Ten-year outcomes of cataract surgery for glaucoma management in patients with primary angle-closure disease.

PURPOSE: To investigate the long-term outcomes of cataract surgery for glaucoma management in patients with primary angle-closure disease (PACD). STUDY DESIGN: Retrospective case series. METHODS: We reviewed the medical records of 87 eyes of 87 patients with PACD who underwent uncomplicated cataract surgery alone at the Kobe City Medical Center General Hospital. Only patients with a minimum follow-up of 10 years were included. The patients were divided into PACD spectrum categories: primary angle-closure glaucoma (PACG), primary-angle closure (PAC), and primary angle-closure suspect (PACS). The treatment outcomes were compared among the 3 groups. Intraocular pressure (IOP), number of glaucoma eye drops, requirement of additional glaucoma treatment, visual field progression, and progression to glaucoma during the follow-up period were evaluated. RESULTS: Among the 87 patients, 39 had PACG; 26, PAC; and 22, PACS. Ten years after surgery, the IOP had significantly decreased from baseline in all 3 groups. The rate of requirement of additional glaucoma treatment during the follow-up period was significantly higher in the PACG group than in the other groups. Almost half of the patients with PACG required additional glaucoma treatment; of those patients, six (15.4%) underwent glaucoma surgery. Three patients (11.5%) with PAC required additional glaucoma medication. Visual field progression was observed in 28.1% of the patients with PACG. In 1 patient with PAC, the condition progressed to PACG, but there was no such progression in any of the patients with PACS. CONCLUSIONS: We confirmed that cataract surgery had a long-term (> 10 years) effect on IOP reduction in eyes with PACD. Early intervention with cataract surgery may be preferable for glaucoma management in patients with PACD.

Comparison of pretreatment measurements of anterior segment parameters in eyes with acute and chronic primary angle closure.

PURPOSE: To compare pretreatment anterior segment parameters between eyes with acute primary angle closure (APAC) and chronic primary angle closure (CPAC), and to identify the characteristics of eyes with APAC. STUDY DESIGN: Retrospective. METHODS: We measured pretreatment anterior chamber depth (ACD), iris convexity (IC), and pupil diameter in eyes with APAC and CPAC using anterior segment optical coherence tomography. The risk of APAC associated with anterior segment parameters was investigated using multiple logistic regression. Eyes with APAC were discriminated from eyes with CPAC using the receiver-operating characteristic (ROC) curve and area under the curve (AUC). The best cutoff for these variables was determined. RESULTS: Thirty-four eyes with APAC and 60 eyes with CPAC were included. The mean intraocular pressure was 52.3 ± 12.6 mmHg in APAC and 15.5 ± 3.5 mmHg in CPAC (P < .001). Eyes with APAC had a shallower ACD (1.407 ± 0.301 mm vs. 1.960 ± 0.205 mm, P < .001) and less IC (0.233 ± 0.087 mm vs. 0.294 ± 0.068 mm, P < .001) than eyes with CPAC. In multivariate analysis, significant variables associated with APAC were ACD (P < .001) and IC (P = .001). The AUC for ACD was 0.931 and for IC, 0.742. The best cutoff for ACD was 1.699 mm (sensitivity 0.824, specificity 0.917) and for IC, 0.282 mm (sensitivity 0.853, specificity 0.533). CONCLUSIONS: Eyes with APAC had a shallower ACD and less IC. Eyes with an ACD < 1.7 mm may be at risk for APAC.

Experimental proliferative vitreoretinopathy in rabbits by delivery of bioactive proteins with gelatin microspheres.

Proliferative vitreoretinopathy (PVR) is a challenging pathological condition, often causing failure of retinal detachment surgery. The purpose of this study was to evaluate the feasibility of a delivery system of bioactive proteins using anionic and cationic gelatin microspheres and to establish a new PVR model in rabbits by intraocular sustained delivery of basic fibroblast growth factor (bFGF) and interferon-beta (IFNß). Anionic and cationic gelatin microspheres were prepared and immersed in bFGF and IFNß solution, respectively, to yield a polyion complex between gelatin matrix and a bioactive protein. The bFGF-impregnated microspheres were injected into the subretinal space in rabbit eyes. At week 2, the IFNß-impregnated microspheres also were injected into the same space. Control eyes received gelatin microspheres without bFGF or IFNß, or both. The eyes then were observed for 8 weeks by ophthalmoscopy, fundus photography, and fluorescein angiography. The eyes also were evaluated histologically. In the group with both bFGF and IFNß, the number of eyes with more severe PVR increased over time. Histologic examination showed retinal folds. In contrast, no proliferative changes were seen in any control groups. Subretinal implantation of bFGF and IFNß-impregnated gelatin microspheres induced reproducible PVR in rabbit eyes. This study guaranteed delivery of bioactive proteins with gelatin microspheres.

Comparison of Mydriatic Provocative and Dark Room Prone Provocative Tests for Anterior Chamber Angle Configuration.

PURPOSE: To investigate the relationship between angle configuration and diagnostic provocation tests such as the mydriatic provocative test (MPT) and the dark room prone provocative test (DRPPT). MATERIALS AND METHODS: Seventy eyes of 70 consecutive patients with primary angle closure suspect, primary angle closure, or primary angle closure glaucoma were included. The anterior chamber depth, angle opening distance 500, trabecular-iris space area 500, and iris thickness (IT) were quantitatively determined by anterior segment optical coherence tomography, and the MPT and DRPPT were used to investigate intraocular pressure variations. RESULTS: Seven eyes were positive and 3 eyes were suspected positive, using the MPT, whereas 10 eyes were positive and 7 eyes were suspected positive using the DRPPT. The anterior chamber depth and angle opening distance 500 of the positive and suspected positive groups (positive group), using the MPT, were significantly less than those of the negative group (P=0.013, P=0.013, respectively). IT of the positive group, using the MPT, was significantly greater than the negative group, using the same test (P=0.003). The trabecular-iris space area 500 of the positive group was significantly less than the negative group, using both the MPT (P<0.001) and the DRPPT (P=0.004). CONCLUSIONS: Eyes from the positive group, using the MPT, contained a shallower anterior chamber, narrower angle, and greater IT than those from the negative group. These results suggested that the MPT results better correlated with the anterior chamber angle configuration in eyes with primary angle closure, than the results using the DRPPT.

Influence of anterior segment biometric parameters on the anterior chamber angle width in eyes with angle closure.

PURPOSE: To predict angle narrowing in eyes with angle closure in a Japanese population using anterior segment optical coherence tomography (AS-OCT) quantitative parameters. PATIENTS AND METHODS: AS-OCT was used to examine 118 eyes of 118 patients with angle closure and 40 eyes of 40 patients with open angle under dark conditions. After measuring the angle opening distance 500 (AOD500), anterior chamber depth, iris thickness (IT), iris convexity (IC), pupil diameter, anterior chamber width, and crystalline lens rise, multivariate regression analyses were performed for the AOD500 in each group. RESULTS: With the exception of IT, significant differences were observed between the AS-OCT parameters for the angle closure and open-angle groups. Anterior chamber depth, IT, and IC were the explanatory variables associated with AOD500 for each group (P≤0.001). A significant negative association was found between IT and IC only in the angle-closure group (P<0.001). CONCLUSIONS: This study quantitatively confirmed that shallow anterior chamber depth was a major mechanism of angle narrowing, and that both IT and IC had a strong impact on angle narrowing. Moreover, the negative association found between IT and IC in only the angle closure group indicated the existence of the stretch force placed on the iris by relative pupillary block.

Light-dark changes in iris thickness and anterior chamber angle width in eyes with occludable angles.

BACKGROUND: The purpose of this study was to investigate and measure light-dark changes in iris thickness (IT) and anterior chamber angle width in eyes with occludable angles and open angles by using anterior segment optical coherence tomography (AS-OCT). METHODS: We examined 153 eyes of 153 Japanese patients with primary angle closure suspect, primary angle closure, primary angle closure glaucoma, or primary open angle glaucoma. AS-OCT was used to determine pupil diameter, IT, angle opening distance at 500 µm (AOD500), and trabecular-iris space area at 500 µm (TISA500) in each quadrant of the anterior chamber angle (superior, inferior, temporal, and nasal) under light and dark conditions. RESULTS: In the angle closure cases, IT, AOD500 and TISA500 in the dark varied significantly among the four quadrants (P < 0.05, analysis of variance). In contrast, in the open angle cases, IT, AOD500 and TISA500 in the dark did not differ significantly among the four quadrants. In the angle closure cases and the open angle cases, significant negative associations were found between IT difference [IT(light)-IT(dark)] and AOD500 difference [AOD500(light)-AOD500(dark)] (R = -0.411, P < 0.001 and R = -0.501, P = 0.001, respectively) and between IT difference and TISA500 difference [TISA500(light)-TISA500(dark)] (R = -0.475, P < 0.001 and R = -0.462, P = 0.002, respectively). CONCLUSION: Our results suggest that thickening of the iris root under dark conditions is related to the mechanism of primary angle closure. It is important to analyze both the angle structure and peripheral IT in each quadrant.

Changes in choroidal thickness and optical axial length accompanying intraocular pressure increase.

PURPOSE: To measure changes in choroidal thickness (CT), retinal thickness (RT), and axial length (AL) accompanying intraocular pressure (IOP) increase and to investigate the changes in axial eye dimensions induced by IOP increase. METHODS: Thirty-four eyes of 34 patients undergoing a diagnostic provocative test for primary angle closure (PAC). Patients with other macular diseases were excluded. Patients underwent the darkroom prone provocative test (DR-PPT) for 1 h. We measured CT and RT at the fovea by optical coherence tomography with the enhanced depth imaging method and AL with noncontact, partial coherence laser interferometry before and after the DR-PPT. RESULTS: There was a statistically significant increase in the mean (SD) IOP of 7.3 (9.2) mmHg and the mean (SD) AL of 0.06 (0.12) mm after the DR-PPT (P < 0.001 and P = 0.014, respectively). There was a statistically significant decrease in the mean (SD) subfoveal CT of 30.0 (36.8) µm (P < 0.001), while there was no significant change in the mean foveal RT. The change in subfoveal CT was negatively correlated with the changes in IOP (r = -0.71, P < 0.001) and AL (r = -0.54, P = 0.004). CONCLUSIONS: In eyes suspected of having PAC, acutely increased IOP accompanies choroid thinning and corresponding elongation of the optical axis.

Hemispherical focal macular photopic negative response and macular inner retinal thickness in open-angle glaucoma.

PURPOSE: To investigate in open-angle glaucoma the focal macular photopic negative response and spectral-domain optical coherence tomography measurements of retinal thicknesses in the superior and inferior macula. DESIGN: Comparative case series. METHODS: We studied 63 eyes of 63 patients with open-angle glaucoma and 41 normal eyes of 41 volunteers. Photopic negative responses were recorded using a spotlight (diameter of 15 degrees of circle), projected onto the whole or superior or inferior macula. Ganglion cell complex (nerve fiber + ganglion cell + inner plexiform layers) thickness was measured using spectral-domain optical coherence tomography. RESULTS: Mean photopic negative response amplitude over the entire macula was significantly (P < .001) decreased compared with that of controls in eyes with early (n = 24; to 62.1%), moderate (n = 21; to 57.2%), and severe (n = 18; to 49.3%) open-angle glaucoma, but not significantly different among eyes with various stages of glaucoma. Mean ganglion cell complex thickness was significantly (P < .001) decreased compared with that of controls in eyes with early (86.0%), moderate (78.3%), and severe (71.2%) glaucoma, and thinning correlated positively with glaucoma severity (P < .001). Mean photopic negative response amplitude correlated significantly (P < .001) with ganglion cell complex thickness over the whole, superior, and inferior macular areas (r = 0.57 to 0.74). In 16 eyes without visual field defect in the inferior hemifield, mean photopic negative response amplitude was 56.5% of normal (P < .001), and mean ganglion cell complex thickness in the superior macula was 92.1% of normal (P = .004). CONCLUSIONS: Focal macular photopic negative response amplitude correlates with ganglion cell complex thickness, but decreases more abruptly in early glaucoma compared with ganglion cell complex thickness.

Three-dimensional imaging of macular inner structures in glaucoma by using spectral-domain optical coherence tomography.

PURPOSE: To profile macular thickness changes in glaucoma by using three-dimensional spectral-domain optical coherence tomography (3D-SD-OCT). METHODS: The study included 30 eyes with suspected glaucoma and preperimetric glaucoma (SGPPG) and 35 healthy eyes. The macular thickness, including those of the total retina, nerve fiber layer (NFL), and combined inner retinal layers (IRLs)-NFL+ganglion cell layer (GCL)+inner plexiform layer (IPL)-was measured by 3D-SD-OCT raster scans in a 6 mm(2) region. The average and sectoral thicknesses were calculated on an Early Treatment of Diabetic Retinopathy Study (ETDRS) chart and a ETDRS chart with a 45° rotation (glaucoma sector chart, GSC). RESULTS: The mean IRL thickness was significantly less in the SGPPG eyes than in the healthy eyes, but the mean total retinal and macular NFL thicknesses were not. In the SGPPG eyes, the IRLs were thinner in the outer macula than in the inner macula, in the inferior hemisphere than in the superior hemisphere, and in the temporal hemisphere than in the nasal hemisphere. The significantly thinned sectors were nearly identical on the GSC but only slightly overlapped on the ETDRS chart. The IRLs in the inferior temporal outer sector (GSC) had the greatest area under the receiver operating characteristic curve, which was significantly greater than those for the IRLs over the entire macula, inferior hemiretinal region, and inferior outer hemicircular region (macular subfields), and that for the circumpapillary NFL in the inferior sectors (P = 0.001-0.036). CONCLUSIONS: Macular IRL thickness measured by using 3D-SD-OCT is useful for profiling macular atrophy in SGPPG.

Early trabeculectomy bleb walls on anterior-segment optical coherence tomography.

BACKGROUND: To correlate the cross-sectional features of filtering blebs on anterior-segment optical coherence tomography (AS-OCT) 2 weeks after trabeculectomy with bleb function at 6 months. METHODS: Forty-eight eyes followed for 6 months or more after trabeculectomy with mitomycin C were included. Bleb wall reflectivity of developing blebs on AS-OCT 2 weeks postoperatively was correlated with mature bleb function at 6-month postoperative visit. RESULTS: Developing bleb walls at 2 weeks were classified as uniform in 10/48 eyes (20.8%) and multiform in 38/48 eyes (79.2%). Blebs with uniform reflectivity were significantly more likely to have worse function at 6 months (P < 0.001). Multiform bleb walls had hyporeflective areas seeming to represent loosely-arranged connective tissue (multiple-layer structures), subconjunctival separation, and microcysts. Blebs with multiple-layer structures at 2 weeks were associated with better bleb function at 6 months (P = 0.025). Intraocular pressure (IOP) of developing blebs at 2 weeks did not correlate with bleb function at 6 months (P = 0.471). CONCLUSIONS: Bleb wall reflectivity on AS-OCT 2 weeks after surgery may predict bleb function at 6 months, whereas IOP of developing blebs may not.

Alteration of leukocyte-endothelial cell interaction during aging in retinal microcirculation of hypertensive rats.

PURPOSE: Hypertension, one of the more common chronic diseases affecting the elderly, has been reported to influence leukocyte-endothelial cell interaction. The leukocyte-mediated inflammatory process contributes to age-related changes in vessels. This study was designed to evaluate age-related changes in leukocyte-endothelial cell interaction in the hypertensive rat retina. METHODS: Male spontaneous hypertensive rats (SHR; 1.5, 3, 6, 12, and 20 months of age) and age-matched Wistar-Kyoto rats (WKY) were used. The number of accumulated leukocytes was counted in sections of flat-mounted retinal tissue. The expression of intercellular adhesion molecule-1 (ICAM-1) and CD18 (the common beta-chain of ICAM-1 ligands) was evaluated. Retinal thickness was evaluated histologically. RESULTS: The number of accumulated leukocytes and the expression of ICAM-1 and CD18 increased in the aged retina. The number of leukocytes that accumulated and the expression of CD 18 were significantly higher in the SHR group than in the WKY group (P < 0.01). In addition, retinal thickness decreased with age. CONCLUSION: Leukocyte-endothelial cell interaction increased in the aged retina and these changes were more severe in SHR retina than in WKY retina. This increased interaction was first observed at 3 months, a relatively young age.

Thrombin inhibitor reduces leukocyte-endothelial cell interactions and vascular leakage after scatter laser photocoagulation.

PURPOSE: Macular edema is one of the most serious adverse effects after retinal scatter laser photocoagulation. It has been suggested that the inflammatory reaction after photocoagulation may be involved in the pathogenesis of macular edema. This study was designed to evaluate quantitatively the inhibitory effects of argatroban, a direct thrombin inhibitor, on leukocyte-endothelial cell interactions and vascular permeability after scatter laser photocoagulation. METHODS: Argon laser photocoagulation was performed in one half of the retina in pigmented male rats (n = 114). Argatroban was administered just before scatter laser photocoagulation. In the other half of the retina, AO leukocyte fluorography was used to evaluate in vivo leukocyte rolling along the retinal vein and accumulation in the retinal capillary bed. The expressions of P-selectin and intercellular adhesion molecule (ICAM)-1 were evaluated by reverse transcription-polymerase chain reaction. Retinal vessel permeability was quantified by using fluorescein isothiocyanate (FITC)-conjugated dextran. RESULTS: Scatter laser photocoagulation caused significant inflammatory leukocyte-endothelial cell interactions in the nonphotocoagulated half of the retina. Treatment with argatroban suppressed leukocyte-endothelial cell interactions. The maximum number of rolling and accumulating leukocytes was reduced by 46.6% (P < 0.01) and 51.4% (P < 0.01), respectively. The expression of P-selectin and ICAM-1 mRNA was suppressed significantly in the argatroban-treated retinas (P < 0.05). Retinal vascular permeability was also suppressed significantly (P < 0.05). CONCLUSIONS: Argatroban suppressed leukocyte-endothelial cell interactions and blood-retinal barrier breakdown after scatter laser photocoagulation, suggesting that argatroban prevents postlaser macular edema.

Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina.

PURPOSE: Recently, intravitreal injection of corticosteroids has been in wide use as a treatment for diabetic macular edema, and the outcomes have been favorable. However, the exact mechanism remains unclear. The hypothesis for the current study was that intravitreal corticosteroids may improve diabetic retinal edema by amelioration of blood-retinal barrier (BRB) breakdown, by inhibiting leukocyte stasis (leukostasis). METHODS: Diabetes was induced in 6-week-old male Long-Evans rats by intraperitoneal injection of streptozotocin (75 mg/kg). Three weeks after induction of diabetes, intravitreal injection of dexamethasone (40 microg/10 microL) was performed. At 2 days after intravitreal injection, accumulated leukocytes were counted in vivo by acridine orange leukocyte fluorography, and BRB breakdown was evaluated by measurement of retinal vascular permeability. The mRNA expression and protein levels of intercellular adhesion molecule (ICAM)-1 in the retina were also studied. RESULTS: The number of leukocytes accumulated in the retina, once increased in the diabetic group, was decreased by 31.6% (P = 0.0001) after dexamethasone injection. The level of BRB breakdown, also elevated in the diabetic group, was suppressed by 61.1% (P = 0.0046) after dexamethasone injection. The level of ICAM-1 mRNA expression and its protein, upregulated in the diabetic group, were downregulated by dexamethasone treatment by 70.0% (P < 0.0001) and 56.4% (P = 0.0003). CONCLUSIONS: Intravitreal injection of corticosteroids improves diabetic retinal edema through inhibiting leukocyte recruitment in the diabetic retina.

In vivo three-dimensional evaluation of leukocyte behavior in retinal microcirculation of mice.

PURPOSE: To evaluate new physiologic and three-dimensional methods for monitoring leukocyte behavior in mouse retina. METHODS: Endotoxin-induced uveitis (EIU) was produced in mice by footpad injection of lipopolysaccharide (LPS). Leukocytes were labeled with acridine orange (AO). Leukocyte rolling in the retinal microcirculation was evaluated in vivo with AO digital fluorography. The number of migrated leukocytes was counted in flatmounted retina. The behavior of leukocyte migration was observed three-dimensionally at the time of peak migration. After leukocytes were labeled with AO, the mice were perfused with rhodamine-labeled concanavalin A lectin to stain the vascular endothelium. Leukocyte migration into the retina was then monitored three-dimensionally with confocal microscopy, and the velocity of the migration was measured. RESULTS: Both leukocyte rolling and migration peaked at 48 hours after LPS injection. Leukocytes were seen to extravasate from the deeper capillary layers and to migrate toward the outer layer of the retina. The traveling velocity of extravasated leukocytes in retinal tissue was 2.0 +/- 0.1 microm/h. CONCLUSIONS: New methods have been demonstrated for the three-dimensional and quantitative evaluation of leukocyte behavior in mouse retina.

Simvastatin inhibits leukocyte accumulation and vascular permeability in the retinas of rats with streptozotocin-induced diabetes.

Leukocytes play important roles in the pathogenesis of diabetic retinopathy. Recently, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors have been reported to exert various effects in addition to their lipid-lowering ability. We investigated the effects of simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, on leukocyte-induced diabetic changes in retinas. Diabetes was induced in Long-Evans rats with streptozotocin, and simvastatin administration was begun immediately after the induction of diabetes. Two weeks of treatment with simvastatin suppressed significantly the number of leukocytes adhering to retinal vessel endothelium and the number of leukocytes accumulated in the retinal tissue by 72.9% and 41.0%, respectively (P < 0.01). The expression of intercellular adhesion molecule-1 (ICAM-1) and the CD18 (the common beta-chain of ICAM-1 ligands) were both suppressed with simvastatin. The amount of vascular endothelial growth factor in the retina was attenuated in the simvastatin-treated group. To evaluate the effects of simvastatin on leukocyte-induced endothelial cell damage, vascular permeability in the retina was measured with fluorescein-labeled dextran. Treatment with simvastatin markedly reduced retinal permeability (P = 0.014). This suggests that simvastatin attenuates leukocyte-endothelial cell interactions and subsequent blood-retinal barrier breakdown via suppression of vascular endothelial growth factor-induced ICAM-1 expression in the diabetic retina. Simvastatin may thus be useful in the prevention of diabetic retinopathy.

In vivo evaluation of retinal injury after transient ischemia in hypertensive rats.

A number of studies have suggested that hypertension affects the pathogenesis of inflammatory reactions in various organs. The objective of this study was to evaluate the effects of hypertension on leukocyte-endothelial interactions after transient retinal ischemia. Transient retinal ischemia was induced for 60 minutes in spontaneously hypertensive rats (SHR) and in age-matched normotensive Wistar-Kyoto rats (WKY). At 4, 12, 24, 48, and 72 hours after reperfusion, flat-mount retinas were prepared to evaluate the density of leukocytes that had been accumulated in the retina. Intercellular adhesion molecule-1 (ICAM-1) mRNA expression was studied by semiquantitative polymerase chain reaction and ICAM-1 protein levels were studied by enzyme-linked immunosorbent assay. At 14 days after reperfusion, the retinal damage and the effect of superoxide dismutase on the damage were evaluated histologically. In SHR, the number of accumulated leukocytes peaked at 48 hours after reperfusion, and it was upregulated to 5.2-fold, as compared with that of WKY (P<0.001). ICAM-1 mRNA expression and ICAM-1 protein levels were increased significantly in the ischemia-reperfused retina in SHR compared with WKY (P<0.05). Histological examination demonstrated marked increase in the retinal ischemia/reperfusion damage in SHR (P<0.01) and a significant amelioration of the damage by treatment with superoxide dismutase in SHR (P<0.05). Oxidative stress may thus be an important mechanism for the deterioration seen in ischemia/reperfusion injury in the SHR retina.