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The aim of this study was to determine the short-term effects of topical tafluprost, a novel prostaglandin F(2) derivative, on feline retinal circulation.Seventeen (17) adult cats were anesthetized with enflurane and mechanically ventilated. One (1) drop of tafluprost (0.0015%; n = 8), latanoprost (0.005%; n = 5), or control vehicle (n = 4) was instilled in 1 eye and the fellow eye was untreated. We measured the intraocular pressure (IOP), vessel diameter, and blood velocity simultaneously for 120 min in the large retinal arterioles and calculated the retinal blood flow (RBF) with a laser Doppler velocimetry system.Tafluprost 0.0015% significantly increased RBF (maximum change, 42.8 +/- 4.2% [mean +/- standard error of the mean; P0.01) and blood velocity (maximum change, 24.1 +/- 3.3%; P0.01) for 120 min after instillation; there was no significant change in vessel diameter. Latanoprost 0.005% significantly increased RBF (maximum change, 31.7 +/- 3.4%; P0.05); there was no significant change in vessel diameter and blood velocity. There were no significant differences in the IOP reduction among the three groups.We observed, for the first time, that topical tafluprost significantly increased RBF in cats, suggesting that dual-action tafluprost may be a beneficial antiglaucomatous agent for reducing IOP and increasing RBF.

To evaluate the effect of nucleotide P2Y(2) receptor agonists INS542 and uridine 5'-triphosphate (UTP) on the outward active transport of fluorescein across rabbit blood-retina barrier (BRB) in vivo.Injection (0.1 ml) of INS542 (0.1 or 1mM), phosphate buffered solution, or UTP (1 or 10mM) was made in Dutch-belted rabbits. Differential vitreous fluorophotometry (DVF) was performed 3hr later and the fluorescein (F)/fluorescein monoglucuronide (FG) ratio was then calculated. F/FG ratios are inversely proportional to outward active transport of F across BRB at the level of the retinal pigment epithelium (RPE). In another set of experiments, the effect of 0.1 ml vitreous injection of INS542 (1mM) on F/FG ratios was evaluated at different time points ranging from 0.5 to 48hr before conducting DVF.F/FG ratios obtained 3hr after intravitreal injection were as follows (mean+/-standard error): 0.49+/-0.14 (0.1mM INS542), 0.19+/-0.04 (1mM INS542), 0.48+/-0.09 (PBS), 0.40+/-0.08 (1mM UTP) and 0.36+/-0.05 (10mM UTP). The F/FG ratio for 1mM INS542 was significantly lower than in the other groups (P0.05). In the time course experiments, a significant decrease in the F/FG ratios was observed between 1 and 12hr following administration of INS542 when compared with F/FG ratios obtained in the contralateral (untreated) eye.Intravitreal administration of INS542 (but not UTP) enhances outward active transport of F across RPE in intact rabbit eye, indicating that activation of P2Y(2) receptors in vivo directly stimulates RPE active transport.

Purpose To describe a newly developed stabilized retinal laser Doppler instrument, to report the reproducibility of retinal blood flow measurements, and to present examples of its clinical application. Design Experimental study. Methods The intrasession, intersession, and interobserver reproducibility of retinal blood flow measurements obtained using the Canon Laser Blood Flowmeter model CLBF 100 was assessed. Intrasession: the coefficients of variation (CV) for repeated measurements (5X) of retinal vessel diameter (D), time-average centerline blood velocity (V av ), and blood flow (F) were calculated at 18 sites along temporal retinal arteries and 18 sites along temporal retinal veins using both eyes in six healthy volunteers. Intersession: the correlation coefficients and average differences between two sets of measurements at the same 36 retinal sites made by one examiner on two different days were calculated. Interobserver: the correlation coefficients and average differences between two sets of measurements at nine sites (five arterial and four venous) in five eyes of five of the volunteers made by two examiners on the same day were calculated. Results from two patients, one with branch retinal vein occlusion (BRVO), and one with central retinal vein occlusion (CRVO), are used to illustrate abnormal retinal circulatory characteristics. Results Intrasession: CV (mean ± SD) for D, V av , and F were 5.5% ± 2.2%, 13.1% ± 6.3%, and 13.8% ± 4.7% in arteries and 3.5% ± 2.1%, 11.9% ± 5.9%, and 12.7% ± 5.5% in veins. Intersession/interobserver: strong correlations between measurements made by one examiner on two different days and by two examiners on the same day were found in D, V av , and F. Average differences in F were 16.4% ± 12.8% for intersession and 12.6% ± 7.0% for interobserver comparisons. Results from the patient with BRVO show marked differences in flow characteristics in the affected quadrant compared with an unaffected quadrant in the same eye, and to the fellow eye. Results from the patient with CRVO show a dramatic improvement in flow characteristics after clearing of the occlusion. Conclusions The reproducibility results and the fact that blood flow is measured in actual units of μl/min indicate that the instrument can be used for reliable comparison of blood flow characterictics at different retinal vascular sites in the same eye, at comparable sites in both eyes, and for comparison between patients and healthy control subjects.

Purpose: To investigate the effect of latanoprost (LP) on the inward and outward permeability (Pin and Pout) of the blood-retinal barrier (BRB). Methods: Four New Zealand white rabbits received topical LP (0.005%) once daily for 3 weeks in one eye and phosphate-buffered saline (PBS) in the fellow eye (topical group). Five New Zealand white rabbits were injected intravitreously with LP (0.1 ml, 0.005%) in one eye and PBS (0.1 ml) in the fellow eye (injection group). In the injection group, vitreous fluorophotometry (VFP) to estimate the Pin and differential vitreous fluorophotometry (DVF) to estimate the Pout were performed 60 min after LP was injected. After the baseline measurements, VFP and DVF were performed 60 and 180 min after intravenous injection of sodium fluorescein, respectively. Fluorescein (F) and fluorescein monoglucuronide (FG) concentrations were obtained by DVF, and the F/FG ratio was calculated as an index of the Pout. Results: In the topical group, there were no significant differences in the Pin or F/FG ratio between the LP- and the PBS-treated eyes. In the injection group, the Pin in the LP-treated eyes was significantly higher than in PBS-treated eyes (p < 0.05). There was no significant difference in the F/FG ratio between the two groups. Conclusion: Although we cannot exclude the effect of differences in species, the physiologic effect of LP, which increased the Pin, was seen in experimental studies. Because antiglaucoma drugs are generally used over an extended period, further clinical studies of the effect of LP on the BRB should be performed in patients who have BRB breakdown, such as in uveitis, and in patients who are pseudophakic and aphakic.

We used scanning laser ophthalmoscope (SLO) microperimetry to evaluate scotomas in patients with clinically significant diabetic macular edema (CSME) in type 2 diabetes mellitus.We studied 19 patients (mean age = 63 years; range, 45-78 years) (19 eyes). SLO microperimetry was performed in all eyes. We divided patients into three groups as follows: dense scotoma, relative scotoma, and no scotoma. The following variables were documented: age; duration of diabetes, hemoglobin A(1c) levels; logarithm of the minimum angle of resolution (Log(MAR)) visual acuity; refractive power; a history of panretinal photocoagulation; presence or absence of proliferative diabetic retinopathy, vitreomacular separation, and cystoid changes; the type of macular edema; and stability of fixation. All variables were compared in the three groups.We identified 4 eyes (21.1%) with dense scotoma, 10 (52.6%) with relative scotoma, and 5 (26.3%) with no scotoma. There were significant differences in log(MAR) visual acuity among those with dense scotoma (1.4 +/- 0.5), relative scotoma (0.6 +/- 0.2), and no scotoma (0.2 +/- 0.3) (P.05), and in the prevalence of cystoid changes, diffuse edema, and unstable fixation among those with dense scotoma (75%, 75%, and 100%, respectively), relative scotoma (20%, 30% and 50%, respectively) and no scotoma (0%, 0% and 0%, respectively) (P.05).Macular scotoma was observed by SLO microperimetry in 74% of the patients in this study. A scotoma in CSME is related to the formation of cystoid changes and the type of macular edema. In eyes with CSME in type 2 diabetes mellitus, a scotoma in the macula causes visual acuity impairment and unstable fixation.

Objective To investigate the relationship between preoperative photoreceptor displacement and postoperative scotoma after unilateral idiopathic macular hole surgery. Design Prospective nonrandomized comparative self-controlled trial. Participants Twenty patients who underwent successful surgery for unilateral idiopathic macular hole participated in the study. Methods Kinetic perimetry using red and green filter glasses, black binocular fixation targets, and red and green selective monocular stimuli was performed preoperatively. Scanning laser ophthalmoscope (SLO) microperimetry was performed preoperatively and postoperatively. Results Sixteen patients had photoreceptor displacement preoperatively. In preoperative SLO microperimetry, all eyes with a macular hole had a scotoma; postoperatively, 12 of 16 had no scotoma. All four eyes with no preoperative photoreceptor displacement were noted to have a postoperative scotoma. The prevalence of postoperative scotoma in patients with preoperative photoreceptor displacement (4 of 16; 25%) was significantly lower than that in patients without preoperative photoreceptor displacement (4 of 4; 100%) ( P = 0.03). Conclusions The presence or absence of photoreceptor displacement preoperatively should affect postsurgical visual function. Photoreceptor damage may occur in eyes without photoreceptor displacement preoperatively, resulting in scotoma postoperatively.

Purpose. To investigate the effect of bucillamine for prevention of increasing blood-retinal barrier (BRB) permeability in streptozotocin (STZ)-induced diabetic rats. Methods. The groups included control and STZ-induced diabetic rats treated with or without bucillamine. Six months after intervention, the concentrations of reduced and oxidative glutathione (GSH and GSSG) in the retina were measured biochemically. In addition, vitreous fluorescein, which leaks from the vessels after intravenous injection of fluorescein sodium, was measured to evaluate BRB permeability. To evaluate the scavenging ability against the reactive oxygen species (ROS) in vitro, the second-order rate constant for the reaction of bucillamine with ROS was estimated from the kinetics based on the rate constant for the reaction of ROS. Results. The BRB permeability was significantly higher (p = 0.01) in diabetic rats not treated with bucillamine, and bucillamine inhibited the BRB permeability. The GSH concentration and the GSH/GSSG ratio in the retinas decreased in diabetic rats not treated with bucillamine; bucillamine inhibited the decrease of the GSH concentrations. The ROS scavenging activity of bucillamine was similar with that of GSH. Conclusions. In diabetic retinas, oxidative stress might increase, which may be one of the causes of BRB breakdown. The antioxidant effects of bucillamine might take part in inhibition of increased permeability of the BRB in diabetes.

Purpose. We investigated the inhibitory effects of bucillamine on formation of laser-induced choroidal neovascularization (CNV) in a rat model. Methods. Bucillamine administration (approximately 150?mg/kg/day) was started 1 week before photocoagulation and continued to the end of the study. Control groups received drinking water. Two weeks after photocoagulation, choroidal neovascularization development was evaluated using simultaneous fluorescein and indocyanine green angiography, and the maximal thickness of the lesions was measured histologically. Results. The incidence of CNV formation was 99.5 ± 0.2% [mean ± standard deviation (SD)] in control rats and 64.3 ± 15.1% with bucillamine (P < 0.01). Histological study showed that the thickness of the CNV lesions was 23.4 ± 6.5 µm (mean ± SD) in the bucillamine-treated rats, which was significantly decreased compared to that in controls (60.8 ± 9.2 µm) (P < 0.01). Conclusions. Our results suggest that bucillamine may inhibit the development of laser-i...

To evaluate serum prorenin levels in preterm infants with or without retinopathy of prematurity (ROP).Noncomparative retrospective case control study.Serum prorenin levels in children with a gestational age younger than 36 weeks were measured with antibody-activating direct enzyme kinetic assay.The mean prorenin concentrations were higher in preterm infants with ROP than in infants without ROP at every time point: from 26 to 30 weeks, 2326 +/- 334 microg/ml (mean +/- SE [standard error]) (n = 3) and 1164 +/- 234 microg/ml (n = 3), respectively (P.05); from 31 to 35 weeks, 1760 +/- 496 microg/ml (n = 10) and 957.1 +/- 139 microg/ml (n = 25) (P.05); from 36 to 40 weeks, 958.2 +/- 194.2 microg/ml (n = 23) and 470.1 +/- 32.6 microg/ml (n = 67) (P.01); and from 41 to 45 weeks, 575.8 +/- 148.4 (n = 9) and 385.6 +/- 47.9 (n = 13), which is not significantly different.Prorenin levels in preterm infants can predict which infants will develop ROP.

To study the early ocular abnormalities in young diabetic patients, corneal and lens autofluorescence was measured by fluorophotometry in 30 eyes of 30 insulin-dependent diabetic patients without retinopathy. The lens [f(l)] and the corneal [f(c)] autofluorescence values in diabetic patients were significantly higher than in controls. In diabetic patients, f(l) was significantly correlated with the duration of diabetes, the f(c) was significantly correlated with the duration of diabetes and the indices of metabolic control, i.e. HbA1c and fructosamine. Our study demonstrated that young diabetic patients clearly had corneal and lens abnormalities before the appearance of overt diabetic retinopathy. The f(c) value might be a good indicator of metabolic control in diabetic patients.

We developed a tree shrew model of diabetes using streptozotocin (STZ), and studied early ocular changes of diabetes (after one week of diabetes) by fluorophotometry. STZ was injected intraperitoneally at doses of sixty to 400 mg/kg body weight. Animals injected with more than 300 mg/kg of STZ developed diabetes. Corneal autofluorescence was significantly increased one week after STZ injection. These changes may be related to impairment of the ocular homeostatic mechanisms due to the onset of diabetes. Using this model, we might be able to obtain diabetic ocular impairment data closer to human data than in previous models of diabetes, because tree shrews are primates.

The effects of topically applied timolol (a nonselective beta-blocker) and UF-021 (a prostaglandin-related compound) on pulsatile ocular blood flow (POBF) were investigated in 9 healthy volunteers. One drop of either UF-021 or timolol was instilled in one randomly selected eye and the fellow eye received physiologic saline. Before and 90 min after drop instillation, we measured intraocular pressure (IOP), POBF, heart rate (HR) and blood pressure (BP). After a washout interval of at least 1 week, the other drug was instilled in the previously treated eye. IOP, POBF, HR, and PB were measured following the same protocol. After timolol administration, IOP and POBF decreased significantly in the treated eye (26%, p = 0.01, and 13%, p = 0.02, respectively) and in the fellow eye (11%, p = 0.01, and 11%, p = 0.03, respectively). HR also decreased (10%, p = 0.03), but BP did not change significantly. After UF-021 administration, no significant changes were found in IOP, POBF, HR, or BP. Our results suggest that in normal subjects timolol decreases POBF in both the treated and the untreated eyes, whereas UF-021 has no action on either IOP or POBF.

We investigated corneal and lens autofluorescence in patients with proliferative diabetic retinopathy (PDR) to determine a correlation between the two parameters and blood glucose levels and HbA1c.Corneal and lens autofluorescence levels in 17 PDR patients and 8 healthy controls were measured with a fluorophotometer fitted with an anterior segment adapter. We measured the lower blood glucose level (BS1), corneal autofluorescence (CA1), and lens autofluorescence (LA1) simultaneously and the higher blood glucose level (BS2), CA2, and LA2 simultaneously on the same day. We defined parameter changes as: delta BS = BS2 - BS1, delta CA = CA2 - CA1, and delta LA = LA2 - LA1.Corneal and lens autofluorescence significantly increased in the patients, compared with the controls (p0.001). Lens autofluorescence had a significant positive correlation with HbA1c (r = 0.656, p0.01) in the patients. delta CA (ngEq/ml) correlated significantly with delta BS (mg/dl) (r = 0.631, P0.01).Results suggest that lens autofluorescence might represent the long-term control of diabetes, and corneal autofluorescence levels may represent short-term changes in the blood glucose level, because hyperglycemia accelerates with increasing corneal autofluorescence in PDR patients. Corneal and lens autofluorescence may be related to the breakdown of the blood-aqueous barrier.

To investigate the serum levels of prorenin and its correlation with the severity of diabetic retinopathy (DR).248 patients with diabetes and 108 control subjects were divided into four groups: no-DR (n = 146), no proliferative diabetic retinopathy (no-PDR) (n = 78), PDR (n = 24), and controls (n = 108). Serum levels of prorenin from all subjects were measured using the new antibody activating direct kinetic (AAD-PR) assay. The serum prorenin levels were compared among the groups.The serum levels of prorenin in the control, no-DR, no-PDR, and PDR groups, respectively, were 109.1 (66.1), 194.6 (160.4), 271.5 (220.3), and 428.4 (358.4) pg/ml (mean (SD)). Prorenin in the PDR group was remarkably high compared with the control and no-DR groups (p0.0001) and with the no-PDR group (p = 0.002). Serum levels of prorenin increased with increasingly severe retinopathy. No correlation was found between the prorenin level and the duration of disease or HbA(1c).The serum levels of prorenin in patients with PDR were found to be markedly high using the AAD-PR assay. Increased levels of prorenin in diabetes may have an important role in the pathogenesis of DR.

In 1981, Hoskin et al 1 described retinal pigment epithelial tears as a newly recognised severe complication of pigment epithelial detachment. Retinal pigment epithelial tears, which may occur either spontaneously or after laser photocoagulation to treat pigment epithelial detachment and choroidal neovascularisation (CNV) in diseases such as age related macular degeneration (AMD), usually cause sudden visual loss at the time of tearing. We report a case of spontaneous bilateral giant tears of the retinal pigment epithelium (RPE). A 79 year old woman was referred on 18 January 2002, because of sudden visual loss in the left eye of 2 weeks’ duration. In October 2001, the patient had undergone bilateral phacoemulsification and lens implantation by her local ophthalmologist. She had no apparent complications postoperatively, and the postoperative visual acuity (VA) was 20/250 in the right eye and 20/20 in the left eye; however, she noticed sudden decreased vision in the left eye on 3 January 2002, and visited the local ophthalmologist 5 days later. When she presented to our hospital, her VA was 20/200 in right eye and hand movements in the left eye. The intraocular pressure was 18 mm Hg in the right eye and 19 mm Hg in the left eye. The external eye examination, pupillary responses, and results …

Background: The effectiveness of losartan for the treatment of leucocyte entrapment in the retinal microcirculation of diabetic rats was evaluated quantitatively. Methods: After diabetes was induced by injection of streptozotocin (STZ), the rats were divided into two subgroups. The first subgroup (n = 6), received no medications; the second subgroup (n = 6) was given fresh drinking water supplemented with losartan (5 mg/kg/day) for 4 weeks. Six rats that were not injected with STZ or given medications served as controls. 4 weeks after intervention, leucocyte dynamics in the retina were observed using acridine orange digital fluorography. Leucocyte entrapment in the retina was compared among the three groups. Results: In the untreated diabetic rats, the number of trapped leucocytes (6.1 (SD 1.4) cells/mm2) increased significantly compared with control rats (2.8 (1.2) cells/mm2; p = 0.005) and diabetic rats treated with losartan (3.1 (0.9) cells/mm2; p = 0.0002). Conclusions: Losartan, an AT1 angiotensin II receptor antagonist, inhibited increased leucocyte entrapment in the diabetic retina. The authors demonstrated that losartan may have therapeutic efficacy in preventing development of diabetic retinopathy. Further clinical studies of the effect of the angiotensin receptor antagonist on preventing development of diabetic retinopathy are needed.

To investigate the inhibitory effects of losartan, an angiotensin receptor antagonist, on angiogenesis in a rat model of laser-induced choroidal neovascularization.Experimental study. Fifteen Brown-Norway male rats received losartan (approximately 5 mg/kg/d) in drinking water, and 15 Brown-Norway male rats received unsupplemented drinking water 1 week before photocoagulation, and it was continued to the end of the study. Two weeks after intense laser photocoagulation, choroidal neovascularization was evaluated by fluorescein angiography and histopathologic evaluation.The incidence of choroidal neovascularization formation was 99.5 +/-.2% (mean +/- standard deviation) in controls and 72.5 +/- 8.8% in losartan-treated rats (P.01). Quantitative morphometric assessment revealed mean choroidal neovascularization lesion thickness of 54 and 44.8 microm, respectively, in controls and losartan-treated rats (P.01).Losartan seems to inhibit development of laser-induced choroidal neovascularization. Angiotensin receptor antagonists may be useful as prophylaxis against choroidal neovascularization associated with age-related macular degeneration.

BACKGROUND Pulsatile ocular blood flow (POBF) is a parameter for evaluating choroidal blood flow. POBF in the patients with non-exudative and exudative age related macular degeneration (AMD) was investigated. METHODS POBF, pulse amplitude (PA), systolic and diastolic blood pressures, intraocular pressure (IOP), refractive error, and axial length were compared among 10 patients with non-exudative AMD, 11 patients with exudative AMD, and 69 age matched controls. A Langham OBF computerised tonometer was used with the participants in the sitting position to measure POBF and PA. RESULTS No significant differences were found in age, systolic and diastolic blood pressures, IOP, or refractive error between patients with exudative and non-exudative AMD and the control subjects. In the patients with exudative AMD the POBF (median, 372.7 μl/min) and PA (median, 1.2 mm Hg) were significantly lower than in the patients with non-exudative AMD (median, 607.0 μl/min (p = 0.02) and 2.2 mm Hg (p = 0.04), respectively) and control subjects (median, 547.4 μl/min (p = 0.01) and 2.0 mm Hg (p = 0.01), respectively). CONCLUSIONS These data show that the POBF and PA in the patients with exudative AMD are lower than in the patients with non-exudative AMD and normal subjects. Decreased choroidal blood flow may have a role in the development of choroidal neovascularisation in AMD.

Nitric oxide (NO) plays an important role in homeostatic vasodilation and the regulation of blood flow. On the other hand, excess release of NO causes various vascular complications. There are only a few reports on the relationship between plasma NO levels and microvascular complications, especially diabetic retinopathy (DR) in patients with type 2 diabetes. The purpose of this study was to determine the relationship between plasma NO levels and DR.In a prospective study, blood samples were obtained from 36 patients with diabetes and no diabetic retinopathy (NDR), 43 patients with nonproliferative diabetic retinopathy (NPDR), 18 patients with proliferative diabetic retinopathy (PDR), and 40 subjects without diabetes mellitus, who served as controls. The levels of plasma NOx (nitrite and nitrate), the stable metabolites of NO, were measured by high-performance liquid chromatography with the Griess method.The plasma NOx levels were 92.8 +/- 16.0, 70.2 +/- 6.8, 90.3 +/- 9.1, and 53.8 +/- 6.1 micromol/l in patients with NDR, NPDR, or PDR, and in the controls, respectively. The plasma NOx levels in the three diabetic groups were significantly higher than those in the control group (P0.05 in each case).The increased plasma NO levels in patients with type 2 diabetes indicate that NO may be associated with the pathogenesis of DR.

To investigate changes in choroidal blood flow (CBF) in the foveal region in patients with type 2 diabetes.Laser Doppler flowmetry was used to determine the CBF in the foveal region in 70 patients with type 2 diabetes and 36 age and sex matched healthy subjects (control group). The patients were classified into three groups: 33 patients (33 eyes) with no diabetic retinopathy (NDR), 20 patients (20 eyes) with non-proliferative diabetic retinopathy and no macular oedema (NPDR/MO-), and 17 patients (17 eyes) with NPDR and MO (NPDR/MO+). Optical coherence tomography was also used to measure the foveal thickness.The group averaged CBF values were 13.5 (4.9), 9.4 (2.5), 10.8 (4.8), and 5.6 (2.0) (arbitrary units) in the control, NDR, NPDR/MO-, and NPDR/MO+ groups, respectively. The group averaged CBF values in the NDR group decreased (30.2%; p0.01) compared with the control group. The average CBF value in the NPDR/MO+ group was also significantly lower (48.2%; p0.01) compared with that in the NPDR/MO- group.The CBF in the foveal region significantly decreases in patients with diabetes, especially those with macular oedema.

To evaluate quantitatively the effects of bucillamine on the entrapment of leukocytes in the retinal microcirculation of diabetic rats.13 male Brown Norway rats were injected with streptozotocin (STZ). After the animals developed diabetes, they were divided into two groups. Group 1 (n=7) received fresh drinking water without bucillamine, and group 2 (n=6) received fresh drinking water supplemented with bucillamine (200 mg/kg per day). Rats that were not injected with STZ and received water without bucillamine served as controls (n=6). Four weeks after the injection of STZ, the leukocytes in the retina were observed by acridine orange digital fluorography. The number of leukocytes trapped in the retinal vessels was compared among the three groups.In the untreated diabetic rats, the number of trapped leukocytes was significantly higher than in control rats or bucillamine-treated diabetic rats (P0.05).We demonstrated an inhibitory effect of bucillamine on leukocyte entrapment in the retinal vessels of diabetic rats. Bucillamine may have therapeutic efficacy in preventing the development of diabetic retinopathy.

To determine the changes in the pulse amplitude (PA) and the pulsatile ocular blood flow (POBF) after scleral buckling (SB).Retrospectively, we studied 24 patients (average age, 52 years) who had undergone SB to repair a retinal detachment in one eye. The patients were divided into two groups: those in whom SB had been performed less than 6 months earlier (n = 10), and those in whom the procedure had been performed more than 6 months previously (n = 14). In each group, the PA and the POBF were determined with a computerized tonometry system, and the values in the SB eyes were compared with those in the control fellow eyes.Within 6 months postoperatively, the mean PA in the SB eyes (0.66 +/- 0.30 mmHg) was significantly lower than that in the control eyes (1.43 +/- 0.34 mmHg; P0.05). The mean POBF in the SB eyes (349.5 +/- 154.1 microl/min) was also significantly lower than that in the control eyes (631.0 +/- 226.6 microl/min; P0.05). After more than 6 months postoperatively, there were no significant differences in the PA or the POBF between the SB eyes (1.08 +/- 0.49 mmHg and 612.4 +/- 341.2 microl/min, respectively) and the control eyes (1.50 +/- 0.51 mmHg and 589.5 +/- 278.4 microl/min, respectively).These results indicate that the choroidal blood flow decreases after SB but returns to normal levels after 6 months.

Keratoconus is an idiopathic, progressive, non-inflammatory ectasia of the axial cornea. Its association of other systemic disorders or ocular disease have been reported, but its specific origin remains unknown. Recently, Munier and associates detected that four types of autosomal dominant corneal dystrophy result from mutation in the human transforming growth factor β induced gene (βigH3), the product of which has shown to be the protein keratoepithelin (R555W for granular corneal dystrophy, R555Q mutation for Reis-Buckler’s corneal dystrophy, R124C mutation for lattice corneal dystrophy type I, and R124H mutation for Avellino corneal dystrophy).1 Molecular genetic analysis of various corneal dystrophies, which had previously presented an insuperable challenge to clinical diagnosis, now clearly demonstrates the distinct phenotypes.2 We report a rare case of bilateral keratoconus in association with Avellino corneal …

To measure fluorescein (F) and fluorescein monoglucuronide (FG) concentrations in the vitreous and evaluate the effect of acetazolamide (AZM) on the outward permeability of the blood-retina barrier (BRB) using differential vitreous fluorophotometry (DVF).DVF was performed 180 minutes after intravenous injection of AZM (5 mg/kg) and 50 mg of sodium fluorescein in six rabbits (AZM group). DVF also was performed in six rabbits injected intravenously with only 50 mg of sodium fluorescein (control group). The F/FG ratio was calculated based on the concentrations of F and FG obtained by DVF. DVF also was performed 180 minutes after 50 mg of intravenous injection of sodium fluorescein in five rabbits given probenecid (150 mg/kg) intraperitoneally (probenecid group).The average F/FG ratio was 0.36 +/- 0.17 (range, 0.22-0.66) in the AZM group, which was significantly smaller than the control value of 0.74 +/- 0.22 (range, 0.50-1.60). The average F/FG ratio at 180 minutes after injection was 1.51 +/- 0.46 (range, 0.94-2.00) in the probenecid group, which was significant higher (p0.05) than that of the AZM or control group.This study showed that the F/FG ratio might be a good indicator of the estimated outward permeability of the BRB using DVF and that AZM may accelerate the outward active transport function of the BRB.

Background: To report an Asian patient with branch retinal vein occlusion secondary to neurofibromatosis 1. Case: A 64-year-old woman presented with a loss of vision in her right eye of 9-month duration. A diagnosis of neurofibromatosis 1 was made. A general medical examination showed no abnormalities except the signs of neurofibromatosis 1. Observations: Fundus examination of the right eye revealed irregularities of the venous caliber, partial sheathing of the corresponding vein and macular edema. Multiple dilated and tortuous collateral channels and an arteriovenous communication bridged the perfused and nonperfused retina. Fundus examination of the left eye showed a tortuous vein in the temporal region of the fovea. Fluorescein angiography of the right eye confirmed delayed filling in a superotemporal artery and in the corresponding vein. The temporal region of the fovea had large areas of capillary loss. The collaterals were tortuous and mimicked a neovascularization. Fluorescein angiography of the left eye confirmed that the vein in the temporal part of the fovea was tortuous and not leaking. A diagnosis of branch retinal vein occlusion of the superotemporal vein was made. Conclusions: Neurofibromatosis 1 should be considered in the differential diagnosis of retinal vascular occlusive disease without other risk factors.

PURPOSE: We used scanning laser ophthalmoscope microperimetry to evaluate the retinal scotoma and the fixation points in the patients with macular dystrophy. METHODS: We studied 10 eyes of five patients with macular dystrophy (three patients with cone dystrophy and two patients with Stargardt disease). The mean patient age was 37 years (range, 13 to 64 years). An estimation of scotoma and fixation points on the retina was performed using scanning laser ophthalmoscope microperimetry. RESULTS: All 10 eyes (100%) had one of two types of dense scotoma: type one was a dense ring scotoma (five eyes, 50%), and type two was a dense central scotoma (five eyes, 50%) that included the center of the fovea. In all eyes with a dense ring scotoma, the fixation points were stable and did not shift. In all eyes with a dense central scotoma, the fixation shifted. The logarithm of minimal angle of resolution of the visual acuity in the eyes with the dense central scotoma was significantly worse than that of eyes with the dense ring scotoma type ( P = .005). CONCLUSIONS: Scanning laser ophthalmoscope microperimetry findings demonstrate two types of dense scotoma (dense ring scotoma and dense central scotoma) in the patients with macular dystrophy. The two types of dense scotoma affect the shifting of the fixation points and the stability of fixation and may result in the difference in visual acuity in the patients with macular dystrophy.

Purpose: To investigate stereo acuity levels in patients with unilateral idiopathic macular hole and after surgical intervention. Methods: In 31 consecutive patients with a unilateral macular hole and 46 consecutive patients who underwent successful unilateral macular hole surgery, complete ocular examinations, including orthoptic examinations and microperimetry using the scanning laser ophthalmoscope, were performed. Results: A significantly positive correlation was found between VA and stereo acuity (r=0.87, P

BACKGROUND—The factors that influence pulsatile ocular blood flow (POBF) were evaluated in normal subjects. METHODS—POBF was measured in 80 normal subjects using Langham OBF computerised tonometry. The effect of age, systolic and diastolic blood pressure, refractive error, intraocular pressure, and axial length on POBF was evaluated using multiple regression analysis. RESULTS—The mean (SD) POBF value was 593.3 (203.6) µl/min (range 290.7-1201.6). Of all the independent variables in the model, only the axial length was statistically significant (p=0.008). The regression coefficient was negative, indicating that the axial length decreased with increasing POBF. CONCLUSIONS—These data suggest that, in normal subjects, the POBF decreases as axial length increases. Choroidal blood flow may decrease as the axial length increases. The axial length may therefore be a major factor affecting POBF.

OBJECTIVE—To evaluate corneal advanced glycation end product (AGE) fluorescence in patients with diabetes and in healthy control subjects. RESEARCH DESIGN AND METHODS—Corneal autofluorescence was measured in 26 eyes of 26 patients with type 2 diabetes (mean age 57.0 years; mean disease duration 12.2 years; mean HbA1c 7.1%) and 13 eyes of 13 healthy age-matched control subjects (mean age 57.9 years). The patients with type 2 diabetes were divided into the following groups: patients without diabetic retinopathy (DR), patients without proliferative diabetic retinopathy (PDR), and patients with PDR. Corneal autofluorescence was measured by fluorophotometry with the wavelength that is characteristic of AGE fluorescence (excitation and emission 360–370 nm and 430–450 nm, respectively). We defined peak corneal autofluorescence levels as corneal AGE fluorescence values. We compared the corneal AGE fluorescence values in the four groups. RESULTS—In the PDR group (11.9 ± 3.9 arbitrary units [mean ± SD]), the corneal AGE fluorescence values were significantly higher compared with the control subjects (6.9 ± 1.3 arbitrary units), the patients without DR (7.4 ± 2.1 arbitrary units), and the patients without PDR (6.9 ± 2.2 arbitrary units) (P < 0.05). CONCLUSIONS—We found that corneal AGEs may increase in patients with diabetes and PDR compared with control subjects, patients without DR, and patients without PDR. In the patients with PDR, increased corneal AGEs may play a role in diabetic keratopathy.

To investigate the relation between foveal findings and visual function in eyes with a resolved idiopathic macular hole after vitreous surgery.We divided 28 eyes with postoperative idiopathic macular hole resolution into 3 groups based on postoperative biomicroscopic foveal findings of complete closure, partial closure, or atrophic closure. To evaluate foveal retinal function, scanning laser ophthalmoscope (SLO) microperimetry was performed preoperatively and 6 months postoperatively.Postoperatively in 18 eyes (64%), the foveal images became normal or almost normal and were classified as having complete closure, 6 eyes (21%) were classified as having partial closure, and 4 eyes (14%) as having atrophic closure. The corresponding visual acuity levels 6 months postoperatively were, respectively, 0.10, 0.35, and 0.64 (P.01) based on LogMAR analysis. Preoperative SLO microperimetry detected an absolute scotoma at the bottom of all macular holes; postoperatively, the absolute scotoma disappeared in the 18 eyes with complete hole closure, but a relative scotoma was detected in 6 eyes. Of 6 eyes with partial closure, 1 had an absolute scotoma and 5 had a relative scotoma. An absolute scotoma was detected in 4 eyes with atrophic closure.After macular hole closure, SLO findings correlate both with biomicroscopic findings and foveal function. Better anatomical foveal recovery in eyes after macular hole closure results in better improvement of vision than in eyes in which the foveal anatomical findings are not as good.

Purpose To examine the diurnal variations in corneal autofluorescence in normal and diabetic patients. Methods We measured corneal autofluorescence using a fluorophotometer fitted with an anterior segment adapter. Corneal autofluorescence was measured 10 times at 3 min intervals to evaluate the reproducibility of this instrument in 4 eyes of 4 normal subjects. The diurnal variation in corneal autofluorescence was determined by measuring the fluctuations in 10 eyes in 10 normal subjects and one unoperated eye each of 10 patients with proliferative diabetic retinopathy (PDR). We performed five consecutive measurements at 1000, 1130, 1400, 1630 and 1900 hours. The mean value of five measurements, the variation range and the coefficient of variation were analysed. Results The mean coefficient of variation in the measurement using this instrument was 8.6 ± 1.0%. In the patients with PDR, the mean corneal autofluorescence value was significantly higher (p < 0.001), the variation range was significantly wider (p < 0.001) and the coefficient of variation was significantly greater (p < 0.01) than in the normal subjects. Conclusions The results of this study suggest that corneal autofluorescence changes over the course of a day in patients with diabetes. This may be caused by the breakdown of the blood-aqueous barrier that we reported previously.

A 62-year-old man, who underwent focal laser photocoagulation in the left eye (OS) for diabetic retinopathy 2 years previously, complained of metamorphopsia OS. The left fundus had a semilunar retinal pigment epithelial (RPE) tear measuring 2×5 disc diameters (DD) temporal to the macula at the margin of a serous retinal pigment epithelial detachment (PED). Two days later, marked cystoid macular oedema and a serous retinal detachment (SRD) developed in the fovea. Seventeen days later, the RPE tear markedly developed over two quadrants, and the best-corrected visual acuity (BCVA) decreased to 20/63 OS. The patient was followed without treatment. Thereafter, the RPE tear began to cicatrise. Four months later, the RPE tear …

Polypoidal choroidal vasculopathy (PCV) has been recognised for almost two decades. In 1990, Yannuzzi and colleagues first described idiopathic polypoidal choroidal vasculopathy (IPCV) macular disorder—a choroidal vasculopathy that causes haemorrhagic and exudative macular degeneration—in 11 patients.1 The patients had peculiar polypoidal subretinal vascular lesions associated with serous and haemorrhagic detachments of the retinal pigment epithelium (RPE). In the late 1990s, Yannuzzi and colleagues expanded the clinical spectrum of IPCV and established the concept of PCV.2,3 In 1995, Spaide and colleagues identified the precise choroidal abnormalities associated with PCV and examined them using indocyanine green angiography (IA).4 IA showed two basic choroidal vascular changes: a branching network of vessels in the inner choroid and polypoidal vascular dilations at the border of the network of vessels. IA confirmed the definitive diagnosis of PCV. In 1999, using optical coherence tomography (OCT), Iijima and colleagues showed that on images of the inner choroid in eyes with PCV orange‐red lesions protruded anteriorly.5 These lesions had a sharper peak than serous RPE detachments in the subretina, suggesting that polypoidal vascular lesions in eyes with PCV lie beneath Bruch's membrane and are covered anteriorly by the RPE and Bruch's membrane.6 IA and OCT, relatively new diagnostic devices, are useful for understanding the pathophysiology and for diagnosing PCV. However, the cause and the pathogenesis of PCV are not clearly known. In 1999, Uyama and colleagues described the nature and clinical features of PCV in 32 Japanese patients.7 IA showed branching vascular networks with polypoidal dilations at the network terminals beneath the RPE in all patients. These lesions were mostly in the macula (94%), with a few in the peripapillary area. The authors concluded that PCV in Japanese patients differs from that in US patients. In 2002, the same investigators clarified the long‐term natural history of PCV.8 Fourteen eyes of 12 untreated Japanese patients with PCV were followed prospectively for at least 2 years after the first visit. The authors concluded that PCV is a chronic disease of long duration, and the patients had varying courses. Fifty per cent of the patients had a favourable course; in the other 50%, the disorder persisted for a long time with occasional episodes of bleeding and leakage, resulting in macular degeneration and visual loss. In 2005, the Japanese Study Group of Polypoidal Choroidal Vasculopathy reported the criteria for this disorder in Japanese patients,9 based on a fundus examination, IA findings or both. Definitive cases meet at least one of the following criteria: 1) protruding elevated orange‐red lesions observed by fundus examination and 2) characteristic polypoidal lesions seen on IA. Probable cases meet at least one of the follwing criteria: 1) only an abnormal vascular network is seen in IA and 2) recurrent haemorrhagic and/or serous detachments of the RPE are observed. On fluorescein angiography, eyes with PCV have primarily occult choroidal neovascularisation (CNV) because most components of PCV are beneath the RPE. However, 9% of eyes with PCV in Japanese patients have classic CNV on fluorescein angiography.10 Otsuji and colleagues evaluated eight eyes of eight Japanese patients with PCV with classic CNV on fluorescein angiography, using IA and OCT.11 All patients had greyish subretinal exudates, which were considered fibrinous. The authors concluded that both type 2 CNV and PCV with fibrin without CNV are present in patients with PCV showing classic CNV. It is important to determine if type 2 CNV is present in eyes with PCV, because the visual prognosis in the presence of type 2 CNV is worse in PCV. In this issue of the BJO (see page 1152), Tamura and colleagues retrospectively reviewed the visual prognosis and ocular characteristics of 38 eyes with PCV of Japanese patients that appear to have classic CNV on fluorescein angiography.12 OCT showed subretinal material with moderate reflectivity that corresponded in location to classic CNV in all cases. At the final visit, the subretinal material resolved completely in 14 eyes but resolved incompletely in 24 eyes after photodynamic therapy (PDT). The visual acuity in the group with resolved lesions was significantly better than in the group in which the lesions persisted at the final visit. The authors hypothesised that eyes with persistent lesions have type 2 CNV, and the eyes with resolved lesions have deposition of pure fibrous tissue without CNV. The subretinal material seen before treatment was more frequent in the subfovea in the group with persistent lesions and adjacent to polypoidal lesions in the group with resolved lesions. The authors suggested that although it is difficult to discriminate type 2 CNV from pure fibrin deposition before treatment, type 2 CNV is seen more often in the subfovea and is typically separate from the polypoidal lesions. Chan and colleagues determined the efficacy of PDT with verteporfin (Visudyne, Novartis, Switzerland) as a treatment for PCV in Asian patients.13 Stable or improved vision was achieved in 21 (95%) of the 22 eyes at the 1 year follow‐up. Severe visual loss due to massive subretinal haemorrhage occurred in one eye. This report showed that PDT is an effective treatment for PCV. Tamura and colleagues reported that stable or improved vision was achieved in 18 (75%) of the 24 eyes with PCV with type 2 CNV at the final visit. The authors suggested that the treatment effect is limited in eyes with PCV with type 2 CNV. Recently, the MARINA and ANCHOR studies reported that intravitreal administration of ranibizumab (Lucentis, Genentech, USA), a recombinant, humanised, monoclonal antibody Fab that neutralises all active forms of vascular endothelial growth factor A, prevented vision loss and improved the mean visual acuity with low rates of serious adverse events in patients with CNV secondary to age‐related macular degeneration.14,15 The efficacy and safety of this new treatment for PCV should be evaluated. I believe that the diagnosis and treatment of PCV require management by a medical retina specialist using new diagnostic devices and therapies such as fluorescein angiography, IA, OCT, and PDT.

The object of this study was to clarify the ocular structural changes of tree shrews during development and the influence of growth on experimental myopia. Eighty-four eyes of 42 tree shrews (43–1604 days old) were included. The body weight was measured. The axial length was measured using A-mode ultrasonography, and the mean value of both eyes was calculated. Monocular form deprivation (FD) was induced in 13 8-week-old tree shrews. The axial length and refractive error were measured before and at 15, 30,45, 60, 90, and 120 days after FD was induced. The body weights increased rapidly from birth until 100 days, the point at which tree shrews reach maturity. The ocular structures changed rapidly during this period, except for the anterior chamber depth. In the animals with FD, myopia increased rapidly by 45 days following FD at approximately 100 days after birth. However, after this time, myopia increased slowly. Almost the same results were found for the vitreous cavity and the axial length. Our study demonstrated that ocular structural growth changes markedly to the point at which tree shrews reach maturity, and FD myopia may be influenced by ocular growth.

The purpose of this study was to evaluate the correlation between corneal and lens autofluorescence and the various degrees of myopia. Forty-five eyes of 45 myopic patients (mean age ± SD, 23.8 ± 2.4 years; range, 18 to 27 years) were included. Subjects wearing contact lenses were excluded. After inducing mydriasis, we mea¬sured corneal and lens autofluorescence levels, refractive error, and axial length. A significant correlation was found between refractive error and length of the vitreous cavity. Neither anterior chamber depth nor lens thickness correlated with refrac¬tive error. Refractive error was significantly correlated with corneal and lens autofluorescence levels (r = 0.415, P 0.0005). Corneal and lens autofluorescence levels increased as the axial length increased in myopic eyes. This increase may be related to the breakdown of the blood-ocular barrier that we previ¬ously reported.

Purpose To determine the effect of vascular endothelial growth factor and retinopathy level on retinal hemodynamics in nondiabetic and diabetic rats and to evaluate retinal hemodynamics in nondiabetic and diabetic patients. Methods Forty-eight diabetic and 22 nondiabetic patients had their diabetic retinopathy levels determined from fundus photographs according to Early Treatment Diabetic Retinopathy Study (ETDRS). Fluorescein angiograms were recorded from the left eye by video fluorescein angiography. Retinal blood flow was calculated from the digitized angiograms. Human recombinant vascular endothelial growth factor or vehicle alone was injected intravitreally into 13 nondiabetic and 11 diabetic rats. Results Retinal blood flow decreased 33% in patients with ETDRS retinopathy level 10 compared with control patients ( P = .001) and increased sequentially in more advanced stages of retinopathy, with a strong correlation between retinal blood flow and retinopathy level ( r 2 = 0.434, P = .001). In the diabetic rats, retinal blood flow was decreased 35.6% ( P = .01). Vascular endothelial growth factor maximally increased retinal blood flow by 36.1% in nondiabetic rats after 25 minutes ( P = .001) and by 73.7% in diabetic rats after only 5 minutes ( P = .01) and caused a greater response in diabetic than in nondiabetic rats. Conclusions Retinal blood flow increases with advancing nonproliferative diabetic retinopathy in humans, and diabetes accentuates the vascular endothelial growth factor–induced increase in retinal blood flow and venous dilation in rats. Vascular endothelial growth factor may contribute to the changes in retinal hemodynamics and morphology observed in early diabetic retinopathy.

Visual conversion reaction is a psychosomatic anomaly that manifests as reduced visual acuity (VA) and visual field defects.1,2 Scanning laser ophthalmoscopy (SLO) can detect a scotoma and VA under direct fundus observation.3–6 However, there have been no reports of patients diagnosed with visual conversion reaction using SLO. We report a patient with visual conversion reaction using SLO. A 20 year old woman presented with a sudden bilateral loss of vision. She reported being under severe stress at work. The best corrected visual acuity (BCVA) was counting fingers in both eyes. The external eye examination and pupillary responses were normal in both eyes. Conventional …

Lenticular autofluorescence was measured in vivo in 25 normal tree shrews using a fluorophotometer with a specially designed small animal adapter to assess the usefulness of this model of lens pathology. The average variability in the lenticular autofluorescence measurements was 8.7%. The average ratio between lenticular autofluorescence of the left eye and that of the right eye was 0.99 +/- 0.13 SD. There was a strong correlation between age and mean lenticular autofluorescence in both eyes (correlation coefficient, 0.988; p0.001). The calculated annual increase in lenticular autofluorescence was 23.7 ngEq/ml. This method of measurement is reliable, and lenticular autofluorescence in tree shrews varies little among animals other than a variation caused by aging. Moreover, the tree shrew, which is believed to be a primate, is small and easy to breed. This could be a useful animal model to study various lens pathologies in humans.

In idiopathic macular hole formation, Gass1 hypothesised that macular holes enlarge with displacement of the photoreceptors without tissue loss around the fovea. Jensen and Larsen2 developed binocular kinetic perimetry that could evaluate local retinal photoreceptor displacement and also confirm centrifugal photoreceptor displacement away from the foveola in eyes with a macular hole. Using the binocular perimetry technique and scanning laser ophthalmoscope microperimetry, we confirmed that the patients with a unilateral macular hole with preoperative photoreceptor displacement had better postoperative visual function when compared to patients without preoperative photoreceptor displacement.3 We also previously reported that the postoperative foveal findings were correlated with the postoperative visual function in eyes with macular hole.4 The purpose of the present study was to investigate whether or not detecting photoreceptor displacement preoperatively affects the postoperative foveal findings …

Diabetic macular edema (DME), which causes retinal thickening, is a main cause of visual impairment in patients with diabetes (1,2). The important pathophysiology of DME is the loss of retinal capillary pericytes, resulting in increased vascular permeability of the blood-retinal barrier (BRB) (3). However, there is only one report about the active transport of the BRB in patients with DME (4). The aim of this study was to evaluate the active transport of the BRB in patients with clinically significant diabetic macular edema (CSME) (5) in type 2 diabetes using differential vitreous fluorophotometry (DVF). We studied six eyes of six patients with …

Retinal abnormalities have been reported worldwide in patients with neurofibromatosis type 1.1–3 However, there have been few reports of choroidal abnormalities.4 We report a patient with choroidal abnormalities, associated with neurofibromatosis type 1, using a scanning laser ophthalmoscope (SLO). A 37 year old woman presented for an examination with hard contact lenses. Her best corrected visual acuity was 20/20 in both eyes. A diagnosis of neurofibromatosis type 1 was made on the basis of multiple cafe au lait spots, plexiform …

Age related macular degeneration (AMD) is the major cause of irreversible blindness in elderly patients worldwide. The pathogenesis of this disease has been investigated from genetic,1histological,2 and haemodynamic perspectives.3-6 AMD is classified as non-exudative—the dry type, or exudative neovascular—the wet type.7 8Choroidal neovascularisation (CNV) in the macula causes severe visual impairment in AMD. Several angiogenic factors (vascular endothelial growth factor (VEGF) and basic fibroblast growth factor), which are induced by hypoxia and ischaemia, may play a part in the development of CNV.9-11 Choroidal haemodynamics are important for CNV development in AMD. Chen and colleagues report abnormal choroidal blood flow in asymmetric exudative AMD by measuring pulsatile ocular blood flow (POBF) using an OBF tonometer in 37 patients with asymmetric exudative AMD in this issue of the BJO (p 1411). Their results demonstrated that POBF was significantly higher in eyes with CNV than in the contralateral eyes with drusen. Eyes with disciform scars had lower POBF than the contralateral eyes with drusen. …

To study the correlation between blood–retinal barrier (BRB) permeability and development of form deprivation (FD) myopia, FD was induced in tree shrews. The refractive error and the axial dimensions of the optical elements were measured. Ocular fluorescence was measured before and after fluorescein-Na injection. The inward permeability (Pin) of the BRB was measured before and 15, 30, and 45 days after FD was induced. FD eyes became significantly myopic 15 days after FD was induced (P

To investigate the effect of an adenosine agonist, 2-5'-N-ethylcarboxamidoadenosine (NECA), on the outward active transport of fluorescein across the retinal pigment epithelium (RPE) in rabbits. High (5x10(-4)-2x10(-3) M) and low (1x10(-5)-1x10(-4) M) concentrations of NECA or phosphate buffered saline (PBS) were intravitreously injected into Dutch-belted rabbits. Sodium fluorescein was injected intravenously 180 min after NECA. Differential vitreous fluorophotometry was performed 3 hr after the sodium fluorescein injection and the vitreal fluorescein/fluorescein monoglucuronide (F/FG) ratio then was calculated. The F/FG ratios are inversely proportional to the outward active transport of fluorescein across the RPE. Retinal detachments were induced by injection of PBS into the subretinal space after the intravitreous injection of low- or high-dose NECA or PBS, and the size of the blebs was monitored. In eyes that received a low-dose injection of NECA, the F/FG ratio was higher compared with controls (P0.05); in eyes that received a high-dose intravitreal injection, the F/FG ratio was significantly lower compared with controls (P0.05). The effect of low-dose NECA on the F/FG ratio was suppressed by the A2 receptor antagonist, ZM241385, and the effect of high-dose NECA was suppressed by the A1 receptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine. The A3 receptor antagonist MRS1191 did not influence the effect of low- or high-dose NECA. Intravitreal injection of high-dose NECA enhanced the reabsorption of subretinal fluid compared with PBS; however, low-dose NECA inhibited reabsorption of subretinal fluid (P0.02 and 0.05, respectively). Intravitreous injection of high-dose NECA accelerates the active outward transport across the RPE via A1 receptors and low-dose NECA decelerates it via A2 receptors.