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Purpose of Review: During prolonged spaceflight, astronauts often experience ocular changes, due to constant head-ward fluid shifts in space as compared with Earth. This article reviews symptoms, likely causes, and potential solutions, such as lower body negative pressure, to counteract space-associated neuroocular syndrome (SANS)., Recent Findings: Low gravity conditions and other aspects of spaceflight affect the eye detrimentally, causing SANS which is characterized by optic disc edema, choroidal thickening, cotton wool spots, and a hyperopic shift. SANS is probably caused by altered hemodynamic flows in the head and neck as well as mildly elevated intracranial and intraocular pressures. Carbon dioxide and other chemicals in space-craft may influence SANS as well. SANS may be counteracted by using lower body negative pressure, thigh cuffs, spacecraft engineering, and/or artificial gravity by a centrifuge., Summary: Prolonged space missions are associated with optic disc edema, choroidal thickening, cotton wool spots, and a hyperopic shift. Possible causes and countermeasures are currently being researched to reduce the risk of SANS. Although many countermeasures to SANS are under investigation lower body negative pressure exhibits great promise in counteracting the headward fluid shifts in space. Understanding and prevention of SANS is critical to future space exploration, especially to long-duration missions to the moon and Mars.

Hypoxia-induced retinal edema primarily induced by vascular lesion is seen in various conditions such as diabetic retinopathy (DR) and retinal vein occlusion (RVO). The edematous changes in these conditions occur mainly in intermediate and deep layers of retina as a result of disruption of the inner blood-retinal barrier (iBRB). However, the effect of direct and acute hypoxia on iBRB remains to be elucidated. To investigate direct and acute hypoxia-induced changes in retina, especially in astrocytes/Müller cells that are involved in the maintenance of retinal structure and function, we developed an adult mouse model of hypoxia-induced retinal edema by 24-h exposure in a 6% oxygen environment. Immunohistochemical staining of glial fibrillary acidic protein (GFAP) was enhanced mainly in the superficial layer of the hypoxic retina, corresponding to edematous change. Electron microscopic observation of the hypoxic retina showed vacuole formation in astrocyte/Müller cell foot processes around capillaries in the superficial layer, while no abnormal findings in the perivascular areas were found in intermediate and deep layers. Increase in vascular leakage quantified by Evans blue dye and tight junction breakdown detected by electron-dense tracer were observed in the hypoxia group. In the hypoxic retina, microglia was activated and relative gene expressions of pro-inflammatory cytokines were significantly upregulated. Dexamethasone suppressed these hypoxia-induced pathological reactions. Thus, unlike DR and RVO that induce iBRB breakdown in deeper retinal layers, atmospheric hypoxia induced iBRB disruption with subsequent edematous change mainly in the superficial layer of the retina, and that dexamethasone prevented these pathological changes. In this mouse model, direct and acute hypoxia induces retinal edema in the superficial layer of the retina with morphological changes of astrocytes/Müller cells, and is potentially useful for ophthalmic research in the field related to retinal hypoxia and its treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Primary empty sella (PES) is characterized by the herniation of the subarachnoid space within the sella, which is often associated with variable degrees of flattening of the pituitary gland in patients without previous pituitary pathologies. PES pathogenetic mechanisms are not well known but seem to be due to a sellar diaphragm incompetence, associated to the occurrence of upper sellar or pituitary factors, as intracranial hypertension and change of pituitary volume. As PES represents in a majority of cases, a neuroradiological findings without any clinical implication, the occurrence of endocrine, neurological and opthalmological symptoms, due to the above describes anatomical alteration, which delineates from the so called PES syndrome. Headache, irregular menses, overweight/obesity and visual disturbances compose the typical picture of PES syndrome and can be the manifestation of an intracranial hypertension, often associated with PES. Although hyperprolactinemia and growth hormone deficit represent the most common endocrine abnormalities, PES syndrome is characterized by heterogeneity both in clinical manifestation and hormonal alterations and can sometime reach severe extremes, as occurrence of papilledema, cerebrospinal fluid rhinorrhea and worsening of visual acuity. Consequently, a multidisciplinary approach, with the integration of endocrine, neurologic and ophthalmologic expertise, is strongly advocated and recommended for a properly diagnosis, management, treatment and follow-up of PES syndrome and all of the related abnormalities., (© 2017 European Society of Endocrinology.)

Background and Purpose: Idiopathic intracranial hypertension is cha-racterized by raised intracranial pressure of unknown origin, leading to persisting visual loss if left untreated. Purpose - We assessed timing of surgery, and the efficacy and safety of ventriculo-peritoneal shunt., Methods: Retrospective analysis of 65 patients treated at our Neuro-ophthalmology Clinic between 2009 and 2017. Patients - We treated 15 children and 50 adults, 42 patients conservatively, and 23 surgically. The median age at presentation was 27 years for adults, 88% were obese, and 86% female. The age of children was 5-17 years, 40% were obese, and 53% girl. The commonest presentation symptom was headache in both groups (64%), followed by obscuration (33%), and double vision (22-31%). Subjective visual loss was only experienced in the surgical group (50%). The time until diagnosis was 2 weeks in both groups. However, the conservative group presented to our institute significantly earlier (3 weeks), than the surgical group (8 weeks). The follow-up time was 25 months., Results: In the conservative group papilla edema was 2D, visual acuity ≥0.7, and visual field loss was only mild. Time to cure was 3 months. In the surgical group both preoperative papilla edema (3D), and visual function were significantly worse. Indications for surgery were papilla edema, deteriorating visual function or relapse resistant to conservative treatment. Papilla edema disappeared 3 months after surgery, and visual field deficit improved significantly. We detected significant improvement in all aspects of visual function even at first neuro-ophthalmic control 4 days after surgery. However, visual acuity only improved in cases of preoperative acuity ≥0.3. Shunt revision occurred in 17%, and shunt infection in 8.5%. One patient suffered from persistent visual deterioration after surgery, and asymptomatic complication (epidural hematoma) was found in another patient. There was no surgical mortality., Conclusion: This is a curable condition with early diagnosis and adequate treatment, and persistent visual loss can be prevented. Surgery is effective and safe, close neuro-ophthalmic monitoring is mandatory for its optimal timing. Visual function of all patients can be preserved when operated on in time, whereas severe visual loss appears to be irreversible despite surgery.

SERIAL CASE REPORTS OF THREE MEN WITH PAPILLEDEMA AND VISUAL LOSS: The patients developed primarily visual loss on one or both sides with angiographically and clinically diagnosed papilledema. The neurological and internistic examinations were unsuspicious; however, serology ultimately confirmed the suspected papillitis in acute syphilis., Conclusion: Papillitis with visual loss can be a symptom of syphilis. Not only the known placoid chorioretinitis syphilis has to be considered but also a detailed medical history and diagnostic measures are essential to determine the cause. The guiding principle is usually also the relatively young age of the patients, male gender, sexual orientation and the lack of classic risk factors for anterior ischemic optic neuropathy (AION) or neurological causes of blurred edge swollen papilla as an intracranial mass lesion (papilledema).

Purpose: To determine whether the beneficial effects of acetazolamide (ACZ) in improving vision at 6 months continues to month 12 in participants of the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT)., Design: Nonrandomized clinical study., Methods: In the IIHTT, subjects were randomly assigned to placebo-plus-diet or maximally tolerated dosage of acetazolamide-plus-diet. At 6 months subjects transitioned from study drug to ACZ. This resulted in the following groups: (1) ACZ to ACZ; n = 34; (2) placebo to ACZ; n = 35; (3) ACZ to no treatment; n = 16; and (4) placebo to no treatment; n = 11. Ninety-six IIHTT subjects had evaluations at 6 and 12 months. Our main outcome measure was change from month 6 to month 12 in visual field mean deviation (MD) with secondary measures being change in papilledema grade, ETDRS scores, and quality-of-life (QoL) measures., Results: The ACZ to ACZ group improved 0.35 dB, P = .05; placebo subjects with no ACZ improved 0.81 dB MD, P = .07 at 12 months. The other groups improved 0.35-0.46 dB MD. Mean improvements in papilledema grade occurred most markedly in the group that exchanged placebo for ACZ (0.91 units, P < .001). QoL and headache disability scores showed significant improvements in the placebo group with added ACZ., Conclusion: Improvements in MD continued from month 6 to month 12 of the IIHTT in all treatment groups, most marked in the placebo group tapered off study drug. Adding ACZ to the placebo group significantly improved papilledema grade, headache, and QoL measures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Typical optic neuritis is often the presenting manifestation of multiple sclerosis (MS). Its incidence in central Europe is 5 cases per 100 000 persons per year., Methods: This review is based on articles retrieved by a selective search of the PubMed database, on the pertinent guidelines, and on the authors' clinical experience., Results: The diagnosis of optic neuritis is based on a constellation of symptoms and signs. The onset is usually with pain on eye movement in one eye and subacute visual loss. In unilateral optic neuritis, the direct pupillary light reflex is weaker in the affected eye. One-third of patients with optic neuritis have a mildly edematous optic disc. The visual disturbance resolves in 95% of cases. A less favorable course may be evidence of neuromyelitis optica, and macular involvement may be evidence of neuroretinitis. High-dosed intravenous methylprednisolone therapy speeds recovery but does not improve the final outcome. The risk that a patient with optic neuritis will later develop multiple sclerosis can be assessed with an MRI scan of the brain., Conclusion: Optic neuritis is easy to distinguish from otherv diseases affecting the optic nerve. Atypical forms of this disease and other optic nerve diseases require special treatment. For patients judged to be at high risk of developing multiple sclerosis, immune prophylaxis with beta- interferon or glatiramer acetate is recommended.

A 35-year-old woman complained of headache, reduced visual acuity, restricted visual field in the right eye and blindness in the left eye. The examination of the retina showed papilledema and peripapillary hemorrhages in both eyes. Magnetic resonance imaging (MRI) revealed a sinus thrombosis. Despite modern imaging technologies sinus thrombosis is an often overlooked, life-threatening disease and needs immediate treatment in order to avoid long-term consequences. An ophthalmological examination can be pioneering as it leads to further imaging.

Background: While pulsed intravenous methylprednisolone (iv-MP) has been shown to be effective and well tolerated in moderate to severe Graves' orbitopathy (GO), limited data are available on dysthyroid optic neuropathy (DON). The objective of this retrospective study was to investigate the efficacy of iv-MP in the treatment of DON and to seek parameters predictive of response., Methods: Twenty-four DON patients (40 eyes) treated with iv-MP from 2007 to 2012 were included in the study. Concurrent neurological or ophthalmologic diseases or signs of corneal exposure were considered as exclusion criteria. Iv-MP was administered daily for three consecutive days and repeated the following week. At six months, eyes not requiring surgery to preserve visual function were considered as responsive to treatment. Visual acuity, color sensitivity, visual field, and optic discs were analyzed at two and four weeks, and at 3, 6, and 12 months after treatment. Activity of GO was graded using a clinical activity score (CAS). Visual and clinical characteristics of the eyes responsive to iv-MP were studied by comparison to those of nonresponsive eyes., Results: At six months, 17 of 40 (42.5%) eyes had complete visual recovery and were spared from surgical decompression. At two weeks, visual acuity, color sensitivity, and visual field improved significantly in almost all eyes, but GO inactivated (CAS<4) only in the eyes that permanently responded to iv-MP (p<0.01). The CAS at two weeks was a good predictor of response (cutoff ≥4; 66.7% sensitivity, 76.9% specificity). Optic disc swelling at diagnosis was highly predictive for unresponsiveness to iv-MP (34% sensitivity, 100% specificity). At baseline, high CAS (cutoff >5; 40.2% sensitivity, 94.1% specificity) and severely altered visual field mean defect (cutoff ≤6.31 dB; 73.9% sensitivity, 58.8% specificity) were associated with unresponsiveness to steroids. No major side effects were observed., Conclusions: High-dose iv-MP was effective in permanently restoring visual function in about 40% of the eyes treated. When successful, it generally induced inactivation of the orbital disease within two weeks and normalization of visual function within one month. The presence of optic disc swelling at diagnosis and persistent active disease at two weeks were good predictors of unresponsiveness to steroids.

Following neurotrauma, cells beyond the initial trauma site undergo secondary degeneration, with excess Ca2+ a likely trigger for loss of neurons, compact myelin and function. Treatment using inhibitors of specific Ca2+ channels has shown promise in preclinical studies, but clinical trials have been disappointing and combinatorial approaches are needed. We assessed efficacy of multiple combinations of three Ca2+ channel inhibitors at reducing secondary degeneration following partial optic nerve transection in rat. We used lomerizine to inhibit voltage gated Ca2+ channels; oxidised adenosine-triphosphate (oxATP) to inhibit purinergic P2X7 receptors and/or 2-[7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo-1,2,3,4-tetrahydro quinoxalin-1-yl]acetic acid (INQ) to inhibit Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Only the three Ca2+ channel inhibitors delivered in combination significantly preserved visual function, as assessed using the optokinetic nystagmus visual reflex, at 3 months after injury. Preservation of retinal ganglion cells was partial and is unlikely to have accounted for differential effects on function. A range of the Ca2+ channel inhibitor combinations prevented swelling of optic nerve vulnerable to secondary degeneration. Each of the treatments involving lomerizine significantly increased the proportion of axons with normal compact myelin. Nevertheless, limiting decompaction of myelin was not sufficient for preservation of function in our model. Multiple combinations of Ca2+ channel inhibitors reduced formation of atypical node/paranode complexes; outcomes were not associated with preservation of visual function. However, prevention of lengthening of the paranodal gap that was only achieved by treatment with the three Ca2+ channel inhibitors in combination was an important additional effect that likely contributed to the associated preservation of the optokinetic reflex using this combinatorial treatment strategy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Branch retinal vein occlusion (BRVO) is the second most frequent retinal vascular disorder. Currently the first-line therapies for BRVO include anti-VEGF and dexamethasone implant treatment, however, with direct or indirect damage on retinal neurons, it has limited effect in improving patients visual acuity. Therefore, novel treatments with neuroprotective effect for BRVO retina were expected. Minocycline is a semisynthetic, broad spectrum tetracycline antibiotic with high penetration through the blood brain barrier. The neuroprotective effects of minocycline have been shown in various central nervous system (CNS) disease. Since both CNS and retina were composed of neurons and glials, it is reasonable to expect a neuroprotective effect by minocycline for BRVO retina. Therefore, the aim of the present study was to study whether minocycline has neuroprotective effect in branch retinal vein occlusion (BRVO) and the possible underlying molecular basis. We created BRVO in rats using laser photocoagulation. The animals were then randomly divided into 4 groups to evaluate the effect of minocycline: group A: minocycline 45 mg/kg intraperitoneal injection (i.p.), group B: minocycline 90 mg/kg i.p., group C: normal saline i.p., group D: sham injection. Fundus photography and fluorescein angiography (FA) were conducted. The changes in thickness of retinal layers were measured with optical coherence tomography (OCT) in vivo. We found that retinal edema occurred predominantly in the inner retinal layers. Intraperitoneal administration of minocycline significantly ameliorated retinal edema in the early stage of BRVO. We performed Full field Electroretinography (ffERG) to evaluate retinal function and found that the reduction of b wave amplitude decreased in the combined maximal response. The expressional levels of apoptosis related genes (Bax, Bcl-2) and inflammation related genes (IL-1 β, TNF α, MCP-1 and CCR2) were measured by real-time PCR, the results showed that minocycline treatment upregulated Bcl-2 expression and inhibits TNF α expression since early stage of BRVO. We also performed Hematoxylin-Eosin (HE) and immunostaining for Iba 1 (a microgilal marker), active caspase-3, Bax, Bcl-2, IL-1 β, TNF α and found that minocycline inhibits retinal microglial activation, prevents retinal ganglion cell loss, and inhibits retinal caspase-3 activation. Thus, our study indicates that systemic administration of minocycline ameliorates retinal edema and preserves retinal function in the early stage of BRVO possibly via inhibiting microglia activation and protecting RGC from apoptosis., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Diabetes, now at epidemic levels, can have devastating effects on the eye and vision. Treatments of the ocular complications are currently focused on relatively advanced stages and are limited to the slowing down of the progressive sight-threatening retinal vasculopathy (diabetic retinopathy). Tiny signals from the neural retina have been shown to reveal early diabetic neuropathy prior to vascular retinopathy. These signals, in a clinical test format, are predictive, by precise retinal location, of impending vasculopathy in the retina within a year, including sight-threatening oedema. The discovery opens possibilities for the future development of treatments to prevent the onset of retinopathy and the more sight-threatening retinal oedema and changes patient management strategies., (© 2012 The Authors. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.)

Background: The objective of this study was to evaluate the neuroprotective effect of brimonidine on retinal ganglion cells in rats with elevated intraocular pressure and to characterize the subpopulation of cells that can be rescued, as well as assess the effect of this drug on retinal ganglion cell soma size., Methods: Episcleral vein cauterization was used to increase intraocular pressure for 5 weeks on left eyes, considering right eyes as intrinsic controls in all cases. All the animals were then given weekly intraperitoneal injections, the experimental group receiving brimonidine, and the control group were administered only phosphate-buffered saline. Surviving retinal ganglion cells were quantified and their area and distribution measured by retrograde labelling with fluorogold., Results: Brimonidine administered systemically has a neuroprotective effect on retinal ganglion cells, which is unrelated to its capacity to lower intraocular pressure. It prevents the increase of cell size that is associated with stages prior to cell death. This phenomenon is particularly evident in the zones of the retina most susceptible to the damage caused by glaucoma (middle and periphery)., Conclusion: This effect of preventing retinal ganglion cell swelling can be considered as a new marker to study neuroprotection from antiglaucomatous drugs in the early stages of neurodegeneration in glaucoma., (© 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.)

Background: The fixation of polyimide stimulator foils as the basic substrate of epiretinal prostheses by using retinal tacks may cause retinal or choroidal alterations such as retinal proliferations or choroidal neovascularizations. During the prospective trial for the semichronical testing of a wireless intraocular retinal implant (EPIRET3) we investigated alterations in angiographic findings during implantation and after explantation of the device, to detect potential vascular pathologies at the fixation site or elsewhere., Methods: As the final step of the implantation surgery in six blind patients, the stimulator was placed on the retinal surface using retinal tacks. For the detection of possible morphological or vascular alterations committed by the implant fluorescein angiography (FA) was performed 1 day before and 4 weeks after implantation surgery, as well as at the final visit 5 months after explantation., Results: Following implantation surgery funduscopy and FA did not reveal any evidence of either vascular pathologies or choroidal neovascularisations (CNV), in addition, no cystoid macular edema (CME) occurred after 4 weeks. At the 6-month follow-up visit, we found a mild epiretinal gliosis formation in four patients. In one patient a retinal break occurred during explantation, requiring a temporary silicone-oil endotamponade. At the final visit, we observed a focal proliferative vitreoretinopathy (PVR) reaction without activity, while there was no evidence for a CNV formation in that area., Conclusions: The FA findings confirm our previous results on the safety of the EPIRET3 system, which was tolerated in all patients but revealed a certain risk profile in regard to the stimulator fixation. While there was no evidence for newly occurred CME or CNV during the follow-up visits, nevertheless gliosis or even PVR reaction at the tack's fixation site suggests the need to develop alternative fixation procedures of epiretinal stimulators.

Retinal ischemic injury is common in patients with diabetes, atherosclerosis, hypertension, transient ischemia attack and amaurosis fugax. Previously, signs of ischemic stress, such as pericyte loss, blood-retinal barrier breakdown and neovascularization, which can lead to occlusion of retinal vessels, have been prevented in diabetic db/db mice with aldose reductase (AR) null mutation. To determine the role in retinal ischemic injury of AR and sorbitol dehydrogenase (SDH), the first and second enzymes in the polyol pathway, mice with deletion of AR (AR(-/-)) or SDH-mutation (SDH(-/-)), or C57BL/6N mice treated with AR or SDH inhibitors were subjected to transient retinal artery occlusion (2h of occlusion and 22h of reperfusion) by the intraluminal suture method. Neuronal loss and edema observed in wildtype (AR(+/+)) retinas after transient ischemia were prevented in the retinas of AR(-/-) mice or C57BL/6N mice treated with an AR inhibitor, Fidarestat. Fewer TUNEL-positive cells and smaller accumulations of nitrotyrosine and poly(ADP-ribose) were also observed in the retinas of AR(-/-) mice. However, SDH(-/-) mice and C57BL/6N mice treated with SDH inhibitor, CP-470,711, were not protected against ischemia-induced retinal damage. Taken together, AR contributes to retinal ischemic injury through increased edema and free radical accumulation. Therefore, AR inhibition should be considered for the treatment of retinal ischemic injury often observed in diabetic patients.

Background: The visual outcome in untreated nonarteritic anterior ischemic optic neuropathy (NAION) is dismal. Because intravitreal triamcinolone (IVTA) has shown promise in improving edematous retinal disorders, a pilot trial of this therapy in NAION was considered reasonable., Methods: Four eyes of 4 patients with severe visual loss due to NAION were treated with 4 mg IVTA (study group). The control group consisted of 6 consecutive patients with NAION who received no treatment. Patients were evaluated by the visual acuity and visual field measurements of the Early Treatment Diabetic Retinopathy Study (ETDRS) and fluorescein angiography., Results: All patients completed at least 9 months of follow-up. In the study group, the mean improvement in visual acuity were 4, 5.8, and 6.2 ETDRS lines at the first and third weeks and final visit, respectively. Optic disc swelling and leakage had markedly decreased at the first postinjection week and had disappeared by the third week examination in all eyes. In the control group, the mean improvements in visual acuity were 0, 0.7, and 1.3 ETDRS lines at the first and third weeks and final visit, respectively. Control eyes showed resolution of the optic disc swelling between the fourth week and third month visits. No marked change in visual field defects was observed in either group., Conclusions: IVTA provided relatively improved recovery of visual acuity and relatively rapid resolution of optic disc swelling in a small sample of patients with acute NAION. It did not provide visual field improvement. A larger trial is merited by the results of this small pilot study.

Objective: Cysts of the septum pellucidum (CSPs) may become symptomatic because of obstruction of cerebrospinal fluid flow, resulting in increased intracranial pressure and hydrocephalus requiring surgical intervention. Endoscopic fenestration may be the most effective and least invasive technique to treat this pathological condition., Clinical Presentation: An 11-year-old boy sought treatment for frequent episodes of severe headache. On examination, he had papilledema. There was evidence on magnetic resonance imaging scans of a space-occupying CSP with obstructive hydrocephalus., Intervention: The endoscopic technique of fenestration of both lateral walls of an enlarged CSP via a left frontal approach under ultrasound guidance using a rigid endoscope was successful. After surgery, the patient became asymptomatic, his papilledema resolved, and magnetic resonance imaging scans demonstrated collapse of the walls of the CSP toward the midline., Conclusion: Neuroendoscopic fenestration should be strongly considered as the treatment of choice for symptomatic CSPs. This procedure alone can lead to complete resolution of clinical symptoms and hydrocephalus, can reduce the size of the CSP, and can obviate the need for an implantable cerebrospinal fluid shunt.

The purpose of this study was to evaluate the ability of the nonsteroidal anti-inflammatory drug nepafenac to prevent development of mitogen-induced pan-retinal edema following topical ocular application in the rabbit. Anesthetized Dutch Belted rabbits were injected intravitreally (30 microg/20 microL) with the mitogen concanavalin A to induce posterior segment inflammation and thickening (edema) of the retina. The Heidelberg Retina Tomograph was used to generate edema maps using custom software. Blood-retinal barrier breakdown was assessed by determining the protein concentration in vitreous humor, whereas analysis of PGE2 in vitreous humor was performed by radioimmunoassay. Inhibition of concanavalin A-induced retinal edema was assessed 72 h after initiation of topical treatment with nepafenac (0.1-1.0%, w/v), dexamethasone (0.1%), VOLTAREN (0.1%), or ACULAR (0.5%). Concanavalin A elicited marked increases in vitreal protein and PGE2 synthesis at 72 h postinjection. Retinal thickness was also increased by 32%, concomitant with the inflammatory response. Topical application of 0.5% nepafenac produced 65% reduction in retinal edema which was correlated with 62% inhibition of blood-retinal barrier breakdown. In a subsequent study, 0.5% nepafenac significantly inhibited (46%) blood-retinal barrier breakdown concomitant with near total suppression of PGE2 synthesis (96%). Neither Voltaren nor Acular inhibited accumulation of these markers of inflammation in the vitreous when tested in parallel. This study demonstrates that nepafenac exhibits superior pharmacodynamic properties in the posterior segment following topical ocular dosing, suggesting a unique therapeutic potential for a variety of conditions associated with retinal edema.

Objective: To determine if adenoviral-mediated transfer of the gene for catalase (CAT), the reactive oxygen species scavenger, suppresses experimental optic neuritis., Clinical Relevance: Gene therapy with CAT delivered by an adeno-associated viral vector was previously shown to suppress experimental optic neuritis. Because the transduction of protein expression with recombinant adeno-associated viral vector is relatively slow, taking weeks to reach full levels, we studied the effects of replication-deficient adenovirus containing CAT in suppressing experimental optic neuritis. Transduction with adenovirus occurs within days of inoculation, thus, it may be more applicable for the treatment of patients with acute optic neuritis., Materials and Methods: Replication-deficient adenovirus containing CAT was injected above the right optic nerve heads of SJL/J mice that were simultaneously sensitized for experimental allergic encephalomyelitis. For controls, the left eyes were injected with the replication-deficient adenovirus without CAT or no virus. The histological effects of CAT on the lesions of experimental allergic encephalomyelitis were measured by computerized analysis of the myelin sheath area (for demyelination), optic disc area (for optic nerve head swelling), the extent of the cellular infiltrate, extravasated serum albumin labeled with immunogold (for disruption of the blood-brain barrier), and the in vivo hydrogen peroxide reaction product., Results: After 1 month, cell-specific catalase activity, evaluated by the quantitation of catalase immunogold, was increased about 2-fold each in endothelia, oligodendroglia, astrocytes, and axons of the CAT-inoculated right optic nerves compared with the control left optic nerves. The increased cellular levels of catalase reduced demyelination by 30%, optic nerve head swelling by 25%, cellular infiltration by 26%, disruption of the blood-brain barrier by 61%, and in vivo levels of hydrogen peroxide by 81%., Conclusions: Adenoviral-mediated gene transfer increased catalase levels in all optic nerve cell types, and it persisted for 1 month after inoculation. The increased cellular levels of catalase suppressed demyelination and blood-brain barrier disruption at the foci in the optic nerve where prior magnetic resonance imaging and histopathologic studies have demonstrated the demyelinating inflammation of experimental and human optic neuritis. Together, they suggest that gene therapy with CAT may be helpful in the treatment of patients with optic neuritis.

We evaluated the prevalence of pathological visually evoked potentials (VEP) before the appearance of papilledema or other signs of elevated intracranial pressure in children suffering from craniosynostosis. In 52 children (19 girls, 33 boys, median age 7.6 months, mean age 7.6 months, range from 3 to 34 months) preoperative VEP were analyzed. In 13 patients, pathological VEP were observed. In all children, both eyes were involved. Only 1 child suffered from papillar anomalies. Latency was pathological in 12 children, whereas the amplitude was suppressed in only 2 children. In all children with preoperative pathological VEP, postoperative controls (n = 4) were improved or normal. Thus, VEP may be the first test for neuronal damage in craniosynostosis.

A 41-year-old male patient in end-stage renal failure presented on two occasions, over an 18-month period, with painless unilateral visual deterioration and optic disc edema. Clinical findings were compatible with a diagnosis of uremic optic neuropathy. On his initial presentation, the patient refused the onset of dialysis, resulting in a permanent visual deficit of the left eye. On his subsequent admission with a similar clinical picture, this time of the right eye, dialysis combined with corticosteroid therapy was promptly instituted. This led to a rapid improvement of the visual acuity and visual field defects of the right eye concomitant with subsidence of the edema of the optic nerve head.

Raised intracranial pressure (ICP) occurs at some time in 50-75% of severely head injured patients. Measurement of ICP alone is not sufficient. Arterial pressure must also be monitored: the important physiological variable is cerebral perfusion pressure. Detailed analysis of the ICP recording yields valuable information on the nature and cause of ICP, with implications for appropriate therapy. Additional measurements of importance include brain electrical activity, arterial and jugular venous oxygen saturation, and blood flow velocity in major intracranial arteries measured by transcranial Doppler sonography. These assessments not only add information about the cause of intracranial hypertension (vascular vs. nonvascular) but also help to regulate therapy, providing early warning that a treatment for reducing the ICP is actually producing global brain ischemia. In the management of raised ICP, all correctable factors must first of all be dealt with, then a choice made between hypnotic drugs and osmotic therapy according to whether the cause of raised ICP is, respectively, vascular or nonvascular.

Twenty-seven patients with tuberculous meningitis (TBM) were treated with ethambutol, isonicotinic acid hydrazide, streptomycin and dexamethasone and 28 were treated with triple anti-tuberculous drugs only. Only two of the patients to whom steroids were given developed ocular complications as compared to seven of those not receiving dexamethasone. High dose dexamethasone apparently prevents optic atrophy in TBM. Controlled double-blind studies with and without dexamethasone are needed to confirm this postulation.