New Findings Contradict Previous Credenda Regarding Paediatric Optic Neuritis
Pineles SL, Repka MX, Liu GT, Waldman AT, Borchert MS, Khanna S, Heidary G, Graves JS, Shah VS, Kupersmith MJ, Kraker RT. Assessment of paediatric optic neuritis visual acuity outcomes at 6 months. JAMA Ophthalmol. 2020;138(12):1253–1261. doi:10.1001/jamaophthalmol.2020.4231
This prospective study was the fruit of the joint efforts of the Paediatric Eye Disease Investigator Group and the Neuro-Ophthalmology Research Disease Investigator Consortium at 23 academic and community-based clinical sites.
Forty-four children aged 3 to 15 years were entered into the study of which 37 completed the six-month follow-up. Sixteen (36%) of the children presented with bilateral optic neuritis and the remainder were unilateral. Optic disk oedema was seen in 41 eyes (75%) and retinal haemorrhages in two eyes (4%). Magnetic resonance imaging (MRI) revealed optic nerve enhancement in 36 (92%) children and white matter lesions in 23 (52%).
Fifteen of the children were tested for NMO antibodies and, of these, only one (7%) tested positive. Thirteen of the enrollees were tested for MOG antibodies and, in this group, seven (54%) tested positive.
The mean distance visual acuity of 54 eyes at enrolment was 20/200. Twenty-eight eyes had a visual acuity of less than 20/200 and 16 eyes were less than 20/800. Factors associated with poor visual acuity included younger age, non-White and non-Hispanic ethnicity, an associated neurological autoimmune diagnosis (such as ADEM, NMO or MOG), and the presence of brain lesions on MRI.
Thirty-seven patients remained in the study at 6 months. Their mean improvement in visual acuity was eight lines on a standard ETDRS chart. Thirty-four (77%) of the children fell within their age-normal range and two children (4%) had a visual acuity worse than 20/200.
These data contradict the standard teachings that most cases of paediatric optic neuritis are bilateral and neurologically isolated.
David A. Bellows
More AI coming up: Differentiating NGON from GON
Yang HK, Kim YJ, Sung JY, Kim DH, Kim KG, Hwang J-M. Efficacy for differentiating nonglaucomatous versus glaucomatous optic neuropathy using deep learning systems. Am J Ophthalmol 2020; 216:140–146. doi:10.1016/j.ajo.2020.03.035
The investigators of this single institute developed an Artificial Intelligence Classification algorithm to differentiate images with normal optic discs, glaucomatous optic neuropathies (GON) and non-glaucomatous optic neuropathies (NGON). Among 3,815 fundus images collected, there were 486 GON images and 446 NGON images where the rest were normal optic disc images. Diagnosis of NGON included compressive optic neuropathy, Leber hereditary optic neuropathy, autosomal dominant optic atrophy, toxic and traumatic optic neuropathy, as well as optic atrophy of unknown cause. They reported a high overall diagnostic accuracy of 99.1%. The accuracies of detecting normal discs, NGON, and GON were 99.7%, 86.4%, and 92.5%, respectively. The sensitivity and specificity in differentiating GON from NGON images were 92.5% and 99.5%, respectively, with an average precision of 0.954. The major reasons for false positive findings were peripapillary atrophy and tilted optic discs.
Limitations of this study include the recruitment of variable stages of GON and NGON. There was also a significant portion (n = 73) with unknown cause of optic atrophy in the NGON group. Nevertheless, the study has certain strengths. High intraocular pressure was not a criterion in the inclusion of GON images; thus, optic discs of normal tension glaucoma (NTG) were also evaluated though the proportion of which was not reported. In real-life practice, it is still controversial to obtain neuroimaging for all NTG patients and differentiating NGON from NTG may pose diagnostic challenges to many. Secondly, the deep learning model also showed good performance without prior control of image acquisition parameters. This makes the system capable of a broader application on images with variable qualities in the future.
This study demonstrates great potential in employing artificial intelligence in the future screening programme. This technology is also helpful in assisting general ophthalmologists to differentiate NGON from GON to decide whether urgent neuroimaging or investigations are required. However, further validation of the system in different populations and ethnicities is necessary. This is particularly important as the colour of the fundus photography may depend on the degree of choroidal pigmentation. Lower accuracy is also expected in regions with a high population of high myopia.
Noel C.Y. Chan
Does time Equal Vision in AQP4-IgG Positive NMOSD Optic Neuritis?
Akaishi T, Takeshita T, Himori N, Takahashi T, Misu T, Ogawa R, Kaneko K, Fujimori J, Abe M, Ishii T, Fujihara, Aoki M, Nakazawa T, Nakashima I. Rapid administration of high-dose intravenous methylprednisolone improves visual outcomes after optic neuritis in patients with AQP4-IgG-positive NMOSD. Front Neurol. 2020. doi:10.3389/fneur.2020.00932
Study design
The investigators retrospectively reviewed 36 optic neuritis (ON) attacks from 32 consecutive aquaporin 4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD) patients and evaluated for factors that influenced the visual outcomes.
Outcomes
Earlier treatment of AQP4-IgG ON with intravenous methylprednisolone (IVMP) pulse therapy was associated with a better visual prognosis 1 year after the attack (Spearman’s rho = 0.50, p = .0018). In addition, the length of the ON lesion on magnetic resonance imaging was associated with the visual outcome (Spearman’s rho = 0.669, p < .001) and younger age was associated with better outcomes on multivariate analysis. The observed impact of early IVMP was independent of the length of the ON lesion on MRI.
Limitations
The main limitation of this study is the relatively small sample size and the retrospective nature of the analysis. In addition, over half of the patients were treated with plasma exchange, which complicates the interpretation of the findings.
Clinical significance
This study suggests that rapid initiation of IVMP may lead to better visual outcomes in ON from AQP4-IgG positive NMOSD. Because AQP4-IgG testing results often take 1–2 weeks to return, the authors recommend early IVMP for any acute ON that is suggestive of AQP4-IgG ON even before confirmation of AQP4-IgG positivity. However, future randomised clinical trials are required to confirm these findings.
John J. Chen
OCT may Help to Monitor Intracranial Pressure
Vijay V, Mollan SP, Mitchell JL, Bilton E, Alimajstorovic Z, Markey KA, Fong A, Walker JK, Lyons HS, Yiangou A, Tsermoulas G, Brock K, Sinclair AJ. Using optical coherence tomography as a surrogate of measurements of intracranial pressure in idiopathic intracranial hypertension. JAMA Ophthalmol. 2020;138(12):1264–1271. doi: 10.1001/jamaophthalmol.2020.4242.
The authors conducted a longitudinal cohort study to investigate whether optical coherence tomography (OCT) can act as a surrogate measure of intracranial pressure (ICP) in patients with idiopathic intracranial hypertension (IIH). They used data collected from three clinical trials, which enrolled 104 women with active IIH. The patients received OCT (Heidelberg Engineering) and either a baseline ICP from a continuous sitting telemetric ICP monitor (Raumedic Neurovent P-tel device) (n = 15) or lumbar puncture assessment of ICP at baseline and after 3, 12, and 24 months (n = 89). They found that optic nerve head central thickness was most closely associated with ICP. In addition, bootstrap surrogacy analysis showed a positive association between central thickness and change in ICP at all points (eg, at 12 months, a decrease in central thickness of 50 μm was associated with a decrease in ICP of 5 cmH2O). The authors suggest that OCT can not only monitor papilloedema but also noninvasively prognosticate ICP levels in patients with IIH.
Hui-Chen Cheng
Topical β-Blockers may help Patients with Acute Migraine
Kurian A, Reghunadhan I, Thilak P, Soman I, Nair U. Short-term efficacy and safety of topical β-blockers (timolol maleate ophthalmic solution, 0.5%) in acute migraine. JAMA Ophthalmol. 2020;138(11):1160–1166. doi:10.1001/jamaophthalmol.2020.3676
The authors conducted a randomised, masked placebo-controlled crossover trial to evaluate the short-term efficacy of topically applied 0.5% timolol maleate ophthalmic solution, compared with topically applied placebo eyedrops in the treatment of acute migraine attacks. Patients were instructed to use 1 drop of the assigned medication in each eye at the earliest onset of migraine. The primary end point was a reduction of pain score by 4 points, or with 0, 20 minutes after instillation of the eyedrop. Of a total of 619 migraine attacks, 284 (46%) were treated with timolol, 271 (44%) were treated with the placebo, and the remaining occurred during the washout period when no study medications were used. They found that a total of 233 (82%) of the timolol-treated migraine attacks attained the primary end point, compared to 38 (14%) of the placebo-treated attacks. A generalised estimating equation analysis revealed that pain score reduction at 20 minutes was greater in the timolol group compared with the placebo group (P < .001). The authors concluded that the result supports the consideration of timolol eyedrops in the acute treatment of migraine. Further research is warranted to determine the long-term efficacy and with larger groups.
Hui-Chen Cheng
Oculomotor Assessment Distinguishes Multiple Sclerosis and Parkinson’s Disease Patients From Healthy Controls
Grillini A, Renken RJ, Vrijling ACL, Heutink J, Cornelissen FW. Eye movement evaluation in multiple sclerosis and Parkinson’s disease using a standardised oculomotor and neuro-ophthalmic disorder assessment (SONDA). Front Neurol. 2020 Sep 8;11:971 doi:10.3389/fneur.2020.00971
This study introduces a short and continuous eye tracking protocol: SONDA (Standardised Oculomotor and Neurological Disorder Assessment). The authors tested multiple sclerosis (MS), n = 12 and Parkinson’s disease (PD), n = 9 patients and found abnormalities that could distinguish them from the healthy control group (n = 50).
For measuring eye movements a Tobii eyetracker was used with a sampling frequency of 60 Hz. A continuous tracking task of 4 min was presented to the subjects, including a smooth pursuit and a saccadic pursuit condition.
The main-sequence (peak velocity in relation to amplitude) was not abnormal in PD and MS patients compared with controls. In contrast, several spatio-temporal properties (STP) were significantly different in MS patients (in the saccadic pursuit condition) and in the PD group (both in smooth pursuit and saccadic pursuit), with the difference being more pronounced in the PD group. A principal component analysis showed that a classification exclusively based on STP is reasonably effective for PD, but ineffective for MS. Investigating the frequency distribution and dynamic properties of saccades, additional information was revealed that contributed to the characterisation of the patient groups.
In conclusion, this study describes a new and fast eye tracking protocol that characterises PD and MS patients and could be relevant in the evaluation of other neurological and psychiatric disorders. To obtain an even more precise reflection of saccadic properties a higher sampling frequency of the eye tracking device could be helpful. The presented approach for a principal component analysis is very relevant in this field. It would be useful to extend this approach in a higher sample size study by including more saccadic features in this analysis.
Jenny A. Nij Bijvank
Neuro-Ophthalmic Injuries With Systemic Neurologic Injury or Traumatic Brain Injury in Operation Iraqi Freedom and Operation Enduring Freedom
Jaksha AF, Justin GA, Brooks DI, Elward CJ, Ryan DS, Weichel ED, Colyer MH. Neuro-ophthalmic injuries with systemic neurologic injury or traumatic brain injury in Operation Iraqi Freedom and Operation Enduring Freedom. J Neuroophthalmol. 2020;40(3):322–327. doi: 10.1097/WNO.0000000000000913
From the Walter Reed Ocular Trauma Database, the authors retrospectively studied US service members and Department of Defence civilians who suffered combat trauma and reviewed the association of neuro-ophthalmologic injuries (NOI) with systemic neurologic injury (SNI) and traumatic brain injury (TBI). Of 890 eyes, 178 eyes had NOI in combat ocular trauma. Optic nerve injury was observed in 79 (44.38%) eyes, other cranial nerve injuries in 68 (38.20%), Horner syndrome in 4 (2.25%), diplopia in 45 (25.28%), and ptosis in 13 (7.30%). In patients with NOI, 76 (42.69%) eyes had a final VA less than 20/200. In injured eyes of patients with TBI, 154 eyes (34.26%) had a final visual acuity (VA) less than 20/200. They discovered that optic nerve injury and cranial nerve injury are associated with TBI and SNI, yet direct optic nerve injury, and not TBI and SNI, was associated with a poor final VA (<20/200).
Michael S. Vaphiades
Stroke Rate, Subtype, and Cardiovascular Risk Factors in Nonarteritic Anterior Ischaemic Optic Neuropathy: A Population-Based Study
Foster RC, Bhatti MT, Crum OM, Lesser E, Hodge D, Klass J, Chen J. Stroke rate, subtype, and cardiovascular risk factors in nonarteritic anterior ischaemic optic neuropathy: A population-based study. J Neuroophthalmol. 2020;40(3):328–332. doi:10.1097/WNO.0000000000000923
The authors conducted a retrospective chart review of 104 patients with nonarteritic anterior ischaemic optic neuropathy (NAION) and 104 control subjects using the Rochester Epidemiology Project database to identify all cases of NAION occurring among Olmsted County, Minnesota residents from January 1, 1990, through December 31, 2016. Stroke events were characterised using clinical and radiologic data. A comparison was made with an age- and sex-matched control group with similar vascular risk factors. Median age at diagnosis was 65 years (range, 40–90 years). Thirteen patients (13%) with NAION and 10 controls (10%) had symptomatic strokes after the age of 40 years. Among patients with NAION, six (46%) suffered a stroke before the diagnosis of NAION, five (39%) at least 5 months after the NAION diagnosis, and two patients (15%) suffered strokes both before and after the NAION. The cumulative probability of symptomatic strokes for patients with NAION was not significantly different than for controls and there were no cardioembolic strokes within 1 month of the NAION diagnosis. The mechanism of symptomatic strokes did not differ between the two groups. The authors concluded that NAION does not confer an increased risk of symptomatic stroke beyond the risk posed by age and existing vascular risk factors and suggests that in isolated NAION (no retinal vascular disease), cardioembolic work-up is unnecessary in these patients.
Michael S. Vaphiades
Association of Retinal Layer Measurements and Adult Cognitive Function: A Population-Based Study
Ward DD, Mauschitz MM, Bönniger MM, Merten N, Finger RP, Breteler MMB. Association of retinal layer measurements and adult cognitive function: A population-based study. Neurology. 2020;95(9):e1144-e1152. doi:10.1212/WNL.0000000000010146.
The authors sought to quantify the associations of peripapillary retinal nerve fibre layer (pRNFL) thickness and macular ganglion cell layer (mGCL) volume with cognitive functioning and to investigate how demographic and vascular health factors affect these associations in a population-based sample of adults. They analysed 2,483 participants who were 54.3 years old on average. After full adjustment, each 1- standard deviation decrease in mGCL volume was associated with a greater decrease in global function than that of pRNFL thickness. These relationships increased in strength with advancing age, were stronger in participants with hypertension, and were reversed in current smokers relative to non-smokers. The authors concluded that mGCL volume is more strongly related to adult cognitive functioning than pRNFL thickness, making it a better potential biomarker of neurodegeneration.
Michael S. Vaphiades
Young Adults with Anterior Ischaemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study
Hamann S, Malmqvist L, Wegener M, Fard MA, Biousse V, Bursztyn L, Citirak G, Costello F, Crum AV, Digre K, Fraser JA, Huna-Baron R, Katz B, Lawlor M, Newman NJ, Peragallo JH, Petzold A, Sibony PA, Subramanian PS, Warner JEA, Wong SH, Fraser CL; Optic Disc Drusen Studies Consortium. Young adults with anterior ischaemic optic neuropathy: A multicenter optic disc drusen study. Am J Ophthalmol. 2020;217:174–181. doi:10.1016/j.ajo.2020.03.052.
The authors retrospectively reviewed 65 patients with nonarteritic anterior ischaemic optic neuropathy (NAAION) 50 years old or younger and evaluated for optic disc drusen (ODD) using enhanced depth imaging optical coherence tomography (EDI-OCT). Of the 74 eyes with NAAION, 51% had ODD-AION, whereas 43% of fellow eyes without NAAION had ODD. The authors concluded that most of these young NAAION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NAAION, at least in younger patients. This study suggests ODD-AION be recognised as a novel diagnosis.
Michael S. Vaphiades
Occipital Cortex and Cerebellum Grey Matter Changes in Visual Snow Syndrome
Puledda F, Bruchhage M, O’Daly O, Ffytche D, Williams SCR, Goadsby PJ. Occipital cortex and cerebellum grey matter changes in visual snow syndrome. Neurology. 2020;95(13):e1792-e1799. doi: 10.1212/WNL.0000000000010530.
The authors performed an magnetic resonance imaging voxel-based morphometry approach on 24 patients with visual snow syndrome and on 24 age- and sex-matched healthy volunteers. All participants were scanned between 9 and 12 AM and told to consume a light breakfast and to avoid caffeine on the morning of the visit. The scanning protocol was the same for both groups and was conducted over a single session. Voxel-based morphometry was used to determine volumetric differences in patients with visual snow and analysis of cerebellar anatomy using a high-resolution spatially unbiased atlas template of the cerebellum. Compared with healthy controls, patients with visual snow syndrome had increased grey matter volume in the left primary and secondary visual cortices, the left visual motion area V5, and the left cerebellar crus I/lobule VI area. These anatomical alterations could not be explained by clinical features of the condition. They concluded that patients with visual snow syndrome have subtle yet significant neuroanatomical differences in visual and lateral cerebellar areas. This may in part explain the pathophysiologic basis of the disorder.
Michael S. Vaphiades
Comparison of Ice Pack Test and Single-Fibre EMG Diagnostic Accuracy in Patients Referred for Myasthenic Ptosis
Giannoccaro MP, Paolucci M, Zenesini C, Di Stasi V, Donadio V, Avoni P, Liguori R. Comparison of ice pack test and single-fibre EMG diagnostic accuracy in patients referred for myasthenic ptosis. Neurology. 2020;95(13):e1800-e1806. doi: 10.1212/WNL.0000000000010619.
This study compared the diagnostic accuracy of ice pack test (IPT) and single-fibre EMG (SF-EMG) in patients with suspected ocular myasthenia (OM) presenting with ptosis. Patients underwent IPT and stimulated SF-EMG on the orbicularis oculi muscle. They included 155 patients, 102 with OM and 53 with other diagnoses (OD). Receiver operating characteristic curve analysis was performed to determine the accuracy of IPT, SF-EMG, and their combination. The IPT had a sensitivity of 86% and a specificity of 79%. SF-EMG showed a sensitivity of 94% and a specificity of 79%. Overall, IPT and SF-EMG showed discordant results in 30 cases, 16 OM and 14 OD. The combination of IPT and SF-EMG, using the positivity of at least one test for OM diagnosis, increased the sensitivity to 98% reducing the specificity to 66%, whereas using the positivity of both tests, they obtained a sensitivity of 82% and a specificity of 92%. The negativity of both tests had a 94% negative predictive value. Comparison of the areas under the curve showed no differences in the diagnostic accuracy of IPT, SF-EMG, and their combinations. The authors concluded that IPT and SF-EMG have similar diagnostic accuracy in patients with OM presenting with ptosis. If both tests were negative then this would strongly suggest another diagnosis apart from OM.
Michael S. Vaphiades