Frequency-doubling technology and retinal measurements with spectral-domain optical coherence tomography in preperimetric glaucoma.

BACKGROUND: To determine the relationship between visual fields and retinal structures measured with spectral-domain optical coherence tomography in preperimetric glaucoma (PPG). METHODS: Twenty-six eyes of 26 patients with PPG and 20 healthy eyes of 20 volunteers were included. All patients underwent Heidelberg retina tomography-2 (HRT2), standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and RTVue-100. SAP and FDT indices, HRT parameters, and circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thicknesses were correlated using Pearson's test. Areas under the receiver operating characteristic curves (AUROCs) and sensitivity/specificity based on each parameter's definition of abnormalities were compared between parameters. RESULTS: Significant differences were found in FDT-MD, FDT-PSD, SAP-PSD, cpRNFL, and mGCC parameters (p < 0.001-0.015), but not in SAP-MD or HRT parameters, between PPG and control groups. Significant correlations were not found between visual field indices and structural parameters, except between FDT-MD and HRT rim area (r = 0.450, p = 0.021) and between FDT-PSD and temporal cpRNFL thickness (r = 0.402, p = 0.021). AUROCs for cpRNFL (p = 0.0047-0.033) and mGCC (p = 0.0082-0.049) parameters were significantly better than those of HRT parameters, whereas significant differences were not found between FDT indices and cpRNFL or mGCC parameters or between cpRNFL and mGCC parameters. Adding average cpRNFL or mGCC thickness to FDT-MD significantly increased sensitivity compared to single parameters (p = 0.016-0.031). CONCLUSIONS: Structural and functional parameters were poorly correlated but complementary for glaucoma detection in PPG. Combining these parameters may improve PPG diagnosis.

Macular ganglion cell layer imaging in preperimetric glaucoma with speckle noise-reduced spectral domain optical coherence tomography.

OBJECTIVE: To visualize the macular ganglion cell layer (GCL) and measure its thickness in normal eyes and eyes with preperimetric glaucoma, using speckle noise-reduced spectral domain optical coherence tomography (SD-OCT). DESIGN: Retrospective consecutive case series. PARTICIPANTS: Thirty-seven eyes of 37 patients with preperimetric glaucoma and 39 normal eyes of 39 volunteers. METHODS: Vertical and horizontal SD-OCT B-scan images were acquired with minimal speckle noise by using eye-tracking to obtain and average 50 B-scans at each identical location of interest. B-scan images were manually analyzed for GCL, retinal nerve fiber layer (RNFL), and inner plexiform layer shapes and thicknesses in the macula. MAIN OUTCOME MEASURES: Macular GCL images and thickness in normal eyes and in eyes with preperimetric glaucoma. RESULTS: The macular GCL was clearly seen on speckle noise-reduced SD-OCT images in normal eyes and eyes with preperimetric glaucoma. In each eye with preperimetric glaucoma, thinning of the macular GCL was visually apparent, particularly on vertical scans. The mean regional macular GCL was most severely thinned in the inferior perifoveal region, where its thickness was <70% of its normal thickness in 30 (81.1%) of the 37 eyes and <50% of its normal thickness in 13 (35.1%) of the 37 eyes. When the sensitivity and specificity for detecting abnormal thinning (outside the lower limit of 99% confidence interval [CI] for the means in the 39 normal eyes) in at least one 0.5-mm segment or sector were compared, the macular GCL on vertical B-scans exhibited higher sensitivity (81.1%) than the other layers on vertical B-scans (99% CI, 5.4%-59.5%; P = 0.00075-0.02100), the macular GCL (99% CI, 40.5%; P = 0.00027) on horizontal B-scans, the other layers (99% CI, 5.4%-48.6%; P<0.00048-0.00400) on horizontal B-scans, and circumpapillary RNFL automatically measured on SD-OCT (54.1%; P = 0.021), and scanning laser polarimetry with variable corneal compensation (24.3%; P = 0.00095). All the macular layers on both the vertical and horizontal B-scans and circumpapillary RNFL thickness exhibited comparable specificity (91.4-100.0%, statistically not different). CONCLUSIONS: Speckle noise-reduced SD-OCT imaging allowed clear visualization and measurement of the macular GCL, which was severely thinned in eyes with preperimetric glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Detection of localized retinal nerve fiber layer defects in glaucoma using enhanced spectral-domain optical coherence tomography.

OBJECTIVE: To compare retinal nerve fiber layer (RNFL) defects on fundus photographs with circumpapillary RNFL (cpRNFL) thinning or disruption on images obtained by speckle-noise-reduced spectral-domain optical coherence tomography (enhanced SD OCT), single-scan SD OCT, and single-scan time-domain OCT (TD OCT). DESIGN: Retrospective, comparative case series. PARTICIPANTS: Forty-four eyes of 44 patients with open-angle glaucoma with localized, wedge-shaped RNFL defects on red-free photographs and 35 normal eyes of 35 volunteers. METHODS: Cross-sectional images of the cpRNFL and cpRNFL thinning, compared with the confidence interval limit of the normative database where the RNFL defect was photographically identified, were compared between the 3 types of OCT instruments: enhanced SD OCT (SD OCT with eye tracking and averaging of 16 images at the same location to reduce speckle noise; Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany), single-scan SD OCT (RTVue-100; Optovue, Fremont, CA), and single-scan TD OCT (Stratus; Carl Zeiss-Meditec, Dublin, CA). MAIN OUTCOME MEASURES: Cross-sectional images of localized RNFL defects on red-free fundus photographs, sensitivity for detecting the photographic RNFL defect, and sensitivity and specificity for detecting glaucoma as having at least 1 abnormally thinned sector on the cpRNFL thickness map on OCT. RESULTS: Among the 44 eyes with glaucoma, 65 RNFL defects were identified on red-free fundus photographs. The cpRNFL boundaries were clearer on enhanced SD OCT images than on single-scan SD OCT or TD OCT images, particularly in regions corresponding to the RNFL defects. Enhanced SD OCT revealed various degrees of cpRNFL thinning, and disruption of cpRNFL reflectivity was seen in the same location as the photographic RNFL defect for 23 (35.4%) of the 65 RNFL defects. The RNFL defects were significantly less likely to be detected by single-scan TD OCT or SD OCT (P = 0.002 and P = 0.006, respectively) when the RNFL was not disrupted. Enhanced SD OCT was more sensitive in detecting the RNFL defects that were not disrupted compared with single-scan TD OCT (P<0.0001) or SD OCT (P<0.0001). Enhanced SD OCT had better sensitivity and specificity for detecting glaucoma compared with single-scan TD OCT or SD OCT (sensitivity, P = 0.006 and P = 0.001; specificity, P = 0.001 and P = 0.004, respectively). CONCLUSIONS: These results suggest that speckle-noise reduction can improve the detection of photographic RNFL defects in which cpRNFL reflectivity on OCT images is not disrupted. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Quantitative evaluation of iris convexity in primary angle closure.

PURPOSE: In eyes with primary angle closure (PAC), we quantitatively evaluated anterior bowing of the iris by means of ultrasound biomicroscopy (UBM). DESIGN: Retrospective, observational, and consecutive case series. METHODS: A total of 203 phakic eyes with PAC that had not undergone any surgical or laser treatment were included. Using UBM, we measured anterior chamber depth (ACD) and iris convexity (IC): the maximum distance from the posterior surface of the iris to the iris plane passing through the pupillary margin of the iris and iris root. RESULTS: The average IC was 0.22 +/- 0.1 mm, although there was considerable individual variation. The IC value was correlated weakly, albeit significantly, with age (r = 0.22, P < .01), and strongly with ACD (r = -0.57, P < .0001). CONCLUSIONS: In eyes with PAC, older age and a more shallow ACD appear to be important causes of increased forward bowing of the iris resulting from pupillary block.

Angle widening and alteration of ciliary process configuration after cataract surgery for primary angle closure.

PURPOSE: To evaluate quantitatively, by means of ultrasound biomicroscopy (UBM), changes in the anterior segment configuration, including the ciliary processes, induced by cataract surgery in eyes with primary angle closure. DESIGN: Retrospective interventional case series. PARTICIPANTS: Thirty-one eyes of 31 patients with primary angle closure or primary angle-closure glaucoma were treated with cataract surgery. Before cataract surgery, 10 eyes had been treated with laser peripheral iridotomy, and 1 with laser peripheral iridoplasty. METHODS: Configuration of the anterior chamber was examined by means of UBM before and at 3 months after cataract surgery. MAIN OUTCOME MEASURES: Using UBM, anterior chamber depth (ACD), angle opening distance at points 500 mum from the scleral spur (AOD500), and trabecular-ciliary process distance (TCPD) were measured. RESULTS: Not only ACD and AOD500, but also TCPD, increased significantly after cataract surgery, compared with measurements obtained before surgery (P<0.001). Postoperative AOD500 was correlated significantly with postoperative TCPD (r = 0.72, P<0.001) and with the amount of change of TCPD caused by cataract surgery (Delta TCPD) (r = 0.52, P<0.01). CONCLUSIONS: Cataract surgery attenuated anterior positioning of the ciliary processes in eyes with primary angle closure, concomitant with significant widening of the angle. Cataract surgery resulted in not only complete dissolution of lens volume and pupillary block, but also attenuation of the anterior positioning of the ciliary processes, all of which contributed to postoperative widening of the angle in eyes with primary angle closure.

Cataract surgery for residual angle closure after peripheral laser iridotomy.

PURPOSE: To investigate the frequency of residual angle closure after resolution of pupillary blocking by laser peripheral iridotomy and the effects of subsequent cataract surgery to resolve angle closure completely. DESIGN: Retrospective, consecutive, interventional study. PARTICIPANTS: Among 70 eyes treated with laser iridotomy, 13 with residual angle closure were treated with cataract surgery. METHODS: The provocative test of angle closure by prone position in a dark room for 1 hour was performed; increases in tension of > or =8 mmHg, 6 or 7 mmHg, and < or =5 mmHg were considered to be positive, suspected positive, and negative, respectively. Configuration of the anterior chamber was examined using ultrasound biomicroscopy (UBM). MAIN OUTCOME MEASURES: Intraocular pressure (IOP), response to the dark room prone position test, and morphologic analysis by UBM were evaluated before and 3 months after cataract surgery. RESULTS: Residual angle closure after iridotomy was seen in 27 (38.6%) of 70 eyes; this was confirmed functionally by the dark room prone position test and morphologically by UBM. Eyes with IOP of > or =20 mmHg or with a glaucomatous visual field defect before iridotomy had a significantly higher incidence of residual angle closure after iridotomy than eyes without these findings (P<0.05). In all the eyes with residual angle closure after iridotomy, the response to the prone position test became negative after cataract surgery, with significant lowering of IOP (P<0.01). CONCLUSIONS: Residual angle closure after iridotomy was common, especially in eyes with primary angle closure and poorly controlled IOP or glaucomatous optic neuropathy. Cataract surgery was effective to resolve completely the residual angle closure after iridotomy and lower IOP.

Retinal cystoid spaces in acute Vogt-Koyanagi-Harada syndrome.

PURPOSE: Exudative retinal detachment in acute Vogt-Koyanagi-Harada syndrome often is associated with subfoveal yellowish round structures. This report describes the incidence and clinical characteristics of these structures. DESIGN: Interventional case series. METHODS: We reviewed the fundus photographs and medical records of 35 eyes of 19 Japanese patients with bilateral diffuse choroiditis at the onset of acute Vogt-Koyanagi-Harada syndrome. RESULTS: All eyes showed subretinal fluid in the posterior pole. In addition, yellowish round structures were seen in 15 eyes (43%). Most of the yellowish structures were subfoveal in location and ranged in size from less than 1 disk diameter to 3 disk diameters. In 6 eyes with these structures, optical coherence tomography showed liquid accumulation in the retina or thin walls, which seemed to separate the cystoid spaces from the subretinal fluid. Late-phase fluorescein angiography showed pooling of dye within these structures as well as within the subretinal fluid. Immediately after corticosteroid administration was initiated, these structures began to be less obvious, and they disappeared completely within several days; there was a concomitant reduction in the subretinal fluid. At the initial visit, visual acuity in eyes with these yellowish structures was slightly less than that in eyes without them, but no differences in visual acuity were found during the period of follow-up. CONCLUSION: Subfoveal yellowish round structures may be a common feature in acute Vogt-Koyanagi-Harada syndrome. However, they appear to have only a minor (if any) effect on visual prognosis.

Argatroban attenuates leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia.

BACKGROUND AND PURPOSE: Argatroban, a direct thrombin inhibitor, has been shown to reduce neural injury after transient cerebral ischemia. It has also been reported that this neuroprotective effect results from an anticoagulant function. This study was designed to evaluate quantitatively the inhibitory effects of argatroban on leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia. METHODS: Retinal ischemia was induced for 60 minutes in male Long-Evans rats by temporary ligation of the optic sheath (n=342). Argatroban was administered just after induction of ischemia. Leukocyte and platelet behavior in the retinal microcirculation was then evaluated in vivo with scanning laser ophthalmoscopy. The expression of P-selectin and intracellular adhesion molecule-1 (ICAM-1) was evaluated by reverse transcription-polymerase chain reaction. After 10 days of reperfusion, ischemia-induced retinal damage was evaluated histologically. RESULTS: Treatment with argatroban suppressed leukocyte-endothelial cell interactions; the maximum numbers of rolling and accumulated leukocytes were reduced by 90.1% (P<0.05) and 58.7% (P<0.05), respectively, at 12 hours after reperfusion. Treatment with argatroban also suppressed platelet-endothelial cell interactions; the maximum numbers of rolling and adhering platelets were reduced by 91.8% (P<0.01) and 78.9% (P<0.01), respectively, at 12 hours after reperfusion. The expression of P-selectin and ICAM-1 mRNA was suppressed significantly in the argatroban-treated retinas (P<0.01). Histologic examination demonstrated the protective effect of argatroban on ischemia-induced retinal damage (P<0.01). CONCLUSIONS: Argatroban treatment suppressed leukocyte- and platelet-endothelial cell interactions after transient retinal ischemia. This inhibitory effect on postischemic blood cell-endothelial cell interactions might partially contribute to its neuroprotective effects.

Platelets adhering to the vascular wall mediate postischemic leukocyte-endothelial cell interactions in retinal microcirculation.

PURPOSE: Recent evidence suggests that platelets play a major role in ischemia-reperfusion injury, not only through thrombus formation but also through participation in inflammatory reactions with leukocytes. This study was designed to investigate the contribution of platelets in leukocyte recruitment to inflamed regions in vivo. METHODS: Thrombocytopenia was produced in male Long-Evans rats by intravenous injection of anti-platelet serum at 4 hours before ischemia-reperfusion. Leukocyte behavior in retinal microcirculation was evaluated with acridine orange digital fluorography. Expression of P-selectin in the postischemia retina was investigated by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. After 14 days of reperfusion, ischemia-induced retinal damage was evaluated histologically. RESULTS: Leukocyte rolling along major retinal veins of thrombocytopenic rats was dramatically suppressed, and subsequent leukocyte accumulation in the postischemia retina was also significantly reduced (72.3%; P < 0.001) at 24 hours after reperfusion. Although RT-PCR revealed no significant reduction of P-selectin mRNA in platelet-depleted rat retina after transient ischemia, immunohistologic examination showed suppression of P-selectin expression on the vascular wall. Another immunologic examination using anti-platelet antibody detected adherent platelets, which can also express P-selectin on their surfaces, on postischemic vascular endothelium in vehicle-treated retina. Moreover, blockage of platelet glycoprotein IIb/IIIa resulted in substantial inhibition of leukocyte rolling. In addition, histologic examination showed the participation of platelets in retinal ischemia-reperfusion injury. CONCLUSIONS: This study demonstrated that the expression of P-selectin on platelets may contribute to the recruitment of leukocytes to tissues after ischemia.

Inhibitory effects of antithrombin III on interactions between blood cells and endothelial cells during retinal ischemia-reperfusion injury.

PURPOSE: Infiltrating leukocytes have long been widely thought to be key mediators of ischemia-reperfusion injury. Recently, however, evidence suggests that platelets accumulating in postischemic tissues also contribute to ischemia-reperfusion injury because of their inflammatory properties and promotion of formation of thrombi. This study was designed to evaluate quantitatively the inhibitory effects of antithrombin (AT)-III on the interactions between blood cells and retinal endothelial cells in vivo after transient retinal ischemia. METHODS: Transient retinal ischemia was induced for 60 minutes in male Long-Evans rats by ligation of the optic nerve. AT III (250 U/kg) was administered intravenously just after induction of ischemia. Leukocyte and platelet behavior in the retina was evaluated in vivo with a scanning laser ophthalmoscope. Expression of P-selectin and intracellular adhesion molecule (ICAM)-1 in the postischemic retina was investigated by reverse transcription-polymerase chain reaction and immunohistochemistry. After 14 days of reperfusion, ischemia-induced retinal damage was evaluated histologically. RESULTS: Administration of AT III significantly inhibited leukocyte rolling along the major retinal veins and subsequent accumulation of leukocytes in the postischemic retina. Furthermore, the maximum number of rolling and adherent platelets was reduced by 76% (P < 0.01) and 48% (P < 0.01), respectively, at 12 hours after reperfusion. Immunohistochemical studies also revealed the suppressive effect of AT III on expression of P-selectin and ICAM-1. Finally, histologic examination demonstrated the protective effects of AT III against retinal damage after transient retinal ischemia. CONCLUSIONS: This study demonstrates the inhibitory effects of AT III on leukocyte and platelet recruitment to the postischemic retina, which may account for the neuroprotective properties of this alpha-2 globulin against retinal ischemia-reperfusion injury.

Inflammatory response after scatter laser photocoagulation in nonphotocoagulated retina.

PURPOSE: Macular edema is one of the most serious adverse effects after retinal scatter laser photocoagulation. It has been suggested that the changes in the distribution of retinal blood flow or the inflammatory reaction after photocoagulation may be involved in the pathogenesis of macular edema, but little information is available about its exact mechanism. This study was designed to evaluate quantitatively leukocyte-endothelial cell interactions and vascular permeability in the nonphotocoagulated portions of the retina after partial scatter laser photocoagulation. METHODS: Argon laser photocoagulation was performed in one half of the retina in male pigmented rats (n = 90). In the other half of the retina, leukocyte dynamics after photocoagulation were evaluated in vivo with acridine orange digital fluorography. Retinal vessel permeability was quantified by using Evans blue dye. RESULTS: Scatter laser photocoagulation caused significant inflammatory leukocyte-endothelial interactions not only in the photocoagulated but also in the untreated half of the retina. In the nonphotocoagulated half of the retina, the number of leukocytes rolling along the major retinal veins increased after photocoagulation and peaked at 12 hours (14.3 +/- 4.5 cells/min per vessel). Leukocyte accumulation in the untreated half of the retina increased after photocoagulation, with a peak of 47.5 +/- 13.0 cells/mm(2) 24 hours after photocoagulation. Retinal vascular permeability in the untreated half of the retina gradually increased after photocoagulation. CONCLUSIONS: Scatter laser photocoagulation increased leukocyte rolling and subsequent accumulation in both the photocoagulated and the untreated portions of the retina. The accumulated leukocytes may be involved in the augmented vascular permeability in the untreated retina, resulting in retinal edema after photocoagulation.

Delayed absorption of macular edema accompanying serous retinal detachment after grid laser treatment in patients with branch retinal vein occlusion.

PURPOSE: To study the detailed process of macular edema (ME) absorption after grid laser photocoagulation in patients with branch retinal vein occlusion (BRVO). The influence of pretreatment serous retinal detachment (SRD) at the fovea on patient outcome was also evaluated. DESIGN: Retrospective, interventional, comparative case series. PARTICIPANTS: Thirty-seven BRVO patients presenting with severe ME. METHODS: Patients were treated with grid laser photocoagulation with 6 months of follow-up examinations. Baseline and post-treatment examinations included measurements of visual acuity (VA), fluorescein angiography, and detailed imaging of ME by optical coherence tomography (OCT). Macular thickness was defined as the distance from the inner retinal surface to the outer border of the sensory retina (foveal retinal thickness) and also to the inner border of the retinal pigment epithelium including the SRD (total foveal elevation). MAIN OUTCOME MEASURES: Post-treatment macular thickness with OCT, VA converted to the logarithm of the minimum angle of resolution, and absorption of SRD, and correlations of macular thickness and VA both before and after treatment. RESULTS: Total foveal elevation and VA were significantly improved at 1, 3, and 6 months after treatment. There was also a significant correlation between reduction of total foveal elevation and increase in VA. Fourteen eyes (37.8%) displayed SRD, as evidenced by OCT at the baseline. In eyes without SRD, foveal retinal thickness and VA had significantly improved in a time-dependent manner. However, although SRD itself was almost absorbed 6 months after treatment, the improvement of both VA and total foveal elevation in eyes with pretreatment SRD was not significant compared with baseline conditions. Both post-treatment total foveal elevation and VA of eyes with SRD tended to be worse than eyes without SRD. CONCLUSION: The presence of subfoveal SRD retards the absorption of ME and recovery of VA after grid laser photocoagulation in patients with BRVO.

Combination of alpha-fetoprotein mRNA-based detection of hematogenously disseminating hepatocellular carcinoma cells and analysis of cancer cell membrane fluidity is more accurate in screening patients at risk of postoperative recurrence.

We developed an mRNA-based, highly specific and sensitive method to detect hepatocellular carcinoma cells present in blood. However, the reason for some patients being positive for blood analysis and negative for recurrence has yet to be found. We recently established a method to measure membrane fluidity of hepatocellular carcinoma cells, and used it to analyze the actual membrane fluidity of human hepatocellular carcinoma cells. We found that patients with carcinoma cells with lower membrane fluidity less frequently developed recurrence. The analysis of both membrane fluidity and alpha-fetoprotein mRNA thus greatly increased the accuracy of the prediction of postoperative recurrence.

Successive cultures of mature hepatocytes for hepatocyte autotransplantation to assist liver function after liver resection for cancer.

We developed a method for the rapid successive cultures of adult rat mature hepatocytes on plastic dishes while avoiding viral transformation or co-culture with other cell lines. This method also allows for culturing adult human mature hepatocytes up to the secondary culture. These can be expected to provide a good source for hepatocyte autotransplantation, and, combined with the previously reported methods for the transplantation of hepatocytes into the spleen, a promising option for the support of liver function after liver resection for cancer without the need for immunosuppressive agents.

Quantitative evaluation for blood-retinal barrier breakdown in experimental retinal vein occlusion produced by photodynamic thrombosis using a new photosensitizer.

Purpose. To establish a rat model of retinal vein occlusion (RVO), we applied photodynamic thrombosis using a new photosensitizer. By measuring the breakdown of the blood-retinal barrier (BRB), we evaluated the model quantitatively. We also investigated how hypertension and retinal pigment epithelium (RPE) influence the breakdown of BRB after RVO. Methods. We modified a slit lamp biomicroscope for photodynamic thrombosis. The light source was changed from white light to argon laser, which made it possible to perform fluorescein angiography (FAG) simultaneously during photodynamic thrombosis. We irradiated with a continuous diode laser to occlude three retinal veins in a rat after PAD-S31 injection. The breakdown of BRB was quantitated by measuring extravasated Evans blue dye in albino and pigmented rats. We compared hypertensive rats (SHR) to normotensive rats (WKY) and sodium iodate-treated rats to normal rats. Results. High photosensitivity of PAD-S31 made it possible to occlude any retinal veins within 120 seconds at a low dose of 10 mg/kg without retinal thermal burn at the occlusion site. Simultaneous FAG enabled us to observe the formation of thrombus during diode laser irradiation. Our measured value of intraretinal Evans blue correlated with the range of serous retinal detachment. Both albino and pigmented rats demonstrated stable and constant values of Evans blue. SHR recovered from the breakdown of BRB after venous occlusion more slowly than WKY. Sodium iodate-treated rats had smaller breakdowns of BRB and recovered earlier than normal rats. Conclusions. In this study, we established the stable and constant rat model of RVO efficiently by using a new photosensitizer. Our simultaneous FAG method was considered to have an advantage of several potential clinical applications. Our rat model of RVO allows us to study factors associated with the recovery from damage by RVO.

Experimental macular edema induced by macular venule occlusion in monkey.

PURPOSE: Visual prognosis after retinal vein occlusion varies, because it may be affected by macular edema or an avascular area. The mechanism describing how macular edema and avascular areas occur, however, has not been clearly understood. We induced macular edema in cynomolgus monkeys by occluding macular venules to evaluate the retinal microcirculation. METHODS: We produced venous occlusion by applying dye laser in three cynomolgus monkeys. Macular edema was examined by slit lamp biomicroscopy and optical coherence tomography. Acridine orange leukocyte fluorography (AOLF) and fluorescein angiography were performed to study blood flow and vascular leakage before and after laser application. RESULTS: We observed three types of retinal changes in the macular area: (1) macular edema did not develop; (2) macular edema developed, but improved with avascular area formation; (3) macular edema developed, but disappeared without avascular area formation. Under physiological conditions, observation revealed that leukocytes flowed from arterioles into either superior or inferior venules. When macular edema did not develop, most leukocytes from arterioles escaped into the adjacent non-occluded venules. In contrast, when macular edema occurred, leukocyte flow became stagnated. Macular edema developed when capillary leakage was observed from venules and subsequently arterioles, but disappeared when an avascular area was formed by arteriole occlusion. CONCLUSIONS: We demonstrated that experimental macular edema could be induced by macular venule occlusion in monkeys. According to our observation by AOLF, whether macular edema is induced or not depends on the function of collateral routes of the remaining non-occluded venules. We could consider that a gradual increase in intravascular pressure was associated with the avascular area formation.

Imaging of localized retinal nerve fiber layer defects in preperimetric glaucoma using spectral-domain optical coherence tomography.

PURPOSE: To characterize preperimetric retinal nerve fiber layer (RNFL) defects on speckle noise-reduced spectral-domain optical coherence tomography (SD-OCT), and to determine whether detection of preperimetric RNFL defects can be improved by speckle noise reduction. PATIENTS AND METHODS: Thirty-two eyes of 32 patients with preperimetric glaucoma and 30 normal eyes of 30 volunteers underwent complete ophthalmic examinations and scanning by speckle noise-reduced SD-OCT (Spectralis), single-scan SD-OCT (RTVue-100), and single-scan time-domain (Stratus) OCT. RESULTS: All 40 RNFL defects identified by photography had angular widths <30 degrees and no disruption of RNFL reflectivity on Spectralis. Circumpapillary RNFL (cpRNFL) boundaries were accurately determined by Spectralis for 38 (95.0%) of the 40 defects, by RTVue-100 for 25 (62.5%), and by Stratus OCT for 23 (57.5%). Sensitivity for the detection of RNFL defects (cpRNFL thinning to <1% of normal for an age-matched database) was 15% for Stratus, 42.5% for RTVue, and 47.5% for Spectralis on sector maps and significantly higher for SD-OCT on temporal-superior-nasal-inferior-temporal (TSNIT) thickness graphs: RTVue-100 (57.5%; P=0.031) and Spectralis (90.0%; P=0.0001). On the basis of TSNIT thickness graphs, sensitivity for the detection of RNFL defects was significantly higher for Spectralis compared with RTVue-100 (P=0.001) and Stratus (P=0.0005). Spectralis TSNIT graphs were more sensitive (P=0.001) for glaucoma detection without significant reduction (P=0.125) in specificity compared with Spectralis sector maps. CONCLUSIONS: Our results suggest that accurate measurement of cpRNFL thickness by speckle noise-reduced SD-OCT and a comparison of the results with normative database using TSNIT graphs are required to improve the sensitivity for detecting preperimetric RNFL defects.

Peripapillary scleral deformation and retinal nerve fiber damage in high myopia assessed with swept-source optical coherence tomography.

PURPOSE: To study peripapillary morphologic changes in highly myopic eyes using swept-source optical coherence tomography at a longer wavelength. DESIGN: Prospective cross-sectional study. METHODS: Peripapillary regions of 196 eyes of 107 patients with high myopia (refractive error, <-8.0 diopters or axial length, >26.0 mm) were analyzed quantitatively and qualitatively with an swept-source optical coherence tomography prototype system that uses a tunable laser light source operated at a 100,000-Hz A-scan repetition rate in the 1-µm wavelength region. The visual field was evaluated by standard automated perimetry. Area of peripapillary atrophy ß and presence of scleral protrusion temporal to the optic disc were assessed. RESULTS: Peripapillary atrophy ß area, but not disc area, was significantly larger in eyes with visual field defect (3.16 ± 2.70 mm(2); range, 0.00 to 12.85 mm(2)) than those without visual field defect (2.31 ± 2.83 mm(2); range, 0.00 to 17.70 mm(2)). Temporal scleral protrusion was detected by color stereo disc photography in 22 (19.5%) of 113 eyes with visual field defect and in 4 (4.8%) of 83 eyes without visual field defect. Scleral bending demonstrated a wide range of angles (mean, 31.0 ± 21.1 degrees; range, 2 to 80 degrees). The angle of scleral bending, but not the distances from scleral bend to disc margin or foveal center, correlated significantly with retinal nerve fiber layer thickness above the bend (r = -0.557, P = .007) and visual field defect severity (r = -0.445, P = .038). CONCLUSIONS: Swept-source optical coherence tomography visualizes peripapillary deep structures in high myopia. Some cases of high myopia may be affected by direct scleral compression or stretching at the peripapillary region.

High-resolution imaging of retinal nerve fiber bundles in glaucoma using adaptive optics scanning laser ophthalmoscopy.

PURPOSE: To detect pathologic changes in retinal nerve fiber bundles in glaucomatous eyes seen on images obtained by adaptive optics (AO) scanning laser ophthalmoscopy (AO SLO). DESIGN: Prospective cross-sectional study. METHODS: Twenty-eight eyes of 28 patients with open-angle glaucoma and 21 normal eyes of 21 volunteer subjects underwent a full ophthalmologic examination, visual field testing using a Humphrey Field Analyzer, fundus photography, red-free SLO imaging, spectral-domain optical coherence tomography, and imaging with an original prototype AO SLO system. RESULTS: The AO SLO images showed many hyperreflective bundles suggesting nerve fiber bundles. In glaucomatous eyes, the nerve fiber bundles were narrower than in normal eyes, and the nerve fiber layer thickness was correlated with the nerve fiber bundle widths on AO SLO (P < .001). In the nerve fiber layer defect area on fundus photography, the nerve fiber bundles on AO SLO were narrower compared with those in normal eyes (P < .001). At 60 degrees on the inferior temporal side of the optic disc, the nerve fiber bundle width was significantly lower, even in areas without nerve fiber layer defect, in eyes with glaucomatous eyes compared with normal eyes (P = .026). The mean deviations of each cluster in visual field testing were correlated with the corresponding nerve fiber bundle widths (P = .017). CONCLUSIONS: AO SLO images showed reduced nerve fiber bundle widths both in clinically normal and abnormal areas of glaucomatous eyes, and these abnormalities were associated with visual field defects, suggesting that AO SLO may be useful for detecting early nerve fiber bundle abnormalities associated with loss of visual function.