An Association Between Large Optic Cupping and Total and Regional Brain Volume: The Women's Health Initiative.

PURPOSE: To investigate the relationships between optic nerve cupping and total and regional brain volumes. DESIGN: Secondary analysis of randomized clinical trial data. METHODS: Women 65 to 79 years of age without glaucoma with cup-to-disc ratio (CDR) measurements from the Women's Health Initiative (WHI) Sight Examination study and magnetic resonance imaging (MRI)-based total and regional brain volumes from the WHI Memory Study MRI-1 were included. Large CDR was defined as 0.6 or greater in either eye. Generalized estimating equation models were used to account for intra-brain correlations between the right and left sides. The final analysis was adjusted for demographic and clinical characteristics and for total brain volume (for regional analyses). RESULTS: Final analyses included 471 women, with the mean age ± SD was 69.2 ± 3.6 years; 92.8% of the subjects were white. Of 471 women, 34 (7.2%) had large CDR. Controlling for total brain volume and for demographic and clinical characteristics, lateral ventricle volume was 3.01 cc larger for subjects with large CDR compared to those without large CDR (95% CI = 0.02 to 5.99; P = .048). Furthermore, frontal lobe volume was 4.78 cc lower for subjects with large CDR compared to those without (95% CI = -8.71, -0.84; P = 0.02), and occipital lobe volume was 1.86 cc lower for those with large CDR compared to those without (95% CI = -3.39, -0.3; P =.02). CONCLUSIONS: Our analysis suggests that in women aged 65 years or more, large CDR is associated with lower relative total brain volume and absolute regional volume in the frontal and occipital lobes. Enlarged CDR in individuals without glaucoma may represent a sign of optic nerve and brain aging, although more longitudinal data are needed.

Accuracy and reliability of magnetic resonance imaging in the diagnosis of idiopathic intracranial hypertension.

PURPOSE: To determine the diagnostic utility of brain magnetic resonance imaging (MRI) findings in patients with idiopathic intracranial hypertension (IIH) and to investigate the significance of evaluating radiological findings together with neurological and ophthalmological data in the diagnosis of IIH. MATERIALS AND METHODS: All consecutive patients diagnosed with IIH in our tertiary neuro-ophthalmology center between January 1, 2018 and March 15, 2020, were included in the study. The clinical, radiological, and ophthalmological findings of IIH patients were compared with the control group with similar demographic characteristics. RESULTS: A total of 98 patients, 49 cases and 49 controls, were included in the study. Lateral ventricular index had the highest area under the curve (AUC) value (0.945) for prediction of disease group followed by sella height category (AUC = 0.915) and optic nerve tortuosity (AUC = 0.855) According to the multivariate model we developed, caudate index (OR = 0.572, 95% CI 0.329-0.996), lateral ventricle index (OR = 3.969, 95% CI 1.851-8.509) and bilateral optic nerve tortuosity (OR = 22,784, 95% CI 2.432-213.450) were significant predictors for disease group. CONCLUSION: Tortuosity in the optic nerve, lateral ventricular index and caudate index can be used as MRI parameters supporting the diagnosis of IIH in clinically suspicious cases. A holistic approach to the clinical and radiological findings of the cases in the diagnosis of IIH can prevent overdiagnosis and enable early correct diagnosis.

A Precise Method to Evaluate 360 Degree Measures of Optic Cup and Disc Morphology in an African American Cohort and Its Genetic Applications.

(1) Background: Vertical cup-to-disc ratio (CDR) is an important measure for evaluating damage to the optic nerve head (ONH) in glaucoma patients. However, this measure often does not fully capture the irregular cupping observed in glaucomatous nerves. We developed and evaluated a method to measure cup-to-disc ratio (CDR) at all 360 degrees of the ONH. (2) Methods: Non-physician graders from the Scheie Reading Center outlined the cup and disc on digital stereo color disc images from African American patients enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. After converting the resultant coordinates into polar representation, the CDR at each 360-degree location of the ONH was obtained. We compared grader VCDR values with clinical VCDR values, using Spearman correlation analysis, and validated significant genetic associations with clinical VCDR, using grader VCDR values. (3) Results: Graders delineated outlines of the cup contour and disc boundaries twice in each of 1815 stereo disc images. For both cases and controls, the mean CDR was highest at the horizontal bisector, particularly in the temporal region, as compared to other degree locations. There was a good correlation between grader CDR at the vertical bisector and clinical VCDR (Spearman Correlation OD: r = 0.78 [95% CI: 0.76-0.79]). An SNP in the MPDZ gene, associated with clinical VCDR in a prior genome-wide association study, showed a significant association with grader VCDR (p = 0.01) and grader CDR area ratio (p = 0.02). (4) Conclusions: The CDR of both glaucomatous and non-glaucomatous eyes varies by degree location, with the highest measurements in the temporal region of the eye. This method can be useful for capturing innate eccentric ONH morphology, tracking disease progression, and identifying genetic associations.

Bilateral optic nerve compression secondary to skull hyperostosis from vitamin A deficiency.

A 15-year-old boy with a history of autism spectrum disorder presented with bilateral progressive blurry vision and nyctalopia. Initial examinations, including optical coherence tomography scans of the macula and optic nerve, were within normal limits. Subsequent examination revealed trace pallor of the right optic nerve. Computed tomography and magnetic resonance imaging of the brain demonstrated diffuse thickening of calvarial bone with bilateral optic nerve compression. Laboratory evaluation was notable for profound vitamin A deficiency. The patient underwent optic nerve decompression and vitamin A supplementation with postoperative improvement in visual acuity of both eyes.

Complete unilateral vision loss and optic nerve cupping from metastatic prostate cancer to the optic canal.

A 71-year-old man, living with metastatic castrate-resistant prostate cancer to the lymph nodes, spine and skull, presented with acute on chronic left eye vision loss. Examination revealed no-light-perception vision, a relative afferent pupillary defect and optic disc cupping. MRI brain revealed optic canal narrowing from metastatic sphenoid bone expansion and extraosseous tumour compressing the intracanalicular optic nerve. The optic disc cupping and excavation without significant pallor of the remaining neuroretinal rim was likely secondary to chronic compression of the optic nerve. The patient was treated with radiation therapy, but did not regain vision and was referred to palliative care as his condition continued to worsen. As patients live longer with advanced cancer, there is a greater risk of metastasis to atypical areas of the body including the optic nerve. This case demonstrates the unique combination of optic disc cupping from optic canal metastasis due to prostate cancer.

Optic Disc Cupping Due to Dolichoectatic Internal Carotid Artery Optic Nerve Compression.

BACKGROUND: To determine whether significant compression of the optic nerve by the internal carotid artery (ICA) can produce an optic neuropathy with optic disc cupping that resembles glaucoma in patients without elevated intraocular pressure (IOP). METHODS: This was a retrospective case series of patients referred to neuro-ophthalmology for a possible nonglaucomatous optic neuropathy. Patients were included in the study if they had preserved visual acuity, optic disc-related visual field defects, optic nerve cupping, IOP less than 21 mm Hg, open angles, and unequivocal radiological compression of the ipsilateral optic nerve by an intracranial blood vessel. RESULTS: Three patients were included with a mean age of 56.3 (range 29-82) years. Patient 1 was a 58-year-old man incidentally noted to have left optic nerve cupping on a routine examination. He had an inferior arcuate defect and the left prechiasmatic optic nerve was elevated and compressed by a tortuous left ICA. Patient 2 was a 29-year-old man with a normal-tension glaucoma (NTG) diagnosis for 7 years in the right eye treated with latanoprost. He had a superior greater than inferior arcuate defect and there was vascular compression of the optic nerve between the supraclinoid ICA and A1 segment of the anterior cerebral artery. Patient 3 was an 82-year-old woman with an NTG diagnosis for 10 years who had progression of her visual field defects despite low IOPs. MRI showed mass effect on the right optic nerve by a dolichoectatic right supraclinoid ICA. CONCLUSIONS: Significant compression of the optic nerve by a normal, tortuous, or dolichoectatic ICA may result in an optic neuropathy with optic disc cupping that resembles glaucoma.

Optic pathway tumor in children: Toward a new classification for neurosurgical use.

OBJECT: Optic pathway tumors (OPT) represent a challenge for pediatric neurosurgeons. Role of surgery is debated due to the high risk of iatrogenic damage, and in lasts decades it lost its importance in favor of chemotherapy. However, in some cases surgery is necessary to make biomolecular and histological diagnosis, to manage intracranial hypertension (IH) and to cooperate with medical therapies in controlling tumor relapse. With the aim to standardize selection of surgical OPT cases, we propose a simple, practical and reproducible classification. METHODS: We retrospectively analyzed data of 38 patients with OPT treated at our institution (1990-2018). After careful analysis of MRI images, we describe a new classification system. Group 1: lesion limited to one or both optic nerve(s). Group 2: chiasmatic lesions extending minimally to hypothalamus. Group 3: hypothalamo-chiasmatic exophitic lesions invading the third ventricle; they can be further divided on the base of concomitant hydrocephalus. Group 4: hypothalamo-chiasmatic lesions extending widely in lateral direction, toward the temporal or the frontal lobes. Patients' data and adopted treatment are reported and analyzed, also depending on this classification. RESULTS: Twenty children were operated on for treatment of OPT during the study period. Permanent clinical impairment was noted in 5 (25%) of operated patients, while visual improvement was noted in 1 patient. OS rate was 100% at 5 years, with a median follow up of 9 years (ranging from 2 to 23). Prevalence of intracranial hypertension and proportion of first-line surgical treatment decision were significantly higher in groups 3-4 compared to groups 1-2 (P<0.001 for both tests). CONCLUSION: Surgery can offer a valuable therapeutic complement for OPT without major risk of iatrogenic damage. Surgery is indispensable in cases presenting with IH, as in groups 3 and 4 lesions. Eligibility of patients to surgery can be based on this new classification system.

Pseudoduplication of the optic disc initially resembling a bifurcated optic nerve in a strabismus child: a case report.

BACKGROUND: Pseudoduplication of the optic disc is a rare clinical condition that is characterized by a circumscribed, disc-like lesion with radiating vessels but only one normal optic nerve. We report a rare case that initially resembled a bifurcated optic nerve in a strabismus child. CASE PRESENTATION: A 6-year-old female child was initially referred to our hospital due to perceptual exotropia of 15 degrees with poor fixation of the left eye. The visual acuity of the left eye was 3/100 with a refraction of + 1.75/- 1.25 × 175. Fundus images of her left eye revealed a circumscribed and disc-like lesion located one disc diameter (DD) below the true optic disc that showed profound central cupping resembling a second optic disc with a vascular supply. B scan ultrasonography showed an optic nerve with a bifurcated weak-echo region, suggesting that two strands originated from the optic nerve. Optic coherence tomography (OCT) demonstrated a large crater-like depression of the lesion, indicating a colobomatous defect covered by a mysterious membranous structure, a disturbed nerve fibre layer and the absence of regular outer retinal layers. A perimetric examination revealed a relatively superior defect. Magnetic resonance imaging (MRI) revealed the left eye globe showed an abnormal morphology and that the optic nerve was abnormally shaped and shifted nasally in the left eye. Fundus fluorescein angiography (FFA) of the left eye revealed the absence of independent vascular vessels in the disc-like lesion. Hyperfluorescence with patchy fluorescence was evident in the inferotemporal area of the disc. Vascular loops surrounding the temporal region were evident in both eyes. Her right eye was normal except for the vascular loop. We proposed that this represented a case of pseudoduplication of the optic disc. The patient did not undergo any treatment, and her visual acuity remained stable during the follow-up period. CONCLUSIONS: Our patient presented with a deep and ectatic coloboma below the optic disc that communicated with the true optic nerve and was originally thought to indicate a bifurcated optic nerve. This case suggests that atypical ectatic colobomas should be considered before diagnosing malformations related to the optic nerve in double optic disc cases.

Current concepts of cerebrospinal fluid dynamics and the translaminar cribrosa pressure gradient: a paradigm of optic disk disease.

Modern advances in measuring and studying cerebrospinal fluid dynamics have furthered our understanding of intracranial pressure and its pathophysiological effects on the eye. In particular, the cerebrospinal fluid pressure and composition within the optic nerve subarachnoid space are key factors in diseases of the optic disk. Intracranial pressure and intraocular pressure establish a pressure gradient across the lamina cribrosa. Alterations in this translaminar cribrosa pressure difference induce structural deformations in the lamina cribrosa manifested clinically by the appearance of optic disk edema or optic disk cupping. Much has been learned about papilledema (i.e., optic disk edema due to elevated intracranial pressure) from clinical observations and studies on patients with idiopathic intracranial hypertension. Furthermore, optic nerve subarachnoid space hydrodynamics and translaminar cribrosa pressure difference are postulated to contribute to the pathogenesis of optic disk edema observed in spaceflight-associated neuroocular syndrome. Recently, a substantial body of literature has accumulated suggesting low intracranial pressure may be a risk factor for the development of glaucomatous optic disk cupping within the context of the translaminar cribrosa pressure difference and posterior scleral biomechanics.

An Association Between Large Optic Nerve Cupping and Cognitive Function.

PURPOSE: To determine if a larger cup-to-disc ratio is associated with poor cognitive function in postmenopausal women without glaucoma or ocular hypertension. METHODS: We used data from the Women's Health Initiative (WHI) hormone trial, originally designed to test effects of hormone therapy (HT) on various health outcomes. Large cup-to-disc ratio was defined as greater than 0.6 in either eye based on stereoscopic optic nerve photographs. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) in the WHI Memory Study. Exclusions were no information on optic nerve grading; no 3MSE scores at the time of the eye examination, ocular hypertension (intraocular pressure >23 mm Hg, Goldmann applanation tonometry), or glaucoma medication use. A generalized linear model for log-transformed 3MSE scores was used for determining the association between large cup-to-disc ratio and 3MSE scores, adjusting for age, race, diabetes, body mass index, cardiovascular disease, smoking, HT randomization, education, and diabetic retinopathy. RESULTS: Analyses included 1636 women (mean age ± standard deviation, 69.57 ± 3.64 years; 90.39% white). Of those, 122 women had large cup-to-disc ratio. The mean 3MSE scores in women with vs without large cup-to-disc ratio were 95.4 ± 6 vs 96.6 ± 5. In the adjusted model, women with large cup-to-disc ratio had statistically significantly lower 3MSE scores, compared with those without large cup-to-disc ratio, yielding the predicted mean difference in 3MSE scores of 0.75 with a standard error of 0.05 units (P = .04). CONCLUSIONS: Postmenopausal women who had large cup-to-disc ratio without glaucoma or ocular hypertension exhibited lower global cognitive function. Further investigation is warranted. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Changes in the optic nerve head induced by horizontal eye movements.

PURPOSE: To investigate the effect of eye movement on the optic nerve head (ONH) using swept-source optical coherence tomography (SS-OCT), and to measure the degree of ONH changes. METHODS: We enrolled 52 healthy subjects, 20 to 40 years of age, and performed a prospective observational study. Both ONH and macula were imaged simultaneously using wide volume scan of the SS-OCT in the primary and different gaze positions. Horizontal eye movements were used to obtain OCT images in abducted and adducted eyeball positions. Multilateral 3-dimensional registration was used to process and analyze the images to measure the degree of ONH changes. RESULTS: The mean axial length (AXL) was 25.73 ± 1.42mm and the mean spherical equivalents was -4.49 ± 2.94 D (The proportion of high myopia was 39.4%). Significant morphologic changes were observed in the ONH during both abduction and adduction. In abduction, the overall ONH tissues were elevated, and the mean area of elevation was 115,134 ± 9,424 µm2 (p<0.001). In adduction, the mean areas from two perspectives, which were nasal or temporal, and peripapillary tissues or optic nerve cupping were 95,277 ± 73,846 µm2, 34,450 ± 44,948 µm2, -108,652 ± 91,246 µm2, and -30,581 ± 46,249 µm2, respectively. Elevation in abduction (overall, nasal cup segment, and temporal cup segment; R = 0.204, 0.195 and 0.225, p = 0.038, 0.047 and 0.021, respectively) and elevation of nasal peripapillary segments in adduction were positively correlated with AXL (R = 0.346, p<0.001). CONCLUSION: We found significant morphologic changes in the ONH in both abduction and adduction and these changes were associated with AXL. Considering these morphologic changes as physical properties, it allows a better understanding of the biomechanical characteristics of the ONH.

Characterization of Retinal Ganglion Cell and Optic Nerve Phenotypes Caused by Sustained Intracranial Pressure Elevation in Mice.

Elevated intracranial pressure (ICP) can result in multiple neurologic sequelae including vision loss. Inducible models of ICP elevation are lacking in model organisms, which limits our understanding of the mechanism by which increased ICP impacts the visual system. We adapted a mouse model for the sustained elevation of ICP and tested the hypothesis that elevated ICP impacts the optic nerve and retinal ganglion cells (RGCs). ICP was elevated and maintained for 2 weeks, and resulted in multiple anatomic changes that are consistent with human disease including papilledema, loss of physiologic cupping, and engorgement of the optic nerve head. Elevated ICP caused a loss of RGC somas in the retina and RGC axons within the optic nerve, as well as a reduction in both RGC electrical function and contrast sensitivity. Elevated ICP also caused increased hypoxia-inducible factor (HIF)-1 alpha expression in the ganglion cell layer. These experiments confirm that sustained ICP elevation can be achieved in mice and causes phenotypes that preferentially impact RGCs and are similar to those seen in human disease. With this model, it is possible to model human diseases of elevated ICP such as Idiopathic Intracranial Hypertension and Spaceflight Associated Neuro-ocular Syndrome.

Evaluation of the optic nerve and scleral-choroidal-retinal layer with ultrasound elastography in glaucoma and physiological optic nerve head cupping.

AIM: To evaluate the strain ratio of the optic nerve and retina-choroid-sclera (RCS) layers in individuals with physiological optic disc cupping (PC) and glaucoma patients using strain elastography. MATERIAL AND METHODS: We evaluated 56 eyes of 56 subjects (20 eyes with glaucoma, 19 eyes with PC, and 17 normal eyes). The strain ratio of orbital fat to optic nerve (SROFON) was calculated as the ratio of the optic nerve to intraconal fat tissue and the strain ratio of orbital fat to retina-choroid-sclera (SROFRCS) was calculated as the ratio of RCS layers to intraconal fat tissue. RESULTS: SROFON was 0.92 in the control group, 1.07 in the PC group and 1.6 in the glaucoma group and a statistically significant difference was present between the three groups (p<0.05). SROFRCS had no statistically significant difference between the three groups. CONCLUSIONS:  SROFON values could contribute to the differentiation of the patients with glaucoma and PC.

Oblique scanning 2-photon light-sheet fluorescence microscopy for rapid volumetric imaging.

Light-sheet fluorescence microscopy (LSFM) is a powerful tool for biological studies because it allows for optical sectioning of dynamic samples with superior temporal resolution. However, LSFM using 2 orthogonally co-aligned objectives requires a special sample geometry, and volumetric imaging speed is limited due to physical sample translation. This paper describes an oblique scanning 2-photon LSFM (OS-2P-LSFM) that eliminates these limitations by using a single objective near the sample and a refractive scanning-descanning system. This system also provides improved light-sheet confinement against scattering by using a 2-photon Bessel beam. The OS-2P-LSFM hold promise for studying structural, functional and dynamic aspects of living tissues and organisms because it allows for high-speed, translation-free and scattering-robust 3D imaging of large biological specimens.

[OCT topographic characteristics of the optic nerve in patients clinically suspected to have large optic disc cupping in Togo]. / Les caractéristiques topographiques à l'OCT du disque optique chez des patients cliniquement suspects de grande excavation papillaire (GEP) au Togo.

PURPOSE: To describe topographic characteristics of optic discs clinically suspected of large cupping. MATERIALS AND METHODS: This is retrospective study conducted from the January 2 to December 31 on the OCT registry and data base of a private ophthalmologic center in Lomé (Togo). We included records of patients with large cupping - CDR (cup-to-disc ratio) ≥ 0.4 -clinically observed and having undergone OCT-optic disc analysis. RESULTS: Three hundred and thirty-five patients (619 eyes) were studied, with a mean age of 41.87 years±17.51 years [6 years and 80 years] and a sex-ratio of 1.01 with a slight female predominance. The mean clinical CDR was 0.51±0.126 [0.4 and 0.9] (95 % CI [0.503 to 0.531]). The clinical CDR was ≥ 0.7 in 7.75 % of cases. The mean neuroretinal rim area was 1.63±0.43 mm2 [0.34 and 2.85 mm2]. The mean cup area was 1.43±0.54 mm2 [0.13 and 4.29 mm2], and the mean cup volume 0.47±0.28 mm3 [0.01 and 1.72 mm3]. The mean global CDR on OCT was 0.46±0.13 [0.21 and 0.87], of which 30.85 % (191 cases) had CDR <0.4. The CDR on OCT was >0.7 in 40 (6.46 %) eyes vs. 48 (7.75 %) eyes on clinical examination. CONCLUSION: On the average, optics discs exhibit large size and large cup volume. Topographic evaluation of the optic disc by the means of OCT offers important data and gives way to etiological research of large cupping in the black African.

Pneumosinus dilatans of the spheno-ethmoidal complex associated with hypovitaminosis D causing bilateral optic canal stenosis.

INTRODUCTION: Pneumosinus dilatans (PSD) is a rare disorder of undetermined etiology characterized by expansion of the paranasal sinuses without bony erosion. Of the few cases of PSD described in indexed pediatric literature, there has been no reported case of this disorder presenting with optic canal stenosis in the setting of a vitamin deficiency. CASE MATERIAL: A 12-year-old girl presented with a 3-month history of progressive, painless, and asymmetric visual deterioration in her eyes. MRI showed prominent perioptic CSF spaces bilaterally and mild atrophy of both the optic nerves. CT head showed hyperpneumatization of the sphenoethmoidal air cells and both anterior clinoid processes with the optic nerves contained within narrowed intact bony canals. Blood investigations showed reduced vitamin D levels, and a subsequent skeletal survey showed diffuse osteopenia. She underwent endoscopic sphenoidotomy and bilateral decompression of the optic nerves. Following surgery, she reported improvement of vision in her left eye. She was started on vitamin D supplements for the endocrine abnormality. At a follow-up visit 6 months later, her visual acuity in both her eyes had improved. CONCLUSION: Pneumosinus dilatans is an unusual cause of progressive optic nerve dysfunction in the pediatric population. In the absence of any associated intracranial pathologies, conditions like hypovitamosis D should be ruled out.

Optic nerve morphology as marker for disease severity in cerebral palsy of perinatal origin.

BACKGROUND: It is difficult to predict the neurologic outcome and ambulatory status in children with perinatal neurologic insult until 2-5years age. This study aims to correlate clinical optic nerve head (ONH) findings-cupping, pallor and hypoplasia, with gestational period and neurologic (motor) outcomes in patients with cerebral palsy (CP) from perinatal insults. METHODS: 54 consecutive patients with CP from perinatal insults were enrolled. Patients with intraocular disease, retinopathy of prematurity and hydrocephalus were excluded. ONH was labeled as pale, hypoplastic or large cup (cup/disc ratio≥0.5) if 2 ophthalmologists independently agreed after an ophthalmoscopic examination. Inter-rater reliability was excellent. RESULTS: Mean age at examination was 10.98±6.49years; mean gestational period was 33.26±4.78weeks. Abnormal ONH (pallor, cupping or hypoplasia) was seen in 38/54 (70%) patients. Of patients with pallor (n=17), 88% were quadriplegic and 82% non-ambulatory. Mean cup/disc ratio was 0.45±0.22; 50% patients had large cup. Multivariate logistic regression models showed that disc pallor was associated with non-ambulatory status (OR: 21.7; p=0.003) and quadriplegia (OR: 12.8; p=0.03). Large cup was associated with age at examination (OR 1.15; p=0.03). Cup/disc ratio showed positive correlation with age at examination (Pearson's r=0.39; p=0.003). There was no significant association of ONH parameters with gestational age. CONCLUSION: Clinically observed ONH changes (pallor, cupping and hypoplasia) are common in CP. Presence of ONH pallor serves as an indicator for poor motor outcome in patients who develop CP from perinatal causes and should prompt early referral for rehabilitation.

Thickening of the optic nerves in metachromatic leucodystrophy: A new MRI finding.

Krabbe's disease (KD) and metachromatic leucodystrophy (MLD) are both lysosomal storage disorders that share some common MRI features. Amongst the imaging findings useful to distinguish one from the other, optic chiasm/nerves thickening have been described as specific key features for differential diagnosis favouring KD. We report the first case of enlargement of the optic nerves and chiasm described in a patient with genetically confirmed MLD.