High incidence of optic disc swelling at very high altitudes

OBJECTIVES: To determine the incidence of optic disc swelling as a possible indicator of cerebral edema in a large group of healthy mountaineers exposed to very high altitudes and to correlate these findings with various clinical and environmental factors and occurrence of acute mountain sickness and high-altitude cerebral edema. METHODS: This multidisciplinary, prospective, observational cohort study was performed in 2005 within the scope of a medical research expedition to Muztagh Ata (7546 m [24,751 ft]) in Western Xinjiang Province, China. Twenty-seven healthy mountaineers aged 26 to 62 years participated. Medical examinations were performed in Switzerland 1 month before and 4 1/2 months after the expedition. Ophthalmologic examinations were performed at 4 high camps (maximum elevation, 6865 m [22,517 ft]). Optic disc status was documented using digital photography. Further assessments included arterial oxygen saturation and cerebral acute mountain sickness scores. RESULTS: Sixteen of 27 study subjects (59%) exhibited optic disc swelling during their stay at high altitudes, with complete regression on return to lowlands. Significant correlation was noted between optic disc swelling and lower arterial oxygen saturation (odds ratio, 0.86 per percentage of arterial oxygen saturation; 95% confidence interval, 0.81-0.92; P < .001), younger age (odds ratio, 0.95 per year; 95% confidence interval, 0.90-0.99; P = .03), and higher cerebral acute mountain sickness scores (odds ratio, 2.32 per 0.1 point; 95% confidence interval, 1.48-3.63; P < .001). CONCLUSION: Optic disc swelling occurs frequently in high-altitude climbers and is correlated with peripheral oxygen saturation and symptoms of acute mountain sickness. It is most likely the result of hypoxia-induced brain volume increase.

Enhanced depth imaging optical coherence tomography of congenital cavitary optic disc anomaly (CODA).

AIM To report the finding of extension of the 4th hyper-reflective band and retinal tissue into the optic disc in patients with cavitary optic disc anomalies (CODAs). METHODS In this observational study, 10 patients (18 eyes) with sporadic or autosomal dominant CODA were evaluated with enhanced depth imaging optical coherence tomography (EDI-OCT) and colour fundus images for the presence of 4th hyper-reflective band extension into the optic disc. RESULTS Of 10 CODA patients (18 eyes), five patients (8 eyes) showed a definite 4th hyper-reflective band (presumed retinal pigment epithelium (RPE)) extension into the optic disc. In these five patients (seven eyes), the inner retinal layers also extended with the 4th hyper-reflective band into the optic disc. Best corrected visual acuity ranged from 20/20 to 20/200. In three patients (four eyes), retinal splitting/schisis was present and in two patients (two eyes), the macula was involved. In all cases, the 4th hyper-reflective band extended far beyond the termination of the choroid into the optic disc. The RPE extension was found either temporally or nasally in areas of optic nerve head excavation, most often adjacent to peripapillary pigment. Compared with eyes without RPE extension, eyes with RPE extension were more myopic (mean dioptres -0.9±2.6 vs -8.8±5, p=0.043). CONCLUSIONS The RPE usually stops near the optic nerve border separated by a border tissue. With CODA, extension of this hyper-reflective band and retinal tissue into the disc is possible and best evaluable using EDI-OCT or analogous image modalities. Whether this is a finding specific for CODA, linked to specific gene loci or is also seen in patients with other optic disc abnormalities needs further evaluation.

Multimodal Registration Procedure for the Initial Spatial Alignment of a Retinal Video Sequence to a Retinal Composite Image

Accurate placement of lesions is crucial for the effectiveness and safety of a retinal laser photocoagulation treatment. Computer assistance provides the capability for improvements to treatment accuracy and execution time. The idea is to use video frames acquired from a scanning digital ophthalmoscope (SDO) to compensate for retinal motion during laser treatment. This paper presents a method for the multimodal registration of the initial frame from an SDO retinal video sequence to a retinal composite image, which may contain a treatment plan. The retinal registration procedure comprises the following steps: 1) detection of vessel centerline points and identification of the optic disc; 2) prealignment of the video frame and the composite image based on optic disc parameters; and 3) iterative matching of the detected vessel centerline points in expanding matching regions. This registration algorithm was designed for the initialization of a real-time registration procedure that registers the subsequent video frames to the composite image. The algorithm demonstrated its capability to register various pairs of SDO video frames and composite images acquired from patients.

Simultaneous, bilateral anterior ischemic optic neuropathy (AION) in polycythemia vera: a case report

BACKGROUND: Polycythemia vera (PV) is a hemopoetic disorder. Apparently, although thrombosis accounts for the majority of morbidity, AION has not been associated with PV so far. PATIENT AND FINDINGS: A 63 y-old woman with PV was hospitalized because of acute liver failure. She also experienced bilateral painless loss of vision. Bilateral, pale optic disc swelling with flame-like hemorrhages, more pronounced in the right eye, constricted visual fields, and relative afferent papillary defect (RAPD) on the right side were present. Computer tomography scan revealed no signs of intraorbital pathology, elevated intracranial pressure or hemorrhages. CLINICAL COURSE: We interpreted the findings as AION associated with the hyperviscosity syndrome. Liver transplantation had to be carried out in the next days. Three weeks later, vision improved slightly, but RAPD persisted, and disc pallor developed in both eyes. The patient died two months later. DISCUSSION: Central retinal artery and vein occlusions have been described as complications of Essential thrombocythemia, but not of PV. We observed a rare case of bilateral neuropathy suggestive of AION. This condition has so far not been associated with PV.

New insights into ocular blood flow at very high altitudes

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

Uveitic glaucoma and Rosai-Dorfman disease (sinus histiocytosis)

PURPOSE: To report a novel association of uveitic glaucoma with Rosai-Dorfman disease. METHODS: Case report. RESULTS: A 67-year-old Caucasian woman presented with a chronic bilateral granulomatous uveitis which did not respond to conventional topical steroid therapy. She also had raised intraocular pressures, glaucomatous optic disc changes and diffuse nodular fibrous skin lesions. Subsequent skin biopsy immuno-cytochemistry showed S-100 staining, consistent with Rosai-Dorfman disease. The uveitis and glaucoma were highly resistant to standard medical treatments, but completely resolved together with the systemic features of the disease after six months. CONCLUSIONS: Rosai-Dorfman disease has not previously been reported to cause uveitic glaucoma and should be considered in non-responsive cases presenting with a rash. The disease is entirely self-limiting and early diagnosis may therefore avoid unnecessary trabeculectomy and/or systemic immune suppression.

Early loss of arteriolar smooth muscle cells: more than just a pericyte loss in diabetic retinopathy

Incipient diabetic retinopathy is characterized by increased capillary permeability and progressive capillary occlusion. The earliest structural change is the loss of pericytes (PC) from the retinal capillaries. With the availability of the XLacZ mouse, which expresses the LacZ reporter in a PC/vascular smooth muscle cell (vSMC) specific fashion, we quantitatively assessed the temporal dynamics of smooth muscle cells in arterioles under hyperglycemic conditions. We induced stable hyperglycemia in XLacZ mice. After 4, 8, and 12 weeks of diabetes retinae were isolated and beta-galactosidase/lectin stained. The numbers of smooth muscle cells were counted in retinal whole mounts, and diameters of retinal radial and branching arterioles and venules were analyzed at different distances apart from the center of the retina. After eight weeks of diabetes, the numbers of vSMCs were significantly reduced in radial arterioles 1000 microm distant from the optic disc. At proximal sites of branching arterioles (400 microm distant from the center), and at distal sites (1000 microm), vSMC were significantly reduced already after 4 weeks (to a maximum of 31 %). These changes were not associated with any measurable variation in vessel diameters. These data indicate quantitatively that hyperglycemia not only causes pericyte loss, but also loss of vSMCs in the retinal vasculature. Our data suggest that arteriolar vSMC in the eye underlie similar regulations which induce early pericyte loss in the diabetic retina.

Unilateral papilledema after trabeculectomy in a patient with intracranial hypertension

BACKGROUND: Increased intracranial pressure usually leads to bilateral disc swelling. HISTORY AND SIGNS: A patient presented with recurrent visual disturbances following trabeculectomy in the right eye. Intraocular pressure in the right and left eye were 11 and 24 mmHg, respectively. The optic nerve head was swollen in the right, but not in the left eye. Lumbar puncture showed an opening pressure of 32 cmH (2)O. Magnetic resonance imaging, neurological examination and composition of cerebrospinal fluid were normal. According to the modified Dandy criteria, an idiopathic intracranial hypertension was diagnosed. THERAPY AND OUTCOME: Treatment with acetazolamide led to resolution of papilledema in the right eye within six months. CONCLUSION: The intracranial-intraocular pressure gradient in the right eye was markedly higher as compared to that of the left eye. We suggest that this pressure gradient induced the collapse of axoplasmatic transport at the lamina cribrosa with subsequent disc swelling. As no significant pressure gradient was present in the left eye, the optic disc remained normal. Based on analogous calculations in three additional published cases of unilateral papilledema we thus suggest that intraocular pressure should be taken into account when evaluating patients with papilledema.

Comparison between confocal scanning laser tomography, scanning laser polarimetry and optical coherence tomography on the ability to detect localised retinal nerve fibre layer defects in glaucoma patients

BACKGROUND/AIM: To compare the ability of confocal scanning laser tomography (CSLT), scanning laser polarimetry (SLP) and optical coherence tomography (OCT) in recognising localised retinal nerve fibre layer (RNFL) defects. METHODS: 51 eyes from 43 patients with glaucoma were identified by two observers as having RNFL defects visible on optic disc photographs. 51 eyes of 32 normal subjects were used as controls. Three masked observers evaluated CSLT, SLP and OCT images to determine subjectively the presence of localised RNFL defects. RESULTS: Interobserver agreement was highest with OCT, followed by SLP and CSLT (mean kappa: 0.83, 0.69 and 0.64, respectively). RNFL defects were identified in 58.8% of CSLT, 66.7% of SLP and 54.9% of OCT (p = 0.02 between SLP and OCT) by at least two observers. In the controls, 94.1% of CSLT, 84.3% of SLP and 94.1% of OCT scans, respectively, were rated as normal (p = 0.02 between CSLT and SLP, and SLP and OCT). CONCLUSION: Approximately 20-40% of localised RNFL defects identified by colour optic disc photographs are not detected by CSLT, SPL or OCT. SLP showed a higher number of false-positive results than the other techniques, but also had a higher proportion of correctly identified RNFL defects in the glaucoma population.

Landmark Detection for Fusion of Fundus and MRI Towards a Patient-Specific Multi-Modal Eye Model

Ophthalmologists typically acquire different image modalities to diagnose eye pathologies. They comprise e.g., Fundus photography, Optical Coherence Tomography (OCT), Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). Yet, these images are often complementary and do express the same pathologies in a different way. Some pathologies are only visible in a particular modality. Thus, it is beneficial for the ophthalmologist to have these modalities fused into a single patient-specific model. The presented article’s goal is a fusion of Fundus photography with segmented MRI volumes. This adds information to MRI which was not visible before like vessels and the macula. This article’s contributions include automatic detection of the optic disc, the fovea, the optic axis and an automatic segmentation of the vitreous humor of the eye.

Morphometric assessment of normal, suspect and glaucomatous optic discs with Stratus OCT and HRT II

AIMS: To compare morphometric parameters and diagnostic performance of the new Stratus Optical Coherence Tomograph (OCT) Disc mode and the Heidelberg Retina Tomograph (HRT); to evaluate OCT's accuracy in determining optic nerve head (ONH) borders. METHODS: Controls and patients with ocular hypertension, glaucoma-like discs, and glaucoma were imaged with OCT Disc mode, HRT II, and colour disc photography (DISC-PHOT). In a separate session, automatically depicted ONH shape and size in OCT were compared with DISC-PHOT, and disc borders adjusted manually where required. In a masked fashion, all print-outs and photographs were studied and discs classified as normal, borderline, and abnormal. The Cohen kappa method was then applied to test for agreement of classification. Bland-Altman analysis was used for comparison of disc measures. RESULTS: In all, 49 eyes were evaluated. Automated disc margin recognition failed in 53%. Misplaced margin points were more frequently found in myopic eyes, but only 31/187 were located in an area of peripapillary atrophy. Agreement of OCT with photography-based diagnosis was excellent in normally looking ONHs, but moderate in discs with large cups, where HRT performed better. OCT values were consistently larger than HRT values for disc and cup area. Compared with HRT, small rim areas and volumes tended to be minimized by OCT, and larger ones to be magnified. CONCLUSIONS: Stratus OCT Disc protocol performed overall well in differentiating between normal and glaucomatous ONHs. However, failure of disc border recognition was frequently observed, making manual correction necessary. ONH measures cannot be directly compared between HRT and OCT.

Do optic nerve head and visual field parameters in patients with obstructive sleep apnea syndrome differ from those in control individuals?

BACKGROUND It has been suggested that sleep apnea syndrome may play a role in normal-tension glaucoma contributing to optic nerve damage. The purpose of this study was to evaluate if optic nerve and visual field parameters in individuals with sleep apnea syndrome differ from those in controls. PATIENTS AND METHODS From the records of the sleep laboratory at the University Hospital in Bern, Switzerland, we recruited consecutive patients with severe sleep apnea syndrome proven by polysomnography, apnea-hypopnea index >20, as well as no sleep apnea controls with apnea-hypopnea index <10. Participants had to be unknown to the ophtalmology department and had to have no recent eye examination in the medical history. All participants underwent a comprehensive eye examination, scanning laser polarimetry (GDx VCC, Carl Zeiss Meditec, Dublin, California), scanning laser ophthalmoscopy (Heidelberg Retina Tomograph II, HRT II), and automated perimetry (Octopus 101 Programm G2, Haag-Streit Diagnostics, Koeniz, Switzerland). Mean values of the parameters of the two groups were compared by t-test. RESULTS The sleep apnea group consisted of 69 eyes of 35 patients; age 52.7 ± 9.7 years, apnea-hypopnea index 46.1 ± 24.8. As controls served 38 eyes of 19 patients; age 45.8 ± 11.2 years, apnea-hypopnea index 4.8 ± 1.9. A difference was found in mean intraocular pressure, although in a fully overlapping range, sleep apnea group: 15.2 ± 3.1, range 8-22 mmHg, controls: 13.6 ± 2.3, range 9-18 mmHg; p<0.01. None of the extended visual field, optic nerve head (HRT) and retinal nerve fiber layer (GDx VCC) parameters showed a significant difference between the groups. CONCLUSION Visual field, optic nerve head, and retinal nerve fiber layer parameters in patients with sleep apnea did not differ from those in the control group. Our results do not support a pathogenic relationship between sleep apnea syndrome and glaucoma.

Optic radiation fiber tracking using anteriorly angulated diffusion tensor imaging: a tested algorithm for quick application

Fiber tracking (FT) of the optic pathways (OPs) is difficult because there is no standard for the parameters of diffusion tensor imaging (DTI), placement of seed volumes, or interpreting the results.

Assessment of the Matrix Degenerative Effects of MMP-3, ADAMTS-4 and HTRA1 injected into a bovine Intervertebral Disc Organ Culture Model

Study Design. In vitro study to develop an intervertebral disc degeneration (IDD) organ culture model, using coccygeal bovine intervertebral discs (IVDs) and injection of proteolytic enzymes MMP-3, ADAMTS-4 and HTRA1.Objective. This study aimed to develop an in-vitro model of enzyme-mediated IDD to mimic the clinical outcome in humans for investigation of therapeutic treatment options.Summary of Background Data. Bovine IVDs are comparable to human IVDs in terms of cell composition and biomechanical behavior. Researchers injected papain and trypsin into them to create an IDD model with a degenerated nucleus pulposus (NP) area. They achieved macroscopic cavities as well as a loss of glycosaminoglycans (GAGs). However, none of these enzymes are clinically relevant.Methods. Bovine IVDs were harvested maintaining the endplates. Active forms of MMP-3, ADAMTS-4 and HTRA1 were injected at a dose of 10μg/ml each. Phosphate buffered saline (PBS) was injected as a control. Discs were cultured for 8 days and loaded diurnally (day 1 to day 4 with 0.4 MPa for 16 h) and left under free swelling condition from day 4 to day 8 to avoid expected artifacts due to dehydration of the NP. Outcome parameters included disc height, metabolic cell activity, DNA content, glycosaminoglycan (GAG) content, total collagen content, relative gene expression and histological investigation.Results. The mean metabolic cell activity was significantly lower in the NP area of discs injected with ADAMTS-4 compared to the day 0 control discs. Disc height was decreased following injection with HTRA1, and was significantly correlated with changes in GAG/DNA of the NP tissue. Total collagen content tended to be lower in groups injected with ADAMTS4 and MMP-3.Conclusion. MMP-3, ADAMTS-4 and HTRA1 neither provoked visible matrix degradation nor major shifts in gene expression. However, cell activity was significantly reduced and HTRA1 induced loss of disc height which positively correlated with changes in GAG/DNA content. The use of higher doses of these enzymes or a combination thereof may therefore be necessary to induce disc degeneration

Bilateral posterior ischaemic optic neuropathy after severe diabetic ketoacidosis, cardiopulmonary resuscitation and respiratory failure

A 44-year-old male European with type I diabetes mellitus fell into diabetic ketoacidosis. In the emergency room, he developed an episode of asystole and respiratory failure requiring one cycle of cardiopulmonary resuscitation and extracorporeal membrane oxygenation (ECMO). Waking up 7 days later, he presented a bilateral complete loss of vision. Ophthalmological examination including funduscopy on days 1 and 10, after extubation, showed bilateral large round pupils non-reactive to light and a normal fundus. Neuroimaging studies, including MRI and MRA of the brain, were all within normal limits. A lumbar puncture and comprehensive serological testing excluded an infectious or rheumatic cause. An empirical high-dose intravenous steroid treatment administered for 5 days had no effect on his vision. His eye examination at 1.5 months follow-up showed a normal fundus except for progressive bilateral optic nerve disc pallor, which pointed towards the diagnosis of a posterior ischaemic optic neuropathy.