Blood-aqueous barrier deterioration following retained metallic corneal foreign body: A laser flare photometric study.

BACKGROUND: This study aims to use laser flare photometry to evaluate flare changes in patients following corneal damage from a metallic foreign body (FB). METHODS: Foreign body injured eyes and the healthy fellow eyes of 54 consecutive patients were studied in this comparative, observational, cross-sectional study. Flare levels were analyzed according to demographics, history of previous exposures, foreign body location, and foreign body penetration into the injured cornea. RESULTS: The mean flare value was significantly higher for the eyes with corneal foreign body injury compared to the fellow-control eyes (11.35±14.17 ph/ms and 6.30±3.81 ph/ms, respectively) (p=0.014). The mean flare values were significantly lower in eyes with a history of more than one previous corneal foreign body removal flare values than in other eyes (p=0.029). CONCLUSION: Flare is increased by corneal foreign body exposure. However, eyes that experience multiple previous corneal foreign body exposures may show relatively low flare, probably due to corneal desensitization.

Damage to the Blood-Aqueous Barrier in Ocular Blunt Trauma and Its Association with Intraocular Pressure Elevation.

BACKGROUND: The aim of this study is to provide a quantitative evaluation of the blood-aqueous barrier (BAB) in patients with ocular blunt trauma and evaluate its association with intraocular pressure (IOP) elevation. METHODS: This is a prospective case-control study, and the following 3 groups were included: elevated IOP (45 patients with an elevated IOP secondary to ocular blunt trauma), normal IOP (27 patients with a normal IOP after ocular blunt trauma), and healthy controls. The main outcome measures were IOP and BAB function evaluated using a laser flare-cell meter (LFCM). RESULTS: Patients had significantly higher flare intensities and cell counts than the normal controls (both p < 0.001), and the elevated-IOP group displayed even higher LFCM readings than the normal-IOP group. Aqueous flare and cell readings were positively correlated with IOP (r = 0.529 and 0.590, respectively, p < 0.001). LFCM readings in the elevated-IOP group were still significantly high even on postraumatic day 120 following anti-inflammatory treatment. CONCLUSION: BAB dysfunction occurred following ocular blunt trauma. Eyes with an elevated IOP displayed a more seriously disturbed BAB and a longer recovery course. Examination with a LFCM provides insight into the pathophysiology of IOP elevation and assists in making decisions concerning anti-inflammatory treatment during follow-up.

Blood-Brain Barrier Disruption Is an Early Event That May Persist for Many Years After Traumatic Brain Injury in Humans.

Traumatic brain injury (TBI) is a risk factor for dementia. Mixed neurodegenerative pathologies have been described in late survivors of TBI, but the mechanisms driving post-TBI neurodegeneration remain elusive. Increasingly, blood-brain barrier (BBB) disruption has been recognized in a range of neurologic disorders including dementias, but little is known of the consequences of TBI on the BBB. Autopsy cases of single moderate or severe TBI from the Glasgow TBI Archive (n = 70) were selected to include a range from acute (10 hours-13 days) to long-term (1-47 years) survival, together with age-matched uninjured controls (n = 21). Multiple brain regions were examined using immunohistochemistry for the BBB integrity markers fibrinogen and immunoglobulin G. After TBI, 40% of patients dying in the acute phase and 47% of those surviving a year or more from injury showed multifocal, abnormal, perivascular, and parenchymal fibrinogen and immunoglobulin G immunostaining localized to the gray matter, with preferential distribution toward the crests of gyri and deep neocortical layers. In contrast, when present, controls showed only limited localized immunostaining. These preliminary data demonstrate evidence of widespread BBB disruption in a proportion of TBI patients emerging in the acute phase and, intriguingly, persisting in a high proportion of late survivors.

Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction.

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain. Our genome-wide association study of Drosophila melanogaster revealed that the probability of death following TBI is associated with single nucleotide polymorphisms in genes involved in tissue barrier function and glucose homeostasis. We found that TBI causes intestinal and blood-brain barrier dysfunction and that intestinal barrier dysfunction is highly correlated with the probability of death. Furthermore, we found that ingestion of glucose after a primary injury increases the probability of death through a secondary injury mechanism that exacerbates intestinal barrier dysfunction. Our results indicate that natural variation in the probability of death following TBI is due in part to genetic differences that affect intestinal barrier dysfunction.

Increased permeability of the blood-brain barrier and Alzheimer's disease-like alterations in slit-2 transgenic mice.

Alzheimer's disease (AD) is a progressive neurological disorder that primarily affects memory, and its prevalence is rising. Increasing evidence suggests that dysfunction of the blood-brain barrier (BBB) may be involved in AD and other neurodegenerative diseases. Herein, we report that the permeability of the BBB is increased and that AD-like alterations are present in Slit-2 overexpressing transgenic mice. We found that behavioral change and the corresponding molecular diagnostic markers of AD, such as hippocampal neuron apoptosis, amyloid-ß (Aß) protein deposition, and acetylcholinesterase expression, were increased in the Slit-2 transgenic mice. Moreover, the endothelial cells were dysfunctional, the size of the lateral ventricle cavity increased, and the permeability of the BBB increased. Additionally, there was an increased serum level of glutamate indicating that the BBB is related to AD. Finally, histopathological analysis of other organs in the Slit-2 overexpressing mice did not show any marked abnormalities. These findings demonstrate that Slit2 overexpression may be responsible for AD-like alterations and the increased BBB permeability in these mice. Our study provides a potential novel mechanism for the development of AD.

Causes and treatment of choroidal effusion after glaucoma surgery.

Choroidal effusion is a prevalent and potentially vision-threatening complication following glaucoma surgery. This review article will introduce readers to the anatomy and physiology of choroidal effusion. Evidence from the literature will be reviewed to discuss the prevalence of choroidal effusion after glaucoma surgery. Etiology, clinical presentation, and differential diagnosis of choroidal effusion will be detailed in this review article. Finally, readers will gain insight into methods to prevent and treat choroidal effusion after glaucoma surgery.

Examination of blood-brain barrier (BBB) integrity in a mouse brain tumor model.

The present study evaluates, both functionally and biochemically, brain tumor-induced alterations in brain capillary endothelial cells. Brain tumors were induced in Balb/c mice via intracranial injection of Lewis Lung carcinoma cells into the right hemisphere of the mouse brain using stereotaxic apparatus. Blood-brain barrier (BBB) permeability was assessed at various stages of tumor development, using both radiolabeled tracer permeability and magnetic resonance imaging with gadolinium diethylene-triamine-pentaacetate contrast enhancement (Gad-DTPA). The expression of the drug efflux transporter, P-glycoprotein (P-gp), in the BBB at various stages of tumor development was also evaluated by Western blot and immunohistochemistry. Median mouse survival following tumor cell injection was 17 days. The permeability of the BBB to (3)H-mannitol was similar in both brain hemispheres at 7 and 10 days post-injection. By day 15, there was a twofold increase in (3)H-mannitol permeability in the tumor bearing hemispheres compared to the non-tumor hemispheres. Examination of BBB permeability with Gad-DTPA contrast enhanced MRI indicated cerebral vascular permeability changes were confined to the tumor area. The permeability increase observed at the later stages of tumor development correlated with an increase in cerebral vascular volume suggesting angiogenesis within the tumor bearing hemisphere. Furthermore, the Gad-DPTA enhancement observed within the tumor area was significantly less than Gad-DPTA enhancement within the circumventricular organs not protected by the BBB. Expression of P-gp in both the tumor bearing and non-tumor bearing portions of the brain appeared similar at all time points examined. These studies suggest that although BBB integrity is altered within the tumor site at later stages of development, the BBB is still functional and limiting in terms of solute and drug permeability in and around the tumor.

Evaluation of four drugs for inhibition of paracentesis-induced blood-aqueous humor barrier breakdown in cats.

OBJECTIVE: To compare inhibitory effects of topically applied 1% prednisolone acetate suspension, 0.03% flurbiprofen solution, 0.1% dexamethasone suspension, and 0.1% diclofenac solution on paracentesis-induced blood-aqueous barrier breakdown in cats. ANIMALS: 9 healthy cats. PROCEDURES: Paracentesis of the anterior chamber was performed in both eyes of each cat. One eye of each cat was treated with a topically administered anti-inflammatory medication (1% prednisolone [n = 7 cats], 0.03% flurbiprofen [7], 0.1% dexamethasone [9], or 0.1% diclofenac [8]) immediately following paracentesis and at 6, 10, and 24 hours after paracentesis. The contralateral untreated eye served as the control eye. Each cat had a 6-day washout period between experimental drugs. Breakdown of the blood-aqueous barrier was quantified by use of laser flaremetry. RESULTS: Topical administration of 1% prednisolone significantly reduced aqueous humor flare at 4, 8, and 26 hours after paracentesis. Topical administration of 0.1% diclofenac significantly reduced aqueous humor flare at 8 and 26 hours after paracentesis. Topical administration of 0.1% dexamethasone and 0.03% flurbiprofen did not significantly decrease flare at any time point. There were significant differences in intraocular pressures between NSAID-treated eyes and untreated contralateral eyes. CONCLUSIONS AND CLINICAL RELEVANCE: Topical administration of 1% prednisolone and 0.1% diclofenac significantly reduced intraocular inflammation in cats with paracentesis-induced uveitis. Topical administration of 1% prednisolone or 0.1% diclofenac may be appropriate choices when treating cats with anterior uveitis. Topical administration of diclofenac and flurbiprofen should be used with caution in cats with a history of ocular hypertension.

[The blood-aqueous barrier changes after laser peripheral iridotomy or surgery peripheral iridectomy].

OBJECTIVE: To investigate the ocular blood-aqueous barrier (BAB) alteration after laser peripheral iridotomy (LPI) or surgery peripheral iridectomy (SPI) in patients with primary chronic angle-closure glaucoma (PCACG). METHODS: This was a clinical randomized controlled trial. Sixty eyes of 60 subjects with early stage of PCACG were randomly received either LPI or SPI and followed up postoperatively at day 3, week 1, 2, 3, and 4. Aqueous flare in anterior chamber was measured by FC-2000 flare-cell photometry, intraocular pressure (IOP) measured by tonometer, central corneal endothelium cell counted by endothelioscopy, peripheral anterior synechiae (PAS) detected by gonioscopy. Data were analyzed by using two-way ANOVA for repeated measures, independent samples t-test, paired t-test, nonparametric test, and Spearman rank correlation test. RESULTS: On follow-ups of pre-operative and post-operative 3 days, 1 week (w), 2w, 3w and 4w respectively, the mean aqueous flare values for LPI group were (5.47 ± 1.09), (11.96 ± 3.07), (8.08 ± 2.18), (5.68 ± 0.83), (5.80 ± 1.00), (5.69 ± 1.12) PC/ms, and for SPI group were (5.43 ± 1.13), (8.44 ± 3.22), (6.42 ± 1.77), (5.35 ± 0.71), (5.53 ± 1.26), (5.45 ± 1.23) PC/ms. During post-operative 1w the flare values in both LPI and SPI groups were significantly higher than that on pre-operation (t = -12.753, -8.101, P < 0.05; t = -5.971, -3.870;P < 0.05) and LPI group had a significantly higher mean flare value than SPI group (t = 4.329, 3.231;P < 0.05). The IOP spike in LPI group was significantly (χ(2) = 5.079, 4.022, P < 0.05) higher than that in SPI group at week 1 of post-operation. Increased IOP was positively correlated with BAB damage (r = 0.899, 0.833; P < 0.05). The numbers of medications required to maintain IOP ≤ 21 mm Hg (1 mm Hg = 0.133 kPa) at week 4 of post-operation in LPI was significantly (Z = -1.984, P < 0.05) more than that in SPI group. There were no significant differences in central corneal endothelium cell count at week 1 (t = -0.696, 0.008) and in extension of PAS at week 4 (Z = -1.270, -1.490) of post-operation when compared to pre-operation (P > 0.05). No obvious complications occurred in both groups. CONCLUSIONS: Our results demonstrated that IOP spike in both of LPI and SPI is due, at least in part, to BAB damage, which appears to be more severe in LPI group and can recover within two weeks. PAS progression and central corneal endothelium cell loss are not aggravated in 1 month after operation.

Blood-aqueous barrier function in a patient with choroideremia.

The purpose was to determine whether there was a breakdown of the blood-aqueous barrier in a patient with choroideremia. A 27-year-old man with typical choroideremia underwent standardized ophthalmo-logical evaluation, including quantitative measurement of aqueous flare intensity, by a laser flare-cell meter. The results showed areas of atrophy of the choriocapillaries and retinal pigment epithelium in the mid-periphery and posterior pole, although not in the macula. Fluorescein angiography showed areas of loss of the choriocapillaries and retinal pigment epithelium. The fovea was spared with a surrounding zone of hy-perfluorescence. Electroretinography showed a subnormal photopic amplitude and extinguished scotopic response. Electrooculography revealed that the light peak/dark trough ratio was reduced. Goldmann perimetry showed constricted peripheral fields. Laser photometry showed an increase in the aqueous flare intensity in both eyes, as compared with normal subjects. We conclude that the function of the blood-aqueous barrier might be affected in patients with choroideremia.

Aqueous flare and cells in Fuchs syndrome.

PURPOSE: To quantitatively evaluate aqueous flare and cells in patients with Fuchs syndrome. METHODS: The medical records of 40 patients (47 eyes) diagnosed with Fuchs syndrome between February 2006 and January 2007 at the Uveitis Study Center of Sun Yat-sen University were retrospectively reviewed. Aqueous flare and cells were clinically evaluated and quantified with laser flare-cell meter. Statistical analysis was performed to investigate the relationship between flare values and cell counts, and clinical parameters including patients' age, sex, duration of disease, best-corrected visual acuity, keratic precipitate, iris depigmentation, intraocular pressure, and posterior subcapsular lens opacities. RESULTS: Aqueous flare values (photon counts/ms) were significantly higher in Fuchs syndrome (9.40+/-5.85) than in normal controls (5.77+/-1.89, P=0.000). Aqueous cell counts (cells/0.5 mm(3)) were also significantly higher in Fuchs syndrome (5.09+/-4.84) than in normal controls (1.14+/-1.03, P=0.000). The flare values were positively correlated with the cell counts (r=0.331, P=0.001). Both flare values and cell counts were higher in eyes with keratic precipitates scored 2+ or 3+ as compared to those with a 1+ score. Higher flare values and cell counts were also observed in eyes with a 2+ or 3+ iris depigmentation score as compared to those with a 1+ score. No difference was found between flare values and cell counts and other parameters. CONCLUSION: Breakdown of blood-aqueous barriers and increased cell counts are present in the affected eyes in patients with Fuchs syndrome. These changes are positively associated with the degree of keratic precipitates and iris depigmentation.

Relationship between blood-aqueous barrier disruption and ischemic macular edema in patients with branch or central retinal vein occlusion: effects of sub-tenon triamcinolone acetonide injection.

PURPOSE: The aim of this study was to study the effects of the sub-Tenon triamcinolone acetonide (STA) injection on ischemic cystoid macular edema (CME) or macular edema (ME) and blood-aqueous barrier (BAB) disruption associated with branch or central retinal vein occlusion (BRVO or CRVO). METHODS: Prior to, and 1, 2, 3, and 4 months after, STA injection, central retinal thickness was measured by using optical coherence tomography and the amount of aqueous flare by using laser flare metry. RESULTS: In the BRVO group treated by STA, the amount of flare was significantly less at 1, 2, and 3 months after injection than in the untreated BRVO group (P < 0.05). In the CRVO group treated by STA, the amount was significantly less at 1 month after injection than in the untreated CRVO group (P < 0.05). In the BRVO group with STA treatment, central retinal thickness was significantly less at 1 and 2 months after the treatment than in the untreated BRVO group (P < 0.05). In the CRVO group with STA treatment, the thickness was significantly less at 1 month after treatment than in the untreated CRVO group (P < 0.05). A correlation test revealed the amount of aqueous flare and the central retinal thickness to be well correlated (P < 0.01). CONCLUSIONS: The effects of STA and its time course on CME or ME correlated well with those on BAB disruption. Since there is the close correlation between the BAB and blood-retinal barrier function, the effects of medical treatment on ME associated with BRVO or CRVO can be evaluated by means of the BAB function.

Src-family kinase dependent disruption of endothelial barrier function by Plasmodium falciparum merozoite proteins.

Pulmonary complication in severe Plasmodium falciparum malaria is manifested as a prolonged impairment of gas transfer or the more severe acute respiratory distress syndrome (ARDS). In either clinical presentation, vascular permeability is a major component of the pathologic process. In this report, we examined the effect of clinical P falciparum isolates on barrier function of primary dermal and lung microvascular endothelium in vitro. We showed that parasite sonicates but not intact infected erythrocytes disrupted endothelial barrier function in a Src-family kinase-dependent manner. The abnormalities were manifested both as discontinuous immunofluorescence staining of the junctional proteins ZO-1, claudin 5, and VE-cadherin and the formation of interendothelial gaps in monolayers. These changes were associated with a loss in total protein content of claudin 5 and redistribution of ZO-1 from the cytoskeleton to the membrane and the cytosolic and nuclear fractions. There was minimal evidence of a proinflammatory response or direct cellular cytotoxicity or cell death. The active component in sonicates appeared to be a merozoite-associated protein. Increased permeability was also induced by P falciparum glycophosphatidylinositols (GPIs) and food vacuoles. These results demonstrate that parasite components can alter endothelial barrier function and thus contribute to the pathogenesis of severe falciparum malaria.

Steroid prophylaxis in eyes with uveitis undergoing phacoemulsification.

AIM: To compare the efficacy of two preoperative steroid regimens for cataract surgery in patients with uveitis. METHODS: 40 uveitis patients with cataract underwent phacoemulsification and intraocular lens (IOL) implantation. Preoperatively they were randomised into two groups: group 1 (20 patients) received a single dose of intravenous methylprednisolone (15 mg/kg) half an hour before surgery, and group 2 (20 patients) received a 2 week course of oral prednisolone (0.5 mg/kg) which was tapered postoperatively. Preoperatively patients had aqueous flare and cells measured with the Kowa laser flare meter. On days 1, 7, 28, and 90 aqueous flare and cells were measured, and on days 7 and 90 fluorescein angiography was performed to determine the incidence of cystoid macular oedema (CMO). RESULTS: At all postoperative visits the mean increase in flare was greater for group 1 (intravenous steroid). Patients with posterior synechiae had greater blood-aqueous barrier damage (BAB) postoperatively. There were no statistically significant differences in logMAR visual acuity and incidences of CMO between the two groups at 7 and 90 days. CONCLUSION: A 2 week course of oral prednisolone, tapered postoperatively, produced a better recovery of the BAB than a single dose of intravenous methylprednisolone and is thus the recommended preoperative regimen.

Disorders of the blood-aqueous barrier after phacoemulsification in diabetic patients.

PURPOSE: To evaluate the function of the blood-aqueous barrier after phacoemulsification with implantation of a foldable intraocular lens (IOL) in diabetic patients. METHODS: All patients were enrolled from those scheduled for phacoemulsification with intraocular lens implantation in Zhongshan Ophthalmic Center Guangzhou from March 2002 to June 2002. The classification on diabetic retinopathy (DR) was based on the fundus examination after cataract surgery. The blood-aqueous barrier function was examined using the laser flare cell meter (Kowa FC-2000) preoperatively and on postoperative days 1, 7, 30, and 90 by an independent examiner who was masked to the DR classification. Patients were operated by one experienced surgeon as per standard clinical protocol and were provided the same postoperative medical care. A linear regression and Wilcoxon test were used for the analysis. RESULTS: A total of 112 patients were divided into three groups: patients without diabetic mellitus as normal control (n=56), diabetic patients without diabetic retinopathy (n=2), with nonproliferation diabetic retinopathy (NPDR) (n=37), and diabetic patients with proliferation diabetic retinopathy (PDR) (n=17). All patients were examined and successfully followed up for 3 months after cataract surgery. Aqueous flare mean photon counts in PDR, NPDR, and control eyes were 8.94+/-0.57, 7.03+/-0.27, and 6.94+/-0.34 before surgery and increased to 32.42+/-0.67, 26.07+/-0.83, 26.27+/-1.37 on the first day after surgery (P<0.05), then decreased to 19.86+/-0.78, 14.08+/-0.54 and 13.96+/-1.05 at 7 days after surgery (P<0.05), 13.24+/-0.29, 9.86+/-0.33, and 9.07+/-0.43 at 30 days after surgery (P<0.05); eventually, the counting decreased to 11.25+/-0.31, 7.24+/-0.67, and 7.16+/-0.27 at 90 days after surgery (P<0.05). Linear regression model suggested that other potential variables, such as age, sex, eye (left/right), phaco time, phaco energy, and hypertension were not related to the outcome. For patients without diabetes mellitus and diabetic patients with NPDR, highly statistically significant differences (P<0.05) were found between preoperative flare value and those measured on days 1, 7, and 30 after surgery, but no statistically significant differences (P>0.05) were found between the preoperative flare value and those measured on postoperative days 90. However, patients with PDR still had a higher flare value even on postoperative day 90. The patients with intraoperative iris prolapse had a higher flare value between days 1 and 7 postoperatively. CONCLUSION: Phacoemulsification with a foldable intraocular lens implantation affects the blood-aqueous barrier more severely in diabetic patients with PDR than patients with NPDR and nondiabetic patients.

Changes of blood aqueous barrier after phacoemulsification in rabbits.

PURPOSE: To evaluate the function and the morphological changes of the blood aqueous barrier (BAB) after phacoemulsification and to provide the physiological mechanism of BAB dysfunction. METHODS: Phacoemulsification was performed on 12 rabbit eyes. Aqueous humor was abstracted and the concentrations of aqueous humor protein were examined preoperatively and on postoperative days 1, 7, 14, 21, 30 with Lowry. After the iris and the ciliary body were removed from the rabbit eyes, we selected lanthanum nitrate as a tracer, then ultrastructural changes of BAB were investigated with transmission electron microscopy. RESULTS: Highly statistically significant differences (P < 0.05) were found between preoperative aqueous humor protein concentration and those measured on days 1, 7, 14, 21 and 30 after surgery. Under transmission electron microscopy, a part of the endothelial cells and BAB damaged as shown by the leakage of lanthanum tracing into intravessels through the broad space were observed. CONCLUSION: The results suggest that there is a blood aqueous barrier breakdown after phacoemulsification. The morphological basis of BAB damage is the reversible opening of tight junctions between endothelial cells.