Francesca Mojana

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.

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.

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 (r2 = 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 (r2 = 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.

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°) 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.

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.

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-&mgr;m)/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.

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.

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.