappa 0.55, 0.58, and 0.92), whereas FECT and LFT received lower intra-observer reliability. The intra-observer reliability varied among general ophthalmologists for all 3 eyelid tests. CONCLUSIONS: CLT is the most reliable test among the 3 eyelid tests. However, all tests should be interpreted with caution by general ophthalmologists.

Validity of Forced Eyelid Closure Test: A Novel Clinical Screening Test for Ocular Myasthenia Gravis.

BACKGROUND: Forced eyelid closure test (FECT) is a clinical screening test developed from the original Cogan lid twitch (CLT) sign to assist in the diagnosis of ocular myasthenia gravis (OMG), We evaluated the sensitivity and specificity of FECT compared with CLT and benchmarked to standard diagnostic tests. METHODS: This study was a retrospective chart review of 48 patients using electronic medical records of those that presented with ptosis and/or diplopia at Doheny Eye Institute, University of California, Los Angeles between February 2015 and April 2016. Patients without FECT testing were excluded. FECT and CLT results, and final diagnosis were recorded. To perform FECT, the patient was asked to squeeze his or her eyelids shut for 5-10 seconds then open quickly and fixate in primary position. The excessive upward overshoot of eyelids movement indicated a positive FECT. The test was performed by a neuro-ophthalmologist before establishing the diagnosis. Patients who had equivocal test results and/or inconclusive final diagnosis were excluded. RESULTS: Of the 48 patients studied, 18 patients (37.5%) had positive FECT; 15 of whom had a final diagnosis of OMG (83.3%). Of the 30 patients with negative FECT, 1 had OMG (3.3%). Of the 48 patients, 35 patients also had a documented CLT result (72.9%). CLT was positive in 11 of these 35 patients (31.4%), and 9 of these 11 had OMG (81.8%). Of the 24 patients with negative CLT, 2 of them had OMG (8.3%). Sensitivity and specificity of FECT were 94% and 91% (joint 95% confidence region: sensitivity × specificity = [0.70, 1] × [0.75, 1]). The relative true-positive fraction (rTPF) between FECT and CLT was 1.15; the relative false-positive fraction was 1.31. CONCLUSIONS: FECT is a simple clinical screening test with good sensitivity and specificity for OMG.

Syphilitic Optic Neuropathy: Re-emerging Cases Over a 2-Year Period.

We report 7 cases of syphilitic optic neuropathy during a 2-year period. All patients were newly diagnosed with human immunodeficiency virus (HIV) infection. Six cases (86%) initially presented with swollen optic disc either unilaterally or bilaterally. Blind spot enlargement was the most common type of visual field defect. Final visual acuity of at least 20/25 was achieved together with visual field improvement and resolution of swollen optic disc. Optic nerve involvement can be the first manifestation of syphilis and HIV co-infection. Syphilitic optic neuropathy has an excellent prognosis if the disease diagnosed promptly and treated properly.

Trauma-Associated Leber Hereditary Optic Neuropathy.

A 19-year-old man developed visual loss in the left eye 1 day following a martial arts kick to the head. Vision worsened over a week, when visual loss was noted in the right eye without further trauma. The fundus was initially normal, but visual field testing showed temporal depression right eye with diffuse depression left eye, and traumatic chiasmopathy was suspected. Magnetic resonance imaging (MRI) of the brain demonstrated an enlarged chiasm with intrinsic signal abnormality, but no enhancement. Treatment with intravenous corticosteroids and hyperbaric oxygen therapy did not result in visual improvement. Ancillary testing for atypical optic neuritis was negative, but testing for LHON was positive for the 11778 mutation. This case raises the question of trauma as a precipitating factor for LHON and illustrates the rare occurrence of intrinsic signal abnormalities of the chiasm in this disorder.

Disagreement of Radial Peripapillary Capillary Density Among Four Optical Coherence Tomography Angiography Devices.

Purpose: This prospective study evaluated the agreement among four optical coherence tomography angiography (OCTA) devices in the assessment of radial peripapillary capillary (RPC) density. Methods: The study included 48 eyes of 48 subjects (14 healthy, 19 glaucomatous, and 15 non-glaucomatous optic neuropathy). Each participant was scanned using four OCTA devices in a random sequence: RTVue XR Avanti (RTVue), DRI OCT Triton (Triton), Revo NX 130 (Revo), and PLEX Elite 9000 (PlexE). All 6 × 6-mm grayscale OCTA images from each device were analyzed for RPC density using a customized algorithm. Agreement between each pair of devices was assessed using intraclass correlation coefficients (ICCs) and Bland-Altman plots. Results: There was a poor correlation between devices in all comparisons (RTVue-Triton, ICC = 0.34; RTVue-Revo, ICC = 0.31; RTVue-PlexE, ICC = 0.28; Triton-Revo, ICC = 0.31; Triton-PlexE, ICC = 0.17; Revo-PlexE, ICC = 0.34). Significant proportional biases (P < 0.05) and wide limits of agreement with apparent constant biases were identified in all comparisons. The mean difference was greatest for the RTVue-Revo pair (-49.3%; 95% confidence interval [CI], -52.9 to -45.8) and smallest for the Triton-PlexE pair (-7.7%; 95% CI, -10.1 to -5.3). Conclusions: The RPC densities obtained from each device had poor inter-device agreement and significant biases and cannot be used interchangeably. Translational Relevance: RPC density obtained from different OCTA devices is not interchangeable; thus, the progression of optic neuropathy should be monitored using the same OCTA device.

Changes in Ocular Biomarkers from Normal Cognitive Aging to Alzheimer's Disease: A Pilot Study.

Purpose: To identify ophthalmic findings in Alzheimer's type dementia (ATD) compared to normal subjects. Patients and Methods: This comparative descriptive study included participants from the institution's cognitive fitness center. Complete ophthalmic examinations were performed. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used to analyze retinal thickness and vascular density. The Ocular Surface Disease Index (OSDI) score and tear breakup time (TBUT) were used to assess dry eye. The blink rate was counted by a well-trained observer. Cognitive function was evaluated using the Thai Mental State Examination (TMSE) score. Correlation analysis was performed to compare OCT, OCTA parameters, and TMSE. Results: We included 24 ATD patients and 39 normal participants as a control group by age and sex-matched. The prevalence of dry eye using the Asia Dry Eye Society criteria was 15% and 13% in normal and ATD patients, respectively. The differences in OSDI scores, TBUT, and blink rate between the two groups were not statistically significant. The parafoveal and perifoveal macular thickness of the ATD group were significantly lower than that of the control group (p<0.01). All parameters of the vessel density of the ATD group were significantly lower than in the control group, including the whole macular vessel density (p<0.01), optic disc vessel density at the nerve head level (p<0.01), and optic disc vessel density at the radial peripapillary capillary level (p<0.05). After age adjustment, there were no statistically significant differences in all the OCT and OCTA parameters. There was a positive correlation between retinal thickness and vessel density in the macular and optic disc region and TMSE scores. Conclusion: Perifoveal and parafoveal retinal thickness might be more sensitive than peripapillary RNFL thickness to detect neurodegenerative changes in patients with ATD. Macular thickness and vessel density reduction were also positively correlated with cognitive decline.

Health-related quality of life of daily-life-affected benign essential blepharospasm: Multi-center observational study.

PURPOSE: To compare Thais' health-related quality of life (HRQOL) and severity grading, efficacy and safety in daily-life-affected benign essential blepharospasm (BEB) patients at baseline and after Botulinum toxin type A (BTX-A) treatment. DESIGN: Prospective-observational study. PARTICIPANTS: BEB patients with Jankovic rating scale (JRS) at least 3 in both severity and frequency graded from 14 institutes nationwide were included from August 2020 to June 2021. METHODS: Demographic data, HRQOL evaluated by the Thai version of EQ-5D-5L and NEI-VFQ-25 questionnaires, and severity grading score evaluated by Jankovic rating scale (JRS) at baseline, 1, and 3 months after the treatment were collected. The impact of the BTX-A injections and their complications were recorded. RESULTS: 184 daily-life-affected BEB patients were enrolled; 159 patients (86.4%) had complete data with a mean age of 61.40±10.09 years. About 88.05% were female, and 10.1% were newly diagnosed. Most of the patients had bilateral involvement (96.9%) and 12.6% had history of BEB-related accident. After BTX-A treatment, HRQOL improved significantly in 4 dimensions of EQ-5D-5L, except self-care. The EQ_VAS (mean±SD) was 64.54±19.27, 75.13±15.37, 73.8±15.85 (p<0.001) and EQ-5D-5L utility score was 0.748±0.23, 0.824±0.19 and 0.807±0.19 at baseline, 1, 3 months after treatment, respectively. From NEI-VFQ-25, HRQOL also improved in all dimensions, except eye pain. The JRS improved in all patients. Self-reported minor adverse events were 22.6%, which mostly resolved within the first month. CONCLUSION: Daily-life-affected BEB impacted HRQOL in most dimensions from both generic and visual-specific questionnaires. BTX-A treatment not only decreased disease severity, but also improved quality of life.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis with COVID-19 infection: A case report and literature review.

Purpose: To demonstrate the association between SARS-CoV-2 infection and MOG antibody associated optic neuritis. Observations: A 35-year-old Thai woman presented with acute blurred vision of her left eye with pain on eye movement for six days and had dry cough for one week before the onset of visual loss. Her visual acuity was 20/32 in the right eye and counting fingers with a RAPD in the left eye. She had bilateral disc swelling, more prominent on the left eye. A CT scan of the brain and orbits showed swollen optic nerve sheath complex both eyes. Serology test was positive for serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody. Her nasopharyngeal swab for SARS-CoV-2 PCR was also positive. The diagnosis of SARS-CoV-2 associated MOG antibody optic neuritis was made. Conclusions and importance: This case of MOG antibody associated optic neuritis after COVID-19 infection, along with several other cases reported in the literature, suggests that there may be an association between COVID-19 infection and MOG antibody-associated disease. However, larger case-controlled studies are required to confirm this association.

The epidemiology and mutation types of Leber's hereditary optic neuropathy in Thailand.

PURPOSE: Leber's hereditary optic neuropathy (LHON), the most common mitochondrial optic neuropathy, causes visual loss, especially in young adults. Due to the absence of epidemiological data in Southeast Asia, we aimed to determine Thai LHON patients' characteristics (demographic data, mutation types, and prognoses) as the first study in this region. METHODS: This retrospective chart review enrolled all Thai LHON patients confirmed by three mitochondrial DNA mutations (G11778A, T14484C, and G3460A) between January 1997 and December 2016. Patients with more than one year of follow-up were included in a visual progression analysis. The Mann-Whitney U-test was applied to compare groups, and prognosis-associated factors were analysed with the generalized estimating equation. RESULTS: In all, 229 patients were enrolled, with only nineteen females. Most mutations were of the G11778A type (91%), with T14484C accounting for the remainder. The age at onset of G11778A (21.9 years; interquartile range [IQR] 14.9, 33.5) was younger than that of T14484C (33.0 years; IQR 19.4, 37.5). Of 45 patients, the T14484C group demonstrated good vision recovery, whereas the G11778A group did not improve (difference in logMAR -0.7 and IQR -1.5, -0.2 versus logMAR 0.0 and IQR -0.3, 0.2, respectively; P value .001). The G11778A mutation, male, and older age were related to poor prognoses. CONCLUSIONS: The leading mutation in Thai LHON patients is the G11778A missense, followed by T14484C, while G3460A was not detected. The vast majority of patients were young adult males. The G11778A mutation, older age, and male gender are associated with poor vision outcomes. Key messageThe G11778A missense mutation is the most common among Thai LHON patients, followed by T14484C, while G3460A was not found. The G11778A mutation, older age, and male gender are associated with poor vision outcomes.

Complications of Preseptal Versus Pretarsal Botulinum Toxin Injection in Benign Essential Blepharospasm: A Randomized Controlled Trial.

PURPOSE: The purpose of this study was to compare ocular complications and efficacy of preseptal (PST) versus those of pretarsal (PTS) botulinum toxin type A (BoNT-A) therapy in cases of benign essential blepharospasm (BEB). DESIGN: Randomized clinical trial. METHODS: Setting: university hospital. PATIENTS: 24 participants with BEB were enrolled from August 2019 to June 2020. All patients and the outcome evaluator were masked to the injection allocation. INTERVENTIONS: for each participant, 1 eye was randomized to receive PST BoNT-A injection, and the fellow eye received PTS BoNT-A injection of the same amount from a single investigator. At baseline, 1, and 3 months after the injection, we collected the symptoms of tearing, lagophthalmos, ptosis, and diplopia and measured margin-to-reflex distance (MRD) 1 and 2 (mm), degree of lagophthalmos (mm), presence of ectropion, entropion, limitation of ocular motility, tear film breakup time (second), Schirmer's test (mm) , ocular surface staining scores (Oxford's scheme), and Jankovic rating scale of both eyes separately. Main outcome measurements were complications of the injection. RESULTS: There were statistically significant higher rates of self-reported lagophthalmos in PTS (n = 12; 52.17%) than in PST (n = 7; 30.43%) BoNT-A injections (P = .024) and significantly higher estimated measurements of lagophthalmos in PTS (0.59 mm; 95% confidence interval [CI]: 0.44-0.72) than in PST (0.26 mm; 95% CI: 0.12-0.40) injection at 1 month using an interaction model (Bonferroni-corrected P = .001). No significant differences in the efficacy and other complication outcomes between the injection locations were observed. CONCLUSIONS: PTS BoNT-A injection had a higher rate of lagophthalmos than PST BoNT-A injection for BEB.

Factors Affecting Generalization of Ocular Myasthenia Gravis in Patients With Positive Acetylcholine Receptor Antibody.

PURPOSE: To evaluate the associated factors of conversion of ocular myasthenia gravis (OMG) to generalized myasthenia gravis (GMG) among patients with seropositive acetylcholine receptor antibody (AchR Ab). DESIGN: Retrospective cohort study. METHODS: Setting: Retrospective chart review. PATIENT: Seventy-one OMG patients with seropositive AchR Ab presented during July 2009 and December 2016. The exclusion criteria were patients who (1) first presented with GMG, (2) were unable to identify the time of onset of OMG or GMG, (3) were unable to provide information about previous treatments before the onset of GMG, and (4) had incomplete or lost medical records. OBSERVATION PROCEDURE: We collected demographic and clinical characteristics, including onset of OMG and GMG, presence of other autoimmune disorders, history of smoking, presence of thymic abnormalities, and medications received. MAIN OUTCOME MEASURES: Conversion to GMG and time to conversion. RESULTS: Thirty-six patients experienced conversion to GMG. Overall incidence of GMG was 14 (95% confidence interval [CI] 10.09-19.4) per 100 patient-years. Probability of conversion at 2 years was .37 (95% CI .27-.49). Overall median conversion time was 4.97 years. Cox proportional hazard model showed that risk factors were female sex (HR 2.52, 95% CI 1.04-6.10), history of smoking (HR 3.42, 95% CI 1.40-8.45), and thymic abnormalities (HR 1.82, 95% CI 0.91-3.67). Protective factors against conversion to GMG were receiving immunosuppressive agents (HR 0.42, 95% CI 0.19-0.97) and pyridostigmine (HR 0.37, 95% CI 0.14-0.93). CONCLUSIONS: OMG patients with seropositive AchR Ab should be informed that taking pyridostigmine and/or immunosuppressive agents as well as smoking cessation might prevent conversion to GMG.

Clinical and Spectral-Domain Optical Coherence Tomography Appearance of Optic Disc Melanocytoma: A New Classification and Differentiation from Pigmented Choroidal Lesions.

AIMS: The aim of this paper was to compare the features of both the classic, darkly pigmented and the atypical, more lightly pigmented optic disc melanocytoma with those of pigmented choroidal lesions. METHODS: We analyzed the spectral-domain optical coherence tomography (SD-OCT) features of 9 eyes with optic disc melanocytoma and compared them with those of choroidal melanoma and nevus. RESULTS AND CONCLUSION: We identified 2 categories of SD-OCT findings in optic disc melanocytoma: (a) type 1, the typical, prominent, hyperpigmented lesion with SD-OCT findings of a hyperreflective, disorganized overlying retina and a posterior hyporeflective shadow, and (b) the less common, atypical, minimally pigmented type 2 lesion overlaid by a relatively well-organized retina that lacks a posterior hyporeflective shadow. Choroidal lesions were characterized by tumor confined beneath the clearly visible hyperreflective line of the photoreceptor and retinal pigment epithelium, with minimal disorganization of the overlying retina.

Clues from Crouzon: Insights into the potential role of growth factors in the pathogenesis of myelinated retinal nerve fibers.

PURPOSE: We present a case of bilateral extensive peripapillary myelinated retinal nerve fibers (MRNF) in an individual with Crouzon syndrome, an inherited form of craniosynostosis caused by overactivation of fibroblast growth factor receptor 2. As a secondary aim, we examine the utility of optical coherence tomography (OCT) angiography for visualization of peripapillary vasculature obscured by myelination on other imaging modalities. METHODS: A 24-year-old woman with Crouzon syndrome was evaluated for suspected optic neuritis in the right eye. RESULTS: Funduscopic examination and photography revealed the incidental finding of bilateral extensive peripapillary MRNF. OCT angiography provided excellent visualization of peripapillary retinal vessels, which were partially obscured by myelination on other imaging modalities. CONCLUSIONS: This association of Crouzon syndrome with bilateral peripapillary MRNF may lend insight into the developmental control of optic nerve myelination, the pathogenesis of MRNF, and the potential role of growth factors in these processes. Further, OCT angiography allowed for excellent blood vessel visualization in this case of MRNF.

Clinical features and etiology of retinal vasculitis in Northern Thailand.

PURPOSE: To report on the clinical features and etiology of patients with retinal vasculitis (RV). MATERIALS AND METHODS: We reviewed medical records of 47 patients (75 affected eyes) diagnosed with RV. Clinical presentations, ocular complications, associated systemic diseases, and treatment regimens were registered. RESULTS: Etiology of RV included infectious causes in 10/47, (21%) while an association with systemic and/or ocular non-infectious disorders was noted in 22/47 (47%). Eales' disease and Behcet's disease represented the most common clinical entities in non-infectious group while tuberculosis-associated RV was diagnosed in 6/10 (60%) among those with infectious disorders. RV was bilateral in 28/47 (60%) patients. Retinal veins were most commonly affected (72%, 34/47). Involvement of arteries was present in 12/47 (25%) and was associated with viral infections and Behcet's disease. Ocular complications developed in 60/75 (80%) eyes. The most common complications were elevated intraocular pressure and/or glaucoma (33/75, 44%). Retinal detachment, vitreous hemorrhage, and cystoid macular edema developed in similar percentages (15%). CONCLUSIONS: RV in Thailand manifested mostly in male patients, was typically bilateral and involved mostly veins. Involvement of arteries was observed in patients with viral infections and Behcet's disease. Tuberculosis was the most common infectious cause.