Search

Gülsenay Citirak, Lasse Malmqvist, Steffen Hamann Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Glostrup, DenmarkCorrespondence: Steffen Hamann, Department of Ophthalmology, Rigshospitalet, University of Copenhagen, Valdemar Hansens Vej 13, Glostrup, 2600, Denmark, Tel +45 3863 4653, Email steffen.hamann@regionh.dkPurpose: Nonarteritic anterior ischemic optic neuropathy (NAION) is associated with vascular as well as anatomical risk factors. Following the insult, the visual development varies from minor to severe deterioration. The aim of this study was to examine possible prognostic systemic risk factors and their eventual impact on post-insult visual development in NAION patients.Methods: A retrospective chart review of all NAION patients (18– 79 years at time of diagnosis) seen a minimum of two times in a tertiary eye department during a 10-year period in regard to systemic diseases, medication, lifestyle factors and ophthalmic examination was performed. Visual outcome was assessed according to the development of best corrected visual acuity (BCVA) and visual field from initial to final visit.Results: There were 163 eligible patients. A greater proportion of the patients in the total cohort were over 50 years of age (79.8%) and men (66.3%). In total, 59.5% of the patients had a stable BCVA, while 25.8% experienced improvement, and 14.7% had deterioration. Seventy-two percent of the patients had a stable visual field, while 14% had improvement, and 14% had deterioration. No association between visual outcome and clinical characteristics, medication or systemic risk factors were identified.Conclusion: We did not find any association between patient characteristics and systemic risk factors at time of diagnosis and visual development post-insult. This could suggest that the optic nerve head anatomy plays a larger role for visual outcome than previously estimated.Keywords: NAION, nonarteritic anterior ischemic optic neuropathy, risk factors, visual outcome, optic neuropathy, NAION

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare demyelinating autoimmune disorder of the central nervous system. MOGAD frequently manifests with severe, bilateral, and episodes of recurrent optic neuritis (ON) and is an important differential diagnosis to multiple sclerosis and aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorders. Besides ON, the clinical manifestations of MOGAD commonly include transverse myelitis, acute disseminated encephalomyelitis, and brain stem encephalitis. In this review, we summarize the current knowledge of the neuro-ophthalmological presentation of MOGAD-ON. We describe epidemiological aspects, including the association with COVID-19 and other infections or vaccinations, clinical presentation, and imaging findings of MOGAD-ON in the acute stage and during remission. Furthermore, we report findings on prognosis, treatment response, and changes in ON-unaffected eyes. We touch upon findings on visual acuity, visual fields, and visual evoked potentials, as well as structural changes assessed with optical coherence tomography. Moreover, we explain how to differentiate MOGAD from its differential diagnoses, including other neuroinflammatory disorders (multiple sclerosis and neuromyelitis optica spectrum disorders), but also idiopathic intracranial hypertension.Die Myelin-Oligodendrozyten-Glykoprotein-Antikörper-assoziierte Erkrankung (MOGAD) ist eine seltene demyelinisierende Autoimmunerkrankung des zentralen Nervensystems. Die MOGAD äußert sich häufig durch schwere, bilaterale und wiederkehrende Episoden von Retrobulbärneuritis (optic neuritis, ON) und ist eine wichtige Differenzialdiagnose der multiplen Sklerose und der Aquaporin-4-IgG-assoziierten Neuromyelitis-optica-Spektrum-Erkrankungen. Zu den klinischen Manifestationen von MOGAD gehören neben ON häufig transversale Myelitis, akute disseminierte Enzephalomyelitis oder Hirnstammenzephalitis. In diesem Artikel fassen wir den aktuellen Kenntnisstand der neuroophthalmologischen Präsentation von MOGAD-ON zusammen. Wir beschreiben epidemiologische Aspekte, einschl. des Zusammenhangs mit COVID-19 und anderen Infektionen oder Impfungen, die klinische Präsentation und die bildgebenden Befunde von MOGAD-ON im akuten Stadium und in Remission. Darüber hinaus berichten wir über Befunde zur Prognose, zum Ansprechen auf Therapie und zu Veränderungen bei nicht betroffenen Augen. Insbesondere diskutieren wir Befunde zu Sehschärfe, Gesichtsfeld, visuell evozierten Potenzialen sowie zu strukturellen Veränderungen, die mittels optischer Kohärenztomografie untersucht werden. Darüber hinaus führen wir aus, wie sich MOGAD von anderen neuroinflammatorischen Erkrankungen (multiple Sklerose und Neuromyelitis-optica-Spektrum-Erkrankungen), aber auch von idiopathischer intrakranieller Hypertonie abgrenzt.

Optic disc drusen (ODD) are acellular calcified deposits within the optic nerve head known to cause visual field defects. An emerging gold standard for the diagnosis of ODD is enhanced depth imaging optical coherence tomography (EDI-OCT). The presence of ODD affects the adjacent peripapillary vasculature, which can be visualized using OCT angiography (OCTA). This study investigates the association between peripapillary vessel density and anatomical ODD location and volume using a newly developed method of multimodal OCT.A case-control study with 16 patients diagnosed with ODD in the period 2008-2017 and 24 healthy controls. All patients and controls had EDI-OCT, OCTA, and demographic data collected. Using EDI-OCT and the medical imaging segmentation tool ITK-SNAP, 3-dimensional (3D) visualization of ODD in patients were created. ODD 3D visualization and corresponding OCTA scans were superimposed, making it possible to correlate ODD volume to the peripapillary vessel density in the corresponding modified Garway-Heath segments of the optic disc.We found that mean peripapillary vessel density across all modified Garway-Heath segments were lower in ODD patients compared with controls with significant reduction of peripapillary vessel density in the superior segment (P = 0.03) and globally (P = 0.05). A significant inverse proportionality between ODD volume and peripapillary vessel density in the corresponding segment was seen (P = 0.002).We found a reduced peripapillary vessel density in regions with close anatomical proximity to ODD and inverse proportionality between ODD volume and peripapillary vessel density.

Giant cell arteritis (GCA) is an ophthalmological emergency that can be difficult to diagnose and prompt treatment is vital. We investigated the sequential diagnostic value for patients with suspected GCA using three biochemical measures as they arrive to the clinician: first, platelet count, then C-reactive protein (CRP), and lastly, erythrocyte sedimentation rate (ESR). This retrospective cross-sectional study of consecutive patients with suspected GCA investigated platelet count, CRP, and ESR using diagnostic test accuracy statistics and odds ratios (ORs) in a sequential fashion. The diagnosis was established by experts at follow-up, considering clinical findings and tests including temporal artery biopsy. A total of 94 patients were included, of which 37 (40%) were diagnosed with GCA. Compared with those without GCA, patients with GCA had a higher platelet count (p < 0.001), CRP (p < 0.001), and ESR (p < 0.001). Platelet count demonstrated a low sensitivity (38%) and high specificity (88%); CRP, a high sensitivity (86%) and low specificity (56%); routine ESR, a high sensitivity (89%) and low specificity (47%); and age-adjusted ESR, a moderate sensitivity (65%) and moderate specificity (65%). Sequential analysis revealed that ESR did not provide additional value in evaluating risk of GCA. Initial biochemical evaluation can be based on platelet count and CRP, without waiting for ESR, which allows faster initial decision-making in GCA.

PURPOSE: To determine the prevalence of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in a population-based child cohort and to study their association with other optic nerve head features and myopia.DESIGN: Observational, population-based cohort study of 1407 children aged 11-12 years.METHODS: Optical coherence tomography scans of optic nerve heads were graded for PHOMS, disc tilt, prelaminar hyperreflective lines, and scleral canal diameter and investigated for associated prenatal and ocular parameters. Children with optic disc drusen or optic disc edema were excluded.RESULTS: PHOMS were found in 8.9% of children. The location of PHOMS was predominantly in the superonasal section of the optic disc. Myopia and optic nerve head tilt were more common in children with PHOMS than in children without PHOMS (P < .001 and P < .001, respectively). Prelaminar hyperreflective lines were found in 17.9% of children with PHOMS compared to 7.3% of children without PHOMS (P < .001). Prelaminar hyperreflective lines with and without PHOMS were associated with a shorter axial length of the eye (P < .001). There were no prenatal factors associated with PHOMS. Prelaminar hyperreflective lines were associated with higher birth weight and continued maternal smoking during pregnancy (P = .01 and P = .02, respectively).CONCLUSIONS: PHOMS had a prevalence of 8.9% in healthy children without optic disc drusen or optic disc edema and was associated with increasing myopic refraction and the presence of a tilted optic nerve head and prelaminar hyperreflective lines. Given the high prevalence of PHOMS, they should not unreservedly be taken as evidence of optic neuropathy.

Purpose: In this study, we investigate the potential of a novel artificial intelligence-based system for autonomous follow-up of patients treated for neovascular age-related macular degeneration (AMD). Methods: A temporal deep learning model was trained on a data set of 84 489 optical coherence tomography scans from AMD patients to recognize disease activity, and its performance was compared with a published non-temporal model trained on the same data (Acta Ophthalmol, 2021). An autonomous follow-up system was created by augmenting the AI model with deterministic logic to suggest treatment according to the observe-and-plan regimen. To validate the AI-based system, a data set comprising clinical decisions and imaging data from 200 follow-up consultations was collected prospectively. In each case, both the autonomous AI decision and original clinical decision were compared with an expert panel consensus. Results: The temporal AI model proved superior at detecting disease activity compared with the model without temporal input (area under the curve 0.900 (95% CI 0.894–0.906) and 0.857 (95% CI 0.846–0.867) respectively). The AI-based follow-up system could make an autonomous decision in 73% of the cases, 91.8% of which were in agreement with expert consensus. This was on par with the 87.7% agreement rate between decisions made in the clinic and expert consensus (p = 0.33). Conclusions: The proposed autonomous follow-up system was shown to be safe and compliant with expert consensus on par with clinical practice. The system could in the future ease the pressure on public ophthalmology services from an increasing number of AMD patients.

Deep optic disc drusen (ODD) are located below Bruch’s membrane opening (BMO) and may go undetected due to the challenges in imaging them. The purpose of this study is a head-to-head comparison of currently widely used imaging technologies: swept-source optical coherence tomography (SS-OCT; DRI OCT-1 Triton, Topcon) and enhanced depth imaging spectral-domain optical coherence tomography (EDI SD-OCT; Spectralis OCT, Heidelberg Engineering) for the detection of deep ODD and associated imaging features. The eyes included in this study had undergone high-resolution imaging via both EDI SD-OCT and SS-OCT volume scans, which showed at least one deep ODD or a hyperreflective line (HL). Grading was performed by three graders in a masked fashion. The study findings are based on 46 B-scan stacks of 23 eyes including a total of 7981 scans. For scan images with ODD located above or below the level of BMO, no significant difference was found between the two modalities compared in this study. However, for HLs and other features, EDI SD-OCT scan images had better visualization and less artifacts. Although SS-OCT offers deep tissue visualization, it did not appear to offer any advantage in ODD detection over a dense volume scan via EDI SD-OCT with B-scan averaging.

PURPOSE: To investigate the prevalence of optic disc drusen (ODD) and optic nerve head (ONH) morphology in patients diagnosed with normal tension glaucoma (NTG).METHODS: In this prospective cross-sectional study, we included patients diagnosed with NTG from two glaucoma units. In both eyes, dense enhanced depth imaging optical coherence tomography volume scans of the ONH by means of standardized scanning guidelines were performed to examine for presence of ODD, and radial ONH scans were used for investigating parameters such as scleral canal diameter, cup/disc ratio and cup depth.RESULTS: We found ODD in 7 (3.6%) of 195 eyes, in 6 (6.1%) out of 98 patients diagnosed with NTG. The ODD were not ophthalmoscopically visible in five out of six patients. Eyes with ODD had lower cup/disc ratio, 0.44 ± 0.4 (p = 0.040), and less-prominent cup depth, 236.6 ± 204.4 μm (p = 0.041) compared to eyes without ODD, 0.81 ± 0.2 and 437.8 ± 139.1 μm, respectively. We found no significant difference in scleral canal diameter between the eyes without (1602.8 ± 193 μm) and those with ODD (1492 ± 123.4 μm, p = 0.057).CONCLUSION: The prevalence of ODD in patients diagnosed with NTG is substantially higher than in the background population. A low cup/disc ratio correlates with ODD presence. Therefore, due to the challenges associated with NTG diagnosis, we recommend examining the deep layers of the ONH in NTG patients with a cup/disc ratio lower than 0.5 to avoid misdiagnosing ODD as NTG.

To identify the most accurate diagnostic imaging modality to detect optic disc drusen (ODD) between B-scan ultrasonography (US), fundus photography, fundus autofluorescence (FAF), and enhanced depth imaging optical coherence tomography (EDI-OCT).Comparative diagnostic analysis METHODS: : Two hundred and five eyes of 105 patients referred to two tertiary care neuro-ophthalmology clinics for suspected ODD were recruited. Of these eyes, 108 had ODD, and 97 did not. All eyes received a full in-person ophthalmic exam with 3D view of the optic nerve and all four imaging modalities. Images were independently reviewed by three masked neuro-ophthalmologists to determine the presence or absence of ODD. Final interpretation was made through consensus. The reference standard was defined as the attending ophthalmologist's clinical judgement based on open chart review, with access to all image modalities and clinical information, including disease course. Main outcome measures were sensitivity, specificity, accuracy, and precision for each imaging modality. Examiner confidence was quantified as the proportion of eyes in which the reviewers were certain of their decision.EDI-OCT had the highest sensitivity and accuracy (95%, 97%) to detect ODD, compared to FAF (84%, 92%), US (74%, 86%), and fundus photography (38%, 66%). All image modalities had high specificity (97%) and precision (93%). EDI-OCT also had highest examiner confidence (96%) compared to all others (88%).Among all modalities, EDI-OCT is the imaging modality with the highest diagnostic utility for the detection of ODD and should be considered as the preferred initial diagnostic modality.

A 23-year-old man presented with right eye blurred vision; he was diagnosed with acute posterior multifocal placoid pigment epitheliopathy (APMPPE), and his symptoms resolved with prednisolone. Two months later, he developed a right arm weakness that resolved after 3 weeks. MR scan of brain identified changes suggesting multiple sclerosis, with four hyperintense FLAIR lesions; there was contrast enhancement of two lesions and no diffusion restriction. Cerebrospinal fluid showed mononuclear pleocytosis. We eventually diagnosed these as APMPPE-associated CNS lesions. APMPPE is a rare inflammatory chorioretinopathy that rarely can resemble multiple sclerosis clinically and radiologically.

Background Our objective was to assess optic nerve sheath diameter (a marker of elevated intracranial pressure) and optic disc elevation (a marker of papilledema) in pseudotumor cerebri syndrome using transorbital sonography. Methods The study was a prospective case-control study. We included patients with new-onset pseudotumor cerebri syndrome and matched healthy controls. All had fundoscopy, lumbar puncture with opening pressure and transorbital sonography. Sonography was assessed by a blinded observer. Results We evaluated 45 patients and included 23 cases. We recruited 35 controls. Optic nerve sheath diameter was larger in pseudotumor cerebri syndrome compared to controls (6.3 ± 0.9 mm versus 5.0 ± 0.5 mm, p Conclusion Optic disc elevation and optic nerve sheath diameter are increased in new-onset pseudotumor cerebri syndrome. Optic disc elevation achieved high specificity and excellent sensitivity for diagnosis of pseudotumor cerebri syndrome. Transorbital sonography (TOS) is a potential, non-invasive screening tool for pseudotumor cerebri syndrome in headache clinics.

Purpose: Optic disc drusen (ODD) is an anatomical risk factor for nonarteritic anterior ischemic optic neuropathy (NA-AION). This study aimed to investigate the anatomical and vascular risk factors of patients with ODD-AION (ODD-associated NA-AION) and compare them with similar data from patients with nODD-AION (NA-AION without ODD). Design:: Case-control study. Methods: Thirty-four ODD-AION and 34 nODD-AION patients who had all been systematically optical coherence tomography scanned using a standardized ODD scanning protocol were retrospectively analyzed and compared regarding demographics, vascular risk factors, clinical characteristics, and specific optic nerve head anatomical characteristics. Results: In patients with ODD-AION, the ODD were predominantly deeply located (82%) but with no significant difference in size (52% large, 48% small). When compared with nODD-AION patients, ODD-AION patients were significantly younger at the time of diagnosis (P = .012) and had fewer vascular risk factors (P = .015). The ODD-AION patients had significantly more peripapillary hyperreflective ovoid mass-like structures (PHOMS) (P < .001) and prelaminar hyperreflective lines (P < .001) as well as smaller Bruch's membrane opening diameters (P = .017) compared with nODD-AION patients. No significant differences were found between ODD-AION and nODD-AION patients regarding visual acuity, refraction, lamina cribrosa position, ganglion cell layer volume, or retinal nerve fiber layer thickness. Conclusion: In ODD-AION, location of the ODD within the optic nerve head is important, while the size of the ODD is not. The ODD-AION and nODD-AION patients presented with distinctly different vascular risk factors and anatomical characteristics, establishing ODD and potentially also PHOMS as independent risk factors for developing NA-AION.

PurposeTo develop a method to determine the volume of peripapillary hyperreflective ovoid masslike structures (PHOMS) and to examine the correlation between PHOMS and anatomic optic nerve head characteristics in a large cohort of patients with optic disc drusen (ODD).DesignRetrospective, observational study of patients with ODD.ParticipantsPatients with ODD seen in a 3-year period.MethodsWe determined the prevalence of PHOMS. We then developed a method to calculate the volume of PHOMS and measured this in all patients where radial scans on OCT were available. We analyzed the correlation between PHOMS volume and patient age, size of Bruch’s membrane opening (BMO), ODD visibility, and anatomic location of ODD in the optic nerve.Main Outcome MeasuresPrevalence and characteristics of PHOMS in patients with ODD.ResultsIn 247 (77%) eyes with ODD, PHOMS were found. Among these, 80% were in the first decade of life, 87% were in the second decade, 89% were in the third decade, 85% were in the fourth decade, 74% were in the fifth decade, 73% were in the sixth decade, 58% were in the seventh decade, 40% were in the eighth decade, and 0% were in the ninth decade. The ophthalmoscopic visibility of ODD increased with age. The volume of PHOMS decreased with age, but with no correlation to the size of BMO. The median volume of PHOMS was 0.27 mm3 (interquartile range [IQR], 0.13–0.49 mm3). Predominantly, PHOMS were observed in the nasal peripapillary area (87.5% nasal, 78.5% superior, 67% inferior, and 63.5% temporal).ConclusionsIn patients with ODD, PHOMS are seen frequently, with the highest prevalence in younger individuals. The volume of PHOMS decreases with age, and PHOMS are seen more frequently in patients with superficial ODD. Purpose: To develop a method to determine the volume of peripapillary hyperreflective ovoid masslike structures (PHOMS) and to examine the correlation between PHOMS and anatomic optic nerve head characteristics in a large cohort of patients with optic disc drusen (ODD). Design: Retrospective, observational study of patients with ODD. Participants: Patients with ODD seen in a 3-year period. Methods: We determined the prevalence of PHOMS. We then developed a method to calculate the volume of PHOMS and measured this in all patients where radial scans on OCT were available. We analyzed the correlation between PHOMS volume and patient age, size of Bruch's membrane opening (BMO), ODD visibility, and anatomic location of ODD in the optic nerve. Main Outcome Measures: Prevalence and characteristics of PHOMS in patients with ODD. Results: In 247 (77%) eyes with ODD, PHOMS were found. Among these, 80% were in the first decade of life, 87% were in the second decade, 89% were in the third decade, 85% were in the fourth decade, 74% were in the fifth decade, 73% were in the sixth decade, 58% were in the seventh decade, 40% were in the eighth decade, and 0% were in the ninth decade. The ophthalmoscopic visibility of ODD increased with age. The volume of PHOMS decreased with age, but with no correlation to the size of BMO. The median volume of PHOMS was 0.27 mm3 (interquartile range [IQR], 0.13–0.49 mm3). Predominantly, PHOMS were observed in the nasal peripapillary area (87.5% nasal, 78.5% superior, 67% inferior, and 63.5% temporal). Conclusions: In patients with ODD, PHOMS are seen frequently, with the highest prevalence in younger individuals. The volume of PHOMS decreases with age, and PHOMS are seen more frequently in patients with superficial ODD.

Optic disc drusen (ODD) are a well-recognised cause of an elevated optic disc appearance. When visible with ophthalmoscopy and fundus photography, ODD are readily identified. Yet, in more subtle cases of ODD, ancillary testing may be needed to render the diagnosis. Facilitating the diagnosis of ODD has clinical relevance, because affected individuals may otherwise undergo unnecessary costly and invasive investigations to rule out raised intracranial pressure and other causes of optic disc oedema. In this review, the role of established and emerging optical coherence tomography (OCT) techniques in the diagnosis and management of ODD cases is reviewed. A practical approach is taken to explain how to optimise use of commercially available OCT technology in the clinical setting. Optical coherence tomography provides many advantages over other imaging modalities in the diagnosis of ODD, including the ability to correlate retinal measures of neuroaxonal structure with drusen characteristics. Earlier spectral domain OCT techniques, however, were hindered by poor penetrance. In the modern imaging era, enhanced depth imaging OCT and swept source OCT enable higher resolution of ODD and other optic nerve head structures that might otherwise be mistaken for drusen. Ongoing studies featuring OCT angiography indicate that this technique may provide complementary information about microvascular supply that correlate with structural measures of optic nerve injury. Advances in OCT will continue to improve diagnostic accuracy and inform clinical understanding regarding structure-function correlations germane to the longitudinal follow up of ODD patients.

Purpose: To examine optic nerve head (ONH) anatomy in young adults with central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO) or nonarteritic anterior ischemic optic neuropathy (NA-AION) in order to look for associated, potentially predisposing anomalies. Methods: Cross-sectional study including 54 patients (ages 16–50 years) diagnosed from 2009 to 2018 with CRVO, BRVO, CRAO, BRAO, or NA-AION. Using Optical Coherence Tomography the presence of optic disc drusen (ODD), prelaminar hyperreflective lines and peripapillary hyperreflective ovoid mass-like structures (PHOMS), and determination of scleral canal size, retinal nerve fiber layer thickness (RNFLT) and macular ganglion cell layer thickness (GCLT) was obtained. Data for retinal vascular occlusion patients were grouped and analyzed together. Results: ODD were found in 13% of all patients, 2% of retinal vascular occlusion patients and 67% of NA-AION patients ( p Conclusion: ODD, prelaminar hyperreflective lines and PHOMS were more frequent in NA-AION patients compared to retinal vascular occlusion patients. The prevalence of ODD in retinal vascular occlusion patients was similar to the reported prevalence in the general population.

Visual field defects are common in patients with optic disc drusen (ODD). Our aim was to examine whether reduced optic nerve head (ONH) microcirculation is related to visual field defects in ODD patients. Vascular and tissue area mean blur rate (MBR(V) and MBR(T)), measured using laser speckle flowgraphy (LSFG), was significantly lower in the 32 included ODD eyes when compared with 40 healthy eyes (p

Background Nonarteritic anterior ischemic optic neuropathy (NA-AION) associated with optic disc drusen (ODD) is termed ODD-AION, where NA-AION with no evidence of ODD is simply termed NA-AION. Patients with ODD-AION have been found to be younger than those with NA-AION but with similar vascular risk factors. This study compares the known risk factors for NA-AION between a group with ODD-AION and a similarly aged group with NA-AION. Methods A case-control study of 13 patients with ODD-AION and 14 patients with NA-AION diagnosed in the period 2008-2017. All patients underwent an interview designed to evaluate history of vascular risk factors and comorbidities and re-examination including enhanced depth imaging optical coherence tomography to confirm the presence or absence of ODD. Results No significant differences were found in demographic or clinical characteristics between the ODD-AION and the NA-AION group. Significantly more ODD-AION patients than NA-AION patients had no vascular risk factors (smoking, arterial hypertension, diabetes mellitus, and dyslipidemia) present (P = 0.047). Significantly fewer patients in the ODD-AION group were diagnosed with arterial hypertension or dyslipidemia than in the NA-AION group. Conclusions In this cross-sectional study, the ODD-AION patients more often had no vascular risk factors as compared to NA-AION patients, which supports the hypothesis that ODD are an independent risk factor for AION.

Background and ObjectivesThe distinction of papilledema from other optic nerve head (ONH) lesions mimicking papilledema, such as optic disc drusen (ODD), can be difficult in clinical practice. We aimed the following: (1) to develop a deep learning algorithm to automatically identify major structures of the ONH in 3-dimensional (3D) optical coherence tomography (OCT) scans and (2) to exploit such information to robustly differentiate among ODD, papilledema, and healthy ONHs.MethodsThis was a cross-sectional comparative study of patients from 3 sites (Singapore, Denmark, and Australia) with confirmed ODD, those with papilledema due to raised intracranial pressure, and healthy controls. Raster scans of the ONH were acquired using OCT imaging and then processed to improve deep-tissue visibility. First, a deep learning algorithm was developed to identify major ONH tissues and ODD regions. The performance of our algorithm was assessed using the Dice coefficient. Second, a classification algorithm (random forest) was designed to perform 3-class classifications (1: ODD, 2: papilledema, and 3: healthy ONHs) strictly from their drusen and prelamina swelling scores (calculated from the segmentations). To assess performance, we reported the area under the receiver operating characteristic curve for each class.ResultsA total of 241 patients (256 imaged ONHs, including 105 ODD, 51 papilledema, and 100 healthy ONHs) were retrospectively included in this study. Using OCT images of the ONH, our segmentation algorithm was able to isolate neural and connective tissues and ODD regions/conglomerates whenever present. This was confirmed by an averaged Dice coefficient of 0.93 ± 0.03 on the test set, corresponding to good segmentation performance. Classification was achieved with high AUCs, that is, 0.99 ± 0.001 for the detection of ODD, 0.99 ± 0.005 for the detection of papilledema, and 0.98 ± 0.01 for the detection of healthy ONHs.DiscussionOur artificial intelligence approach can discriminate ODD from papilledema, strictly using a single OCT scan of the ONH. Our classification performance was very good in the studied population, with the caveat that validation in a much larger population is warranted. Our approach may have the potential to establish OCT imaging as one of the mainstays of diagnostic imaging for ONH disorders in neuro-ophthalmology, in addition to fundus photography.

Introduction Retinal vessel dynamics analysis has proven to be a viable, non-invasive surrogate marker for increased intracranial pressure. We aimed to test this method in patients with suspected idiopathic intracranial hypertension. Methods Patients with suspected idiopathic intracranial hypertension were prospectively enrolled for hand-held fundus-videography during diagnostic lumbar puncture. After extracting optic disc images, peripapillary arteriole-to-venule-ratios were measured using machine-learning algorithms with manual identification control. A general linear model was applied to arteriole-to-venule-ratios and corresponding lumbar opening pressures to estimate cerebrospinal fluid pressure. Results Twenty-five patients were included with a significant difference in arteriole-to-venule-ratio between patients with ( n = 17) and without ( n = 8) idiopathic intracranial hypertension (0.78 ± 0.10 vs 0.90 ± 0.08, p = 0.006). Arteriole-to-venule-ratio correlated inversely with lumbar opening pressure (slope regression estimate −0.0043 (95% CI −0.0073 to −0.0023), p = 0.002) and the association was stronger when lumbar opening pressure exceeded 15 mm Hg (20 cm H2O) (slope regression estimate −0.0080 (95% CI −0.0123 to −0.0039), p 20 mm Hg (27 cm H2O) with 78% sensitivity and 92% specificity (AUC 0.81, p = 0.02). A stand-alone arteriole-to-venule-ratio measurement predicting lumbar opening pressure >20 mm Hg (27 cm H2O) was inferior with a 48% sensitivity and 92% specificity (AUC 0.73, p = 0.002). Conclusion Retinal vessel dynamics analysis with the described model for estimating cerebrospinal fluid pressure is a promising non-invasive method with a high sensitivity and specificity for detecting elevated intracranial pressure at follow-up assessments of patients with confirmed idiopathic intracranial hypertension if initial lumbar opening pressure and arteriole-to-venule-ratio data are available.

Elevated intracranial pressure (ICP) is observed in many brain disorders. Obesity has been linked to ICP pathogenesis in disorders such as idiopathic intracranial pressure (IIH). We investigated the effect of diet induced obesity (DIO) on ICP and clinically relevant sequelae. Rats were fed either a control or high fat diet. Following weight gain long term ICP, headache behavior, body composition and retinal outcome were examined. Post-hoc analysis of retinal histology and molecular analysis of choroid plexus and trigeminal ganglion (TG) were performed. DIO rats demonstrated raised ICP by 55% which correlated with the abdominal fat percentage and increased non-respiratory slow waves, suggestive of altered cerebral compliance. Concurrently, DIO rats demonstrated a specific cephalic cutaneous allodynia which negatively correlated with the abdominal fat percentage. This sensitivity was associated with increased expression of headache markers in TG. Additionally, DIO rats had increased retinal nerve fiber layer thickness in vivo associated with raised ICP with a subsequent post-hoc demonstration of neuroretinal degeneration. This study demonstrates for the first time that DIO leads to raised ICP and subsequent clinically relevant symptom development. This novel model of non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP such as IIH.

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber’s hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

Idiopathic intracranial hypertension (IIH) is a challenging disease characterized by an increase in intracranial pressure which occurs without any known cause. The disease is mainly seen in obese females of child-bearing age. While originally described as rare, the incidence is increasing in parallel with pandemic obesity, and clinicians in all fields are increasingly likely to meet patients with IIH. The condition causes major morbidity due to chronic headache and visual loss if untreated. In the past ten years new diagnostic criteria and guidelines for management have been published.

Elevated intracranial pressure (ICP) is a feature of critical cerebral disorders. Obesity has been linked to raised ICP, and especially to disorders such as idiopathic intracranial pressure (IIH). We aimed to explore the impact of diet-induced obesity (DIO) on ICP, cephalic sensitivity and structural retinal changes with the dual goal of developing a disease model for non-traumatic raised ICP and IIH. Rats were fed high-fat diet or matched control diet. To assess pain sensitivity, Von Frey and light/dark box testing were performed. Dual energy x-ray absorptiometry scanning was used to measure body composition. Optic nerve head and retinal structures were evaluated using optical coherence tomography. Intraocular pressure was assessed. Rats were then implanted with telemetric device for continuous ICP recording. At the end, eye histology and molecular analysis on choroid plexus (CP) and trigeminal ganglion (TG) were performed. The DIO rats had double the abdominal fat mass. ICP was 55% higher in obese rats (p=0.003). Altered pain thresholds were found in DIO rats as denoted by a lower periorbital threshold (p=0.0002). Expression of Calca and Trpv1 was elevated in TG. Furthermore, a peripapillary retinal nerve fiber layer swelling (p=0.0026) with subsequent neuroretinal degeneration p=0.02) was detected in DIO rats. There was a trend to increased expression of AQP1 and NKCC1 at CP. This study demonstrates for the first time that DIO leads to raised ICP, with clinically relevant sequalae. Our novel model for non-traumatic raised ICP could expand the knowledge regarding disorders with elevated ICP and IIH.

Loss of vision is a feared consequence of idiopathic intracranial hypertension (IIH). Optic nerve sheath fenestration (ONSF) may be an effective surgical approach to protect visual function in medically refractory IIH. In this study, we evaluate the impact of unilateral superomedial transconjunctival ONSF on bilateral visual outcome using a comprehensive follow-up program. A retrospective chart review of IIH patients who underwent unilateral ONSF between January 2016 and March 2021 was conducted. Patients fulfilling the revised Friedman criteria for IIH and who had exclusively received ONSF as a surgical treatment were included. Main outcomes were visual acuity (VA), perimetric mean deviation (PMD), papilledema grade, and optic nerve head elevation (maxONHE) 1 week, 2 weeks, and 1, 3, and 6 months after surgery. VA (p &lt, 0.05), PMD (p &lt, 0.05), papilledema grade (p &lt, 0.01), and maxOHNE (p &lt, 0.001) were improved after 6 months on both the operated and non-operated eye. Prolonged surgical delay impedes PMD improvement (r = −0.78, p &lt, 0.01), and an increasing opening pressure initiates a greater ganglion cell loss (r = −0.79, p &lt, 0.01). In this small case series, we demonstrate that unilateral superonasal transconjunctival ONSF is a safe procedure with an effect on both eyes. Optic nerve head elevation and PMD are feasible biomarkers for assessing early treatment efficacy after ONSF.

We aimed to systematically examine the optic nerve head anatomy in patients with idiopathic intracranial hypertension (IIH) using a standardized optical coherence tomography (OCT) protocol. The study retrospectively included 32 patients diagnosed from 2014 to 2021 with IIH. Using OCT, in accordance with a standardized scanning protocol for patients with optic disc drusen, the presence of optic disc drusen, prelaminar hyperreflective lines, peripapillary hyperreflective ovoid mass-like structures, the retinal nerve fiber layer thickness, and macular ganglion cell layer volume was obtained. Optic disc drusen were found in 3.1%, hyperreflective lines in 31.3%, and peripapillary hyperreflective ovoid mass-like structures in 81.3% of all IIH patients at least three months after the time of diagnosis. We found no significant differences in retinal nerve fiber layer thickness or macular ganglion cell layer volume in patients with hyperreflective lines or PHOMS respectively compared to patients without hyperreflective lines (p = 0.1285 and p = 0.1835). In conclusion, the prevalence of optic disc drusen in IIH patients is similar to the reported prevalence in the general population. The high prevalence of hyperreflective lines and peripapillary hyperreflective ovoid mass-like structures in IIH patients suggest these structures be a result of crowding in the optic nerve head caused by papilledema.

Purpose Optic disc drusen (ODD) are calcified optic nerve head deposits. Objectives of this study were to examine the prevalence of ODD in eyes removed by enucleation and to describe related histopathological signatures of ODD and surrounding tissues. Methods The study was a retrospective observational case series study assessing and re-evaluating enucleated eyes in Denmark from 1980 to 2015 by microscopy. Individual ODD were described based on size, number and location (superficial and/or deep) within the optic nerve. Optic nerve heads with ODD were assessed for elevated discs, retinal nerve fibre layer (RNFL) thickness, oedematous axons and presence of localized peripapillary axonal distension (LPAD) equivalent to the peripapillary hyperreflective ovoid mass-like structures seen on optical coherence tomography. Results Microscopy of 1713 eyes revealed ODD in 31 eyes equivalent to a prevalence of 1.8%. Optic disc drusen (ODD) were seen as circular shapes of different sizes and varying number. Elevated discs were present in 15 (54%) of the cases. Thickening of the superficial RNFL was present in eyes with large deeply located ODD. For more superficial ODD of approximately same size, the RNFL was thinner. Oedematous axons were present in three eyes. Localized peripapillary axonal distension (LPAD) was seen in five eyes. Conclusions Prevalence of ODD in this study of histopathological signatures was higher than the prevalence found in clinical studies. Our results suggest that large, deep ODD might cause crowding and herniation of axons in the optic nerve head leading to a thickened superficial nerve fibre layer, pseudopapilledema and LPAD.

Background The kaolin induced obstructive hydrocephalus (OHC) model is well known for its ability to increase intracranial pressure (ICP) in experimental animals. Papilledema (PE) which is a predominant hallmark of elevated ICP in the clinic has not yet been studied in this model using high-resolution digital fundus microscopy. Further, the long-term effect on ICP and optic nerve head changes have not been fully demonstrated. In this study we aimed to monitor epidural ICP after induction of OHC and to examine changes in the optic disc. In addition, we validated epidural ICP to intraventricular ICP in this disease model. Method Thirteen male Sprague-Dawley rats received an injection into the cisterna magna containing either kaolin-Ringer’s lactate suspension (n = 8) or an equal amount of Ringer’s lactate solution (n = 5). Epidural ICP was recorded post-operatively, and then continuously overnight and followed up after 1 week. The final epidural ICP value after 1 week was confirmed with simultaneous ventricular ICP measurement. Optic disc photos (ODP) were obtained preoperatively at baseline and after one week and were assessed for papilledema. Results All animals injected with kaolin developed OHC and had significant higher epidural ICP (15.49 ± 2.47 mmHg) compared to control animals (5.81 ± 1.33 mmHg) on day 1 (p p Conclusions We demonstrated that the raised ICP at day 1 in the hydrocephalus animals was completely normalized within 1 week and that epidural ICP measurements are valid method in this model. No acute papilledema was identified in the hydrocephalus animals, but the peripapillary changes indicate a potential gliosis formation or an early state of a growing papilledema in the context of lateral ventricle dilation and increased ICP.

Giant cell arteritis (GCA) is the most common form of large vessel vasculitis. GCA is a medical and ophthalmological emergency, and rapid diagnosis and treatment with high-dose corticosteroids is critical in order to reduce the risk of stroke and sudden irreversible loss of vision. GCA can be difficult to diagnose due to insidious and unspecific symptoms—especially if typical superficial extracranial arteries are not affected. In these cases, verification of clinical diagnosis using temporal artery biopsy is not possible. This example illustrates the diagnostic value of hybrid imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT), and the limitations of the temporal artery biopsy in bilateral vertebral GCA, causing transient ischemic attack in the visual cortex. In addition it indicates that inflammation in the artery wall can be visualized on 2-[18F]FDG PET/CT despite long term and ongoing high dose glucocorticoid treatment.

Giant cell arteritis (GCA) is a medical and ophthalmological emergency due to risk of stroke and sudden irreversible loss of vision. Fast and accurate diagnosis is important to prevent complications and long-term high dose glucocorticoids toxicity. Temporal artery biopsy is gold standard for diagnosing GCA. However, temporal artery ultrasound is a fast and non-invasive procedure which may provide a supplement or an alternative to biopsy. This study assesses the diagnostic performance of ultrasound and biopsy in the diagnosis of GCA.Examination results of patients suspected of having GCA in the period from August 2018 to June 2019 were reviewed. Patients underwent clinical examination and blood tests. Within a few days of starting glucocorticoid treatment, temporal ultrasound and unilateral biopsy were performed. Experienced physicians established the final clinical diagnosis at 6-months follow-up.Seventy-eight patients underwent both ultrasound and biopsy. Thirty-five (45%) received the final clinical diagnosis of GCA. Compared with the final clinical diagnosis, biopsy had a sensitivity of 69% (51-83%) and a specificity of 100% (92-100%), and ultrasound a sensitivity of 63% (45-79%) and a specificity of 79% (64-94%). Area under the receiver operating characteristics curves were 0.84 and 0.71 for biopsy and ultrasound respectively (p = 0.048). False negative rate of ultrasound was 4 out of 78 (5%).Sensitivity of ultrasound is almost on par with that of biopsy although the overall diagnostic accuracy of ultrasound was slightly lower. We find that ultrasound is a reliable tool for first line diagnosis of GCA.

BACKGROUND: With the development and widespread adoption of spectral-domain optical coherence tomography (OCT), peripapillary hyper-reflective ovoid mass-like structures (PHOMS) have become a frequent OCT finding in neuro-ophthalmic practice. Although originally assumed to represent a form of buried optic disc drusen (ODD), PHOMS differ from ODD in many important ways. The histopathological underpinnings of PHOMS are now becoming more clearly understood. EVIDENCE ACQUISITION: Review of literature. RESULTS: PHOMS can be broadly classified as disk edema-associated PHOMS, ODD-associated PHOMS, or anomalous disk-associated PHOMS. PHOMS are seen in many conditions, including papilledema, nonarteritic anterior ischemic optic neuropathy, central retinal vein occlusion, acute demyelinating optic neuritis, ODD, and tilted disks (myopic obliquely inserted disks) and in many cases resolve along with the underlying condition. The histopathological study of these diverse entities reveals the common feature of a bulge of optic nerve fibers herniating centrifugally over Bruch membrane opening into the peripapillary space, correlating exactly with the location, shape, and space-occupying nature of PHOMS on OCT. Because of the radial symmetry of these herniating optic nerve fibers, PHOMS are best thought of as a complete or partial torus (i.e., donut) in 3 dimensions. CONCLUSIONS: PHOMS are a common but nonspecific OCT marker of axoplasmic stasis in the optic nerve head. They are not themselves ODD or ODD precursors, although they can be seen in association with ODD and a wide spectrum of other conditions. They do not exclude papilledema and often accompany it. The circumferential extent and characteristic 3D toroidal nature of a PHOMS are best appreciated by scrolling through consecutive OCT images.

Idiopathic intracranial hypertension (IIH) is an enigmatic disorder characterized by raised intracranial pressure (ICP) with no known cause and it affects both children and adults [...]

Purpose: To meet the demands imposed by the continuing growth of the Age-related macular degeneration (AMD) patient population, automation of follow-ups by detecting retinal oedema using deep learning might be a viable approach. However, preparing and labelling data for training is time consuming. In this study, we investigate the feasibility of training a convolutional neural network (CNN) to accurately detect retinal oedema on optical coherence tomography (OCT) images of AMD patients with labels derived directly from clinical treatment decisions, without extensive preprocessing or relabelling. Methods: A total of 50 439 OCT images with associated treatment information were retrieved from databases at the Department of Ophthalmology, Rigshospitalet, Copenhagen, Denmark between 01.06.2007 and 01.06.2018. A CNN was trained on the retrieved data with the recorded treatment decisions as labels and validated on a subset of the data relabelled by three ophthalmologists to denote presence of oedema. Results: Moderate inter-grader agreement on presence of oedema in the relabelled data was found (76.4%). Despite different training and validation labels, the CNN performed on par with inter-grader agreement in detecting oedema on OCT images (AUC 0.97, accuracy 90.9%) and previously published models based on relabelled datasets. Conclusion: The level of performance shown by the current model might make it valuable in detecting disease activity in automated AMD patient follow-up systems. Our approach demonstrates that high accuracy is not necessarily constrained by incongruent training and validation labels. These results might encourage the use of existing clinical databases for development of deep learning based algorithms without labour-intensive preprocessing in the future.

Purpose To describe two cases of severe acute bilateral optic disc edema that occurred in patients with diabetes mellitus shortly after the initiation of intensified antihyperglycemic therapy. Methods Retrospective observational case report. Case description Two patients with type 1 diabetes presented for routine retinopathy screening with asymptomatic optic disc edema. One case was bilateral, the other unilateral. Neither patient had visual complaints. Both patients’ glycemia history was characterized by a recent bout of poor regulation and both had optic disc edema consistent with diabetic papillopathy in combination with prominent Optic disc drusen (ODD). The swelling that appeared to constitute the edematous diabetes-related component of the disease resolved within 10–12 weeks during which diabetes therapy was optimized. Visual field deficits were seen early on in both patients and had resolved to some extent in one patient after 9 months but persisted in the one affected eye in the other patient up to at least 30 months. Conclusion Two cases of ODD-associated diabetic papillopathy were observed: One with classic, bilateral disc edema and minor visual field defects, the other with unilateral disc edema, severe visual field defects and a phenotype that resembled non-arteritic anterior ischemic optic neuropathy. The cases suggest that ODD may increase the risk of diabetic papillopathy, a condition that is associated with rapid glycemia reduction and crowded optic discs, which may combine to produce nerve fiber swelling and hypoperfusion with venous congestion in a compartment with limited room for expansion.

Purpose The purpose of this study was to investigate seasonal variation in cases of biopsy-proven GCA in eastern Denmark in a 29-year period. Methods Pathology records of all temporal artery biopsies in eastern Denmark between 1990 and 2018 were reviewed. For each patient, data were collected which included age, sex, date of birth and biopsy result. Seasonality was evaluated using logistic regression and Poisson regression analysis. Lastly, an explorative pilot study was conducted to investigate a possible association between three weather parameters (average temperature, amount of rain and hours of sunshine) and the biopsy outcome. Results One thousand three hundred twenty-three biopsies were included of which 336 fulfilled objective criteria for GCA diagnosis. Mean age at diagnosis was 75.6 years (range 52-94 years). Among the biopsy-proven cases of GCA, there were 223 women (66.3%, mean age 76.2 years) and 113 men (33.7%, mean age 74.4 years) giving a female to male ratio of 1.97:1. The peak occurrence of GCA was in the 70-79 years age group. Statistical analysis of seasonal variation showed an increased risk of a positive biopsy during summer compared to autumn (p = 0.037). No association between the three weather parameters and the biopsy outcome was found. Conclusion In this study of biopsy-proven GCA in a large Danish patient cohort, the occurrence of GCA showed seasonal variation with higher occurrence in the summer months when compared to autumn. Future studies pooling all cases of GCA worldwide are needed to determine seasonality in the occurrence of GCA.

Objective: Peripapillary hyper-reflective ovoid masslike structures (PHOMS) are a new spectral domain optical coherence tomography (OCT) finding. Methods: This prospective, longitudinal study included patients (n = 212) with multiple sclerosis (MS; n = 418 eyes), 59 healthy controls (HCs; n = 117 eyes), and 267 non-MS disease controls (534 eyes). OCT and diffusion tensor imaging were used. Results: There were no PHOMS in HC eyes (0/117, 0%). The prevalence of PHOMS was significantly higher in patients with MS (34/212, p = 0.001) and MS eyes (45/418, p = 0.0002) when compared to HCs (0/59, 0/117). The inter-rater agreement for PHOMS was 97.9% (kappa = 0.951). PHOMS were present in 16% of patients with relapsing–remitting, 16% of patients with progressive, and 12% of patients with secondary progressive disease course (2% of eyes). There was no relationship of PHOMS with age, disease duration, disease course, disability, or disease-modifying treatments. The fractional anisotropy of the optic radiations was lower in patients without PHOMS (0.814) when compared to patients with PHOMS (0.845, p = 0.03). The majority of PHOMS remained stable, but increase in size and de novo development of PHOMS were also observed. In non-MS disease controls, PHOMS were observed in intracranial hypertension (62%), optic disc drusen (47%), anomalous optic discs (44%), isolated optic neuritis (19%), and optic atrophy (12%). Interpretation: These data suggest that PHOMS are a novel finding in MS pathology. Future research is needed to determine whether development of PHOMS in MS is due to intermittently raised intracranial pressure or an otherwise impaired “glymphatic” outflow from eye to brain. ANN NEUROL 2020;88:309–319.

Background Nonarteritic anterior ischemic optic neuropathy (NAION) in young patients (age ≤50) accounts for a minority of all cases of NAION and is more highly associated with crowding of the optic nerves and bilateral involvement than NAION in older patients. Optic disc drusen (ODD) are likewise associated with crowded optic nerves and are located in the prelaminar optic nerve head where they could contribute to NAION pathogenesis. The purpose of this study was to determine the prevalence of ODD in the eyes of young NAION patients using modern imaging methods and to compare it to the baseline 1.8%-2.0% prevalence of ODD in the general population. Methods In this retrospective study, all young NAION patients (ages 18-50 years, inclusive) seen in 2 tertiary care neuro-ophthalmology clinics (in London, Canada and Copenhagen, Denmark) in the ten-year interval between April 1, 2009, and March 31, 2019, were identified and their medical charts reviewed. Patients were included in the study if ODD were diagnosed by any method (including ophthalmoscopy, ultrasound [US], fundus autofluorescence [FAF], computed tomography [CT], or any optical coherence tomography [OCT] method), or if ODD were excluded by enhanced-depth imaging OCT (EDI-OCT) using the ODD Studies (ODDS) Consortium protocol. The presence or absence of ODD was recorded for each eye. Results There were 37 eligible patients (74 eyes). Mean age of NAION onset was 38.5 ± 10.0 years, and 23 patients (62%) were men. Patients had undergone the following methods of ODD detection: ophthalmoscopy (37 patients), EDI-OCT (36 patients), FAF (31 patients), US (9 patients), and CT orbits (8 patients). We found a prevalence of ODD of 56.7% in NAION-affected patients and 53.3% in NAION-affected eyes. Only 35.9% of ODD were visible on ophthalmoscopy. Twenty of 21 ODD patients (95.2%) had bilateral ODD. Age of onset and sex did not differ significantly between the ODD-positive group and the ODD-negative group. EDI-OCT outperformed any combination of ophthalmoscopy, US, FAF, and CT at detecting ODD. Conclusion ODD were found with much higher prevalence in young patients with NAION than in the general population and were usually bilateral and buried. ODD may contribute to NAION pathogenesis by exacerbating an underlying compartment syndrome in the crowded "disc at risk." EDI-OCT may be the best imaging modality for ODD detection in future studies.

Objective To compare the diagnostic performance of an artificial intelligence deep learning system with that of expert neuro-ophthalmologists in classifying optic disc appearance. Methods The deep learning system was previously trained and validated on 14,341 ocular fundus photographs from 19 international centers. The performance of the system was evaluated on 800 new fundus photographs (400 normal optic discs, 201 papilledema [disc edema from elevated intracranial pressure], 199 other optic disc abnormalities) and compared with that of 2 expert neuro-ophthalmologists who independently reviewed the same randomly presented images without clinical information. Area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity were calculated. Results The system correctly classified 678 of 800 (84.7%) photographs, compared with 675 of 800 (84.4%) for Expert 1 and 641 of 800 (80.1%) for Expert 2. The system yielded areas under the receiver operating characteristic curve of 0.97 (95% confidence interval [CI] = 0.96-0.98), 0.96 (95% CI = 0.94-0.97), and 0.89 (95% CI = 0.87-0.92) for the detection of normal discs, papilledema, and other disc abnormalities, respectively. The accuracy, sensitivity, and specificity of the system's classification of optic discs were similar to or better than the 2 experts. Intergrader agreement at the eye level was 0.71 (95% CI = 0.67-0.76) between Expert 1 and Expert 2, 0.72 (95% CI = 0.68-0.76) between the system and Expert 1, and 0.65 (95% CI = 0.61-0.70) between the system and Expert 2. Interpretation The performance of this deep learning system at classifying optic disc abnormalities was at least as good as 2 expert neuro-ophthalmologists. Future prospective studies are needed to validate this system as a diagnostic aid in relevant clinical settings. ANN NEUROL 2020;88:785-795.

BACKGROUND: The purpose of the study was to examine 5-year changes in eyes with optic disc drusen at baseline on optical coherence tomography (OCT) scans and the relation of incident drusen to hyperreflective prelaminar lines. METHODS: The study included children who presented at baseline, when participants were aged 11-12 years, and again 5 years later. Grading for optic disc drusen was made in all. Grading for prelaminar lines was made in all children at follow-up and in eyes with optic disc drusen at baseline. Analyses included associations with scleral canal diameter at baseline in all children with optic disc drusen and a nested control group of 115 children without optic disc drusen. Data are reported as the number of children having at least one drusen or at least one hyperreflective line per person. RESULTS: The analysis included 724 children who attended both rounds of the study. Of these, 11 (1.5%) had optic disc drusen at baseline. Five additional children had developed optic disc drusen at follow-up, whereas optic disc drusen had disappeared in none, so that 16 (2.2%) children had optic disc drusen in one or both eyes at follow-up. Children with optic disc drusen at the 5-year follow-up had had a mean scleral canal diameter of 1,364 µm (interquartile range [IQR] 81 µm), compared with 1,457 µm (IQR 197) µm in 115 nested controls without optic disc drusen (P < 0.001). Optic disc drusen at follow-up were associated with more hypermetropic refraction. All children who had optic disc drusen at follow-up also had prelaminar hyperreflective lines. In addition, such lines were found at follow-up in 24 of the remaining 708 children without optic disc drusen (P < 0.001). Prelaminar hyperreflective lines with or without optic disc drusen were associated with a narrower scleral canal (diameter 1,364 µm, IQR 119 µm) compared with absence of prelaminar lines (1,486 µm, IQR 206 µm; P < 0.0001). CONCLUSION: This study provides the first evidence from a prospective study that small optic discs and prelaminar hyperreflective lines on OCT are risk factors for the development of optic disc drusen. The association between prelaminar hyperreflective lines, hypermetropia, and a narrow scleral canal supports that a crowded disc is an essential predisposing factor for the development of optic disc drusen.

BACKGROUND: Nonophthalmologist physicians do not confidently perform direct ophthalmos-copy. The use of artificial intelligence to detect papilledema and other optic-disk abnormalities from fundus photographs has not been well studied METHODS: We trained, validated, and externally tested a deep-learning system to classify optic disks as being normal or having papilledema or other abnormalities from 15,846 retrospectively collected ocular fundus photographs that had been obtained with pharmacologic pupillary dilation and various digital cameras in persons from multiple ethnic populations. Of these photographs, 14,341 from 19 sites in 11 coun-tries were used for training and validation, and 1505 photographs from 5 other sites were used for external testing. Performance at classifying the optic-disk ap-pearance was evaluated by calculating the area under the receiver-operating-characteristic curve (AUC), sensitivity, and specificity, as compared with a reference standard of clinical diagnoses by neuro-ophthalmologists RESULTS: The training and validation data sets from 6779 patients included 14,341 photo-graphs: 9156 of normal disks, 2148 of disks with papilledema, and 3037 of disks with other abnormalities. The percentage classified as being normal ranged across sites from 9.8 to 100%; the percentage classified as having papilledema ranged across sites from zero to 59.5%. In the validation set, the system discriminated disks with papilledema from normal disks and disks with nonpapilledema abnor-malities with an AUC of 0.99 (95% confidence interval [CI], 0.98 to 0.99) and normal from abnormal disks with an AUC of 0.99 (95% CI, 0.99 to 0.99). In the external-testing data set of 1505 photographs, the system had an AUC for the detection of papilledema of 0.96 (95% CI, 0.95 to 0.97), a sensitivity of 96.4% (95% CI, 93.9 to 98.3), and a specificity of 84.7% (95% CI, 82.3 to 87.1).CONCLUSIONSA deep-learning system using fundus photographs with pharmacologically dilated pupils differentiated among optic disks with papilledema, normal disks, and disks with nonpapilledema abnormalities. (Funded by the Singapore National Medical Research Council and the SingHealth Duke–NUS Ophthalmology and Visual Sci-ences Academic Clinical Program.)

Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are a new retinal optical coherence tomography (OCT) finding. The Optic Disc Drusen Studies Consortium had made recommendations to distinguish PHOMS from true optic disc drusen (ODD) in 2018. While publications on PHOMS have increased since then, the accuracy of the definition of PHOMS and reliability of detection is unknown. In this multi-rater study, we demonstrate that the 2018 definition of PHOMS resulted in a poor multi-rater kappa of 0.356. We performed a Delphi consensus process to develop a consistent and refined definition of PHOMS with clear principles around the nature of PHOMS and how they differ from normal anatomy. Fifty explanatory teaching slides, provided as supplementary material, allowed our expert group of raters to achieve a good level of agreement (kappa 0.701, 50 OCT scans, 21 raters). We recommend adopting the refined definition for PHOMS.