Faculty Bibliography

PURPOSE/OBJECTIVE:To summarize the results of 2 consensus meetings (Classification of Atrophy Meeting [CAM]) on conventional and advanced imaging modalities used to detect and quantify atrophy due to late-stage non-neovascular and neovascular age-related macular degeneration (AMD) and to provide recommendations on the use of these modalities in natural history studies and interventional clinical trials. DESIGN/METHODS:Systematic debate on the relevance of distinct imaging modalities held in 2 consensus meetings. PARTICIPANTS/METHODS:A panel of retina specialists. METHODS:During the CAM, a consortium of international experts evaluated the advantages and disadvantages of various imaging modalities on the basis of the collective analysis of a large series of clinical cases. A systematic discussion on the role of each modality in future studies in non-neovascular and neovascular AMD was held. MAIN OUTCOME MEASURES/METHODS:Advantages and disadvantages of current retinal imaging technologies and recommendations for their use in advanced AMD trials. RESULTS:Imaging protocols to detect, quantify, and monitor progression of atrophy should include color fundus photography (CFP), confocal fundus autofluorescence (FAF), confocal near-infrared reflectance (NIR), and high-resolution optical coherence tomography volume scans. These images should be acquired at regular intervals throughout the study. In studies of non-neovascular AMD (without evident signs of active or regressed neovascularization [NV] at baseline), CFP may be sufficient at baseline and end-of-study visit. Fluorescein angiography (FA) may become necessary to evaluate for NV at any visit during the study. Indocyanine-green angiography (ICG-A) may be considered at baseline under certain conditions. For studies in patients with neovascular AMD, increased need for visualization of the vasculature must be taken into account. Accordingly, these studies should include FA (recommended at baseline and selected follow-up visits) and ICG-A under certain conditions. CONCLUSIONS:A multimodal imaging approach is recommended in clinical studies for the optimal detection and measurement of atrophy and its associated features. Specific validation studies will be necessary to determine the best combination of imaging modalities, and these recommendations will need to be updated as new imaging technologies become available in the future.

PURPOSE: To study eyes with Type 2 (subretinal) neovascularization (NV) secondary to neovascular age-related macular degeneration (nAMD) that shows lesion regression into a Type 1 (subretinal pigment epithelium) pattern after treatment with intravitreal anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Retrospective consecutive case series. Patients showing regression of Type 2 neovascularization into a Type 1 pattern after envelopment by retinal pigment epithelium were included in this analysis. A review of the clinical records and multimodal imaging of these cases was performed at baseline, 1, 3, 6, and 12 months. Demographic data, best-corrected visual acuity (BCVA), color fundus photography, fundus autofluorescence (FAF), fluorescein angiography, near-infrared reflectance (NIR), and structural spectral-domain optical coherence tomography (SD-OCT) were reviewed and analyzed. When available, optical coherence tomography angiography images were analyzed as well. RESULTS: Ten eyes of 9 patients (6 males) diagnosed with treatment-naive pure Type 2 neovascularization secondary to nAMD were included. The mean age was 80.7 years (SD +/- 4.30). Mean best-corrected visual acuity expressed in logMAR (Snellen) was 0.45 +/- 0.20 (20/55) at baseline and significantly improved to 0.22 +/- 0.13 (20/32) at 3-month follow-up (P-value: 0.007). At baseline, color photographs and fundus autofluorescence showed a pigment ring around the neovascular lesion in 6 eyes. A hyperreflective ring was visible on NIR in all eyes at 3-month follow-up. Color photographs showed a tessellated fundus appearance in 9 of the 10 eyes. Serial structural spectral-domain optical coherence tomography scans showed the gradual regression of the Type 2 lesions into a Type 1 pattern with envelopment by the retinal pigment epithelium. En face and cross-sectional optical coherence tomography angiography showed baseline subretinal flow patterns which, after treatment, exhibited reduced flow beneath an intact hyperreflective retinal pigment epithelium (RPE) band. CONCLUSION: Pure Type 2 lesions are infrequent in nAMD, often leading to poor visual outcomes related to subretinal fibrosis. We describe an alternate regression pattern occurring in eyes with early Type 2 lesions treated with intravitreal anti-vascular endothelial growth factor therapy in which the neovascular tissue is enveloped by retinal pigment epithelium producing a Type 1 pattern. These eyes appear to have better visual outcomes than typically seen with Type 2 lesions related to reduced outer retinal damage.

PURPOSE: To study the cross-sectional and en face optical coherence tomography angiography (OCTA) findings in Type 3 neovascularization (NV). METHODS: Optical coherence tomography angiography imaging of 27 eyes of 23 patients with Type 3 NV was analyzed with 9 eyes having consecutive follow-up OCTA studies. RESULTS: Type 3 NV appeared as a linear high-flow structure on cross-sectional OCTA corresponding to a high-flow tuft of vessels seen on en face OCTA. Cross-sectional OCTA seemed to enable the distinction between vascular and nonvascular intraretinal hyperreflective foci. Two patterns of flow were observed; Pattern 1 (11%): a flow signal confined to the neurosensory retina and Pattern 2 (74%): a flow signal extending through the retinal pigment epithelium. No definitive retinal-choroidal anastomosis was observed; however, projection artifacts confounded the interpretation of deeper structures. An increase in the intensity of the high-flow tuft was seen during the progression or recurrence of Type 3 NV. Intravitreal anti-vascular endothelial growth factor therapy caused a reduction in the intensity of the high-flow tuft which was not sustained. CONCLUSION: Compared with conventional imaging, OCTA may improve detection and delineation of vascular changes occurring in Type 3 NV. Cross-sectional and en face OCTA may prove useful in studying the pathogenesis and guiding the management of these lesions.

PURPOSE: To review the literature regarding focal choroidal excavation and show its association with pachychoroid features through case examples. METHODS: The clinical manifestations of focal choroidal excavation are illustrated with various imaging modalities inclusive of fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral domain optical coherence tomography (OCT), enhanced depth imaging OCT, and swept-source OCT. RESULTS: Diffuse or focal areas of choroidal thickening with dilated choroidal vessels (pachyvessels) on OCT and choroidal hyperpermeability on indocyanine green angiography are present in many eyes with focal choroidal excavation. Clinical and imaging features of associated comorbidities including central serous chorioretinopathy and choroidal neovascularization are described. CONCLUSION: Focal choroidal excavation appears to be a manifestation of pachychoroid spectrum disease associated with choroidal thickening and pachyvessels on structural OCT and choroidal hyperpermeability on indocyanine green angiography.

PURPOSE: To report an unusual case of delayed-onset bilateral diffuse uveal melanocytic proliferation in a patient with a remote history of gastric adenocarcinoma 17 years earlier. METHODS: Case report of a patient with bilateral diffuse uveal melanocytic proliferation including comprehensive systemic and ocular examinations. RESULTS: A 78-year-old man presented with a history of progressive bilateral vision loss during the 4 previous years associated with fever of unknown origin. He underwent total gastrectomy 17 years earlier as a treatment for gastric adenocarcinoma. Funduscopic examination revealed multiple subretinal pigmented and nonpigmented lesions involving the posterior pole of both eyes. These lesions showed early hyperfluorescence on fluorescein angiography, producing a giraffe pattern. Spectral-domain optical coherence tomography showed intraretinal and subretinal fluid with multiple hyperreflective mounds involving the retinal pigment epithelium. Treatment with the intravitreal anti-vascular endothelial growth factor agent, ranibizumab, produced anatomical improvement in both eyes but visual improvement in just the right eye. CONCLUSION: Although delayed-onset bilateral diffuse uveal melanocytic proliferation may occur, it is important to rule out a second malignancy. To the knowledge of the authors, this is the first report of delayed-onset bilateral diffuse uveal melanocytic proliferation associated with gastric adenocarcinoma. Treatment with intravitreal anti-vascular endothelial growth factor therapy warrants further evaluation.