Vittorio Capuano

Optical Coherence Tomography Angiography in Central Serous Chorioretinopathy

Purpose. To analyze optical coherence tomography angiography (OCTA) findings in eyes with central serous chorioretinopathy (CSC) and to compare them with those obtained with multimodal imaging. Methods. A series of consecutive patients diagnosed with CSC, underwent OCTA and multimodal imaging, including spectral domain OCT, fluorescein, and indocyanine green angiography. OCTA images were performed at three main depth intervals: automatically segmented outer retina, manually adjusted outer retina, and automatically segmented choriocapillaris. Results. Thirty-three eyes of 32 consecutive patients were analyzed. OCTA showed 3 main anomalies at the choriocapillaris: the presence of dark areas (19/33 eyes) which were frequently associated with serous retinal detachment, presence of dark spots (7/33 eyes) which were frequently associated with retinal pigment epithelium detachment, and presence of abnormal vessels (12/33 eyes) which were frequently, but not systematically, associated with choroidal neovascularization, as confirmed by multimodal imaging. Conclusions. OCTA revealed dark areas and dark spots, which were commonly observed. An abnormal choroidal pattern was also observed in one-third of cases, even when multimodal imaging did not evidence any choroidal neovascularization. Abnormal choroidal vessels should be interpreted with caution, and we could assume that this pathological choroidal vascular pattern observed in many CSC cases could be distinct from CNV.

Associations Between Retinal Pigment Epithelium and Drusen Volume Changes During the Lifecycle of Large Drusenoid Pigment Epithelial Detachments

Purpose Drusenoid pigment epithelial detachments (PEDs) are a defined path to atrophy in age-related macular degeneration (AMD). We analyzed the relationships between retinal pigment epithelium (RPE) and drusen volume changes during the PED lifecycle, using spectral-domain optical coherence tomography (SD-OCT). Methods Twenty-one cases of drusenoid PED tracked using SD-OCT through periods of growth and collapse were evaluated. Volumetric calculations and piece-wise linear regression analysis were used to determine the breakpoint between growth and collapse. Spectral-domain OCT scans were independently evaluated for the appearance of intraretinal hyperreflective foci, acquired vitelliform lesions (AVLs), and disruptions to the RPE+basal lamina band. Timing of these events with respect to the breakpoint was statistically evaluated. Morphometric characteristics of drusenoid PEDs were correlated with rate of PED collapse and final visual acuity. Results Mean age of subjects was 75.3 years and mean period of follow up was 4.1 years (median 4.5 years; range, 0.6–6.6 years). The lifecycle of drusenoid PEDs was asymmetric, in that the rate of collapse (0.199 mm3/month) is significantly faster (P < 0.001) than the rate of growth (0.022 mm3/month). Appearance of intraretinal hyperreflective foci and AVLs preceded the breakpoint (both P < 0.001). The timing of disruptions to the RPE+basal lamina band did not differ from the breakpoint (P = 0.510). Maximal height, volume, and diameter of drusenoid PEDs were inversely correlated with final visual acuity (all P < 0.001) and positively correlated with the rate of PED collapse (all P < 0.001). Conclusions Spectral-domain OCT signatures, plausibly attributable to anteriorly migrated RPE and disintegration of the RPE layer, precede or occur simultaneously with changes in volume of drusenoid PED during the lifecycle of this lesion.

WEDGE-SHAPED SUBRETINAL HYPOREFLECTIVITY IN GEOGRAPHIC ATROPHY.

Purpose: To describe wedge-shaped subretinal hyporeflectivity, a peculiar spectral domain optical coherence tomography finding in geographic atrophy (GA) areas of atrophic age-related macular degeneration. Methods: We reviewed the charts of consecutive patients with GA who presented between January 2012 and December 2013. A standardized imaging protocol was performed in all patients, which included blue fundus autofluorescence, and spectral domain optical coherence tomography. Results: Wedge-shaped subretinal hyporeflective lesions were found in 12 of 161 included eyes (11 of 94 consecutive patients, 6 males/5 females, mean age 79.6 ± 9.3 years). On spectral domain optical coherence tomography, regions immediately adjacent to the wedge-shaped subretinal hyporeflective lesions were characterized by absence of the hyporeflective outer nuclear layer, the hyperreflective external limiting membrane, the ellipsoid zone, the interdigitation zone, and the retinal pigment epithelium. On “en face” images, they appeared as round-oval hyporeflectivities delimited by hyperreflective borders, which we interpreted as the outer plexiform layer. Mean GA area was significantly larger in eyes with as compared with eyes without wedge-shaped subretinal hyporeflective lesions. Overall, the dimensions of the wedge-shaped subretinal hyporeflective lesions did not change after a mean of ∼15 months. Conclusion: Wedge-shaped subretinal hyporeflectivity, a previously unreported peculiar finding in GA areas of atrophic age-related macular degeneration eyes, appears delimited internally by the hyperreflective outer plexiform layer and externally by the hyperreflective Bruch membrane. These lesions, which are detected in eyes with large GA (even though stable over time), should be recognized and distinguished from subretinal fluid (and other exudative signs of age-related macular degeneration) because their presence should not require prompt treatment.

Appearance of medium–large drusen and reticular pseudodrusen on adaptive optics in age-related macular degeneration

Purpose To investigate the appearance of medium–large drusen and reticular pseudodrusen on adaptive optics (AO). Methods In 14 consecutive patients, AO infrared (IR) images were overlaid with confocal scanning-laser-ophthalmoscope IR reflectance images and IR-referenced spectral-domain optical coherence tomography. Results In eight eyes of six patients, a total of 19 images of medium–large drusen were investigated by AO imaging. En face AO revealed medium–large drusen as highly hyper-reflective round/oval lesions, always centred and/or surrounded by a continuous/discontinuous hyporeflectivity. Cone photoreceptors were detected overlying drusen, appearing either as continuous ‘bright’ hyper-reflective dots over a ‘dark’ hyporeflective background, or as continuous ‘dark’ hyporeflective dots over a ‘bright’ hyper-reflective background. In eight eyes from eight patients, a total of 14 images of pseudodrusen were investigated by AO imaging. En face AO revealed reticular pseudodrusen as isoreflective lesions, always surrounded by a continuous/discontinuous hyporeflectivity. Cone photoreceptors were detected overlying pseudodrusen as ‘bright’ hyper-reflective dots over either a hyporeflective or isoreflective background. No ‘dark’ hyporeflective dots were detected in eyes with reticular pseudodrusen only. Cone photoreceptors were counted on the border of the drusen and pseudodrusen, respectively, and in a visibly healthy zone in its absolute vicinity. A similar decrease in cone appearance was observed for drusen and pseudodrusen (15.7% vs 16.2%). Conclusions AO allows differences in reflectivity between medium–large drusen and reticular pseudodrusen to be appreciated. The cone mosaics may be detected as continuous ‘bright’ hyper-reflective dots overlying/on the border of drusen and pseudodrusen deposits, and possibly as continuous ‘dark’ hyporeflective dots overlying drusen only.

Choroidal structure in eyes with drusen and reticular pseudodrusen determined by binarisation of optical coherence tomographic images

Purpose To compare luminal and stromal area of the choroid in eyes with drusen and reticular pseudodrusen (RPD) and to investigate their changes over 24 months. Methods In eyes with drusen and RPD and control subjects, total choroidal, luminal and stromal area were measured on optical coherence tomography B-scans converted to binary images, at baseline and after 24 months. Results Eighteen eyes of 18 subjects for each group were included. In drusen and RPD, we found reduction of mean total choroidal (p=0.0005 and p<0.0001, respectively), luminal (p=0.003 and p<0.0001, respectively) and stromal area (p=0.007 and p=0.0002, respectively) from baseline to month 24; no change of ratio between luminal–stromal and the choroidal area was recorded. Mean luminal, stromal and total choroidal areas were reduced in RPD, as compared with drusen and controls at both baseline and month 24 (p<0.05 for all). In RPD, the stromal area was more represented, as we found lower mean ratio of luminal and total choroidal area compared with drusen and control at both baseline and month 24 (p<0.05 for all). Conclusions Mean total choroidal, luminal and stromal area decreased over 24 months similarly in eyes with drusen and RPD. Mean total choroidal, luminal and stromal area were more reduced in eyes with RPD, as compared with eyes with drusen and controls; however, stromal area was more represented in eyes with RPD suggesting a possible role of choroidal vascular depletion and fibrotic replacement in the pathogenesis and disease progression.

ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

Background: To describe adaptive optics (AO) imaging of foveal sparing in geographic atrophy (GA) secondary to age-related macular degeneration. Methods: Flood-illumination AO infrared (IR) fundus images were obtained in four consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes). Adaptive optics IR images were overlaid with confocal scanning laser ophthalmoscope near-IR autofluorescence images to allow direct correlation of en face AO features with areas of foveal sparing. Adaptive optics appearance of GA and foveal sparing, preservation of functional photoreceptors, and cone densities in areas of foveal sparing were investigated. Results: In 5 eyes of 4 patients (all female; mean age 74.2 ± 11.9 years), a total of 5 images, sized 4° × 4°, of foveal sparing visualized on confocal scanning laser ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face AO images revealed GA as regions of inhomogeneous hyperreflectivity with irregularly dispersed hyporeflective clumps. By direct comparison with adjacent regions of GA, foveal sparing appeared as well-demarcated areas of reduced reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of note, in these areas, en face AO IR images revealed cone photoreceptors as hyperreflective dots over the background reflectivity (mean cone density 3,271 ± 1,109 cones per square millimeter). Microperimetry demonstrated residual function in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence. Conclusion: Adaptive optics allows the appreciation of differences in reflectivity between regions of GA and foveal sparing. Preservation of functional cone photoreceptors was demonstrated on en face AO IR images in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence.

Optical Coherence Tomography Angiography Changes In Early Type 3 Neovascularization After Anti-vascular Endothelial Growth Factor Treatment.

Purpose: To investigate the morphologic changes on optical coherence tomography angiography (OCTA) of treatment-naive Type 3 neovascularization secondary to exudative age-related macular degeneration after 1 year of anti–vascular endothelial growth factor therapy. Methods: Consecutive patients diagnosed with treatment-naive early-stage Type 3 neovascularization were enrolled in this retrospective study. All patients underwent color fundus photographs/MultiColor (Heidelberg Engineering) imaging, fluorescein angiography, indocyanine green angiography, structural spectral domain OCT, and OCTA Optovue RTVue XR Avanti (Optovue) at baseline, and repeated OCTA and structural spectral domain OCT at Month 12. Qualitative analysis of the 3 × 3 OCTA examinations at baseline and Month 12 was then compared, to assess changes after anti–vascular endothelial growth factor therapy. Results: A total of 15 treatment-naive eyes of 15 consecutive patients were included in the analysis. At 12-month follow-up after pro-re-data anti–vascular endothelial growth factor therapy (5.75 ± 1.48 injections of ranibizumab, and injections of 6.33 ± 1.21 of aflibercept), OCTA demonstrated persistence of the deep capillary plexus abnormalities in 13/15 eyes. In the outer retina and choriocapillaris, the initial lesion became undetectable in 7/15 cases, accompanied by choriocapillaris atrophy. The abnormal vascular complex persisted in the form of a tuft-shaped lesion in the outer retinal segmentation in 9/15 eyes, which in the choriocapillaris segmentation was associated with sub–retinal pigment epithelium neovascularization in 8 cases. Conclusion: Optical coherence tomography angiography showed that the tuft-shaped abnormal outer retinal lesion, frequently associated with a small clew-like flow signal in the choriocapillaris, after 1 year of anti–vascular endothelial growth factor therapy, either becomes undetectable or develops sub–retinal pigment epithelium neovascularization.

Choroidal Caverns: A Novel Optical Coherence Tomography Finding in Geographic Atrophy.

Purpose To describe and interpret “choroidal caverns,” an unreported optical coherence tomography (OCT) finding in the choroid of patients with geographic atrophy (GA) secondary to atrophic AMD. Methods Retrospective analysis of patients with GA. Main outcomes measures included estimation of the prevalence of choroidal caverns, their localization and relation with retinal-choroidal structures by reviewing medical records and multimodal imaging. Results One hundred twenty consecutive patients (mean age 80.5 ± 8.61 years) were included. Among the 201 eyes with GA, 17 eyes of 15 patients presented choroidal caverns on OCT B-scan in GA areas (a total of 43 choroidal caverns, mean 2.5/eye, variably localized in the Sattler and Haller layers, with relative preservation of the choriocapillaris). This accounts for 12.5% estimated prevalence (6.5–18.5, 95% confidence interval [CI]) of choroidal caverns in GA areas of atrophic AMD patients. Choroidal caverns appeared on OCT (both B-scan and en face) as gaping hyporeflective cavities in the choroid, typically empty, angular, without hyperreflective borders, often with punctate/linear hyperreflectivities internally. Indocyanine angiography and OCT-Angiography confirmed that the areas occupied by these cavities do not represent perfused choroidal blood vessels. Conclusions Choroidal caverns represent a relatively infrequent peculiar finding in GA areas of atrophic AMD eyes. They appear as gaping angular hyporeflective cavities in areas devoid of choroidal vessels, often with punctate/linear hyperreflectivities internally. Choroidal caverns may possibly arise from nonperfused ghost vessels and persistence of stromal pillars where the vessels were originally situated.

A Central Hyporeflective Subretinal Lucency Correlates With a Region of Focal Leakage on Fluorescein Angiography in Eyes With Central Serous Chorioretinopathy.

BACKGROUND AND OBJECTIVE To correlate the appearance of a hyporeflective lucency on spectral-domain optical coherence tomography (SD-OCT) with a focal leak on fluorescein angiography (FA) in eyes with central serous chorioretinopathy (CSC). PATIENTS AND METHODS Multimodal imaging of 18 patients with CSC who had hyperreflective fibrin surrounding a hyporeflective lucency on SD-OCT was analyzed to investigate any potential correlation with an active leak on FA. The lucent area was evaluated using en face imaging and followed for resolution of the active leak. RESULTS High-resolution SD-OCT images of the lucency were found to correlate with the active leak. In certain cases, the lucent area could be visualized as communicating with a defect in a pigment epithelial detachment. En face imaging of the lucency revealed a smoke-stack appearance, and resolution of the leak correlated with the disappearance of the lucency on SD-OCT. CONCLUSION Visualization of a lucency within surrounding fibrin may suggest an active leak. En face imaging of the lucency may provide insight into the pathophysiology of the smoke-stack leak on FA.

Emerging therapeutic options in age-related macular degeneration.

Intravitreal injection of anti-VEGF drugs currently represents the standard of treatment for exudative age-related macular degeneration. Several therapeutic options including steroids, inhibitors of complement factors, anti-platelet-derived growth factor agents, new anti-VEGF drugs, designed ankyrin repeat proteins, sustained drug delivery devices as an alternative to intravitreal injections and encapsulated cell technology are the objects of several studies and trials worldwide in association with anti-VEGF therapy or not. Expectations are that such efforts will help overcome limitations of current therapy with anti-VEGF, extending the duration of effects and hopefully contributing to the regression of neovascular lesions.