Case Report: Asymmetric Visual Field Progression in Melanoma-Associated Retinopathy Heralding Recurrent Malignancy.

PURPOSE: To report a case of asymmetric melanoma-associated retinopathy (MAR) associated with metastatic melanoma which was thought to be in remission for 6 years. Identification of MAR led to the discovery of recurrent malignancy. METHOD: A man in his 60s presented with monocular visual disturbances with a large relative afferent pupillary defect, rapidly progressing visual field defect and otherwise normal eye examination. Initial work-up for retrobulbar optic neuropathy was inconclusive. After a few months, similar symptoms developed in his fellow eye and a full-field electroretinogram revealed a reduced b:a wave ratio suspicious for MAR. RESULTS: Visual field defects were present in both eyes at initial examination, but the visual field of one eye progressed rapidly while the fellow eye did not develop symptoms or progress until roughly 3 months later. Visual field defects and symptoms improved following resection of the lymph node with active metastatic disease and serum plasmapheresis. CONCLUSION: This report highlights a case of MAR with asymmetric objective findings and progression of visual field defects. It also demonstrates the success of plasmapheresis, in combination with treating recurrent metastatic disease, in improving visual function.

Does Inter-Eye Asymmetry of Disc Area Explain Differences in Onset of Nonarteritic Anterior Ischemic Optic Neuropathy?

BACKGROUND: Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common acute optic neuropathy in individuals over the age of 50 years. It is associated with conventional vascular risk factors and structural vulnerabilities including "disc-at-risk." We aim to ascertain if a correlation exists between optic nerve head size and the onset of NAION. METHODS: We performed a retrospective chart review of patients with an ICD-10 diagnosis of unilateral or bilateral NAION who underwent optical coherence tomography (OCT) and visual field testing. The primary outcome measure was the disc area as measured on OCT at a follow-up (minimum 6 months after acute vision loss) of the involved (or first involved for bilateral cases) vs fellow eye. The secondary outcome was the cup-to-disc ratio (CDR) of the first vs fellow eye. RESULTS: Seventy-three patients were included, of which 58 (79%) had unilateral and 15 (21%) had bilateral NAION, with a median follow-up of 23 months. Between the first eye involved and the fellow eye, there were no statistically significant differences in the mean disc area (1.69 ± 0.29 vs 1.71 ± 0.29, P = 0.7). However, average CDR (0.41 ± 0.20 vs 0.28 ± 0.18, P < 0.001) and vertical CDR (0.42 ± 0.20 vs 0.28 ± 0.19, P < 0.0001) were significantly larger in the involved eye. CONCLUSIONS: Despite no statistically significant differences in the disc area between the affected eye and the fellow eye, CDR was larger in eyes with a history of NAION compared with fellow eyes. Further research is required to elucidate local factors that may increase the risk of NAION in one eye relative to the other.

Orthostatic Hemifacial Spasm in Idiopathic Intracranial Hypertension.

BACKGROUND: Among the symptoms seen in idiopathic intracranial hypertension (IIH), hemifacial spasm (HFS) is rare. Orthostatic-induced HFS preceding lumbar puncture (LP) is previously unreported. We treated two patients with unusual IIH presentations. This case series reviews the few reports of HFS in IIH and proposes a mechanism for spasm occurrence. METHODS: Case 1: A woman in her mid-40s with previously controlled IIH developed daily headache, pulsatile tinnitus, right-sided trigeminal paresthesia, and right-sided HFS. The latter 2 symptoms occurred exclusively when moving from a sitting to a standing position. Imaging was unremarkable; opening pressure (OP) on LP was 46 cmH2O with normal cerebrospinal fluid (CSF) components. Case 2: A woman in her late 40s presented with severe daily headache, pulsatile tinnitus, and left-sided HFS following weight gain. Imaging was unremarkable; OP on LP was 32 cmH2O with normal CSF components. RESULTS: HFS episodes persisted following LP in both patients. Increasing and initiating acetazolamide, respectively, resolved all symptoms. CONCLUSIONS: Earlier suggested mechanisms of HFS are based on elevated intracranial pressure (ICP) shifting the facial nerve into proximity of a vascular structure. HFS appearing upon standing and continuing after LP, and thus a lower ICP, contradicts this. We propose a mechanism based on the degree of ICP change. This theory is grounded in the lack of intracranial compliance in IIH, wherein substantial pressure changes occur following small volume changes.

Denial.

A 51-year-old man presented with decreased vision, fever, confusion, headaches, agitation, nausea, vomiting and diarrhea. Magnetic resonance imaging of the brain demonstrated bilateral T2 hyperintense lesions in the region of the mesial temporal lobe and optic radiations. There was a predominantly polymorphonuclear leukocyte pleocytosis in the cerebrospinal fluid (CSF) with hyperproteinorachia. A meningoencephalitis was diagnosed. Intravenous fluorescein angiography (IVFA) demonstrated a multifocal chorioretinitis that was in a linear pattern in the left eye. CSF enzyme-linked immunosorbent assay was positive for West Nile virus (WNV) IgM. We review the clinical manifestations of WNV disease and highlight the value of IVFA in determining the diagnosis.

Looking beyond blurred margins.

A 60-year-old man presented to an outside ophthalmology clinic with 1 month of progressive vision loss in the right eye (OD). Right optic disc edema was noted. Brain and orbit magnetic resonance imaging revealed right optic nerve and left occipital lobe enhancement. He was seen initially by neurology and neurosurgery and subsequently referred to neuro-ophthalmology for consideration of optic nerve biopsy. He was seen 3 months after his initial symptom onset where vision was light perception OD and a relative afferent pupillary defect with optic nerve edema. OS was unremarkable. A lumbar puncture with flow cytometry was negative for multiple sclerosis and lymphoma. At his oculoplastic evaluation for optic nerve biopsy, his vision was noted to be no light perception OD. Optic nerve biopsy demonstrated non-caseating granulomatous inflammation consistent with neurosarcoidosis. The patient was started on high-dose oral steroids with improvement of disc edema, as well as significant improvement in optic nerve and intracranial parenchymal enhancement, although his vision never improved.

Clinical Characteristics of Idiopathic Intracranial Hypertension in Older Adults.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition that classically affects obese women of child-bearing age. However, it is sometimes encountered in older patients. The purpose of this study was to help clinicians better understand how this disease can present differently in these age groups. METHODS: This is a retrospective chart review from a single academic center of baseline characteristics of adult patients diagnosed with IIH based on the modified Dandy criteria. The patients were divided into 2 groups: (1) those 18-44 years old and (2) those older than 45 years at diagnosis. RESULTS: One hundred sixty-seven patients were identified; 135 in the younger group and 32 in the older group. The younger group had a higher rate of headaches (90% vs 63%, P = 0.0004), higher body mass index (38.9 vs 36.1, P = 0.046), higher opening pressure (38 vs 31 cm H2O, P = 0.005), and thicker peripapillary retinal nerve fiber layer average thickness (right eye 178 vs 131 µm, P = 0.02; left eye 184 vs 136 µm, P = 0.045). The older group had higher rates of empty sella (90% vs 62%, P = 0.0039). In addition in the younger group, there was a trend toward higher rates of pulsatile tinnitus (63% vs 45%, P = 0.08), transient visual obscurations (50% vs 32%, P = 0.07), and lower rates of spontaneous cerebrospinal fluid leak (4% vs 13%, P = 0.08). Sex, rates of obesity, other MRI findings typical of elevated intracranial pressure, frequency and Frisen grading of papilledema, and visual field loss were not statistically different between the groups. CONCLUSIONS: The older age group had milder signs and symptoms of IIH and a higher prevalence of empty sella than the younger group, but otherwise had typical characteristics. These findings suggest that IIH in the older age group may represent milder chronic disease that was previously undiagnosed.

Objective Diplopia Outcomes for Patients Treated With Teprotumumab for Thyroid Eye Disease.

BACKGROUND: Thyroid eye disease (TED) is a condition caused by inflammatory damage to the periocular tissue that often leads to double vision. Teprotumumab is an insulin-like growth factor 1 receptor antibody that was FDA approved for the management of TED in 2020, although much is yet to be elucidated regarding its effects on diplopia outcomes among patients with TED. Diplopia is a significant and life-altering effect of TED. Previous studies have reported the effect of teprotumumab on double vision subjectively using the Gorman diplopia score. However, there is a gap in the literature addressing the effect of teprotumumab treatment on objective ocular alignment measures. The purpose of our study was to address this gap. METHODS: We performed a retrospective review of patients who were diagnosed with TED, presented with diplopia, and treated with teprotumumab in a single-center academic ophthalmology practice. The primary outcome was change in ocular alignment in primary gaze position at 6 months (completion of teprotumumab treatment). Secondary outcomes included change in ocular alignment in other gaze positions, proptosis, eyelid position, and clinical activity score (CAS) at 6 months compared with baseline. To determine what factors may predict ocular alignment response to teprotumumab, we analyzed baseline characteristics among 3 groups, divided based on whether ocular alignment was worsened, stable, or improved at 6 months. RESULTS: Seventeen patients met inclusion criteria, 3 (18%) worsened, 10 (59%) were stable, and 4 (24%) improved. CAS ( P = 0.02) was significantly different among the groups and was higher in those who worsened and those who improved compared with those who remained stable. Right gaze horizontal prism deviation ( P = 0.01) and left gaze horizontal prism deviation ( P = 0.03) were significantly different among the groups, with a greater degree of left gaze horizontal prism deviation in the worse group than the stable group ( P = 0.04). CONCLUSIONS: Our study demonstrated that most patients remained stable after teprotumumab treatment regarding ocular alignment in primary gaze and the number of patients who improved was slightly higher than the number of patients who worsened after teprotumumab treatment. There are some baseline measures, such as CAS and right and left gaze horizontal prism deviation that can help better predict how a patient will respond to teprotumumab treatment. Our results can better inform physicians of how to counsel patients with TED when considering teprotumumab therapy.

Stability of Ocular Alignment After Teprotumumab Therapy in a Cohort of Patients With Thyroid Eye Disease and Baseline Diplopia.

BACKGROUND: Teprotumumab is a monoclonal antibody that is effective in treating patients with thyroid eye disease (TED) and has been shown to produce subjective improvements in diplopia in this group. The aims of this study were to evaluate the rate and timing of recurrence/worsening of diplopia after teprotumumab treatment in a cohort of patients with TED presenting with diplopia at baseline. METHODS: A retrospective chart review of 15 patients with diplopia secondary to TED, treated with teprotumumab, was conducted in a single-center academic institution. The primary outcome was the rate of recurrence/worsening of diplopia after completing teprotumumab. Secondary outcomes include the time to recurrence/worsening of diplopia and clinical activity scores (CAS) to correlate with changes in ocular alignment. RESULTS: Fifteen patients met the inclusion criteria for this study, and 7 of these had recurrence of diplopia (46.7%). Two patients had worsening of CAS to ≥4, 6 had worsening of CAS to 3, and the other 7 had CAS ≤2 during the follow-up period. The mean follow-up period was 20.4 months (SD 7.2) after completing teprotumumab. The mean time to diplopia recurrence/worsening was 8.8 months (range 6.7-12.2, SD 1.8). CONCLUSIONS: Patients with TED and baseline diplopia have a substantial rate of recurrence/worsening of diplopia after teprotumumab therapy, suggesting that they may not have stable ocular alignment immediately after treatment. Strabismus surgeons may need to weigh the significant risk of disease relapse when planning optimum timing for surgical correction.

Bilateral Dilated Superior Ophthalmic Veins in a Patient With an Arteriovenous Dialysis Fistula.

A 64-year-old man presented with 4 months of diplopia. He had end-stage renal disease requiring a cephalic transposition brachiocephalic fistula that was no longer in use following successful renal transplantation. On presentation, he had bilateral proptosis, extraocular movement restriction, chemosis, tortuous episcleral vessels, and caruncular injection. Non-contrast CT of the orbits demonstrated dilation of both superior ophthalmic veins, and CT angiography showed asymmetric enlargement of both cavernous sinuses and superior ophthalmic veins. A carotid-cavernous fistula was suspected, but cerebral angiography revealed shunting from the old fistula with intracranial drainage and cerebral venous hypertension. Aberrant retrograde drainage resulted from anatomical compression of the left brachiocephalic vein. The fistula was ligated, and at 1-week follow-up, the patient had marked improvement in extraocular movements and orbital congestion with near complete resolution of diplopia. Postoperative CT angiography obtained 2 months later demonstrated decreased size of both superior ophthalmic veins, consistent with improvement of venous hypertension.

Optic Neuritis and Cranial Neuropathies Diagnosis Rates before Coronavirus Disease 2019, in the Initial Pandemic Phase, and Post-Vaccine Introduction.

PURPOSE: To compare rates of diagnosis of neuro-ophthalmic conditions across the Coronavirus Disease 2019 (COVID-19) pandemic with pre-pandemic levels. DESIGN: Multicenter, retrospective, observational study. PARTICIPANTS: Patients seen for eye care between March 11, 2019, and December 31, 2021. METHODS: A multicenter electronic health record database, Sight Outcomes Research Collaborative (SOURCE), was queried for new diagnoses of neuro-ophthalmic conditions (cranial nerve [CN] III, IV, VI, and VII palsy; diplopia; and optic neuritis) and new diagnoses of other ophthalmic conditions from January 1, 2016, to December 31, 2021. Data were divided into 3 periods (pre-COVID, pre-COVID vaccine, and after introduction of COVID vaccine), with a 3-year look-back period. Logistic regressions were used to compare diagnosis rates across periods. Two-sample z-test was used to compare the log odds ratio (OR) of the diagnosis in each period with emergent ocular conditions: retinal detachment (RD) and acute angle-closure glaucoma (AACG). MAIN OUTCOME MEASURES: Diagnosis rate of neuro-ophthalmic conditions in each study period. RESULTS: A total of 323 261 unique patients (median age 59 years [interquartile range, 43-70], 58% female, 68% White) across 5 academic centers were included, with 180 009 patients seen in the pre-COVID period, 149 835 patients seen in the pre-COVID vaccine period, and 164 778 patients seen in the COVID vaccine period. Diagnosis rates of CN VII palsy, diplopia, glaucoma, and cataract decreased from the pre-COVID period to the pre-vaccine period. However, the optic neuritis diagnoses increased, in contrast to a decrease in RD diagnoses (P = 0.021). By comparing the diagnosis rates before and after widespread vaccination, all eye conditions evaluated were diagnosed at higher rates in the COVID vaccination period compared with pre-COVID and pre-vaccine periods. The log OR of neuro-ophthalmic diagnosis rates across every period comparison were largely similar to emergency conditions (RD and AACG, P > 0.05). However, the log OR of cataract and glaucoma diagnoses were different to RD or AACG (P < 0.05) in each period comparison. CONCLUSIONS: Neuro-ophthalmic diagnoses had a similar reduction in diagnosis rates as emergent eye conditions in the first part of the pandemic, except optic neuritis. After widespread COVID-19 vaccination, all ophthalmic diagnosis rates increased compared with pre-pandemic rates, and the increase in neuro-ophthalmic diagnosis rates did not exceed the increase in RD and AACG diagnosis rates. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Copy number variants and fetal structural abnormalities in stillborn fetuses: A secondary analysis of the Stillbirth Collaborative Research Network study.

OBJECTIVE: To examine the association of placental and fetal DNA copy number variants (CNVs) with fetal structural malformations (FSMs) in stillborn fetuses. DESIGN: A secondary analysis of stillbirth cases in the Stillbirth Collaborative Research Network (SCRN) study. SETTING: Multicenter, 59 hospitals in five geographic regions in the USA. POPULATION: 388 stillbirth cases of the SCRN study (2006-2008). METHODS: Fetal structural malformations were grouped by anatomic system and specific malformation type (e.g. central nervous system, thoracic, cardiac, gastrointestinal, skeletal, umbilical cord and craniofacial defects). Single-nucleotide polymorphism array detected CNVs of at least 500 kb. CNVs were classified into two groups: normal, defined as no CNVs >500 kb or benign CNVs, and abnormal, defined as pathogenic or variants of unknown clinical significance. MAIN OUTCOME MEASURES: The proportions of abnormal CNVs and normal CNVs were compared between stillbirth cases with and without FSMs using the Wald Chi-square test. RESULTS: The proportion of stillbirth cases with any FSMs was higher among those with abnormal CNVs than among those with normal CNVs (47.5 versus 19.1%; P-value <0.001). The most common organ system-specific FSMs associated with abnormal CNVs were cardiac defects, followed by hydrops, craniofacial defects and skeletal defects. A pathogenic deletion of 1q21.1 involving 46 genes (e.g. CHD1L) and a duplication of 21q22.13 involving four genes (SIM2, CLDN14, CHAF1B, HLCS) were associated with a skeletal and cardiac defect, respectively. CONCLUSION: Specific CNVs involving several genes were associated with FSMs in stillborn fetuses. The findings warrant further investigation and may inform counselling and care surrounding pregnancies affected by FSMs at risk for stillbirth.

Big Data Analysis of Inflammatory Conditions Associated With Optic Neuritis.

BACKGROUND: Previous studies in the United States established multiple sclerosis (MS) as the most common cause of optic neuritis (ON). ON can be associated with other systemic inflammatory conditions including sarcoidosis, neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and lupus; however, prospective studies to establish risk of ON associated with these diseases are lacking. Furthermore, appropriate workup for ON is still debated. METHODS: A deidentified electronic medical record of a tertiary care academic center was searched for ON and rheumatologic/neuro-inflammatory diseases in the medical history, diagnoses, and laboratory results; followed by the intersection of ON with each condition. We calculated frequency of systemic conditions among patients with ON and prevalence of ON in those conditions. We also calculated relative risk (RR) of underlying systemic conditions among patients with ON compared with the study patient population. RESULTS: In 6.7 million charts, 5,344 cases of ON were identified. Among those, MS occurred most commonly (20.6%), followed by NMOSD (10.5%). Conversely, ON occurred in 98.4% of NMOSD cases, 53.3% of MOGAD, and 10.0% of MS. NMOSD (RR = 1,233), MOGAD (RR = 688), and MS (RR = 126) had the highest RR among the conditions we evaluated. The subset analysis showed similar findings. CONCLUSIONS: The high RR for ON among patients with NMOSD and MOGAD suggests that clinical suspicion for ON should be high among patients with these conditions presenting with vision changes. Conversely, MS and NMOSD should initially be high on the differential diagnosis for any patient presenting with optic neuritis.

Durable tumor regression and restoration of neurologic function after treatment with anti-PD-1 in patients with functionally unresectable cutaneous squamous cell carcinoma with perineural spread into the cavernous sinus.

PURPOSE: To describe tumor response and cranial nerve function outcomes after administration of anti-PD-1 to patients with cutaneous squamous cell carcinoma (CSCC) with perineural spread to cranial nerves (CN) extending into the cavernous sinus. METHODS: Electronic patient records from a single institution were queried for patients with CSCC of the head and neck causing diplopia (ICD-10 H53.2) who were treated with anti-PD-1. Data extracted included demographics, duration of anti-PD-1 therapy, immune-mediated adverse reactions, tumor response per adapted RECIST v1.1, and changes in CN function and symptoms (e.g., pain). All patients were prescribed cemiplimab 350 mg IV q3 weeks. RESULTS: Four patients met inclusion criteria. They had varying degrees of pain and sensory deficits in branches of the trigeminal nerve (CN V). One, 2, 3 and 1 patients had baseline involvement of CN III, IV, VI and VII, respectively. MRI confirmed perineural cavernous sinus involvement in all patients. Duration of anti-PD-1 therapy ranged 15-60 weeks. All patients experienced an objective anti-tumor response to anti-PD-1; partial response n = 2, complete response n = 2. At a median follow-up of 22 months, responses were ongoing in all patients. All patients demonstrated improvement in ocular motility deficits and pain with resolution of symptoms in 3 and 1 patients, respectively. CONCLUSION: Administration of anti-PD-1 to patients with CSCC with perineural spread into the cavernous sinus can generate durable anti-tumor regressions and restore CN function, while sparing the morbidity associated with surgical resection and/or radiotherapy. Our findings add to emerging literature supporting this treatment approach for this patient population.

Myopathy and Ophthalmologic Abnormalities in Association With Multiple Skeletal Muscle Mitochondrial DNA Deletions.

BACKGROUND: Establishing a molecular diagnosis of mitochondrial diseases due to pathogenic mitochondrial DNA (mtDNA) variants can be difficult because of varying levels of tissue heteroplasmy, and identifying these variants is important for clinical management. Here, we present clinical and molecular findings in 8 adult patients with classical features of mitochondrial ophthalmologic and/or muscle disease and multiple mtDNA deletions isolated to muscle. METHODS: The patients were identified via a retrospective review of patients seen in both a tertiary ophthalmology center and a genetics clinic with a clinical diagnosis of chronic progressive external ophthalmoplegia, optic nerve abnormalities, and/or mitochondrial myopathy. Age at onset of symptoms ranged from 18 to 61 years. Ocular manifestations included bilateral optic neuropathy in one patient, bilateral optic disc cupping without optic neuropathy in 2 patients, ptosis in 4 patients, and ocular motility deficits in 2 patients. Five patients had generalized weakness. RESULTS: Pathogenic variants in mtDNA were not found in the blood or buccal sample from any patient, but 7 of 8 patients had multiple mtDNA deletions identified in muscle tissue. One patient had a single mtDNA deletion identified in the muscle. Heteroplasmy was less than 15% for all of the identified deletions, with the exception of one deletion that had a heteroplasmy of 50%-60%. None of the patients were found to have a nuclear gene variant known to be associated with mitochondrial DNA maintenance. CONCLUSIONS: mtDNA deletions were identified in adult patients with ophthalmologic and/or musle abnormalities and may underlie their clinical presentations.

A Role for Genitourinary Reconstruction in Locally Advanced Bilateral Wilm's Tumor.

Wilm's tumor, an embryonal tumor that develops from remnants of the immature kidney, is the most common primary malignant renal tumor of childhood and accounts for approximately 6%-7% of all childhood cancers. Here, we present a case of a 10-year-old female with stage IV Wilm's tumor involving the bilateral kidneys. She ultimately required complex genitourinary reconstruction via a transureteroureterostomy following extensive oncologic resection. This case highlights the critical role of Urologists at an early stage in cases requiring complex genitourinary reconstruction.

Presenting Features of Giant Cell Arteritis with Active Versus Healed Arteritis on Biopsy.

Giant cell arteritis (GCA) is often categorised as "active" or "healed" on temporal artery biopsy (TAB). The purpose of this study was to compare the initial clinical presentation of patients with GCA according to active versus healed arteritis on TAB. A retrospective chart review was performed for patients with biopsy-proven GCA (BP-GCA) at a single academic medical institution from a previously reported cohort. The arteritis on TAB was categorised as "active" or "healed" based on the pathological reports. Demographic information, clinical presentation, past medical history, and test results were collected from the date of TAB. These baseline characteristics were entered into the GCA Risk Calculator. Of 85 patients with BP-GCA, 80% had active and 20% had healed disease according to histopathology. A higher percentage of those with active arteritis had ischaemic optic neuropathy (ION) (36% versus 6%, p = .03), elevated erythrocyte sedimentation rates (92% versus 63%, p = .01), elevated C-reactive protein levels (79% versus 46%, p = .049), GCA risk score > 7.5% (99% sensitivity, 100% versus 71%, p < .001), higher mean GCA risk calculator scores (neural network p = .001; logistic regression p = .002). Patients with healed arteritis were less likely to have visual manifestations than the active arteritis group (38% versus 71%, p = .04). Patients with active vasculitis on biopsy had higher rates of ION and elevated inflammatory markers, as well as higher predictive scores from the GCA risk calculator. Further research is needed regarding correlation of biopsy findings and risk of complications or relapses.