Optical coherence tomography angiography macular biomarkers of peripheral retinal ischemia in diabetic macular edema: secondary endpoints from the clinical study "FOVEA".

PURPOSE: To investigate the relationship between the macular values of fractal dimension (FD) and lacunarity (LAC) on optical coherence tomography angiography (OCTA) images and the presence of peripheral retina non-perfusion areas (NPAs) on fluorescein angiography (FA) in patients with treatment-naïve diabetic macular edema (DME). METHODS: Fifty patients with treatment-naïve DME underwent a full ophthalmic examination, including best-corrected visual acuity measurement, FA, spectral-domain optical coherence tomography, and OCTA. Specifically, FA was performed to detect the presence of retinal NPAs, whereas fractal OCTA analysis was used to determine macular FD and LAC values at the level of the superficial and deep capillary plexus (SCP and DCP). FA montage frames of the posterior pole and peripheral retina, as well as macular OCTA slabs of the SCP and DCP, were obtained. RESULTS: Thirty (60%) eyes with FA evidence of peripheral retinal NPAs in at least one quadrant showed significantly lower FD and higher LAC in both SCP and DCP, when compared with eyes presenting a well-perfused peripheral retina. Furthermore, macular FD and LAC values were found to be significantly associated with the extent of retinal NPAs. CONCLUSIONS: Macular FD and LAC of both SCP and DCP seem to be strongly associated with the extent of peripheral retinal NPAs, thus suggesting that may be useful predictive biomarkers of peripheral ischemia in treatment-naïve DME eyes.

Vascular density normative data of radial peripapillary capillary plexus in healthy Caucasian subjects.

PURPOSE: To establish a normative database for vascular density (VD) of radial peripapillary capillary plexus (RPC) in healthy Caucasian subjects. METHODS: 633 healthy Caucasian subjects underwent a complete ophthalmological examination, including slit-lamp biomicroscopy, best corrected visual acuity measurement with Early Treatment Diabetic Retinopathy Study charts, intraocular pressure measurement, fundus examination, and macular and optic nerve head (ONH) structural optical coherence tomography (OCT). En-face 4.5 × 4.5 mm OCT angiography scans of the RPC plexus were recorded and VD values, automatically provided by the AngioAnalytics™ software, noted. We statistically estimated the impact of age and gender on RPC VD values using a linear mixed model. RESULTS: 560 subjects fully met inclusion criteria and, according to age, were stratified into 5 groups: 18-50 years (77), 51-60 years (160), 61-70 years (110), 71-80 years (132), and ≥ 81 years (81). Overall, mean RPC VD of the whole en-face image was 53.03 ± 4.27%. Age was significantly related to RPC VD values of whole en-face image (r = -0.454; p < 0.0001), which decreased with aging. The linear mixed model disclosed that age has a statistically significant effect on RPC VD values in whole en-face image (p = 0.0006). As age increases, RPC VD values decrease by 0.12 per year. Conversely, no significant gender-related differences were found in terms of RPC VD values of whole en-face image and each parapapillary quadrant analyzing all age group. CONCLUSIONS: Results show that RPC VD values in healthy Caucasian subjects decrease with aging. These data may be used to create a reference normative database useful for clinical use. KEY MESSAGES: What is known Radial peripapillary capillary (RPC) plexus, consisting of long parallel capillaries with rare bifurcations and anastomosis and extending straight along the course of the retinal nerve fiber layer to the posterior pole, may be affected early in some optic nerve head (ONH) and retinal diseases. What is new This study reports RPC vascular density (VD) values, automatically measured on optical coherence tomography angiography, in healthy Caucasian subjects, demonstrating that age is negatively related to RPC VD values. Results show that RPC VD values in healthy Caucasian subjects decrease with aging. These data may be used to create a reference normative database useful for clinical use.

Final 4-year results of the RAINBOW real-world study: intravitreal aflibercept dosing regimens in France in treatment-naïve patients with neovascular age-related macular degeneration.

PURPOSE: The purpose of this study is to evaluate real-world treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in routine clinical practice in France. METHODS: RAINBOW (NCT02279537) was an ambispective, observational, 4-year study assessing IVT-AFL effectiveness, treatment patterns, and safety in patients with nAMD in France. Treatment-naïve patients prescribed IVT-AFL and treated according to local practice (pro re nata or treat-and-extend) were eligible. Three treatment cohorts were retrospectively identified based on their treatment pattern within the first 12 months: regular (3 initial monthly IVT-AFL injections received within 45-90 days after the first injection in month 0 and followed by injections every 2 months), irregular with the initial monthly injections, and irregular without the initial monthly injections. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline to month 12. The 48-month results are described here. RESULTS: Overall, the study included 516 patients (each with one study eye), and 30.2% of patients completed 48 months of IVT-AFL treatment. Mean change in BCVA from baseline (56.5 letters) to month 48 for patients with an assessment at both time points was + 1.1 (regular cohort, n = 47), + 0.1 (irregular cohort with initial monthly injections, n = 115), and - 1.3 letters (irregular cohort without initial monthly injections, n = 26), representing a decrease from the gains achieved at month 12. Mean number of IVT-AFL injections received by month 48 in the treatment cohorts was 14.9, 13.7, and 11.9, respectively. The safety profile of IVT-AFL was consistent with previous studies. CONCLUSION: In RAINBOW, the 48-month results demonstrate a lack of long-term effectiveness of IVT-AFL treatment of nAMD due to progressive undertreatment in routine clinical practice in France. These real-world findings highlight the importance of 3 initial monthly IVT-AFL injections followed by continuous proactive treatment beyond the first year to achieve optimal functional outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02279537.

Polygenic risk score and biochemical/environmental variables predict a low-risk profile of age-related macular degeneration in Sardinia.

PURPOSE: To ascertain the prevalence and clinical and genetic features of age-related macular degeneration (AMD) in subjects living in the Lanusei valley, Central Sardinia, Italy, involved in a study on ageing (SardiNIA project). METHODS: A total of 814 volunteers aged ≥ 50 years, randomly selected from the SardiNIA project dataset, were included. A color fundus (CF) photograph of the 30° central retina of each eye was obtained and graded according to the Age-Related Eye Disease Study system. Life-style choices were investigated using standardized questionnaires. The concentrations of several inflammatory biomarkers (i.e., complement component, fibrinogen, and C-reactive protein) were measured. Polygenic risk score (PRS) was calculated and compared with results obtained from a European cohort. RESULTS: A total of 756 subjects had gradable CF photographs for AMD detection. In 91.3%, no signs of AMD were observed. The prevalence rates of early and late AMDs were 6.9% and 0.6%, respectively. A total of 85% of subjects were physically active; only 13.5% were current smokers. Low concentrations of complement component, fibrinogen, and C-reactive protein were found. We calculated the polygenic risk scores (PRS) using 40 AMD markers distributed on several candidate genes in Europeans and Sardinians. The mean PRS value was significantly lower in Sardinians than in the Europeans (0.21 vs. 0.248, respectively, p = 1.18 × 10-77). CONCLUSIONS: In our cohort, most subjects showed no sign of any AMD type and late AMD was a condition rarely observed. Results of genetic, biochemical, and life-style investigation support the hypothesis that Sardinia population may present of a peculiar background with a protective effect against AMD development.

POLYPOIDAL CHOROIDAL NEOVASCULARIZATION VERSUS TYPE 1 CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION: A Fractal Analysis Study.

PURPOSE: To compare quantitative optical coherence tomography angiography parameters between polypoidal choroidal neovascularizations (PCNVs) and Type 1 choroidal neovascularizations (CNVs) in patients with age-related macular degeneration. METHODS: PCNV and Type 1 CNV lesions were retrospectively recruited in a cohort of patients with age-related macular degeneration. All the patients underwent a comprehensive ophthalmic evaluation, including best-corrected visual acuity, fluorescein and indocyanine green angiography, structural optical coherence tomography (OCT), and optical coherence tomography angiography.Vascular perfusion density, fractal dimension, and lacunarity were computed by means of fractal analysis of neovascular en face optical coherence tomography angiography slabs. RESULTS: Sixty-eight eyes were included in the analysis. Of them, 35 of 68 eyes (51.5%) had PCNV and 33 of 68 (48.5%) had Type 1 CNV. Patients with PCNV were significantly younger (P = 0.0003) and had a higher best-corrected visual acuity (P < 0.0001). The mean vascular perfusion density was 0.83 ± 0.11% in PCNVs and 0.46 ± 0.10% in Type 1 CNVs (P < 0.0001). The mean fractal dimension was 1.44 ± 0.1 in PCNVs and 1.45 ± 0.09 in Type 1 CNVs (P = 0.86) while the mean lacunarity was 2.46 ± 1.03 in PCNVs and 1.86 ± 0.52 in Type 1 CNVs (P = 0.006). CONCLUSION: PCNVs resulted to be more heterogeneous and characterized by higher vascular perfusion density and lacunarity values than Type 1 CNVs. These interesting findings seem to support the idea that PCNVs and Type 1 CNVs are two separate clinical entities. However, future studies based on optical coherence tomography angiography fractal analysis, but also involving other relevant parameters such as demographics, presentation, morphology on multimodal imaging, and response to treatment, are necessary before drawing any definitive conclusions on whether PCNV is a specific clinical entity or a neovascular age-related macular degeneration variant.

QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF INACTIVE MACULAR NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare quantitative optical coherence tomography angiography parameters between treatment-naïve quiescent macular neovascularizations (MNVs) and previously treated nonexudative Type 1 MNVs, in patients with age-related macular degeneration. METHODS: The eyes included in the study were analyzed by fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. According to their medical history and multimodal imaging evaluation, Type 1 MNVs were divided into 2 groups: 1) treatment-naïve quiescent MNVs; 2) previously treated nonexudative Type 1 MNVs. Quantitative optical coherence tomography angiography parameters, including perfusion density (PD), fractal dimension (FD), and lacunarity (LAC) were calculated. Receiver operating characteristic curves, showing the ability of PD, FD, and LAC to discriminate between the two MNV groups, were built. RESULTS: Twenty-two eyes with treatment-naïve quiescent MNVs and 20 eyes with MNVs previously treated nonexudative Type 1 MNVs were analyzed. Mean FD and LAC were statistically different between the two study groups (P < 0.05). Lacunarity showed the best discrimination ability, followed by FD and PD (area under curve = 0.83, 0.78, 0.62, respectively). CONCLUSION: Results suggest that FD and LAC may be useful optical coherence tomography angiography biomarkers to objectively discriminate inactive MNVs with different prognosis, such as treatment-naïve quiescent MNVs and previously treated nonexudative Type 1 MNVs, in age-related macular degeneration patients.

IMPLICATIONS OF THE MORPHOLOGIC PATTERNS OF TYPE 1 MACULAR NEOVASCULARIZATION ON MACULAR ATROPHY GROWTH ON PATIENTS UNDER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT.

PURPOSE: To evaluate the correspondence between macular atrophy (MA) progression and Type 1 macular neovascularization morphology during long-term anti-vascular endothelial growth factor treatment for exudative neovascular age-related macular degeneration. METHODS: Retrospective review of consecutive patients with complete retinal pigment epithelium and outer retina atrophy overlying or in the proximity of macular neovascularization. The assessment of MA was based on spectral domain optical coherence tomography, en-face near infra-red imaging and fundus autofluorescence. Macular neovascularization blood flow morphology was evaluated by swept-source optical coherence tomography-angiography. Qualitative features were categorized per ETDRS sector as: immature, mature; and hypermature pattern. An automatic analysis was designed in MATLAB coding language to compute MA per ETDRS. Measurements were compared between the baseline and the last follow-up visit. RESULTS: Twenty eyes from 20 patients were included; the mean age was 85.4 (8.3) years. The median follow-up was 1.85 (1.0-2.4) years and the median anti-vascular endothelial growth factor injection rate during follow-up was 4.0 (2.0-5.0) injections/year. During follow-up, sectors with persistence of an immature blood flow pattern had a lower MA growth rate than sectors with mature macular neovascularization flow patterns (P = 0.001). CONCLUSION: The presence of an immature blood flow pattern on optical coherence tomography-angiography is associated with a lower progression rate of MA.

PREDICTIVE ACTIVATION BIOMARKERS OF TREATMENT-NAIVE ASYMPTOMATIC CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the long-term evolution of treatment-naive quiescent choroidal neovascularization (CNV), in age-related macular degeneration (AMD), to identify predictive activation biomarkers. METHODS: Patients with quiescent CNV underwent a comprehensive ophthalmological examination, including fluorescein and indocyanine green angiographies, structural optical coherence tomography (OCT), and OCT angiography. Qualitative and quantitative analyses of structural OCT and OCT angiography images were performed during the study period. At the last follow-up evaluation, the enrolled eyes were divided into two groups: eyes with quiescent CNV converting to exudative AMD (eAMD) and those not progressing to eAMD. RESULTS: Sixty-eight eyes of 68 patients were enrolled in the study. Mean follow-up duration was 40 ± 28 months using multimodal imaging and 22 ± 13 months using OCT angiography. On structural OCT, quiescent CNV not converting to eAMD showed a preferential growth of the pigment epithelium detachment greatest linear diameter (P = 0.009), whereas the eAMD group presented a preferential growth of the pigment epithelium detachment maximal height (P < 0.0001) during the study period. Quantitative analysis of choriocapillaris OCT angiograms confirmed the CNV area growth during follow-up (from 4.18 ± 4.77 mm at baseline to 5.10 ± 5.06 mm at the last follow-up visit; P = 0.02). CONCLUSION: A close follow-up is recommended to early identify predictive activation biomarkers of treatment-naive quiescent CNV.

Impact of intravitreal aflibercept dosing regimens in treatment-naïve patients with neovascular age-related macular degeneration: 2-year results of RAINBOW.

BACKGROUND: To review treatment outcomes from real-world data of patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) injection. METHODS: RAINBOW (ClinicalTrials.gov, NCT02279537) is an ongoing, observational, 4-year study to monitor the effectiveness and safety of IVT-AFL in patients with nAMD in clinical practice in France. Treatment-naïve patients diagnosed with nAMD who had been prescribed IVT-AFL by their treating physician were eligible. The regimens of interest were regular treatment interval cohort (patients who received three initial monthly IVT-AFL injections followed by regular injections every 2 months) and two irregular treatment interval cohorts (with and without three initial monthly injections). Here we describe results at 24 months in patients according to IVT-AFL treatment regimen. RESULTS: The mean change in best-corrected visual acuity (BCVA) with IVT-AFL from baseline to 24 months was + 3.0 letters in the overall population (P < 0.05 vs baseline). The mean change was positive for the regular and irregular treatment interval cohorts with initial doses (+ 4.9 and + 4.0 letters, respectively; P < 0.05 vs baseline) and negative for the irregular treatment interval cohort without initial doses (- 2.5 letters; P = 0.365 vs baseline) at 24 months. The mean overall number of IVT-AFL injections over 12 and 24 months was 6.0 and 8.8, respectively. The most common ocular adverse events were lack of efficacy (6.3%), vitreous floaters (2.7%), and increased lacrimation (1.7%). CONCLUSIONS: In the real-world RAINBOW study, visual outcomes observed at 24 months were consistent with results from the primary endpoint at 12 months. In this study, treatment-naïve patients who received three initial IVT-AFL doses and regular IVT-AFL treatment over the first 24 months experienced better visual outcomes than patients who received no initial doses and an irregular treatment regimen. TRIAL REGISTRATION: www.ClinicalTrials.gov (NCT02279537). Registered 29 October 2014.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN RETINAL VEIN OCCLUSION: Correlations Between Macular Vascular Density, Visual Acuity, and Peripheral Nonperfusion Area on Fluorescein Angiography.

PURPOSE: To study correlations in patients with retinal vein occlusion between the automatically quantified macular vascular densities in the superficial and deep capillary plexus (DCP) obtained using optical coherence tomography angiography (OCTA) and the data from conventional examination, particularly visual acuity and peripheral retinal nonperfusion assessed using fluorescein angiography (FA). METHODS: Retrospective, observational study of patients with retinal vein occlusion who underwent a comprehensive ophthalmic examination including FA and OCTA using the AngioVue OCTA system version 2015.100.0.35 (OptovueRTVue XR 100; AVANTI, Inc, Fremont, CA). Vascular densities in the superficial capillary plexus and DCP, as well as the area of the foveal avascular zone, were measured using the AngioAnalytics software. RESULTS: Our study of 65 eyes of 61 patients (33 men, mean age: 67 years) showed a significant correlation between peripheral nonperfusion on FA and (1) automatically quantified global vascular density in both plexus (P = 0.021 for the DCP) and (2) foveal avascular zone area (P = 0.037). We also found significant correlations between capillary dropouts in both plexus and peripheral nonperfusion (P < 0.001 for both) and between visual acuity and vascular densities (P = 0.002 for the global density in the DCP). Global density less than 46% in the DCP was associated to the presence of peripheral nonperfusion area on FA (P = 0.003) and to enlargement of the superficial foveal avascular zone (P = 0.002). CONCLUSION: Our study demonstrated a significant correlation between automatically quantified macular vascular density on OCTA and peripheral nonperfusion on FA; OCTA could help identify high-risk retinal vein occlusion patients who may benefit from further evaluation using FA.

AFLIBERCEPT AFTER RANIBIZUMAB INTRAVITREAL INJECTIONS IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION: The ARI2 Study.

PURPOSE: To analyze the efficacy of aflibercept switch treatment for regression of pigment epithelial detachment (PED) in patients previously treated with ranibizumab. METHODS: Multicenter, prospective, nonrandomized clinical trial. One eye of patients presenting neovascular age-related macular degeneration with PED of more than 250 µm in height, with persistent fluid, was included. Patients had to have received at least six ranibizumab intravitreal injections during the 12 months before enrollment. Patients were switched from ranibizumab pro re nata to aflibercept (fixed regimen, 3 monthly intravitreal injections, and then Q6). Main outcome measure was change in PED height from baseline to Week 12 after switch. Secondary outcomes were best-corrected visual acuity and PED volume changes. RESULTS: Eighty four patients were included. Mean delay between last ranibizumab intravitreal injection and switch was 44.7 days. Mean maximal PED height at baseline visit was 347 µm (±109) and reduced to a mean of 266 µm (±114) at Week 12 (P < 0.001) and 288.2 µm at Week 32 (P < 0.001). Mean PED volume was reduced from 1.3 mm to 0.98 mm at Week 12 (P < 0.001). Best-corrected visual acuity improved by 3.3 Early Treatment Diabetic Retinopathy Study letters at Week 32 (P = 0.003). CONCLUSION: Aflibercept switch therapy seems to be effective on large PED in patients previously treated with pro re nata ranibizumab.

Optical Coherence Tomography Angiography in Healthy Subjects and Diabetic Patients.

Fluorescein angiography and indocyanine green angiography provide information about the normal retinal and choroidal vascular perfusion. They allow the evaluation of different diseases and increase the capability to define and diagnose several pathological conditions. Fluorescein angio graphy is the "gold standard" in imaging the retinal vascular bed and its changes, although not all the different layers of the capillary network can be visualized in a bidimensional examination. Optical coherence tomography angiography allows a depth-resolved visualization of the retinal and choroidal microvasculature, by calculating the difference (decorrelation) between static and nonstatic tissue. Given that the main moving elements in the eye fundus are contained in vessels, determining a vascular decorrelation signal permits a three-dimensional visualization of the retinal and choroidal vascular network without the administration of an intravenous dye. Moreover, a complete morphofunctional assessment may help in defining both the origin and the clinical activity of different vascular diseases such as diabetic retinopathy.

Aflibercept Treatment in Polypoidal Choroidal Vasculopathy: Results of a Prospective Study in a Caucasian Population.

INTRODUCTION: Polypoidal choroidal vasculopathy (PCV) is a choroidal pathology characterized by frequent occurrences of subretinal hemorrhages and resistance to monotherapies such as ranibizumab or bevacizumab intravitreal injections (IVT). The purpose of this study is to evaluate both the anatomical and functional efficacy of aflibercept IVT as a monotherapy in PCV in a Caucasian population. METHODS: We conducted a prospective multicenter study in either treatment-naïve patients with PCV or PVC patients who had not been treated with anti-VEGF within the previous 3 months or with photodynamic therapy (PDT) within the previous 6 months. All patients had been treated with 3 initial monthly loading doses of aflibercept followed by a Q8 regimen for 28 weeks in total. All patients underwent a complete ophthalmic examination including the measurement of best-corrected visual acuity (BCVA) before each IVT and after 28 weeks as well as an optical coherent tomography (OCT) of the macula. At baseline and 28 weeks, the polypoidal dilations were analyzed with indocyanine green angiography. RESULTS: Thirty-four eyes of 34 patients were included in this study. All patients were followed for 28 weeks and received 5 aflibercept IVT. The mean baseline BCVA was 55 letters. After 28 weeks, significant +13 letters in BCVA and a regression of exudative signs on OCT in all patients were observed. In 62% of the cases, polyp disappearance was observed on indocyanine green angiography. DISCUSSION: In this study on a Caucasian population, we showed that aflibercept as a monotherapy provided both a significant visual gain and the regression of polypoidal dilations. Aflibercept use in monotherapy may contribute to reduce the hemorrhagic risk and atrophy linked to PDT.

QUALITATIVE AND QUANTITATIVE FOLLOW-UP USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL VEIN OCCLUSION TREATED WITH ANTI-VEGF: Optical Coherence Tomography Angiography Follow-up of Retinal Vein Occlusion.

PURPOSE: To evaluate changes of vascular flow of patients treated with intravitreal injections of anti-vascular endothelial growth factor for macular edema secondary to retinal vein occlusion (RVO) with optical coherence tomography angiography (OCTA). METHODS: Patients with RVO with macular edema and treated with intravitreal injections of anti-vascular endothelial growth factors were retrospectively evaluated. The following examinations were performed before and after treatment: best-corrected visual acuity, spectral domain optical coherence tomography, fluorescein angiography, and OCTA (Optovue, Inc). Automatic measurement of vascular density of the superficial and deep capillary plexus was also performed and compared with age- and sex-matched healthy subjects. RESULTS: Twenty-eight eyes of 28 patients (mean age 66.2 years; males 19%) were evaluated, including 13 central RVO, 11 branch RVO, and 4 hemicentral RVO. After treatment, mean central macular thickness significantly decreased from 644 µm to 326 µm and best-corrected visual acuity increased from 20/125 to 20/63 (P < 0.01 for both results). On OCTA, perifoveal capillary disruption (P = 0.029) and the number of cysts in the superficial capillary plexus and deep capillary plexus (P < 0.002) significantly decreased after treatment. The mean vascular density in the superficial capillary plexus slightly decreased during follow-up from 46.44% to 45.01% (not significantly). These densities were significantly less than those observed in healthy controls (P < 0.001). CONCLUSION: Optical coherence tomography angiography showed regression of macular edema, reduced capillary disruption and cysts, and slight decrease in mean macular vascular density with time and despite treatment. Thus, OCTA enables qualitative and quantitative evaluation during follow-up of patients treated for RVO.

Retinal Microvasculature in Nonproliferative Diabetic Retinopathy: Automated Quantitative Optical Coherence Tomography Angiography Assessment.

PURPOSE: To perform a qualitative and quantitative assessment of the foveal microvasculature in eyes with diabetic maculopathy using optical coherence tomography angiography (OCT-A). METHODS: Retrospective case series of 48 eyes with diabetic maculopathy and 47 healthy eyes evaluated by Spectralis OCT-A. Perifoveal arcade disruptions, linear vascular dilations, microaneurysms, intraretinal microvascular abnormalities and flow-void areas were qualitatively analyzed on OCT angiograms both for the superficial (SCP) and deep (DCP) capillary plexuses. A fully automated microstructural analysis of the foveal avascular zone (FAZ) metrics, vascular and avascular surfaces was performed. Quantitative values from diabetic patients were compared with those of healthy subjects. RESULTS: A moderate agreement between SCP and DCP in terms of diabetes-induced vascular lesions in the qualitative assessment was shown. The comparative quantitative analysis between SCP and DCP in diabetic patients revealed a statistically significant difference (p < 0.05) in terms of FAZ perimeter and FAZ surface. No statistically significant difference was shown in total vascular and avascular surfaces. A statistically significant difference between the diabetic and control groups was noticed both for SCP and DCP considering FAZ metrics and vascular surfaces. CONCLUSIONS: A qualitative and quantitative OCT-A approach on retinal vascular perfusion may offer an objective and reliable method for monitoring disease progression in diabetic retinopathy.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VERSUS TRADITIONAL MULTIMODAL IMAGING IN ASSESSING THE ACTIVITY OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION: A New Diagnostic Challenge.

PURPOSE: To compare optical coherence tomography angiography (OCTA) with traditional multimodal imaging in patients with exudative age-related macular degeneration in terms of guiding the treatment decision. METHODS: Prospective case series of 80 eyes of 73 consecutive patients with exudative age-related macular degeneration (39 women, mean age: 79.4 ± 5.3 years) diagnosed with different types of choroidal neovascularization (CNV) (58 Type I, 2 Type II, 6 mixed Type I and II, 3 retinal angiomatous proliferation, and 11 age-related macular degeneration-related polyps). The data obtained from traditional multimodal imaging, based on fluorescein angiography, indocyanine green angiography, and OCT were used to assess the need for treatment, those obtained from OCTA to identify two different patterns of CNV. Traditional multimodal imaging and OCTA findings were then compared with evaluate possible correspondence between treatment decision and CNV aspect on OCTA. RESULTS: A CNV lesion was identified as Group A (requiring treatment) in 58 eyes (72.5%) in traditional multimodal imaging. On OCTA in 59 eyes (73.7%), the lesion was defined as Pattern I and the remaining 21 (26.3%) as Pattern II. There was 94.9% correspondence between the Pattern I CNV on OCTA and the cases Group A on conventional multimodal imaging. It was also computed 90.5% correspondence between Pattern II CNV on OCTA and the Group B (not requiring treatment) cases on conventional multimodal imaging. There was high (P < 0.05) interobserver agreement both for treatment decision in conventional multimodal and for Patterns (I or II) defining on OCTA imaging analysis. CONCLUSION: This study demonstrates a high level of correspondence, in patients with exudative age-related macular degeneration, between different CNV patterns identified on OCTA and treatment decisions established on conventional multimodal imaging. Although fluorescein angiography remains the gold standard for determining the presence of leakage, and OCT shows fluid accumulation and its variations, OCTA may now offer noninvasive monitoring of the CNV, aiding for each treatment decision during the follow-up.

Optical coherence tomography angiography during follow-up: qualitative and quantitative analysis of mixed type I and II choroidal neovascularization after vascular endothelial growth factor trap therapy.

PURPOSE: To report the optical coherence tomography angiography (OCT-A) findings in an exudative age-related macular degeneration (AMD) patient presenting mixed type I and II choroidal neovascularization (CNV) during follow-up after intravitreal vascular endothelial growth factor (VEGF) trap treatment. METHODS: The clinical assessment included both traditional multimodal imaging, based on fluorescein angiography (FA), indocyanine green angiography (ICGA) and B-scan OCT, and OCT-A at baseline and follow-up. OCT-A images were obtained using a Spectralis OCT-A prototype able to acquire 70,000 A-scans per second, with a resolution of 7 µm axially and 14 µm laterally. An amplitude decorrelation algorithm developed by Heidelberg Engineering was applied to a volume scan, on a 15 × 5° area, which was composed of 131 B-scans (35 frames per scan) at a distance of 11 µm each. The borders of type I and type II CNV were manually outlined and then the areas were analyzed using the provided automated software before and after treatment. RESULTS: The qualitative approach revealed a substantial decrease in the visibility of tiny branching vessels and anastomoses both in type I and type II components of the neovascular complex, associated with persistence of a clear hyperintense signal coming from the larger trunks, which remained well-perfused. Quantitative analysis confirmed a reduction of the lesion area after VEGF trap treatment: the type II component decreased from 0.25 to 0.19 mm(2), while the type I component decreased from 2.03 to 1.80 mm(2). CONCLUSIONS: Our study qualitatively and quantitatively demonstrated the response of a mixed type I-II CNV to intravitreal VEGF trap therapy. Although FA remains the gold standard for determining the presence of leakage and OCT easily shows fluid accumulation and its variations, OCT-A offers noninvasive monitoring of the retinal and choriocapillaris microvasculature in patients with CNV, aiding in diagnosis and treatment decisions during follow-up.

En face enhanced depth imaging optical coherence tomography features in adult onset foveomacular vitelliform dystrophy.

BACKGROUND: Our purpose was to describe the different morphological features in adult onset foveomacular vitelliform dystrophy (AOFVD), using en face enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). METHODS: Thirty eyes of 22 consecutive patients presenting with diagnosis of AOFVD were enrolled. Diagnosis of AOFVD was concluded based on fundus examination, autofluorescence imaging, fluorescein angiography and SD-OCT. En face OCT imaging was obtained with the Spectralis EDI SD-OCT; 97 inverted sections (nine averaged B-scans per image) were acquired. RESULTS: On en face OCT, vitelliform lesions appeared as regular concentric rings of different reflectivity. From the periphery to center of the ring, we observed: (1) the hypereflective ring representing the inner segment/ outer segment (IS/OS) junction, which was continuous in 23 out of 30 eyes, and (2) a well-detectable hyporeflective ring between the IS/OS junction and vitelliform material in 20 out of 30 eyes; the innermost composant of the lesion was hypereflective, and it corresponded to vitelliform material. In eight out of 30 eyes, a hyporeflective "croissant"-shaped lesion with inferior concavity in the upper part of the hyperreflective material was present. Hypereflective retinal pigment epithelium (RPE) elevations or bumps were detected in 25 out of 30 eyes. These areas of focal RPE thickening or bumps appeared to be intensely hypereflective on infrared reflectance imaging. CONCLUSION: En face imaging of the retina helps visualizing the distribution of vitelliform material in AOFVD. The sedimentation of vitelliform lesions is characterized by a upper "croissant"-shaped hypoflectivity. The bumps/thickening of RPE appeared as hypereflective lesions on IR imaging.

Hyperreflective dots: a new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration.

PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) enables high-resolution analysis of retinal layers and previously unseen hyperreflective dots (HRD). HRD morphological characteristics, evolution, possible origin and prognostic value are discussed. METHODS: We conducted a prospective study of 100 patients with exudative age-related macular degeneration (AMD), who were treated and followed up with monthly imaging examinations. Statistical correlations between visual acuity (VA) and pre-/post- treatment HRD characteristics were evaluated. RESULTS: HRD were present in all cases, mainly in the outer retinal layers but also elsewhere. After treatment, HRD regressed in a few days, 1 month (p < 0.04) and 3 months (p < 0.01). Regression was evident in all VA and morphological subsets. Resolution was associated with better final VA (p < 0.001). CONCLUSIONS: Presence of initial/recurrent HRD, rapid treatment response and the growing role that early biological inflammatory reaction plays in AMD suggests HRD are activated microglia cells. The correlation between VA and HRD could make HRD a clinical marker for early decisions about treatment and retreatment.

Predictive Factors of Visual Outcome in Treatment-Naïve Diabetic Macular Edema: Preliminary Results from the Clinical Study "FOVEA".

Diabetic macular edema (DME) is a common cause of vision impairment in diabetic retinopathy. The aim of this study was to analyze the relationship between visual outcome and anatomic changes detected by traditional multimodal retinal imaging and optical coherence tomography angiography (OCTA) in DME eyes under treatment with Aflibercept. METHODS: Sixty-six DME eyes of 62 patients under treatment with intravitreal Aflibercept and with one-year follow-up were enrolled. All participants underwent a full ophthalmic evaluation, including best correct visual acuity (BCVA) measurement, spectral-domain optical coherence tomography, fluorescein angiography and OCTA, both at baseline and final examination. Fractal OCTA analysis of the superficial and deep capillary plexus (SCP and DCP) was performed to estimate vascular perfusion density and lacunarity (LAC). RESULTS: At the final examination, there was a significant improvement in terms of BCVA and central macular thickness (CMT). Furthermore, eyes with CMT <373 µm at baseline reached the higher BCVA at the last follow-up. Eyes with CMT ≥373 µm and DCP LAC <0.41 reached a higher final BCVA, if compared with eyes showing the same CMT but higher initial LAC. CONCLUSION: A 12-month treatment with intravitreal Aflibercept for DME resulted in significant visual and anatomic improvement. Multimodal retinal imaging, together with fractal OCTA analysis, may provide useful biomarkers, predictive of visual outcome in DME.