CORRELATION BETWEEN MICROPERIMETRY AND IMAGING IN EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE.

PURPOSE: To determine the correlation between microperimetry and imaging findings in extensive macular atrophy with pseudodrusen-like appearance (EMAP). METHODS: This cross-sectional, observational study included 44 consecutive patients with EMAP (88 eyes) and 30 healthy subjects (60 eyes). Both groups underwent visual acuity assessment, mesopic and scotopic microperimetry, fundus photography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography. Retinal sensitivity was also subdivided in macular (0-4°) and paramacular areas (8-10°). Scotopic sensitivity loss was defined as the difference between scotopic and mesopic sensitivities for each tested point. Eyes with EMAP were further classified into the three stages described by Romano et al: 19 eyes in Stage 1, 31 in Stage 2, and 38 in Stage 3. RESULTS: Mesopic and scotopic retinal sensitivity were significantly reduced in patients with EMAP compared with controls, particularly in the macular area (all P < 0.001). Mesopic retinal sensitivity progressively declined in more advanced EMAP stages (all P < 0.01), but no scotopic differences were observed between Stages 2 and 3 ( P = 0.08). Remarkably, scotopic sensitivity loss was significantly higher in Stage 1 ( P < 0.05).On multivariate analysis, mesopic dysfunction was associated with larger atrophic areas ( P < 0.01), foveal involvement ( P = 0.03), and fibrosis ( P = 0.02). Conversely, no independent variable was associated with a reduced scotopic retinal sensitivity (all P > 0.05). CONCLUSION: The findings highlight that patients with EMAP suffer from a severe cone- and rod-mediated dysfunction on microperimetry. The predominant rod impairment in the early cases (Stage 1) emphasizes the importance of dark-adapted scotopic microperimetry as a clinical end point and suggests defective transportation across the RPE-Bruch membrane complex in its pathogenesis.

NATURAL COURSE AND CLASSIFICATION OF EXTENSIVE MACULAR ATROPHY WITH PSEUDODRUSEN-LIKE APPEARANCE.

PURPOSE: To describe the imaging characteristics and topographic expansion of retinal pigment epithelium (RPE) and outer retinal atrophy in extensive macular atrophy with pseudodrusen-like appearance. METHODS: Three-year, prospective, observational study. Nine patients with extensive macular atrophy with pseudodrusen-like appearance (17 eyes; 6 women) with no other ocular conditions were annually examined; one eye was excluded because of macular neovascularization. Best-corrected visual acuity measurement, fundus photographs, blue-light autofluorescence, and optical coherence tomography were performed at each visit. Formation of atrophy was analyzed on optical coherence tomography at foveal and extrafoveal areas following the Classification of Atrophy Meeting recommendations. Spatial enlargement throughout four sectors was assessed on blue-light autofluorescence after placing an Early Treatment for Diabetic Retinopathy Study grid centered on the foveola. RESULTS: Mean age was 53.0 ± 2.1 years at baseline with a follow-up of 36.6 ± 0.7 months. Thinning of the outer nuclear layer and disruption of the ellipsoid zone initially appeared above areas of RPE-Bruch membrane separation and preceded RPE atrophy. Subfoveal fibrosis was seen in 65% of the eyes. Superior sector involvement was found in all patients at baseline and was significantly larger than the other sectors at any time point ( P < 0.001). Best-corrected visual acuity declined from 68.0 ± 15.7 letters to 44.8 ± 14.9 letters during the follow-up and was significantly associated with subfoveal atrophy ( P < 0.001) and fibrosis ( P = 0.02). CONCLUSION: Our findings suggest that primary alterations in patients with extensive macular atrophy with pseudodrusen-like appearance are present at the outer segment-RPE interface, with the superior Early Treatment for Diabetic Retinopathy Study sector being the most vulnerable, which progresses to extensive atrophy of the RPE and outer retinal layers. Accordingly, we propose a three-stage disease classification.

QUANTITATIVE ASSESSMENT OF AUTOMATED OPTICAL COHERENCE TOMOGRAPHY IMAGE ANALYSIS USING A HOME-BASED DEVICE FOR SELF-MONITORING NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate a prototype home optical coherence tomography device and automated analysis software for detection and quantification of retinal fluid relative to manual human grading in a cohort of patients with neovascular age-related macular degeneration. METHODS: Patients undergoing anti-vascular endothelial growth factor therapy were enrolled in this prospective observational study. In 136 optical coherence tomography scans from 70 patients using the prototype home optical coherence tomography device, fluid segmentation was performed using automated analysis software and compared with manual gradings across all retinal fluid types using receiver-operating characteristic curves. The Dice similarity coefficient was used to assess the accuracy of segmentations, and correlation of fluid areas quantified end point agreement. RESULTS: Fluid detection per B-scan had area under the receiver-operating characteristic curves of 0.95, 0.97, and 0.98 for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid, respectively. On a per volume basis, the values for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid were 0.997, 0.998, and 0.998, respectively. The average Dice similarity coefficient values across all B-scans were 0.64, 0.73, and 0.74, and the coefficients of determination were 0.81, 0.93, and 0.97 for intraretinal fluid, subretinal fluid, and subretinal pigment epithelium fluid, respectively. CONCLUSION: Home optical coherence tomography device images assessed using the automated analysis software showed excellent agreement to manual human grading.

Prechoroidal cleft thickness correlates with disease activity in neovascular age-related macular degeneration.

PURPOSE: The purpose of this study was to investigate the structural variations of the hyporeflective pocket of fluid (prechoroidal cleft) located between Bruch's membrane and the hyperreflective material within the pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD). METHODS: In this retrospective, observational case series study, patients diagnosed with nAMD and prechoroidal cleft associated with other activity signs of the macular neovascularization (MNV) were included. Structural optical coherence tomography (OCT) scans were evaluated to obtain anatomical measurements of prechoroidal cleft and PED at three different visits (T0, inactive MNV; T1, active MNV; T2, treated inactive MNV). The variations in size of the cleft and the PED were correlated with nAMD activity. RESULTS: Twenty-nine eyes from 27 patients were included. The subfoveal measurements showed a significant increase of prechoroidal cleft height and width from T0 to T1 (P < 0.05) and a subsequent decrease of the cleft height after treatment with anti-VEGF agents (P = 0.004). A similar significant trend was observed for the greatest prechoroidal cleft height and width, obtained assessing the whole OCT raster. In the multivariate analysis, the cleft height was significantly affected by both time (P = 0.001) and PED height (P < 0.0001). By contrast, the effect of fibrovascular tissue size within the PED was not significant. Visual acuity did not correlate with prechoroidal cleft size. CONCLUSION: Prechoroidal cleft increased in association with MNV reactivation and decreased after treatment. Our results suggest that prechoroidal cleft could represent an accumulation of fluid actively exudating from the MNV and should be considered a sign of nAMD activity.

Macular neovascularization lesion type and vision outcomes in neovascular age-related macular degeneration: post hoc analysis of HARBOR.

PURPOSE: To characterize relationships between Consensus on Neovascular Age-Related Macular Degeneration Nomenclature (CONAN) Study Group classifications of macular neovascularization (MNV) and visual responses to ranibizumab in patients with neovascular age-related macular degeneration (nAMD). METHODS: This was a post hoc analysis of the phase 3 HARBOR trial of ranibizumab in nAMD. Analyses included ranibizumab-treated eyes with baseline multimodal imaging data; baseline MNV; subretinal and/or intraretinal fluid at screening, baseline, or week 1; and spectral-domain optical coherence tomography images through month 24 (n = 700). Mean best-corrected visual acuity (BCVA) over time and mean BCVA change at months 12 and 24 were compared between eyes with type 1, type 2/mixed type 1 and 2 (type 2/M), and any type 3 MNV at baseline. RESULTS: At baseline, 263 (37.6%), 287 (41.0%), and 150 (21.4%) eyes had type 1, type 2/M, and any type 3 lesions, respectively. Type 1 eyes had the best mean BCVA at baseline (59.0 [95% CI: 57.7-60.3] letters) and month 24 (67.7 [65.8-69.6] letters), whereas type 2/M eyes had the worst (50.0 [48.6-51.4] letters and 60.8 [58.7-62.9] letters, respectively). Mean BCVA gains at month 24 were most pronounced for type 2/M eyes (10.8 [8.9-12.7] letters) and similar for type 1 (8.7 [6.9-10.5] letters) and any type 3 eyes (8.3 [6.3-10.3] letters). CONCLUSION: Differences in BCVA outcomes between CONAN lesion type subgroups support the use of an anatomic classification system to characterize MNV and prognosticate visual responses to anti-vascular endothelial growth factor therapy for nAMD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00891735. Date of registration: April 29, 2009.

MULTIMODAL IMAGING CHARACTERISTICS AND FUNCTIONAL CORRELATES IN RIP HEALING.

PURPOSE: To report the imaging and functional features of the repair tissue following retinal pigment epithelium (RPE) tears. METHODS: This cross-sectional observational study included patients with RPE tears secondary to neovascular age-related macular degeneration and at least 12 months of follow-up. The following variables were analyzed: best-corrected visual acuity; retinal sensitivity using microperimetry; outer retinal layers status and RPE resurfacing on optical coherence tomography; fibrosis; autofluorescence signal recovery using blue-light and near-infrared autofluorescence. RESULTS: Overall, 48 eyes were included (age: 82 ± 5 years) and 34 of them showed signs of healing. Retinal pigment epithelium resurfacing was noticed in 22 cases, whereas fibrosis appeared in 21 eyes. Autofluorescence improved in 17 cases using blue-light infrared autofluorescence and 7 eyes on near-infrared autofluorescence. Outer retinal layers were more frequently preserved when RPE resurfacing and autofluorescence improvement occurred ( P < 0.05). Although best-corrected visual acuity was higher for smaller RPE tears ( P = 0.01), retinal sensitivity of the healing tissue was positively affected by autofluorescence improvement ( P < 0.001) and by absence of fibrosis ( P = 0.03). CONCLUSION: Autofluorescence signal recovery after rip occurrence possibly reflects the underlying status of the RPE and is associated with better functional outcomes. Our findings highlight the importance of blue-light infrared autofluorescence and especially near-infrared autofluorescence assessment in the setting of rip healing.

Quantitative autofluorescence findings in patients undergoing hydroxychloroquine treatment.

BACKGROUND: To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) and at risk of retinal toxicity but with no apparent signs of retinal toxicity and to compare it with that of untreated subjects. METHODS: Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight [ABW]) but no alterations on spectral domain-optical coherence tomography, short-wavelength autofluorescence and 10-2 visual field examination were recruited. Healthy subjects matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analysed using the conventional qAF grid by Delori calculating the qAF of eight sectors of the intermediate ring and the mean of those values (qAF8 ). RESULTS: Thirty-nine patients treated with HCQ (38 females, mean age 52.1 ± 8.6 years) and 39 untreated subjects (38 females, mean age 51.2 ± 8.6 years) were included. In both HCQ patients and untreated subjects, qAF8 was positively correlated with age (p = 0.004). Although HCQ patients showed a higher mean qAF8 compared with untreated subjects (294.7 ± 65.3 vs. 268.9 ± 57.5), the difference was not significant (p = 0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared with untreated subjects (all p < 0.05). CONCLUSIONS: These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure.

Comparison between two multimodal imaging platforms: Nidek Mirante and Heidelberg Spectralis.

PURPOSE: To investigate the reliability and comparability of retinal measurements obtained with spectral-domain optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), confocal scanning laser ophthalmoscopy (cSLO) colour images, and fundus autofluorescence (FAF) between two multimodal imaging platforms in eyes with macular pathology and normal, healthy volunteers. METHODS: This cross-sectional, multi-centre, instrument validation study recruited 94 consecutive subjects. All participants underwent a dilated examination and were scanned consecutively on the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) and Nidek Mirante (Nidek Co. Ltd., Gamagori, Japan) devices. Agreement between device images were evaluated from measures of the central retinal thickness (CRT), presence of segmentation and fixation imaging artefacts (IA), foveal avascular zone (FAZ) measurements; as well as sensitivity and specificity values from the detection of atrophy on fundus autofluorescence (FAF), drusen, subretinal drusenoid deposits, geographic atrophy, epiretinal membrane, fibrosis and haemorrhage on multicolour imaging, and agreement between devices and groups. RESULTS: Compared with reference clinical examination, sensitivity values for the identification of retinal features using sole device images ranged from 100% for epiretinal membranes to 66.7% for subretinal drusenoid deposits (SSD). Mean absolute difference for CRT between OCT devices was 3.78 µm (95% confidence interval [CI]: - 21.39 to 28.95, P = 0.809). Differences in the superficial and deep capillary plexus FAZ area on OCTA between devices were not statistically significant (P = 0.881 and P = 0.595, respectively). IAs were significantly increased in the presence of macular pathology. CONCLUSION: Comparison of retinal measurements between the OCT devices did not differ significantly. Common ultrastructural biomarkers of multiple macular pathologies were identified with high sensitivities and specificities, with good agreement between graders, indicating that they can be identified with comparable confidence in retinal imaging between the two devices.

Quantitative assessment of choriocapillaris flow deficits in eyes with macular neovascularization.

PURPOSE: To investigate choriocapillaris flow deficits (CC FD) in a group of eyes with Type 3 macular neovascularization (MNV) versus a group of eyes with Type 1 and/or 2 MNV versus healthy eyes. METHODS: In this cross-sectional, retrospective, multicenter, observational study, consecutive patients with Type 3 MNV, Type 1 and/or 2 MNV, and age-matched controls were included. PLEX Elite optical coherence tomography angiography was performed with a 6 × 6 mm scan pattern centered on the fovea. The CC FD was computed in 4 peripheral 1 × 1 mm squares to allow comparison between equidistant regions unaffected by MNV. RESULTS: Twenty Type 3, 20 Type 1 and/or 2 MNV [13 (65%) Type 1 MNV, 1 (5%) Type 2 MNV, and 6 (30%) mixed Type 1 and 2 MNV], and 20 age-matched controls were included. The mean impairment in the CC in the 4 peripheral squares was 16.07 ± 7.27% in Type 3 MNV eyes, 11.48 ± 5.59% in Type 1/2 MNV eyes, and 9.64 ± 3.59% in controls. Type 3 MNV displayed a statistically significantly higher CC FD compared with both Type 1/2 MNV (P = 0.031) and controls (P < 0.0001). No significant differences were observed between Type 1/2 MNV and controls (P = 0.223). CONCLUSIONS: CC FD was significantly greater in the peripheral macular regions of eyes with Type 3 MNV compared to eyes with Type 1/2 MNV and normal control eyes. Pathogenic choroidal mechanisms may differ in eyes with different MNV subtypes. Whereas focal CC impairment may drive the development of Type 1/2 MNV, diffuse CC disruption may be more important in eyes with Type 3 MNV.

Optical coherence tomography angiography for detection of macular neovascularization associated with atrophy in age-related macular degeneration.

PURPOSE: To evaluate the ability of optical coherence tomography angiography (OCTA) to detect macular neovascularization (MNV) in eyes with atrophy compared with fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). METHODS: In this prospective study, eyes with MNV and atrophy (termed macular atrophy or MA) secondary to age-related macular degeneration (AMD), and AMD eyes with geographic atrophy (GA) without MNV underwent multimodal imaging with FA, ICGA, structural OCT, and OCTA. The presence of MNV was determined using all imaging modalities by senior retina specialists and was considered the gold standard reference. Each individual imaging modality was then evaluated independently by two expert readers for the presence of MNV in a masked fashion. Morphologic characteristics of the MNV were evaluated on the custom OCTA slab. RESULTS: Twenty-one patients with MA+MNV and 21 with GA only were enrolled. Manual segmentation on OCTA allowed detection of the MNV in 95.2% of eyes with MA+MNV and in 4.7% of eyes with GA, showing high specificity (95.2%) and sensitivity (95.2%). FA, ICGA, and OCT detected MNV in 57.1%, 52.3%, and 66.7% of eyes with MA+MNV and in 14.2%, 9.5%, and 42.8% with GA. Sensitivity and specificity were 85.7% and 57.1% for FA, 90.5% and 52.4% for ICGA, and 66.7% and 57.1% for OCT. CONCLUSIONS: OCTA appears to be superior to other imaging modalities for identification of MNV in eyes with macular atrophy. OCTA should be considered as part of the multimodal imaging evaluation of eyes with atrophy, particularly in the context of clinical trials.

ACUTE IDIOPATHIC MACULOPATHY: A Proposed Disease Staging Based on Multimodal Imaging.

PURPOSE: To describe the clinical course and the multimodal imaging of acute idiopathic maculopathy. METHODS: Medical records and multimodal imaging including color fundus photography, optical coherence tomography, and fundus autofluorescence were retrospectively reviewed. Recognition of the fundus autofluorescence patterns and their relationship with the disease duration, best-corrected visual acuity, and optical coherence tomography features represented the main outcome measures. RESULTS: Seventeen eyes of 16 patients (7 women; mean age 29.9 years) with a mean follow-up of 23.9 months were included. The mean best-corrected visual acuity at presentation was 0.63 ± 0.54 logarithm of the minimum angle of resolution (Snellen equivalent, 20/85). All but one patient had the best-corrected visual acuity recovery to 20/20. Four sequential patterns of fundus autofluorescence corresponding to 4 proposed stages of disease were observed. Patterns 1 (central hypoautofluorescence with surrounding hyperautofluorescence) and 2 (stippled hyperautofluorescence and hypoautofluorescence) were found at presentation. Patterns 3 (central hyperautofluorescence surrounded by hypoautofluorescence) and 4 (hypoautofluorescence) were observed during the disease course and/or at the last follow-up visit. Duration of the disease was significantly different between patterns at baseline and last visit. Pattern 1 significantly related to the presence of subretinal detachment (Fisher's exact test; P =0.003) on optical coherence tomography in comparison with Pattern 2. Pattern 4 showed unique homogeneously decreased autofluorescence with corresponding attenuation of retinal pigment epithelium and restored outer retinal layers on optical coherence tomography. CONCLUSION: A sequential disease staging based on multimodal imaging for acute idiopathic maculopathy is proposed. The recognition of the observed imaging patterns may help clinicians in the correct diagnosis and patient counseling.

Macular Atrophy Incidence and Progression in Eyes with Neovascular Age-Related Macular Degeneration Treated with Vascular Endothelial Growth Factor Inhibitors Using a Treat-and-Extend or a Pro Re Nata Regimen: Four-Year Results of the MANEX Study.

PURPOSE: To compare the incidence and progression of macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents using either a treat-and-extend (T&E) or a pro re nata (PRN) regimen over 4 years in a real-world setting. DESIGN: Four-year, multicenter, retrospective comparative study. PARTICIPANTS: Two hundred sixty-four patients with treatment-naive nAMD. METHODS: Consecutive patients with nAMD received anti-VEGF therapy according to a T&E (n = 163) or PRN (n = 101) regimen. Eyes were included if they had received anti-VEGF injections for a period of at least 4 years and had undergone annual fundus autofluorescence (FAF) and OCT imaging using Heidelberg Spectralis. Two masked graders independently delineated areas of MA from serial FAF images using Heidelberg region finder software, and growth rates were calculated. Incident MA was assessed using proportional hazard ratios. MAIN OUTCOMES MEASURES: Macular atrophy incidence and progression over 4 years, association between treatment strategies, and number of injections. RESULTS: At baseline, MA was present in 24% and 20% of study eyes in T&E and PRN groups, respectively (P = 0.45). At year 4, 27% (34/124) and 25% (20/81) of eyes without baseline MA showed detectable MA in the T&E and PRN groups, respectively. In those with MA at baseline, the mean square root area of MA progressed by a rate of 0.4 ± 0.2 mm/year and 0.4 ± 0.1 mm/year in the T&E and PRN groups, respectively (P = 0.23). Multivariate analysis for baseline predictors of MA growth demonstrated that older age, poorer baseline visual acuity, and presence of retinal angiomatous proliferation had a higher risk of greater MA progression (P = 0.03). Regression analysis demonstrated no association between T&E and PRN treatment strategies with the risk of new MA developing during the 4 years of follow-up or the progression of pre-existing MA at year 4 (P = 0.692). CONCLUSIONS: Over 4 years, neither incidence nor progression of MA in eyes with nAMD treated with anti-VEGF injections was influenced by the treatment regimen and injection frequency. Eyes treated with a T&E regimen received more injections and achieved better visual outcomes compared with those treated with a PRN approach.

Multicolor imaging in macular telangiectasia-a comparison with fundus autofluorescence.

PURPOSE: To describe various clinical features of idiopathic juxtafoveal retinal telangiectasis group 2A or idiopathic macular telangiectasia type 2 (MacTel) on multicolor imaging (MCI) and compare imaging findings of MacTel on MCI with fundus autofluorescence (FAF). METHODS: Patients with a clinical diagnosis of MacTel based on Gass and Blodi's classification were included. FAF and MCI images were graded qualitatively for stage of disease, margins of involvement, hyperautofluorescence on FAF (corresponding retinal atrophy on MCI), and detection of crystals. FAF and MCI were graded quantitatively for the area and number of quadrants involved, hypoautofluorescene on FAF (corresponding intraretinal pigment hyperplasia or retinal pigment epithelium [RPE] atrophy on MCI), and foci of right-angled venules. RESULTS: Seventy-eight eyes of forty five patients were included with both imaging modalities showing no difference with respect to staging of non-proliferative MacTel. Retinal crystals were recognized on MCI but not on FAF. Neurosensory retinal atrophy and  subretinal neovascular membranes were detected using MCI with 92.3 and 83.3% sensitivity, respectively. Intraretinal pigmented hyperplasia was more accurately detected (70.1 vs 58.4%) compared with RPE atrophy on MCI. MCI showed larger area of involvement, higher number of quadrants involved (p < 0.001), and better delineation of margins (p = 0.002) compared with FAF. A higher mean number of vessel dipping foci was noted on MCI in comparison with FAF (3.34 vs 3.1). CONCLUSION: Various parameters were more easily defined using MCI compared with FAF which qualifies MCI as an enface depth-resolved imaging adjunct to conventional multimodal imaging in MacTel. The ability to detect enface as well as cross-sectional imaging features makes MCI a valuable tool in MacTel.

COMPARISON BETWEEN SEVERAL OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY DEVICES AND INDOCYANINE GREEN ANGIOGRAPHY OF CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To compare indocyanine green angiography and four different optical coherence tomography angiography (OCTA) devices and to test their reproducibility in the evaluation of choroidal neovascularization (CNV). METHODS: This study was an observational case series of Type 1 and Type 2 CNV presenting at the Eye Clinic, Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, imaged with indocyanine green angiography and four different OCTA devices: prototype PlexElite (Carl Zeiss Meditec), prototype Spectralis OCTA (Spectralis; Heidelberg Engineering, Heidelberg, Germany), Optovue RTVue XR Avanti (Optovue, Inc, Fremont, CA), and AngioPlex (Cirrus 5000 HD-OCT; Carl Zeiss Meditec, Inc, Dublin, CA). Optical coherence tomography angiography examinations were performed using a 3 × 3-mm or 6 × 6-mm volume scan pattern to capture the full lesion. The mean area of CNV, vessel density, and fractal dimension were compared between the devices. RESULTS: Seventeen eyes of 17 patients with CNV were enrolled. The CNV area was significantly larger in indocyanine green angiography than in the OCTA devices. Moreover, the four different instruments produced measurements with different mean values of CNV area, vessel density, and fractal dimension. The Bland-Altman analysis revealed that the limits of agreement for the comparisons were not acceptable. CONCLUSION: The choroidal neovascularization area is larger when imaged with standard indocyanine green angiography than with different OCTA devices with different algorithms, wavelengths, and scan patterns. The differences between several OCTA devices in the evaluation of quantitative parameters of CNV, such as CNV area, vessel density, and fractal dimension, suggest the necessity to standardize OCTA measurements for research and clinical practice.

OPTICAL COHERENCE TOMOGRAPHY 2: Diagnostic Tool to Study Peripheral Vitreoretinal Pathologies.

PURPOSE: To investigate the utility of new wide-field optical coherence tomography (OCT) device in the evaluation of mid and far retinal periphery and to show its feasibility and advantages in clinical practice. METHODS: Consecutive patients underwent a complete ophthalmologic examination including standard OCT and new prototype OCT2 derived from Heidelberg Spectralis. RESULTS: Thirty-one eyes of 31 patients were studied with a total of 44 lesions, including 18 retinal detachments, 15 retinal holes and tears, 9 retinoschisis, and 2 retinal tufts. Fourteen (32%) lesions were found in mid and 30 (68%) in far periphery with 9 (20%) lesions in the superior region, 10 (23%) in the superior temporal, 8 (18%) in the temporal, 4 (9%) in the inferior temporal, 7 (16%) in the inferior, 4 (9%) in the nasal, and 2 (5%) in the superior nasal. Among the lesions evaluated by OCT2, 10 (71%) in mid periphery and 11 (37%) in far periphery could be imaged by standard OCT. CONCLUSION: The introduction of OCT2 into clinical practice may provide significant benefits for imaging peripheral retinal disorders. The application of OCT2 technology with 55° lens and scan length and angle modulation could improve our understanding of peripheral vitreoretinal disorders and facilitate their management.

Optical coherence tomography and optical coherence tomography angiography in uveitis: A review.

Optical coherence tomography (OCT) has dramatically changed the understanding and management of uveitis and other ocular conditions. Currently, OCT angiography (OCTA) combines structural information with the visualization of blood flow within the imaged area. The aim of this review is to present the basic principles of OCT and OCTA interpretation and to investigate the role of these imaging techniques in the diagnosis and management of uveitis. Common complications of intraocular inflammation such as macular oedema and inflammatory choroidal neovascularization are often diagnosed and followed with OCT/OCTA scans. However, uveitis specialists can obtain much more information from tomographic scans. This review provides a comprehensive description of typical OCT/OCTA findings characterizing different ocular structures in uveitis, proceeding from the cornea to the choroid. A careful interpretation of OCT/OCTA images can help in the differential diagnosis, the prediction of clinical outcomes, and the follow-up of patients with uveitis.

Choroidal and Sub-Retinal Pigment Epithelium Caverns: Multimodal Imaging and Correspondence with Friedman Lipid Globules.

PURPOSE: To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. DESIGN: Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. PARTICIPANTS: Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). METHODS: Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. MAIN OUTCOME MEASURES: Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. RESULTS: Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 µm and 65.4±27.9 µm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. CONCLUSIONS: Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FINDINGS IN ENDOGENOUS CANDIDA ENDOPHTHALMITIS AND THEIR CLINICAL RELEVANCE.

PURPOSE: To describe vitreal, retinal, and choroidal features of eyes affected by Endogenous candida endophthalmitis (ECE) analyzed by spectral domain optical coherence tomography (SD-OCT) and to evaluate their clinical impact. METHODS: Medical records and SD-OCT images from eyes diagnosed with ECE at four retina and uveitis tertiary referral centers were retrospectively evaluated. Spectral domain optical coherence tomography images were analyzed to evaluate the structural changes occurring in the vitreous, the retina, and the choroid in areas involved by ECE. Baseline and final best-corrected visual acuity were correlated with SD-OCT findings. RESULTS: Fifteen eyes from nine patients were enrolled. Vitreous involvement (vitreous cells, posterior hyaloid thickening) was detected in 13/15 eyes. Peculiar hyper-reflective preretinal aggregates obscuring the underlying retina because of a shadowing effect ("rain-cloud" sign) were noticed in all eyes with vitreous involvement. Two patterns of retinal and choroidal findings were identified: the first (six eyes) confined within the inner retinal layers (Intraretinal Pattern), the second (nine eyes) involving both retina (full thickness) and choriocapillaris (Chorioretinal Pattern). None of the eyes showed both patterns. None of the eyes, regardless the pattern, showed choroidal thickening. Baseline best-corrected visual acuity was not associated with OCT pattern (P = 0.09). On the contrary, final best-corrected visual acuity was significantly higher in patients showing Intraretinal Pattern (∼20/25, 0.06 ± 0.08 LogMAR) than in subjects with Chorioretinal Pattern (∼20/50, 0.44 ± 0.30 LogMAR) (P = 0.01). CONCLUSION: Endogenous candida endophthalmitis showed peculiar features on SD-OCT. Two distinct patterns of chorioretinal involvement influencing the final best-corrected visual acuity were identified. Spectral domain optical coherence tomography could be useful in the diagnosis, management, and outcome prediction in ECE.

OCRIPLASMIN FOR VITREOMACULAR TRACTION: LOOKING OUTSIDE THE MACULA: A Wide-Field Optical Coherence Tomography Study.

PURPOSE: To evaluate baseline features and morphologic changes of vitreoretinal adhesion and outer retinal layers outside the macula after intravitreal ocriplasmin injection. To study the relation between vitreous detachment and attenuation of retinal outer segments signal. METHODS: Retrospective cases series of 15 eyes. Each eye was scanned with the 55° wide-field optical coherence tomography lens in 6 different locations, three horizontal B-scan (central, temporal, and nasal) and three vertical B-scan (central, superior, and inferior) at baseline, 1 week, 1 month, 3 months, and 6 months after injection. RESULTS: After ocriplasmin injection, vitreomacular traction (VMT) resolved in 12 patients (80%), 3 of them presenting a complete posterior vitreous detachment. Eight patients (53%) showed a panretinal attenuation of photoreceptors outer segment signal, 7 with VMT resolution and 1 with non-posterior vitreous detachment and no VMT resolution. In three patients after VMT resolution the attenuation involved also areas with no posterior vitreous detachment. The attenuation resolved during follow-up in 7/8 eyes (87.5%). CONCLUSION: Intravitreal ocriplasmin injection induced resolution of VMT in most cases and more rarely a release of vitreopapillary adhesion and a complete posterior vitreous detachment. An acute panretinopathy was visible in more than half of the patients and was not related to vitreous detachment.