Fundus autofluorescence not predictive of treatment response to intravitreal bevacizumab in exudative age-related macular degeneration.

PURPOSE: Foveal autofluorescence (AF) has been suggested to be a potential predictor of treatment outcome in choroidal neovascularization (CNV) secondary to age-related macular degeneration and could be a useful marker to help prognosticate for patients and for clinical trials. This retrospective study aims to determine if pretreatment foveal AF can predict treatment response to intravitreal bevacizumab monotherapy in CNV secondary to age-related macular degeneration. METHODS: Ninety-five eyes (85 patients) with naive CNV secondary to age-related macular degeneration, treated with intravitreal bevacizumab monotherapy were included in this study. Lesion size, CNV type on fluorescein angiography, pretreatment best-corrected visual acuity, and foveal AF pattern (intact/nonintact) were used as predictors. Multivariate linear regression and logistic regression were performed using best-corrected visual acuity change and anatomical response at 6 months as the dependent variables separately. RESULTS: Pretreatment foveal AF (intact or nonintact) did not predict visual outcome (P = 0.17) nor did lesion size (P = 0.2) or CNV type (P = 0.61). Foveal AF did correlate with the visual acuity but it did not predict any treatment response. Pretreatment best-corrected visual acuity was the only predictive factor for the visual outcome (P = 0.043). CONCLUSION: Pretreatment AF is not a predictor for the treatment response to intravitreal bevacizumab monotherapy in eyes with CNV secondary to age-related macular degeneration.

Spectral-domain optical coherence tomography imaging of postoperative scleral buckles.

PURPOSE: To describe the appearance on spectral domain optical coherence tomography of the peripheral retina and overlying vitreous after scleral buckling surgery. METHODS: Retrospective case series of patients who underwent scleral buckle surgery and had subsequent scanning laser ophthalmoscopy/spectral-domain optical coherence tomography images over the area of buckled retina. Twelve eyes from 11 patients were identified and show a variety of retinal anatomies, vitreous configurations, and clinical applications. RESULTS: Twelve eyes from 11 patients were studied, and in all eyes, the peripheral retina could be visualized with 10 cases of successful retinal reattachment and 2 cases of scleral buckle failure. Vitreous including strands to the causative retinal tear was seen in three eyes and overlying vitreous in four additional eyes. The scleral buckle indentation was seen in nine eyes, and in the two failed scleral buckles, unsupported retinal breaks, residual vitreous traction, and persistent subretinal fluid over the scleral buckle could be visualized and followed as it resolved. CONCLUSION: Simultaneous scanning laser ophthalmoscopy/spectral-domain optical coherence tomography allows detailed examination of the peripheral retina and overlying vitreous after scleral buckle surgery. Along with confirmation that the retina is attached and retinal breaks are closed, the scanning laser ophthalmoscopy/spectral-domain optical coherence tomography can be used in the postoperative management of scleral buckles to identify residual vitreous traction and monitor areas of subretinal fluid.

Prognosti implications of pigment epithelial detachment in bevacizumab (avastin)-treated eyes with age-related macular degeneration and choroidal neovascularization.

PURPOSE: To evaluate the response to primary bevacizumab treatment of eyes with age-related macular degeneration (AMD) and choroidal neovascularization (CNV) with a large pigment epithelial detachment (PED) component and to compare the increase in visual acuity and reabsorption of retinal fluid in PED eyes with eyes with CNV in AMD with a minimal to no PED component. METHODS: We reviewed 43 consecutive eyes with CNV and AMD on primary bevacizumab therapy. There were 13 eyes with a large PED component in AMD with CNV and 30 eyes with a minimal to no PED in CNV. Only patients with no previous treatment for AMD and those started on purely intravitreal bevacizumab treatment were taken in the study. Pigment epithelial detachment size, time to PED collapse, and retinal or subretinal fluid resolution were determined as was Early Treatment Diabetic Retinopathy Study vision. Time to resolution of intraretinal and subretinal fluid was compared between the PED group and the non-PED group using survival analysis. RESULTS: In AMD with CNV eyes having a large PED component, sub- and intraretinal fluid initially resolved faster than the sub-PED fluid (P = 0.03). The subretinal pigment epithelial fluid itself was highly resistant. Visual acuity improvement was similar in both groups. CONCLUSION: Despite monthly intravitreal bevacizumab injections for neovascular AMD patients with a large component PED, the majority had minimal to no response of the PED. Sub- and intraretinal fluid response was faster in neovascular AMD without large PEDs, but after 7 months, vision change and reabsorption of intra- and subretinal fluid were similar in the two groups. Sub- and intraretinal fluid response did not appear to be related to PED size. Bevacizumab was very effective in reducing more of the sub- and intraretinal fluid than the PED fluid in AMD with CNV.

Long-term SD-OCT/SLO imaging of neuroretina and retinal pigment epithelium after subthreshold infrared laser treatment of drusen.

PURPOSE: The purpose of this study was to determine the long-term effect of subthreshold diode laser treatment for drusen in patients with nonexudative age-related macular degeneration with spectral domain optical coherence tomography combined with simultaneous scanning laser ophthalmoscope. METHODS: Eight eyes of four consecutive age-related macular degeneration patients with bilateral drusen previously treated with subthreshold diode laser were imaged with spectral domain optical coherence tomography/scanning laser ophthalmoscope. Abnormalities in the outer retinal layers' reflectivity as seen with spectral domain optical coherence tomography/scanning laser ophthalmoscope were retrospectively analyzed and compared with color fundus pictures, and autofluorescence images were acquired immediately before and after the laser treatment. RESULTS: A focal discrete disruption in the reflectivity of the outer retinal layers was noted in 29% of the laser lesions. The junction in between the inner and outer segment of the photoreceptor was more frequently affected, with associated focal damage of the outer nuclear layer. Defects of the retinal pigment epithelium were occasionally detected. These changes did not correspond to threshold burns on color fundus photography but corresponded to focal areas of increased autofluorescence in the majority of the cases. CONCLUSION: Subthreshold diode laser treatment causes long-term disruption of the retinal photoreceptor layer as analyzed by spectral domain optical coherence tomography/scanning laser ophthalmoscope. The concept that subthreshold laser treatment can achieve a selected retinal pigment epithelium effect without damage to rods and cones may be flawed.

Dynamics of the macular hole-silicone oil tamponade interface with patient positioning as imaged by spectral domain-optical coherence tomography.

PURPOSE: The purposes of this study were to evaluate with spectral domain-optical coherence tomography the relationship between the retina and overlying silicone oil tamponade after macular hole surgery and to evaluate how this relationship changes with patient positioning. METHODS: We studied a retrospective consecutive case series of 10 eyes from 9 patients who underwent macular hole surgery with silicone oil tamponade and subsequent spectral domain-optical coherence tomography scans. Four of the included eyes were also imaged with patients in face-down posture to determine whether the silicone-retina apposition changes with prone positioning. Finally, a single patient was also scanned in the lateral and supine positions. RESULTS: The posterior surface of the silicone oil bubble was well visualized in all 10 eyes. In the majority of eyes (7 of 10), the oil tamponade bridged the macular hole, creating a prefoveal fluid space, but in 3 eyes the silicone oil filled the macular hole and was seen in touch with the underlying foveal depression or retinal pigment epithelium. In 75% of eyes (3 of 4), the silicone oil-retinal approximation did not vary with face-down position. Supine positioning clearly floated the silicone tamponade anteriorly and off the retinal surface. CONCLUSION: Silicone oil tamponade can either bridge macular holes or, in a novel finding, fill the underlying foveal depression or macular hole space. Generally, the oil position is stable between face-forward and prone spectral-domain optical coherence tomography images, suggesting that either of these patient positions allows waterproofing of the underlying macular hole. Finally, our images confirm that supine positioning should be avoided postoperatively because it leads to loss of oil-retinal tamponade.

Disruption of the photoreceptor inner segment/outer segment layer on spectral domain-optical coherence tomography is a predictor of poor visual acuity in patients with epiretinal membranes.

PURPOSE: The purpose of this study was to evaluate the predictive value of spectral domain-optical coherence tomography-determined integrity of the photoreceptor inner segment/outer segment (IS/OS) junction on visual acuity in patients with epiretinal membranes (ERMs). METHODS: This is a retrospective consecutive case series of 54 eyes from 48 patients with primary ERMs who underwent spectral domain-optical coherence tomography scans. Regression analysis was used to calculate the relative contribution of several variables, including photoreceptor IS/OS disruption, grade of IS/OS disruption, macular thickness, and ERM grade on fundus imaging to visual acuity. RESULTS: The strongest individual predictor of visual acuity among patients with ERM was central retinal thickness on spectral domain-optical coherence tomography (r(2) = 0.16, P = 0.0024), but the most efficient model was the combination of macular thickness and presence or absence of photoreceptor IS/OS disruption (r(2) = 0.24, P = 0.0008). Additional measured variables did not significantly contribute to visual acuity prediction. Inner segment/outer segment layer integrity was also an independent predictor of visual acuity, and patients with IS/OS disruption were 6.88 times as likely to have 20/50 or worse vision than patients with intact photoreceptor layers (odds ratio: 6.88, confidence interval: 1.56-30.43, P = 0.01). CONCLUSION: Disruption of the photoreceptor IS/OS junction is a statistically significant predictor of poor visual acuity among patients with ERM and is most useful when combined with central retinal thickness measurement.

Correlation between morphologic features on spectral-domain optical coherence tomography and angiographic leakage patterns in macular edema.

PURPOSE: The purpose of this study was to determine the morphologic patterns of angiographic macular edema using simultaneous colocalization of fluorescein angiography and spectral-domain optical coherence tomography (SD-OCT) images in diabetes, epiretinal membrane, uveitic and pseudophakic cystoid macular edema, and vein occlusion. METHODS: Eighty-seven consecutive patients (107 eyes) with macular edema from 5 different etiologies were imaged by simultaneous scanning laser ophthalmoscopy/OCT to study the morphologic patterns of edema on SD-OCT and then correlated/colocalized with the fluorescein angiographic patterns of leakage. Statistical analysis was done to analyze the differences in the morphologic OCT pattern by different diseases. RESULTS: Spectral-domain OCT characteristics of macular edema showed a significant difference across different diseases (P = 0.037). Cystic fluid pockets were found to be more commonly seen in patients with diabetic macular edema and retinal vein occlusions, whereas those cases with macular edema secondary to epiretinal membrane showed noncystic changes on OCT. Seventy of the 107 eyes had diffuse angiographic leakage, and the remaining 37 eyes had cystoid leakage on angiography. Of the 70 eyes with diffuse leakage, 24.28% showed microcysts on SD-OCT in the area of edema, and 70% eyes had diffuse thickening or distorted architecture without cyst. All 37 eyes with cystoid leakage showed cysts in the area of edema by SD-OCT. A total of 3.73% of eyes with fluorescein angiographic leakage had no abnormalities on SD-OCT. CONCLUSION: Eyes with diabetic macular edema and retinal vein occlusions have a significantly higher incidence of cyst formation on SD-OCT. There was no correlation between visual acuity and cyst formation. Diffuse noncystoid angiographic macular edema may show microcysts on SD-OCT, but diffuse edema is more commonly associated with thickening or distortion of the retinal layers without cyst formation. Cystoid leakage on fluorescein angiography is always associated with cystic changes on SD-OCT.

Optical coherence tomography-raster scanning and manual segmentation in determining drusen volume in age-related macular degeneration.

PURPOSE: Drusen are the hallmark of age-related macular degeneration (AMD), and substantial evidence exists that the amount of drusen and their effect on retinal pigment epithelium is a strong predictor of progression of AMD and vision loss. Until recently, it was not possible to quantitate the volume of the drusen. However, the use of image-stabilized scanning laser ophthalmoscope or spectral domain-optical coherence tomography (OCT) has enabled determination of drusen volume of this abnormal material. The purpose of this study was to assess the correlation of drusen volume with Age-Related Eye Disease Study (AREDS) grade and drusen area in dry AMD. METHODS: Thirty-six eyes from 18 patients with nonexudative AMD with visual acuity between 20/16 and 20/160 were studied. Spectral domain-OCT or simultaneous OCT scans were taken as color fundus photographs (35 degrees ) of each eye. Early Treatment Diabetic Retinopathy Study visions were also recorded. The full AREDS score excluding late-stage AMD was determined by agreement between two trained observers. Drusen volume was determined by examination of a series of 96 spectral domain-OCT scans taken from arcade to arcade for a length of 6 mm. The volume was determined by calculating the drusen area in each scan and determining the drusen volume by calculating the effective volume of each cut using National Institutes of Health Image J. Drusen were identified and outlined manually, not using an automated algorithm. RESULTS: There was a strong and significant correlation between drusen volume and AREDS-determined drusen area (P < 0.0001, r = 0.78). In addition, there was a correlation between AREDS classification and drusen volume (P = 0.023, r = 0.43) as determined by pairwise correlation. CONCLUSION: Drusen volume as determined by spectral domain-OCT correlates with AREDS-determined drusen area and AREDS grade in nonexudative AMD. The correlation is not perfect, however, because drusen area and volume average 40% and 82% of the variation, respectively. Drusen volume can provide additional information in grading the severity of eyes with dry AMD.

Spectral domain optical coherence tomography for imaging ERM, retinal edema, and vitreomacular interface.

PURPOSE: To evaluate images taken with OTI-OPKO Spectral domain optical coherence tomography (OCT; OTI-OPKO Health Inc, Miami, FL)/scanning laser ophthalmoscope (resolution of 5-8 microm) and compare them with conventional StratusOCT (Carl Zeiss Meditec Inc, Dublin, CA) in eyes with epiretinal membranes (ERMs), macular edema, and vitreoretinal interface abnormalities. METHODS: We evaluated 79 consecutive eyes with retinal pathologies using Spectral OCT/scanning laser ophthalmoscope and StratusOCT at the Jacobs Retina Center, University of California San Diego, CA. Pathologies included ERM, macular edema, and vitreomacular traction. Two masked reviewers graded the pathologic findings on the basis of visibility (scale 0-III). A quantitative continuous scale grading system was also used. RESULTS: Statistical analysis showed significant differences in ERM visibility between the spectral OCT/scanning laser ophthalmoscope and StratusOCT (P < 0.0001; signed-rank test). Furthermore, posterior hyaloid visibility was significantly different (P < 0.0001) as was the macular edema grading (P < 0.0001). The Gaussian noise grading system was performed for a smaller subset of 40 eyes and it gave the same results. Spectral OCT was particularly useful in the diagnosis of subtle ERM, minimal diffuse macular edema, and morphology of macular cystic spaces, posterior vitreous detachment, and attachments of the posterior hyaloid. CONCLUSION: The Spectral OTI-OPKO instrument allows significantly better visualization of vitreoretinal surface diseases like ERM, posterior hyaloid, and retinal edema than StratusOCT. High-speed Spectral OCT/scanning laser ophthalmoscope allows rapid image acquisition, higher number of cuts, and better sampling yielding superior imaging of retinal pathology.

Vitreoretinal interface abnormalities in healed cytomegalovirus retinitis.

PURPOSE: The purpose of this study was to use spectral domain-optical coherence tomography in imaging retina and vitreoretinal relationship in healed cytomegalovirus (CMV) retinitis. METHODS: Patients with a history of confirmed CMV retinitis and a healed CMV scar on clinical examination underwent spectral domain-optical coherence tomography examinations using a Spectralis Heidelberg retinal angiograph/optical coherence tomography instrument (Heidelberg Engineering, Heidelberg, Germany). Horizontal and vertical cross-sectional B-scans 6 mm x 6 mm passing through the center and margins of healed CMV scars and adjacent retina were obtained. We analyzed the integrity of retinal layers in the area of the CMV scar, integrity of retinal layers at the margins of the CMV scar, margins of the scar and adjacent nonaffected retina, and any structural alterations in the retina or vitreous. RESULTS: Eleven eyes (50%) had vitreous detached, and 11 eyes attached over the area of healed retinitis. Nineteen eyes (86%) had an epiretinal membrane, and 12 eyes (54%) had vitreoretinal gliosis present over the healed retinitis or in its vicinity. The epiretinal membrane and vitreoretinal gliosis occurred concomitantly in 10 eyes and could be well differentiated on scans. None of these were found in control eyes. CONCLUSION: This first in vivo study of vitreoretinal interface in inactive CMV retinitis shows that the vitreoretinal interface in healed CMV is pathologically changed. The presence of epiretinal membranes, vitreoretinal gliosis, and traction may help explain the higher incidence of retinal elevation, retinal breaks, and retinal detachment in these eyes.

Imaging of long-term retinal damage after resolved cotton wool spots.

PURPOSE: Patients infected with the human immunodeficiency virus (HIV) develop noninfectious retinopathy characterized by retinal cotton wool spots (CWS) and microvascular abnormalities. Ophthalmoscopically, CWS fade with time. We hypothesized that structural changes should be permanent and possibly visible well after ophthalmoscopic resolution. We used simultaneous spectral domain optical coherence tomography (SD-OCT)/scanning laser ophthalmoscope (SLO) to allow colocalization of the lesions and determine the extent and location of residual damage after ophthalmoscopic resolution of the lesions. DESIGN: Retrospective, noninterventional case series. PARTICIPANTS: Eight eyes of 7 HIV patients with 19 resolved retinal CWS. METHODS: Nineteen retinal CWS were imaged between 2 and 16 years (median, 7.84) after the acute lesions using simultaneous SD-OCT and SLO examinations. The areas of the previous CWS were scanned by overlaying the color retinal image over the SLO image and scanning at high resolution in the horizontal plane through the resolved lesion. Each CWS lesion had a control area taken from the same eye within 2 disc diameters of the lesion. The thickness of each of the retinal layers was compared between lesions and control areas using a paired t-test with multitest correction. MAIN OUTCOME MEASURES: Thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL). RESULTS: The greatest loss of thickness was seen in the retinal GCL with a 43% reduction in thickness. There was a statistically significant thinning of the RNFL, GCL, IPL, INL, and OPL. The median thickness differences ranged from 5 to 7 microns. This difference was highly significant. Another striking finding was the displacement of the ONL toward the retinal surface resulting in an apparent increase in thickness of the ONL by >15% (median difference, 12 microns). CONCLUSIONS: Our data, using ultrahigh resolution and high-speed SD-OCT/SLO, show and quantify the presence of permanent retinal destruction associated with retinal CWS in HIV disease.

The role of abnormal vitreomacular adhesion in age-related macular degeneration: spectral optical coherence tomography and surgical results.

PURPOSE: To assess the incidence of vitreomacular adhesion and traction in age-related macular degeneration (AMD), and to evaluate surgical treatment in a subset of patients with choroidal neovascularization (CNV) nonresponsive to anti-neovascular growth factor (anti-VEGF) treatment. DESIGN: Retrospective observational case-control and interventional case series. METHODS: Spectral optical coherence tomography, combined with simultaneous scanning laser ophthalmoscope (Spectral OCT/SLO), was performed in 170 eyes of 94 elderly patients, 61 with exudative AMD, 59 with nonexudative AMD, and 50 control eyes. The presence of hyaloid adhesion to the posterior pole, and vitreomacular traction (VMT) were determined. Five patients with VMT underwent surgical hyaloid removal. Best-corrected visual acuity (BCVA) and retinal thickness were evaluated as outcomes. RESULTS: Hyaloid adhesion was present in 17 eyes with exudative AMD (27.8%), 15 eyes with nonexudative AMD (25.4%), and eight control eyes (16%). Significant difference was found among the groups (P = .002). Among the eyes with hyaloid adhesion, VMT was shown in 10 eyes (59%) with exudative AMD, two eyes (13%) with nonexudative AMD, and one control eye (12%). VMT was associated with the severity of AMD (P = .0082). The area of hyaloid adhesion was significantly smaller than and concentric to the area of CNV complex in eyes with exudative AMD. Eyes with VMT that underwent surgery experienced a modest improvement of BCVA and decrease of retinal thickness. CONCLUSIONS: Hyaloid adhesion to the macula is associated with AMD, and frequently causes VMT in eyes with CNV. Tractional forces may antagonize the effect of anti-VEGF treatment, and cause pharmacological resistance in a subpopulation of patients. Future studies are needed to define the role of vitreoretinal surgery in such cases. Spectral OCT/SLO allows careful diagnosis and follow-up.

Accuracy of the Heidelberg Spectralis in the alignment between near-infrared image and tomographic scan in a model eye: a multicenter study.

PURPOSE: To evaluate temporal changes and predictors of accuracy in the alignment between simultaneous near-infrared image and optical coherence tomography (OCT) scan on the Heidelberg Spectralis using a model eye. DESIGN: Laboratory investigation. METHODS: After calibrating the device, 6 sites performed weekly testing of the alignment for 12 weeks using a model eye. The maximum error was compared with multiple variables to evaluate predictors of inaccurate alignment. Variables included the number of weekly scanned patients, total number of OCT scans and B-scans performed, room temperature and its variation, and working time of the scanning laser. A 4-week extension study was subsequently performed to analyze short-term changes in the alignment. RESULTS: The average maximum error in the alignment was 15 ± 6 µm; the greatest error was 35 µm. The error increased significantly at week 1 (P = .01), specifically after the second imaging study (P < .05); reached a maximum after the eighth patient (P < .001); and then varied randomly over time. Predictors for inaccurate alignment were temperature variation and scans per patient (P < .001). For each 1 unit of increase in temperature variation, the estimated increase in maximum error was 1.26 µm. For the average number of scans per patient, each increase of 1 unit increased the error by 0.34 µm. CONCLUSION: Overall, the accuracy of the Heidelberg Spectralis was excellent. The greatest error happened in the first week after calibration, and specifically after the second imaging study. To improve the accuracy, room temperature should be kept stable and unnecessary scans should be avoided. The alignment of the device does not need to be checked on a regular basis in the clinical setting, but it should be checked after every other patient for more precise research purposes.

A degenerative retinal process in HIV-associated non-infectious retinopathy.

HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner-retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV-positive patients.

Ocular safety profile and intraocular pharmacokinetics of an antagonist of EphB4/EphrinB2 signalling.

AIMS: To characterise the ocular safety profile of sEphB4 and its pharmacokinetics in rabbit eyes. METHODS: 15 rabbits with single intravitreal injection of sEphB4 in the right eye (1000 µg, 465 µg, 160 µg or 80 µg) and phosphate-buffered saline in the left eye were studied at different time points by monitoring inflammatory changes, intraocular pressure, electroretinogram and histological changes. The dose of 80 µg/eye was injected intravitreally into 21 rabbits, and the fellow eyes were used as controls for sEphB4 ocular pharmacokinetics. sEphB4 concentrations were measured in the vitreous, retina, choroids and plasma using ELISA at the designated time points. RESULTS: The study showed that there was no evidence of intraocular toxicity at any time point with any dose tested. No statistically significant differences were seen in the intraocular pressure, scotopic and photopic ERGs, and histopathology between the control and sEphB4 injected eyes. A pharmacokinetic study demonstrated a vitreous half-life of 4.1 days and 6.3 days in the retina. The mean residence time of the drug was 10.45 days in the retina and 7.95 days in the choroid. CONCLUSION: It seems that sEphB4 at the concentrations studied did not appear to be toxic to rabbit eyes and may be a longer-acting treatment option to the current therapies for ocular abnormal neovascularisation.

The association between percent disruption of the photoreceptor inner segment-outer segment junction and visual acuity in diabetic macular edema.

PURPOSE: To evaluate the integrity of the photoreceptor inner segment/outer segment (IS/OS) junction using spectral-domain optical coherence tomography (SD OCT) in patients with diabetic macular edema and to correlate the relationship between the integrity of the IS/OS junction and visual acuity. DESIGN: Retrospective, comparative, consecutive case series. METHODS: Sixty-two eyes from 38 patients with diabetic macular edema underwent SD OCT imaging. For each patient, 2 experienced observers masked to visual acuity measured several SD OCT variables, including central macular thickness, retinal volume, global disruption scale of outer retina, percentage disruption of the outer retina, and history of previous treatments. Visual acuity recorded as number of Early Treatment Diabetic Retinopathy Study letters was used as the outcome variable in univariate and multivariate analysis testing the measured SD OCT variables as predictors. RESULTS: A statistically significant correlation between percentage disruption of the IS/OS junction and visual acuity was found (P = .0312). Additionally, there was a strong trend suggesting a relationship between macular volume and visual acuity, although borderline significance was found (P = .07). CONCLUSIONS: Disruption of the photoreceptor IS/OS junction is an important predictor of visual acuity among diabetic macular edema patients.

Observations by spectral-domain optical coherence tomography combined with simultaneous scanning laser ophthalmoscopy: imaging of the vitreous.

PURPOSE: To determine the ability to detect normal vitreous structure, evolving posterior vitreous detachment (PVD), and related vitreoretinal changes with combined spectral-domain optical coherence tomography (SD-OCT) and scanning laser ophthalmoscopy (SLO). DESIGN: Observational cross-sectional study. METHODS: Simultaneous SD-OCT and SLO imaging instruments (SD-OCT/SLO) were used to image both eyes of patients with symptoms of PVD. The vitreous cortex, preretinal lacunae, hyaloid, and its relations to the retinal surface were analyzed. In addition, ultrasound was performed in a subset of patients to determine the stage of PVD. RESULTS: Two-hundred two eyes of 113 subjects were scanned. There was a high correlation between diagnosis of complete PVD by clinical examination and OCT (95 vs 93 eyes, respectively; kappa, 0.82). A partial PVD was detected more frequently by SD-OCT/SLO than by biomicroscopy examination (45 vs 7 eyes; P < .0001). Ultrasound was performed in a subset of 30 eyes. A high agreement was found between ultrasound and SD-OCT/SLO results for both complete PVD (kappa, 0.933) and incomplete PVD (kappa, 0.91). Vitreous cortex was detected in 181 eyes, and posterior precortical vitreous pocket was detected in 85 eyes. The effects of PVD, including vitreoretinal traction, paravascular lamellar holes, and fine changes at the fovea, could be visualized reliably in detail only with SD-OCT/SLO. In all these eyes, SD-OCT/SLO allowed improved visualization of the vitreoretinal relationship. CONCLUSIONS: SD-OCT/SLO provides unprecedented in vivo information about the physiologic and pathologic vitreous structure; it allows an extremely detailed analysis of the vitreoretinal interface, and it is particularly useful for defining focal changes and PVD.

Correlation between spectral-domain optical coherence tomography and fundus autofluorescence at the margins of geographic atrophy.

PURPOSE: To study the appearance of margins of geographic atrophy in high-resolution optical coherence tomography (OCT) images and to correlate those changes with fundus autofluorescence (FAF) imaging. DESIGN: Retrospective, observational case study. METHODS: Patients with geographic atrophy secondary to dry age-related macular degeneration were assessed by means of spectral-domain OCT (Spectralis Heidelberg Retinal Angiograph/OCT; Heidelberg Engineering, Heidelberg, Germany; or OTI Inc, Toronto, Canada) as well as autofluorescence imaging (Heidelberg Retinal Angiograph or Spectralis; Heidelberg Engineering). The outer retinal layer alterations were analyzed in the junctional zone between normal retina and atrophic retina and were correlated with corresponding FAF. RESULTS: Twenty-three eyes of 16 patients between 62 and 96 years of age were examined. There was a significant association between OCT findings and the FAF findings (r = 0.67; P < .0001). Severe alterations of the outer retinal layers at margins on spectral-domain OCT correspond significantly to increased autofluorescence; smooth margins on OCT correspond significantly to normal FAF (kappa, 0.7348; P < .0001). CONCLUSIONS: Spectral-domain OCT provides in vivo insight into the pathogenesis of geographic atrophy and its progression. Visualization of reactive changes in the retinal pigment epithelial cells at the junctional zone and correlation with increased FAF; secondary to increased lipofuscin, together these methods may serve as determinants of progression of geographic atrophy.

Discrepancy between fluorescein angiography and optical coherence tomography in detection of macular disease.

PURPOSE: To compare high-resolution optical coherence tomography (OCT) and fluorescein angiography (FA) in detection of macular edema (ME) of various etiologies. METHODS: In a retrospective study over a 12-month period at one retina center, data for consecutive eyes that had undergone simultaneous conventional FA (HRA; Heidelberg Engineering, Vista, CA) and StratusOCT (Carl Zeiss Meditec, Dublin, CA) to rule out ME were reviewed. A subset of patients underwent additional examination with extremely high-resolution (6-microm)/ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy (OTI, Inc., Toronto, Ontario, Canada). RESULTS: Of 1,272 eyes, 1,208 (94.97%) had the finding of ME or subretinal fluid confirmed by both techniques. There were 49 eyes (3.86%) for which FA showed dye leakage in the macular area and OCT showed normal foveal contour. Of 10 eyes in this group that underwent imaging with ultrahigh-speed spectral OCT/scanning laser ophthalmoscopy, 8 had subtle diffuse lucencies in the retina. For 15 eyes (1.17%), OCT showed intraretinal and subretinal fluid, which was missed by FA. CONCLUSIONS: Both FA and high-resolution OCT are highly sensitive techniques and correlate well in detection of ME. However, there is a small chance that when performed alone they might miss existing subtle ME.