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.

Ten-year outcomes of congenital cataract surgery performed within the first six months of life.

PURPOSE: To investigate the long-term outcomes of congenital cataract surgery performed within the first 6 months of life. SETTING: 11 ophthalmic surgical sites in Japan. DESIGN: Retrospective chart review. METHODS: Medical charts were retrospectively reviewed for 216 eyes of 121 patients. The age at surgery was 2.9 ± 1.7 months, with follow-up duration 13.0 ± 2.3 years. The cohort consisted of 83 cases with bilateral aphakia, 12 with bilateral pseudophakia, 20 with unilateral aphakia, and 6 with unilateral pseudophakia. RESULTS: Surgical intervention within the critical period of visual system development (10 weeks for bilateral and 6 weeks for unilateral cases) led to significantly better final visual acuity than surgery conducted after this time frame. The incidence of secondary glaucoma was similar between groups while the occurrence of visual axis opacification was more frequent with earlier surgery. A forward stepwise multiple regression analysis revealed that the final visual acuity was significantly associated with laterality of cataract (better outcomes in bilateral cases), phakic status (with pseudophakia outperforming aphakia), presence of systemic and ocular comorbidities, and development of secondary glaucoma. Secondary glaucoma was significantly more prevalent in aphakic eyes than pseudophakic eyes. CONCLUSIONS: In patients with genuine congenital cataract, surgery within the critical period of visual development results in better final visual acuity, albeit with an increased risk of visual axis opacification. The use of IOL with sophisticated surgical techniques shows promise even in congenital cataract surgery.

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.

Long-term surgical outcomes of pediatric cataract-multivariate analysis of prognostic factors.

We assessed the 10-year postoperative outcomes of pediatric cataract patients who underwent surgery at the age of 6 years or younger. A retrospective review of medical charts was conducted for 457 eyes of 277 patients, with the age at surgery averaging 1.3 ± 1.5 years (mean ± SD) and the follow-up duration averaging 12.8 ± 2.4 years (ranging from 10 to 17 years). The cohort included 250 eyes of 125 cases with bilateral aphakia (age at surgery 0.5 ± 0.8 years), 110 eyes of 55 cases with bilateral pseudophakia (1.9 ± 1.6 years), 42 cases with unilateral aphakia (1.1 ± 1.3 years), and 55 cases with unilateral pseudophakia (2.6 ± 1.7). A forward stepwise multiple regression analysis revealed that the best-corrected visual acuity at the final visit was significantly associated with laterality of cataract (with bilateral cases showing better results compared to unilateral cases), presence of systemic comorbidities, presence of ocular comorbidities, development of glaucoma, and phakic status (with better results in the pseudophakia group than the aphakia group). The age at surgery did not significantly affect visual acuity outcomes. A multiple logistic regression analysis demonstrated that the incidence of secondary glaucoma was significantly linked to younger age at surgery, phakic status (higher in aphakic than pseudophakic eyes), and presence of systemic comorbidities. In conclusion, after pediatric cataract surgery, final visual acuity was better in patients with bilateral cataracts, those treated with an intraocular lens, and cases without systemic or ocular comorbidities and secondary glaucoma. The development of secondary glaucoma was linked to younger age at surgery, aphakic status, and presence of systemic comorbidities.

Geographic pattern of central retinal sensitivity after intravitreal triamcinolone for diabetic macular edema.

PURPOSE: To evaluate the geographic pattern of central retinal sensitivity and its resolution shortly after intravitreal injection of triamcinolone acetonide (IVTA) for diabetic macular edema (DME). METHODS: Twenty eyes of 20 patients who underwent IVTA for the treatment of DME were reviewed retrospectively. Early changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), photoreceptor inner and outer segments (IS/OS) line and central retinal sensitivity were analyzed. Retinal sensitivity was measured at 40 points within the central 10 degrees of the macula with the Micro Perimeter 1 before treatment, and at 1 week and 1 month after IVTA. RESULTS: Mean BCVA and CMT improved significantly at 1 week and 1 month after IVTA. Mean retinal sensitivity, however, showed no significant improvement at 1 week (P = 0.238), but did show significant improvement at 1 month (P = 0.0003). Mean retinal sensitivity of the points at the central 2 degrees, which was significantly lower than that at 6 and 10 degrees before treatment, showed improvement similar to those of 6 and 10 degrees after IVTA. Mean retinal sensitivity in the nasal quadrant of the macular area had the best sensitivity at all time points, and improved more than it did in the other quadrants. Mean retinal sensitivity in the central 2 degrees was better in the eyes with complete IS/OS line (P < 0.0001). CONCLUSIONS: BCVA and CMT improved significantly after IVTA for DME. Retinal sensitivity also showed significant, albeit relatively slow, improvement. The nasal quadrant of the macular area showed more improvement than did any other quadrant.

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.

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.

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.

Retinal sensitivity loss and structural disturbance in areas of capillary nonperfusion of eyes with diabetic retinopathy.

PURPOSE: To assess light sensitivity and morphologic changes of capillary nonperfused areas in diabetic retinopathy. DESIGN: Prospective, observational cross-sectional study. METHODS: Seventeen consecutive patients (20 eyes) with areas of capillary nonperfusion resulting from severe nonproliferative or proliferative diabetic retinopathy were included in the study. All eyes underwent fluorescent angiography and fundus-related microperimetry. Nonperfused areas of the retina were scanned with optical coherence tomography (OCT). RESULTS: In all 20 diabetic eyes, areas of capillary nonperfusion detected by fluorescein angiography were associated with the loss of retinal sensitivity. At the edges of the nonperfused area, retinal sensitivity tended to be reduced. The OCT images suggested a structural disturbance of the inner retina and high-reflectivity deposition located between the outer segments of photoreceptor and the retinal pigment epithelium corresponding to the areas of capillary nonperfusion. CONCLUSIONS: Areas of capillary nonperfusion resulting from severe nonproliferative or proliferative diabetic retinopathy show morphologic changes of the retinal structure, which may lead to a loss of sensitivity.

Expression of hypothalamic neurohormones and their receptors in the human eye.

Extrapituitary roles for hypothalamic neurohormones have recently become apparent and clinically relevant, based on the use of synthetic peptide analogs for the treatment of multiple conditions including cancers, pulmonary edema and myocardial infarction. In the eye, it has been suggested that some of these hormones and their receptors may be present in the ciliary body, iris, trabecular meshwork and retina, but their physiological role has yet to be elucidated. Our study intends to comprehensively demonstrate the expression of some hypothalamic neuroendocrine hormones and their receptors within different retinal and extraretinal structures of the human eye. Immunofluorescence, Western blot analysis, and RT-PCR were used to evaluate the qualitative and quantitative expression of Luteinizing Hormone Releasing Hormone (LHRH), Growth Hormone Releasing Hormone (GHRH), Thyrotropin Releasing Hormone (TRH), Gastrin Releasing Peptide (GRP) and Somatostatin as well as their respective receptors (LHRH-R, GHRH-R, TRH-R, GRP-R, SST-R1) in cadaveric human eye tissue and in paraffinized human eye tissue sections. The hypothalamic hormones LHRH, GHRH, TRH, GRP and Somatostatin and their respective receptors (LHRH-R, GHRH-R, TRH-R, GRPR/BB2 and SST-R1), were expressed in the conjunctiva, cornea, trabecular meshwork, ciliary body, lens, retina, and optic nerve.

White Dots as a Novel Marker of Diabetic Retinopathy Severity in Ultrawide Field Imaging.

PURPOSE: To characterize white dots in diabetic retinopathy (DR) and their association with disease severity using ultra-wide-field scanning laser ophthalmoscopy. METHODS: We randomly selected 125 eyes of 77 patients (25 eyes from individual categories of the international classification of DR severity) for which ultrawide field photographs were obtained. We characterized white dots, which were delineated by higher signal levels on green but not red laser images, and evaluated the relationship between the number of white dots and the international severity scale of DR. RESULTS: Most white dots were located in nonperfused areas, and the number of total white dots was significantly correlated to that of dots in nonperfused areas. White dots corresponded to microaneurysms around the boundary between nonperfused areas and perfused areas or unknown lesions in nonperfused areas. Eyes with DR had significantly more white dots than those with no apparent retinopathy. The numbers of white dots in moderate nonproliferative diabetic retinopathy (NPDR) or more severe grades were significantly higher than in mild NPDR. The area under the receiver operating characteristics curve (AROC) analyses demonstrated that the number of white dots had the significance in the diagnosis of DR (0.908-0.986) and moderate NPDR or more severe grades (0.888-0.974). CONCLUSIONS: These data suggest the clinical relevance of white dots seen on ultrawide field images in the diagnosis of the severity of DR.

Macular morphologic findings on optical coherence tomography after microincision vitrectomy for proliferative diabetic retinopathy.

PURPOSE: To investigate macular morphology on spectral-domain optical coherence tomography (SD-OCT) images after microincision vitrectomy for vitreous hemorrhage associated with proliferative diabetic retinopathy (PDR). METHODS: In this retrospective case series, 69 eyes (57 consecutive patients) that underwent 23-gauge microincision vitrectomy for vitreous hemorrhage due to PDR were investigated. Qualitative and quantitative characteristics on SD-OCT images [central retinal thickness, external limiting membrane (ELM), and the ellipsoid zone, epiretinal membranes involving the fovea, and hyperreflective foci at the fovea] were assessed 6 months postoperatively. Their association with the logarithm of the minimum angle of resolution visual acuity (logMAR VA) was evaluated. RESULTS: The ELM was disrupted in 15 and the ellipsoid zone in 27 eyes, and associated significantly (P < 0.001, for both comparisons) with poor visual outcomes 6 months postoperatively. Hyperreflective foci in the outer retinal layers were associated with either a disrupted ELM or ellipsoid zone and poor prognoses (P < 0.001, for all comparisons). The accumulation of hyperreflective foci at the fovea in five eyes was correlated significantly (P < 0.001) with poorer logMAR VA. Twenty-nine eyes had center-involved diabetic macular edema 6 months postoperatively, whereas the central thickness was not correlated with the logMAR VA (R = -0.148, P = 0.224). Eight eyes with either epiretinal membrane on SD-OCT images had greater central thickness (P = 0.003), although there were no differences in the logMAR VA between eyes with and without it (P = 0.648). CONCLUSIONS: Foveal photoreceptor damage is associated with poor visual outcomes after microincision vitrectomy for vitreous hemorrhage due to PDR.

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.

Parallelism as a novel marker for structural integrity of retinal layers in optical coherence tomographic images in eyes with epiretinal membrane.

PURPOSE: To propose a new parameter, "Parallelism," to evaluate retinal layer integrity on spectral-domain optical coherence tomography (SDOCT), and to investigate the association between parallelism and visual function in eyes with idiopathic epiretinal membrane (ERM). DESIGN: Retrospective, observational evaluation of a diagnostic test. METHODS: We evaluated a consecutive series of 57 eyes of 57 patients with ERM and 30 healthy eyes of 30 volunteers for whom M-CHARTS testing and SDOCT were performed on the same day. OCT images were skeletonized, and the orientation of segmented lines in the image was termed "Parallelism" and was expressed as a value ranging from 0-1 and increasing as the retinal layers ran more parallel with each other. The relationships between parallelism and visual acuity and between parallelism and metamorphopsia score were evaluated. RESULTS: In normal eyes, parallelism was nearly homogeneous and varied slightly with the location. Parallelism in eyes with ERM was significantly lower than that in normal eyes. In the horizontal and vertical scans, parallelism was significantly correlated with visual acuity, horizontal metamorphopsia score, and vertical metamorphopsia score. Parallelism of the center (1 mm) in the horizontal scan was strongly correlated with horizontal metamorphopsia score (R = -0.632; P < .0001). Significant negative correlation was found between parallelism and retinal thickness both in horizontal and vertical scans. CONCLUSIONS: Parallelism was significantly lower in eyes with ERM than in normal eyes, and correlated strongly with metamorphopsia and visual acuity in eyes with ERM.

Parallelism for quantitative image analysis of photoreceptor-retinal pigment epithelium complex alterations in diabetic macular edema.

PURPOSE: To propose a new method to quantitatively and comprehensively evaluate photoreceptor-RPE complex alterations on spectral-domain optical coherence tomography (SD-OCT) imaging in eyes with diabetic macular edema (DME). METHODS: Spectral-domain OCT images from a consecutive series of 90 eyes in 79 patients with DME and 30 healthy eyes in 30 volunteers were analyzed retrospectively. The subfoveal area covering the photoreceptor layers was skeletonized and the orientation of the segmented lines was termed "parallelism," which reflects image complexity. Photoreceptor layer status at the fovea was categorized by graders, including continuity of the external limiting membrane (ELM) line, inner segment ellipsoid line, and the presence of hyperreflective foci in the outer retinal layers. The relationships among parallelism, visual acuity, and photoreceptor layer status were evaluated. RESULTS: Parallelism was significantly lower in eyes with DME than in normal eyes (P < 0.0001), and correlated strongly with visual acuity in eyes with DME (R = -0.592; P < 0.0001). Eyes with an intact inner segment ellipsoid line or ELM line had significantly better visual acuity (VA) and higher parallelism than eyes with a discontinuous or absent inner segment ellipsoid line or ELM line. Parallelism was significantly higher (P < 0.0001) and logMAR VA significantly better (P < 0.0001) in the group without hyperreflective foci in the outer retinal layers than in the group with hyperreflective foci in the outer retinal layers. CONCLUSIONS: Parallelism has the potential to reflect structural changes of the photoreceptor layers in DME.

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.

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 ß-peripapillary atrophy (PPA) lengths with and without Bruch's 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.

Time-lapse imaging of retinal angiogenesis reveals decreased development and progression of neovascular sprouting by anecortave desacetate.

PURPOSE: To elucidate the effects of anecortave desacetate (AD) treatment on the kinetics of neovascular sprouting and its molecular mechanisms in retinal explants and during retinal vascular development in mice. METHODS: The antiangiogenic effects of AD on retinal angiogenesis were evaluated using two different models: a retinal explant model treated with vascular endothelial growth factor (VEGF) and a mouse model of postnatal retinal vascular development. 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: AD treatment significantly reduced the number of neovascular sprouts in retinal explants in a dose-dependent manner. Time-lapse imaging demonstrated that AD suppressed the new development and elongation of neovascular sprouts and the motility of tip cells. Moreover, AD treatment disturbed the filopodial extension and significantly decreased the transcriptional levels of KDR and platelet-derived growth factor-B, which are highly expressed in tip cells. In addition, it was confirmed that AD inhibited postnatal development of the retinal vasculature in mice, including filopodial extension in tip cells. These data suggest that AD suppresses both the development and the progression of sprouting angiogenesis. Interestingly, VEGF-induced microglial movements were also reduced in the retinal explants treated with AD. These changes were consistent with decreased mRNA levels of SDF-1 and Flt-1, which regulate the activation of inflammatory cells. CONCLUSIONS: AD inhibited both the development and the progression of VEGF-induced retinal angiogenesis mediated, in part, by the suppression of tip cell motility in two angiogenic models.

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.