Christopher Kiss

A Systematic Comparison of Spectral-Domain Optical Coherence Tomography and Fundus Autofluorescence in Patients with Geographic Atrophy

PURPOSE To evaluate spectral-domain optical coherence tomography (SD-OCT) in providing reliable and reproducible parameters for grading geographic atrophy (GA) compared with fundus autofluorescence (FAF) images acquired by confocal scanning laser ophthalmoscopy (cSLO). DESIGN Prospective observational study. PARTICIPANTS A total of 81 eyes of 42 patients with GA. METHODS Patients with atrophic age-related macular degeneration (AMD) were enrolled on the basis of total GA lesion size ranging from 0.5 to 7 disc areas and best-corrected visual acuity of at least 20/200. A novel combined cSLO-SD-OCT system (Spectralis HRA-OCT, Heidelberg Engineering, Heidelberg, Germany) was used to grade foveal involvement and to manually measure disease extent at the level of the outer neurosensory layers and retinal pigment epithelium (RPE) at the site of GA lesions. Two readers of the Vienna Reading Center graded all obtained volume stacks (20×20 degrees), and the results were correlated to FAF. MAIN OUTCOME MEASURES Choroidal signal enhancements and alterations of the RPE, external limiting membrane (ELM), and outer plexiform layer by SD-OCT. These parameters were compared with the lesion measured with severely decreased FAF. RESULTS Foveal involvement or sparing was definitely identified in 75 of 81 eyes based on SD-OCT by both graders (inter-grader agreement: κ=0.6, P < 0.01). In FAF, inter-grader agreement regarding foveal involvement was lower (48/81 eyes, inter-grader agreement: κ=0.3, P < 0.01). Severely decreased FAF was measured over a mean area of 8.97 mm(2) for grader 1 (G1) and 9.54 mm(2) for grader 2 (G2), consistent with the mean SD-OCT quantification of the sub-RPE choroidal signal enhancement (8.9 mm(2) [G1] -9.4 mm(2) [G2]) and ELM loss with 8.7 mm(2) (G1) -10.2 mm(2) (G2). In contrast, complete morphologic absence of the RPE layer by SD-OCT was significantly smaller than the GA size in FAF (R(2)=0.400). Inter-reader agreement was highest regarding complete choroidal signal enhancement (0.98) and ELM loss (0.98). CONCLUSIONS Absence of FAF in GA lesions is consistent with morphologic RPE loss or advanced RPE disruption and is associated with alterations of the outer retinal layers as identified by SD-OCT. Lesion size is precisely determinable by SD-OCT, and foveal involvement is more accurate by SD-OCT than by FAF.

Evaluation of anterior chamber inflammatory activity in eyes treated with intravitreal bevacizumab.

Purpose: To evaluate the effect of intravitreal bevacizumab on anterior chamber inflammatory activity. Methods: Sixty-one consecutive patients with neovascular age-related macular degeneration were examined before, 1 day, and 1 week after intravitreal administration of 1 mg of bevacizumab (0.04 mL) for neovascular age-related macular degeneration. The intravitreal injection was performed under sterile conditions. Twenty-one fellow eyes served as controls. The anterior chamber inflammatory activity was evaluated using biomicroscopy and the laser flare meter (Kowa FM-500, Kowa Company, Ltd., Tokyo, Japan). Results: None of the 61 consecutive patients had a significant, clinically detectable inflammatory response within 1 week of follow-up. Anterior chamber inflammatory activity measured by the laser flare meter ranged from 1.9 counts/ms to 70.0 counts/ms (mean ± SD, 13.2 ± 16.9 counts/ms; 95% confidence interval [CI], 7.8–18.6) before treatment. One day and 1 week after injection, values were between 3.2 counts/ms and 30.0 counts/ms (mean ± SD, 9.1 ± 6.2 counts/ms; 95% CI, 7.2–11.1) and 2.0 counts/ms and 25.1 counts/ms (mean ± SD, 7.3 ± 4.6 counts/ms; 95% CI, 5.8–8.8), respectively. There was a significant reduction of anterior chamber flare at 1 week compared with baseline (P = 0.031). The control eyes had constantly low flare measures. Conclusion: No inflammatory response was detected clinically and by the laser flare meter after intravitreal bevacizumab administration. The slight reduction in anterior chamber flare could be due to the known antiinflammatory effect of anti–vascular endothelial growth factor therapy.

Evaluation of Ranibizumab-Induced Changes in High-Resolution Optical Coherence Tomographic Retinal Morphology and Their Impact on Visual Function

PURPOSE To evaluate the effects of intravitreal ranibizumab on retinal function and morphology and to identify a correlation between anatomy and function by using spectral domain optical coherence tomography (SDOCT). METHODS Twenty-three patients affected by neovascular AMD received three injections of ranibizumab in three consecutive months and were monitored by assessment of best corrected visual acuity (BCVA), central retinal sensitivity (CRS) and morphologic changes at the level of the retina and the retinal pigment epithelium (RPE). The morphologic changes, identified by SDOCT segmentation, were mean retinal thickness (MRT), central retinal thickness (CRT), and the pathologic area (lesion area) of the RPE. RESULTS BCVA increased from a mean 60.1 +/- 8.7 letters at baseline to 67.0 +/- 10.9 at month 3 (P = 0.0003). The CRS at the 0 degrees position increased from 2.8 +/- 3.1 dB at baseline to 4.0 +/- 5.7 at week 1, remaining stable until month 3. Absolute scotoma size decreased continuously from baseline to month 3, in a mean of 5.3 +/- 5.8 to 3.6 +/- 4.0 test point locations. By SDOCT, MRT decreased from 308.6 +/- 25.9 microm at baseline to 268.4 +/- 22.4 microm at month 3 (P = 0.0001). CRT was 365.8 +/- 84.9 and 254.9 +/- 95.1 microm at month 3 (P = 0.0002). The mean RPE lesion area was 6.0 +/- 3.0 mm(2) at baseline, which decreased to 5.0 +/- 3.1 mm(2) at month 3 (P = 0.115). The only significant correlation was identified between the lesion area and CRS. CONCLUSIONS In ranibizumab therapy, the condition of the RPE lesion may be more relevant for visual function than the usual OCT parameters, retinal thickness.

Correlation of High-Definition Optical Coherence Tomography and Fluorescein Angiography Imaging in Neovascular Macular Degeneration

PURPOSE To correlate the morphologic characteristics of choroidal neovascular lesions (CNV) in age-related macular degeneration (AMD) using raster scanning high-definition optical coherence tomography (HD-OCT) and conventional fluorescein angiography (FA). METHODS In this comparative clinical study, 37 consecutive patients with classic, minimally classic, or occult CNV; 13 patients with early AMD; and 10 age-matched healthy individuals were included. HD-OCT imaging (Topcon, Tokyo, Japan) and FA (scanning retinal ophthalmoscope; HRA2; Heidelberg Engineering, Dossenheim, Germany) were performed after a complete standardized ophthalmic examination. Only one eye of each patient was included in the study. A point-to-point correlation between HD-OCT and FA images was performed. Early and late FA images at defined locations were correlated with OCT measurements, including 3D maps, 2D single scans, a thickness linear graph, and the 3D retinal pigment epithelium (RPE) segmentation. RESULTS With HD-OCT imaging used to delineate the lesion morphology, early AMD was detected as having a normal foveal contour and minimal alteration in the macular area; classic CNV as a well-defined lesion with steep margins and a craterlike configuration, occult CNV as an ill-defined, flat lesion with a convex surface; and minimally classic CNV as having classic and occult components. FA-OCT overlay images provided a significant correlation between FA patterns and OCT features such as retinal thickness (RT). CONCLUSIONS 3D-OCT provided realistic anatomic maps of the retina, RPE, and RT in patients with AMD. Discrimination between the predominant CNV lesion types was achieved, and their precise shape was identified, together with information about the lesions localization and leakage activity.

Diagnostic Evaluation of Type 2 (Classic) Choroidal Neovascularization: Optical Coherence Tomography, Indocyanine Green Angiography, and Fluorescein Angiography

PURPOSE To evaluate the diagnostic characteristics of type 2 (classic) choroidal neovascularizations secondary to age-related macular degeneration using spectral domain-optical coherence tomography (SD OCT), indocyanine green angiography (ICGA), and fluorescein angiography (FA). DESIGN Observational case series. METHODS SETTING Institutional. STUDY POPULATION Thirteen treatment-naïve eyes with type 2 choroidal neovascularization without an occult component. MAIN OUTCOME MEASURES Greatest horizontal dimension, based on the anatomic features of the neovascular complex by SD OCT (Spectralis; Heidelberg Engineering), ICGA, and FA; retinal leakage area in late-phase FA and ICGA; and the area of retinal edema in SD OCT. OBSERVATION PROCEDURES For direct comparison, ICGA and FA images were overlaid manually on infrared plus SD OCT images using VirtualDub and Paint.NET software. Greatest horizontal dimension was measured using Image J software (National Institutes of Health). RESULTS The mean greatest horizontal dimension of the neovascular complex and the retinal leakage area consistently were smaller on ICGA compared with the area of retinal edema on SD OCT. According to FA, the greatest horizontal dimension of early, well-demarcated hyperfluorescence was significantly smaller than the neovascular complex on SD OCT. In addition, the greatest horizontal dimension of the retinal leakage area in late-phase FA consistently was smaller than the area of retinal edema on SD OCT. CONCLUSIONS In classic choroidal neovascularization, ICGA and FA seem to underestimate the extension of the neovascular complex and the associated retinal pathologic features compared with SD OCT imaging.

Effect of intravitreal ranibizumab in avascular pigment epithelial detachment

PurposeTo evaluate long-term morphologic and functional changes after intravitreal ranibizumab in avascular pigment epithelial detachment (PED) secondary to age-related macular degeneration (AMD).Patients and methodsInterventional, prospective case series; the first group of six patients received three and the second group of six patients received six intravitreal injections of ranibizumab (0.5 mg) at monthly intervals. Outcome measures included the change of PED and retinal volume as determined by spectral domain optical coherence tomography (Cirrus), best-corrected visual acuity (BCVA; Early Treatment Diabetic Retinopathy Study), and macular sensitivity using microperimetry (MP-1; Nidek Co. Ltd).ResultsThe mean baseline PED volume of 1.33 mm3 decreased significantly by 42% at month 6 (−0.55 mm3, P<0.05). Compared to baseline no significant change was observed at months 9 and 12. BCVA, retinal volume, and macular sensitivity remained stable during the entire follow-up. In one case a tear of the retinal pigment epithelium was observed after five injections with a consequent decrease of BCVA of four lines.ConclusionTreatment with intravitreal injections of ranibizumab may temporarily decrease the volume of avascular PED secondary to AMD, however this effect was not maintained over the 1-year study period. The treatment was ineffective for improving retinal function as measured with BCVA and microperimetry.

Comparing retinal thickness measurements from cirrus spectral domain- and stratus time domain-optical coherence tomography

Purpose: The purpose of this study was to compare retinal measurements obtained using spectral domain-optical coherence tomography with measurements obtained using time domain-optical coherence tomography. Methods: Three hundred and seventy subjects were recruited at three university-based and one community-based retina practice for a cross-sectional observational study. For each subject, one eye was enrolled as the study eye. A Stratus Fast Macular scan was performed, and a Cirrus 200 × 200 Macular Cube scan was performed. Both instruments segment the acquired images to generate retinal thickness values and report averages measured in nine subfields defined by the Early Treatment Diabetic Retinopathy Study. These average values were compared with each other quantitatively using linear regression and Bland-Altman plots. Results: Of the recruited subjects, 283 had acceptable images taken on the same day with both the Cirrus and Stratus devices. Mean differences between the instruments were noted in all subfields for all disease categories and ranged from 29 &mgr;m (outer superior subfield) to 54 &mgr;m (central subfield). Conclusion: Differences between time domain and spectral domain measurements of retinal thickness depend on pathology and location. Comparisons across instruments should be made with caution.

High-Resolution Optical Coherence Tomography after Surgery for Vitreomacular Traction: A 2-Year Follow-up

PURPOSE To characterize the morphologic changes in vitreomacular traction (VMT) before and after surgery using spectral-domain optical coherence tomography (SD OCT) and to identify patterns relevant to visual function. DESIGN Prospective, interventional case series. PARTICIPANTS Thirty eyes of 30 consecutive patients with visual acuity of less than 20/32 resulting from idiopathic VMT. METHODS A conventional 20-gauge 3-port vitrectomy was performed, including removal of the epiretinal membrane (ERM) and internal limiting membrane. Examinations were performed 1 day before surgery and 1 and 3 days as well as 1, 3, 6, 12, and 24 months after surgery. The SD OCT scan sets were analyzed with regard to central retinal thickness (CRT), retinal volume (RV), graded parameters of inner/outer retinal layer integrity (ILI/OLI), presence of retinal surface folds (RSF), and foveal contour. MAIN OUTCOME MEASURES Visual acuity and morphologic characteristics of the inner and outer retinal layers revealed by SD OCT. RESULTS Spectral-domain OCT revealed a complete absence of the ERM and early release of traction forces in each eye. Best-corrected visual acuity increased progressively over 24 months. Morphologically, RSF resolved within 1 month after surgery, followed by a marked decrease in CRT and RV over the next 3 months. There was no significantly correlation between RSF, CRT, or RV with functional improvement, and CRT and RV did not return to physiologic values. Recovery of ILI and OLI proceeded slowly, reaching significance at 12 months, and correlated strongly with visual function. CONCLUSIONS Spectral-domain OCT seems to be a valuable method for evaluating retinal changes after surgery for VMT. Reconstitution of neurosensory layers was identified as the most relevant parameter for visual improvement.

Combination of verteporfin photodynamic therapy and ranibizumab: effects on retinal anatomy, choroidal perfusion and visual function in the protect study

Objective: To evaluate verteporfin and same-day ranibizumab on retina, choroid, vasculature, choroidal neovascularisation (CNV) and visual function. Methods: Eleven patients with occult or predominantly classic subfoveal CNV secondary to age-related macular degeneration received verteporfin and four monthly intravitreal ranibizumab injections. Eyes were examined using fluorescein angiography (FA) and indocyanine green angiography (ICGA), optical coherence tomography (OCT), visual acuity (VA) and microperimetry. Results: Over 9 months, seven patients gained three to 24 letters and one had unchanged VA. Three patients lost eight to 24 letters due to recurrence and received another verteporfin treatment at month 6. Median retinal sensitivity of the central 4° of the macula increased from 0.9 (SD 2.3) dB (baseline) to 5.2 (1.8) dB (only baseline verteporfin) and 4.1 (4.5) dB (second verteporfin treatment) at study end. OCT showed sub- and intraretinal leakage increased with verteporfin, but resolved after 2 weeks. After combination treatment, CNV was completely occluded on FA within 1 week. ICGA showed non-perfusion of small/medium choroidal vessels. Recovery of choroidal perfusion began after 1 month, but remained impaired throughout follow-up. Conclusion: Verteporfin/ranibizumab was associated with CNV occlusion, reduced oedema, improved visual function and retinal sensitivity. The clinical significance of these findings requires further investigation.

A systematic correlation of morphology and function using spectral domain optical coherence tomography and microperimetry in patients with geographic atrophy

Aims This study has been designed to describe the functional impact of distinct pathologies within the retinal layers in patients with geographic atrophy (GA) by means of a point-to-point correlation between optical coherence tomography (OCT) and microperimetry. Methods Retinal morphology and function of 23 patients suffering from GA of the retinal pigment epithelium (RPE) have been investigated using the Spectralis OCT (Heidelberg Engineering) and the MP1 microperimeter (Nidek Technologies). The point-to-point overlay of morphology and function has been done using proprietary software, allowing OCT image grading to define distinct alterations of the neurosensory retina, the RPE and the choroid. By overlaying the retinal sensitivity map on the OCT data set, retinal layer alterations could be evaluated regarding their impact on visual function. Results A total of 1005 stimulation points in the lesion area in 2107 spectral domain OCT B-scans were graded in 43 eyes of 23 patients (mean best corrected visual acuity=20/70). Retinal sensitivity decreases with an increasing number of morphological alterations graded (p<10−13). Alterations of the RPE and the external limiting membrane (p<0.02) were associated with absolute scotomas. Furthermore, the loss of the external limiting membrane as the largest area of morphological alteration among our patients with GA (mean area=5.65 mm2), had a significant impact (p<10−4) on sensitivity (−1.3 dB). Conclusions Mapping retinal sensitivity to distinct retinal pathologies revealed outer retinal layers, in addition to the RPE, as significant for sensitivity loss. Therefore in GA the RPE loss and the alteration of outer retinal layers should be analysed, which could also provide insight into lesion progression.