Muller's muscle conjunctival resection versus external levator advancement for ptosis repair: systematic review and meta-analysis.

PURPOSE: To compare the outcome of Muller's muscle conjunctival resection (MMCR) versus external levator advancement (ELA) in patients undergoing ptosis surgery. METHODS: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and a search of electronic information was conducted to identify all comparative studies of MMCR versus ELA in ptosis repair. The primary outcome measures were the post-operative marginal reflex distance (MRD1), ptosis under-correction, over-correction, and re-operation rate. Secondary outcome measures included cosmetic appearance, complications, operative time, and learning curve. Fixed-effect modelling was used for the analysis. RESULTS: Seven studies that enrolled 1038 eyelids were identified in the literature. There was no statistically significant difference between the MMCR and ELA groups in post-operative MRD1 (Mean Difference [MD] = 0.13, P = 0.28) and the rate of under-correction odds ratio [OR] = 0.49, P = 0.14). However, ELA had a significantly higher rate of over-correction (OR = 0.17, P = 0.04) and re-operations (OR = 0.26, P = 0.0001) compared to MMCR. For secondary outcomes, MMCR had an improved cosmetic appearance, lower total number of complications and shorter operation time (MD = - 10.96, P < 0.00001). Finally, the two techniques had no significant difference in the learning curves. CONCLUSION: Both MMCR and ELA are effective techniques for the surgical correction of ptosis; however, MMCR surgery is a more predictable and robust technique compared to, ELA with lower rates of over-correction and re-operation.

Normative Data and Conversion Equation for Spectral-Domain Optical Coherence Tomography in an International Healthy Control Cohort.

BACKGROUND: Spectral-domain (SD-) optical coherence tomography (OCT) can reliably measure axonal (peripapillary retinal nerve fiber layer [pRNFL]) and neuronal (macular ganglion cell + inner plexiform layer [GCIPL]) thinning in the retina. Measurements from 2 commonly used SD-OCT devices are often pooled together in multiple sclerosis (MS) studies and clinical trials despite software and segmentation algorithm differences; however, individual pRNFL and GCIPL thickness measurements are not interchangeable between devices. In some circumstances, such as in the absence of a consistent OCT segmentation algorithm across platforms, a conversion equation to transform measurements between devices may be useful to facilitate pooling of data. The availability of normative data for SD-OCT measurements is limited by the lack of a large representative world-wide sample across various ages and ethnicities. Larger international studies that evaluate the effects of age, sex, and race/ethnicity on SD-OCT measurements in healthy control participants are needed to provide normative values that reflect these demographic subgroups to provide comparisons to MS retinal degeneration. METHODS: Participants were part of an 11-site collaboration within the International Multiple Sclerosis Visual System (IMSVISUAL) consortium. SD-OCT was performed by a trained technician for healthy control subjects using Spectralis or Cirrus SD-OCT devices. Peripapillary pRNFL and GCIPL thicknesses were measured on one or both devices. Automated segmentation protocols, in conjunction with manual inspection and correction of lines delineating retinal layers, were used. A conversion equation was developed using structural equation modeling, accounting for clustering, with healthy control data from one site where participants were scanned on both devices on the same day. Normative values were evaluated, with the entire cohort, for pRNFL and GCIPL thicknesses for each decade of age, by sex, and across racial groups using generalized estimating equation (GEE) models, accounting for clustering and adjusting for within-patient, intereye correlations. Change-point analyses were performed to determine at what age pRNFL and GCIPL thicknesses exhibit accelerated rates of decline. RESULTS: The healthy control cohort (n = 546) was 54% male and had a wide distribution of ages, ranging from 18 to 87 years, with a mean (SD) age of 39.3 (14.6) years. Based on 346 control participants at a single site, the conversion equation for pRNFL was Cirrus = -5.0 + (1.0 × Spectralis global value). Based on 228 controls, the equation for GCIPL was Cirrus = -4.5 + (0.9 × Spectralis global value). Standard error was 0.02 for both equations. After the age of 40 years, there was a decline of -2.4 µm per decade in pRNFL thickness ( P < 0.001, GEE models adjusting for sex, race, and country) and -1.4 µm per decade in GCIPL thickness ( P < 0.001). There was a small difference in pRNFL thickness based on sex, with female participants having slightly higher thickness (2.6 µm, P = 0.003). There was no association between GCIPL thickness and sex. Likewise, there was no association between race/ethnicity and pRNFL or GCIPL thicknesses. CONCLUSIONS: A conversion factor may be required when using data that are derived between different SD-OCT platforms in clinical trials and observational studies; this is particularly true for smaller cross-sectional studies or when a consistent segmentation algorithm is not available. The above conversion equations can be used when pooling data from Spectralis and Cirrus SD-OCT devices for pRNFL and GCIPL thicknesses. A faster decline in retinal thickness may occur after the age of 40 years, even in the absence of significant differences across racial groups.

Ocular Myasthenia: Clinical Course and the Diagnostic Utility of Assaying Acetylcholine Receptor Antibodies.

Myasthenia gravis (MG) is an autoimmune disease that causes neuromuscular junction transmission defect and has a predilection for the with neuromuscular junction transmission defect and predilection for extra-ocular and eyelid muscles. Most cases of ocular MG (OMG) convert later to generalised MG (GMG). Assaying acetylcholine receptor antibodies (AchRA) has been used to diagnose MG, but the reported sensitivity in OMG is lower (50%) than in GMG. We report the clinical course and the diagnostic yield of assaying AchRA in a Kuwaiti cohort of patients with OMG. We carried out a retrospective review of 47 patients diagnosed with OMG who were tested for AchRA. Ancillary tests included the ice test, single-fibre electromyography (SFMEG), and repetitive nerve stimulation electromyography (RNS). Progression to GMG occurred in 51% of OMG patients with a mean time to progression of 12.1 months (range 4 to 20 months). AchRAs were positive in 46 of 47 cases (98%), while SFEMG was positive in 31 of 34 cases (91.1%). Older age (44.25 years versus 38 years, p < .05) and higher AchRA titre (2.0 nmol/L versus 1.27 nmol/L, p < .05) were significantly associated with conversion to GMG. We have found a high rate of AchRA seropositivity in relatively younger subjects of OMG. Higher AchRA titres and older age were associated with conversion to GMG, usually within the first 2 years.

Course and Predictors of Visual Outcome of Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a clinical syndrome characterised by headache and papilloedema that can lead to significant visual morbidity. There are few studies in the literature about the visual outcome of IIH. We have reviewed the record of 76 patients with IIH according to the modified Dandy criteria. There was a significant improvement in the Humphrey 24-2 mean deviation (MD) in the study eyes (worse affected eye at presentation) in both the medically treated group (+2.0 dB; from -5.60 dB at baseline to -3.60 dB at final follow-up, p < .01) and in the fellow eyes in the medically treated group (+1.70 dB, from -4.40 dB at baseline to -2.74 dB at final follow-up, p < .01). Higher papilloedema grade (beta -0.66, p < .001) and age (p < .02) were inversely correlated with the final visual field MD in the study eye. The visual outcome for the IIH patients in our study was predominantly favourable, but patients with high-grade papilloedema had a worse visual prognosis and required more aggressive treatment.

Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: An international study.

OBJECTIVE: To determine the optimal thresholds for intereye differences in retinal nerve fiber and ganglion cell + inner plexiform layer thicknesses for identifying unilateral optic nerve lesions in multiple sclerosis. Current international diagnostic criteria for multiple sclerosis do not include the optic nerve as a lesion site despite frequent involvement. Optical coherence tomography detects retinal thinning associated with optic nerve lesions. METHODS: In this multicenter international study at 11 sites, optical coherence tomography was measured for patients and healthy controls as part of the International Multiple Sclerosis Visual System Consortium. High- and low-contrast acuity were also collected in a subset of participants. Presence of an optic nerve lesion for this study was defined as history of acute unilateral optic neuritis. RESULTS: Among patients (n = 1,530), receiver operating characteristic curve analysis demonstrated an optimal peripapillary retinal nerve fiber layer intereye difference threshold of 5µm and ganglion cell + inner plexiform layer threshold of 4µm for identifying unilateral optic neuritis (n = 477). Greater intereye differences in acuities were associated with greater intereye retinal layer thickness differences (p ≤ 0.001). INTERPRETATION: Intereye differences of 5µm for retinal nerve fiber layer and 4µm for macular ganglion cell + inner plexiform layer are robust thresholds for identifying unilateral optic nerve lesions. These thresholds may be useful in establishing the presence of asymptomatic and symptomatic optic nerve lesions in multiple sclerosis and could be useful in a new version of the diagnostic criteria. Our findings lend further validation for utilizing the visual system in a multiple sclerosis clinical trial setting. Ann Neurol 2019;85:618-629.

Mitochondrial Chronic Progressive External Ophthalmoplegia.

BACKGROUND: Chronic progressive external ophthalmoplegia (CPEO) is a rare disorder that can be at the forefront of several mitochondrial diseases. This review overviews mitochondrial CPEO encephalomyopathies to enhance accurate recognition and diagnosis for proper management. METHODS: This study is conducted based on publications and guidelines obtained by selective review in PubMed. Randomized, double-blind, placebo-controlled trials, Cochrane reviews, and literature meta-analyses were particularly sought. DISCUSSION: CPEO is a common presentation of mitochondrial encephalomyopathies, which can result from alterations in mitochondrial or nuclear DNA. Genetic sequencing is the gold standard for diagnosing mitochondrial encephalomyopathies, preceded by non-invasive tests such as fibroblast growth factor-21 and growth differentiation factor-15. More invasive options include a muscle biopsy, which can be carried out after uncertain diagnostic testing. No definitive treatment option is available for mitochondrial diseases, and management is mainly focused on lifestyle risk modification and supplementation to reduce mitochondrial load and symptomatic relief, such as ptosis repair in the case of CPEO. Nevertheless, various clinical trials and endeavors are still at large for achieving beneficial therapeutic outcomes for mitochondrial encephalomyopathies. KEY MESSAGES: Understanding the varying presentations and genetic aspects of mitochondrial CPEO is crucial for accurate diagnosis and management.

The clinical profile of new-onset optic neuritis in arabs, a tertiary center experience in Kuwait.

Background: Optic neuritis is an inflammatory disorder of the optic nerve and is often the initial manifestation of systemic demyelinating diseases such as multiple sclerosis (MS), neuromyelitis optic spectrum disorder (NMOSD), and myelin-oligodendrocyte glycoprotein (MOG) antibody-mediated disease. There are ethnic variations in the etiology of optic neuritis across the world. While multiple sclerosis is common in the West, NMOSD and MOG are more common causes in Asian patients. There is a paucity of reports on the clinical profile of optic neuritis in the Middle East. Objectives: To study the demographic and clinical features of patients with new onset optic neuritis in a main tertiary care center. Methods: A retrospective study of cases with new-onset optic neuritis at a tertiary care center between 2012 and 2022. The clinical and demographic characteristics were obtained from medical records and were summarized using descriptive statistics. Univariate analysis and multivariate analysis to assess the short-term visual outcome. Results: Seventy-one patients with new-onset optic neuritis (70 unilateral and one bilateral) were included in the study. The mean age was 33.3 years, they were predominantly females (73 %), and most of the cases were MS (53 %) followed by idiopathic optic neuritis (42.3 %). Final visual acuity of at least 20/40 was seen in at least 91.5 %. Conclusion: While the clinical profile of patients in this study closely resembles the Optic Neuritis Treatment Trial with a high incidence of MS and a good visual outcome in most patients and a good response to intravenous steroids, there is a significant proportion of idiopathic optic neuritis cases that may need to be better characterized with longer follow up and repeated serum biomarker testing.

Ocular Myasthenia Gravis: A Current Overview.

Ocular myasthenia gravis (OMG) is a neuromuscular disease characterized by autoantibody production against post-synaptic proteins in the neuromuscular junction. The pathophysiological auto-immune mechanisms of myasthenia are diverse, and this is governed primarily by the type of autoantibody production. The diagnosis of OMG relies mainly on clinical assessment, the use of serological antibody assays for acetylcholine receptors (AchR), muscle-specific tyrosine kinase (MusK), and low-density lipoprotein 4 (LPR4). Other autoantibodies against post-synaptic proteins, such as cortactin and agrin, have been detected; however, their diagnostic value and pathogenic effect are not yet clearly defined. Clinical tests such as the ice test and electrophysiologic tests, particularly single-fiber electromyography, have a valuable role in diagnosis. The treatment of OMG is primarily through cholinesterase inhibitors (pyridostigmine), and steroids are frequently required in cases of ophthalmoplegia. Other immunosuppressive therapies include antimetabolites (azathioprine, mycophenolate mofetil, methotrexate) and biological agents such as B-cell depleting agents (Rituximab) and complement inhibitors (eculizumab). Evidence is scarce on the effect of immunosuppressive therapy on altering the natural course of OMG. Clinicians must be vigilant of a myasthenic syndrome in patients using immune-check inhibitors. Reliable and consistent biomarkers are required to assess disease severity and response to therapy to optimize the management of OMG. The purpose of this review is to summarize the current trends and the latest developments in diagnosing and treating OMG.

Antiglutamate acid decarboxylase seropositive brain stem encephalitis.

This is a case of a previously healthy female in her fourties presenting with a subacute presentation of bilateral horizontal gaze restriction, with bilateral lower motor facial palsy. The patient's daughter has type 1 diabetes. On investigation, the patient's MRI revealed a lesion in the dorsal medial pons. Cerebrospinal fluid analysis revealed albuminocytological dissociation, with a negative autoimmune panel. The patient was treated with intravenous immunoglobulin, and methylprednisolone for a total of 5 days and showed mild improvement. The patient had raised serum antiglutamic acid decarboxylase (anti-GAD) levels, and the final diagnosis of GAD seropositive brain stem encephalitis was made.

Congenital optic disc pits and optic disc pit maculopathy: a review.

Optic disc pits are a rare but significant anomaly of the optic nerve head that can lead to visual impairment and associated complications. These pits are characterized by a small, oval-shaped depression in the disc, which can cause fluid accumulation and subsequent damage to the adjacent retina. Although the etiology and pathogenesis of optic disc pits are not fully understood, several theories have been proposed, including abnormal embryonic development and degenerative changes. Diagnosis is typically made through a comprehensive eye examination, including a dilated fundus exam and optical coherence tomography. Management options vary depending on the severity of the condition and associated complications, ranging from observation to surgical intervention.

Sellar masses: diagnosis and treatment.

Sellar mases can cause a variety of neuro-ophthalmic manifestations, including compressive optic neuropathy, chiasmal syndrome, and ophthalmoplegia due to cranial nerve palsy. Diagnosis involves a thorough history, neuro-ophthalmic examination, and ancillary tests and investigations. Visual field testing is critical in diagnosing and localizing the lesion and determining the extent of visual field loss. Appropriate neuro-imaging is essential in characterizing and localizing the lesion. Neuro-ophthalmologic assessment include meticulous clinical examination and ancillary tests including,visual field testing, which is useful in localizing the lesion, and optical coherence tomography, which is helpful in assessing the degree of axonal and neuronal loss and predicting the visual outcome. Treatment requires a multidisciplinary approach by different specialties, including radiologists, neuro-ophthalmologists, and neurosurgeons. The two primary treatment modalities for these tumors are surgery and radiation therapy. We review the main types of sellar lesions, their neuro-ophthalmologic evaluation, and treatment options.

Leber's hereditary optic neuropathy: Update on current diagnosis and treatment.

Leber's hereditary optic neuropathy (LHON) is a fairly prevalent mitochondrial disorder (1:50,000) arising from the dysfunction of the mitochondrial respiratory chain, which eventually leads to apoptosis of retinal ganglion cells. The usual presentation is that of a young male with a sequential reduction in visual acuity. OCT has been used to study the pattern of optic nerve involvement in LHON, showing early thickening of the inferior and superior retinal nerve fibre layer and ganglion cell layer thinning corresponding with the onset of symptoms. Of the three primary mutations for LHON, the m.14484T>C mutation has the best visual prognosis. Recent emerging therapeutic options for LHON include idebenone and the introduction of genetic vector therapy, which is currently in phase III clinical trials. Screening of family members and adequate advice to avoid environmental triggers, such as smoking and alcohol consumption, are also cornerstones in the management of LHON.

Familial non-obese idiopathic intracranial hypertension.

Purpose: To report a series of cases of non-obese familial idiopathic intracranial hypertension. Observation: One father and three offsprings (two brothers and one sister) with idiopathic intracranial hypertension and different phenotypic presentations. Conclusion and Importance: Familial idiopathic intracranial hypertension may underrecognized and may not be associated with obesity. Symptomatic family members may need to be screened for IIH in some cases.

The Role of Optical Coherence Tomography Criteria and Machine Learning in Multiple Sclerosis and Optic Neuritis Diagnosis.

BACKGROUND AND OBJECTIVES: Recent studies have suggested that intereye differences (IEDs) in peripapillary retinal nerve fiber layer (pRNFL) or ganglion cell + inner plexiform (GCIPL) thickness by spectral domain optical coherence tomography (SD-OCT) may identify people with a history of unilateral optic neuritis (ON). However, this requires further validation. Machine learning classification may be useful for validating thresholds for OCT IEDs and for examining added utility for visual function tests, such as low-contrast letter acuity (LCLA), in the diagnosis of people with multiple sclerosis (PwMS) and for unilateral ON history. METHODS: Participants were from 11 sites within the International Multiple Sclerosis Visual System consortium. pRNFL and GCIPL thicknesses were measured using SD-OCT. A composite score combining OCT and visual measures was compared individual measurements to determine the best model to distinguish PwMS from controls. These methods were also used to distinguish those with a history of ON among PwMS. Receiver operating characteristic (ROC) curve analysis was performed on a training data set (2/3 of cohort) and then applied to a testing data set (1/3 of cohort). Support vector machine (SVM) analysis was used to assess whether machine learning models improved diagnostic capability of OCT. RESULTS: Among 1,568 PwMS and 552 controls, variable selection models identified GCIPL IED, average GCIPL thickness (both eyes), and binocular 2.5% LCLA as most important for classifying PwMS vs controls. This composite score performed best, with area under the curve (AUC) = 0.89 (95% CI 0.85-0.93), sensitivity = 81%, and specificity = 80%. The composite score ROC curve performed better than any of the individual measures from the model (p < 0.0001). GCIPL IED remained the best single discriminator of unilateral ON history among PwMS (AUC = 0.77, 95% CI 0.71-0.83, sensitivity = 68%, specificity = 77%). SVM analysis performed comparably with standard logistic regression models. DISCUSSION: A composite score combining visual structure and function improved the capacity of SD-OCT to distinguish PwMS from controls. GCIPL IED best distinguished those with a history of unilateral ON. SVM performed as well as standard statistical models for these classifications. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that SD-OCT accurately distinguishes multiple sclerosis from normal controls as compared with clinical criteria.

Diagnosis and classification of optic neuritis.

There is no consensus regarding the classification of optic neuritis, and precise diagnostic criteria are not available. This reality means that the diagnosis of disorders that have optic neuritis as the first manifestation can be challenging. Accurate diagnosis of optic neuritis at presentation can facilitate the timely treatment of individuals with multiple sclerosis, neuromyelitis optica spectrum disorder, or myelin oligodendrocyte glycoprotein antibody-associated disease. Epidemiological data show that, cumulatively, optic neuritis is most frequently caused by many conditions other than multiple sclerosis. Worldwide, the cause and management of optic neuritis varies with geographical location, treatment availability, and ethnic background. We have developed diagnostic criteria for optic neuritis and a classification of optic neuritis subgroups. Our diagnostic criteria are based on clinical features that permit a diagnosis of possible optic neuritis; further paraclinical tests, utilising brain, orbital, and retinal imaging, together with antibody and other protein biomarker data, can lead to a diagnosis of definite optic neuritis. Paraclinical tests can also be applied retrospectively on stored samples and historical brain or retinal scans, which will be useful for future validation studies. Our criteria have the potential to reduce the risk of misdiagnosis, provide information on optic neuritis disease course that can guide future treatment trial design, and enable physicians to judge the likelihood of a need for long-term pharmacological management, which might differ according to optic neuritis subgroups.

Risk factors and visual outcome of Non-Arteritic Ischemic Optic Neuropathy (NAION): Experience of a tertiary center in Kuwait.

BACKGROUND: Non-arteritic ischemic optic neuropathy (NAION) is the most common acute optic neuropathy over the age of 50 years. NAION is commonly associated with systemic vascular risk factors (diabetes, hypertension, hyperlipidemia) and small cup-to-disc-ratio. We have assessed the prevalence risk factors of NAION and the visual outcome in patients referred to a tertiary ophthalmology center in Kuwait. MATERIALS AND METHODS: A retrospective review of new cases of NAION presenting within 2 weeks of onset were included and baseline clinical and demographics characteristic were determined. The prevalence of risk factors and the visual outcome (change in logMAR visual acuity, mean deviation of visual field) was compared between young NAION patients (below 50 years of age) and older NAION patients (over 50 years of age). The odds ratio of a final favorable visual outcome (visual acuity 20/40 or better) by age category was determined. RESULTS: Seventy-eight eyes of 78 patients with recent onset NAION were included in the study. The most prevalent risk factors for NAION in our subjects were diabetes (64.1%), small cup-to-disc ratio (61.5%), hyperlipidemia (51.3%) and hypertension (38.5%). Young NAION patients had better final logMAR visual acuity (0.55 +- 0.57) then older NAION patients (0.9 +- 0.73), (p = 0.03). Furthermore, young NAION patients were 2.8 times more likely to have a final visual acuity of 20/40 or better than older NAION patients, odds ratio (OR), 2.87; 95% confidence interval (CI), 1.12-7.40, Chi-square p-value = 0.03). CONCLUSION: There is a high prevalence of systemic vascular risk factors and small cup-to-disc ratio in NAION patients referred to our center across different age groups (below and above 50 years). Patients below the age of 50 years with NAION are more likely to have a final visual acuity of 20/40 or better than NAION patients above the age of 50 years.

Optimization of spectral domain optical coherence tomography and visual evoked potentials to identify unilateral optic neuritis.

BACKGROUND: Optic neuritis is a common manifestation of multiple sclerosis and frequently the presenting sign. The diagnosis of MS is heavily based on MRI findings but the latter is relatively insensitive in detecting optic nerve lesions. Identification of optic nerve lesion using ancillary tools such spectral-domain optical coherence tomography (SDOCT) by measuring the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL), and visual-evoked potentials latencies (VEP) may facilitate early diagnosis and treatment of multiple sclerosis. OBJECTIVE: To determine the optimal of SDOCT measures in RFNL and GCIPL and the VEP latency value for the identification of a prior symptomatic optic nerve lesion. METHODS: Thirty patients with diagnosed clinically with optic neuritis and fifty healthy control subjects were tested with SDOCT and VEP and the sensitivity, specificity, negative and positive predictive values of optimal values from healthy controls and optic neuritis patients were determined of for the identification unilateral optic nerve lesion. RESULTS: The inter-eye GCIPL difference of 3.5 µm is highly sensitive (100%) and specific (98%) in identifying unilateral optic nerve lesion, while lowest 5th percentile normal GCIPL threshold values of 71 µm was highly sensitive (100%) but less specific (83.3%). The inter-eye RNFL difference of 5.5 µm had a sensitivity of 70% and specificity of 90% in identifying optic nerve lesion while the lower 5th percentile normal RNFL value of 92.3 µm was poorly sensitive (40%). Finally, the 95th percentile normal VEP latency of 104.50 milliseconds had sensitivity of 80% and specificity of 76% in identifying optic nerve lesion. CONCLUSIONS: The inter-eye GCIPL difference is a powerful index for identifying unilateral optic nerve lesion, while the inter-eye RNFL difference and 95th percentile normal VEP latency had very good sensitivity and specificity. These measures can be useful in the evaluation of the first demyelinating event of MS and therefor can facilitate early diagnosis and therapy.