Toward a Specific Classification of Polypoidal Choroidal Vasculopathy: Idiopathic Disease or Subtype of Age-Related Macular Degeneration

PURPOSE To suggest a clinical distinction between idiopathic polypoidal choroidal vasculopathy (PCV) and secondary polyps associated with neovascular age-related macular degeneration (NV-AMD). METHODS The study was a retrospective case series of 52 eyes of 52 consecutive patients (31 females and 21 males) diagnosed with PCV. Initial diagnosis was based on scanning laser ophthalmoscope-indocyanine green angiography (SLO-ICGA) in association with fluorescein angiography (FA) and optical coherence tomography (OCT). All the data and images were analyzed in a masked fashion by four experienced examiners in two different sessions: the first, to classify patients into the two hypothesized groups (idiopathic polyps or NV-AMD-related polyps); the second, following a predetermined scheme, to describe objective features. The results obtained in each session underwent a cross multivariate analysis to identify statistically significant differences (P ≤ 0.05) between the two groups. RESULTS The two groups were clinically different on the basis of FA (leakage origin [P = 0.001] and presence of drusen [P = 0.001]), ICGA (evidence of choroidal neovascularization [CNV; P = 0.001] and/or branching vascular network [BVN; P = 0.001]), OCT imaging (type of pigmented epithelium detachment [P = 0.001], presence of BVN [P = 0.001], and subfoveal choroidal thickness [P = 0.001]). Further significant differences were observed according to the location of lesion (uni- or multifocal) (P = 0.001), type of CNV (P = 0.001), and best-corrected visual acuity (P = 0.001). CONCLUSIONS Our study demonstrated clinical and statistically significant differences between idiopathic PCV and NV-AMD-related polyps that could be considered as distinct entities. Although they share some similarities, mainly the sub-RPE location, the ability to identify a specific clinical pattern suggests a more specific therapeutic approach for these two entities

Two-Year Outcome of Aflibercept in Patients with Pigment Epithelial Detachment due to Neovascular Age-Related Macular Degeneration (nAMD) Refractory to Ranibizumab

Purpose. To evaluate the response of intravitreal aflibercept injection (IAI) in eyes with detachment of retinal pigment epithelium (DEP) secondary to nAMD refractory to monthly ranibizumab. Patients and Methods. This is a retrospective, multicenter study. All patients received 3 IAI then treated as needed every 4 weeks for 12 months. During the second year, the eyes were treated with a treat- and-extend regimen. Results. Forty-four eyes were included. Best-corrected visual acuity improved significantly after the loading phase (3.1 ± 6.4 letters) and at 6 months (2.8 ± 6.4 letters), but change was not significant at 1 year and 2 years. The height of the DEP was significantly decreased at 3 months and 6 months, but the difference did not reach statistical difference at 1 and 2 years. Rate of eyes with complete resolution of exudation was 59% after the loading phase and 34.3% at 2 years. Mean interval of anti-VEGF injection was extended from 31 ± 2.6 days to 61 ± 5 days after conversion. Conclusions. Aflibercept intravitreal injection in patients with fibrovascular DEP due to nAMD who respond poorly to monthly ranibizumab led to short-term functional and anatomical improvement. Reduction of intravitreal injection frequency was obtained until 2 years of follow-up

Volume Rendering of Dense B-Scan Optical Coherence Tomography Angiography to Evaluate the Connectivity of Macular Blood Flow

Purpose: To characterize macular blood flow connectivity using volume rendering of dense B-scan (DB) optical coherence tomography angiography (OCTA) data. Methods: This was a prospective, cross-sectional, observational study. DB OCTA perifoveal scans were performed on healthy subjects using the Spectralis HRA+OCT2. A volumetric projection artifact removal algorithm and customized filters were applied to raw OCTA voxel data. Volume rendering was performed using a workflow on Imaris 9.5 software. Vascular graphs were obtained from angiographic data using the algorithm threshold-loops. Superficial arteries and veins were identified from color fundus photographs and connections between adjacent arteries and veins displayed using the shortest path algorithm. Connective pathway locations were analyzed with cross-sectional OCT and OCTA to determine their course through the superficial vascular complex (SVC) and the deep vascular complex (DVC). Results: Fourteen eyes from seven subjects (mean age: 28 ± 5 years; 3 women) were included in this analysis. One hundred and twenty-six vascular connections were analyzed. In all cases, the shortest path connections between superficial arteries and veins coursed through the DVC. We did not identify shortest path connections confined to the SVC. Conclusions: Volumetric analysis of vascular connectivity supports a predominantly in-series arrangement of blood flow between the SVC and DVC within the human perifoveal macula.publishersversionpublishe

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.publishersversionpublishe

Optical coherence tomography angiography in macular edema

OCT angiography is a promising new method to visualize the retinal vasculature and choroidal vascular layers in the macular area and provides depth resolved functional information of the blood flow in the vessels. Given that the main moving elements in the eye fundus are contained in vessels, determining a vascular decorrelation signal enables visualization of 3-dimensional retinal and choroidal vascular network without the administration of intravenous dye and thus reducing the risk of potential adverse events

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

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

OCT Angiography Fractal Analysis of Choroidal Neovessels Secondary to Central Serous Chorioretinopathy, in a Caucasian Cohort

Central serous chorioretinopathy (CSCR) can be complicated by different types of choroidal neovascularization (CNV). The purpose of this study was to investigate the incidence and quantitative optical coherence tomography angiography (OCT-A) features of CSCR-related CNVs. Methods: This was a retrospective multicenter study including 102 eyes of 102 Caucasian patients with acute or complex CSCR. All patients underwent a comprehensive ophthalmological examination. Quantitative OCT-A parameters, including vascular perfusion density (VPD), fractal dimension (FD), and lacunarity (LAC), were measured in CNV eyes. Results: Forty eyes (39.2%) had acute CSCR, whereas the remaining sixty-two (60.8%) had complex CSCR. CNV was observed in 37 (36.27%) eyes, all of which had the complex form. CNVs were classified as type 1 CNV in 11/37 (29.73%) cases and as polypoidal choroidal vasculopathy (PCV) in the remaining 26/37 (70.27%). Overall, the mean VPD, FD, and LAC of CSCR-related CNVs were 0.52 &plusmn; 0.20%, 1.44 &plusmn; 0.12, and 2.40 &plusmn; 1.1, respectively. No significant difference between type 1 CNV and PCV was found. Conclusion: Complex CSCR is often complicated by type 1 CNV and PCV with similar neovascular architecture and branching complexity, a finding supporting the idea that they might be different stages of the same neovascular process. Future OCT-A fractal analysis-based studies that also include other relevant parameters, such as demographics, presentation, morphology on multimodal imaging, and response to treatment, are necessary before drawing any definitive conclusions

Retinal Granuloma Associated with Primary HHV6 Infection in an Immunocompetent Patient: A Case Report and Review of the Literature

Purpose: To report a case of unilateral retinal granuloma in a girl with concomitant primary HHV6 infection. Case report: An otherwise healthy 15-year-old girl complained of progressive visual loss in her right eye (1.0 LogMar). The ocular features and medical history were consistent with the possibility of a viral infection. This diagnostic hypothesis was confirmed by the result of multiplex polymerase chain reaction analysis performed on a serum sample, which revealed the presence of HHV6 DNA. Serological HHV6 tests for the detection of IgG and IgM against HHV6 showed elevated IgM levels, a result suggestive of primary HHV6 infection. Accordingly, at first, intravenous ganciclovir and, then, oral valganciclovir were given. After 8 weeks, the retinal granuloma healed and visual acuity progressively reached 0.0 LogMar. Conclusions: HHV6 primary infection may be associated with unilateral retinal granuloma in otherwise healthy patients. Antiviral drugs may be helpful in the treatment of this condition