Pearls & Oy-sters: ATX-FGF14 Mimicking Autoimmune Pathology.

ATX-FGF14 (formerly spinocerebellar ataxia 27, OMIM #193003) is an autosomal dominant condition caused by a pathogenic variant in the fibroblast growth factor 14 (FGF14, OMIM #601515) gene located on chromosome 13. The phenotypic expression can vary in patients with the same genotype, often delaying diagnosis, especially in probands without known affected relatives and/or with limited available family history. We describe 2 cases of ATX-FGF14 in 1 family with a focus on the importance of differentiating episodic manifestations of neurogenetic conditions from inflammatory/autoimmune neurologic conditions. A 68-year-old male patient (case 1) presented with episodic dysarthria, dizziness, imbalance, and encephalopathy, creating suspicion for a possible autoimmune etiology. At the first evaluation, the patient reported no significant family history. Four years later, on revisiting the family history, he noted that his 49-year-old niece (case 2) had also developed neurologic symptoms of an unclear etiology. On evaluation, she had tremor and ataxia. Both patients also had coexistent evidence of systemic autoimmunity that likely contributed to the initial suspicion of neurologic autoimmunity, and neither had cerebellar or brainstem volume loss. Ultimately, their genetic testing revealed a pathogenic structural variant in the FGF14 gene, consistent with ATX-FGF14. These 2 cases highlight the importance of a detailed interval family history at each visit, especially in undiagnosed adult patients, as well as the importance of objectively analyzing the impact of immunotherapy diagnostic treatment trials to avoid unnecessary immunomodulatory medications.

Sharp Edge Eye Syndrome: A Case Report and Survey of Self-Identified Individuals.

BACKGROUND: Sharp edge eye syndrome (SEES), sometimes known as visual looming syndrome, is a condition in which the patient experiences ocular pain or discomfort when viewing or mentally picturing sharp objects and edges. Patients may present for medical care because they perceive the condition to represent an ophthalmic problem or a sign of a more serious underlying condition. An individual case report of SEES is included to aid in illustrating syndrome characteristics. Our aim is to describe the syndrome, vision-related quality of life (VRQOL), and psychosocial characteristics in patients with self-identified SEES. METHODS: A cross-sectional web-based survey was made available on social media webpages dedicated to SEES. The study included 22 questions developed by the research team, demographic questions, and 4 standardized questionnaires [ID Migraine, the National Eye Institute's Visual Function Questionnaire (NEI-VFQ-25), General Anxiety Disorder-2 (GAD-2), and Patient Health Questionnaire (depression) Scale-2]. RESULTS: Seventy-seven respondents had an average age of 29 and were 57% male. 92% reported symptoms before age 18. The main site of pain or discomfort was the eyes, with onset resulting from viewing or thinking of sharp objects and edges. Symptoms lasted from seconds to hours and could be prolonged even after closing eyes or avoiding viewing the trigger. The composite and subscale scores on the NEI-VFQ-25 were low, with a mean composite score of 78 and selected subscores of general health (61), general vision (73), ocular pain (68), driving (79), mental health (61), and role difficulties (72). Anxiety was reported in 58% of participants, and depression in 57%. Migraine or headache was reported in 46% of participants. Participants reported Alice in Wonderland syndrome, visual snow, obsessive-compulsive disorder, attention deficit hyperactivity disorder, stripe-induced visual discomfort, and synesthesia. CONCLUSION: From this survey, we have the beginnings of an understanding of the characteristics of SEES, as well as VRQOL impacts. These survey responses lead us to postulate that SEES may be a distinct visual phenomenon and to propose SEES criteria. Systematic studies of this condition's clinical features and treatment responses will be additional steps toward improving patient care.

Interdisciplinary Protocol for the Management of Vision-Threatening Papilledema.

BACKGROUND: This study evaluates the effectiveness of a multidisciplinary protocol for management of patients with papilledema and vision loss secondary to increased intracranial pressure. METHODS: Retrospective record review of all adult patients who presented with vision-threatening papilledema (VTPE) and were treated under this protocol. Patients are admitted for lumbar drain placement and diuretics and followed daily to determine if they may be managed medically or require surgery (optic nerve sheath fenestration [ONSF] and/or cerebrospinal fluid [CSF] shunting). RESULTS: Nineteen patients were included. Twelve had body mass index in the obese range and 6 were morbidly obese. Fourteen had idiopathic intracranial hypertension. Five had secondary pseudotumor cerebri syndrome related to medication use, dural venous sinus thrombosis, hypothyroidism, end-stage renal disease, pulmonary disease, and diastolic heart failure. Three patients did not require surgery and were discharged on oral diuretics; 3 patients underwent unilateral ONSF, 9 underwent bilateral ONSF, and 4 underwent bilateral ONSF followed by ventriculoperitoneal shunt placement. The average follow-up was 10.1 months. The visual acuity improved bilaterally in 12 patients and unilaterally in 4 patients. The remaining 3 patients had worsened vision in both eyes. Fifteen patients had bilateral improvement in their visual fields. Five eyes in 3 patients showed further constriction of the visual field at follow-up. CONCLUSIONS: We demonstrate how a multidisciplinary complex care protocol for treating VTPE can expedite and streamline treatment and restore vision. We found that most patients had improved symptoms and signs, including visual acuity, visual fields, and papilledema. We encourage institutions that manage VTPE to adopt similar institutional protocols.

The Unmet Challenge of Diagnosing and Treating Photophobia.

BACKGROUND: Although patients with abnormal light sensitivity may present to an ophthalmologist or optometrist for the evaluation of photophobia, there are no previous reviews of the most common causes of this symptom. METHODS: We conducted a retrospective chart review of patients who presented to our eye center between 2001 and 2009 primarily for the evaluation of photophobia. We recorded demographics, ocular examination findings, and diagnoses of these patients. RESULTS: Our population included 58 women and 53 men. The mean age at presentation to the clinic was 37 years (range 6 months-94 years). The most frequent cause of photophobia was migraine headache (53.7%), followed by dry eye syndrome (36.1), ocular trauma (8.2%), progressive supranuclear palsy (6.8%), and traumatic brain injury (4.1%). A significant proportion of patients (25.9%) left the clinic without a cause for their photophobia documented by the examining physician (11.7% of adults and 69.4% of children). CONCLUSIONS: Photophobia affects patients of all ages, and many patients are left without a specific diagnosis, indicating a significant knowledge gap among ophthalmologists and optometrists evaluating these patients.

Increased Incidence of Pseudotumor Cerebri Syndrome Among Users of Tetracycline Antibiotics.

BACKGROUND: To determine whether the use of a tetracycline-class antibiotic is associated with an increased risk of developing pseudotumor cerebri syndrome (PTCS). METHODS: We identified patients in the University of Utah Health system who were prescribed a tetracycline-class antibiotic and determined what percentage of those individuals were subsequently diagnosed with PTCS secondary to tetracycline use. We compared this calculation to the number of patients with PTCS unrelated to tetracycline use. RESULTS: Between 2007 and 2014, a total of 960 patients in the University system between the ages of 12 and 50 were prescribed a tetracycline antibiotic. Among those, 45 were diagnosed with tetracycline-induced PTCS. We estimate the incidence of tetracycline-induced PTCS to be 63.9 per 100,000 person-years. By comparison, the incidence of idiopathic intracranial hypertension (IIH) is estimated to be less than one per 100,000 person-years (Calculated Risk Ratio = 178). CONCLUSIONS: Although a causative link between tetracycline use and pseudotumor cerebri has yet to be firmly established, our study suggests that the incidence of pseudotumor cerebri among tetracycline users is significantly higher than the incidence of IIH in the general population.

Multiple Cranial Neuropathies and Pachymeningitis in a Patient With a Pathogenic Nucleotide-Binding Oligomerization Domain 2 Polymorphism.

ABSTRACT: An 11-year-old boy presented with 2 weeks of intermittent headache, right orbital pain, and constant diplopia. Brain MRI showed dural thickening and enhancement of the right lateral cavernous sinus, right orbital apex, and tentorium. Initial cerebral spinal fluid analysis showed only mild pleocytosis, and serum diagnostics were unrevealing. The working diagnosis was Tolosa-Hunt syndrome. His pain and sixth nerve palsy resolved with corticosteroids. Five months after initial presentation, he developed new numbness of the right cheek, complete right ophthalmoplegia, and weakness and numbness of his right hand and leg, all of which were responsive to steroids. Fifteen months later, he returned to the emergency department with 2 weeks of left-sided headaches and acute diplopia. On examination, he had a left cranial nerve 6 palsy. Dural biopsy showed diffuse mononuclear inflammatory cell reaction consisting mostly of lymphocytes with no signs of granuloma formation, nor any epithelioid or giant cells. His clinical course was consistent with an autoinflammatory condition of unknown etiology. Genetic testing with an immunodeficiency panel showed a risk allele in NOD2 (nucleotide-binding oligomerization domain 2) c.3019dup (p.Leu1007Prof*2) that is associated with an increased risk for Crohn disease. His clinical condition had similarities to central nervous system sarcoidosis. Because of the similarities between our patient's clinical, imaging, and genetic findings and neurosarcoidosis, he was switched to a more targeted therapy-infliximab. His condition has since been stable for nearly 2 years. In conclusion, genetic testing should be considered in patients with suspected occult autoimmunity.

Ophthalmology Residency Virtual Interviews in the Setting of the COVID-19 Pandemic: Perspectives of Applicants, Selection Committee Members, and Current Residents.

Background In the setting of the COVID-19 pandemic, residency programs implemented videoconferencing "virtual" interviews for the 2020 to 2021 match cycle. There is limited published information on virtual ophthalmology residency interviews. Objective The study aimed (1) to assess applicant, selection committee member, and resident opinions of technical quality, communication quality, and ability to assess applicant or program "fit" during virtual interviews; (2) to determine which interview format-in-person or virtual-each party would prefer in the future; and (3) to survey which residency resources applicants found helpful. Design Surveys were sent to applicants, selection committee members, and residents to assess the above objectives for the 2020 to 2021 match cycle virtual interviews at the Moran Eye Center, University of Utah. Setting This study was conducted in a single residency program interview season from 2020 to 2021. Participants Forty applicants, eight committee members, and seven residents who participated in the virtual interview process were surveyed. Intervention or Exposure Prior to interviews, various avenues were implemented to connect with applicants. A videoconferencing software was utilized for interviews. Applicants and selection committee members met in one-on-one or small group interviews. Residents communicated with applicants in a large group setting between interviews. Main Outcome and Measure The study aims to survey the participants as stated in the objectives. There was no planned outcome for this quality improvement study. Results Survey response rate was 98.2% (54/55). All parties rated the technical components as good or very good. Applicants and selection committee members rated communication as overall good or very good, although residents thought communication was very poor. A total of 92.3% applicants, 75% selection committee members, and 0% residents were reported that they were able to appropriately assess fit of the program with the applicant. However, 46.3% respondents preferred in-person interviews in the future. Popular applicant resources were resident-produced videos (82.1%), conversations with residents (46.2%), and a gift bag (43.6%). Conclusion and Relevance Overall, the technical components of the interview were successful. Small, structured group interactions led to better communication and assessment of fit. There were variable opinions regarding future interview format preference between in-person, virtual, or choice. Amid the COVID-19 pandemic, connecting with applicants via various means can optimize the match process.

A Comparison Between the Clinical Features of Pseudotumor Cerebri Secondary to Tetracyclines and Idiopathic Intracranial Hypertension.

PURPOSE: Comparisons between clinical features of tetracycline-induced pseudotumor cerebri (PTC-T) and those of idiopathic intracranial hypertension (IIH) are absent in the literature. We hypothesized that significant clinical differences between these etiologies exist and could be better understood by retrospective analysis. DESIGN: Retrospective cohort study. METHODS: We reviewed patients diagnosed with pseudotumor cerebri syndrome (PTCS) at our center and identified those who developed PTC-T after treatment with a tetracycline-class antibiotic and those with IIH. Groups were compared by demographics, body mass index, ophthalmic examination, treatment, clinical course, and visual outcomes. RESULTS: We identified 52 cases of PTC-T and 302 cases of IIH. Obesity rates were significantly different (43.8% for PTC-T vs 79.2% for IIH, P < .001). The mean age at diagnosis was younger for PTC-T (19.8 years vs 28.1 years for IIH, P < .001). Diplopia was more common with PTC-T (40.4% vs 20.1% for IIH, P = .001). The mean illness duration was shorter for PTC-T (18.3 weeks vs 62.9 weeks for IIH, P <.0001). Recurrence rates were significantly different (4.0% for PTC-T vs 16.5% for IIH, P <.001). The frequency of surgical intervention was similar. Vision loss was uncommon but occurred with similar frequency. CONCLUSION: We identified significant clinical differences but also identified important similarities between the 2 groups. There appear to be nonobese patients who develop PTC-T, discontinue the antibiotic, and never develop PTCS again. There are other patients who develop PTC-T, discontinue the antibiotic, and later develop IIH. We conclude that PTC-T represents a spectrum of disease in susceptible individuals.

Posterior Cortical Atrophy: Characteristics From a Clinical Data Registry.

Background: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome that presents with higher-order visual dysfunction with relative sparing of memory and other cognitive domains, and it is most commonly associated with Alzheimer's disease pathology. There is a lack of data regarding the presentation of PCA to non-cognitive specialists. Therefore, we collected clinical data from neuro-ophthalmologists regarding the presentation of PCA to their practices and compared data to published cohorts and a published survey of cognitive specialists. Methods: Members of the North American Neuro-Ophthalmology Society Listserv (NANOSnet) were invited to complete an online, retrospective, chart-review data-entry survey regarding their patients with PCA, and REDCap was used for data collection. Results: Data for 38 patients were entered by 12 neuro-ophthalmologists. Patient mean age at presentation was 67.8 years, and 74% of patients were women. Difficulty reading was reported at presentation by 91% of patients, and poor performance on color vision, stereopsis, and visual field testing (performed reliably by 36/38 patients) were common findings. Most patients who were treated were treated with donepezil and/or memantine. Conclusions: Compared to published data from cognitive specialists, patients presenting to neuro-ophthalmology with PCA were more likely to be older and female and have a reading complaint. Reliable visual field testing was the norm with homonymous defects in the majority of patients. The neuro-ophthalmologist plays an important role in diagnosing PCA in older adults with unexplained visual signs and symptoms, and future studies of PCA should involve multiple specialists in order to advance our understanding of PCA and develop effective treatments.

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

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.