Quantitative comparison of optical coherence tomography after pegaptanib or bevacizumab in neovascular age-related macular degeneration.

PURPOSE: To demonstrate the benefit of enhanced quantitative analysis of optical coherence tomography (OCT) images using computer-assisted grading to compare the short-term morphologic effects of pegaptanib and bevacizumab treatment for neovascular age-related macular degeneration (AMD). DESIGN: Retrospective consecutive case series. PARTICIPANTS: Fifty-three cases with neovascular AMD undergoing pegaptanib or bevacizumab therapy. METHODS: Fifty-three consecutive cases of patients who underwent StratusOCT imaging followed by treatment with either intravitreal pegaptanib (n = 18) or bevacizumab (n = 35) for neovascular AMD were retrospectively collected. Raw exported StratusOCT images were analyzed using publicly available custom software (OCTOR) designed to define the boundaries of various spaces manually. Changes in thickness and volume of the retina, subretinal fluid (SRF), subretinal tissue, and pigment epithelial detachments (PEDs) before treatment and at 3 months after treatment were calculated and compared between treatment groups. OCTOR software measurements after manual grading were also compared with the automated StratusOCT output. MAIN OUTCOME MEASURES: Volume and thickness measurements calculated by the automated StratusOCT software and the manual grading software OCTOR. RESULTS: Intravitreal bevacizumab resulted in a statistically significant greater reduction of total retinal volume than pegaptanib (-0.88+/-1.4 mm(3) vs. -0.07+/-0.5 mm(3), P = 0.003). Mean foveal central subfield (FCS) retinal volume decreased from 0.26+/-0.1 mm(3) to 0.21+/-0.1 mm(3) (P = 0.001) in the bevacizumab group and remained constant at 0.22+/-0.1 in the pegaptanib group 3 months after injection. Subanalysis of the SRF, subretinal tissue, and PEDs revealed statistically significant reductions of the total volume of all 3 spaces after bevacizumab injections but no significant change after pegaptanib treatment. Automated StratusOCT output measurements of FCS thickness, foveal center point thickness, and total volume of the retina did not reveal a statistically significant difference between the treatments. CONCLUSIONS: Differences in morphologic response between treatments were less apparent on automated StratusOCT output than on computer-assisted analysis. Although intravitreal bevacizumab was associated with a greater short-term reduction in features of exudation than pegaptanib therapy, the retrospective design of the study limits the significance of this finding. Computer-assisted subanalysis of OCT data, however, may be a useful tool in more precisely defining the anatomic effects of therapies for neovascular AMD.

Error correction and quantitative subanalysis of optical coherence tomography data using computer-assisted grading.

PURPOSE: To demonstrate feature subanalysis and error correction of optical coherence tomography (OCT) data by using computer-assisted grading. METHODS: The raw exported StratusOCT (Carl Zeiss Meditec, Inc., Dublin, CA) scan data from 20 eyes of 20 patients were analyzed using custom software (termed OCTOR) designed to allow the user to define manually the retinal borders on each radial line scan. Measurements calculated by the software, including thickness of the nine standard macular subfields, foveal center point (FCP), and macular volume, were compared between two graders and with the automated Stratus analysis. Mean and range of differences for each parameter were calculated and assessed by Bland-Altman plots and Pearson correlation coefficients. Additional cases with clinically relevant subretinal findings were selected to demonstrate the capabilities of this system for quantitative feature subanalysis. RESULTS: Retinal thickness measurements for the various subfields and the FCP showed a mean difference of 1.7 mum (maximum, 7 microm) between OCTOR graders and a mean difference of 2.3 microm (maximum of 8 microm) between the OCTOR and Stratus analysis methods. Volume measurements between Stratus and OCTOR methods differed by a mean of 0.06 mm(3) (in reference to a mean macular volume of 6.81 mm(3)). The differences were not statistically significant, and the thicknesses correlated highly (R(2) > or = 0.98 for all parameters). CONCLUSIONS: Manual identification of the inner and outer retinal boundaries on OCT scans can produce retinal thickness measurements consistent with those derived from the automated StratusOCT analysis. Computer-assisted OCT grading may be useful for correcting thickness measurements in cases with errors of automated retinal boundary detection and may be useful for quantitative subanalysis of clinically relevant features, such as subretinal fluid volume or pigment epithelial detachment volume.

Reproducibility of quantitative optical coherence tomography subanalysis in neovascular age-related macular degeneration.

PURPOSE: To determine the intergrader reproducibility for computer-assisted grading of optical coherence tomography (OCT) images in eyes with neovascular age-related macular degeneration (AMD), by using a standardized grading procedure. METHODS: Sixty OCT image sets (of six radial lines each) were independently analyzed by two graders using validated custom software (OCTOR) to draw boundaries manually on OCT B-scans. Spaces delineated by these boundaries included retina, subretinal fluid, subretinal tissue, and pigment epithelial detachments (PEDs). Volume measurements for the nine Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields and the mean foveal center point (FCP) thickness were calculated by the software and compared by using weighted kappa statistics and intraclass correlation coefficients (ICCs). RESULTS: Intergrader comparison of the foveal central subfield (FCS) volume, total volume, and mean FCP thickness showed a high level of agreement and strong correlation between measurements for all spaces (kappa(weighted) = 0.72-0.97; ICC = 0.92-0.99). The best agreement was observed for total volume of the combination of all four graded spaces (kappa(weighted) = 0.97, mean difference = 0.31 mm(3), or 2.51%). The highest ICCs were seen for FCP thickness measurements. The poorest agreement was found for grading of subretinal tissue. Eyes with advanced choroidal neovascularization (CNV) and poor visibility of the retinal pigment epithelium (RPE) band appeared to show the greatest intergrader discrepancies. CONCLUSIONS: Analysis of OCT images by trained graders using computer-assisted grading software allows for highly reproducible quantitative measurements, even in eyes with complex diseases such as neovascular AMD. Quantitative subanalysis may be useful in studying the differential morphologic effect of therapies on various anatomic components.

Autologous translocation of the choroid and retinal pigment epithelium in patients with geographic atrophy.

PURPOSE: To evaluate the functional and anatomical outcomes of autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in patients with geographic atrophy. DESIGN: Prospective nonrandomized study. PARTICIPANTS: Twelve consecutive patients with geographic atrophy secondary to age-related macular degeneration presenting with recent loss of reading vision. METHODS: An autologous peripheral full-thickness graft of RPE, Bruch's membrane, and choroid was positioned under the macula in patients with geographic atrophy. MAIN OUTCOME MEASURES: Functional tests included Early Treatment Diabetic Retinopathy Study distant vision, reading (Radner Test, measured as logarithm of the reading acuity determination [logRAD]), threshold static perimetry, and determination of the point of fixation. Fluorescein and indocyanine green angiography, autofluorescence, and optical coherence tomography served to evaluate the anatomical outcome in a 6-month follow-up (12 months in 7 patients). RESULTS: Preoperative visual acuity (VA) ranged from 20/800 to 20/40 (mean, 0.6+/-0.4 logarithm of the minimum angle of resolution), and reading vision from 1.1 to 0.5 logRAD (mean, 0.8+/-0.2). Three patients were unable to read. Six months after surgery, VA ranged from hand movements to 20/32, with an increase of > or =5 letters in 2 eyes. Two patients without reading ability preoperatively were able to read after surgery. Reading was possible in a total of 8 patients after 6 months (1.3-0.4 logRAD). In 7 patients who were observed for 1 year, VA remained stable (+/-1 line) in 5 eyes and decreased in 2 eyes between 6 months' and 1 year's follow-up. In all eyes but 2, revascularization was visible on indocyanine green angiography as early as 3 weeks after surgery. Autofluorescence of the RPE was independent of revascularization of the graft and persisted throughout follow-up. Four eyes had unstable fixation and/or extrafoveal fixation before surgery. Two of these eyes stabilized during follow-up. Areas overlying atrophic areas demonstrated low threshold sensitivities that persisted after translocation of a free graft with only limited recovery. Revisional surgery due to proliferative vitreoretinopathy was required in 5 eyes. CONCLUSIONS: The translocation of a full-thickness graft usually results in a vascularized and functioning graft in patients with geographic atrophy, although is associated with a high risk of complications and visual loss. Longer follow-up is necessary to learn about the long-term survival and functionality of the graft.

Benefits and limitations in vitreoretinal surgery for proliferative diabetic retinopathy and macular edema.

Surgical therapy for diabetic retinopathy has been refined since the 1960s (Early Treatment Diabetic Retinopathy Study). While the Early Treatment Diabetic Retinopathy Study abstained from panretinal photocoagulation at the time of surgery, today, endophotocoagulation is the most important singular reason for vitrectomy, e.g., in vitreous hemorrhage. Despite improved techniques, the surgical prognosis is lagging behind patient expectations, especially in cases of advanced proliferative stages. The following review addresses current surgical options and indications of diabetic retinopathy/maculopathy.

Autologous translocation of the choroid and retinal pigment epithelium in age-related macular degeneration.

PURPOSE: To evaluate the autologous translocation of peripheral choroid and retinal pigment epithelium (RPE) in 45 eyes of 43 patients with age-related macular degeneration (AMD). DESIGN: Prospective nonrandomized study. METHODS: All patients had visual loss due to AMD (n = 5 classic membranes, n = 14 occult, n = 2 mixed, n = 16 pigment epithelial detachment (PED), n = 5 subretinal hemorrhage, n = 3 geographic atrophy). After extraction of the neovascular complex, an autologous peripheral full-thickness explant of RPE, Bruch membrane, and choroid was translocated from the midperiphery to the macula. RESULTS: Preoperative distant visual acuity ranged from 20/800 to 20/40. Reading vision ranged from 1.4 logarithm of reading acuity determination (logRAD) to 0.5 logRAD (0.04 to 0.32 Snellen equivalent). Revision surgery was required in 22 eyes as a result of proliferative vitreoretinopathy (PVR), retinal detachment, macular pucker, or vitreous hemorrhage. In eight patients, the patch was renewed. At six months, distant visual acuity ranged from light perception to 20/50 (increase of 15 letters in four eyes). Reading vision ranged from 1.4 to 0.4 logRAD. Visual outcome was unrelated to the type of AMD. Vascularization of the transplant was visible on indocyanine green (ICG) angiography in 40 of 42 eyes. In most patients, autofluorescence of the pigment epithelium was coincident with revascularization of the graft. Fixation on the patch was positively related to visual acuity. CONCLUSIONS: Autologous translocation of a full-thickness transplant of choroid and RPE usually results in a vascularized and functioning graft. Vascularization was even achieved in patients with geographic atrophy. Fixation stability and microperimetry before the patch translocation may be helpful in selecting patients who will profit from surgery.

Retinal imaging with adaptive optics scanning laser ophthalmoscopy in unexplained central ring scotoma.

Adaptive optics scanning laser ophthalmoscopy allows for noninvasive, in vivo visualization of retinal abnormalities at a cellular level. We herein describe for the first time, to our knowledge, the utility of high-resolution retinal imaging in studying the photoreceptor mosaic in an otherwise unexplained visual disturbance. Imaging of the cone mosaic was performed in a 64-year-old man with a unilateral ringlike paracentral distortion that could not be explained using common clinical imaging instruments. Adaptive optics scanning laser ophthalmoscopy findings revealed a parafoveal circular abnormality of the cone mosaic approximately 3 degrees in diameter that corresponded to the ring of visual disturbance. Visualization of the cone mosaic with adaptive optics scanning laser ophthalmoscopy can reveal photoreceptor damage that may not be detectable with standard imaging devices. Optical axial sectioning of the retina may help in identifying and localizing abnormalities within the retinal layers.

Bevacizumab (Avastin) treatment in patients with retinal angiomatous proliferation.

AIM: To determine the anatomical and functional outcome after injection of bevacizumab (Avastin, Genentech) in eyes with retinal angiomatous proliferation (RAP). DESIGN: Prospective interventional case series. METHODS: Sixteen eyes of 16 consecutive patients with visual loss due to RAP underwent intravitreal injections of 1.25 mg (0.05 ml) bevacizumab. Best corrected visual acuity testing, fluorescein and ICG-angiography as well as OCT imaging were performed at baseline and at each follow-up visit within a 3-month period. RESULTS: Mean visual acuity pre-injection was 0.68 +/- 0.36 logMAR (n = 16), mean reading ability 0.58 +/- 0.26 logRAD (n = 11). Far vision increased significantly by a mean of 1.7 +/- 2 lines 4 weeks after the injection (p = 0.004), as did reading (0.6 +/- 2.3 lines, p > 0.05). Both remained stable up to 3 months. Central retinal thickness decreased from 367 +/- 112 microm (mean+/-SD) to 272 +/- 123 microm 3 months after injection (p = 0.006). Leakage decreased angiographically in 12 eyes (75%) and remained stable in four eyes (25%). Re-injection of bevacizumab within the 3-month follow-up period was performed once in eight eyes, and twice in one eye. No adverse events were observed. CONCLUSION: Intravitreal bevacizumab (Avastin) resulted in a reduction of leakage, intra- and subretinal fluid. An increase in visual acuity was seen already 4 weeks after first injection. However, a complete occlusion of feeder vessels could not be achieved within this 3-month period. Randomized clinical trials would be required to evaluate dose and frequency of injections and possible beneficial effects of combination therapies, as well as the long-term results.