Internuclear Ophthalmoplegia Characterizes Multiple Sclerosis Rather Than Neuromyelitis Optica Spectrum Disease.

BACKGROUND: Neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS) share clinical presentations including optic neuritis and brainstem syndromes. Internuclear ophthalmoplegia (INO) is characterized by slowed ipsilateral adduction saccades and results from a lesion in the medial longitudinal fasciculus (MLF). Although INO is a common clinical finding in MS, its prevalence in NMOSD is unknown. The objective of this work is to determine the comparative frequencies of INO in patients with NMOSD and MS and compare clinical features of both disease processes. METHODS: This is a retrospective study of patients 18 years and older who have an established diagnosis of NMOSD or MS and were evaluated by both neuro-ophthalmology and neuro-immunology specialists between 2014 and 2020. Electronic medical records were screened for documentation of an acute INO at any time during follow-up. Incidence rates were calculated from number of cases of new-onset INO and patient years observed. Logistic regression was used to evaluate the likelihood of developing an INO at any time point for NMOSD vs MS patients. Multivariable analysis was performed by adjusting for age, race, gender, and length of follow-up. RESULTS: Two hundred eighty patients (80 NMOSD, 200 MS) were included. Age range was 18-79 years with a mean age of 35.14 (SD ± 12.41 years). Average length of follow-up in MS and NMOSD patients was 4.18 years vs 3.79 years, respectively (P > 0.05), and disease duration before the start of the study in MS and NMOSD was 8.76 years vs 4.65 years, respectively (P < 0.01). Mean disease duration and follow-up time of both groups was 7.58 years and 4.07 ± 2.51 years, respectively. NMOSD patients were predominantly seropositive for AQP4 antibody (61.25%, n = 49). Individuals who had MOG antibody but also met NMOSD criteria were also included (18.75%, n = 15). The frequency of INO at any time point was 1.25% (n = 1) in NMOSD compared with 16% (n = 32) in MS. The incidence rate of new-onset INO in NMOSD (excluding MOGAD) was 3.8/1,000 person years and 23.9/1,000 person years in MS. Adjusted analysis showed that NMOSD patients were 13.89 times (odds ratio [OR] 0.07, 95% confidence interval [CI] 0.01-0.598, P = 0.015) less likely to develop an INO compared with those with MS when including MOGAD patients, 12.5 times less likely (OR 0.08, 95% CI: 0.10-0.67, P = 0.02) when excluding MOGAD patients and 9.62 times less likely (OR 0.10, 95% CI: 0.01-0.87, P = 0.036) for AQP4+ patients. CONCLUSIONS: Our study shows that the incidence of new INO (3.8 vs 23.9 per 1,000 person years), and the odds of having INO at any time point are significantly lower in NMOSD than MS. This suggests that INO and consequently MLF lesions are less common in NMOSD. The presence of an INO may help in the differentiation of NMOSD from MS and may aid in earlier implementation of disease appropriate therapy.

Surgical Outcomes of Transposition Surgery for the Correction of Large-Angle Strabismus.

BACKGROUND: Many potential surgical options exist to address large-angle deviations and head turns that result from various forms of paralytic strabismus. Muscle transposition surgeries serve as suitable alternatives to simple resection-recessions. Here, we report outcomes of augmented Hummelsheim and X-type transpositions for the correction of large-angle strabismus and provide insights for surgical planning. METHODS: We performed a retrospective chart review of 40 consecutive patients with strabismus who were treated with an augmented Hummelsheim or X-type transposition surgery at a single academic medical center. Etiologies included cranial nerve palsies (n = 26), monocular elevation palsy (n = 3), Duane syndrome (n = 1), traumatic extraocular muscle damage (n = 8), and chronic progressive external ophthalmoplegia (n = 2). All patients were followed for a minimum of 2 months postsurgery. Logistic regression analyses were performed to assess for predictors of surgical outcome. RESULTS: Forty consecutive patients were enrolled in our series. The median preoperative deviation was 46.5Δ (interquartile range [IQR] 35-70). The median postoperative deviation 2 months after surgery was 0.5Δ (IQR 0-9.5), which represented a significant improvement (P < 0.001). Thirty-three patients (82.5%) experienced an improvement in range and/or centration of binocular single vision (BSV). More patients who underwent an augmented Hummelsheim procedure and had a small overcorrection at postoperative day 3 had a favorable result on postoperative month 2 (79%) compared with those that were initially under-corrected (38%). Multiple logistic regressions found larger preoperative deviation (P < 0.005) and esotropia (P < 0.021) to be predictors of a less favorable surgical outcome (C-statistic = 0.83). Subgroup analysis revealed that less, favorable outcome after X-type transposition occurred most frequently in patients undergoing correction of an esodeviation. CONCLUSION: Augmented Hummelsheim transposition techniques offer effective treatment options for paralytic strabismus with esotropic deviations, whereas X-type transpositions are effective for exotropic deviations and deviations from severe inferior rectus damage. In addition to potentially providing a wider field of BSV, improved centration is often achieved.

Clinical correlation recommended: accuracy of clinician versus radiologic interpretation of the imaging of orbital lesions.

Purpose: To assess the accuracy of radiographic interpretation between the clinician and radiologist when compared to histopathology of orbital lesions. Methods: A retrospective chart review of patients at the University of California Davis Eye Center who underwent orbitotomy from 1/1/2000 to 5/22/2019 was performed. Charts with a preoperative imaging report, preoperative clinical assessment including the clinician's interpretation of imaging, and histopathologic diagnosis were included. The specific diagnoses were grouped into related classes of pathology for the analysis. The clinical and radiologic assessments were compared against the final histopathologic diagnosis for concordance. A concordance analysis was performed. Results: 242 patients (mean age 49 years, 53.5% female) were reviewed. Of these records 185 documented the clinician's clinical impression, the radiology report, as well as the histopathology report. The clinician's preoperative assessment had substantial agreement [kappa = 0.72 (0.65,0.79)] with the final histopathologic result and was correct in 75.7% (140/185) of cases whereas the radiology report was correct in 52.4% (97/185) with a moderate level of agreement [kappa = 0.47 (0.39, 0.55)]. In 49.2% (91/185) of cases the final histopathology correlated with both the clinical impression and radiology report [kappa = 0.58 (0.55, 0.61)]. Conclusions: The accurate interpretation of orbital imaging is a challenge and histopathologic examination remains the gold standard for diagnosis. While orbital imaging is a valuable diagnostic tool the interpretation of these studies is most accurate when conducted in the context of the patient's medical history, clinical exam, and with the physician most familiar with various orbital lesions.

Neuro-protection and neuro-regeneration of the optic nerve: recent advances and future directions.

PURPOSE OF REVIEW: Optic neuropathies refer to a collection of diseases in which retinal ganglion cells (RGCs), the specialized neuron of the retina whose axons make up the optic nerve, are selectively damaged. Blindness secondary to optic neuropathies is irreversible as RGCs do not have the capacity for self-renewal and have a limited capacity for self-repair. Numerous strategies are being developed to either prevent further RGC degeneration or replace the cells that have degenerated. In this review, we aim to discuss known limitations to regeneration in central nervous system (CNS), followed by a discussion of previous, current, and future strategies for optic nerve neuroprotection as well as approaches for neuro-regeneration, with an emphasis on developments in the past two years. RECENT FINDINGS: Neuro-regeneration in the CNS is limited by both intrinsic and extrinsic factors. Environmental barriers to axon regeneration can be divided into two major categories: failure to clear myelin and formation of glial scar. Although inflammatory scars block axon growth past the site of injury, inflammation also provides important signals that activate reparative and regenerative pathways in RGCs. Neuroprotection with neurotrophins as monotherapy is not effective at preventing RGC degeneration likely secondary to rapid clearance of growth factors. Novel approaches involve exploiting different technologies to provide sustained delivery of neurotrophins. Other approaches include application of anti-apoptosis molecules and anti-axon retraction molecules. Although stem cells are becoming a viable option for generating RGCs for cell-replacement-based strategies, there are still many critical barriers to overcome before they can be used in clinical practice. Adjuvant treatments, such as application of electrical fields, scaffolds, and magnetic field stimulation, may be useful in helping transplanted RGCs extend axons in the proper orientation and assist with new synapse formation. SUMMARY: Different optic neuropathies will benefit from neuro-protective versus neuro-regenerative approaches. Developing clinically effective treatments for optic nerve disease will require a collaborative approach that not only employs neurotrophic factors but also incorporates signals that promote axonogenesis, direct axon growth towards intended targets, and promote appropriate synaptogenesis.

Optic Nerve Regeneration: How Will We Get There?

BACKGROUND: Restoration of vision in patients blinded by advanced optic neuropathies requires technologies that can either 1) salvage damaged and prevent further degeneration of retinal ganglion cells (RGCs), or 2) replace lost RGCs. EVIDENCE ACQUISITION: Review of scientific literature. RESULTS: In this article, we discuss the different barriers to cell-replacement based strategies for optic nerve regeneration and provide an update regarding what progress that has been made to overcome them. We also provide an update on current stem cell-based therapies for optic nerve regeneration. CONCLUSIONS: As neuro-regenerative and cell-transplantation based strategies for optic nerve regeneration continue to be refined, researchers and clinicians will need to work together to determine who will be a good candidate for such therapies.

Seasonal incidence of biopsy-proven giant cell arteritis: a 20-year retrospective study of the University of California Davis Medical System.

OBJECTIVES: Giant cell arteritis (GCA) is a vasculitis that affects large and medium sized arteries. The aetiology of GCA is unknown and numerous risk factors have been proposed. In this article, we evaluate the incidence of biopsy-positive GCA in Northern California and assess for seasonal variation. METHODS: We performed a retrospective review based on billing codes of temporal artery biopsies performed at the University of California, Davis from 2003 to 2014. RESULTS: We identified 174 biopsies (119 female, 55 male). Of these, 21 positive biopsies were female while 8 were male. Although three times as many women had a positive biopsy compared to men, twice as many biopsies were performed on women. Women were not found to have a significantly higher risk of developing GCA over men. Patients with a positive biopsy averaged 76.4±8.9 years of age. The odds of having a positive biopsy increased significantly with age. Positive biopsies were significantly more likely to occur in the months of May through July than the rest of the year (p<0.028). CONCLUSIONS: Our retrospective study is the first report of the seasonal incidence of biopsy-proven GCA in California. Our data suggest that increased age and summer months are risk factors for developing biopsy-proven GCA in our region.

Activin and GDF11 collaborate in feedback control of neuroepithelial stem cell proliferation and fate.

Studies of the olfactory epithelium model system have demonstrated that production of neurons is regulated by negative feedback. Previously, we showed that a locally produced signal, the TGFß superfamily ligand GDF11, regulates the genesis of olfactory receptor neurons by inhibiting proliferation of the immediate neuronal precursors (INPs) that give rise to them. GDF11 is antagonized by follistatin (FST), which is also produced locally. Here, we show that Fst(-/-) mice exhibit dramatically decreased neurogenesis, a phenotype that can only be partially explained by increased GDF11 activity. Instead, a second FST-binding factor, activin ßB (ACTßB), inhibits neurogenesis by a distinct mechanism: whereas GDF11 inhibits expansion of INPs, ACTßB inhibits expansion of stem and early progenitor cells. We present data supporting the concept that these latter cells, previously considered two distinct types, constitute a dynamic stem/progenitor population in which individual cells alternate expression of Sox2 and/or Ascl1. In addition, we demonstrate that interplay between ACTßB and GDF11 determines whether stem/progenitor cells adopt a glial versus neuronal fate. Altogether, the data indicate that the transition between stem cells and committed progenitors is neither sharp nor irreversible and that GDF11, ACTßB and FST are crucial components of a circuit that controls both total cell number and the ratio of neuronal versus glial cells in this system. Thus, our findings demonstrate a close connection between the signals involved in the control of tissue size and those that regulate the proportions of different cell types.

Extraocular Muscle Enlargement in Thyroid Eye Disease Using Volumetric Analysis.

BACKGROUND AND OBJECTIVES: It is commonly taught that thyroid eye disease (TED) causes enlargement of the extraocular muscles (EOMs) in the following descending order: inferior rectus (IR), medial rectus (MR), superior rectus (SR), lateral rectus (LR), superior oblique (SO) and inferior oblique (IO). However, with recent literature challenging this notion, we aimed to compare EOM volumes in our cohort of TED patients.  Methods: We conducted a retrospective, non-randomized case-control study. Twenty-eight orbits from 28 unique patients with TED who had high-resolution CT scans were compared to 31 normal orbits, all from a single academic institution. Orbital soft tissues were manually segmented using ITK-SNAP 3.8.0 (http://itksnap.org), and soft tissue volumes of the control and TED orbits were compared using independent-sample t-tests. RESULTS: Of the TED orbits, 54% of SR/levator palpebrae superioris complex volumes (SRC) and 50% of IR volumes were greater than two standard deviations above the normal orbit average. Compared to controls, the mean SRC volume in TED subjects was 2.3 times enlarged, followed by the IR (2.1 times), SO (1.8 times), MR (1.7 times), LR (1.6 times), IO (1.6 times), and orbital fat (1.4 times) (p < 0.01 for all).  Conclusions: Our findings suggest that contrary to previous teaching, the SRC may be the most severely affected in TED.

Advances and Challenges in Wearable Glaucoma Diagnostics and Therapeutics.

Glaucoma is a leading cause of irreversible blindness, and early detection and treatment are crucial for preventing vision loss. This review aims to provide an overview of current diagnostic and treatment standards, recent medical and technological advances, and current challenges and future outlook for wearable glaucoma diagnostics and therapeutics. Conventional diagnostic techniques, including the rebound tonometer and Goldmann Applanation Tonometer, provide reliable intraocular pressure (IOP) measurement data at single-interval visits. The Sensimed Triggerfish and other emerging contact lenses provide continuous IOP tracking, which can improve diagnostic IOP monitoring for glaucoma. Conventional therapeutic techniques include eye drops and laser therapies, while emerging drug-eluting contact lenses can solve patient noncompliance with eye medications. Theranostic platforms combine diagnostic and therapeutic capabilities into a single device. Advantages of these platforms include real-time monitoring and personalized medication dosing. While there are many challenges to the development of wearable glaucoma diagnostics and therapeutics, wearable technologies hold great potential for enhancing glaucoma management by providing continuous monitoring, improving medication adherence, and reducing the disease burden on patients and healthcare systems. Further research and development of these technologies will be essential to optimizing patient outcomes.

Endoscopic Endonasal Transsphenoidal Resection of Pituitary Adenomas in Patients Presenting With Monocular Blindness.

BACKGROUND AND OBJECTIVES: Suprasellar tumors, particularly pituitary adenomas (PAs), commonly present with visual decline, and the endoscopic endonasal transsphenoidal approach (EETA) is the primary management for optic apparatus decompression. Patients presenting with complete preoperative monocular blindness comprise a high-risk subgroup, given concern for complete blindness. This retrospective cohort study evaluates outcomes after EETA for patients with PA presenting with monocular blindness. METHODS: Retrospective analysis of all EETA cases at our institution from June 2012 to August 2023 was performed. Inclusion criteria included adults with confirmed PA and complete monocular blindness, defined as no light perception, and a relative afferent pupillary defect secondary to tumor mass effect. RESULTS: Our cohort includes 15 patients (9 males, 6 females), comprising 2.4% of the overall PA cohort screened. The mean tumor diameter was 3.8 cm, with 6 being giant PAs (>4 cm). The mean duration of preoperative monocular blindness was 568 days. Additional symptoms included contralateral visual field defects (n = 11) and headaches (n = 10). Two patients presented with subacute PA apoplexy. Gross total resection was achieved in 46% of patients, reflecting tumor size and invasiveness. Postoperatively, 2 patients experienced improvement in their effectively blind eye and 2 had improved visual fields of the contralateral eye. Those with improvements were operated within 10 days of presentation, and no patients experienced worsened vision. CONCLUSION: This is the first series of EETA outcomes in patients with higher-risk PA with monocular blindness on presentation. In these extensive lesions, vision remained stable for most without further decline and improvement from monocular blindness was observed in a small subset of patients with no light perception and relative afferent pupillary defect. Timing from vision loss to surgical intervention seemed to be associated with improvement. From a surgical perspective, caution is warranted to protect remaining vision and we conclude that EETA is safe in the management of these patients.

AxonQuantifier: A semi-automated program for quantifying axonal density from whole-mounted optic nerves.

BACKGROUND: Here, we present a semi-automated method for quantifying retinal ganglion cell (RGC) axon density at different distances from the optic nerve crush site using longitudinal, confocal microscopy images taken from whole-mounted optic nerves. This method employs the algorithm AxonQuantifier which operates on the freely available program, ImageJ. NEW METHOD: To validate this method, seven adult male Long Evans rats underwent optic nerve crush injury followed by in vivo treatment with electric fields of varying strengths for 30 days to produce optic nerves with a wide range of axon densities distal to the optic nerve crush site. Prior to euthanasia, RGC axons were labelled with intravitreal injections of cholera toxin B conjugated to Alexa Fluor 647. After dissection, optic nerves underwent tissue clearing, were whole-mounted, and imaged longitudinally using confocal microscopy. COMPARISON WITH EXISTING METHODS: Five masked raters quantified RGC axon density at 250, 500, 750, 1000, 1250, 1500, 1750, and 2000 µm distances past the optic nerve crush site for the seven optic nerves manually and using AxonQuantifier. Agreement between these methods was assessed using Bland-Altman plots and linear regression. Inter-rater agreement was assessed using the intra-class coefficient. RESULTS: Semi-automated quantification of RGC axon density demonstrated improved inter-rater agreement and reduced bias values as compared to manual quantification, while also increasing time efficiency 4-fold. Relative to manual quantification, AxonQuantifier tended to underestimate axon density. CONCLUSIONS: AxonQuantifier is a reliable and efficient method for quantifying axon density from whole mount optic nerves.

The Retinal Ganglion Cell Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration Consortium.

Purpose: The Retinal Ganglion Cell (RGC) Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) consortium was founded in 2021 to help address the numerous scientific and clinical obstacles that impede development of vision-restorative treatments for patients with optic neuropathies. The goals of the RReSTORe consortium are: (1) to define and prioritize the most critical challenges and questions related to RGC regeneration; (2) to brainstorm innovative tools and experimental approaches to meet these challenges; and (3) to foster opportunities for collaborative scientific research among diverse investigators. Design and Participants: The RReSTORe consortium currently includes > 220 members spanning all career stages worldwide and is directed by an organizing committee comprised of 15 leading scientists and physician-scientists of diverse backgrounds. Methods: Herein, we describe the structure and organization of the RReSTORe consortium, its activities to date, and the perceived impact that the consortium has had on the field based on a survey of participants. Results: In addition to helping propel the field of regenerative medicine as applied to optic neuropathies, the RReSTORe consortium serves as a framework for developing large collaborative groups aimed at tackling audacious goals that may be expanded beyond ophthalmology and vision science. Conclusions: The development of innovative interventions capable of restoring vision for patients suffering from optic neuropathy would be transformative for the ophthalmology field, and may set the stage for functional restoration in other central nervous system disorders. By coordinating large-scale, international collaborations among scientists with diverse and complementary expertise, we are confident that the RReSTORe consortium will help to accelerate the field toward clinical translation. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium.

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.

Cell lineages and the logic of proliferative control.

It is widely accepted that the growth and regeneration of tissues and organs is tightly controlled. Although experimental studies are beginning to reveal molecular mechanisms underlying such control, there is still very little known about the control strategies themselves. Here, we consider how secreted negative feedback factors ("chalones") may be used to control the output of multistage cell lineages, as exemplified by the actions of GDF11 and activin in a self-renewing neural tissue, the mammalian olfactory epithelium (OE). We begin by specifying performance objectives-what, precisely, is being controlled, and to what degree-and go on to calculate how well different types of feedback configurations, feedback sensitivities, and tissue architectures achieve control. Ultimately, we show that many features of the OE-the number of feedback loops, the cellular processes targeted by feedback, even the location of progenitor cells within the tissue-fit with expectations for the best possible control. In so doing, we also show that certain distinctions that are commonly drawn among cells and molecules-such as whether a cell is a stem cell or transit-amplifying cell, or whether a molecule is a growth inhibitor or stimulator-may be the consequences of control, and not a reflection of intrinsic differences in cellular or molecular character.

The Influence of Electrode Properties on Induced Voltage Gradient Along the Rat Optic Nerve.

Significant interest exists in the potential of electric field (EF) application to be developed into a technology to direct neuronal regeneration. In vitro, EFs were shown to direct the growth of retinal ganglion cell (RGC) axons, the neurons that make up the optic nerve. As larger EF gradients were shown to direct more efficient growth, investigations into the most effective stimulation strategies that can generate the greatest voltage gradient are needed before EF application can be developed into a technology to direct optic nerve regeneration in vivo. We performed ex-vivo experiments to compare the ability of different electrode materials, platinum vs. tungsten, to generate an EF gradient along the rat optic nerve. Platinum electrodes at both source and ground positions were found to generate the greatest voltage gradient along the optic nerve. Experimental results were used to inform an equivalent computational model of the optic nerve, which was subsequently employed to predict more effective electrode pair combinations. Our results confirmed that the platinum-platinum electrode pair generates the maximum voltage gradient which are highly dependent on electrode size and electrode-electrolyte interfaces. This computational platform can serve as a foundation for the development of electrical stimulation therapies for nerve regeneration.

Electrical devices for visual restoration.

Given the rising number of patients with blindness from macular, optic nerve, and visual pathway disease, there is considerable interest in the potential of electrical stimulation devices to restore vision. Electrical devices for restoration of visual function can be grouped into three categories: (1) visual prostheses whose goal is to bypass damaged areas and directly activate downstream intact portions of the visual pathway; (2) electric field stimulation whose goal is to activate endogenous transcriptional and molecular signaling pathways to promote neuroprotection and neuro-regeneration; and (3) neuromodulation whose stimulation would resuscitate neural circuits vital to coordinating responses to visual input.  In this review, we discuss these three approaches, describe advances made in the different fields, and comment on limitations and potential future directions.

Sphenoethmoidal air cell sinusitis: A rare cause of recurrent optic neuritis.

Purpose: To describe the clinical presentation, imaging characteristics and management of a rare case of Onodi cell sinusitis associated with optic neuropathy. Observations: A 46-year-old male presented to the emergency department with progressive left eye vision loss over the course of ten days. The constellation of findings from this patient's history, physical, and fundoscopic exam, as well as CT and MR imaging led to the diagnosis of Onodi air cell sinusitis complicated by optic neuropathy. The patient's symptoms resolved fully and vision returned to baseline with oral antibiotics. Conclusions and Importance: The sphenoethmoidal air cell, also known as the Onodi cell, is an anatomic variant of the paranasal sinuses whose spatial relationship with important neurovascular structures carries significant clinical implications when it becomes inflamed or infected. Our case of Onodi cell sinusitis complicated by optic neuropathy demonstrates how vision loss secondary to sinusitis may resolve with oral antibiotic treatment. We additionally review the relevant anatomy, clinical course and treatment of Onodi cell pathologies.

Metastatic neuroendocrine tumors mimicking as primary ocular disease.

PURPOSE: To report two cases of metastatic neuroendocrine tumors masquerading as primary ocular disease. OBSERVATIONS: Case 1 is a 38-year-old man who was referred with subacute onset diplopia and fluctuating ptosis suggestive of myasthenia gravis. Case 2 is a 21-year-old man who presented with blurry vision and was found to have a pigmented ciliary body mass and retinal detachment suggestive of uveal melanoma. Both patients were ultimately diagnosed with metastatic neuroendocrine tumors. CONCLUSIONS AND IMPORTANCE: Neuroendocrine tumors, though rare and infrequently metastatic to the eye and orbit, can initially present with ocular signs. A broad differential and careful consideration of ocular and systemic symptoms are critical in such challenging cases.