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.

Quantitative Optical Coherence Tomography Angiography Biomarkers in a Treat-and-Extend Dosing Regimen in Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the association between quantitative optical coherence tomography angiography (OCT-A) parameters and clinical outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with a treat-and-extend dosing regimen on a 12-month follow-up interval. Methods: Observational, prospective study of consecutive patients. The treatment protocol was based on a loading dose of three anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVI) followed by a treat-and-extend regimen. Eyes were evaluated by swept-source OCT-A at baseline, 1 month after the loading dose and at 12 months. A quantitative analysis was issued for fractal dimension (FD), lacunarity index (LAC), blood flow surface area (SA), and vessel density (VD). An association of these parameters with the anatomic response and functional responses, and IVI number at 12 months of follow-up was assessed. A level of significance α = 0.05 was considered. Results: Sixty-four patients were included, 52 of whom (81%) completed the 12-month study protocol. The median number of injections at 12 months was 7 (P25-P75: 6-12). FD and SA were reduced 1 month after the loading dose of anti-VEGF (P < 0.001). The generalized linear models using baseline FD and baseline SA achieved the best performance in discriminating a lower treatment burden (area under the curve [AUC] = 0.78; 95% confidence interval [CI]: 0.64-0.91 and AUC = 0.76; 95% CI: 0.63-0.90, respectively). Conclusions: Baseline OCT-A may provide useful biomarkers for the treatment burden in nAMD. Translational Relevance: The application of fractal dimension and automatic blood flow area algorithms to OCT-A data can distinguish patients with distinct treatment burdens in the first year of nAMD.

Optical coherence tomography angiography in exudative age-related macular degeneration: a predictive model for treatment decisions.

AIMS: To evaluate on optical coherence tomography angiography (OCT-A), the predictive role of different qualitative findings of choroidal neovascularisations (CNV) in assessing the status of exudative age-related macular degeneration (eAMD) and to develop a potential model to predict the CNV activity. METHODS: Retrospective review of the multimodal imaging records of patients with eAMD obtained during treatment for type 1 or type 2 CNV. The qualitative analysis of CNVs on OCT angiograms assessed the presence or absence of tiny branching vessels, loops, peripheral anastomotic arcades and choriocapillaris hypointense halo. These findings were then correlated with those of structural OCT scans. A score forecast was built and validated. RESULTS: One hundred and twenty-six eAMD eyes were enrolled in the study. Exudation was observed in 90 eyes (71%) on structural OCT. The qualitative OCT-A analysis revealed: tiny branching vessels in 82.5% of the cases, vascular loops in 81.7%, peripheral anastomotic arcades in 66.7% and choriocapillaris hypointense halo in 54.8%. In the univariate analysis, each OCT-A parameter showed a statistically significant correlation with exudation on structural OCT (p<0.001). The overall analysis demonstrated a sensitivity of 96.7% and a positive predictive value of 87.9%. In the multivariate analysis, a model with four criteria predicted an exudative lesion in 97.6% of cases and one with two criteria (tiny branching vessels and peripheral anastomotic arcades) in 71.2%. CONCLUSIONS: The presence of tiny branching vessels and a peripheral anastomotic arcade appears to predict the lesion activity with a good accuracy and the model based on four criteria enables optimal decisions regarding retreatment in eAMD.

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.

EXPANDED CLINICAL SPECTRUM OF MULTIPLE EVANESCENT WHITE DOT SYNDROME WITH MULTIMODAL IMAGING.

PURPOSE: To evaluate and characterize multiple evanescent white dot syndrome abnormalities with modern multimodal imaging modalities. METHODS: This retrospective cohort study evaluated fundus photography, fluorescein angiography, indocyanine green angiography, optical coherence tomography, enhanced depth imaging optical coherence tomography, short-wavelength autofluorescence, and near-infrared autofluorescence. RESULTS: Thirty-four multiple evanescent white dot syndrome patients with mean age of 28.7 years were studied (range, 14-49 years). Twenty-six patients were women, and eight were men. Initial mean visual acuity was 0.41 logMAR. Final mean visual acuity was 0.03 logMAR. Fluorescein angiography shows a variable number of mid retinal early fluorescent dots distributed in a wreathlike pattern, which correlate to fundus photography, fundus autofluorescence, and indocyanine green angiography. Indocyanine green angiography imaging shows the dots and also hypofluorescent, deeper, and larger spots, which are occasionally confluent, demonstrating a large plaque of deep retinal hypofluorescence. Optical coherence tomography imaging shows multifocal debris centered at and around the ellipsoid layer, corresponding to the location of spots seen with photography, indocyanine green angiography, and fluorescein angiography. Protrusions of the hyperreflectant material from the ellipsoid layer toward the outer nuclear layer correspond to the location of dots seen with photography, indocyanine green angiography, and fluorescein angiography. CONCLUSION: Multimodal imaging analysis of the retina in patients with multiple evanescent white dot syndrome shows additional features that may help in the diagnosis of the disease and in further understanding its etiology. Multiple evanescent white dot syndrome is predominantly a disease of the outer retina, centered at the ellipsoid zone, but also involving the interdigitation zone and the outer nuclear layer.

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.

Restoration of Outer Retinal Layers After Aflibercept Therapy in Exudative AMD: Prognostic Value.

PURPOSE: To evaluate the outer retinal layer (ellipsoid zone [EZ] and external limiting membrane [ELM]) changes following intravitreal aflibercept injections in eyes with treatment-naïve exudative age-related macular degeneration (eAMD) and to correlate these changes with fluid response and visual improvement. METHODS: A retrospective case series of 50 treatment-naïve eAMD eyes followed-up for 18 months. All patients underwent regular comprehensive ophthalmic examinations. The presence of EZ disruption, ELM disruption, EZ swelling, subretinal hyper-reflective exudation (SHE), central macular thickness (CMT), cystoid spaces, subretinal fluid, and pigmented epithelium detachment were evaluated by two different retinal specialists at baseline and final visits, and correlated with best corrected visual acuity (BCVA) improvement. RESULTS: At 18 months, BCVA, EZ disruption, ELM disruption, EZ swelling and SHE improved significantly (P = 0.001) at 18 months. Improvement of BCVA showed a statistically significant correlation with ELM restoration (P = 0.018), but not with EZ restoration (P = 0.581). Swelling of the EZ decreased from 72% of the cases at baseline to 30% in 18 months while SHE decreased from 52% to 6% in 18 months (P = 0.001). We observed a statistically significant (P = 0.001) reduction between the baseline and final value of CMT. CONCLUSIONS: Aflibercept is safe and effective in treating exudative AMD with the restoration of the outer retinal layers. Restoration of the EZ is not statistically correlated with the final BCVA, even though persistent EZ changes could be associated with irreversible decrease in vision. On the contrary, the final status of the ELM is directly correlated with final BCVA. Also, baseline changes in outer retinal layers, especially the ELM, appear to predict photoreceptor restoration and final BCVA, and must be comprehensively analyzed to enable and determine a future prognosis.

Comparison of macular choroidal thickness in adult onset foveomacular vitelliform dystrophy and age-related macular degeneration.

PURPOSE: To compare macular choroidal thickness (MCT) in eyes with adult onset foveomacular vitelliform dystrophy (AOFVD) and eyes with AMD. METHODS: Five groups of 38 eyes each were included in a prospective, observational, comparative study: AOFVD eyes with fluid accumulation; AOFVD fellow eyes without fluid (early stage); advanced exudative (wet) AMD; advanced dry AMD; and healthy normal eyes. All study eyes underwent a comprehensive ophthalmologic examination. Macular choroidal thickness was measured using enhanced depth imaging optical coherence tomography (EDI-OCT). RESULTS: Subfoveal choroidal thickness (SFCT) in AOFVD with subretinal fluid (325.66 ± 85.98 µm) was significantly (P < 0.001) thicker compared with that in exudative AMD (158.55 ± 57.87 µm) and in dry AMD (157.53 ± 67.08 µm). Also, in AOFVD, the choroid was significantly (P = 0.001) thicker than that in the normal group (255.87 ± 87.46 µm). However, in AOFVD, there was no significant difference (P = 0.69) between the SFCT in the study eye and in the fellow eye (317.66 ± 90.04 µm). The choroidal thickness at each of the other 12 measured points showed similar results. CONCLUSIONS: This study demonstrates choroidal thickening in AOFVD in contrast with the choroidal thinning observed in advanced AMD. These findings suggest that the pathogenic mechanisms in AOFVD are different from those in exudative AMD. Choroidal thickness measurement could help differentiate the challenging diagnosis between exudative AMD and the advanced stage of AOFVD (with fluid accumulation but without choroidal neovascularization).

Intravitreal bevacizumab as first local treatment for uveitis-related choroidal neovascularization: long-term results.

PURPOSE: To report long-term results of intravitreal (IVT) bevacizumab as first local treatment for choroidal neovascularization (CNV) secondary to uveitis. METHODS: Files of patients receiving 1.25 mg/0.05 ml bevacizumab as primary local treatment for CNV were retrospectively reviewed. Main outcomes were change in best-corrected visual acuity (BCVA) and central foveolar thickness (CFT), treatment-related adverse events, and number and frequency of injections. RESULTS: Fifteen eyes from fifteen patients were included. Multifocal choroiditis and panuveitis were the diagnosis in seven, ampiginous choroiditis in two, and for six remaining, serpiginous choroiditis, sympathetic ophthalmia, Vogt-Koyanagi-Harada syndrome, punctuate inner choroidopathy, tuberculosis and idiopathic inflammation. In 13 eyes, neovascularization was subfoveal, and peripapillary in two. Intraocular inflammation was strictly controlled in all cases by the time of injections. BCVA improved from logMar 0.53 to logMar 0.29 in 12 eyes (80%), while CFT decreased from 239.06 to 195.2 µm in 13 (87%). Twelve eyes received more than one injection; mean number in this group was 4.25 (2-8), and frequency 1 every 12.97 weeks. There were no adverse events related to bevacizumab or the procedure. Median follow-up was 17.6 months (8-25). CONCLUSIONS: First-intention IVT bevacizumab for inflammatory CNV showed transient improvement in BCVA and CFT, in eyes under controlled inflammation. Reinjection was needed in most cases. Further work should conclude about safety related to repeated injections.