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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.

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.

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.

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.

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: 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.

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.

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.

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.

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.

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.

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.