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.

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.

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.

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.

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.

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.

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.

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 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.