Typical Neovascular Age-related Macular Degeneration Research Articles

Importance of optical coherence tomography raster scans in early detection of active fellow-eye neovascularization in unilateral neovascular age-related macular degeneration

PurposeTo investigate the incidence of and risk factors for failure of detection of active fellow-eye neovascularization on optical coherence tomography(OCT) crosshair scans in patients with unilateral neovascular age-related macular degeneration(AMD).MethodsIn this retrospective study, patients who experienced the development of active neovascularization in the fellow eye during the follow-up period were included(n = 75). Cases in which the neovascularization in the fellow eye could be identified solely through crosshair scans were defined as the crosshair scan detection group(n = 63). Cases in which the aforementioned findings could not be identified through crosshair scans but could be identified through raster scans were defined as the raster scan detection group(n = 12). The factors were compared between the two groups. Risk factors related to undetected neovascularization on crosshair scans were additionally identified.ResultsActive fellow-eye neovascularization, was not detected on OCT crosshair scans in 12 cases(16.0%) but was identified on raster scans in all cases. There was a significant difference in the proportion of neovascularization types between the crosshair scan detection group and the raster scan detection group(P = 0.023). Among the 35 fellow-eye neovascularization cases in patients with type 3 macular neovascularization(MNV), 10(28.6%) were not detected on crosshair scans. Multivariate analysis revealed a significantly higher risk for undetectable fellow-eye neovascularization on crosshair scans in patients with type 3 MNV than in those with typical neovascular AMD(P = 0.037,β = 9.600).ConclusionsOur findings suggest the need for routine OCT raster scans during fellow-eye examinations in patients with unilateral neovascular AMD, particularly when the first-affected eye is diagnosed with type 3 MNV.

Long-term efficacy and safety of brolucizumab in neovascular age-related macular degeneration: A multicentre retrospective real-world study.

To investigate the long-term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age-related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow-up duration of ≥12 months. Changes in best-corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow-up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow-up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes)and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management.

Influence of submacular hemorrhage at baseline on the long-term outcomes of aflibercept treatment for typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

To investigate the influence of submacular hemorrhage (SMH) at baseline on long-term visual outcomes of patients with typical age-related macular degeneration (tAMD) and polypoidal choroidal vasculopathy (PCV) treated with intravitreal aflibercept (IVA). In this retrospective study, eyes of treatment-naïve patients with tAMD and PCV who initiated IVA under a treat-and-extend regimen and were followed up for ≥ 5years were classified into the tAMD-SMH ( +), tAMD-SMH (-), PCV-SMH ( +), and PCV-SMH (-) groups based on the presence of SMH at baseline. Best-corrected visual acuity (BCVA) changes and macular fibrosis and atrophy incidences were assessed. This study included 127 eyes (127 patients), including 51 with tAMD and 76 with PCV; 18 eyes had SMH at baseline. In the tAMD-SMH ( +) group (n = 6), the mean logMAR BCVA significantly deterioratedfrom 0.59 ± 0.45 at baseline to 0.88 ± 0.47 at the final visit (P = 0.024). No significant BCVA changes were observed in the tAMD-SMH (-) (n = 45), PCV-SMH ( +) (n = 12), or PCV-SMH (-) (n = 64) groups (all P > 0.05). The tAMD-SMH ( +) group showed a significantly higher incidence of macular fibrosis at the final visit than did the tAMD-SMH (-) group (P = 0.042). There was no influence of baseline SMH on the macular fibrosis incidence in eyes with PCV and the macular atrophy incidence in eyes with tAMD and PCV. The presence of SMH at baseline resulted in poorer long-term visual acuity in eyes with tAMD, even with aflibercept treatment. However, no such influence was observed in eyes with PCV.

Choroidal thickness after anti‐vascular endothelial growth factor in treatment‐naïve typical neovascular age‐related macular degeneration patients: A systematic review and meta‐analysis

Aims/Purpose: To evaluate the effect of anti‐vascular endothelial growth factor (anti‐VEGF) on choroidal thickness (CT) in treatment‐naïve typical neovascular age‐related macular degeneration (AMD) patients during the loading phase.Methods: A systematic literature search was conducted in CENTRAL, MEDLINE, EMBASE, Scopus, Web of Science, Clinical Trials, ICTRP and ISRCTN from inception to October 19, 2022. The protocol was registered with PROSPERO (CRD42022371192). We included both retrospective and prospective randomized controlled trials, cohort studies, case control and case series of typical neovascular AMD patients. Studies with polypoidal choroidal vasculopathy or unclear diagnoses and reports in other languages than English were excluded. Risk of bias was assessed using critical appraisal tools provided by Joanna Briggs Institute.Results: 43 studies were included in the review. Meta‐analysis of all studies reporting sufficient data and simultaneously disregarding measurement technique, macular neovascularization (MNV) type and anti‐VEGF type, yielded a significant decrease of CT with anti‐VEGF treatment. To decrease bias, sub‐analyses for Type 1 and 2 MNV sorted by anti‐VEGF type found a significant effect for both aflibercept and ranibizumab, and the effect appears greater in the aflibercept group. For Type 3 MNV, the baseline CT was generally thinner and the decrease more modest.Conclusions: Anti‐VEGF drugs decrease CT in typical neovascular AMD. There is a greater effect of aflibercept compared to ranibizumab. For bevacizumab and brolucizumab there are few studies, but available data show a tendency of greater effect in the latter. There are low numbers of randomized trials on the topic and publication bias might affect the results. More studies randomized to treatment of patients with a thin baseline choroid should be conducted.

Polypoidal Choroidal Vasculopathy: Evaluation Based on 3-Dimensional Reconstruction of OCT Angiography

Three-dimensional (3D) reconstruction using swept-source OCT angiography (SS-OCTA) can provide insights into the nature and structure of polypoidal choroidal vasculopathy (PCV) and its component parts, the polypoidal lesion (PL) and the branching neovascular network (BNN). This study aims to describe novel observations of PCV using 3D reconstruction of SS-OCTA, and to compare these observations with similar images of type I macular neovascularization (MNV) typical neovascular age-related macular degeneration (nAMD). Clinical case series. Patients with PCV in either eye from clinical studies conducted in a tertiary retina center. Images with prespecified SS-OCTA imaging protocol were obtained and reconstructed in 3D. Forty neovascularization lesions (30 PCV and 10 typical nAMD) based on SS-OCTA were analyzed. The following 3 specific features were evaluated: (1) the pattern of flow signal within the PLs as either homogenous or showing internal vascular architecture; (2) the configuration of the BNN as hypermature, mature, or immature; and (3) the spatial arrangement of the PLs in relation to the BNN. Comparisons were made between PCV and typical nAMD. All PLs exhibited internal vascular architecture in the form of coil-like loops and none exhibited homogenous flow. Small focal nodules were present within this internal vascular architecture in 70% of PLs. Branching neovascular networks exhibited a hypermature/mature configuration (100 vs. 50%, P < 0.01) and were associated with thicker choroid compared with typical nAMD type 1 MNV (238.7 ± 104.3 vs. 155.6 ± 49.2, P= 0.02). The BNN and PL were located at distinct anteroposterior planes in 81% of the eyes. We identified proliferating vasculature in both the PL and the BNN. Comparison of the configuration suggests that the BNN represents a more chronic and inactive lesion than the PL. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Discontinuation of treatment and retreatment of neovascular age-related macular degeneration in the real-world: Bundang AMD cohort study report 5.

This single-center retrospective cohort study investigated the incidence rate and risk factors for the discontinuation of anti-vascular endothelial growth factor (VEGF) injections and retreatment in typical neovascular age-related macular degeneration (tnAMD) and polypoidal choroidal vasculopathy (PCV) in the real-world setting. A total of 488 eyes with either tnAMD (n = 334) or PCV (n = 154) followed up for ≥3 years were analyzed. The discontinuation of treatment was defined as the cessation of anti-VEGF injections for 1 year or longer. Eyes with discontinuing treatment were subdivided into group A: eyes with stable responses (complete or incomplete resolution) and group B: those with no expectation of visual gain or poor response. The proportion and median time of discontinuation of treatment or retreatment were analyzed. The visual prognosis and the associated risk factors for the discontinuation of treatment or retreatment were also investigated. The mean follow-up period was 8.1 ± 3.4 years. Of 488 eyes, discontinuation of the treatment occurred in 322 eyes (66.0%), and the median time to discontinuation was 1.5 years after the initial injection. Of 297 eyes with discontinuation of treatment excluding 25 eyes with vitrectomy or photodynamic therapy after the discontinuation of the injection, 277 eyes belonged to group A and the remaining 20 eyes belonged to group B. Of the 277 eyes discontinuing treatment with a stable response, 185 eyes (66.8%) were given retreatment. The median time to retreatment was 3.3 years after the discontinuation of the injections. PCV and the lower annual number of injections were the significant factors associated with discontinuation. Younger age, male gender, and PCV were the significant factors for the retreatment. Our long-term real-world study showed that two-thirds of eyes with neovascular age-related macular degeneration (nAMD) had the discontinuation of the anti-VEGF injections and two-thirds of eyes discontinuing treatment with stable responses experienced retreatment. Long-term follow-up and regular monitoring are needed to detect the recurrence.

CHOROIDAL VASCULAR ALTERATIONS IN AGE-RELATED MACULAR DEGENERATION AND POLYPOIDAL CHOROIDAL VASCULOPATHY.

To evaluate morphologic alterations in choroidal veins in eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). A retrospective review of baseline indocyanine green angiography in eyes with typical nAMD and PCV. We evaluated Haller layer veins in the early-phase indocyanine green angiography (before 2 minutes) for 1) macular anastomosis, 2) dilated Haller veins, and 3) focal variation in vessel caliber by at least 50% from the narrowest to largest diameters. We included 70 patients with gradable indocyanine green angiography for the prespecified features in the study eye (36 typical nAMD and 34 PCV) and 59 fellow eyes. The median subfoveal choroidal thickness was 167 µm versus 219 µm, P = 0.08, in the presenting eyes in typical nAMD and PCV, respectively. Macular anastomosis was common in both typical nAMD and PCV (presenting eyes 58.3% vs. 58.8%. P = 0.97; fellow eyes 65.5% vs. 63.3%, P = 0.86). Dilated Haller veins were numerically less common in typical nAMD than PCV (presenting eyes 52.8% vs. 67.6%, P = 0.21; fellow eyes 65.5% vs. 70.0%, P = 0.71), while vascular caliber variation was numerically more common in typical nAMD than PCV (presenting eyes 72.2% vs. 63.8%, P = 0.45; fellow eyes 69.0% vs. 56.7%, P = 0.33). The presence of all three features was more common in the presenting eyes with PCV compared with typical nAMD (35.3% vs. 13.9%, P = 0.03). In a multivariable analysis, every increase of 100 µm of CT conferred a 2.75 risk of having all three features present. Choroidal vascular remodeling is common in both tAMD and PCV but may be driven by different stimuli.

Comparison of brain-derived neurotrophic factor among subtypes of exudative age-related macular degeneration.

To compare the levels of brain-derived neurotrophic factor (BDNF) in serum and aqueous humor (AH) in eyes with typical neovascular age-related macular degeneration (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP). This prospective study included 20 patients with tAMD, 20 patients with PCV, 20 patients with RAP, and 20 healthy controls. BDNF levels in the serum and AH were assessed using enzyme-linked immunosorbent assay. Serum and AH BDNF levels were significantly lower in the age-related macular degeneration groups (tAMD, PCV, and RAP) than in the control group (p < 0.05). There was no significant difference in the mean BDNF levels in the serum and AH among the different nAMD subtypes (p = 0.538). We confirmed that serum and AH BDNF levels were independent of the nAMD subtype.

Choroidal Neovascularization and Haller Vessel Morphology Associated with Vision and Treatment Number after 1 Year in Age-related Macular Degeneration.

PurposeThe present study aimed to quantify various factors of vessel morphology, including vessel diameter, length, and complexity (fractal dimension and lacunarity) of both choroidal neovascularization (CNV) and en face Haller vessels using optical coherence tomography angiography (OCTA) and en face structural optical coherence tomography in typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) and to identify factors associated with visual acuity (VA) loss and number of injections within a year after the day of OCTA.MethodsWe retrospectively analyzed 43 eyes of nAMD patients and 33 eyes of PCV patients whose OCTA was performed at least 12 months after an initial anti-vascular endothelial growth factor treatment. Quantitative parameters, including vessel area, vessel diameter, vessel length, fractal dimension, and lacunarity were analyzed from en face images of CNV and Haller vessels. Clinical information, including logarithm of the minimum angle of resolution visual acuity and injection number of anti-vascular endothelial growth factor were acquired after 12 months from OCTA date. Using logistic regression analyses, parameters associated with logarithm of the minimum angle of resolution VA loss of 0.2 or more (VA loss group) and a number of injections of four or more (unstable group) after 12 months were analyzed.ResultsIn typical nAMD, the VA loss group was associated with a smaller number of intersections of Haller vessels. The unstable group was associated with an increased lacunarity of CNV in typical nAMD. In PCV, both VA loss and unstable groups were associated with a higher maximal diameter of Haller vessels.ConclusionsVA loss and injection number of nAMD and PCV 12 months after OCTA imaging were associated with different morphological parameters of CNV and Haller vessels. Therefore, quantitative analyses of both CNV and Haller vessels from OCTA and en face optical coherence tomography might provide prognostic information about visual outcome and injection frequency within 12 months after OCTA imaging.

This issue of ACTA

This issue of ACTA

Long-term outcomes of ranibizumab vs. aflibercept for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

To evaluate the long-term outcomes of ranibizumab (RBZ) vs. aflibercept (AFL) in treatment-naïve eyes with typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV). This multicenter, retrospective, matched-cohort analysis was conducted on data up to 4 years of follow-ups. The primary outcome was the visual acuity (VA) change from baseline. The secondary outcomes included the number of injections, proportion of eyes without a yearly injection, and the number of eyes with treatment switching. Subgroup analyses were performed for typical nAMD and PCV. Typical nAMD was defined as nAMD other than PCV. We included VA-matched 215 eyes of 209 patients (131 and 84 eyes with RBZ and AFL, respectively). The crude mean VA changes from baseline were + 6.7 vs. + 2.6, + 2.1 vs. − 0.4, − 1.3 vs. − 1.8, and − 2.2 vs. − 5.0 letters in the RBZ and AFL groups, at 1, 2, 3, and 4 years, respectively (p > 0.05). The adjusted predicted VA by linear mixed model, proportion of eyes stratified by VA, and the survival curve for significant vision loss were comparable during the 4-year follow-up (p > 0.05). The mean number of injections were similar between the RBZ and AFL groups (2.9 vs. 3.0, respectively, p = 0.692). The subgroup analysis for typical nAMD and PCV showed similar results between the groups. The visual outcomes did not differ between RBZ and AFL during 4 years with comparable numbers of injections. Our study reflects the long-term, real-world clinical practice and treatment pattern of two treatments for typical nAMD and PCV.

Пахихориоидальная неоваскулопатия при нормальной субфовеолярной толщине хориоидеи

Pachychoriod neovasculopathy and typical neovascular age-related macular degeneration often look similar, but some differences have been described both genotypically and in the level of cytokine profile, which explains the difference in response to antiangiogenic therapy. It is known that pachychoriod diseases are characterized by choroidal subfoveolar thickening. However, there is currently no data on the structural features of the choroid in the presence of pachychoriod neovasculopathy outside the fovea. Purpose. To perform a detailed analysis of choroial structure on OCT scans of patients with neovascular AMD with normal choroidal subfoveolar thickness and to reveal the frequency of pachychoriodal neovasculopathy identification. Material and methods. In retrospective study, the data of 30 treatment-naive patients (30 eyes) aged 71.5±7.6 years with CNV type 1 were analyzed, including 18 women and 12 men, with a subfeolar thickness of the choroidal membrane not exceeding 250 µm. The patients underwent OCT and OCT-angiography using a Spectralis device (Heidelberg Engineering, Germany). In the foveolar zone and under the neovascular complex, if it is located outside the fovea, the structure of the choroid was analyzed: the choroidal thickness, Haller layer and choriocapillaries / layer of Sattler vessels were measured. Results. The average thickness of the choroid in the fovea in all patients was 170.1±40 µm. The thickness of Haller vessels layer was on average 112.3±20 μm, and the layer of choriocapillaries / Sattler vessels was 57.8±12 μm. In 22 eyes, the structure of the choroid and the ratio of all layers were similar in all analyzed OCT scans. However, in 8 eyes, under the CNV located extrafoveally, a thickening of the choroid was revealed up to 210.5±51 µm, the main volume of the choroid was presented by pachyvessels – dilated and enlarged vessels of the Haller layer which thickness was 189.4 ± 48 µm, and thinning of the choriocapillary / Sattler layer to 21.1±16 µm. Conclusion. Among 30 patients with normal subfoveolar thickness of the choroid, the frequency of PNV was 26.6%. Taking into account the literature data on different responses to antiangiogenic therapy in patients with PNV and typical AMD, we can once again emphasize the importance of a detailed assessment of changes in the choroid not only in the foveolar zone, but also specifically in the area of the neovascular complex. Key words: pachychoriod neovasculopathy, choroid, OCT.

Multimodal deep learning with feature level fusion for identification of choroidal neovascularization activity in age-related macular degeneration.

This study aimed to determine the efficacy of a multimodal deep learning (DL) model using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) images for the assessment of choroidal neovascularization (CNV) in neovascular age-related macular degeneration (AMD). This retrospective and cross-sectional study was performed at a multicentre, and the inclusion criteria were age >50 years and a diagnosis of typical neovascular AMD. The OCT and OCTA data for an internal data set and two external data sets were collected. A DL model was developed with a novel feature-level fusion (FLF) method utilized to combine the multimodal data. The results were compared with identification performed by an ophthalmologist. The best model was tested on two external data sets to show its potential for clinical use. Our best model achieved an accuracy of 95.5% and an area under the curve (AUC) of 0.9796 on multimodal data inputs for the internal data set, which is comparable to the performance of retinal specialists. The proposed model reached an accuracy of 100.00% and an AUC of 1.0 for the Ningbo data set, and these performance indicators were 90.48% and an AUC of 0.9727 for the Jinhua data set. The FLF method is feasible and highly accurate, and could enhance the power of the existing computer-aided diagnosis systems. The bi-modal computer-aided diagnosis (CADx) system for the automated identification of CNV activity is an accurate and promising tool in the realm of public health.

Long-term outcome of intravitreal anti-vascular endothelial growth factor treatment for pachychoroid neovasculopathy

To compare the long-term effectiveness of intravitreal anti-vascular endothelial growth factor (VEGF) treatment for pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy/aneurysmal type 1 neovascularization (PCV/AT1), and typical neovascular age-related macular degeneration (nAMD). Forty-one eyes with PNV, 68 eyes with PCV/AT1, and 56 eyes with typical nAMD were retrospectively included for analysis. All patients were treatment-naïve and received a three-monthly loading injection of anti-VEGF, followed by further injections, as required. The visual and anatomical outcomes after treatment were evaluated up to 36 months from baseline. No significant intergroup difference was found in terms of best-corrected visual acuity (BCVA) and changes in central foveal thickness at 12, 24, and 36 months after the baseline. In addition, no significant difference was found between the groups regarding the proportions of improved or worsened (increased or decreased more than 3-lines) visual acuity. However, the PNV group participants received significantly fewer anti-VEGF injections (11.7 ± 6.9) than those in the PCV/AT1 (12.4 ± 7.0; P = 0.031) and typical nAMD groups (13.2 ± 7.4; P = 0.016). The incidence of macular atrophy (MA) development was also significantly lower for the PNV (4/41 eyes, 9.8%) than the typical nAMD (15/56 eyes, 26.8%; P = 0.033) eyes. There was no significant difference between PNV, PCV/AT1, and typical nAMD regarding visual acuity improvement after anti-VEGF treatment over 36 months. However, the number of injections for PNV was significantly lower compared to that for PCV/AT1 and typical nAMD, and the incidence of MA development was significantly lower than in typical nAMD.

Eyes that Do Not Meet the Eligibility Criteria of Clinical Trials on Age-Related Macular Degeneration: Proportion of the Real-World Patient Population and Reasons for Exclusion.

Background To evaluate the proportion of eyes that do not meet the eligibility criteria of clinical trials on neovascular age-related macular degeneration (AMD) and the reasons for exclusion. Methods This retrospective, observational study included 512 eyes of 463 patients diagnosed with treatment-naïve neovascular AMD. The proportion of eyes that did not meet the eligibility criteria of the Vascular Endothelial Growth Factor Trap-Eye: Investigation of Efficacy and Safety in Wet AMD (VIEW) studies were evaluated. The two most common reasons for exclusion were also evaluated in each subtype of neovascular AMD (typical neovascular AMD, polypoidal choroidal vasculopathy (PCV), and type 3 neovascularization). Results Among the 512 eyes, 229 (44.7%) did not meet the eligibility criteria. In all the included eyes, the most common reasons for exclusion were good or poor visual acuity (169 eyes, 33.0%), followed by the presence of subretinal hemorrhage (47 eyes, 9.5%). Moreover, good or poor visual acuity was the most common reason for exclusion in all three subtypes of neovascular AMD. The second most common reason was a fovea-involving scar or fibrosis in typical neovascular AMD, subretinal hemorrhage in PCV, and other vascular diseases affecting the retina in type 3 neovascularization. Conclusions Among the included cases, 44.7% did not meet the eligibility criteria for VIEW study, suggesting that the conclusion derived from clinical trials may not directly reflect the real-world outcomes. Additionally, the reasons for ineligibility differed among the different subtypes of neovascular AMD.

Non-ICGA treatment criteria for Suboptimal Anti-VEGF Response for Polypoidal Choroidal Vasculopathy: APOIS PCV Workgroup Report 2

To develop and validate OCT and color fundus photography (CFP) criteria in differentiating polypoidal choroidal vasculopathy (PCV) from typical neovascular age-related macular degeneration (nAMD) in eyes with suboptimal response to anti-vascular endothelial growth factor (VEGF) monotherapy and to determine whether OCT alone can be used to guide photodynamic therapy (PDT) treatment. Clinical study evaluating diagnostic accuracy. Patients with nAMD who received 3-month anti-VEGF monotherapy but had persistent activity defined as subretinal fluid or intraretinal fluid at month 3 assessments. In phase 1, international retina experts evaluated OCT and CFP of eyes with nAMD to identify the presence or absence of features due to PCV. The performance of individual and combinations of these features were compared with ICGA. In phase 2, these criteria were applied to an independent image set to assess generalizability. In a separate exercise, retinal experts drew proposed PDT treatment spots using only OCT and near-infrared (NIR) images in eyes with PCV and persistent activity. The location and size of proposed spot were compared with ICGA to determine the extent of coverage of polypoidal lesions (PLs) and branching neovascular network (BNN). Sensitivity and specificity of CFP and OCT criteria to differentiate PCV from nAMD and accuracy of coverage of OCT-guided PDT compared with ICGA. In eyes with persistent activity, the combination of 3 non-ICGA-based criteria (sharp-peaked pigment epithelial detachment [PED], subretinal pigment epithelium [RPE] ring-like lesion, and orange nodule) to detect PCV showed good agreement compared with ICGA, with an area under the receiver operating characteristic curve of 0.85. Validation using both an independent image set and assessors achieved an accuracy of 0.77. Compared with ICGA, the OCT-guided PDT treatment spot covered 100% of PL and 90% of the BNN. In nAMD eyes with persistent activity, OCT and CFP can differentiate PCV from typical nAMD, which may allow the option of adjunct PDT treatment. Furthermore, OCT alone can be used to plan adjunct PDT treatment without the need for ICGA, with consistent and complete coverage of PL.

Effects of Intravitreous Aflibercept Injection in Pachychoroid Neovasculopathy: Comparison with Typical Neovascular Age-Related Macular Degeneration.

PurposeTo compare the 12-month efficacy of intravitreous aflibercept (IVA) injection between eyes with pachychoroid neovasculopathy and neovascular age-related macular degeneration (AMD).MethodsRetrospective, comparative case series analysis. Twenty-seven eyes with pachychoroid neovasculopathy and sixty-three eyes with neovascular AMD. All patients received three initial monthly, followed by bimonthly, IVA injections.ResultsTwelve months after initial treatment, the mean best-corrected visual acuity (BCVA) had improved both in pachychoroid neovasculopathy (from 0.28 to 0.14 logMAR; P = 0.001) and neovascular AMD (from 0.40 to 0.29 logMAR; P < 0.001). Twelve months after initial treatment, eyes with pachychoroid neovasculopathy exhibited decreased mean central retinal thickness (CRT) and subfoveal choroidal thickness (both, P < 0.001) and presence of polyps (P = 0.039) and improved integrity of external limiting membrane (ELM) (P = 0.008) and ellipsoid zone band (P = 0.001). At the 12-month follow-up, 77% and 68% of eyes with pachychoroid neovasculopathy and neovascular AMD, respectively, exhibited dry macula (P = 0.30). Baseline CRT was correlated with 12-month BCVA in eyes with pachychoroid neovasculopathy (P = 0.02). In eyes with neovascular AMD, CRT (P = 0.005) and presence of intact ELM (P = 0.007) were significant predictors of 12-month BCVA.ConclusionPeriodic IVA injection leads to anatomical and functional improvement in eyes with pachychoroid neovasculopathy and in eyes with neovascular AMD.

Massive submacular haemorrhage in polypoidal choroidal vasculopathy versus typical neovascular age-related macular degeneration.

To investigate the incidence rate of massive submacular haemorrhage (SMH) and risk factors in polypoidal choroidal vasculopathy (PCV) and typical neovascular age-related macular degeneration (tnAMD). A total of 465 patients who were diagnosed with either PCV (n=245) or tnAMD (n=220) from 2003 to 2014 were enrolled. Cumulative incidence of massive SMH in PCV and that in tnAMD were compared. Risk factors of massive SMH were also analysed. Massive SMH occurred in 32 patients (13.1%) with PCV and 9 patients (4.1%) with tnAMD. Incidence rates of massive SMH 5 and 10years after the first visit were 11.1% and 29.9% in PCV and 4.3% and 9.9% in tnAMD, respectively. Incidence rates of massive SMH in PCV were significantly higher than those in tnAMD (hazard ratio [HR], 2.66; p=0.007). Cox regression analysis revealed that mean number of photodynamic therapies (PDTs) per year (HR, 4.24; p<0.001), cluster type of polypoidal lesion (HR, 3.42; p=0.003) in PCV, and mean number of anti-VEGF injections per year (HR, 1.58; p<0.001) in tnAMD were significantly associated with risk of massive SMH. For patients with severe vision loss, proportion of incident massive SMH was significantly higher in PCV (29.5%) than in tnAMD (6.9%, p<0.001). The incidence rate of massive SMH in eyes with PCV was about three times higher than that in eyes with tnAMD. Treatment methods that can reduce the incidence of massive SMH should be considered, especially for eyes with PCV.

Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non–Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup

To develop consensus terminology in the setting of polypoidal choroidal vasculopathy (PCV) and to develop and validate a set of diagnostic criteria not requiring indocyanine green angiography (ICGA) for differentiating PCV from typical neovascular age-related macular degeneration (nAMD) based on a combination of OCT and color fundus photography findings. Evaluation of diagnostic test results. Panel of retina specialists. As part of the Asia-Pacific Ocular Imaging Society, an international group of experts surveyed and discussed the published literature regarding the current nomenclature and lesion components for PCV, and proposed an updated consensus nomenclature that reflects our latest understanding based on imaging and histologic reports. The workgroup evaluated a set of diagnostic features based on OCT images and color fundus photographs for PCV that may distinguish it from typical nAMD and assessed the performance of individual and combinations of these non-ICGA features, aiming to propose a new set of diagnostic criteria that does not require the use of ICGA. The final recommendation was validated in 80 eyes from 2 additional cohorts. Consensus nomenclature system for PCV lesion components and non-ICGA-based criteria to differentiate PCV from typical nAMD. The workgroup recommended the terms polypoidal lesion and branching neovascular network for the 2 key lesion components in PCV. For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-retinal pigment epithelium [RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset 80 eyes achieved an accuracy of 82%. We propose updated terminology for PCV lesion components that better reflects the nature of these lesions and is based on international consensus. A set of practical diagnostic criteria applied easily to spectral-domain OCT results can be used for diagnosing PCV with high accuracy in clinical settings in which ICGA is not performed routinely.

Association of CRP levels with ARMS2 and CFH variants in age-related macular degeneration.

To investigate whether plasma high sensitivity C-reactive protein (hs-CRP) level is associated with exudative age-related macular degeneration (AMD) as well as variants of ARMS2 A69S and CFH I62V in patients with exudative AMD. A case-control study was done comparing CRP among patients with exudative AMD including those with polypoidal choroidal vasculopathy, typical AMD and retinal angiomatous proliferation, and CRP were also compared between cases and controls. Plasma CRP was measured from peripheral blood using latex nepherometry for all participants. Genotyping of ARMS2 A69S and CFH I62V was performed for all patients with exudative AMD using TaqMan technology. Among 125 patients with exudative AMD, including 31 with typical neovascular AMD, 73 with PCV and 21 with RAP lesions and 150 controls, CRP levels were higher in exudative AMD than in controls. (P = 2.7 × 10-5) There was not a significant difference in hs-CRP levels among AMD subtypes. Neither variants of ARMS2 nor CFH was associated with hs-CRP level in patients with exudative AMD. A multiple regression analysis revealed that gender male, presence of exudative AMD and presence of cardiovascular diseases were associated with increased plasma hs-CRP. Plasma hs-CRP was elevated independent of variants of ARMS2 A69S and CFH I62V in patients with exudative AMD.