Deep Learning to Discriminate Arteritic From Nonarteritic Ischemic Optic Neuropathy on Color Images.

Importance: Prompt and accurate diagnosis of arteritic anterior ischemic optic neuropathy (AAION) from giant cell arteritis and other systemic vasculitis can contribute to preventing irreversible vision loss from these conditions. Its clinical distinction from nonarteritic anterior ischemic optic neuropathy (NAION) can be challenging, especially when systemic symptoms are lacking or laboratory markers of the disease are not reliable. Objective: To develop, train, and test a deep learning system (DLS) to discriminate AAION from NAION on color fundus images during the acute phase. Design, Setting, and Participants: This was an international study including color fundus images of 961 eyes of 802 patients with confirmed AAION and NAION. Training was performed using images from 21 expert neuro-ophthalmology centers in 16 countries, while external testing was performed in a cohort from 5 expert neuro-ophthalmology centers in the US and Europe. Data for training and external testing were collected from August 2018 to January 2023. A mix of deidentified images of 2 fields of view (optic disc centered and macula centered) were used. For training and internal validation, images were from 16 fundus camera models with fields of 30° to 55°. For external testing, images were from 5 fundus cameras with fields of 30° to 50°. Data were analyzed from January 2023 to January 2024. Main Outcomes and Measures: The performance of the DLS was measured using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy. Results: In the training and validation sets, 374 (54.9%) of patients were female, 301 (44.2%) were male, and 6 (0.9%) were of unknown sex; the median (range) age was 66 (23-96) years. When tested on the external dataset including 121 patients (35 [28.9%] female, 44 [36.4%] male, and 42 [34.7%] of unknown sex; median [range] age, 69 [37-89] years), the DLS achieved an AUC of 0.97 (95% CI, 0.95-0.99), a sensitivity of 91.1% (95% CI, 85.2-96.9), a specificity of 93.4% (95% CI, 91.1-98.2), and an accuracy of 92.6% (95% CI, 90.5-96.6). The accuracy of the 2 experts for classification of the same dataset was 74.3% (95% CI, 66.7-81.9) and 81.6% (95% CI, 74.8-88.4), respectively. Conclusions and Relevance: A DLS showing disease-specific averaged class-activation maps had greater than 90% accuracy at discriminating between acute AAION from NAION on color fundus images, at the eye level, without any clinical or biomarker information. A DLS that identifies AAION could improve clinical decision-making, potentially reducing the risk of misdiagnosis and improving patient outcomes.

The Association Between Craniofacial Fracture Patterns and Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) is a rare but potentially devastating complication of craniofacial trauma. Approximately half of patients with TON sustain permanent vision loss. In this study, we sought to identify the most common fracture patterns associated with TON. We performed a retrospective review of craniomaxillofacial CT scans of trauma patients who presented to the R Adams Cowley Shock Trauma Center from 2015 to 2017. Included were adult patients who had orbital fractures with or without other facial fractures. Patients diagnosed with TON by a formal ophthalmologic examination were analyzed. Craniofacial fracture patterns were identified. Bivariate analysis and multivariate logistic regression were performed to identify craniofacial fracture patterns most commonly associated with TON. A total of 574 patients with orbital fractures who met inclusion criteria [15 (2.6%)] were diagnosed with TON. The median [interquartile range (IQR)] age was 44 (28-59) years. Patients with optic canal fractures and sphenoid sinus fractures had greater odds of TON compared with patients who did not have these fracture types [adjusted odds ratio (aOR) 95% confidence interval (CI) 31.8 (2.6->100), 8.1 (2.7-24.4), respectively]. Patients who sustain optic canal and sphenoid sinus fractures in the setting of blunt facial trauma are at increased odds of having a TON. Surgeons and other physicians involved in the care of these patients should be aware of this association.

Ophthalmic and Systemic Factors of Acute Nonarteritic Anterior Ischemic Optic Neuropathy in the Quark207 Treatment Trial.

PURPOSE: We describe the baseline ophthalmic and cardiovascular risk factors across countries, race, and sex for the Quark207 treatment trial for acute nonarteritic anterior ischemic optic neuropathy (NAION). DESIGN: Prospective, randomized controlled clinical trial. PARTICIPANTS: Adults 50 to 80 years of age with acute NAION recruited from 80 sites across 8 countries. MAIN OUTCOME MEASURES: Ophthalmic features of NAION and cardiovascular risk factors. METHODS: We evaluated demographics and clinical and ophthalmologic data, including best-corrected visual acuity (BCVA) and average visual field total deviation (TD), in affected eyes and cup-to-disc ratio in fellow eyes at enrollment. We report the prevalence (mean and standard devition, and median and interquartile range [IQR]) of ophthalmic features and cardiovascular risk factors, stratified by country, race, and sex. We corrected for multiple comparisons using Dunn's test with Bonferroni correction for continuous variables and chi-square testing with Holm-Bonferroni correction for categorical variables. RESULTS: The study enrolled 500 men and 229 women with a median age of 60 and 61 years (P = 0.027), respectively. Participants were predominantly White (n = 570) and Asian (n = 149). The study eye BCVA was 71 characters (IQR, 53-84 characters; approximately 0.4 logarithm of the minimum angle of resolution), and the TD was -16.5 dB (IQR, -22.2 to -12.6 dB) for stimulus III and -15.7 dB (IQR, -20.8 to -10.9 dB) for stimulus V. The vertical and horizontal cup-to-disc ratio was 0.1 (IQR, 0.1-0.3) for unaffected fellow eyes. The prevalence of cardiovascular risk factors varied among countries. The most notable differences were in the baseline comorbidities and ophthalmologic features, which differed between Asian and White races. Men and women differed with respect to a few clinically meaningful features. CONCLUSIONS: The cardiovascular risk factors in the NAION cohort varied among the 7 countries, race, and sex, but were not typically more prevalent than in the general population. Ophthalmic features, typical of NAION, generally were consistent across countries, race, and sex, except for worse BCVA and TD in China. Men have a frequency of NAION twice that of women. Having a small cup-to-disc ratio in the fellow eye was the most prevalent risk factor across all demographics. This study suggests that factors, not yet identified, may contribute to the development of NAION. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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.

Guidelines of the International Headache Society for Controlled Clinical Trials in Idiopathic Intracranial Hypertension.

The quality of clinical trials is essential to advance treatment, inform regulatory decisions and meta-analysis. With the increased incidence of idiopathic intracranial hypertension and the emergence of clinical trials for novel therapies in this condition, the International Headache Society Guidelines for Controlled Clinical Trials in Idiopathic Intracranial Hypertension aims to establish guidelines for designing state-of-the-art controlled clinical trials for idiopathic intracranial hypertension.

Visual Field Pointwise Analysis of the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT).

Purpose: This study was designed to determine if point analysis of the Humphrey visual field (HVF) is an effective outcome measure for people with idiopathic intracranial hypertension (IIH) compared with mean deviation (MD). Methods: Using the IIH Weight Trial data, we performed a pointwise analysis of the numerical retinal sensitivity. We then defined a medically treated cohort as having MDs between -2 dB and -7 dB and calculated the number of points that would have the ability to change by 7 dB. Results: The HVF 24-2 mean ± SD MD in the worse eye was -3.5 ± 1.1 dB (range, -2.0 to -6.4 dB). Total deviation demonstrated a preference for the peripheral and blind spot locations to be affected. Points between 0 dB and -10 dB demonstrated negligible ability to improve, compared with those between -10 dB and -25 dB. For the evaluation of the feasibility for a potential medical intervention trial, only 346 points were available for analysis between -10 dB and -25 dB bilaterally, compared with 4123 points in baseline sensitivities of 0 to -10 dB. Conclusions: Patients with IIH have mildly affected baseline sensitivities in the visual field based on HVF analyzer findings, and the majority of points do not show substantial change over 24 months in the setting of a randomized clinical trial. Most patients with IIH who are eligible for a medical treatment trial generally have the mildest affected baseline sensitivities. In such patients, pointwise analysis offers no advantage over MD in detection of visual field change.

Optic Neuropathies: Current and Future Strategies for Optic Nerve Protection and Repair.

Processes that damage the optic nerve, including elevated intraocular pressure, trauma, ischemia, and compression, often cause visual loss for which there is no current treatment [...].

Differentiating Glaucomatous Optic Neuropathy From Non-glaucomatous Optic Neuropathies Using Deep Learning Algorithms.

PURPOSE: A deep learning framework to differentiate glaucomatous optic disc changes due to glaucomatous optic neuropathy (GON) from non-glaucomatous optic disc changes due to non-glaucomatous optic neuropathies (NGONs). DESIGN: Cross-sectional study. METHOD: A deep-learning system was trained, validated, and externally tested to classify optic discs as normal, GON, or NGON, using 2183 digital color fundus photographs. A Single-Center data set of 1822 images (660 images of NGON, 676 images of GON, and 486 images of normal optic discs) was used for training and validation, whereas 361 photographs from 4 different data sets were used for external testing. Our algorithm removed the redundant information from the images using an optic disc segmentation (OD-SEG) network, after which we performed transfer learning with various pre-trained networks. Finally, we calculated sensitivity, specificity, F1-score, and precision to show the performance of the discrimination network in the validation and independent external data set. RESULTS: For classification, the algorithm with the best performance for the Single-Center data set was DenseNet121, with a sensitivity of 95.36%, precision of 95.35%, specificity of 92.19%, and F1 score of 95.40%. For the external validation data, the sensitivity and specificity of our network for differentiating GON from NGON were 85.53% and 89.02%, respectively. The glaucoma specialist who diagnosed those cases in masked fashion had a sensitivity of 71.05% and a specificity of 82.21%. CONCLUSIONS: The proposed algorithm for the differentiation of GON from NGON yields results that have a higher sensitivity than those of a glaucoma specialist, and its application for unseen data thus is extremely promising.

Cranial Polyneuropathy Secondary to Remote Iophendylate Myelography.

A 68-year-old woman with controlled hypertension, and degenerative joint disease of the spine for which she had undergone several myelograms and three surgeries 30-32 years earlier, presented with a 2 year history of painless, oblique, binocular diplopia. Her prior ophthalmic evaluations were consistent with an isolated left trochlear nerve paresis. She had magnetic resonance imaging (MRI) showing multiple foci of T1-weighted hyperintensities around the midbrain and brainstem thought to represent subarachnoid fat from a ruptured dermoid cyst. An extensive evaluation revealed a left trochlear nerve paresis as well as diminished sensation in the distributions of the first and second divisions of the left trigeminal nerve. Review of her MRI and history of myelograms raised the possibility of focal inflammation from intrathecal iophendylate (Pantopaque®). Repeat MRI was obtained that showed T1-weighted hyperintensities similar to her previous MRI, but in this study, T1-weighted fat suppression imaging also was performed and revealed these foci to be of low signal intensity, consistent with retained iophendylate.

Neuroprotection and Neuroregeneration Strategies Using the rNAION Model: Theory, Histology, Problems, Results and Analytical Approaches.

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve (ON)-related vision loss in humans. Study of this disease has been limited by the lack of available tissue and difficulties in evaluating both treatments and the window of effectiveness after symptom onset. The rodent nonarteritic anterior ischemic optic neuropathy model (rNAION) closely resembles clinical NAION in its pathophysiological changes and physiological responses. The rNAION model enables analysis of the specific responses to sudden ischemic axonopathy and effectiveness of potential treatments. However, there are anatomic and genetic differences between human and rodent ON, and the inducing factors for the disease and the model are different. These variables can result in marked differences in lesion development between the two species, as well as in the possible responses to various treatments. These caveats are discussed in the current article, as well as some of the species-associated differences that may be related to ischemic lesion severity and responses.

Elevated perioptic lipocalin-type prostaglandin D synthase concentration in patients with idiopathic intracranial hypertension.

The pathophysiology of vision loss and loss of visual field in patients with idiopathic intracranial hypertension with papilloedema is not fully understood. Although elevated CSF pressure induces damage to the optic nerve due to stasis of axoplasmic flow, there is no clear relationship between the severity of papilloedema and CSF pressure. Furthermore, there are cases of purely unilateral papilloedema and cases without papilloedema despite significantly elevated intracranial pressure as well as papilloedema that can persist despite a successfully lowered intracranial pressure. We hypothesize that at least in some of such cases, in addition to purely pressure-induced damage to the optic nerve, the biochemical composition of the CSF in the subarachnoid space surrounding the orbital optic nerve may play a role in the pathogenesis of vision loss. In this retrospective study, we report on lipocalin-type prostaglandin D synthase concentrations in the CSF within the perioptic and lumbar subarachnoid space in 14 patients with idiopathic intracranial hypertension (13 females, mean age 45 ± 13 years) with chronic persistent papilloedema resistant to maximum-tolerated medical therapy and visual impairment. CSF was collected from the subarachnoid space of the optic nerve during optic nerve sheath fenestration and from the lumbar subarachnoid space at the time of lumbar puncture. CSF was analysed for lipocalin-type prostaglandin D synthase and the concentrations compared between the two sites using nephelometry. The mean lipocalin-type prostaglandin D synthase concentration in the perioptic subarachnoid space was significantly higher compared with the concentration in the lumbar subarachnoid space (69 ± 51 mg/l without correction of serum contamination and 89 ± 67 mg/l after correction of serum contamination versus 23 ± 8 mg/l; P < 0.0001, Mann-Whitney U-test). These measurements demonstrate a change and imbalance in the biochemical environment of the optic nerve. Its possible effect is discussed.

Post-cataract surgery optic neuropathy: a chronological narrative review of the literature and speculation on pathogenesis.

PURPOSE OF REVIEW: To appraise the literature on the incidence of an acute anterior optic neuropathy resembling spontaneous nonarteritic anterior ischemic optic neuropathy (NAION) following uncomplicated cataract surgery and to explore the proposed pathogenesis of both immediate and delayed onset post-cataract surgery optic neuropathy (PCSON). RECENT FINDINGS: A number of case reports, case series, and retrospective case-controlled, big data, and population-based studies have identified an apparent association between cataract surgery and the occurrence of an acute anterior optic neuropathy that can either be immediate or delayed in onset. However, a recent study found no link between modern day cataract surgery and an increased risk of an acute anterior optic neuropathy. SUMMARY: Immediate PCSON appears to be related to negative perfusion pressure at the level of the optic disc due to increased intraocular pressure. The pathogenesis of delayed PCSON is unknown but probably multifactorial. Patients who have experienced spontaneous NAION or PCSON in one eye may be at risk of PCSON in the fellow eye.

Atypical Blepharospasm with Oromandibular Dystonia Associated with Cerebral Amyloid Angiopathy.

A case of atypical blepharospasm with oromandibular dystonia is presented in a patient found to have cerebral amyloid angiopathy on magnetic resonance imaging and a shared mechanism is discussed.

Cavernous Malformation of the Optic Nerve and Chiasm: Prompt Suspicion and Surgery Matter.

BACKGROUND: Cavernous malformations (CMs) of the optic nerve and chiasm are extremely rare, accounting for less than 1% of all intracranial CMs. Acute, subacute, or progressive visual loss from CM may occur with or without hemorrhage. Prompt surgical excision of the CM offers the best hope to improve or stabilize vision. Given its rarity, optic nerve and chiasm CMs may not be readily suspected. We provide 3 cases of optic nerve and chiasm CM, highlighting key neuroimaging features and the importance of expedited intervention. METHODS: Case records of the neuro-ophthalmology clinics of the Bascom Palmer Eye Institute and the University of Colorado, and literature review of reported cases of optic CM. RESULTS: A 49-year-old woman reported acute progressive painless vision loss in the right eye. MRI showed a suprasellar mass with heterogeneity in signal involving the right prechiasmatic optic nerve. Surgical excision of the CM 5 days after onset of visual loss improved vision from 20/300 to 20/30. A 29-year-old woman with acute painless blurred vision in the right eye had anterior chiasmal junctional visual field defects corresponding to a heterogeneously minimally enhancing mass with blood products enlarging the optic chiasm and proximal right optic nerve. Surgical excision of the CM 8 weeks after onset of visual loss improved vision from 20/40 to 20/15 with improved visual fields. A 33-year-old woman with a history of familial multiple CMs, diagnosed at age 18, reported new-onset severe headache followed by blurred vision. MRI showed a hemorrhagic lesion of the optic chiasm and right optic tract. She was 20/20 in each eye with a reported left superior homonymous hemianopia. No intervention was recommended. Vision of the right eye worsened to 20/400 2 months later. The patient was followed over 13 years, and the MRI and visual function remained unchanged. Literature review yielded 87 optic CM cases occurring across gender and nearly all ages with visual loss and headache as the most common presenting symptoms. Optic chiasm is the most common site of involvement (79%). Nearly 95% of reported CM cases were treated with surgery with 81% with improved vision and 1% with worsened vision. CONCLUSION: MRI features are critical to the diagnosis of optic nerve and chiasm CM and may mimic other lesions. A high index of suspicion by the neuro-ophthalmologist and neuroradiologist leads to early recognition and intervention. Given optic CM displaces and does not infiltrate neural tissue, expedited surgical resection by a neurosurgeon after consideration of other diagnostic possibilities improves visual function in most cases.

Developing a "Fast-Track" Strategy for Interventional Management of Patients With Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) has an increasing incidence worldwide over the past decade, with a high economic burden on patients and society. Up to 10% of patients with IIH have progressive visual decline requiring an invasive intervention (including cerebrospinal fluid shunting, cerebral dural sinus stenting, or optic nerve sheath fenestration [ONSF]). IIH patients with visual decline usually undergo evaluation and initial management through the emergency department (ED) and commonly have a long hospital stay due to the lack of a dedicated methodology for evaluation and management, particularly in patients who present with visual loss (i.e., fulminant IIH). An innovative practice approach is needed to improve the means of multidisciplinary communication in care and evaluation of IIH patients. This paper aims to discuss the need for the development and implementation of a multidisciplinary "fast-track" strategy for the evaluation and management of patients with fulminant IIH or those with a suboptimal response to maximum tolerated medical treatment at risk for visual loss. We suggest that such a program could reduce hospital stay and ED visits and therefore reduce healthcare costs and improve patient outcomes by accelerating the management process.