Retinal Angiomatous Proliferation Research Articles

Incidence and risk of advanced age-related macular degeneration in eyes with drusenoid pigment epithelial detachment

To investigate the incidence and risk of advanced age-related macular degeneration (AMD), including geographic atrophy (GA) and macular neovascularization (MNV), in eyes with drusenoid pigment epithelial detachment (PED). Eighty-five eyes with drusenoid PED from 85 patients (77.2 ± 7.0 years, male/female: 44/41) were included in this study. Patients were followed up every 1–3 months via spectral-domain optical coherence tomography (SD-OCT) and color fundus photography. If exudation was observed on SD-OCT, fluorescein and indocyanine green angiography were performed to confirm the MNV subtype accordingly. The maximum follow-up period was 60 months. During the study period, GA developed in 8 eyes while MNV also developed in 8 eyes. The Kaplan–Meier estimator revealed that the cumulative incidence for 60 months was 17.9% and 12.2% for GA and MNV, respectively. In eyes developing MNV, retinal angiomatous proliferation was the most common. Cox regression analysis revealed that baseline PED width was the only factor associated with advanced AMD. (p = 0.0026, Cox regression analysis). The 5-year cumulative incidence of advanced AMD, including GA and MNV, was approximately 30% in eyes with drusenoid PED among the Japanese elderly. A larger baseline PED width was the only risk factor for advanced AMD.

Retinal Angiomatous Proliferations as a Rare Form of Age Related Macular Degenerations

Retinal Angiomatous Proliferations as a Rare Form of Age Related Macular Degenerations

Classifying neovascular age-related macular degeneration with a deep convolutional neural network based on optical coherence tomography images

Neovascular age-related macular degeneration (nAMD) is among the main causes of visual impairment worldwide. We built a deep learning model to distinguish the subtypes of nAMD using spectral domain optical coherence tomography (SD-OCT) images. Data from SD-OCT images of nAMD (polypoidal choroidal vasculopathy, retinal angiomatous proliferation, and typical nAMD) and normal healthy patients were analyzed using a convolutional neural network (CNN). The model was trained and validated based on 4749 SD-OCT images from 347 patients and 50 healthy controls. To adopt an accurate and robust image classification architecture, we evaluated three well-known CNN structures (VGG-16, VGG-19, and ResNet) and two customized classification layers (fully connected layer with dropout vs. global average pooling). Following the test set performance, the model with the highest classification accuracy was used. Transfer learning and data augmentation were applied to improve the robustness and accuracy of the model. Our proposed model showed an accuracy of 87.4% on the test data (920 images), scoring higher than ten ophthalmologists, for the same data. Additionally, the part that our model judged to be important in classification was confirmed through Grad-CAM images, and consequently, it has a similar judgment criteria to that of ophthalmologists. Thus, we believe that our model can be used as an auxiliary tool in clinical practice.

Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative Age-Related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical trial

BackgroundNeovascular (wet) age-related macular degeneration (AMD) can be associated with large submacular haemorrhage (SMH). The natural history of SMH is very poor, with typically marked and permanent loss of central vision in the affected eye. Practice surveys indicate varied management approaches including observation, intravitreal anti-vascular endothelial growth factor therapy, intravitreal gas to pneumatically displace SMH, intravitreal alteplase (tissue plasminogen activator, TPA) to dissolve the clot, subretinal TPA via vitrectomy, and varying combinations thereof. No large, published, randomised controlled trials have compared these management options.MethodsTIGER is a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial. Eligible participants have large, fovea-involving SMH of no more than 15 days duration due to treatment-naïve or previously treated neovascular AMD, including idiopathic polypoidal choroidal vasculopathy and retinal angiomatous proliferation. A total of 210 participants are randomised in a 1:1 ratio to pars plana vitrectomy, off-label subretinal TPA up to 25 μg in 0.25 ml, intravitreal 20% sulfahexafluoride gas and intravitreal aflibercept, or intravitreal aflibercept monotherapy. Aflibercept 2 mg is administered to both groups monthly for 3 doses, then 2-monthly to month 12. The primary efficacy outcome is the proportion of participants with best-corrected visual acuity (BCVA) gain of ≥ 10 Early Treatment Diabetic Retinopathy (ETDRS) letters in the study eye at month 12. Secondary efficacy outcomes (at 6 and 12 months unless noted otherwise) are proportion of participants with a BCVA gain of ≥ 10 ETDRS letters at 6 months, mean ETDRS BCVA, Radner maximum reading speed, National Eye Institute 25-item Visual Function Questionnaire composite score, EQ-5D-5L with vision bolt-on score, Short Warwick and Edinburgh Mental Wellbeing score, scotoma size on Humphrey field analyser, and presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using independent reading centre multimodal image analysis (12 months only). Key safety outcomes are adverse events, serious adverse events, and important medical events, coded using the Medical Dictionary for Regulatory Activities Preferred Terms.DiscussionThe best management of SMH is unknown. TIGER aims to establish if the benefits of SMH surgery outweigh the risks, relative to aflibercept monotherapy.Trial registrationClinicalTrials.govNCT04663750; EudraCT: 2020-004917-10.

Long-term characteristics of exudative age-related macular degeneration in Japanese patients.

PurposeThe present study aimed to evaluate the clinical characteristics of exudative age-related macular degeneration (AMD) in Japanese patients over a 10-year period and to compare the past our report.MethodsWe retrospectively reviewed 1,600 treatment-naïve patients (1,777 eyes) with exudative AMD. The 10 years were divided into 2-year phases I to V.ResultsOf the 1,600 patients, 720 (45.0%), 733 (45.8%), 98 (6.1%), and 49 (3.1%) were diagnosed with typical AMD, polypoidal choroidal vasculopathy (PCV), retinal angiomatous proliferation, and combined subtypes, respectively. The prevalence of PCV decreased from 54.7% in phase I to 46.0% at phase V. Of the 1,777 eyes, the mean baseline logarithm of the minimum angle of resolution best-corrected visual acuities (BCVAs) in phases I, II, III, IV, and V were 0.70, 0.66, 0.55, 0.50, and 0.48, respectively. Phases III, IV, and V had significantly (P = 0.0012, P<0.0001, P<0.0001, respectively) better baseline VAs compared with phase I. The mean lesion sizes in phases I, II, III, IV, and V were 8.6, 6.7, 5.3, 5.7, and 5.7 Macular Photocoagulation Study disc areas, respectively. The sizes were significantly (P<0.0001 for all comparisons) smaller in phases III, IV, and V compared with phase I.ConclusionsAlthough the prevalence of PCV decreased from 54.7% in phase I to 46.0% at phase V, PCV has nevertheless been highly prevalent in Japanese patients with AMD compared with Caucasian patients. The annual better baseline VAs and smaller lesion sizes over time might be related to development of treatment and better concerns about AMD.

GEOGRAPHIC ATROPHY INCIDENCE AND PROGRESSION AFTER INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS FOR AGE-RELATED MACULAR DEGENERATION: A Meta-Analysis.

Geographic atrophy (GA) is a complication of advanced neovascular age-related macular degeneration that can lead to permanent vision loss. We sought to estimate the incidence and progression of GA after intravitreal injections of antivascular endothelial growth factor agents in eyes with neovascular age-related macular degeneration. Ovid MEDLINE, EMBASE, and Cochrane CENTRAL were searched from inception to May 2020. Included studies reported on the progression or development of GA in eyes with neovascular age-related macular degeneration after antivascular endothelial growth factor therapy. Thirty-one articles and 4,609 study eyes (4,501 patients) were included. Eyes received a mean of 17.7 injections over 35.2 months. The prevalence of GA at baseline was 9.7%. The pooled incidence of GA was 30.5% at the end of follow-up. There was a positive, moderate linear correlation between the mean total number of injections and GA incidence at the final follow-up (R2 = 0.30; P = 0.01). Monthly treatment was associated with a significantly higher risk for GA development relative to pro re nata (relative risk = 1.40, 95% confidence interval = [1.21-1.61], P < 0.001). Risk factors for GA development included GA in the fellow eye, retinal angiomatous proliferation, drusen, and reticular pseudodrusen. We found an association between the frequency and number of treatments with antivascular endothelial growth factor agents and the development of GA in neovascular age-related macular degeneration. Future studies should clarify risk factors, population characteristics, and relative contributions of treatment and disease progression on GA development in this context.

The Influence of COVID-19 on the Stability of Patients with Neovascular Age-Related Macular Degeneration with Different Treatment Regimens.

IntroductionTo explore the impact of coronavirus disease 2019 (COVID-19) on the stability of patients with neovascular age-related macular degeneration (nAMD) receiving the treat and extend (T&E) or the pro re nata (PRN) treatment regimen and to identify indicators that may predict the disease stability of nAMD.MethodsThis is a retrospective study of patients with nAMD treated at the Second Affiliated Hospital of Harbin Medical University whose treatment schedule was interrupted at least once between 1 February and 31 May 2020. The demographic and clinical characteristics, including the best corrected visual acuity (BCVA), optical coherence tomography (OCT) features, subfoveal choroidal thickness (SFCT), interval between the last injection and the beginning of the pandemic, and the number of anti-vascular endothelial growth factor (VEGF) injections, were analyzed.ResultsA total of 209 stable patients with nAMD (122 eyes received the T&E regimen; 87 eyes received the PRN regimen) were identified. Compared to those who received the PRN regimen, the patients who received the T&E regimen were more stable during the first visit after COVID-19 (53.3% vs. 33.3%, P = 0.004), the BCVA was significantly better (58.5 letters vs. 56 letters, P = 0.006), and the CRT fluctuated only slightly (15 μm vs. 35 μm, P = 0.001). Furthermore, a multivariate logistic regression analysis showed that stable patients with nAMD with type 1 choroidal neovascularization (CNV) (OR 2.493 [95% CI 1.179–5.272], compared with type 2 CNV; P = 0.017; OR 2.912 [95% CI 1.133–7.485], compared with retinal angiomatous proliferation; P = 0.026) or with pigment epithelial detachment (PED) were more likely to remain stable when treatment was interrupted (OR 0.392 [95% CI 0.181–0.852], compared with no PED; P = 0.018).ConclusionCompared to patients who received the PRN treatment regimen, stable patients with nAMD who received the T&E treatment regimen could better maintain stability when the treatments were suddenly interrupted by the COVID-19 pandemic. In addition, patients with type 1 CNV or patients with PED were more likely to remain stable. At present, the COVID-19 pandemic is becoming increasingly normalized, and the T&E regimen can become a more advanced treatment option for patients undergoing therapy.

Clinical Pathological Features and Current Animal Models of Type 3 Macular Neovascularization.

Type 3 macular neovascularization (MNV3), or retinal angiomatous proliferation (RAP), is a distinct type of neovascular age-related macular degeneration (AMD), which is a leading cause of vision loss in older persons. During the past decade, systematic investigation into the clinical, multimodal imaging, and histopathological features and therapeutic outcomes has provided important new insight into this disease. These studies favor the retinal origin of MNV3 and suggest the involvement of retinal hypoxia, inflammation, von Hippel–Lindau (VHL)–hypoxia-inducible factor (HIF)–vascular endothelial growth factor (VEGF) pathway, and multiple cell types in the development and progression of MNV3. Several mouse models, including the recently built Rb/p107/Vhl triple knockout mouse model by our group, have induced many of the histological features of MNV3 and provided much insight into the underlying pathological mechanisms. These models have revealed the roles of retinal hypoxia, inflammation, lipid metabolism, VHL/HIF pathway, and retinoblastoma tumor suppressor (Rb)–E2F cell cycle pathway in the development of MNV3. This article will summarize the clinical, multimodal imaging, and pathological features of MNV3 and the diversity of animal models that exist for MNV3, as well as their strengths and limitations.

Drusen and pigment abnormality predict the development of neovascular age-related macular degeneration in Japanese patients.

Drusen are known to be the important hallmark to predict the development of age-related macular degeneration (AMD). The prevalence of drusen is lower in Asians compared with Caucasians so that the role of signs constituting early AMD is not well established in Asian populations as in Western countries. In this study, we retrospectively investigated clinical characteristics and 5-year incidence of neovascular AMD (nAMD) in the fellow eye of unilateral nAMD patients. Of 296 consecutive unilateral nAMD patients who had been followed up more than 5 years, 170 typical AMD, 119 polypoidal choroidal vasculopathy, and 7 retinal angiomatous proliferation were included. To examine factors associated with nAMD occurrence in the fellow eye, drusen and pigmentary abnormality in the fellow eye were classified into 4 categories; Category 1: no or small drusen < 63 μm (37.2%), Category 2: 63–125 μm medium drusen or pigmentary abnormality (22.2%), Category 3: large drusen > 125 μm (25.0%), Category P: pachydrusen (15.5%). The mean sub-foveal choroidal thickness (SFCT) was Category 1: 276 μm, Category 2: 308 μm, Category 3: 246 μm, and Category P: 302 μm, respectively. Of note, SFCT in Category 2 and Category P was significantly larger than those of Category 3. Finally, the 5-year incidence of nAMD in the fellow eye was 32/296 (10.8%); Category 1: 0/110 (0%), Category 2: 12/66 (18.2%), Category 3: 20/74 (27.0%), and Category P: 0/46 (0%). Thus, signs of intermediate AMD (large drusen) as well as those of early AMD, especially the pigmentary abnormality, may contribute to development of bilateral nAMD in Japanese patients.

Анализ применения антиангиогенной терапии у пациентов с ретинальной ангиоматозной пролиферацией

Retinal angiomatous proliferation (RAP) is a separate form of neovascular age-related macular degeneration (nAMD), which accounts for 12-15% of newly diagnosed patients with nAMD [14]. It is believed that the development of RAP is associated with vascular endothelial growth factor (VEGF) [12]. Purpose. The main goal of our work was to conduct a retrospective analysis of the use of anti-VEGF therapy in patients with retinal angiomatous proliferation. Material and methods. Under observation in 14 patients (14 eyes) with retinal angiomatous proliferation. The age of the patients ranged from 52 to 80 years. The observation period was 4 years. OCT data were used to assess the presence / absence of neuroepithelial detachment, the presence / absence of retinal pigment epithelium detachment and the presence / absence of intraretinal fluid, and the incidence of RP rupture was assessed. Results. The maximally corrected visual acuity increased already in the first year of follow-up compared to BCVA before treatment, under the condition of intravitreal injections (IVI) of anti-VEGF drug aflibercept, and continued to remain at the same level throughout the observation period. In most patients, subretinal fluid was resorbed as early as 1 year of follow-up against the background of antiangiogenic therapy; by 3 years of follow-up, ONE remained only in 2 patients. Before treatment, 71.4% of patients had intraretinal fluid (IRF) in the macular zone according to OCT data; by the 3rd year of follow-up, the percentage of patients with IRF was 33.3%. Conclusion. In the course of this work, we have shown a positive effect of intravitreal administration of the anti-VEGF drug aflibercept in patients with retinal angiomatous proliferation. Key words: age-related macular degeneration, retinal angiomatous proliferation, anti- VEGF, macular edema.

Proportion and Reasons for Ineligibility to Re-register for Extended Health Insurance in Neovascular Age-related Macular Degeneration

Purpose: To evaluate the proportion and reasons for ineligibility to re-register for extended health insurance at 5 years in patients diagnosed with neovascular age-related macular degeneration (AMD) and registered for extended health insurance. Methods: This retrospective study was performed in patients diagnosed with neovascular AMD and registered for extended health insurance with follow-up for at least 5 years. The criteria for re-registration for extended health insurance were determined along with the ineligibility for re-registration. Results: In total, 263 patients were included in the analysis. Of these, 148 (56.3%) did not satisfy the criteria for re-registration. No active treatment was performed in 98 patients during the last 6 months of the study period (no recurrence, 51 patients; additional treatment was not considered beneficial due to retinal damage even without disciform scar formation, 44 patients). Macular disciform scar formation was noted in 50 patients (33.8%). Older age (p = 0.013), poor visual acuity (p = 0.004), and retinal angiomatous proliferation (p &lt; 0.001) were associated with ineligibility for re-registration due to severe retinal damage. Conclusions: Among the patients who were initially registered for extended health insurance, 56.3% failed to satisfy the re-registration criteria. The primary reason was advanced retinal damage. The results of this study provide useful information for patient education and to establish long-term treatment strategies.

Distinguishing retinal angiomatous proliferation from polypoidal choroidal vasculopathy with a deep neural network based on optical coherence tomography

This cross-sectional study aimed to build a deep learning model for detecting neovascular age-related macular degeneration (AMD) and to distinguish retinal angiomatous proliferation (RAP) from polypoidal choroidal vasculopathy (PCV) using a convolutional neural network (CNN). Patients from a single tertiary center were enrolled from January 2014 to January 2020. Spectral-domain optical coherence tomography (SD-OCT) images of patients with RAP or PCV and a control group were analyzed with a deep CNN. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUROC) were used to evaluate the model’s ability to distinguish RAP from PCV. The performances of the new model, the VGG-16, Resnet-50, Inception, and eight ophthalmologists were compared. A total of 3951 SD-OCT images from 314 participants (229 AMD, 85 normal controls) were analyzed. In distinguishing the PCV and RAP cases, the proposed model showed an accuracy, sensitivity, and specificity of 89.1%, 89.4%, and 88.8%, respectively, with an AUROC of 95.3% (95% CI 0.727–0.852). The proposed model showed better diagnostic performance than VGG-16, Resnet-50, and Inception-V3 and comparable performance with the eight ophthalmologists. The novel model performed well when distinguishing between PCV and RAP. Thus, automated deep learning systems may support ophthalmologists in distinguishing RAP from PCV.

Clinical and Multimodal Imaging Features of Subretinal Drusenoid Deposits.

PurposeTo describe the multimodal imaging (MMI) features of subretinal drusenoid deposits (SDD) in Indian population.MethodsPatients diagnosed to have SDD from January 2016 to December 2018 at our tertiary care center were recruited. The diagnosis of SDD was made on the basis of MMI consisting of a combination of color fundus photography (CFP), optical coherence tomography (OCT), red-free (RF) imaging, blue autofluorescence (BAF), and near-infra red reflectance (NIR) imaging. The morphological type and distribution of SDD and the associated retinal lesions were reviewed.Results Twenty-three patients with SDD were included. The mean age of the patients was 68.1 12.2 years. SDD were noted in 77.8% of eyes clinically (n = 35/45) and could be detected in 100% of these eyes with OCT. The morphology of SDD was nodular in 65.7% of eyes (n = 23/35), reticular in 5.7% (n = 2/35), and mixed pattern in the remaining cases. BAF and NIR showed hyporeflective nodular lesions often with a target configuration. The location was commonly in the perifoveal area, mostly involving the superotemporal quadrant (74.3%, n = 26/35). Associated retinal lesions were type-3 neovascularization or retinal angiomatous proliferation in 17.1% (n = 6/35), disciform scar in 11.4% (n = 4/35), type-1 neovascularization in 8.5% (n = 3/35), and geographic atrophy in 5.7% (n = 2/35) of eyes. The mean subfoveal choroidal thickness was 186.2 57.8 µm.ConclusionSDD commonly have a nodular morphology and their identification often requires confirmations with OCT. Advanced age-related macular degeneration features are frequently present in eyes with SDD and the fellow eyes.

Drusenoid Pigment Epithelial Detachment: Genetic and Clinical Characteristics.

Few studies report drusenoid pigment epithelial detachment (DPED) in Asians. In this multicenter study, we report the clinical and genetic characteristics of 76 patients with DPED, and, for comparison, 861 patients with exudative age-related macular degeneration (AMD) were included. On the initial presentation, the mean best-corrected visual acuity was 0.087 ± 0.17 (logMAR unit), and mean DPED height and width were 210 ± 132 and 1633 ± 1114 µm, respectively. Fifty-one (67%) patients showed macular neovascularization in the contralateral eye. The risk allele frequency of both ARMS2 A69S and CFH I62V was significantly higher in DPED than in typical AMD and polypoidal choroidal vasculopathy (PCV) (ARMS2 A69S risk allele frequency: DPED 77% vs. typical AMD 66% vs. PCV 57%, CFH I62V risk allele frequency: DPED 87% vs. typical AMD 73% vs. PCV 73%), although the risk allele frequency of both genes was similar between the DPED group and retinal angiomatous proliferation (RAP) group (ARMS2 A69S: p = 0.32, CFH I62V, p = 0.11). The prevalence of reticular pseudodrusen (RPD) was highest in RAP (60%), followed by DPED (22%), typical AMD (20%), and PCV (2%). Although the prevalence of RPD differs between DPED and RAP, these entities share a similar genetic background in terms of ARMS2 and CFH genes.

Macular fibrosis in Coats' disease demonstrated by Optical Coherence Tomography Angiography - new data toward pathophysiology.

To analyze if Segmented Swept-Source Optical Coherence Tomography Angiography (SS OCT-A) can provide additional information on morphology and pathophysiology of macular fibrosis in Coats' patients. A consecutive case series of three male patients (5, 7 and 15 years old), with Coats' disease-related macular fibrosis (stage 2b-2 patients, 3b-1 patient). SS OCT-A 3×3 mm macular scans of affected eyes were performed. In all three cases the inner portion of macular fibrosis displayed a dense network of vessels, continuing into deeper layers. This structure was similar to that observed in retinal angiomatous proliferations (RAP). There was associated loss of the foveal avascular zone. In one case we observed evolution of the lesion. SS-OCT imaging of macular fibrosis in Coats' disease reveals a distinct intralesional vascular structure with elements resembling RAP, probably developing as a secondary process.

Fundus autofluorescence of retinal angiomatous proliferation.

PurposeThe present study aimed to evaluate the characteristics of fundus autofluorescence in Japanese patients with retinal angiomatous proliferation (RAP).MethodsWe retrospectively reviewed 100 eyes from 76 patients (male, n = 45; female, n = 31; age range, 50–94 years; mean ± standard deviation, 81.4 ± 6.4 years) with treatment-naïve RAP, which was diagnosed based on the identification of retinal–retinal anastomosis on early-phase fluorescein angiography or indocyanine green angiography (ICGA) and the identification of a hot spot on late-phase ICGA. RAP was classified into the following three stages: stage 1, proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization); stage 2, growth of the retinal vessels into the subretinal space (subretinal neovascularization); and stage 3, clinically or angiographically observed choroidal neovascularization. In all cases, short-wavelength and near-infrared autofluorescence (SW-AF, NIR-AF) was evaluated using a confocal scanning laser ophthalmoscope.ResultsThe conditions of the 100 eyes were as follows: stage 1 RAP, n = 6 (6%); stage 2 RAP without retinal pigment epithelial detachment (PED), n = 40 (40%); stage 2 RAP with PED, n = 44 (44%); and stage 3 RAP, 10 (10%). On NIR-AF imaging, the number of abnormalities that were observed to correspond to the RAP lesions on ICGA (87 eyes, 87%) was significantly greater in comparison to SW-AF imaging (27 eyes, 27%). The mean follow-up period in all 76 patients was 39.2 months. In the 76 patients with unilateral disease, 21 (21%) eyes developed RAP in the fellow eye during the follow-up period. Among 18 eyes that were examined by both SW-AF and NIR-AF imaging before the onset of RAP lesions, NIR-AF imaging showed hypoautofluorescence in 15 (83%) eyes before the onset of RAP lesions.ConclusionsSW-AF and NIR-AF abnormalities may be related to the dysfunction of the photoreceptor/retinal pigment epithelium complex. Hypoautofluorescence on NIR-AF imaging may accurately indicate the presence or onset of RAP lesions.

Fixed Regimen Treatment in Unselected Naïve Patients Cohort with Neovascular Age-Related Macular Degeneration

The current treatment of neovascular age-related macular degeneration (nAMD) generates an excessive care pressure in the public health system. The search for a satisfactory treatment regimen, whose anatomical and functional stability may be achieved, is a challenge and a goal to be reached. We analyzed the outcomes in a patient cohort under fixed regimen treatment with intravitreal aflibercept (IVA). A retrospective study, with at least 1-year follow-up, in consecutive treated unselected naïve patients was carried out. Standard protocol was performed and evaluated at baseline, month 4 (after loading dose, LD), and month 12 (after fixed bimonthly regimen). One hundred six patients (123 eyes) aged 80.3 ± 7.7 years were included, receiving 6.8 ± 0.7 IVA. Visual acuity gain after LD was 5.5 ± 12.0 letters ( p &lt; 0.0001 ). At month 12, 23 eyes (18.7%) gained ≥15 letters and 58 (47.1%) had best-corrected visual acuity ≥20/40 (70 letters). The improvement in visual acuity was lower in patients with polypoidal choroidal vasculopathy (+4.9 ± 18.1 letters; p = 0.2544) and somewhat higher in patients with retinal angiomatous proliferation (+5.4 ± 12.3 letters; p = 0.0373 ). Dry macula was present in only 9.8% of cohort at baseline vs. 69.7% at month 12 ( p &lt; 0.0001 ). Atrophy was the most observed complication and related to the elderly patients. The average of follow-up visits was 3 ± 0.5. Functional and anatomical improvement were observed with IVA in a fixed bimonthly regimen treatment after LD, with results maintained up to one year with a good compliance. The fixed bimonthly regimen optimized patient management and logistic issues.

Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis

BackgroundPreviously, we and others have reported higher populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients’ responsiveness to anti-VEGF therapy.ResultsOne hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 healthy controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r = 0.29, P = 0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r = 0.34, p = 0.0007) but not in healthy controls (r = 0.057, p = 0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients’ responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls.ConclusionsOur results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.

Incidence and Natural History of Retinochoroidal Neovascularization in Enhanced S-Cone Syndrome

We examined the incidence and natural history of macular retinochoroidal neovascularization (RCN) in enhanced S-cone syndrome (ESCS). Retrospective case series. This single-center study included 14 of 93 patients with ESCS who had signs of active or inactive RCN in ≥1 eye. We conducted multimodal retinal imaging, full-field electroretinography, and molecular genetic analysis of NR2E3 gene. Our main outcome measures included the cumulative incidence of RCN in ESCS, type of RCN, and mode of evolution of RCN. Fourteen (15.1%) of 93 patients with ESCS had RCN in ≥1 eye at 2 to 27 years of age. All 22 RCNs (21 eyes of 14 patients) were macular. Twelve of the RCNs were active with exudates/hemorrhages. Of these, 5 appeared de novo in a subretinal location, with photographic evidence of no pre-existing lesions. The latter were compatible with type 3 neovascularization or retinal angiomatous proliferation and subsequently evolved into unifocal fibrotic nodules. The remaining active lesions all had some degree of pre-existing fibrosis and remained stable. Ten inactive fibrotic nodules, identical to end-stage de novo lesions, were found and were presumed to represent healed RCNs. RCN, a treatable condition, may occur as early as 2 years of age and may be much more common in patients with ESCS than previously estimated. It may be the primary cause of the unifocal submacular fibrosis that is commonly observed in this condition. Additional research is needed to establish the pathogenesis of RCN in patients with ESCS and its optimal management.

Laser and anti-vascular endothelial growth factor treatment for drusenoid pigment epithelial detachment in age-related macular degeneration

This study aims to report the 12 months results of efficacy and safety of laser photocoagulation and anti-vascular endothelial growth factor (VEGF) injections for drusenoid pigment epithelial detachment (dPED). In this prospective study, patients with treatment naïve bilateral intermediate age-related macular degeneration, featuring dPED, with visual acuity ≤ 83 letters were enrolled. The study group received PASCAL laser (532 nm) along the periphery of the dPED, and the fellow eye served as a control group. To prevent complications of choroidal neovascularization, intravitreal anti-VEGF injections to laser treated eye were performed on a 3-month interval up to 1 year. Primary outcomes—drusen area, PED height—and secondary outcomes—best-corrected visual acuity (BCVA), contrast sensitivity, degree of metamorphopsia, NEI-VFQ 25, and fundus autofluorescence—were analyzed. Among 21 patients, a total of 20 patients satisfied the 12 months follow-up. Drusen area and PED height decreased significantly in the laser group, while no significant change appeared in the control group (74.1% vs. − 3.5%, P < 0.001; 76.6% vs. 0.1%, P < 0.001). Mean BCVA improved 4.6 letters in the laser group (vs. 1.1 letters in the control group, P = 0.019). As for safety, one study eye developed retinal pigment epithelial tear, and one control eye developed retinal angiomatous proliferation. Low energy laser photocoagulation and anti-VEGF injection in eyes with dPED showed some improvement in visual acuity. dPED regressed without developing center involving GA in the study eye, but a longer term follow-up is necessary to reveal the efficacy and safety of these treatments. The 2-year results of this study will be followed to reveal long term efficacy and safety of the treatment for dPED.