Title | JNO Literature Commentary |
OCR Text | Show Literature Commentary Section Editors: Mark L. Moster, MD M. Tariq Bhatti, MD JNO Literature Commentary June 2021’ In this issue of JNO, Drs. M. Tariq Bhatti and Mark L. Moster discuss the following 6 articles: 1. Vynckier J, Demeestere J, Lambert J. Black-blood MRI in Giant Cell Arteritis. J Rheumatol. 2021;48:301–302. 2. Hwang CJ, Nichols EE, Chon BH, Perry JD. Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab. Eur J Ophthalmol. 2021:1120672121991042. doi: 10.1177/1120672121991042. Epub ahead of print. PMID: 33525898. 3. Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A, Gilhus NE, Illa I, Kuntz NL, Massey J, Melms A, Murai H, Nicolle M, Palace J, Richman D, Verschuuren J. International Consensus Guidance for Management of Myasthenia Gravis: 2020 Update. Neurology. 2021;96:114–122. 4. Mastrangelo V, Merli E, Rucker JC, Eggenberger ER, Zee DS, Cortelli P. Neuro-Ophthalmological Findings in Early Fatal Familial Insomnia. Ann Neurol. 2021. doi: 10.1002/ana.26008. Epub ahead of print. PMID: 33386648. 5. D’Antona L, Jaime Merchan MA, Vassiliou A, et al. Clinical Presentation, Investigation Findings, and Treatment Outcomes of Spontaneous Intracranial Hypotension Syndrome: A Systematic Review and Meta-analysis. JAMA Neurol. Published online January 04, 2021. doi:10.1001/jamaneurol.2020.4799. 6. Simonett JM, Skalet AH, Lujan BJ, Neuwelt EA, Ambady P, Lin P. Risk Factors and Disease Course for Blood– Brain Barrier Disruption-Associated Maculopathy. JAMA Ophthalmol. 2021;139:143–149. doi: 10.1001/ jamaophthalmol.2020.5329. PMID: 33270081; PMCID: PMC7716256. Vynckier J, Demeestere J, Lambert J. Black-blood Magnetic Resonance Imaging in Giant Cell Arteritis. J Rheumatol. 2021 Feb;48(2):301–302. COMMENTS This case report literally caught my eye. Figure 1 shows enhancement of the temporal arteries using black-blood MRI (BB-MRI), a technique that suppresses intraluminal gadolinium allowing for better visualization of blood vessel wall enhancement. BB-MRI is commonly used in patients with suspected vasculitis (Fig. 1) or arterial dissection. I went back to the Sommer et al’s study that is cited in the case report as I had not seen that article before (1). In this study, 14 of 18 patients with giant cell arteritis (GCA) demonstrated enhancement along the posterior ciliary arteries on 3 dimensional T1 BB-MRI. None of the 9 patients without GCA had enhancement. The BB-MRI had a sensitivity of 92.9%, specificity of 92.3%, positive predictive value of 92.9%, and a negative predictive value of 92.3%. I had my “go to” neuroradiologist look at the images published in the article, and this is what he had to say, “enhancement does show up on black blood imaging—but I think all this enhancement would also show up on regular post contrast fat suppressed imaging.. not overly impressed.” —M. Tariq Bhatti, MD 272 1. Sommer NN, Treitl KM, Coppenrath E, Kooijman H, Dechant C, Czihal M, Kolben TM, Beyer SE, Sommer WH, Saam T. Threedimensional high-resolution black-blood magnetic resonance imaging for detection of arteritic anterior ischemic optic neuropathy in patients with giant cell arteritis. Invest Radiol. 2018;53:698–704. Tariq, Tariq, Tariq! Trying to get away easy by reviewing a single case report? Well, you’ve actually got a good one here. It looks very impressive on the images in the paper, but we don’t know how sensitive or specific the finding of enhancement of the vessel wall is for vasculitis or GCA. Time will tell whether this will be THE technique that finally convinces neuro-ophthalmologists to abandon temporal artery biopsies or be one of the many “false prophets” we’ve been accustomed to over the years (ultrasound, standard MRI, positron emission tomography scan etc.). —Mark L. Moster, MD Hwang CJ, Nichols EE, Chon BH, Perry JD. Bilateral dysthyroid compressive optic neuropathy responsive to teprotumumab. Eur J Ophthalmol. 2021 Feb 1:1120672121991042. doi: 10.1177/ 1120672121991042. Epub ahead of print. PMID: 33525898 Abstract: Thyroid eye disease is an auto-immune mediated orbitopathy, which can cause dysthyroid compressive optic Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 272-277 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary FIG. 1. Black-blood MRI. A. Precontrast and (B) postcontrast high-resolution proton density sequence. Red circles indicate arterial wall enhancement consistent with vasculitis. Courtesy of Laurence J. Eckel MD, Mayo Clinic. neuropathy. Traditional management of active thyroid eye disease includes temporizing high-dose steroids, orbital radiation, and surgical decompression, which each possess significant limitations and/or side effects. Teprotumumab is an IGF-IR inhibitor recently FDA approved for active thyroid eye disease. The authors report reversal of bilateral dysthyroid compressive optic neuropathy managed medically using teprotumumab. COMMENTS I know what you are thinking Mark, “another case report, can’t this guy give me more to work with?” Well, my friend let me remind you that the idea for many great studies often starts from one patient! I chose this case report to highlight for our devoted groupies the potential for teprotumumab as a potential treatment for dysthyroid optic neuropathy (DON). To date, there have been only 2 other similar cases published, and interestingly one of them was published the same month as this one (1,2). Also, in the just completed (and highly successful) virtual NANOS annual meeting, there was a poster of a case report of successful treatment of DON with teprotumumab (3). As you know in the clinical studies of teprotumumab for thyroid eye disease, there were no patients enrolled who had DON, and all cases had a clinical activity score (CAS) . 4. I reviewed the teprotumumab package insert for its indication and usage, and all it reads is “thyroid eye disease.” (4) So, technically using teprotumumab for DON would not be “off label,” but a more robust study would be needed to determine its efficacy, but then again maybe all that is needed is more clinical experience. —M. Tariq Bhatti, MD Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 272-277 1. SearsCM, AzadAD, DosiouC, KosslerAL. Teprotumumab for dysthyroid optic neuropathy: early response to therapy. Ophthalmic Plast Reconstr Surg. 2020. doi: 10.1097/ IOP.0000000000001831. 2. SlentzDH, SmithTJ, KimDS, JosephSS. Teprotumumab for optic neuropathy in thyroid eye disease. JAMA Ophthalmol. 2021;139:244–247. 3. LopezML, ThomasD, ThomasC. Temprotumumab treats sightthreatening thyroid disease. Presented as a poster (#2) at 47th annual NANOS meeting. 2021. 4. Available at: https://www.accessdata.fda.gov/drugsatfda_ docs/label/2020/761143s000lbl.pdf. When I saw this I was thinking “another case report, can’t this guy give me more to work with?” Plus, let me remind you that you and I are likely our only “groupies.” Seriously, this case report is very encouraging, and as you mentioned, numerous others have been reported in addition to the growing anecdotal experience of many neuroophthalmologist and oculoplastic subspecialists. This case report also shows a dramatic reduction in size of the extraocular muscles but interestingly shows worsening of lid retraction with treatment. It is fortunate that the Food and Drug Administration has not restricted the approval to the criteria in the clinical trials, which excluded patients with DON from the studies. —Mark L. Moster, MD Narayanaswami P, Sanders DB, Wolfe G, Benatar M, Cea G, Evoli A, Gilhus NE, Illa I, Kuntz NL, Massey J, Melms A, Murai H, Nicolle M, Palace J, Richman D, Verschuuren J. International Consensus Guidance 273 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary for Management of Myasthenia Gravis: 2020 Update. Neurology. 2021 Jan 19;96(3):114–122 Objective: To update the 2016 formal consensus-based guidance for the management of myasthenia gravis (MG) based on the latest evidence in the literature. Methods: In October 2013, the Myasthenia Gravis Foundation of America appointed a task force to develop treatment guidance for MG, and a panel of 15 international experts was convened. The RAND/UCLA appropriateness method was used to develop consensus recommendations pertaining to 7 treatment topics. In February 2019, the international panel was reconvened with the addition of one member to represent South America. All previous recommendations were reviewed for currency, and new consensus recommendations were developed on topics that required inclusion or updates based on the recent literature. Up to 3 rounds of anonymous e-mail, votes were used to reach consensus, with modifications to recommendations between rounds based on the panel input. A simple majority vote (80% of panel members voting “yes”) was used to approve minor changes in grammar and syntax to improve clarity. Results: The previous recommendations for thymectomy were updated. New recommendations were developed for the use of rituximab, eculizumab, and methotrexate as well as for the following topics: early immunosuppression in ocular MG and MG associated with immune checkpoint inhibitor treatment. Conclusion: This updated formal consensus guidance of international MG experts, based on new evidence, provides recommendations to clinicians caring for patients with MG worldwide. COMMENTS I think it is always wonderful to get advice from an international group of experts on a specific disease. This 2020 management guideline on myasthenia gravis (MG) is an update from 2016. There is a lot of excellent information in this article, but I want to concentrate on ocular MG: Ophthalmoparesis or ptosis in ocular MG that is not responding to anticholinesterase agents should be treated with immunosuppressant (IS) agents if symptoms are functionally limiting or troublesome to the patient. Corticosteroids should be used as the initial IS agent in ocular MG. Steroid-sparing IS agents may be needed when corticosteroids alone are ineffective, contraindicated, or not tolerated. Data from a single small randomized controlled trial suggest that low-dose corticosteroids may be effective for ocular MG and may avoid side effects associated with high-dose corticosteroids. Seropositive acetylcholine receptor antibody patients with ocular MG who do not respond adequately to acetylcholinesterases and who either prefer not to take IS therapy or have contraindications to or are refractory to IS agents may be offered thymectomy. 274 Verma et al just published a retrospective chart review of 103 patients with ocular MG to determine the effectiveness of long-term (.3 years) low-dose (,7.5 mg/day) prednisone. Forty six percent of patients required low-dose prednisone to maintain binocular single vision, and 37% required an IS agent (1). —M. Tariq Bhatti, MD 1. VermaR, WolfeGI, KupersmithMJ. Ocular myasthenia gravis How effective is low dose prednisone long term? J Neurol Sci. 2021;420:117274. This update is quite useful, but it would have been better if they had reiterated the prior recommendations so one can see it all in one place. For instance, they do not discuss their prior recommendations about using azathioprine and mycophenolate mofetil. This group of experts has a huge collective experience with MG. What is missing, although, is that not one of them is a neuro-ophthalmologist. If one considers that each of us likely follow hundreds of ocular MG patients and that many of them do not see neuromuscular subspecialists, there may be some missing expertise in this article when it comes to ocular MG. For instance, I would not agree that “corticosteroids should be used as the initial IS agent in ocular MG.” It is just as reasonable to try a different IS agent such as mycophenolate mofetil. I believe it was one of our society’s founders, Bob Daroff, who said, “the number of different treatment regimens for MG equals the number of treatment centers.” —Mark L. Moster, MD Mastrangelo V, Merli E, Rucker JC, Eggenberger ER, Zee DS, Cortelli P. Neuro-Ophthalmological Findings in Early Fatal Familial Insomnia. Ann Neurol. 2021 Jan 2. doi: 10.1002/ana.26008. Epub ahead of print. PMID: 33386648 Abstract: Fatal familial insomnia (FFI) is a rare inherited prion disease characterized by sleep, autonomic, and motor disturbances. Neuro-ophthalmological abnormalities have been reported at the onset of disease, although not further characterized. We analyzed video recordings of eye movements of 6 patients with FFI from 3 unrelated kindreds, seen within 6 months from the onset of illness. Excessive saccadic intrusions were the most prominent findings. In patients with severe insomnia, striking saccadic intrusions are an early diagnostic clue for FFI. The fact that the thalamus is the first structure affected in FFI also suggests its role in the control of steady fixation. Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 272-277 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary COMMENTS I am taking the opportunity to review an article on another disease outside of our subspecialty expertise but with prominent eye movement abnormalities. The article reviews 6 patients with familial fatal insomnia (FFI), a rare inherited prion disease caused by D178N pathogenic mutation of the prion protein (PRNP) gene, coupled with methionine at methionine (M)—valine (V) polymorphic codon 129. It presents in the fourth to 6th decade with insomnia, autonomic and motor overactivity, and dream-like behavior. The article describes a patient recently seen in Bologna, Italy, and a review of 5 prior patients from 2 other families who were seen in the past 30 years in Bologna. These patients have normal visual acuity, pupillary function, and fundus examinations. Videos taken within 6 months of onset of the symptom of insomnia of the 6 patients were sent to our colleagues and coauthors Dr. Janet Rucker, Eric Eggenberger, and David Zee for review and documentation of eye movement abnormalities, which forms the basis of this report. The examination of the index patient (52-year-old man with severe insomnia, binocular horizontal diplopia, and gait disturbance) with illustrated eye movement recordings showed continuous horizontal saccadic intrusions that were separated by an intersaccadic interval, resembling squarewave jerks (SWJs), macro-SWJs, and macrosaccadic oscillations, the latter related to saccadic hypermetria. Vertical saccades were accompanied by a large horizontal component, resulting in a “zig-zag” pattern of eye movement. Saccade speed appeared normal. Oculography showed continuous SWJs during fixation straight ahead and a large horizontal component with attempted vertical saccades. Other patients had similar findings, and video can be seen online (https://onlinelibrary-wiley-com.proxy1.lib.tju.edu/ action/downloadSupplement?doi=10.1002%2Fana. 26008&file=ana26008-sup-0001-Video+1.mp4). MRI and pathology in this condition shows first thalamic and then cerebellar degeneration. Because the ocular motor findings are early in the presentation, the authors suggest that the thalamus has an important role in fixation. Similar saccadic abnormalities occur in Friedreich ataxia and progressive supranuclear palsy, but there are other abnormalities and different symptomatic presentations. The bottom line is that we can be helpful in the early diagnosis of FFI. —Mark L. Moster, MD Kudos to our colleagues Drs. Rucker, Eggenberger, and Zee for their expertise in reviewing the eye movement videos of these patients. It is amazing how technology has allowed us to be truly a global medical community. Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 272-277 Did you notice that 5 of the 6 patients had decrease blink rate, and 4 of the 6 patients had an esotropia? I wonder if the sporadic form of fatal insomnia has similar eye movement findings? Some people reading this article may think to themselves, who cares because I will never see a case of FFI. But I would say to those people, “never say never”. As you said Mark, we as neuroophthalmologists can be helpful in the early diagnosis of FFI, if we are asked to see a patient with “funny eye movements” and can recall this case series. Yes, I agree this is a rare disease, but I think this is an important observation (so important in fact that the Annals of Neurology, one of the leading neurology journals in the world, accepted it for publication) because the findings can be extrapolated to other neurological diseases with similar eye movement findings to explain the underlying pathophysiology. —M. Tariq Bhatti, MD D’Antona L, Jaime Merchan MA, Vassiliou A, et al. Clinical Presentation, Investigation Findings, and Treatment Outcomes of Spontaneous Intracranial Hypotension Syndrome: A Systematic Review and Meta-analysis. JAMA Neurol. Published online January 04, 2021. doi:10.1001/ jamaneurol.2020.4799 Importance: Spontaneous intracranial hypotension (SIH) is a highly disabling but often misdiagnosed disorder. The best management options for patients with SIH are still uncertain. Objective: To provide an objective summary of the available evidence on the clinical presentation, investigations findings, and treatment outcomes for SIH. Data Sources: Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline– compliant systematic review and meta-analysis of the literature on SIH. Three databases were searched from inception to April 30, 2020: PubMed/MEDLINE, Embase, and Cochrane. The following search terms were used in each database: spontaneous intracranial hypotension, low CSF syndrome, low CSF pressure syndrome, low CSF volume syndrome, intracranial hypotension, low CSF pressure, low CSF volume, CSF hypovolemia, CSF hypovolaemia, spontaneous spinal CSF leak, spinal CSF leak, and CSF leak syndrome. Study Selection: Original studies in English language reporting 10 or more patients with SIH were selected by consensus. Data Extraction and Synthesis: Data on clinical presentation, investigations findings, and treatment outcomes were collected and summarized by multiple observers. Randomeffect meta-analyses were used to calculate pooled estimates of means and proportions. Main Outcomes and Measures: The predetermined main outcomes were the pooled estimate proportions of symptoms of SIH, imaging findings (brain and spinal imaging), and treatment outcomes (conservative, epidural blood patches, and surgical). 275 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Results: Of 6,878 articles, 144 met the selection criteria and reported on average 53 patients with SIH each (range, 10–568 patients). The most common symptoms were orthostatic headache (92% [95% CI, 87%–96%]), nausea (54% [95% CI, 46%–62%]), and neck pain/stiffness (43% [95% CI, 32%–53%]). Brain MRI was the most sensitive investigation, with diffuse pachymeningeal enhancement identified in 73% (95% CI, 67%–80%) of patients. Brain MRI findings were normal in 19% (95% CI, 13%–24%) of patients. Spinal neuroimaging identified extradural cerebrospinal fluid in 48%–76% of patients. Digital subtraction myelography and magnetic resonance myelography with intrathecal gadolinium had high sensitivity in identifying the exact leak site. Lumbar puncture opening pressures were low, normal (60– 200 mm H2O), and high in 67% (95% CI, 54%–80%), 32% (95% CI, 20%–44%), and 3% (95% CI, 1%–6%), respectively. Conservative treatment was effective in 28% (95% CI, 18%– 37%) of patients, and a single epidural blood patch was successful in 64% (95% CI, 56%–72%). Large epidural blood patches (.20 mL) had better success rates than small epidural blood patches (77% [95% CI, 63%–91%] and 66% [95% CI, 55%–77%], respectively). Conclusions and Relevance: Spontaneous intracranial hypotension should not be excluded on the basis of a nonorthostatic headache, normal neuroimaging findings, or normal lumbar puncture opening pressure. Despite the heterogeneous nature of the studies available in the literature and the lack of controlled interventional studies, this systematic review offers a comprehensive and objective summary of the evidence on SIH that could be useful in guiding clinical practice and future research. COMMENTS The location of the CSF leak was typically spinal, most often thoracic, followed by cervical and least often lumbar. Multiple leak sites occurred in 24%. Lumbar puncture showed that 67% had opening pressure below 60 mm H2O, and the rest had normal pressures, the highest being 228 mm H2O. Conservative treatment with bed rest and hydration was successful in 28%, but the best treatment was blood patch, successful 64% of the time. Results were similar with targeted or nontargeted injections. Although this study has the limitations of a meta-analysis of many studies, it does provide much insight into SIH. I was surprised that only 6% had diplopia. Before reading this article, I believed that we see many of these patients in neuro-ophthalmology practice with sixth nerve palsy. However, there are obviously many out there that do not have any visual symptoms. Another surprise was 15% with a reduced level of consciousness. As the authors emphasize, SIH can be seen without orthostatic headache and without MRI findings so one must maintain a high level of suspicion. —Mark L. Moster, MD My personal experience with SIH has been that it often does not result neuro-ophthalmic manifestations. Yes, I have seen sixth in nerve palsy because of SIH, but more often when asked to examine patients with nonspecific visual complaints (such as blurred vision), the examination was normal. —M. Tariq Bhatti, MD This article is a review and meta-analysis of the clinical presentation, investigations, findings, and treatment outcomes in 144 studies on spontaneous intracranial hypotension (SIH) syndrome, an often misdiagnosed and underdiagnosed condition. Typically, these patients present with postural headache because of cerebrospinal (CSF) leak or CSF hypotension of ,60 mm H2O. In these 144 articles analyzed, the mean age of patients was 42.5 years with a range of 2–88 years, and 63% were female. Connective tissue disorders, spinal arthritic conditions, and bariatric surgery were identified as risk factors for SIH. Clinical presentation was mainly headache in 97% of patients with 92% of these being orthostatic in nature. Nausea/vomiting was seen in 54%, neck pain in 43%, hearing disturbances in 28%, dizziness in 27%, tinnitus in 20%, and vertigo in 17%. Visual symptoms included photophobia in 11%, diplopia in 6%, and other visual symptoms (blurred vision, nystagmus, and/or visual loss) was seen in 14%. MRI was the most important diagnostic test, and 73% showed diffuse pachymeningeal enhancement, 35% had subdural collections, 43% brain sagging, 57% venous engorgement, and 38% pituitary gland enlargement. However, 19% had a normal MRI. 276 Simonett JM, Skalet AH, Lujan BJ, Neuwelt EA, Ambady P, Lin P. Risk Factors and Disease Course for Blood–Brain Barrier Disruption-Associated Maculopathy. JAMA Ophthalmol. 2021 Feb 1;139(2):143–149. doi: 10.1001/ jamaophthalmol.2020.5329. PMID: 33270081; PMCID: PMC7716256 Importance: Blood–brain barrier disruption (BBBD) is a systemic therapy for malignant central nervous system (CNS) tumors that has been linked to poorly understand pigmentary maculopathy. Objectives: To examine the rate of and risk factors for the development of BBBD-associated maculopathy and to assess whether there can be visually significant progression after completion of systemic therapy. Design, setting, and participants: In this retrospective case series, data from February 1, 2006, through December 31, 2019, were collected from patients treated with osmotic BBBD at a single tertiary referral center who had subsequent ophthalmic evaluation. Exposures: Treatment with BBBD therapy for any malignant CNS tumor. Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 272-277 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Literature Commentary Main outcomes and measures: Rate and potential risk factors for developing BBBD-associated maculopathy and changes in visual acuity and retinal imaging characteristics after completion of BBBD therapy. Results: Of 283 patients treated with BBBD and chemotherapy for a CNS malignant neoplasm, 68 (mean [SD] age, 46.0 [17.9] years; 25 [38.5%] female) had an ophthalmic examination after starting systemic therapy. After excluding 3 patients because of bilateral media opacities, pigmentary maculopathy was present in 32 of 65 patients (49.2%) treated with BBBD. The number of BBBD treatment sessions, but not age, CNS malignant cancer type, or systemic chemotherapy agent, was associated with maculopathy development (odds ratio, 1.30; 95% CI, 1.12–1.50; P = 0.001). After completion of BBBD therapy, progressive enlargement of geographic atrophy occurred in 5 eyes of 3 patients, and choroidal neovascularization developed in 1 eye. Conclusions and relevance: In this case series, an association was found between BBBD-related maculopathy and the number of BBBD treatment sessions, suggesting a dose-dependent effect. In some cases, maculopathy progression, including enlargement of geographic atrophy, occurred years after completion of systemic therapy. These findings may have important implications for patient education and ophthalmic monitoring. COMMENTS Osmotic blood–brain barrier disruption (BBBD) is a treatment modality used to open the BBB, allowing enhanced access to the central nervous system (CNS) of chemotherapy for brain cancer treatment. It consists of intra-arterial injection of a warmed, hypertonic mannitol solution to disrupt the tight junctions of vascular endothelial cells that form the blood–brain barrier followed by intraarterial or intravenous chemotherapy. Pigmentary maculopathy has been described in patients with primary CNS lymphoma treated with BBBD. This retrospective case series looked at the rate of and potential risk factors for maculopathy development in patients with a variety of malignant CNS tumors treated with BBBD therapy. All patients received either methotrexate or carboplatin. Of 283 patients treated with osmotic BBBD, 68 patients had a documented ophthalmoscopic examination and/or retinal imaging after their BBBD therapy start date. Tumors included primary CNS lymphoma in 51%, glioma in 32%, Moster and Bhatti: J Neuro-Ophthalmol 2021; 41: 272-277 pineal tumor in 9%, and others in 8%. The average number of BBBD treatment sessions was 20. Macular pigmentary changes or retinal pigment epithelial (RPE) atrophy was present in 32 patients (49.2%) and occurred in all CNS tumor categories. Maculopathy appearance was variable and included central RPE stippling, reticular pigmentary changes, parafoveal bull’s eye, and parafoveal or subfoveal geographic atrophy. Fourteen of the 15 (93.3%) patients with maculopathy and OCT imaging had evidence of focal ellipsoid zone disruption. The only feature associated with development of maculopathy was the number of BBBD treatment sessions and not age, sex, type of CNS tumor, presence of intraocular lymphoma, or which chemotherapy was administered. The authors postulate disruption of the blood– retinal barrier as a likely mechanism for the damage. Limitations of the study as the authors describe include its retrospective nature, limited follow-up, lack of a standardized retinal imaging protocol, and the possibility of other coexisting causes of maculopathy. This study, despite limitations, demonstrates that maculopathy can start late after BBBD and progress way beyond the treatments. It also occurs in tumors other than primary CNS lymphoma. —Mark L. Moster, MD Let me honest, I was not aware of osmotic BBBDassociated maculopathy in the treatment of CNS lymphoma, and as this study has shown in other CNS tumors as well. I have a couple thoughts I would like to share. First, it appears none of the patients had an eye examination before treatment, which raises the question (as you alluded to) if some of these patients had a pre-existing maculopathy that could be a risk factor for the development of BBBDassociated maculopathy? Second, the authors discuss the inner blood–retinal barrier of the RPE tight junctions as the possible site of pathology. But as you know there is a second retinal barrier, the outer-retinal barrier composed the nonfenestrated retinal capillaries. I wonder why this barrier is not disrupted with osmotic BBBD resulting in macular edema? —M. Tariq Bhatti, MD 277 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |
Date | 2021-06 |
Language | eng |
Format | application/pdf |
Type | Text |
Publication Type | Journal Article |
Source | Journal of Neuro-Ophthalmology, June 2021, Volume 41, Issue 2 |
Collection | Neuro-Ophthalmology Virtual Education Library: Journal of Neuro-Ophthalmology Archives: https://novel.utah.edu/jno/ |
Publisher | Lippincott, Williams & Wilkins |
Holding Institution | Spencer S. Eccles Health Sciences Library, University of Utah |
Rights Management | © North American Neuro-Ophthalmology Society |
ARK | ark:/87278/s6gpjt8m |
Setname | ehsl_novel_jno |
ID | 1996610 |
Reference URL | https://collections.lib.utah.edu/ark:/87278/s6gpjt8m |