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This study investigated the preventive effect of 5-aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) on blood–aqueous barrier (BAB) breakdown induced after anterior chamber paracentesis (ACP) in beagles. 5-ALA/SFC (1/0.64 mg/kg or 3/1.92 mg/kg) or carprofen (4.0 mg/kg) was orally administered daily for 7 days prior to ACP. Then, a sample of the aqueous humor (AH) was collected from one eye via ACP (first sample) and again 60 min later (second sample). The protein and prostaglandin E2 (PGE2) concentrations in both samples were measured. Compared with the control group, high-dose 5-ALA/SFC and carprofen significantly reduced the AH protein and PGE2 concentrations in the second sample. Our findings suggest that 5-ALA/SFC suppresses BAB breakdown in dogs. [ABSTRACT FROM AUTHOR]

This review discusses the experience in applying laser flare photometry, a non-invasive technique, in ophthalmology, to assess quantitatively the state of the blood-aqueous barrier (BAB) in patients with certain ocular and systemic disorders. The method allows reliable detection of such biomarkers of the state of the BAB as the intensity of the scattered light (flare) and number of cells in the aqueous of the anterior chamber, sometimes even at the subclinical level, which significantly improves the capability for early diagnosis and objective treatment monitoring.

Objectives: The aim of this study was to assess intraocular inflammation in patients with active and inactive Graves' ophthalmopathy (GO) using an aqueous laser flash meter and to assess its relationship with thyroid hormones, antibodies, and clinical activity score (CAS). Methods: Forty patients (29 females and 11 males) were included in the study. The patients were divided into two groups according to CAS; patients with CAS <3 (inactive) were included in Group 1 and patients with CAS =≥3 (active) were included in Group 2. The laser flare meter was used to measure the flare of aqueous humor. Each patient's ocular findings, thyroid hormone, and antibody levels were also recorded. Results: The mean age of patients was 46.88±11.79 years in Group 1 and 44.50±12.59 years in Group 2 (p=0.555). The mean CAS was 0.88±0.65 in Group 1 and 3.57±0.85 in Group 2 (p<0.001). The mean aqueous flare was 6.5±2.2 ph/ms in Group 1 and 7.0±6.4 ph/ms in Group 2 (p=0.73). Hertel exophthalmometry, intraocular pressure (IOP), antithyroglobulin antibody, and thyroid stimulating hormone receptor antibody (TRAb) levels were similar in both groups (each p>0.05). There was no correlation between aqueous flare value and CAS, Hertel exophthalmometry, IOP, thyroid hormone, and antibody levels (each p>0.05). There was a significant correlation between CAS and antibody levels (each p<0.05). Conclusion: Flare values that are not much above the normal range may be an indication that intraocular inflammation is not elevated in GO patients. This suggests that the damage to the blood-aqueous barrier in these patients is not severe enough to increase intraocular inflammation. [ABSTRACT FROM AUTHOR]

Exfoliation glaucoma (XFG) is the most recognizable form of secondary open-angle glaucoma associated with a high risk of blindness. This disease is characterized by white flaky granular deposits in the anterior chamber that leads to the elevation of intraocular pressure (IOP) and subsequent glaucomatous optic nerve damage. Conventionally, XFG is known to respond poorly to medical therapy, and surgical intervention is the only management option in most cases. Various genetic and nongenetic factors are known to be linked to the development of XFG. Despite decades of research on the genetic factors in exfoliation syndrome (XFS) by study groups and global consortia involving different ethnic populations, the pathogenesis of XFS and the mechanism of onset of glaucoma still remains an unsolved mystery. The key lies in understanding how the function of a gene (or set of genes) is altered by environmental triggers, along with other molecular events that underlie the key disease attributes, namely, oxidative stress and the disruption of the blood–aqueous barrier (BAB). It remains a challenge to evolve a theory encompassing all factions of molecular events occurring independently or parallelly that determine the disease manifestation (phenotype) or the stage of the disease in the eye (or in any tissue) in exfoliation. Our enhanced understanding of the underlying molecular pathophysiology of XFG, beyond the known genes or polymorphisms involved in the disease, will lead to improved diagnosis and management and the ability to recognize how the environment influences these key events that lead to the disease phenotype or disease progression. This review summarizes the recent observations and discoveries of four key factors that may hold the answers to the non-lysyl oxidase-like 1 (LOXL1) mechanisms behind XFG pathogenesis, namely, the epigenetic factor miRNA, disordered autophagy along with the potential involvement of mitochondrial mutations, and a compromised aqueous–blood barrier.

This study investigated the preventive effect of 5-aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) on blood-aqueous barrier (BAB) breakdown induced after anterior chamber paracentesis (ACP) in beagles. 5-ALA/SFC (1/0.64 mg/kg or 3/1.92 mg/kg) or carprofen (4.0 mg/kg) was orally administered daily for 7 days prior to ACP. Then, a sample of the aqueous humor (AH) was collected from one eye via ACP (first sample) and again 60 min later (second sample). The protein and prostaglandin E2 (PGE2) concentrations in both samples were measured. Compared with the control group, high-dose 5-ALA/SFC and carprofen significantly reduced the AH protein and PGE2 concentrations in the second sample. Our findings suggest that 5-ALA/SFC suppresses BAB breakdown in dogs.

Objective: We investigated the early posttreatment effects of two steroidal anti‐inflammatory ophthalmic drugs on blood‐aqueous barrier (BAB) breakdown by paracentesis in dogs. Animal studies: We studied 21 healthy beagles with normal eyes. Procedures: Controlled anterior chamber paracentesis (0.5 mL) was performed in one eye of each dog. Control group dogs (n = 7) received no medication, whereas those in the treatment groups received a topical anti‐inflammatory medication (difluprednate [DFBA] ophthalmic emulsion 0.05% [n = 7] or betamethasone [BMZ] sodium phosphate ophthalmic solution 0.1% [n = 7]) at 0, 15, 30, and 45 minutes after initial paracentesis in the paracentesed eyes. Secondary aqueous humor (AH) was collected 60 minutes after initial paracentesis. Protein and prostaglandin E2 (PGE2) concentrations in AH were determined using the bicinchoninic acid assay and commercially available immunoassay kit, respectively. All mean values in the three groups were compared using analysis of variance followed by Tukey's post hoc test. Results: Aqueous protein and PGE2 concentrations were markedly increased at 60 minutes following paracentesis. Both concentrations in the secondary AH of the DFBA group were significantly lower than those of the control group; however, treatment with BMZ had no significant effects. Conclusions: Early postparacentesis treatment with DFBA was more effective than that with BMZ for reducing aqueous protein and PGE2 contents in dogs with paracentesis‐induced BAB breakdown. DFBA may be an appropriate treatment during the early stage of anterior uveitis caused by intraocular surgery in dogs. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the study is to quantify aqueous flare using laser flare photometry (LFM) in patients undergoing 25-G pars plana vitrectomy (PPV) and assess the need for postoperative topical corticosteroid administration . Methods: Prospective evaluation of 50 eyes (50 patients) was performed using LFM until day 30 postoperative. Duration of surgery, indication of PPV, and use of laser and/or cryotherapy were noted. Topical corticosteroids were used if mean LFM values were >50, or if there was anterior chamber fibrin. Results: Mean age of the subjects was 48.62 ± 10.07 years. The preoperative LFM value for 50 subjects was 17.42 ± 25.20. Topical corticosteroids were initiated in only 22 patients. The LFM values of subjects were not different from baseline at 1 month whether or not the subjects received corticosteroids (p > 0.106). Conclusions: With 25-G PPV, there is minimal breakdown of blood-aqueous barrier. LFM helps in monitoring postoperative inflammation, obviating the need for topical corticosteroids in significant number of patients. [ABSTRACT FROM AUTHOR]

We investigated the effects of tyrosol (Tyr) on anterior chamber paracentesis (ACP)-induced anterior uveitis in beagle dogs, as determined by protein and prostaglandin E2 (PGE2) concentrations in the aqueous humor (AH). Tyr at a dose of 100 or 200 mg/kg or 2.2 mg/kg of carprofen as a positive control was administered orally twice daily from 2.5 days before paracentesis. The initial ACP was performed in one eye of individual dogs and 0.5 ml AH was aspirated. The secondary AH was collected 60 min later. Pretreatment with 200 mg/kg of Tyr and carprofen significantly decreased aqueous protein and PGE2 concentrations compared to the control group. Overall, these findings suggested that Tyr was useful for the management of canine anterior uveitis. [ABSTRACT FROM AUTHOR]

Background: Considering the effect of beclomethasone on allergic rhinitis or nasal polyps, it has been attempted to find the best method of using this drug to have the maximum effect and increase the patients' satisfaction. Therefore, the aim of this study was to compare the efficacy of beclomethasone aerosol and aqueous nasal sprays in the patients with nasal polyps. Materials and Methods: This double-blind randomized clinical trial was conducted on 60 patients with nasal polyps. The patients were divided into two groups. The first group (beclomethasone dipropionate aqueous [BD-AQ] group) was treated with daily two puffs of beclomethasone aqueous nasal spray 50 μg in each nostril, and the second group (beclomethasone dipropionate aerosol [BD-A] group) was treated with two puffs of aerosol beclomethasone 50 μg in each nostril daily for 6 months. At the beginning of the study, the sino-nasal outcome test-22 (SNOT-22) and Lund-Mackay scores were recorded after the evaluation of disease status and the severity of symptoms. Results: The results of this study demonstrated that the mean changes in Lund-Mackay and SNOT-22 scores (83 ± 6.30 and 4.25 ± 31.60, respectively) in the BD-A group were significantly higher than the BD-AQ group (2.01 ± 3.87and 9.83 ± 24.13, respectively) (P < 0.05), but there was no significant difference in the patients' satisfaction between the two groups (P > 0.05). Conclusion: According to the results of this study, patients with nasal polyps showed a significant improvement following both the interventions, but the disease severity in the BD-A group was significantly higher than the BD-AQ group based on the mean values of Lund-Mackay score.

The blood-aqueous barrier plays a key role in regulating aqueous humor homeostasis by selectively restricting passage of proteins into the eye. The kinetics of aqueous flow are traditionally measured using artificial markers; however, these marker molecules do not address the barrier's selective permeability to plasma proteins. Here we applied stable isotope labeling of all serum proteins with nitrogen-15 (15N) atoms. Following systemic injection of this "heavy" serumin mice, the 15N-to-endogenous nitrogen-14 (14N) ratio of each protein in aqueous wasmeasured bymass spectrometry. By monitoring the kinetic changes in these ratios, we determined the permeability profiles of hundreds of serum proteins. Meanwhile, we subjected one of the eyes to neoangiogenic wound healing by inflicting injury to the corneal limbus and compared the 15N proteomes between the normal eyes and the recovering eyes at 2 weeks after injury. In the injured eye, we detected markedly enhanced permeability to inhibitory complement regulator proteins, such as Cfh, Cfhr, Cfb, Cfi, Cfd, and Vtn. Many of the proteins in this group are implicated in age-related macular degeneration associated with leakage of the blood-retinal barrier due to inflammation. To rule out the possibility that the observed leakage was due simply to physical damage of the blood vessels, we separately created a neovascularization model using an alkali burn of the avascular cornea. In this latter model, elevated levels of Cfh and Cfb were evident. These findings suggest that ocular neovascularization is associated with enhanced permeability to serum complement regulators. [ABSTRACT FROM AUTHOR]

The eye is protected by several tissues that limit the permeability and entry of potentially harmful substances, but also hamper the delivery of drugs in the treatment of ocular diseases. Active transport across the ocular barriers may affect drug distribution, but the impact of drug transporters on ocular drug delivery is not well known. We have collected and critically reviewed the literature for ocular expression and activity of known drug transporters. The review concentrates on drug transporters that have been functionally characterized in ocular tissues or primary cells and on transporters for which there is available expression data at the protein level. Species differences are highlighted, since these may explain observed inconsistencies in the influence of specific transporters on drug disposition. There is variable evidence about the pharmacokinetic role of transporters in ocular tissues. The strongest evidence for the role of active transport is available for the blood-retinal barrier. We explored the role of active transport in the cornea and blood retinal barrier with pharmacokinetic simulations. The simulations show that the active transport is important only in the case of specific parameter combinations. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the significance of the anterior ciliary vessels (ACVs) preservation during the conventional horizontal strabismus surgery. Methods: Patients (≥ 8 years) with horizontal strabismus were randomly allocated into group 1 (with ACV preservation) and group 2 (without ACV preservation). The surgical eyes in group 1 were further divided into group A (one rectus muscle operated) and group B (two rectus muscles operated). Similarly, eyes in group 2 were divided into group C (one rectus muscle operated) and group D (two rectus muscles operated). The success rate of ACV preservation was calculated. The anterior chamber flare measurements of each eye by laser flare photometry were recorded on the day prior to and after operation. The flare values between groups and between pre- and post-operation in each group were compared by one-way analysis of variance and a paired t-test respectively. Results: In groups A and B, the success rate of ACV preservation was 82% (27/33) and 70% (28/40)respectively, and the flare values between pre- and post-operation showed no significant differences(4.378 ± 1.527, 4.544 ± 1.452, P = 0.526; 4.625 ± 1.090, 4.989 ± 1.468, P = 0.101 respectively). However, the postoperative values were significantly increased in group C and group D(4.661 ± 1.031, 5.039 ± 1.310, P = 0.025; 4.933 ± 1.691, 5.502 ± 1.430, P = 0.000 respectively). The postoperative flare readings of group D were significantly higher than group B, while group A and group C had no significant variation. Conclusion: ACV preservation probably has clinical significance in reducing the undesirable influence on the blood-aqueous barrier. [ABSTRACT FROM AUTHOR]

Purpose Of Review: The purpose of this review is to determine the prevalence of uveitis in the diabetic population, the clinical features of the uveitis and diabetes when coexisting and pathophysiology of a possible correlation. We also aim to review the cases of diabetes and uveitis in the literature.Recent Findings: The basis of an association between uveitis and diabetes mellitus (DM) is the common pathophysiology of inflammation. There are several reports on a DM-related uveitis, defined as idiopathic anterior uveitis in the presence of poorly controlled DM, but causation has not been established. There are conflicting results in the literature regarding an association between uveitis and DM. More studies are needed to determine if an association truly exists. [ABSTRACT FROM AUTHOR]

A slit-lamp examination is an indispensable and essential clinical evaluation method in ophthalmology, but, it is qualitative subjective. To complement its weaknesses in making a quantitative evaluation of flare intensity and number of cells in the aqueous humor in the eye, we invented the laser flare-cell photometer in 1988. The instrument enables a non-invasive quantitative evaluation of flare intensity and number of cells in the aqueous with good accuracy and repeatability as well as maneuverability equal to slit-lamp microscopy. The instrument can elucidate the pathophysiology in the blood-aqueous barrier (BAB) function in a variety of ocular disorders. The accuracy of the instrument makes it possible to investigate not only the pathophysiology of intraocular disorders but also the effects of various drugs and surgical procedures in BAB. The instrument does not only lighten the burden on patients in clinical examinations and study but it also helps minimize the sacrifice of experimental animals and improves the reliability of the results by minimizing inter-individual variations through its good repeatability. Here I shall relate how the instrument has been applied to clinical and basic studies in ophthalmology and what novel knowledge its application contributed to pathophysiology in ophthalmology. [ABSTRACT FROM AUTHOR]

The permeability of iris blood vessels has an important role in maintaining aqueous humor (AH) homeostasis, contributing to variation in iris volume and probably the pathogenesis of angle closure glaucoma. This study investigates the permeability of the iris microvasculature to plasma-derived protein and correspond it with the morphologic characteristics of vascular mural cells (MCs). Twenty-two enucleated porcine eyes were used in this study. 12 eyes were micro-perfused with vehicle alone as control or with FITC-albumin as a marker of protein leakage and histological sections subsequently made to examine for FITC-albumin presence. The other 10 eyes were immunolabeled via micro-perfusion for αSMA and VE-cadherin to investigate their topographic distribution in the porcine iris vasculature, and to cross correspond with the locations of FITC-albumin deposits. Distribution of FITC-signals exhibited a site-dependent pattern and time-dependent change in the iris. Fluorescence was initially detected around capillaries in the superficial and deep layer of the iris microvascular network. The pupillary region and the iris root retained more fluorescent signal than the iridal ciliary region. At low magnification, αSMA labelling displayed a regional variation which was inversely correlated with vascular permeability. At the cellular level, αSMA labeling corresponded with vascular MCs distribution in the iris vascular network. The correspondence between iris microvascular permeability to FITC-albumin and the pattern of αSMA distribution and MCs coverage adds to the understanding of the elements comprising the blood-aqueous barrier with implications for the bio-mechanics of iris volume change. • Iris vasculature showed zone- and layer-specific permeability to FITC-albumin. • FITC- albumin permeability is inversely correlated with αSMA distribution in iris vasculature. • αSMA was present in endothelial cells throughout the iris vasculature. [ABSTRACT FROM AUTHOR]

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.

Background: The blood-aqueous barrier (BAB) separates immunoprivileged tissue of the eye from the blood circulation. Disruption of the BAB is therefore a risk factor for rejection after keratoplasty., Purpose: The present work provides a review of the work of our group and others on BAB disruption in penetrating and posterior lamellar keratoplasty and its implications for clinical outcome., Methods: A PubMed literature search was performed to generate a review paper., Results: Laser flare photometry provides an objective and reproducible method to assess the integrity of the BAB. Studies of the flare after penetrating and posterior lamellar keratoplasty demonstrate a mostly regressive disruption of the BAB in the postoperative course, which is influenced in extent and duration by multiple factors. Persistently elevated flare values or an increase in flare after initial postoperative regeneration may indicate an increased risk of rejection., Discussion: In case of persistent or recurrent elevated flare values after keratoplasty, intensified (local) immunosuppression may potentially be useful. This could become important in the future, especially for the monitoring of patients after high-risk keratoplasty. Whether an increase of the laser flare is a reliable early indicator of an impending immune reaction after penetrating or posterior lamellar keratoplasty has to be shown in prospective studies., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht./The authors declare that there is no conflict of interest., (Thieme. All rights reserved.)

Purpose: Periodontitis causes low-grade systemic inflammation e.g., through circulatory periodontal endotoxins, and it has been associated with cardiovascular morbidity and wet age-related macular degeneration., Methods: To assess the association between clinical severity of periodontitis and aqueous flare levels in the eyes. Patients with periodontitis (N = 15) who underwent periodontal treatment by a specialized dentist between the years 2020 and 2021 at the Chin and Mouth Disease Unit, Kymenlaakso Central Hospital, Kotka, Finland were enrolled. Aqueous flare levels, a surrogate marker for blood-aqueous and blood-retinal-barrier disruption, were measured using Laser Flare Meter (FM-600, Kowa Company, Ltd., Nagoya, Japan) before and right after the periodontal treatment and at 3 months. The number of teeth, periodontal probing depth (PPD), periodontal pathogens and antimicrobial treatment were recorded., Results: At baseline, aqueous flare levels correlated with the number of clinically-relevant PPD (>5 mm) pockets (R = 0.789, P  < 0.001) and inversely correlated with the number of teeth (R = -0.587, P  = 0.035). At baseline, aqueous flare levels were 15.39 ± 13.24 photon units (pu)/ms among patients with periodontal pathogens, compared with 3.29 ± 1.67 pu/ms among those without any peridontal pathogens in PCR ( P  = 0.018). At 3 months compared to baseline values, aqueous flare levels were reduced to <50% from baseline among 6 patients (40%), whereas the levels increased to >200% from baseline in 1 patient (7%) (repeated measures ANOVA, P  < 0.026)., Conclusions: Poor periodontal status was associated with blood-ocular-barrier breakdown. These findings could expand our understanding of the potential mechanisms and therapeutic targets against retinal vascular diseases and systemic comorbidities in patients with periodontitis.

A laser flare-cell meter was used to examine blood-aqueous barrier function in a 57-year-old male patient who had typical reticular dystrophy of the retinal pigment epithelium with a bilateral hyperpigmented reticular pattern at the posterior pole in both eyes. Fluorescein angiography showed hypofluorescent reticular net resembling a fishing net with knots associated with a central diffuse hyperfluorescence. Dark adaptation test revealed that the final rod threshold was elevated. Laser photometry showed an increase in the aqueous flare intensity in both eyes, as compared to the results in normal subjects. Quantitative measurement of the aqueous flare intensity by a laser flare-cell meter might indicate abnormalities in the blood-aqueous barrier in patients with reticular dystrophy of the retinal pigment epithelium.

The purpose of this study is to compare the effect of topical diclofenac and topical dexamethasone on anterior chamber flare and postoperative pain following rhegmatogenous retinal detachment (RRD) surgery. This prospective study included 40 eyes of 40 patients treated for RRD. Twenty-eight patients underwent scleral buckling and 12 patients underwent 20-gauge pars plana vitrectomy (PPV). For each surgical procedure, patients were postoperatively randomly divided into two groups: the first group received topical dexamethasone phosphate 0.1 % four times daily for 28 days; the second group received topical diclofenac sodium 0.1 % three times daily for 28 days. The inflammatory reaction in the anterior chamber was measured with laser flare photometry preoperatively and 1, 7, 14, 28, and 90 days postoperatively. Pain level was evaluated with Scott's visual analog scale at day 1, 7, 14, and 28 postoperatively. For patients treated with scleral buckling, there was no significant difference between the two groups regarding mean aqueous flare at day 1 ( p = 0.096), day 7 ( p = 0.435), day 14 ( p = 0.510), day 28 ( p = 0.583), and day 90 ( p = 0.423). The group who received diclofenac had significantly lower pain score at days 7, 14, and 28 ( p = 0.048, p = 0.017, and p = 0.028, respectively). For patients treated with PPV, there was no significant difference between the two groups regarding mean aqueous flare at day 1 ( p = 0.400), day 7 ( p = 0.728), day 14 ( p = 0.843), day 28 ( p = 0.939), and day 90 ( p = 0.568). Patients who received diclofenac had significantly lower pain score at days 7, 14, and 28 ( p = 0.032, p = 0.030, and p = 0.023, respectively). Topical diclofenac seems to be as potent as topical dexamethasone in managing postoperative inflammatory response induced by surgery for RRD with better analgesic effect. Both of them are consequences of blood-aqueous barrier and blood-retinal barrier breakdown. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The majority of trabecular outflow likely crosses Schlemm's canal (SC) endothelium through micron-sized pores, and SC endothelium provides the only continuous cell layer between the anterior chamber and episcleral venous blood. SC endothelium must therefore be sufficiently porous to facilitate outflow, while also being sufficiently restrictive to preserve the blood-aqueous barrier and prevent blood and serum proteins from entering the eye. To understand how SC endothelium satisfies these apparently incompatible functions, we examined how the diameter and density of SC pores affects retrograde diffusion of serum proteins across SC endothelium, i.e. from SC lumen into the juxtacanalicular tissue (JCT). Opposing retrograde diffusion is anterograde bulk flow velocity of aqueous humor passing through pores, estimated to be approximately 5 mm/s. As a result of this relatively large through-pore velocity, a mass transport model predicts that upstream (JCT) concentrations of larger solutes such as albumin are less than 1% of the concentration in SC lumen. However, smaller solutes such as glucose are predicted to have nearly the same concentration in the JCT and SC. In the hypothetical case that, rather than micron-sized pores, SC formed 65 nm fenestrae, as commonly observed in other filtration-active endothelia, the predicted concentration of albumin in the JCT would increase to approximately 50% of that in SC. These results suggest that the size and density of SC pores may have developed to allow SC endothelium to maintain the blood-aqueous barrier while simultaneously facilitating aqueous humor outflow. [ABSTRACT FROM AUTHOR]

AIM: To explore the clinical value of quantitative determination of aqueous flare in patients with uveitis by FM-600 laser flare cell meter(LFCM). METHODS:According to clinical manifestation, 129 patients(171 eyes)with uveitis were divided into 3 groups in our hospital from July 2009 to July 2010: 87 cases(87 eyes)in anterior uveitis group, 10 cases(20 eyes)in intermediate uveitis group, 32 cases(64 eyes)in posterior uveitis group. The other 50 cases(100 normal eyes)were in the control group. Flare in patients with uveitis at different stages was graded and measured by LFCM(FM-600)and slit-lamp microscope. RESULTS: Flare of grade 1+, 2+, 3+ and 4+ were noted in 48, 35, 2 and 2 eyes in anterior uveitis patients, respectively. LFCM examination revealed that the mean flare values in anterior uveitis eyes with flare of grade 1+ and 2+ were 28.6±6.7pc/ms and 144.3±28.1pc/ms, and 5.1±1.8pc/ms in the control group. In patients with flare of grade 3+ and 4+, LFCM readings were unreliable because of increased background noise. The differences between the two groups were statistically significant(Pr=0.901, PPr=0.867, PPCONCLUSION:LFCM(FM-600)is able to evaluate precisely the mild and moderate breakdown of blood aqueous barrier in uveitis, therefore it provides an important parameter for the determination of inflammatory response in anterior segment and the clinical treatment of uveitis.

Graft rejection is still the major obstacle causing corneal transplantation failure. However, the underlying pathogenesis remains largely unclear. The iris-ciliary body (I–C) is enriched with blood vessels and various immune cell populations, presumably predisposed to be involved in corneal transplantation rejection. After penetrating keratoplasty, compared to the normal (Nor) and syngeneic (Syn) groups, I–C tissues in the allogeneic (Allo) group displayed stronger alloimmune responses, with more infiltrations of CD45+ inflammatory cells and CD3+ lymphocytes, increased transcriptional levels of pro-inflammatory cytokines, and elevated NF-κB activity. This histopathology was similar to the pathological alterations of corneal allografts. Angiography analysis revealed the abnormal vasculature in the iris during allograft rejection, characterized by vasodilatation, increased vessel density, and vascular permeability. While, immunofluorescence staining showed the intact tight junction of the posterior iris epithelium. In vitro , human microvascular endothelial cells (HMECs) stimulated by tumor necrosis factor-α (TNF-α) showed an increased Evans blue (EB)-albumin leakage, with lower expression of zonula occludens-1 (ZO-1) and Occludin. The increased EB-albumin leakage, up-regulated NF-κB activity, and reduced expression of ZO-1 and Occludin could be partially reversed after cyclosporine A (CsA) administration. In contrast, the barrier function in primary mouse iris pigment epithelial cells (IPEs) after TNF-α treatment remained largely unchanged. These findings revealed the vigorous alloimmunity in I–C tissues, characterized with impaired vascularization but intact posterior epithelial barrier in the iris, which allowed proteins and immune cells to be exudated from the front surface of I–C tissues, and facilitated immune reaction in the anterior chamber, thereby contributing to aggravated corneal transplantation rejection. • During corneal transplantation rejection: • Iris-ciliary body showed vigorous alloimmunity. • Iris experienced impaired vascular barrier. • The posterior epithelium barrier in iris sustained. • Iris-ciliary body predisposed to be involved in the process. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association between anatomical features of rhegmatogenous retinal detachment (RRD) and the extent of blood-aqueous barrier disorder measured by non-invasiv laser flare photometry., Methods: Retrospective evaluation of consecutive patients with RRD that underwent surgery between November 2016 and October 2018. Descriptive evaluation of pre- and postoperative parameters and correlation to preoperative laser flare value, extent of retinal detachment and re-detachment rate were performed., Results: 266 patients (mean age 62.73 ± 10.40 years, 62.8% male) were included. Mean preoperative flare value was 11.0 ± 11.9 pc/ms. In pseudophakia flare values were higher than in phakia (12.7 ± 10.4 pc/ms versus 9.8 ± 12.9 pc/ms; p  = 0.042). Flare increased and correlated significantly with the number of affected retinal quadrants (Q) (1 Q 6.4 ± 3.3 pc/ms; 2 Q 10.5 ± 8.8 pc/ms; 3 Q 15.6 ± 9.1 pc/ms; 4 Q 27.5 ± 33.3 pc/ms; p  < 0.001; r  = 0.40). Macular status correlated significantly with flare values (macula on 8.6 ± 7.1 pc/ms, off 13.1 ± 15.0 pc/ms; p  = 0.004; r  = 0.17)., Conclusion: The level of objective tyndallometry in RRD seems to be influenced by lens status and extent of retinal detachment. Thus, the greater the affected retinal area is, the more blood-aqueous barrier disruption seems to be present.

Purpose: To evaluate renal function in patients with pseudoexfoliation syndrome. Materials and Methods: This prospective, cross-sectional, case-control study involved 49 patients with pseudoexfoliation syndrome (PEX) and 42 control subjects. Renal function was examined by biochemical parameters and Doppler ultrasonography. Serum creatinine, blood urea nitrogen, urea levels, urine microalbumin level and creatinine clearance were measured. Renal volume, resistive index and pulsatility index were calculated using Doppler ultrasonography. Results: The mean laboratory values for both groups were as follows: Creatinine, PEX: 0.81 ± 0.28 mg/dL - Control: 0.79 ± 0.22 mg/dL; urea, PEX: 31.6 ± 9.7 mg/dL - Control: 32.2 ± 8.4 mg/dL; blood urea nitrogen, PEX: 14.8 ± 4.6 mg/dL - Control: 15.1 ± 4.0 mg/dL; creatinine clearance, PEX: 89.1 ± 35.6 mL/min - Control: 99.0 ± 47.2 mL/min; microalbumin, PEX: 5.8 ± 22.7 mg/dL - Control: 2.7 ± 6.0 mg/dL. The differences between groups were not significant ( p > 0.300). Renal volume, resistive index and pulsatility index values were similar in both groups ( p > 0.200). Conclusions: This study showed that pseudoexfoliation syndrome does not affect biochemical and ultrasonographic parameters associated with renal function. [ABSTRACT FROM AUTHOR]

Objective To investigate fibrinolytic activity in aqueous humor ( AH) of healthy and sick dogs, with and without cataracts. Procedure Prospective observational clinical study. A total of 45 dogs were included in the study. Physical and ophthalmic examinations, complete blood cell count ( CBC) and serum biochemistry panel were performed in all animals. According to the ocular and systemic diagnoses, animals were classified into three groups: sick dogs without cataracts (20 dogs; 40 eyes), diabetic dogs with cataracts (11 dogs; 22 eyes), and healthy dogs with cataracts (14 dogs; 25 eyes). Bilateral AH and blood samples were collected during intraocular surgery (25 dogs; 47 eyes), or immediately after euthanasia (20 dogs; 40 eyes). Citrated samples were centrifuged and stored at −81 °C until analysis. Plasma and AH D-dimer concentration were determined using a quantitative immunoturbidimetric latex agglutination assay. Results A total of 108 canine samples (45 plasma and 87 AH samples) were obtained. D-dimer concentration in log-scale, in AH of eyes with diabetic cataract was significantly higher than AH of eyes with nondiabetic cataract, with a difference of 0.9 ng/mL 95% confidence interval ( CI) (0.2; 1.6) P = 0.0116 and higher than that of sick animals with healthy eyes, with a estimated difference of −0.89 ng/mL 95% CI (−1.52; −0.25) P = 0.0061. Plasma D-dimer concentration was significantly higher in the group of animals with systemic disease [median 606 ng/mL, Interquartil Range ( IQR) 145-1956 ng/mL] than in healthy dogs (median 47.5 ng/mL, IQR 4-250 ng/mL) ( P = 0.002) and diabetic dogs (median 60.5 ng/mL, IQR 0-147.5 ng/mL) ( P < 0.001). Conclusion AH fibrinolysis is present in dogs, being significantly higher in animals with diabetic cataracts than in those without cataracts, and those with nondiabetic cataracts. [ABSTRACT FROM AUTHOR]

Abstract: An elevated aqueous humor protein level (aka flare) has always been considered to represent a pathological breakdown of the blood-aqueous barrier (BAB), regardless of the etiology. Recent studies in humans, using magnetic resonance imaging (MRI) to directly observe BAB kinetics in the posterior chamber of the human eye in-vivo, showed that pilocarpine-induced flare resulting from administration of a single drop of pilocarpine is not the result of breakdown of the BAB in the ciliary body. These MRI studies could not confirm whether pilocarpine caused an increase in iris vascular permeability. In the current studies we completed combined cell-flare meter and intravascular tracer studies, using intravenous horseradish peroxidase (HRP) in rabbits. One hour after receiving 3% pilocarpine in one eye, pupil size significantly decreased and aqueous flare significantly increased in pilocarpine-treated eyes. Light and electron microscopy demonstrated no leakage across either the iris vascular endothelium or the non-pigmented ciliary epithelium in either pilocarpine-treated or control eyes. One animal received HRP directly after pilocarpine to control for a transient increase in permeability before the peak flare response occurred. No leakage was found in the ciliary body or iris of this animal. Additional animals received topical pilocarpine in one eye but after 1 h they were sacrificed without tracer studies. Uveal tissues from these animals were used to assess the distribution of non-HRP protein in the ocular anterior segment and to assess the amount of elutable protein in the iris stromas of both treated and untreated eyes. Immunohistochemistry confirmed the presence of a reservoir of protein in the iris stroma. Analysis of elutable total protein from the iris stroma of pilocarpine-treated and control eyes showed significantly less total elutable protein in pilocarpine-treated eyes. Eyes with the greatest percent change in pupil size (i.e. the strongest miosis) correlated with lowest amounts of residual protein in the iris stroma. The tracer studies confirmed recent MRI studies in humans showing that the source of pilocarpine-induced flare is not disruption of the ciliary epithelial barrier. Extending this work, the current studies also showed no pilocarpine-induced leakage from the iris vasculature. The elutable protein experiments suggested that a primary source of pilocarpine-induced flare was extrusion of a portion of the reservoir of protein in the iris stroma. Taken together, these studies strongly suggest that not all clinically observable flare results from breakdown of the BAB. [Copyright &y& Elsevier]

Intraocular inflammation causes disruption of the blood-ocular barriers and entry of proteins and inflammatory cells into the aqueous humor. Slit-lamp examination allows only a subjective and arbitrary grading of cells and flare (protein) in the anterior chamber. Laser flare photometry is the only objective and quantitative method to reliably measure intraocular inflammation. Flare measurements by laser flare photometry enables exact monitoring of both acute and chronic uveitic entities. Recent studies showing the predictive value of flare levels for disease outcomes have revolutinized therapeutic approach in uveitis, placing flare to the center of inflammatory parameters to be targeted for better outcomes. [ABSTRACT FROM AUTHOR]

Toxoplasmic retinochoroiditis is deemed a local event, which may fail to evoke a detectable systemic immune response. A correct diagnosis of the disease is a necessary basis for estimating its clinical burden. This is not so difficult in a typical clinical picture. In atypical cases, further diagnostic efforts are to be installed. Although the aqueous humor may be analyzed for specific antibodies or the presence of parasitic DNA, the DNA burden therein is low, and in rare instances a confirmation would necessitate vitreous sampling. A laboratory confirmation of the diagnosis is frustrated by individual differences in the time elapsing between clinical symptoms and activation of specific antibody production, which may result in false negatives. In congenital ocular toxoplasmosis, a delay in the onset of specific local antibody production could reflect immune tolerance. Herein, the authors attempt to provide a simple and practicable algorithm for a clinically tailored diagnostic approach in atypical instances. [ABSTRACT FROM AUTHOR]

The purpose of this article is to discuss the literature on the clinical role of the ocular fluorophotometer in different ocular conditions. The ocular fluorophotometer measures the fluorescent compounds present in the cornea, lens, vitreous body and retinal pigment epithelium. These compounds can be present naturally, known as autofluorescent, or fluorescent after application of fluorescein either topically or systemically. The fluorophotometer measures the changes in barrier function in both corneal epithelium and endothelium. It is a quantitative method of detecting a breakdown in the blood-ocular barriers. It helps to measure the inward and outward movements of fluorescein across the blood-retinal barrier as well as blood-aqueous barrier permeability. The measurement of ocular barrier permeability by the fluorophotometer helps to improve our understanding of ocular conditions. It is also useful to assess the effect specific therapeutic approaches in some diseases and clinical research. [ABSTRACT FROM AUTHOR]

Purpose To quantitatively evaluate aqueous flare and cells in patients with Behcet's disease. Methods This study included 30 Behcet's patients (52 eyes) with active uveitis. The patients were treated with immunosuppressive agents. Aqueous flare and cells were quantified using the laser flare-cell photometry before treatment and 1 and 2 months after treatment. Result Before treatment, mean aqueous flare (ph/ms) in Behcet's eyes was 25.7 ± 20.5. After treatment, flare values were significantly reduced after 1 and 2 months compared with those before treatment. No significant difference was found between flare values after 1 and 2 months. Before treatment, mean cell counts (cells/0.5 mm) in Behcet's eyes were 23.2 ± 29.4. After treatment, cell counts were also significantly reduced after 1 and 2 months compared with those before treatment. Cell counts were further significantly reduced from 1 to 2 months. Conclusion Both aqueous flare and cells were significantly increased in Behcet's patients with active uveitis and improved after a two-month treatment. Breakdown of the blood-aqueous barrier lasts longer than aqueous cells in these patients. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

Objective To determine the effects of 0.005% latanoprost and 2% dorzolamide/0.5% timolol on the blood-aqueous barrier (BAB) in normal dogs. Animals studied Eight mixed-breed and pure-breed dogs. Procedures Baseline anterior chamber fluorophotometry was performed on eight normal dogs. Sodium fluorescein was injected and the dogs were scanned 60–90 min post-injection. Seventy-two hours following the baseline scan, one eye received one drop of latanoprost. Fluorophotometry was repeated 4 h after drug administration. Following a washout period, the identical procedure was performed 4 h after the administration of dorzolamide/timolol. The degree of BAB breakdown was determined by comparing the concentrations of fluorescein within the anterior chamber before and after drug administration. BAB breakdown was expressed as a percentage increase in the post-treatment fluorescein concentration over the baseline concentration: %INC [Fl] = {([Fl]post – [Fl]baseline)/[Fl]baseline} × 100. The percentage increase in fluorescein concentration in the treated eye was compared to that in the nontreated eye using a paired t-test with significance set at P ≤ 0.05. Results Following administration of latanoprost, the fluorescein in the treated eyes increased 49% (± 58%) from baseline compared to 10% (± 31%) in the untreated eyes ( P = 0.016). Following administration of dorzolamide/timolol, the fluorescein concentration increased 38% (± 54%) compared to baseline vs. 24% (± 38%) in the untreated eyes ( P = 0.22). Conclusions The results of this study show that topical latanoprost may cause BAB disruption in normal dogs while topical dorzolamide/timolol may have no effect on the BAB in normal dogs. [ABSTRACT FROM AUTHOR]

Abstract: There are two main blood-ocular barriers, the blood-aqueous barrier and the blood-retinal barrier. The blood-aqueous barrier is formed by the nonpigmented ciliary epithelium of the ciliary body and the vascular endothelium of the iris vessels. The blood-retinal barrier is formed by the vascular endothelium of the retinal vessels and the retinal pigment epithelium. Four methods of examination are currently used to study the function of blood-ocular barriers. Among these, laser flare-cell photometry is a noninvasive, quantitative method to evaluate the permeability of the blood-aqueous barrier. Vitreous fluorophotometry is an excellent technique to quantitate blood-retinal barrier function. Fluorescein angiography and optical coherence tomography are excellent qualitative imaging techniques to evaluate blood-retinal barrier function. Current basic research shows prostaglandin E2 and other mediators may produce breakdown of the blood-aqueous barrier, and vascular endothelial growth factor plays an important role in the breakdown of the blood-retinal barrier. Retinal laser photocoagulation can induce breakdown of both the blood-aqueous and blood-retinal barriers in pigmented rabbits. The four methods of examination described herein are excellent measures for clinical application to evaluate blood-ocular barrier function in various ocular diseases, many of which are discussed here. [Tzu Chi Med J 2008;20(1):25–34] [Copyright &y& Elsevier]

Intraocular levels of ofloxacin are documented after topical and systemic administration, but systemic administration of ofloxacin in ocular compression has not yet been studied. This study was undertaken to determine the intraocular penetration of systemic ofloxacin into aqueous and vitreous humor after the application of ocular compression in rabbit eyes. Ocular compression with the Honan balloon was applied for 30 min to the right eyes of 11 albino New Zealand white rabbits. After the application of ocular compression, 2 mg/mL of ofloxacin was administered intravenously. Samples from aqueous and vitreous humor were collected 30 min after infusion. Ofloxacin concentrations were determined through high-performance liquid chromatography. The mean aqueous level of ofloxacin was significantly higher in the compression group (2.40±1.00 gmg/mL) than in the no-compression group (1.61 ±1.06 μg/mL) ( P < .05). The mean vitreous concentrations of ofloxacin were 0.70+-0.33 μg/mL and 0.50±0.18 μg/mL in the compression and no-compression groups, respectively. A significant difference was observed between vitreous levels of ofloxacin in the compression and nocompression groups ( P < .05). Ocular compression enhanced the penetration of ofloxacin in both aqueous and vitreous humor. The drug level in the aqueous humor was sufficient for the minimum inhibitory concentration for 90% of isolates (MIC90) to inhibit most microorganisms. Although the mean vitreous ofloxacin concentration was increased by previous ocular compression, it was not sufficiently above the MIC90 for most ocular pathogens that caused endophthalmitis. [ABSTRACT FROM AUTHOR]

Purpose : To examine the role of EP 2 and EP 4 receptors in murine ocular inflammation. Methods : Prostaglandin EP 2 and EP 4 receptor knockout and wild-type mice were treated topically with prostaglandin E 2 , SDF-1, and RANTES and lipopolysaccharide by intravitreal injection. Paracentesis was performed by puncturing the cornea. The increase in the level of aqueous humor protein and the number of leukocytes were measured and the vascular leakage of protein was visualized using fluorescein angiography. Results : In the EP 2 receptor knockout mice, there was significant inhibition of the disruption of the blood-aqueous barrier caused by lipopolysaccharides, paracentesis, prostaglandin E 2 , SDF-1, and RANTES. Reductions in the disruption in the blood-aqueous barrier and leukocyte infiltration after lipopolysaccharide injection and paracentesis were significant, but there was no increase in the aqueous humor protein level after prostaglandin E 2 treatment in EP 4 receptor knockout mice. Conclusions : The results of the present experiments suggest that EP 2 and EP 4 receptors partly mediate the disruption of the blood-aqueous barrier and leukocyte infiltration induced by prostaglandin E 2 , SDF-1, RANTES, and lipopolysaccharides. [ABSTRACT FROM AUTHOR]