Publications by authors named "Prem S Subramanian"

102 Publications

Embolic abducens palsy and central retinal artery occlusion in a patient with COVID-19.

J Neuroophthalmol 2021 Mar 30. Epub 2021 Mar 30.

Sue Anschutz-Rodgers University of Colorado Eye Center and Departments of Ophthalmology Neurology Neurosurgery, University of Colorado School of Medicine, Aurora, CO Division of Ophthalmology, Uniformed Services University of the Health Sciences, Bethesda, MD.

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http://dx.doi.org/10.1097/WNO.0000000000001291DOI Listing
March 2021

Ocular, Orbital, and Sinus Damage Induced by a Fierce Fishhook Trauma.

Asia Pac J Ophthalmol (Phila) 2021 Mar 23;10(2):226-227. Epub 2021 Mar 23.

Ophthalmology Department, University of Colorado School of Medicine, Aurora, CO, USA.

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http://dx.doi.org/10.1097/APO.0000000000000375DOI Listing
March 2021

Meningiomas of the Planum Sphenoidale and Tuberculum Sella.

J Neurol Surg B Skull Base 2021 Feb 12;82(1):72-80. Epub 2021 Feb 12.

Department of Ophthalmology, Sue Anschutz-Rodgers UCHealth Eye Center, University of Colorado School of Medicine, Aurora, Colorado, United States.

Patients with meningiomas of the planum sphenoidale and tuberculum sella often present with insidious vision loss in one or both eyes as the only sign or symptom of their disease, although other sensory, oculomotor, and even endocrine abnormalities may be seen in a minority of cases. Incidentally discovered tumors also are common, as patients may undergo neuroimaging for unrelated symptoms or events. Depending on the size and orientation of the tumor, central vision loss from optic nerve compression may be a later sign, and loss of peripheral vision in one or both eyes may not be recognized until it has progressed to areas closer to fixation. A thorough neuroophthalmologic assessment including visual field testing will help to define the extent of optic pathway involvement. Both fundus examination and optical coherence tomography of the retinal nerve fiber layer and macular ganglion cell complex will aid in determining prognosis after treatment of the tumor. Orbital surgery rarely is indicated as primary therapy for meningiomas in this location, and surgical resection or debulking is usually pursued before consideration is given to radiation therapy. Because of the long-term risk of residual tumor growth or recurrence, neuroophthalmic surveillance along with serial neuroimaging is required for years after tumor resection and/or radiation therapy.
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http://dx.doi.org/10.1055/s-0040-1722703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987389PMC
February 2021

Mismatch in Supply and Demand for Neuro-Ophthalmic Care.

J Neuroophthalmol 2021 Mar 23. Epub 2021 Mar 23.

Department of Ophthalmology (AD), Wills Eye Hospital, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania; Departments of Ophthalmology, Neurology, and Neurosurgery (PSS), Sue Anschutz-Rodgers UCHealth Eye Center, University of Colorado School of Medicine, Aurora, Colorado; Institute for Minority Health Research (MSB), University of Illinois College of Medicine, Chicago, Illinois; Departments of Ophthalmology and Neurology (MLM), Wills Eye Hospital, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Neurology (PCC), Johns Hopkins School of Medicine, Baltimore, Maryland; and Departments of Ophthalmology and Neurosciences (LPF), Rutgers-New Jersey Medical School, Newark, New Jersey.

Background: Previous research suggests the number of neuro-ophthalmologists in the United States may be below a level that provides sufficient access to neuro-ophthalmic care in much of the United States. However, national estimates of the amount of clinical time spent on neuro-ophthalmology are lacking.

Methods: The North American Neuro-Ophthalmology Society administered a survey on professional time allocation to its active members. Survey response was 95%. The survey characterized the hours each week each respondent allocated to overall work, clinical work, clinical work in ophthalmology/neurology, and clinical work in neuro-ophthalmology specifically. The survey additionally collected information regarding demographics, current wait times to be seen for new patients, and the difference in clinical time spent in neuro-ophthalmology spent between the current day compared with that shortly after completing clinical training. Linear regression was used to identify potential relationships between the above and average wait time.

Results: On average, responding physicians spent 70% of their clinical time on neuro-ophthalmology. In 6 states, there were no reported practicing neuro-ophthalmologists, and in only 8 states was the clinical full-time equivalent to population ratio below the suggested threshold of 1 for every 1.2 million. The median wait time for a new patient was 6 weeks. This wait time was associated with the fraction of clinical time spent in neuro-ophthalmology (0.2 weeks longer wait for a 10 percentage point increase in the fraction of time spent in neuro-ophthalmology; P = 0.02), and suggestively associated with training (training in ophthalmology was associated with 1.0 week shorter wait time; P = 0.06).

Conclusion: The survey suggests that neuro-ophthalmologists are unable to see patients in a timely manner and a decreasing number of clinicians are entering the field. Future interventions should be considered to incentivize neuro-ophthalmology training in ophthalmology and neurology residents such that the United States population is able to appropriately access neuro-ophthalmic care.
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http://dx.doi.org/10.1097/WNO.0000000000001214DOI Listing
March 2021

Neuro-Ophthalmology at American Academy of Ophthalmology 2020 Virtual.

J Neuroophthalmol 2021 Mar 23. Epub 2021 Mar 23.

Departments of Ophthalmology, Sue Anschutz-Rodgers University of Colorado Eye Center, Neurology, and Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado.

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http://dx.doi.org/10.1097/WNO.0000000000001209DOI Listing
March 2021

Persistent Globe Flattening in Astronauts following Long-Duration Spaceflight.

Neuroophthalmology 2021 3;45(1):29-35. Epub 2020 Sep 3.

Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas, USA.

Posterior globe flattening has been well-documented in astronauts both during and after long-duration space flight (LDSF) and has been observed as early as 10 days into a mission on the International Space Station. Globe flattening (GF) is thought to be caused by the disc centred anterior forces created by elevated volume and/or pressure within the optic nerve sheath (ONS). This might be the result of increased intracranial pressure, increased intraorbital ONS pressure from compartmentalisation or a combination of these mechanisms. We report posterior GF in three astronauts that has persisted for 7 years or more following their return from LDSFs suggesting that permanent scleral remodelling may have occurred.
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http://dx.doi.org/10.1080/01658107.2020.1791189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946045PMC
September 2020

Acute Complete Oculomotor Nerve Palsy in a Young Male Due to a Skull Base Myofibroma.

J Neuroophthalmol 2021 Jan 11. Epub 2021 Jan 11.

Ophthalmology Department (TTH, NHTL), Hanoi Medical University, Hanoi, Vietnam; Ophthalmology Unit (TTH, NHTL), Hanoi Medical University Hospital, Hanoi, Vietnam; Save Sight Institute (TTH), the University of Sydney School of Medicine, Sydney, Australia; Neurology Unit (TVL), Hanoi Medical University Hospital, Hanoi, Vietnam; Neurosurgery Department I (DT), Viet Duc Hospital, Hanoi, Vietnam; Pathology Department (TDH), Viet Duc Hospital, Hanoi, Vietnam; and Ophthalmology Department (PSS), University of Colorado School of Medicine, Aurora, Colorado.

Abstract: A 25-year-old male patient visited the ophthalmology clinic because of upper eye lid ptosis in the right eye, binocular double vision, and light sensitivity. He was diagnosed with a complete third nerve palsy caused by a skull base myofibroma, a rare clinical entity that has not been described before in oculomotor nerve palsy.
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http://dx.doi.org/10.1097/WNO.0000000000001177DOI Listing
January 2021

Contralateral Ocular Manifestations of a Carotid Cavernous Fistula Associated With Primitive Persistent Trigeminal Artery.

J Neuroophthalmol 2021 Jan 11. Epub 2021 Jan 11.

Ophthalmology Department (TTH, VTP), Hanoi Medical University, Vietnam; Ophthalmology Unit (TTH), Hanoi Medical University Hospital, Vietnam; Save Sight Institute (TTH), the University of Sydney School of Medicine, Australia; Radiology Department (CNN), Hanoi Medical University Hospital, Vietnam; Oculoplastic and Cosmesis Surgery Department (AQN), Vietnam National Eye Hospital; Cardiology Center (HLN), Hanoi Medical University Hospital, Vietnam; and Ophthalmology Department (PSS), University of Colorado School of Medicine.

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http://dx.doi.org/10.1097/WNO.0000000000001181DOI Listing
January 2021

Neuro-Ophthalmic Complications in Patients Treated With CTLA-4 and PD-1/PD-L1 Checkpoint Blockade.

J Neuroophthalmol 2020 Oct 28. Epub 2020 Oct 28.

Department of Ophthalmology (MMS, NS, LKG), Jules Stein Eye Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, California; Department of Ophthalmology (JJC), Mayo Clinic, Rochester, Minnesota; Department of Neurology (JJC, AZ, ES), Mayo Clinic, Rochester, Minnesota; Department of Ophthalmology & Visual Sciences (RDW), Medical College of Wisconsin, Milwaukee, Wisconsin; Department of Ophthalmology (JDB), Park Nicollet Health Services, Minneapolis, Minnesota; Department of Ophthalmology (OS), University of Kentucky/Retina Associates of Kentucky, Lexington, Kentucky; Department of Neurology (LJM), SUNY Upstate Medical University, Syracuse, New York; Department of Ophthalmology (LJM), SUNY Upstate Medical University, Syracuse, New York; Department of Neurology (SG), University of Missouri-Kansas City, Kansas City, Missouri; Department of Ophthalmology (PMS), University of Vermont Medical Center, Burlington, Vermont; The Medical Eye Center (DAB), Manchester, New Hampshire; Department of Ophthalmology (JF), Oregon Health & Science University, Portland, Oregon; Department of Ophthalmology (CLF), University of Sydney, Sydney, Australia; Department of Neurology & Neurophysiology (CC-S), Liverpool Hospital, NSW, Australia; Department of Neurology (SRH), Virginia Commonwealth University School of Medicine, Richmond, Virginia; Department of Neurology (BH), INI Eye Center, OSF Healthcare, University of Illinois College of Medicine, Peoria, Illinois; Department of Ophthalmology (MDS), University of Utah, Salt Lake City, Utah; Department of Ophthalmology (PSS), University of Colorado, Aurora, Colorado; and Department of Ophthalmology (ZW), University of Rochester Medical Center, Rochester, New York.

Background: In recent years, CTLA-4 and PD-1/PD-L1 checkpoint inhibitors have proven to be effective and have become increasingly popular treatment options for metastatic melanoma and other cancers. These agents work by enhancing autologous antitumor immune responses. Immune-related ophthalmologic complications have been reported in association with checkpoint inhibitor use but remain incompletely characterized. This study seeks to investigate and further characterize the neuro-ophthalmic and ocular complications of immune checkpoint blockade treatment.

Methods: A survey was distributed through the secure electronic data collection tool REDCap to neuro-ophthalmology specialists in the North American Neuro-Ophthalmology Society listserv. The study received human subjects approval through the University of California at Los Angeles Institutional Review Board. The survey identified patients sent for neuro-ophthalmic consultation while receiving one or more of a PD-1 inhibitor (pembrolizumab, nivolumab, or cemiplimab); PD-L1 inhibitor (atezolizumab, avelumab, or durvalumab); or the CTLA-4 inhibitor ipilimumab. Thirty-one patients from 14 institutions were identified. Patient demographics, neuro-ophthalmic diagnosis, diagnostic testing, severity, treatment, clinical response, checkpoint inhibitor drug used, and cancer diagnosis was obtained.

Results: The checkpoint inhibitors used in these patients included pembrolizumab (12/31), nivolumab (6/31), combined ipilimumab with nivolumab (7/31, one of whom also received pembrolizumab during their course of treatment), durvalumab (3/31), ipilimumab (2/31), and cemiplimab (1/31). Malignant melanoma (16/31) or nonsmall cell lung carcinoma (6/31) were the most common malignancies. The median time between first drug administration and the time of ophthalmological symptom onset was 14.5 weeks. Eleven patients had involvement of the optic nerve, 7 patients had inflammatory orbital or extraocular muscle involvement, 6 patients had ocular involvement from neuromuscular junction dysfunction, 4 patients had cranial nerve palsy, and 4 patients had non neuro-ophthalmic complications. Use of systemic corticosteroids with or without stopping the checkpoint inhibitor resulted in improvement of most patients with optic neuropathy, and variable improvement for the other ophthalmic conditions.

Conclusion: This study describes the variable neuro-ophthalmic adverse events associated with use of immune checkpoint inhibitors and contributes a more thorough understanding of their clinical presentations and treatment outcomes. We expect this will increase awareness of these drug complications and guide specialists in the care of these patients.
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http://dx.doi.org/10.1097/WNO.0000000000001148DOI Listing
October 2020

Spaceflight Associated Neuro-Ocular Syndrome (SANS): A Systematic Review and Future Directions.

Eye Brain 2020 19;12:105-117. Epub 2020 Oct 19.

Sue Anschutz-Rodgers/UCHealth Eye Center and Departments of Ophthalmology, Aurora, CO, 80045, USA.

Purpose: To present a systematic review of the current body of literature surrounding spaceflight associated neuro-ocular syndrome (SANS) and highlight priorities for future research.

Methods: Three major biomedical databases were searched with the following terms: ((neuro ocular) OR ((brain) AND (eye))) AND ((spaceflight) OR (astronaut) OR (microgravity)) AND (ENGLISH[Language]). Once duplicates were removed, 283 papers were left. Articles were excluded if they were not written in English or conference abstracts only. We avoided including review papers which did not provide any new information; however, two reviews on the pathophysiology of SANS were included for completeness. No limitations on date of publication were used. All included entries were then summarized for their contribution to knowledge about SANS.

Results: Four main themes among the publications emerged: papers defining the clinical entity of SANS, its pathophysiology, technology used to study SANS, and publications on possible prevention of SANS. The key clinical features of SANS include optic nerve head elevation, hyperopic shifts, globe flattening, choroidal folds, and increased cerebrospinal fluid (CSF) volume in optic nerve sheaths. Two main hypotheses are proposed for the pathophysiology of SANS. The first being elevated intracranial pressure and the second compartmentalization of CSF to the globe. These hypotheses are not mutually exclusive, and our understanding of the pathophysiology of SANS is still evolving. The use of optical coherence tomography (OCT) has greatly furthered our knowledge about SANS, and with the deployment of OCT to the International Space Station, we now have ability to collect intraflight data. No effective prevention for SANS has been found, although fortunately, even with persistent anatomic and physiologic neuro-ocular changes, any functional impact has been correctable with spectacles.

Conclusion: This is the first systematic review of SANS. Despite the limitations of studying a syndrome that can only occur in a small, discrete population, we present a thorough overview of the literature surrounding SANS and several key areas important for future research are identified.
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http://dx.doi.org/10.2147/EB.S234076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585261PMC
October 2020

Visual hallucinations in psychiatric, neurologic, and ophthalmologic disease.

Curr Opin Ophthalmol 2020 Nov;31(6):475-482

Department of Ophthalmology.

Purpose Of Review: Recent studies have increased our understanding of the biochemical and structural bases of visual hallucinations in patients with a variety of underlying causes.

Recent Findings: Visual hallucinations may be related to disruption of functional connectivity networks, with underlying biochemical dysfunction such as decreased in cholinergic activity. Structural abnormalities in primary and higher order visual processing areas also have been found in patients with visual hallucinations. The occurrence of visual hallucinations after vision loss, the Charles Bonnet syndrome, may have more functional similarity to psychiatric and neurodegenerative causes than previously suspected despite retained insight into the unreal nature of the phenomena.

Summary: Visual hallucinations are common, and patients may not report them if specific inquiries are not made. Presence or absence of hallucinations may be of diagnostic and therapeutic importance, especially in patients with neurodegenerative conditions that have overlapping features. Treatment of visual hallucinations remains challenging and must be tailored to each patient based on the underlying cause and comorbid conditions.
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http://dx.doi.org/10.1097/ICU.0000000000000701DOI Listing
November 2020

Considerations for the Treatment of Inflammatory Neuro-Ophthalmologic Disorders During the COVID-19 Pandemic.

J Neuroophthalmol 2020 09;40(3):305-314

Departments of Ophthalmology (YMP, JLB, PSS, VSP), Neurology (YMP, JLB, PSS, VSP), and Neurosurgery (PSS), University of Colorado School of Medicine, Aurora, Colorado; and Programs in Neuroscience and Immunology (JLB), University of Colorado School of Medicine, Aurora, Colorado.

The initiation and continuation of immune-based therapies to treat and prevent complications of inflammatory neuro-ophthalmologic disorders during the 2019 novel coronavirus (COVID-19) pandemic is the subject of considerable debate. In each case, a treatment decision must be reached based on best clinical practices for the disorder, patient comorbidities, the current state of knowledge about the pathogenesis and infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the utilization of hospital and community resources. Unfortunately, the evidence needed to standardize the decision-making process for each neuro-ophthalmologic disorder is currently absent and is likely to require months or years to develop based on the accrual of robust international data sets. In this article, we review the current understanding of SARS-CoV-2 and COVID-19 complications to provide a framework for approaching the treatment of inflammatory neuro-ophthalmic disorders during the COVID-19 viral pandemic.
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http://dx.doi.org/10.1097/WNO.0000000000001016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418184PMC
September 2020

New Initiatives at Journal of Neuro-Ophthalmology: Highlighting Technology, Social Media, and Content for Trainees.

J Neuroophthalmol 2020 09;40(3):285

USC Roski Eye Institute (VRP), Keck School of Medicine, Los Angeles, California; UCHealth Sue Anschutz-Rodgers Eye Center (PSS), Aurora, Colorado; Massachusetts Eye & Ear Infirmary (EF), Harvard Medical School, Boston, Massachusetts; Wilmer Eye Institute (ARC), Johns Hopkins University, Baltimore, Maryland.

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http://dx.doi.org/10.1097/WNO.0000000000001044DOI Listing
September 2020

Less-Lethal Weapons Resulting in Ophthalmic Injuries: A Review and Recent Example of Eye Trauma.

Ophthalmol Ther 2020 Sep 5;9(3):1-7. Epub 2020 Aug 5.

Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA.

Introduction: Prior reports have highlighted the dangers of crowd control weapons such as rubber bullets, paintball guns, and pepper spray. Many of these reports were written decades ago and outside of the USA. We summarize a review of the literature and discuss a contemporary case of a ruptured globe and facial trauma secondary to a projectile weapon. This case serves to highlight the severity of eye trauma caused by less-lethal weapons; severe morbidity or even mortality can occur.

Clinical Description: A civilian presented after a projectile weapon reportedly fired by Denver law enforcement struck his face during one of the recent protests in May 2020 in Denver. Upon ophthalmic examination, we observed no light perception (NLP) vision, periorbital ecchymosis, and devastating globe trauma.

Primary Diagnosis, Interventions, And Outcomes: Further examination revealed a severely ruptured globe with extensive hemorrhage and extrusion of intraocular contents. Attempts to repair the ruptured globe failed because of the lack of remaining scleral tissue and expulsion of intraocular contents. Postoperatively, the visual acuity remained NLP and the eye was unable to hold pressure. Subsequently, the patient elected for enucleation.

Conclusion: Despite the purported safety advancements of less-lethal weapons, we continue to see high levels of morbidity and mortality. Permanent vision loss, loss of the eye, and death caused by these weapons have been reported. We hope that this information will serve as an example to help promote judicious use of these weapons by the proper authorities. Additionally, protesters and bystanders should be aware of these dangers and utilize high-quality eye protection.
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http://dx.doi.org/10.1007/s40123-020-00271-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406611PMC
September 2020

Young Adults With Anterior Ischemic Optic Neuropathy: A Multicenter Optic Disc Drusen Study.

Am J Ophthalmol 2020 09 13;217:174-181. Epub 2020 Apr 13.

Save Sight Institute Faculty of Health and Medicine, The University of Sydney, Sydney, New South Wales, Australia.

Purpose: Optic disc drusen (ODD), present in 2% of the general population, have occasionally been reported in patients with nonarteritic anterior ischemic optic neuropathy (NA-AION). The purpose of this study was to examine the prevalence of ODD in young patients with NA-AION.

Design: Retrospective, cross-sectional multicenter study.

Methods: All patients with NA-AION 50 years old or younger, seen in neuro-ophthalmology clinics of the international ODDS (Optic Disc Drusen Studies) Consortium between April 1, 2017, and March 31, 2019, were identified. Patients were included if ODD were diagnosed by any method, or if ODD were excluded by enhanced-depth imaging optical coherence tomography (EDI-OCT) using ODDS Consortium guidelines. NA-AION eyes with ODD were termed "ODD-AION"; those without were termed "NODD-AION".

Results: A total of 65 patients (127 eyes) with NA-AION were included (mean 41 years old). Of the 74 eyes with NA-AION, 51% had ODD-AION, whereas 43% of fellow eyes without NA-AION had ODD (P = .36). No significant differences were found between ODD-AION and NODD-AION eyes in terms of Snellen best-corrected VA or perimetric mean deviation. According to EDI-OCT results, 28% of eyes with NODD-AION had peripapillary hyperreflective ovoid mass-like structures (PHOMS); 7% had hyperreflective lines, whereas 54% with ODD-AION had PHOMS; and 66% had hyperreflective lines (P = .006 and P < .001, respectively).

Conclusions: Most of these young NA-AION patients had ODD. This indicates that ODD may be an independent risk factor for the development of NA-AION, at least in younger patients. This study suggests ODD-AION be recognized as a novel diagnosis.
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http://dx.doi.org/10.1016/j.ajo.2020.03.052DOI Listing
September 2020

Automated Evaluation of Parapapillary Choroidal Microvasculature in Ischemic Optic Neuropathy and Open Angle Glaucoma.

Invest Ophthalmol Vis Sci 2020 03;61(3):35

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Purpose: To determine whether parapapillary choroidal microvasculature (PPCMv) density as measured by optical coherence tomography angiography differs between nonarteritic anterior ischemic optic neuropathy (NAION) and primary open angle glaucoma (POAG).

Methods: Thirty-seven eyes with chronic NAION, 34 unaffected fellow eyes with NAION, 47 moderate and severe POAG eyes, and 54 healthy control subjects were evaluated. Automated PPCMv density was calculated using custom Matlab software in inner and outer annuli around the optic nerve region in addition to peripapillary superficial retinal vessels.

Results: Linear models showed no difference in peripapillary retinal nerve fiber layer between NAION and POAG eyes. Mean peripapillary superficial small vessels in the NAION and POAG groups were 36.62 ± 7.1% and 39.72 ± 8.18% without a statistically difference between them (P = 0.16). Mean inner and outer annular region PPCMv densities in the NAION group were 26.55 ± 9.2% and 17.81 ± 6.9%, which were not different from unaffected fellow eyes and the control group. However, the POAG group had significantly reduced PPCMv density in both inner and outer annuli with values of 15.84 ± 6.5% and 12.80 ± 5.0%, respectively, compared with normal subjects (both P < 0.001). Inner and outer circle PPCMv densities were also significantly reduced in the POAG group compared with the NAION group.

Conclusions: Reduced PPCMv density in POAG eyes shows that deep optic nerve head ocular blood flow may contribute to axonal damage in patients with glaucoma.
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http://dx.doi.org/10.1167/iovs.61.3.35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401492PMC
March 2020

Perineural Spread of Squamous Cell Carcinoma Without Enlargement or Enhancement of Involved Nerves.

J Neuroophthalmol 2020 03;40(1):e3-e4

Departments of Ophthalmology, Neurology, and Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado.

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http://dx.doi.org/10.1097/WNO.0000000000000906DOI Listing
March 2020

Presentation and Progression of Papilledema in Cerebral Venous Sinus Thrombosis.

Am J Ophthalmol 2020 05 9;213:1-8. Epub 2020 Jan 9.

Department of Ophthalmology, Duke University, Durham, North Carolina, USA. Electronic address:

Purpose: To determine the natural history and visual outcomes of papilledema in cerebral venous sinus thrombosis (CVST).

Design: Retrospective observational case series.

Methods: This multicenter study included 7 tertiary care neuro-ophthalmology clinics. Sixty-five patients with CVST were identified who received serial eye examinations with documented papilledema from 2008-2016. Outcome measures included time from diagnosis to papilledema documentation, papilledema progression, time to papilledema resolution, treatment interventions and final visual outcomes.

Results: Papilledema was present on initial presentation in 54% of patients or detected later during the course of the disease in 46% of patients. The average time from CVST diagnosis to papilledema documentation was 29 days with a mean (SD) initial Frisén grade of 2.7 (1.3). In 21.5% of cases, papilledema progressed over an average of 55.6 (56.6) days. Time to papilledema resolution was approximately 6 months. Final visual acuity ranged from 20/20 to light perception, with 40% of patients having residual visual field defects on standard automated perimetry. Frisén grade ≥3 (odds ratio [OR] 10.21, P < .0053) and cases with worsening papilledema (3.5, P < .043) were associated with permanent visual field deficits.

Conclusions: Our study indicates the importance of serial ophthalmic evaluation in all cases of CVST. Follow-up fundoscopy is critical given that a subset of cases can show delayed onset and/or worsening of papilledema with time. Specifically, we recommend an ophthalmic examination at the time of initial diagnosis, with repeat examination within a few weeks and further follow-up depending on the level of papilledema or vision changes.
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http://dx.doi.org/10.1016/j.ajo.2019.12.022DOI Listing
May 2020

Deep Learning and Transfer Learning for Optic Disc Laterality Detection: Implications for Machine Learning in Neuro-Ophthalmology.

J Neuroophthalmol 2020 06;40(2):178-184

Department of Ophthalmology (TYAL, NRM), Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland; Department of Ophthalmology (DSWT), Singapore Eye Research Institute, Singapore National Eye Center, Duke-NUS Medical School, National University of Singapore, Singapore; Department of Radiology (PHY, FKH), Johns Hopkins University, Baltimore, Maryland; Department of Biomedical Engineering (JW), Johns Hopkins University, Baltimore, Maryland; Computational Interaction and Robotics Lab (HZ, GDH), Johns Hopkins University, Baltimore, Maryland; Department of Ophthalmology (PSS), University of Colorado School of Medicine, Aurora, Colorado; School of Medicine (TL), Johns Hopkins University, Baltimore, Maryland; and Malone Center for Engineering in Healthcare (GDH), Johns Hopkins University, Baltimore, Maryland.

Background: Deep learning (DL) has demonstrated human expert levels of performance for medical image classification in a wide array of medical fields, including ophthalmology. In this article, we present the results of our DL system designed to determine optic disc laterality, right eye vs left eye, in the presence of both normal and abnormal optic discs.

Methods: Using transfer learning, we modified the ResNet-152 deep convolutional neural network (DCNN), pretrained on ImageNet, to determine the optic disc laterality. After a 5-fold cross-validation, we generated receiver operating characteristic curves and corresponding area under the curve (AUC) values to evaluate performance. The data set consisted of 576 color fundus photographs (51% right and 49% left). Both 30° photographs centered on the optic disc (63%) and photographs with varying degree of optic disc centration and/or wider field of view (37%) were included. Both normal (27%) and abnormal (73%) optic discs were included. Various neuro-ophthalmological diseases were represented, such as, but not limited to, atrophy, anterior ischemic optic neuropathy, hypoplasia, and papilledema.

Results: Using 5-fold cross-validation (70% training; 10% validation; 20% testing), our DCNN for classifying right vs left optic disc achieved an average AUC of 0.999 (±0.002) with optimal threshold values, yielding an average accuracy of 98.78% (±1.52%), sensitivity of 98.60% (±1.72%), and specificity of 98.97% (±1.38%). When tested against a separate data set for external validation, our 5-fold cross-validation model achieved the following average performance: AUC 0.996 (±0.005), accuracy 97.2% (±2.0%), sensitivity 96.4% (±4.3%), and specificity 98.0% (±2.2%).

Conclusions: Small data sets can be used to develop high-performing DL systems for semantic labeling of neuro-ophthalmology images, specifically in distinguishing between right and left optic discs, even in the presence of neuro-ophthalmological pathologies. Although this may seem like an elementary task, this study demonstrates the power of transfer learning and provides an example of a DCNN that can help curate large medical image databases for machine-learning purposes and facilitate ophthalmologist workflow by automatically labeling images according to laterality.
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http://dx.doi.org/10.1097/WNO.0000000000000827DOI Listing
June 2020

Effect of Foveal Location on Retinal Nerve Fiber Layer Thickness Profile in Superior Oblique Palsy Eyes.

J Glaucoma 2019 10;28(10):916-921

Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.

PRéCIS:: Superior oblique palsy (SOP) eyes show thinner inferotemporal retinal nerve fiber layer (RNFL) without adjusting for foveal position. There was a strong correlation between the degree of torsion and the difference in the RNFL thickness before and after adjusting foveal location.

Purpose: The impact of foveal position on RNFL thickness has been shown. In this study, we evaluate RNFL thickness profiles according to the disc-foveal angle in SOP and control eyes.

Materials And Methods: In 44 eyes of 22 patients with unilateral congenital SOP and 42 eyes of 42 normal controls, the position of the fovea relative to the optic disc was calculated by optical coherence tomography using FoDi (fovea-to-disc) technology. After measuring RNFL thickness with FoDi alignment technology, each optical coherence tomography image was reevaluated with FoDi turned off, and the measurements were repeated to determine RNFL values according to the disc-foveal angle.

Results: The average disc-foveal angle was -10.85±6.60 degrees and -10.71±6.63 degrees in the affected and fellow eyes of SOP patients; these values were significantly greater than control subjects (-5.88±4.09 degrees). There was no significant difference in RNFL sector values between SOP and control eyes with FoDi. From all RNFL sectors, the measured inferotemporal thickness was less in SOP eyes without FoDi than in SOP eyes with FoDi (129.7±20.5 µm vs. 144.6±17.8 µm, respectively, P=0.001). Differences of the RNFL thicknesses with and without FoDi in SOP eyes in the superotemporal and inferotemporal sectors were 5.40±13.42 and 14.84±15.00, respectively, which were significantly more than the same changes in control eyes with amount of 0.30±6.57 and 8.52±10.4 (P=0.02 for both sectors).

Conclusions: In SOP eyes with large amounts of torsion, a correction for the disc-foveal angle is necessary for accurate determination of the RNFL thickness profile.
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http://dx.doi.org/10.1097/IJG.0000000000001347DOI Listing
October 2019

An overview of spaceflight-associated neuro-ocular syndrome (SANS).

Neurol India 2019 May-Jun;67(Supplement):S206-S211

Blanton Eye Institute, Department of Ophthalmology, Houston Methodist Hospital, Houston; Departments of Ophthalmology, Neurology, and Neurosurgery, Weill Cornell Medicine, New York City, New York; Department of Ophthalmology, Baylor College of Medicine (BCM) and the BCM Center for Space Medicine, Houston, Texas, and University of Texas Medical Branch (UTMB), Galveston; Texas A and M College of Medicine (College Station, Texas), UT MD Anderson Cancer Center, Houston, Texas; University of Iowa Hospitals and Clinics (Iowa City Iowa), and the University of Buffalo, Buffalo, New York, USA.

Over the last decade, the National Aeronautics and Space Administration's (NASA) Space Medicine Division has documented a variety of unusual physiological and pathological neuro-ophthalmic findings in astronauts during and following long duration space flight. These ndings include optic disc swelling, globe flattening, choroidal folds, and hyperopic shifts in refraction. Cephalad fluid shift has been proposed as a possible unifying etiology, but the specific mechanism responsible for these changes remains obscure. This manuscript reviews the history, clinical findings, and potential neurophysiological etiologies for spaceflight-associated neuro-ocular syndrome.
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http://dx.doi.org/10.4103/0028-3886.259126DOI Listing
December 2019

Periocular Histiocytoid Carcinoma: Potential Diagnostic Challenges.

Ocul Oncol Pathol 2019 Feb 5;5(2):94-101. Epub 2018 Jul 5.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Cutaneous histiocytoid carcinoma can occur as a primary tumor of the periocular region. Morphologically similar histiocytoid carcinomas arising as primary tumors of the breast have a predilection for orbital metastases. They can occasionally contain regions with prominent vacuolated cytoplasm and minimal nuclear atypia, which mimic benign histiocytic lesions. Differentiating nonneoplastic, primary neoplastic, and metastatic histiocytoid lesions involving the periorbita can be challenging for both the clinician and the pathologist, and this distinction has management implications. Herein, we present 3 cases to illustrate the challenges of diagnosing periocular histiocytoid carcinoma.
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http://dx.doi.org/10.1159/000490250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6422134PMC
February 2019

Early Ganglion Cell or Macular Vessel Loss After Acute Nonarteritic Anterior Ischemic Optic Neuropathy?

Transl Vis Sci Technol 2019 Apr 4;8(2):12. Epub 2019 Apr 4.

Department of Ophthalmology, Neurology, and Neurosurgery, University of Colorado School of Medicine, Aurora, CO, USA.

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http://dx.doi.org/10.1167/tvst.8.2.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6450639PMC
April 2019

Optical Coherence Tomography Angiography of a Pale Optic Disc in Demyelinating Optic Neuritis and Ischemic Optic Neuropathy.

J Neuroophthalmol 2019 09;39(3):339-344

Farabi Eye Hospital (MAF, SY, HG, SM), Eye Research Center, Department of Ophthalmology, Tehran University of Medical Science, Tehran, Iran; Department of Ophthalmology (RSM), Rasht University of Medical Science, Rasht, Iran; and Department of Ophthalmology, Neurology, and Neurosurgery (PSS), University of Colorado School of Medicine, Aurora, Colorado.

Background: In the setting of a pale optic disc, distinguishing a previous episode of optic neuritis (ON) from that of nonarteritic anterior ischemic optic neuropathy (NAION) may be difficult on clinical examination. Differences in peripapillary vascular network structures, if present, might be of diagnostic utility.

Methods: Thirty-five eyes with demyelinating ON, 33 eyes with NAION, and 81 eyes of normal subjects were imaged with optical coherence tomography angiography (OCT-A) to assess peripapillary vascular density (VD). In addition, OCT was used to measure peripapillary retinal nerve fiber layer (RNFL) thickness. Areas under the receiver operating characteristic curves were used to differentiate ON vs NAION.

Results: NAION eyes had significantly thinner RNFL thickness than ON eyes. Age-adjusted analysis showed that the peripapillary VD values were significantly reduced in NAION (48.3 ± 7.4%) and ON eyes (54.7 ± 6.1%) compared with healthy controls (62.1 ± 4.6%); pairwise comparisons showed statistically significant differences among all 3 groups. After adjustment for severity of optic nerve injury according to mean RNFL thickness, all VD parameters were not significantly different between ON and NAION eyes. The area under the receiver operating characteristic curves for differentiating NAION from ON eyes was similar for VD (0.75) and RNFL thickness (0.74).

Conclusions: Peripapillary VD measurement performs as well as RNFL thickness for distinguishing previous episodes ON and NAION. VD decline might be secondary to RNFL damage and, therefore, VD data have a limited role differentiating these 2 disorders.
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http://dx.doi.org/10.1097/WNO.0000000000000775DOI Listing
September 2019

Perceptual Postural Imbalance and Visual Vertigo.

Curr Neurol Neurosci Rep 2019 03 16;19(5):19. Epub 2019 Mar 16.

Department of Neurology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.

Purpose Of Review: Disorders of posture and balance cause significant patient morbidity, with reduction of quality of life as patients refrain from critical activities of daily living such as walking outside the home and driving. This review describes recent efforts to characterize visual disorders that interact with the neural integrators of positional maintenance and emerging therapies for these disorders.

Recent Findings: Abnormalities of gait and body position sense may be unrecognized by patients but are correlated with focal neurological injury (stroke). Patients with traumatic brain injury can exhibit visual vertigo despite otherwise normal visual functioning. The effect of visual neglect on posture and balance, even in the absence of a demonstrable visual field defect, has been characterized quantitatively through gait analysis and validates the potential therapeutic value of prism treatment in some patients. In addition, the underlying neural dysfunction in visual vertigo has been explored further using functional imaging, and these observations may allow discrimination of patients with structural causes from those whose co-morbid psychosocial disorders may be primarily contributory.
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http://dx.doi.org/10.1007/s11910-019-0939-6DOI Listing
March 2019

Optical Coherence Tomography Angiography in Papilledema Compared With Pseudopapilledema.

Invest Ophthalmol Vis Sci 2019 01;60(1):168-175

Department of Ophthalmology, University of Colorado, School of Medicine, Aurora, Colorado, United States.

Purpose: The purpose of this study is to evaluate differences in optical coherence tomography angiography (OCT-A) findings between patients with papilledema and pseudopapilledema.

Methods: In this prospective, comparative study, 41 eyes of 21 subjects with papilledema, 27 eyes of 15 subjects with pseudopapilledema, and 44 eyes of 44 healthy normal subjects were included and were imaged using OCT-A. In addition to peripapillary total vasculature maps obtained with commercial vessel density mapping, major vessel removal using customized image analysis software was also used to measure whole image capillary density and peripapillary capillary density (PCD). Peripapiilary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) were recorded.

Results: Average RNFL thicknesses were greater in papilledema eyes than in pseudopapilledema and control subjects. GCC thickness was not different among three groups. Peripapillary vasculature values were significantly lower in papilledema (58.5 ± 6.1%) and pseudopapilledema (58.9 ± 4.7%) eyes compared with healthy eyes (63.2 ± 3.1%) using commercial machine software, without a difference between papilledema and pseudopapilledema eyes. However, using our customized software, peripapillary "capillary" density of papilledema eyes was 29.8 ± 9.4%, which was not significantly different from healthy subjects (31.8 ± 7.4%; P = 0.94). Pseudopapilledema eyes with peripapillary density of 25.5 ± 8.3% had significantly lower capillary values compared with control eyes (P = 0.01). There was a significantly lower whole image and nasal sector peripapillary capillary density of inner retina in pseudopapilledema eyes than papilledema eyes (P = 0.03 and P = 0.02, respectively).

Conclusions: Whole image and nasal peripapillary sector capillary densities using OCT-A had diagnostic accuracy for differentiating true and pseudo-disc swelling.
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http://dx.doi.org/10.1167/iovs.18-25453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333108PMC
January 2019

Traumatic brain injury in children: how does it affect the eye and vision?

J AAPOS 2018 12 23;22(6):413-414. Epub 2018 Oct 23.

Departments of Ophthalmology, Neurology, and Neurosurgery, University of Colorado School of Medicine, Aurora, Colorado. Electronic address:

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http://dx.doi.org/10.1016/j.jaapos.2018.10.001DOI Listing
December 2018