|Creator||Mark L. Moster, M. Tariq Bhatti|
|Abstract||In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, ND and Mark L. Moster, MD will discuss the following 6 articles: 1. Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marino M, Antonelli A, Dailey R, Harris GJ, Eckstein A, Schiffman J, Tang R, Nelson C, Salvi M, Wester S, Sherman JW, Vescio T, Holt RJ, Smith TJ. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382:341-352. 2. Kunchok A, Krecke KN, Flanagan EP, Jitprapaikulsan J, Lopez-Chiriboga AS, Chen JJ, Weinshenker BG, Pittock SJ. Does area postrema syndrome occur in myelin oligodendrocyte glycoprotein-IgG-associated disorders (MOGAD)? Neurology. 2020;94:85-88. 3. Puledda F, Schankin C, Goadsby PJ. Visual snow syndrome: A clinical and phenotypical description of 1,100 cases. Neurology. 2020;94:e564-e574. 4. Muhlemann F, Grabe H, Fok A, Wagner F, Brugger D, Sheldon CA, Abegg M. Homonymous hemiatrophy of ganglion cell layer from retrochiasmal lesions in the visual pathway. Neurology. 2020;94:e323-e329. 5. Engelke H, Shajari M, Riedel J, Mohr N, Priglinger SG, Mackert MJ. OCT angiography in optic disc drusen: comparison with structural and functional parameters. Br J Ophthalmol. [published ahead of print November 19, 2019] doi: 10.1136/bjophthalmol-2019-314096. 6. Roberts DR, Asemani D, Nietert PJ, Eckert MA, Inglesby DC, Bloomberg JJ, George MS, Brown TR. Prolonged Microgravity Affects Human Brain Structure and Function. AJNR Am J Neuroradiol. 2019;40:1878-1885.|
Literature Commentary Section Editors: Mark L. Moster, MD M. Tariq Bhatti, MD Literature Commentary In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, ND and Mark L. Moster, MD will discuss the following 6 articles: 1. Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marinò M, Antonelli A, Dailey R, Harris GJ, Eckstein A, Schiffman J, Tang R, Nelson C, Salvi M, Wester S, Sherman JW, Vescio T, Holt RJ, Smith TJ. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382:341-352. 2. Kunchok A, Krecke KN, Flanagan EP, Jitprapaikulsan J, Lopez-Chiriboga AS, Chen JJ, Weinshenker BG, Pittock SJ. Does area postrema syndrome occur in myelin oligodendrocyte glycoprotein-IgG-associated disorders (MOGAD)? Neurology. 2020;94:85-88. 3. Puledda F, Schankin C, Goadsby PJ. Visual snow syndrome: A clinical and phenotypical description of 1,100 cases. Neurology. 2020;94:e564-e574. 4. Mühlemann F, Grabe H, Fok A, Wagner F, Brügger D, Sheldon CA, Abegg M. Homonymous hemiatrophy of ganglion cell layer from retrochiasmal lesions in the visual pathway. Neurology. 2020;94:e323-e329. 5. Engelke H, Shajari M, Riedel J, Mohr N, Priglinger SG, Mackert MJ. OCT angiography in optic disc drusen: comparison with structural and functional parameters. Br J Ophthalmol. [published ahead of print November 19, 2019] doi: 10.1136/bjophthalmol-2019-314096. 6. Roberts DR, Asemani D, Nietert PJ, Eckert MA, Inglesby DC, Bloomberg JJ, George MS, Brown TR. Prolonged Microgravity Affects Human Brain Structure and Function. AJNR Am J Neuroradiol. 2019;40:1878-1885. Douglas RS, Kahaly GJ, Patel A, Sile S, Thompson EHZ, Perdok R, Fleming JC, Fowler BT, Marcocci C, Marinò M, Antonelli A, Dailey R, Harris GJ, Eckstein A, Schiffman J, Tang R, Nelson C, Salvi M, Wester S, Sherman JW, Vescio T, Holt RJ, Smith TJ. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020 Jan 23;382:341-352 Background: Thyroid eye disease is a debilitating, disﬁguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. Methods: In a randomized, double-masked, placebocontrolled, Phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the ﬁrst infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at Week 24. The primary outcome was a proptosis response (a reduction in proptosis of $ 2 mm) at Week 24. Prespeciﬁed secondary outcomes at Week 24 were an overall response (a reduction of $2 points in the Clinical Activity Score (CAS) plus a reduction in proptosis of $2 mm), a CAS of 0 or 1 (indicating no or minimal inﬂammation), the mean change in proptosis across trial visits (from baseline through Week 24), a diplopia response (a reduction in diplopia of $1 grade), and the mean change in overall score on the Graves' ophthalmopathy-speciﬁc quality-of-life (GO-QOL) questionnaire across trial visits 274 (from baseline through week 24; a mean change of $6 points is considered clinically meaningful). Results: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At Week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs 10% [4 patients], P , 0.001), with a number needed to treat of 1.36. All secondary outcomes were signiﬁcantly better with teprotumumab than with placebo, including overall response (78% of patients  vs 7% ), CAS of 0 or 1 (59%  vs 21% ), the mean change in proptosis (22.82 vs 20.54 mm), diplopia response (68% [19 of 28] vs 29% [8 of 28]), and the mean change in GOQOL overall score (13.79 points vs 4.43 points) (P # 0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; 2 serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. Conclusions: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, CAS, diplopia, and quality of life than placebo; serious adverse events were uncommon (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.). COMMENTS Teprotumumab (Tepezza; Horizon Therapeutics Ireland DAC, Dublin, Ireland) has recently become the ﬁrst US Moster and Bhatti: J Neuro-Ophthalmol 2020; 40: 274-280 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Food and Drug administration (FDA)-approved treatment for thyroid ophthalmopathy. This report is of OPTIC, a Phase III clinical trial of this human monoclonal antibody targeting the IGF-IR, which plays a role in the disease. Patients received 8 infusions 3 weeks apart. The primary outcome was the percent of patients achieving a decrease in proptosis of 2 mm at week 24. Secondary outcomes at week 24 were a reduction of $2 points in the clinical activity score (CAS), a CAS of 0 or 1, the mean change in proptosis across trial visits (from baseline through week 24), a reduction in diplopia, and change in overall score on the Graves' ophthalmopathy-speciﬁc quality-of-life (GO-QOL) questionnaire. All outcomes were met. Eighty-three percent of patients reached the primary proptosis outcome compared with 10% receiving placebo. The response began at a median of 6.4 weeks with an average improvement at 24 weeks of 3.32 mm. Those with the most proptosis had the best response. At one site, orbital imaging was performed in 6 patients receiving teprotumumab. All 6 had reduction in extraocular muscle and/or orbital fat volume associated with the improved proptosis. It is wonderful to have an alternative to our suboptimal current treatments. However, we have to learn which patients are best for treatment since many patients were excluded from the study, including those with optic neuropathy or previous treatment with steroids, rituximab, or tocilizumab. Also, there was no long-term follow-up. Although the treatment seems safe, we will need real-world treatment experience to determine where this medication will be most helpful. -Mark L. Moster, MD I am very fortunate to have Jim Garrity as a colleague who is truly a thought leader in thyroid eye disease. I asked him his thoughts on teprotumumab and here is what he said: Finally, there is something new we have to offer our patients with Graves' orbitopathy. The new drug is teprotumumab, and early treatment results are encouraging. How does this drug work? How effective is it? Who should get the drug? What are the side effects and is it expensive? Teprotumumab is a monoclonal antibody, which blocks the insulin-like growth factor-1 (IGF-1) receptor. It has been shown that there is cross talk between the IGF-1 receptor and the thyroid-stimulating hormone receptor. Blocking the IGF-1 receptor seems to fundamentally affect the eye manifestations and in that proptosis and the CAS respond typically within the ﬁrst 6 weeks. By study end, both diplopia and quality of life had improved. Who would be a candidate to receive teprotumumab? Immunomodulatory therapy is effective only during the "active" phase of the disease deﬁned as a 7-point Moster and Bhatti: J Neuro-Ophthalmol 2020; 40: 274-280 composite of eyelid erythema, eyelid edema, conjunctival injection, chemosis, caruncle edema, pain with eye movement, and pain at rest. A CAS of 4 or greater would be an ideal candidate. Side effects worthy of note were hyperglycemia in 2 of 41 patients, and interestingly, 5 patients had reversible hearing loss ranging from hypoacusis to deafness. Weight loss (at least 5 kg) was also noted in 5 patients but was intentional in one. Anecdotally, we have heard a price tag of around $15,000 per treatment. The study listed treatments every 3 weeks for 21 weeks. What remains to be seen is if the number of treatment sessions can be reduced or if teprotumumab can reduce or eliminate the need for subsequent surgery. If so, the drug may represent a "bargain." Let me add that in the warning and precaution section of the prescribing information (https://www.hzndocs.com/ TEPEZZA-Prescribing-Information.pdf), the following 3 items are listed: 1. Infusion reactions 2. Exacerbation of preexisting inﬂammatory bowel disease 3. Hyperglycemia -M. Tariq Bhatti, MD Kunchok A, Krecke KN, Flanagan EP, Jitprapaikulsan J, Lopez-Chiriboga AS, Chen JJ, Weinshenker BG, Pittock SJ. Does area postrema syndrome occur in myelin oligodendrocyte glycoprotein-IgG-associated disorders (MOGAD)? Neurology. 2020 Jan 14;94:85-88 No abstract. COMMENTS The Mayo clinic group continues to reﬁne our understanding of the antibody-mediated syndromes that were initially believed to be multiple sclerosis variants. Until recently, many believed that neuromyelitis optica (NMO) and antimyelin oligodendrocyte glycoprotein (MOG) presentations were the same disease because of similar presentations of myelitis and optic neuritis. However, with the availability aquaporin 4 (AQP4) and MOG antibody testing to separate the 2 entities, differences have become clearer. For instance, MOG has a less prominent female preponderance, is frequently associated with acute disseminated encephalomyelitis (ADEM), has better recovery of optic neuritis, may have more disc swelling, and MRI may show optic perineuritis. 275 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary This study looked at the frequency of the area postrema syndrome (APS), one of the 6 core clinical characteristics of NMO spectrum disorder (NMOSD), in the Mayo patients with MOG-associated disorder (MOGAD). They looked for patients with intractable nausea, vomiting, and hiccups (INVH) for over 48 hours with discrete area postrema lesions on MRI. In AQP4 + patients with NMOSD, the APS occurs in isolation at onset in 7.1%-10.3% and throughout the disease in 9.4%-14.5%. In this study of 56 children with MOGAD, 8 (14%) had nausea and/or vomiting but not hiccups for .48 hours (median 14 days, range 2-42 days). Seven of these patients had ADEM and the MRIs showed that 4 had large, multifocal, pontine, or medullary MR FLAIR/T2 hyperintense lesions with minimal contrast enhancement. Unfortunately, the patient without ADEM did not have MRI at the time of the INVH. Of 117 adults, 10 (9%) had intractable symptoms of $1 of nausea (8), vomiting (6), or hiccups (5) lasting .48 hours (median 5 days, range 2-42 days). Of 5 adults with ADEM, 4 had contemporaneous MRI, which demonstrated patchy, poorly demarcated pontine, or medullary FLAIR/ T2 hyperintense lesions, with minimal contrast enhancement. Three had associated cervical/thoracic myelopathies. Only one patient (0.6%), without a history of ADEM, optic neuritis, or myelitis, had isolated INVH with an isolated MR FLAIR/T2 hyperintensity at the area postrema without contrast enhancement. In summary, INVH suggestive of the APS occurs in a similar percentage of AQP4 patients and MOGAD patients. However, when associated with an MRI lesion in the area postrema, it is highly suggestive of AQP4 + NMOSD rather than MOGAD. -Mark L. Moster, MD As you said Mark, the Mayo group is deﬁnitely expanding our knowledge of NMOSD and MOGAD. The ﬁrst paragraph of the discussion summarizes the results of the study very well and is what I will try to remember, "APS with isolated INVH and a discrete lesion in the area postrema was encountered in only 1 patient (patient 4) representing 0.6% of our MOGAD cohort compared with 9.4%-14.5% in AQP4-IgG+ NMOSD." -M. Tariq Bhatti, MD Puledda F, Schankin C, Goadsby PJ. Visual snow syndrome: A clinical and phenotypical description of 1,100 cases. Neurology. 2020;94:e564-e574. Objective: To validate the current criteria of visual snow and to describe its common phenotype using a substantial clinical database. 276 Methods: We performed a web-based survey of patients with self-assessed visual snow (n = 1,104), with either the complete visual snow syndrome (VSS) (n = 1,061) or visual snow without the syndrome (n = 43). We also describe a population of patients (n = 70) with possible hallucinogen persisting perception disorder who presented clinically with VSS. Results: The visual snow population had an average age of 29 years and had no sex prevalence. The disorder usually started in early life, and z40% of patients had symptoms for as long as they could remember. The most commonly experienced static was black and white. Floaters, afterimages, and photophobia were the most reported additional visual symptoms. A latent class analysis showed that visual snow does not present with speciﬁc clinical endophenotypes. Severity can be classiﬁed by the amount of visual symptoms experienced. Migraine and tinnitus had a very high prevalence and were independently associated with a more severe presentation of the syndrome. Conclusions: Clinical characteristics of visual snow did not differ from the previous cohort in the literature, supporting validity of the current criteria. Visual snow likely represents a clinical continuum, with different degrees of severity. On the severe end of the spectrum, it is more likely to present with its common comorbid conditions, migraine and tinnitus. Visual snow does not depend on the effect of psychotropic substances on the brain. COMMENTS This paper describes a web-based survey of 1,104 patients experiencing visual snow (VS) and goes a long way in deﬁning the clinical symptoms in this phenomenon. Forty-three patients had isolated VS, and 1,061 had the full blown VSS, deﬁned as VS plus at least 2 of the following symptoms: 1. palinopsia 2. entoptic phenomena 3. photophobia 4. nyctalopia. The visual features of the VS seem similar in the isolated VS patients and those with full blown VSS. The authors suggest that there may be a spectrum with VS being a mild case of VSS. Associated features include tinnitus in 42% of VS and 75% of VSS patients and migraine in 39% of VS and 72% of VSS patients, and the authors speculate on similar pathophysiologic mechanisms for VSS, migraine and tinnitus. They suggest that VS and tinnitus represent 2 different manifestations of a similar disorder, that is, the perception of a sensory stimulus that is not present or is subthreshold. This points to a central neuronal mechanism, which could involve aberrant sensory processing at the level of association cortices or the thalamo-cortical network. An added bonus of this study is the description of 70 patients with hallucinogen persisting perception disorder, Moster and Bhatti: J Neuro-Ophthalmol 2020; 40: 274-280 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary a group with VS occurring within 12 months of ingestion of hallucinogens. These patients had some differences in the appearance of the static but otherwise seemed quite similar to those with VSS not associated with hallucinogens. The limitations of the study are related to recruitment bias of a group of self-volunteering participants and it being a web-based survey. This might exclude milder cases and older patients. However, it is a very large group of responders that paint a very consistent picture of their symptoms. In the early 1990s, a group of Philadelphia neuroophthalmologists was sitting in my backyard discussing possible research collaborations. We discussed patients that seemed to have persistent positive visual phenomena that many neuro-ophthalmologists at that time considered "functional," but that a few of the colleagues present were convinced were real. Shortly thereafter, Liu et al1 described the phenomenon in migraine patients. By now I have seen so many VS patients, and their presentation is so similar to what is described in this paper that I am convinced it is a real entity. Although a real symptomatic nuisance, it is not likely a true disease. My bias is also that we in neuro-ophthalmology should take ownership of VSS in addition to the headache specialists currently deﬁning it. -Mark L. Moster, MD 1. Liu GT, Schatz NJ, Galetta SL, Volpe NJ, Skobieranda F, Kosmorsky GS. Persistent positive visual phenomena in migraine. Neurology. 1995;45:664-668. Great story Mark. It is so inspiring to hear how great minds can come together in a casual setting and start a conversation on a complex mankind problem. I listened to the podcast that interviewed the lead author Dr. Puledda. The 5 points I came away after listening were: 1. VSS is on a spectrum of severity from mild static with no associated symptoms (which Dr. Puledda states she has friends and colleagues with this) to very disabling often associated with migraine and tinnitus. 2. VS has variable clinical characteristics, but common features are a panﬁeld phenomenon often associated with palinopsia and photophobia. 3. Ophthalmological disorders (2 that were mentioned in the podcast were retinitis and retinopathy) rarely have features of visual snow. Personally, I can't think of any cases I have seen where VS was due to retinal dysfunction. 4. Associative visual cortex dysfunction or disruption of the complex brain network seems to be the underlying etiology Moster and Bhatti: J Neuro-Ophthalmol 2020; 40: 274-280 5. Patients should be reassured that this is not a degenerative process and that they may develop tolerance over time. -M. Tariq Bhatti, MD Mühlemann F, Grabe H, Fok A, Wagner F, Brügger D, Sheldon CA, Abegg M. Homonymous hemiatrophy of ganglion cell layer from retrochiasmal lesions in the visual pathway. Neurology. 2020;94:e323-e329 Objective: To determine the temporal evolution, morphology, and frequency of macular ganglion cell atrophy in patients with retrochiasmal lesions of the visual pathway. Methods: In a consecutive retrospective case series, we identiﬁed 47 patients with homonymous hemianopia and accessible macular optical coherence tomography scans. We estimated the time of lesion onset and the location of the lesion within the afferent visual pathway. Using semiautomatic layer segmentation, we determined ganglion cell layer (GCL) thickness in areas projecting to the side of the retrochiasmal lesion and compared it with GCL thickness on the healthy side. Results: We found that retrochiasmal lesions at any level may be associated with an atrophy of ganglion cells. This atrophy respects the vertical midline through the fovea and thus the anatomic separation of the nasal and temporal visual ﬁeld. The vertical line separating the affected from the unaffected side has signiﬁcantly less tilt as compared with the disc-fovea angle. Lesions of the optic tract are associated with earlier macular ganglion cell atrophy than retrogeniculate lesions. Macular ganglion cell atrophy may be present in cases with normal peripapillary nerve ﬁber layer analysis and vice versa. Conclusions: Macular GCL thickness shows a topographic hemiatrophy in retrochiasmal lesions, which manifests earlier for tract lesions than for retrogeniculate lesions. This additional examination of ganglion cell homonymous hemiatrophy has a higher sensitivity in detecting retrograde transsynaptic degeneration than the analysis of the peripapillary nerve ﬁber layer alone. COMMENTS I came away with 2 points from this macular optical coherence tomography (OCT) retrospective study of 47 patients with postchiasmal pregeniculate and retrogeniculate lesions. First, transsynaptic degeneration can occur in adults. Second, and something I emphasize to trainees, is that OCT can not only point to certain diseases, but just as importantly determine the anatomical site of the lesion. Let's take, for example, this case I recently saw (Fig. 1). The patient seems to have a unilateral (left eye) superonasal visual ﬁeld defect suggesting a prechiasmal lesion. However, the OCT clearly demonstrates a left homonymous 277 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary FIG. 1. Automated perimetry (top) and optical coherence coherence tomography ganglion cell analysis (bottom), shows an incongruous right homonymous hemianopsia associated with left homonymous hemi-macular atrophy. hemiatrophy of the GCL indicating a postchiasmal lesion. In fact, if you look back carefully at the visual ﬁeld of the right eye, there is a superotemporal defect indicating the patient actually has an incongruous right homonymous hemianopsia due to a left optic tract lesion. -M. Tariq Bhatti, MD This paper, although worthy of reading, merely corroborates what we've now seen for years with spectral domain OCT, that is, that GCL atrophy is more prominently seen than retinal nerve ﬁber layer (RNFL) atrophy in all hemianopic lesions and that trans-synaptic degeneration is seen in recent as well as longstanding lesions. This study found GCL atrophy occurring in 94% of patients with pregeniculate lesions and 65% with postgeniculate lesions. The timing of the atrophy averaged 1 278 month with pregeniculate and 5 months with postgeniculate lesions. In 70% of those with GCL homonymous hemiatrophy, the RNFL was also thin. The RNFL was thin in 7% who did not show GCL hemiatrophy. However, not mentioned in the paper is whether the RNFL thinning was in a pattern that suggests a retrochiasmal lesion or was a less speciﬁc type of thinning. I think this is very important information that is missing. I am also surprised that with the Spectralis OCT [Heidelberg Engineering, Heidelberg, Germany], which was used in this study, the authors chose to look at a segment of GCL + inner plexiform layer (IPL) rather than just segment the GCL layer, which is available on the Spectralis software. GCL would likely be more sensitive. Perhaps, they wanted to be in line with publications Moster and Bhatti: J Neuro-Ophthalmol 2020; 40: 274-280 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary using the Cirrus OCT (Zeiss, Oberkachen, Germany), which does not separate GCL from IPL in its segmentation software. -Mark L. Moster, MD Engelke H, Shajari M, Riedel J, Mohr N, Priglinger SG, Mackert MJ. OCT angiography in optic disc drusen: comparison with structural and functional parameters. Br J Ophthalmol. [published ahead of print November 19, 2019] doi: 10.1136/ bjophthalmol-2019-314096. Background: Optic disc drusen (ODD) can cause retinal nerve ﬁber layer (RNFL) defects with progressive visual ﬁeld (VF) loss. Microvascular changes are discussed as a cause. We measured the vessel density (VD) of the optic disc in ODD using optical coherence tomography angiography and compared it with a normal population. Another intent was to determine the sensitivity and correlations in comparison with functional (VF) and structural parameters (RNFL, minimum rim width [MRW], and ganglion cell complex [GCC]). Methods: We analyzed the VD of 25 patients with ODD and an age-matched control population including 25 healthy participants using AngioVue (Optovue, Fremont, CA). We obtained data about RNFL, GCC, Bruch's membrane opening MRW (Spectralis HRA & OCT; Heidelberg Engineering, Heidelberg, Germany) and VF (standard automated perimetry; SITA 24-2). Low image quality and pathologies interfering with the diagnostics were excluded. Parametric data were analyzed using the t test and nonparametric values using the Mann-Whitney U test. Linear regression analysis was used to determine correlations using the Bravais-Pearson test. Results: The VD was signiﬁcantly reduced in the ODD group especially the peripapillary capillary VD (n = 45 vs 50 eyes; mean 43.15% vs 51.70%). Peripapillary RNFL thickness correlated with the VD signiﬁcantly (r = 0.902 [n = 44], 0.901 [n = 44], 0.866 [n = 45]). The RNFL analysis showed a reduction in ODD, especially the superior hemisphere (mean 107 mm, 129 mm; 49 vs 50 eyes). The GCC was signiﬁcantly lower in the ODD group (n = 38 vs 40; mean 87 vs 98 mm). Positive correlation between the VD and the GCC was signiﬁcant (n = 37, r = 0.532). There is a signiﬁcant negative correlation (n = 19; r = 20.726) between the VD and the pattern SD (PSD). Conclusion: This study reveals signiﬁcant peripapillary microvascular changes in patients with ODD correlating with the RNFL and GCC reduction. There is a negative correlation between the PSD and the VD. COMMENTS New technology is always exciting because it may help us in our daily practice but also shed light on disease pathophysiology. I think optical coherence tomography angiography (OCTA) falls into that category of new technology with signiﬁcant potential. In this retrospective, case-control Moster and Bhatti: J Neuro-Ophthalmol 2020; 40: 274-280 study, totaling 50 patients (25 with ODD and 25 controls), the vessel density (VD) of the optic disc was measured to quantify microstructural changes between these 2 groups. The authors also looked at the relationship between retinal nerve ﬁber layer (RNFL), ganglion cell complex (GCC), and visual ﬁeld defects. In terms of calculating the VD, the capillary density and all vessels of the optic disc area, peripapillary area, and the total area were analyzed. Compared with healthy controls, patient with ODD had a signiﬁcant reduction in the capillary only VD and total VD in all 3 areas. There was a positive correlation of the RNFL thickness to the peripapillary capillary VD and total VD to the GCC. Only in a subanalysis was there negative correlation between capillary VD and pattern SD. What this study shows is that there are peripapillary microvascular changes associated with ODD. What that means in terms of the pathogenesis of ODD, visual loss associated with ODD and complications of ODD remain unknown and require more studying. -M. Tariq Bhatti, MD Tariq, if you keep choosing to review these papers that are so intuitive, I'm going to have to label you Doctor Obvious!! It seems that every optic nerve disease has been reported with abnormal OCTA, including optic neuritis, ischemic optic neuropathy, Leber hereditary optic neuropathy, and compressive optic neuropathy. Sure, there are some papers suggesting some diagnostic value for this technique, but I'm still Doctor Skeptical! -Mark L. Moster, MD Sir Arthur Conan Doyle said, "The world is full of obvious things which nobody by any chance ever observes." -M. Tariq Bhatti, MD Roberts DR, Asemani D, Nietert PJ, Eckert MA, Inglesby DC, Bloomberg JJ, George MS, Brown TR. Prolonged microgravity affects human brain structure and function. AJNR Am J Neuroradiol. 2019;40:1878-1885 Background and purpose: Widespread brain structural changes are seen after extended spaceﬂight missions. The purpose of this study was to investigate whether these structural changes are associated with alterations in motor or cognitive function. Materials and methods: Brain MR imaging scans of National Aeronautics and Space Administration astronauts were retrospectively analyzed to quantify preﬂight to postﬂight changes in brain structure. Local structural changes were assessed using the Jacobian determinant. Structural changes were compared with clinical ﬁndings and cognitive and motor function. 279 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Results: Long-duration spaceﬂights aboard the International Space Station, but not short-duration Space Shuttle ﬂights, resulted in a signiﬁcant increase in total ventricular volume (10.7% vs 0%, P , 0.001, n = 12 vs n = 7). Total ventricular volume change was signiﬁcantly associated with mission duration (r = 0.72, P = 0.001, n = 19) but negatively associated with age (r = 20.48, P = 0.048, n = 19). Longduration spaceﬂights resulted in signiﬁcant crowding of brain parenchyma at the vertex. Preﬂight to postﬂight structural changes of the left caudate correlated signiﬁcantly with poor postural control, and the right primary motor area/ midcingulate correlated signiﬁcantly with a complex motor task completion time. Change in volume of 3 white matter regions signiﬁcantly correlated with altered reaction times on a cognitive performance task (bilateral optic radiations and splenium of the corpus callosum). In a post hoc ﬁnding, astronauts who developed spaceﬂight-associated neuroocular syndrome demonstrated smaller changes in total ventricular volume than those who did not (12.8% vs 6.5%, n = 8 vs n = 4). Conclusions: Although cautious interpretation is appropriate given the small sample size and number of comparisons, these ﬁndings suggest that brain structural changes are associated with changes in cognitive and motor test scores and with the development of spaceﬂight-associated neuro-optic syndrome. was a correlation between the brain structure changes and the negative motor and cognitive changes in the longduration astronauts. In particular, local structural changes of the left caudate nucleus predicted poorer postural control, local structural change of the right lower extremity primary motor area/midcingulate was associated with prolonged completion time, and local structural changes seen in the optic radiations and the splenium of the corpus callosum were found to be predictors of altered reaction time. Interestingly, younger astronauts were noted to be more affected compared with older astronauts. Thomas Mader, Andy Lee et al, have been leading the way in our understanding of spaceﬂight associated neuroocular syndrome (SANS) (2). This study also looked at the eye ﬁndings in the 12 long-duration astronauts and found that 1 had optic disc edema and 3 had choroidal folds. In a post hoc analysis, there was a smaller change in percentage change in total ventricular volume of these 4 astronauts compared with the 8 astronauts who did not have SANS. The authors did not have a good explanation of this ﬁnding but just stated ventricular enlargement may not be a characteristic feature of SANS. -M. Tariq Bhatti, MD COMMENTS Mark, can you think back to March 2018? I think you were still a baby neuro-ophthalmologist at that time. Remember that in that month's issue of Literature Commentary, we discussed a New England Journal of Medicine (NEJM) article on this subject matter of space ﬂight and its effect on the brain (1). This study is from the same authors from that NEJM article, in which the investigators retrospectively assessed the cognitive and motor performance of 19 astronauts compared with the brain structural changes. Cognitive testing was performed using the Spaceﬂight Cognitive Assessment Tool for Windows (WinSCAT) in 12 astronauts participating in the international space station (ISS) or long-duration space mission. Motor performance was assessed using the Functional Task Test in 7 longduration space mission astronauts and 1 short-duration space mission (space shuttle) astronaut. A signiﬁcant increase in total postﬂight ventricular volume was found in the ISS astronauts but not the short-ﬂight astronauts (10.7% vs 0%, respectively, P = 0.001). In particular, there was signiﬁcant crowding of brain parenchyma at the vertex involving supplementary motor, premotor, and primary sensorimotor regions. There 280 1. Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV, Zhu X, Chimowitz MI, Antonucci MU. Effects of space ﬂight on astronaut brain structure as indicated on MRI. N Engl J Med. 2017;377:1746-1753. 2. Lee AG, Mader TH, Gibson CR, Tarver W, Rabiei P, Riascos RF, Galdamez LA, Brunstetter T. Spaceﬂight associated neuro-ocular syndrome (SANS) and the neuro-ophthalmologic effects of microgravity: a review and an update. NPJ Microgravity. 2020;6:7. These ﬁndings are very interesting and concerning for neurologic deﬁcits after prolonged periods in space. I wonder whether the cerebrospinal ﬂuid (CSF) migrates upward because of loss of gravity and that the CSF space around the lower spinal cord would be lessened. I question the claim of increased intracranial pressure in the one astronaut who had a lumbar puncture (LP) because the measurement was only 21.5 cm H2O. Although most of the LPs in these astronauts have been performed after a while back on earth, there may be other mechanisms for the eye ﬁndings in SANS than elevated intracranial pressure. -Mark L. Moster, MD Moster and Bhatti: J Neuro-Ophthalmol 2020; 40: 274-280 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.
|Publisher||Lippincott, Williams & Wilkins|
|Source||Journal of Neuro-Ophthalmology, June 2020, Volume 40, Issue 2|
|Rights Management||© North American Neuro-Ophthalmology Society|
|Publication Type||Journal Article|