Orbital fat swelling: A biomechanical theory and supporting model for spaceflight-associated neuro-ocular syndrome (SANS).

Spaceflight-Associated Neuro-ocular Syndrome (SANS) is a descriptor of several ocular and visual signs and symptoms which commonly afflicts those exposed to microgravity. We propose a new theory for the driving force leading to the development of Spaceflight-Associated Neuro-ocular Syndrome which is described via a finite element model of the eye and orbit. Our simulations suggest that the anteriorly directed force produced by orbital fat swelling is a unifying explanatory mechanism for Spaceflight-Associated Neuro-ocular Syndrome, as well as producing a larger effect than that generated by elevation in intracranial pressure. Hallmarks of this new theory include broad flattening of the posterior globe, loss of tension in the peripapillary choroid, decreased axial length, consistent with findings in astronauts. A geometric sensitivity study suggests several anatomical dimensions may be protective against Spaceflight-Associated Neuro-ocular Syndrome.

Characteristics of the cerebrospinal fluid pressure waveform and craniospinal compliance in idiopathic intracranial hypertension subjects.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition of abnormally high intracranial pressure with an unknown etiology. The objective of this study is to characterize craniospinal compliance and measure the cerebrospinal fluid (CSF) pressure waveform as CSF is passively drained during a diagnostic and therapeutic lumbar puncture (LP) in IIH. METHODS: Eighteen subjects who met the Modified Dandy Criteria, including papilledema and visual field loss, received an ultrasound guided LP where CSF pressure (CSFP) was recorded at each increment of CSF removal. Joinpoint regression models were used to calculate compliance from CSF pressure and the corresponding volume removed at each increment for each subject. Twelve subjects had their CSFP waveform recorded with an electronic transducer. Body mass index, mean CSFP, and cerebral perfusion pressure (CPP) were also calculated. T-tests were used to compare measurements, and correlations were performed between parameters. RESULTS: Cerebrospinal fluid pressure, CSFP pulse amplitude (CPA), and CPP were found to be significantly different (p < 0.05) before and after the LP. CSFP and CPA decreased after the LP, while CPP increased. The craniospinal compliance significantly increased (p < 0.05) post-LP. CPA and CSFP were significantly positively correlated. CONCLUSIONS: Both low craniospinal compliance (at high CSFP) and high craniospinal compliance (at low CSFP) regions were determined. The CSFP waveform morphology in IIH was characterized and CPA was found to be positively correlated to the magnitude of CSFP. Future studies will investigate how craniospinal compliance may correlate to symptoms and/or response to therapy in IIH subjects.

Visual outcomes following optic nerve sheath fenestration via the medial transconjunctival approach.

This article determines the safety of optic nerve sheath fenestration (ONSF) for the treatment of patients with intracranial hypertension in the immediate 6-month post-operative period and its efficacy in reducing optic disk edema. Retrospective, non-comparative interventional case series. 207 eyes in 104 patients undergoing ONSF between the years 2005 and 2014. Papilledema grade based on modified Frisen scale and mean deviation of Humphrey visual field. 207 eyes of 104 patients (102 IIH, 2 IH due to dural sinus thrombosis) were included in the study. The patients were 96.1% female (N = 100) and 3.9% male (N = 4). The average patient age was 28.8 years (SD ± 9.5 years) and had a mean opening pressure of 39.85 cmH2O (SD ± 8.4 cmH2O). Mean follow-up period was 6.0 months (SD ± 5.9 months). Papilledema resolved in 76.1% of eyes at 1 week (N = 102 eyes), 75% of eyes at 1 month (N = 90 eyes), and 71% of eyes at 6 months (N = 94 eyes). Visual field comparison had a mean of the paired differences in MD at 1 week, 1 month, and 6 months of 1.59dB (P = 0.006), 2.53dB (P < 0.001), and 1.30dB (P = 0.016), respectively. ONSF is effective in reducing optic disk edema and does not cause vision loss in the 6-month post-operative period regardless of severity of IIH (as judged by elevation of opening pressure measured at pre-operative assessment).

Increased Ocular Pulse Amplitude Associated with Unilateral Dysgenesis of the Orbital Roof.

INTRODUCTION: Two patients (one with neurofibromatosis type 1) presented with unilateral ocular pulsation. METHODS: A CT scan of the orbits revealed extensive dysgenesis of the orbital roof with herniation of the frontal lobe into the orbit in both cases. PASCAL dynamic contour tonometry was performed. RESULTS: The ipsilateral ocular pulse amplitude (OPA) was greater than the contralateral side, and the ocular pulse waveform morphology more closely approximated the known intracranial waveform in these patients. CONCLUSIONS: We hypothesize that the greater OPA was due to stronger transmission of the intracranial pressure waveform amplitude and morphology in the absence of the orbital roof.

Ocular pressure waveform reflects ventricular bigeminy and aortic insufficiency.

Ocular pulse amplitude (OPA) is defined as the difference between maximum and minimum intraocular pressure (IOP) during a cardiac cycle. Average values of OPA range from 1 to 4 mmHg. The purpose of this investigation is to determine the source of an irregular IOP waveform with elevated OPA in a 48-year-old male. Ocular pressure waveforms had an unusual shape consistent with early ventricular contraction. With a normal IOP, OPA was 9 mmHg, which is extraordinarily high. The subject was examined by a cardiologist and was determined to be in ventricular bigeminy. In addition, he had bounding carotid pulses and echocardiogram confirmed aortic insufficiency. After replacement of the aortic valve, the bigeminy resolved and the ocular pulse waveform became regular in appearance with an OPA of 1.6-2.0 mmHg. The ocular pressure waveform is a direct reflection of hemodynamics. Evaluating this waveform may provide an additional opportunity for screening subjects for cardiovascular anomalies and arrhythmias.

Sino-orbital spelunking: stalagmite formation in fibrous dysplasia with dystrophic calcification.

Fibrous dysplasia (FD) involving the mid-face may be associated with cystic and other secondary changes that make diagnosis more difficult. We present a case of FD associated with a remote history of blunt facial trauma and extensive cystic changes involving the medial orbit and sinuses. An endoscopic exploration revealed "stalagmites" along the floor of the cystic cavity that were consistent with dystrophic calcification. This case was unusual given the degree of dystrophic calcification and the presence of sino-orbital stalagmites within the cystic cavity. Radiologic and pathologic features of the stalagmites are characterized.

Annuloaortic ectasia in a patient with congenital absence of the left pericardium.

We report a patient with congenital absence of the left pericardium with development of progressive annuloaortic ectasia and aortic insufficiency during a 12-year period. The patient was treated with a Bentall procedure. Pathologic examination of the aorta revealed cystic medial necrosis. The surgical management and a possible association between congenital absence of pericardium and Marfan syndrome are discussed.

Hidradenoma papilliferum of the orbit.

PURPOSE: Hidradenoma papilliferum (HP) is a cystic lesion of apocrine gland origin that occurs most commonly in the perineal region. Although there are scattered reports of HP involving the eyelid, to our knowledge, we present the first case of HP of the orbit. METHODS: A 63 year-old female presented with progressive left upper eyelid fullness over an 18 month period. RESULTS: The lesion was excised via transconjunctival anterior orbitotomy without incident. CONCLUSIONS: The pathologic features of HP are presented.

Scleral erosion, phthisis bulbi, and orbital pseudocyst formation as a late complication of miragel scleral buckle surgery.

PURPOSE: The purpose of this study was to report a case of scleral erosion as a late complication of Miragel scleral buckle surgery. The resulting defect in the eye wall was associated with a phthisical eye and an inferior orbital pseudocystic lesion. METHODS: Case report. RESULTS: An 81-year-old white woman presented with a Miragel scleral buckle 23 years after retinal detachment repair in the right eye. She complained of redness, swelling, and pain in the right eye, which was completely blind from glaucoma. There was evidence of implant extrusion in the inferior cul-de-sac. Orbital computed tomography scan revealed an inferior orbital cystic-appearing lesion. At the time of surgery, a fragmented Miragel implant was removed and 5 mL of clear fluid were drained from the pseudocyst. A 2.5-cm defect in the eye wall was partially repaired. CONCLUSION: Scleral erosion as a late complication of scleral buckle surgery is relatively well described with the buckle becoming visible in the subretinal space on funduscopic evaluation. Progression to a full-thickness scleral defect is uncommon. We present a unique case of postbuckle scleral necrosis associated with involution of the globe and development of a contiguous orbital pseudocyst.

Pyogenic granuloma presenting as an orbital mass.

Pyogenic granuloma (PG) of the eyelid and orbit is typically associated with trauma or surgery. We report a rare case of an orbital intraconal PG arising de novo in association with an orbital artery.

Intercollegiate usage schedule and the impact resistance of used football helmet faceshields.

PURPOSE: Although new polycarbonate helmet faceshields can withstand impacts exceeding forces of 2,400 N, repeated impacts and ultraviolet radiation degrade the structural integrity. In this study, the impact resistances of unused, solar-radiated, and of game-used faceshields were analyzed. Also, Division 1 National Collegiate Athletic Association football programs were surveyed concerning their faceshield practices. METHODS: Impact resistance was tested by impacting faceshields with baseballs at velocities exceeding 67.1 m/s. Twenty-four new faceshields were exposed to southern daylight, 3 hours per day for 3 months before testing. Subsequent testing was performed on 60 game-used faceshields. Additionally, a faceshield utilization survey was distributed to 117 college programs. RESULTS: Solar-irradiated shields did not fail at maximum test velocity. The survivability of nonimpacted shields was greater than game-worn shields (P = 0.0003). Fifty-nine surveys were returned with 58 programs reporting faceshield use. Approximately 21 players per program use a faceshield. The main reason reported for use was aesthetic. Only 21% of reporting programs require a faceshield for players with reduced visual acuity in 1 eye. CONCLUSION: Faceshields lose impact resistance with typical use. Programs should incorporate a policy for replacement and require that players with reduced vision in at least 1 eye wear a faceshield.

Cerebrospinal fluid outflow: an evolving perspective.

Cerebrospinal fluid (CSF) serves numerous important functions in the central nervous system. Despite numerous reports characterizing CSF and its circulation in the subarachnoid space, our understanding of CSF outflow remains limited. Although initial work suggested that both arachnoid granulations and lymphatic capillaries shared in the role of CSF outflow, predominant work since then has focused on the arachnoid granulations. A growing body of recent evidence not only suggests the importance of both arachnoid granulations and lymphatic capillaries, but also additional contributions through transependymal passage likely share in the role of CSF outflow. Consideration of all mechanisms and pathways will help us to better understand the significance of CSF outflow, in health and disease. Here we review how the present concept of CSF outflow has evolved, including a historical review of significant findings and a discussion of the latest innovative developments.

Optical quality and impact resistance comparisons of 2 football helmet faceshields.

BACKGROUND: Currently there is no standard that specifically addresses the optical and impact performance of football protective faceshields. This study compared the impact resistance and optical quality between 2 popular football faceshields. Testing was performed only on new faceshields. METHODS: To test impact resistance, baseballs were propelled at the faceshields with velocities up to 66.4 m/sec. Structural integrity was evaluated after each impact. Ten visors from each of 2 companies underwent a single impact at various velocities. Two visors from each company were impacted 3 times to evaluate the effects of repeated blows. Additional visors were conditioned to -10 degrees C and impacted once. Additionally, prismatic power, refractive power, haze, visible light, and ultraviolet (UV) transmittance, and optical distortion were measured to evaluate optical quality. All testing was done with faceshields mounted to facemask and, when appropriate, to a helmet. RESULTS: None of these new faceshields fractured even with impact velocities up to 66.4 m/sec. With regard to optical quality, both protectors met the optical requirements for the standards of faceshields for selected sports (ASTM F803-2003). CONCLUSIONS: Both faceshields tested should protect football players from anticipated impacts while providing adequate optical quality for satisfactory visual performance.

Human arachnoid granulations Part I: a technique for quantifying area and distribution on the superior surface of the cerebral cortex.

BACKGROUND: The arachnoid granulations (AGs) are herniations of the arachnoid membrane into the dural venous sinuses on the surface of the brain. Previous morphological studies of AGs have been limited in scope and only one has mentioned surface area measurements. The purpose of this study was to investigate the topographic distribution of AGs on the superior surface of the cerebral cortex. METHODS: En face images were taken of the superior surface of 35 formalin-fixed human brains. AGs were manually identified using Adobe Photoshop, with a pixel location containing an AG defined as 'positive'. A set of 25 standard fiducial points was marked on each hemisphere for a total of 50 points on each image. The points were connected on each hemisphere to create a segmented image. A standard template was created for each hemisphere by calculating the average position of the 25 fiducial points from all brains. Each segmented image was mapped to the standard template using a linear transformation. A topographic distribution map was produced by calculating the proportion of AG positive images at each pixel in the standard template. The AG surface area was calculated for each hemisphere and for the total brain superior surface. To adjust for different brain sizes, the proportional involvement of AGs was calculated by dividing the AG area by the total area. RESULTS: The total brain average surface area of AGs was 78.53 +/- 13.13 mm2 (n = 35) and average AG proportional involvement was 57.71 x 10(-4) +/- 7.65 x 10(-4). Regression analysis confirmed the reproducibility of AG identification between independent researchers with r2 = 0.97. The surface AGs were localized in the parasagittal planes that coincide with the region of the lateral lacunae. CONCLUSION: The data obtained on the spatial distribution and en face surface area of AGs will be used in an in vitro model of CSF outflow. With an increase in the number of samples, this analysis technique can be used to study the relationship between AG surface area and variables such as age, race and gender.

In vitro model of cerebrospinal fluid outflow through human arachnoid granulations.

PURPOSE: To describe and validate an in vitro model of the arachnoid granulation (AG) outflow pathway for cerebrospinal fluid (CSF), by using human AG cells grown on a filter membrane support and perfused in a modified Ussing chamber at pressures analogous to normal human intracranial pressures. METHODS: Human AG cells were grown, characterized, seeded onto filter membranes, and perfused in the physiologic (basal to apical, B-->A) or nonphysiologic (apical to basal, A-->B) directions. Cells were fixed under pressure after perfusion and prepared for electron microscopy (EM). RESULTS: The average cellular hydraulic conductivity in the B-->A direction (10 total) was 4.52 +/- 0.43 microL/min per mm Hg/cm(2) with an average transcellular pressure decrease of 3.13 +/- 0.09 mm Hg. The average cellular hydraulic conductivity in the A-->B direction (six total) was 0.29 +/- 0.16 microL/min per mm Hg/cm(2) with an average transcellular decrease in pressure of 3.33 +/- 0.16 mm Hg. Cells perfused nonphysiologically showed a large number of dead and dying cells. EM postperfusion analysis showed that AG cells were integrally attached to the underlying filter membrane. Large extracellular cisternal spaces were visible between overlapping AG cells and vacuoles within the cytoplasm. It is possible that these spaces within and between cells represent pathways for transcellular and paracellular transport of fluid. CONCLUSIONS: The results demonstrate that AG cells in vitro show a statistically significant greater flow rate and cellular hydraulic conductivity when perfused in the physiologic versus the nonphysiologic direction under normal intracranial pressures. These results suggest that this in vitro model of the AGs can accurately replicate the unidirectional flow of CSF in vivo.

Characterization of cytoskeletal and junctional proteins expressed by cells cultured from human arachnoid granulation tissue.

BACKGROUND: The arachnoid granulations (AGs) are projections of the arachnoid membrane into the dural venous sinuses. They function, along with the extracranial lymphatics, to circulate the cerebrospinal fluid (CSF) to the systemic venous circulation. Disruption of normal CSF dynamics may result in increased intracranial pressures causing many problems including headaches and visual loss, as in idiopathic intracranial hypertension and hydrocephalus. To study the role of AGs in CSF egress, we have grown cells from human AG tissue in vitro and have characterized their expression of those cytoskeletal and junctional proteins that may function in the regulation of CSF outflow. METHODS: Human AG tissue was obtained at autopsy, and explanted to cell culture dishes coated with fibronectin. Typically, cells migrated from the explanted tissue after 7-10 days in vitro. Second or third passage cells were seeded onto fibronectin-coated coverslips at confluent densities and grown to confluency for 7-10 days. Arachnoidal cells were tested using immunocytochemical methods for the expression of several common cytoskeletal and junctional proteins. Second and third passage cultures were also labeled with the common endothelial markers CD-31 or VE-cadherin (CD144) and their expression was quantified using flow cytometry analysis. RESULTS: Confluent cultures of arachnoidal cells expressed the intermediate filament protein vimentin. Cytokeratin intermediate filaments were expressed variably in a subpopulation of cells. The cultures also expressed the junctional proteins connexin43, desmoplakin 1 and 2, E-cadherin, and zonula occludens-1. Flow cytometry analysis indicated that second and third passage cultures failed to express the endothelial cell markers CD31 or VE-cadherin in significant quantities, thereby showing that these cultures did not consist of endothelial cells from the venous sinus wall. CONCLUSION: To our knowledge, this is the first report of the in vitro culture of arachnoidal cells grown from human AG tissue. We demonstrated that these cells in vitro continue to express some of the cytoskeletal and junctional proteins characterized previously in human AG tissue, such as proteins involved in the formation of gap junctions, desmosomes, epithelial specific adherens junctions, as well as tight junctions. These junctional proteins in particular may be important in allowing these arachnoidal cells to regulate CSF outflow.

Depsipeptide inhibits migration of primary and metastatic uveal melanoma cell lines in vitro: a potential strategy for uveal melanoma.

Uveal melanoma (UM) is a highly malignant primary intraocular tumour in adults that has a high mortality rate due to haematogenous dissemination. The migration of UM cells through the basement membrane requires the presence of proteolytic enzymes, such as matrix metalloproteinases (MMPs). The expression of MMP-2, MMP-9 and membrane type-1/MMP (MT-1/MMP) in UM cells is a known risk factor for metastatic disease. We tested the effect of depsipeptide (DP) on UM cell migration and the level and activity of MMP-2, MMP-9, MT-1/MMP and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1 and TIMP-2). Three primary and two metastatic (liver metastasis) UM cell lines were treated with DP (0, 1, 5 and 10 nmol/l) for 24 h. Migration of UM cells was studied in modified Boyden migration chambers for 24 h and only viable cells on both sides of the membrane were counted. Enzyme-linked immunosorbent assays (ELISAs) were used to quantify the level of MMP-2, MMP-9, MT-1/MMP, TIMP-1 and TIMP-2 after the cells had been exposed to DP (0, 1, 5 and 10 nmol/l) for 24 h. In addition, the activities of MMP-2, MMP-9 and MT-1/MMP were determined after DP treatment. A dose-dependent decrease in the migration of viable UM cells was observed for primary and metastatic cell lines (30-50% inhibition). We detected a dose-dependent: (1) decrease in the protein level of MMP-2, MMP-9 and MT-1/MMP; (2) decrease in the activity of MMP-2, MMP-9 and MT-1/MMP; and (3) increase in the protein level of TIMP-1 and TIMP-2. It can be concluded that DP is a potent inhibitor of primary and metastatic UM cell migration in vitro. Our data suggest that this inhibition is mediated by the downregulation of MMPs and the upregulation of TIMPs. DP may be a valuable adjunctive treatment modality for primary and metastatic UM in humans.

Somatostatin inhibits IGF-1 mediated induction of VEGF in human retinal pigment epithelial cells.

Neovascularization stimulated by IGF-1 mediated induction of vascular endothelial growth factor (VEGF) is one of the leading causes of blindness in humans. It plays a central role in the pathogenesis of proliferative diabetic retinopathy (DR), neovascular glaucoma, exudative age-related macular degeneration (AMD) and retinopathy of prematurity. Neovascularization is a multi-step process that involves complex interactions of a variety of mitogenic factors such as VEGF and IGF-I which are produced locally in the human eye by a variety of cells including retinal pigment epithelial (RPE) cells, retinal capillary pericytes, endothelial cells, Mueller cells and ganglion cells. We hypothesized that somatostatin would inhibit the IGF-1 signal transduction pathway in RPE cells, resulting in decreased VEGF production. We have observed expression of somatostatin receptor protein in retinal pigment epithelial (RPE) cells of the human eye using immunohistochemistry and have confirmed expression of somatostatin receptors in cultured human RPE cells using reverse transcriptase-PCR. IGF-1 induced a dose dependent increase in IGF-1R phosphorylation and in VEGF mRNA levels in cultured human RPE cells. Somatostatin and octreotide, a somatostatin analogue, inhibited IGF-1 receptor (IGF-1R) phosphorylation and decreased VEGF production. Both IGF-1R phosphorylation and accumulation of VEGF mRNA were inhibited by physiological levels of somatostatin and octreotide (1 nM). These results demonstrate somatostatin and octreotide mediated attenuation of both IGF-1R signal transduction and VEGF mRNA accumulation via somatostatin receptor type 2 (sst2). Furthermore, these data suggest a rationale for the use of octreotide as a prophylactic and therapeutic option in disease states that cause ocular neovascularization.