Noriyuki Unoki

Spectral-domain optical coherence tomography imaging of the detached macula in rhegmatogenous retinal detachment.

Purpose: To assess detached macula in rhegmatogenous retinal detachment by using spectral-domain optical coherence tomography. Methods: This retrospective study included 15 eyes of 15 patients with macula-off rhegmatogenous retinal detachment and 16 eyes of 16 patients with acute central serous chorioretinopathy. These patients were examined with a prototype spectral-domain optical coherence tomography system. Results: Spectral-domain optical coherence tomography of eyes with rhegmatogenous retinal detachment revealed macular structural abnormalities, such as small cystoid cavities in the inner nuclear layer (2/15 eyes, 13%), cystoid and/or diffuse edema in the outer nuclear layer (10/15 eyes, 67%), undulations of the photoreceptor layer (7/15 eyes, 47%), and dropout of the photoreceptor inner and outer segment layers in the fovea (6/15 eyes, 40%); such changes were not seen in eyes with acute central serous chorioretinopathy. The dropout of foveal photoreceptor inner and outer segment layers was correlated with preoperative and postoperative visual acuities (rs = 0.78, P < 0.005 and rs = 0.63, P < 0.05, respectively), thickness of the outer nuclear layer at the fovea (rs = −0.69, P < 0.01), and height of the retinal detachment at the fovea (rs = 0.60, P < 0.05). Conclusion: Dropout of the foveal photoreceptor inner and outer segment layers seen on spectral-domain optical coherence tomography imaging may be involved in incomplete recovery of visual acuity after successful retinal reattachment surgery.

SDF-1/CXCR4 Contributes to the Activation of Tip Cells and Microglia in Retinal Angiogenesis

PURPOSE. Although stromal cell-derived factor (SDF)-1 contributes to angiogenesis, its effects on sprouting angiogenesis remain ill defined. The authors investigated how SDF-1 and its receptor, CXCR4, influence neovascular sprouting. METHODS. In vivo retinal vascular development was evaluated and ex vivo retinal angiogenesis induced by vascular endothelial growth factor (VEGF). Time-sequential observation was followed by the quantification of movements in neovascular sprouts and microglia. Real-time PCR was performed for the measurement of mRNA levels. RESULTS. Neutralizing antibodies against SDF-1 or an antagonist of CXCR4, AMD3100, reduced the radius of the vascularized area in retinal vascular development. These inhibitions disturbed the filopodial extensions in tip cells and proliferation in stalk cells, reduced the number of microglia, and decreased the mRNA levels of KDR/Flk-1, UNC5B, and PDGFB, which are abundantly expressed in tip cells. In ex vivo experiments, VEGF induced SDF-1 mRNA expression, and the inhibition of SDF-1/CXCR4 decreased the number of VEGF-induced neovascular sprouts. The authors further evaluated the kinetics of sprouts using time-lapse imaging and found that SDF-1/CXCR4 contributes to the elongation of neovascular sprouts and to the extension and retraction of leading edges. The movements of resident microglia after VEGF treatment were also reduced by SDF-1/CXCR4 inhibition. Interestingly, microglial depletion decreased VEGF-induced neovascular sprouts with the partial effects of SDF-1/CXCR4 blockade. CONCLUSIONS. SDF-1/CXCR4 promotes retinal angiogenesis by both tip cell activation and the indirect angiogenic effects of microglia.

Retinal Hemorheologic Characterization of Early-Stage Diabetic Retinopathy Using Adaptive Optics Scanning Laser Ophthalmoscopy

PURPOSE Adaptive optics scanning laser ophthalmoscopy (AO-SLO) is a noninvasive technique that allows for the direct monitoring of erythrocyte aggregates in retinal capillaries. We analyzed the retinal hemorheologic characteristics in normal subjects, diabetic patients without diabetic retinopathy (NDR), and diabetic patients with nonproliferative diabetic retinopathy (NPDR), using spatiotemporal (ST) blood flow images to visualize blood corpuscle trajectory. METHODS AO-SLO images of the parafoveal capillary network were acquired for three groups: 20 healthy volunteers, 17 diabetic patients with NDR (8 type 1 and 9 type 2 patients), and 10 diabetic patients with NPDR (4 type 1 and 6 type 2). The erythrocyte aggregate velocity assigned to a relative cardiac cycle and the elongation rate of the erythrocyte aggregate were calculated. RESULTS Careful observation revealed that flow velocity fluctuations were found with higher frequency in diabetic patients than in normal subjects. The total average velocities were 1.26 ± 0.22 mm/s in the normal group, 1.31 ± 0.21 mm/s in the NDR group, and 1.63 ± 0.35 mm/s in the NPDR group. The average velocities of the NPDR group were higher than those in the normal (P = 0.001) and NDR (P = 0.009) groups. The average elongation rates of the 3 groups were 0.67 ± 0.20, 0.39 ± 0.19, and 0.33 ± 0.11, respectively. Elongation rate differed significantly between the normal and NDR (P = 0.003) groups as well as the normal and NPDR (P = 0.001) groups. CONCLUSIONS AO-SLO can be used to detect retinal hemorheologic changes in the early stages of diabetic retinopathy.

Structural changes of fovea during remission of Behçet's disease as imaged by spectral domain optical coherence tomography

PurposeTo acquire the image of the fovea during remission of ocular Behçets disease using spectral domain optical coherence tomography (SD-OCT) and to further assess the correlation between best-corrected visual acuity (BCVA) and SD-OCT findings.MethodsA total of 24 eyes of 14 patients with ocular Behçets disease were examined with SD-OCT. The relationships between BCVA and other clinical characteristics, including foveal thickness and status of external limiting membrane (ELM) or the junction between photoreceptor inner and outer segments (IS/OS), were analysed for statistical significance.ResultsBCVA in eyes with intact IS/OS was significantly better than that in eyes with ill-defined IS/OS (P=0.0001). Foveal thickness (P=0.0001) and male sex (P=0.03) were also significantly different between eyes with and without complete IS/OS line.ConclusionsDefinition of the IS/OS line by SD-OCT, but not status of the ELM line, appears to be associated with BCVA in patients with ocular Behçets disease. Accordingly, SD-OCT may prove useful in the evaluation of visual function after ocular attacks of Behçets disease.

Lamina Cribrosa Defects and Optic Disc Morphology in Primary Open Angle Glaucoma with High Myopia

Purpose To investigate whether lamina cribrosa (LC) defects are associated with optic disc morphology in primary open angle glaucoma (POAG) eyes with high myopia. Methods A total of 129 POAG patients and 55 age-matched control subjects with high myopia were evaluated. Three-dimensional scan images obtained by swept source optical coherence tomography were used to detect LC defects. Radial B-scans and infrared images obtained by spectral domain optical coherence tomography were used to measure β-peripapillary atrophy (PPA) lengths with and without Bruchs membrane (BM) (temporal, nasal, superior, and inferior), tilt angle (vertical and horizontal), and disc diameter (transverse and longitudinal). Peripapillary intrachoroidal cavitations (PICCs), disc area, ovality index, and cyclotorsion of the optic disc were analyzed as well. Results LC defects were found in 70 of 129 (54.2%) POAG eyes and 1 of 55 (1.8%) control eyes (P<0.001). Age, sex, spherical equivalent, axial length, intraocular pressure, and central corneal thickness were not significantly different among POAG eyes with LC defects, POAG eyes without LC defects, and control eyes. Temporal PPA lengths without BM in all three groups correlated significantly with vertical and horizontal tilt angles, although no PPA length with BM correlated significantly with any tilt angle. PICCs were detected more frequently in POAG eyes with LC defects than those without LC defects (P = 0.01) and control eyes (P = 0.02). POAG eyes with LC defects showed a smaller ovality index (P = 0.004), longer temporal PPA without BM (P<0.001), and larger vertical/horizontal tilt angles (vertical, P<0.001; horizontal, P = 0.01), and transverse diameter (P = 0.01). In multivariate analysis for the presence of LC defects, presence of POAG (P<0.001) and vertical tilt angle (P<0.001) were identified as significant. Conclusions The presence of LC defects was associated with myopic optic disc morphology in POAG eyes with high myopia.

Lamellar macular hole formation in patients with diabetic cystoid macular edema.

Purpose: To report lamellar macular hole formation in four patients with diabetic cystoid macular edema (CME). Methods: A review of the medical records of four patients with diabetic CME in whom lamellar macular hole formation was observed. The morphologic changes of CME, seen using optical coherence tomography (OCT), and best-corrected visual acuity were evaluated. Results: Lamellar macular hole formation had occurred, as determined by slit-lamp biomicroscopy and OCT. Although the inner retinal layer had disappeared, the outer retinal layer was preserved. On OCT, the reflective line of an epiretinal membrane or a posterior hyaloid membrane was seen on the surface of juxtafoveal retina, and visual acuity remained unchanged in all four patients. Conclusion: In diabetic patients with CME, the CME occasionally changes spontaneously to a lamellar macular hole. Although the central cystoid space disappears and foveal thickness decreases after this transformation, visual acuity may be little affected as long as the structure of the outer retina remains intact.

Microcystic inner nuclear layer changes and retinal nerve fiber layer defects in eyes with glaucoma

Objective To examine microcystic inner nuclear layer (INL) changes in glaucomatous eyes and to determine associated factors. Design Retrospective, cross-sectional, observational study. Methods Two hundred seventeen eyes of 133 patients with primary open angle glaucoma (POAG), 41 eyes of 32 patients with preperimetric glaucoma and 181 normal eyes of 117 subjects were ultimately included. Microcystic INL lesions were examined with infrared fundus images and with 19 vertical spectral domain optical coherence tomography (SD-OCT) images in the macular area. Results Microcystic INL changes were observed in 6.0% of eyes with POAG, but none of the normal eyes or eyes with preperimetric glaucoma showed microcystic INL changes. The proportion of eyes with advanced glaucoma was significantly larger (P = 0.013) in eyes with microcystic lesions than without. The visual field mean deviation (MD) slope was also significantly worse (P = 0.027) in eyes with microcystic lesions. No significant differences were observed in age, sex, refraction, axial length, intraocular pressure, or MD value between eyes with and without microcystic INL lesions. In several cases, microcystic INL lesions occurred along with glaucomatous visual field progression. The retinal nerve fiber layer (RNFL) thickness (P = 0.013) and ganglion cell layer (GCL) + inner plexiform layer thickness (P = 0.023) were significantly lower in areas with microcystic lesions than without. The INL was also significantly thicker (P = 0.002) in areas with microcystic lesions. Conclusions Microcystic INL lesions in glaucomatous eyes are closely associated with RNFL and GCL thinning and correlated with worse MD slope. These INL lesions may indicate focal and progressive damage in glaucoma.

Randomised controlled trial of posterior sub-Tenon triamcinolone as adjunct to panretinal photocoagulation for treatment of diabetic retinopathy

Aims: To evaluate the efficacy of a single posterior sub-Tenon capsule injection of triamcinolone acetonide (PSTA) before panretinal photocoagulation (PRP). Methods: This 6-month study involved the randomisation of 82 eyes of 41 patients, with bilateral severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy to a single PSTA 20 mg or to no injection before PRP. The primary end-point was change in best-corrected visual acuity (BCVA) at 6 months compared with that at baseline using the logarithm of the minimum angle of resolution (logMAR). Secondary end-points were changes in retinal thickness and intraocular pressure. Results: The mean changes in logMAR BCVA at 6 months compared with that at baseline were a worsening of 0.010 (SD 0.029) in the control group (no injection) and an improvement of 0.072 (0.028) in the PSTA group (p = 0.04). The mean changes in foveal thickness at 6 months compared with baseline measurements were an increase of 32.8 (82.8) μm in the control group and a lessening of 9.7 (85.6) μm in the PSTA group (p = 0.03). Conclusions: PSTA before PRP appears to be beneficial in preventing PRP-induced visual loss in eyes with diabetic retinopathy by reducing the chance of macular thickening.

Association between perifoveal hyperfluorescence and serous retinal detachment in diabetic macular edema.

OBJECTIVE To study the association between the fluorescence levels on fluorescein angiography images and the characteristics on spectral-domain optical coherence tomography (SD OCT) images in diabetic macular edema (DME). DESIGN Retrospective, observational, cross-sectional study. PARTICIPANTS One hundred sixty-seven consecutive eyes of 116 patients with diabetic retinopathy for whom FA and SD OCT were performed on the same day. METHODS Fluorescein angiography using the Heidelberg Retina Angiograph 2 and OCT images using Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany) were obtained. The leakage of fluorescein dye in each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid was quantified and defined as fluorescence levels, which were compared with the retinal thickness and foveal pathomorphologic features evaluated by SD OCT. MAIN OUTCOME MEASURES The relationship between fluorescence levels and the foveal pathomorphologic features on SD OCT images. RESULTS One hundred twelve (67%) eyes with center-involved DME had significantly higher fluorescence levels in all subfields of the ETDRS grid than 55 (33%) eyes without DME. Fluorescence levels were correlated modestly with the retinal thickness in individual subfields in eyes with center-involved DME. Thirty-seven eyes with foveal serous retinal detachment (SRD) had greater retinal thickness in all subfields and higher levels of fluorescence in most subfields, except the superior subfield of the inner ring. After adjusting for the central retinal thickness using multivariate analyses, eyes with SRD had significantly (P = 0.0085) higher fluorescence levels in the nasal subfield of the inner ring and the superior, nasal, and inferior subfields of the outer ring (P = 0.0117, P = 0.0020, and P = 0.0017, respectively). However, the fluorescence levels in any subfields of the inner or outer ring did not differ significantly between eyes with and without foveal cystoid spaces. CONCLUSIONS The correlation between the fluorescence levels and retinal thickness suggests that the vascular hyperpermeability in the perifovea contributes to the pathogenesis of foveal SRD in DME.

Qualitative and Quantitative Characteristics of Near-Infrared Autofluorescence in Diabetic Macular Edema

OBJECTIVE To study the characteristics of near-infrared autofluorescence (NIR-AF) imaging and its association with spectral-domain optical coherence tomography (SD-OCT) findings and logarithm of the minimal angle of resolution (logMAR) visual acuity (VA) in diabetic macular edema (DME). DESIGN Retrospective, observational, cross-sectional study. PARTICIPANTS One hundred twenty-one consecutive eyes of 87 patients with center-involved DME for whom NIR-AF and SD-OCT images of sufficient quality were obtained. METHODS The NIR-AF images were acquired using Heidelberg Retina Angiograph 2 (Heidelberg Engineering, Heidelberg, Germany), and sectional retinal images were obtained using Spectralis OCT (Heidelberg Engineering). The presence of a mosaic pattern and cystoid signs were determined qualitatively. We quantified the average fluorescence intensity in the central 1-mm subfield. The characteristics of the NIR-AF images were compared with the OCT findings and logMAR VA. MAIN OUTCOME MEASURES Qualitative and quantitative characteristics of the NIR-AF images and their association with SD-OCT findings and logMAR VA. RESULTS Fifty-seven eyes with a mosaic pattern in the NIR-AF macular images had worse logMAR VA (0.355±0.239 vs. 0.212±0.235; P = 0.001), a thicker central subfield (CSF) (530±143 μm vs. 438±105 μm; P <0.001), and disrupted external limiting membrane (ELM; P <0.001) compared with 64 eyes without these findings. Forty-one eyes with a cystoid sign in the NIR-AF images had worse logMAR VA (0.393±0.233 vs. 0.221±0.234; P <0.001) and a thicker CSF (557±155 μm vs. 443±100 μm; P <0.001) than those without them; there were no significant differences in the ELM status. The relative fluorescence intensity in the central subfield in the NIR-AF images was correlated negatively with the CSF thickness and logMAR VA (R = 0.492, P <0.001 and R = 0.377, P <0.001, respectively). Eyes with foveal serous retinal detachment had lower levels of relative fluorescence intensity than those without it (0.751±0.191 vs. 0.877±0.154; P = 0.007); there was no association with the presence of foveal cystoid spaces, disrupted ELM, or hyperreflective foci in the outer retinal layers. CONCLUSIONS Novel qualitative and quantitative NIR-AF characteristics in the macula indicated the clinical relevance and suggested the pathogenesis in DME.