Sub-retinal Pigment Epithelium Research Articles

Visual Outcome and Fluid Changes Between Eyes With Polypoidal Choroidal Vasculopathy Receiving Biosimilar CKD-701 or Reference Ranibizumab Therapy: A Post Hoc Analysis of a Phase 3 Randomized Clinical Trial

Purpose To compare the visual outcome and fluid features of a proposed biosimilar, CKD-701, versus the reference ranibizumab in eyes with polypoidal choroidal vasculopathy (PCV). Methods This was a post hoc analysis of a phase 3 randomized clinical trial assessing the efficacy and safety of CKD-701 and ranibizumab. A total of 73 PCV eyes were assigned randomly to either CKD-701 (36 eyes) or ranibizumab (37 eyes). The mean changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), pigment epithelial detachment (PED) volume, and fluid features were compared. Results After three loading injections, the mean change in BCVA (letters) was +7.50 in the CKD-701 group and +6.32 in the ranibizumab group (p = .447). The changes in CRT and PED volume of the CKD-701 group (−107.25 ± 102.66 μm and −0.22 ± 0.46 mm3) were similar to those of the ranibizumab group (−96.78 ± 105.00 μm and −0.23 ± 0.54 mm3) (p = .668 and p = .943, respectively). Proportions of eyes with subretinal, intraretinal and sub-retinal pigment epithelium (RPE) fluids after three loading injections were not different between CKD-701 group (33.3%, 13.9% and 42.9%) and ranibizumab group (51.4%, 16.2% and 40.0%) (p = .071, p = 1.000 and p = .808). The visual and anatomical changes were similar between two groups at month 6 and 12 (all, p > .05). Conclusion Biosimilar CKD-701 monotherapy resulted in comparable visual and anatomical changes to those achieved with reference ranibizumab in PCV eyes.

Factors related to central nervous system involvement of primary vitreoretinal lymphoma.

This single center retrospective study aimed to investigate the factors associated with central nervous system (CNS) involvement of primary vitreoretinal lymphoma (PVRL). Clinical features of patients with PVRL (Group 1), those diagnosed with vitreoretinal lymphoma (VRL) after primary CNS lymphoma diagnosis (Group 2), and those concurrently diagnosed with CNS lymphoma and VRL (Group 3), were compared. The main outcomes included sex, age, types of treatment, survival, visual acuity, diagnostic methods, VRL recurrence, ocular manifestations, and interleukin levels in the aqueous humor. Groups 1, 2, and 3 included 66 eyes in 38 patients, 29 eyes in 18 patients, and 14 eyes in 8 patients, respectively. Group 3 had shorter overall survival (OS) than Groups 1 and 2 (P = 0.042 and P = 0.009, respectively). The three groups did not differ in progression-free survival (P = 0.060). The 5-year survival rates of Groups 1, 2, and 3 were 56.5%, 44.0%, and 25.0%, respectively (P = 0.001). Patients with CNS involvement in Group 1 exhibited VRL recurrence (P < 0.001), high interleukin-10 (P = 0.024), and sub-retinal pigment epithelium (RPE) infiltration (P = 0.009). Patients experiencing VRL recurrence in Group 1 tended to show CNS involvement (P < 0.001). Patients concurrently diagnosed with CNS lymphoma and VRL had a shorter OS and a lower 5-year survival rate. In patients with PVRL, the recurrence of VRL, high interleukin-10, and sub-RPE infiltration were associated with CNS involvement.

Analysis of OCT Scanning Parameters in AMD and RVO.

Optical coherence tomography (OCT) is an extensively used imaging tool for disease monitoring in both age-related macular degeneration (AMD) and retinal vein occlusion (RVO). However, there is limited literature on minimum requirements of OCT settings for reliable biomarker detection. This study systematically investigates both the influence of scan size and interscan distance (ISD) on disease activity detection. We analyzed 80 OCT volumes of AMD patients and 12 OCT volumes of RVO patients for the presence of subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelium detachment (PED). All volume scans had a scan size of 6 × 6 mm and an ISD of 125 µm. We analyzed both general fluid distribution and how biomarker detection sensitivity decreases when reducing scan size or density. We found that in AMD patients, all fluids were nearly normally distributed, with most occurrences in the foveal center and concentric decrease towards the periphery. When reducing the scan size to 3 × 3 and 2 × 2 mm, disease activity detection was still high (0.98 and 0.96). Increasing ISD only slightly can already compromise biomarker detection sensitivity (0.9 for 250 µm ISD against 125 µm ISD).

BASELINE SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHIC RETINAL LAYER FEATURES IDENTIFIED BY ARTIFICIAL INTELLIGENCE PREDICT THE COURSE OF CENTRAL SEROUS CHORIORETINOPATHY.

To identify optical coherence tomography (OCT) features to predict the course of central serous chorioretinopathy (CSC) with an artificial intelligence-based program. Multicenter, observational study with a retrospective design. Treatment-naïve patients with acute CSC and chronic CSC were enrolled. Baseline OCTs were examined by an artificial intelligence-developed platform (Discovery OCT Fluid and Biomarker Detector, RetinAI AG, Switzerland). Through this platform, automated retinal layer thicknesses and volumes, including intaretinal and subretinal fluid, and pigment epithelium detachment were measured. Baseline OCT features were compared between acute CSC and chronic CSC patients. One hundred and sixty eyes of 144 patients with CSC were enrolled, of which 100 had chronic CSC and 60 acute CSC. Retinal layer analysis of baseline OCT scans showed that the inner nuclear layer, the outer nuclear layer, and the photoreceptor-retinal pigmented epithelium complex were significantly thicker at baseline in eyes with acute CSC in comparison with those with chronic CSC ( P < 0.001). Similarly, choriocapillaris and choroidal stroma and retinal thickness (RT) were thicker in acute CSC than chronic CSC eyes ( P = 0.001). Volume analysis revealed average greater subretinal fluid volumes in the acute CSC group in comparison with chronic CSC ( P = 0.041). Optical coherence tomography features may be helpful to predict the clinical course of CSC. The baseline presence of an increased thickness in the outer retinal layers, choriocapillaris and choroidal stroma, and subretinal fluid volume seems to be associated with acute course of the disease.

Predictors of 24-month onset of macular fibrosis in type 3 macular neovascularisation

AimsTo explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV).MethodsThis retrospective, exploratory, single-centre, cohort study comprised 65 eyes...

Long-term choroidal thickness changes based on the subtype of macular neovascularization in neovascular age-related macular degeneration (5-year follow-up).

To evaluate the long-term choroidal thickness changes in combination with other morphological and functional outcomes during anti-vascular endothelial growth factor (VEGF) treatment for neovascular age-related macular degeneration (nAMD) based on the subtype of macular neovascularization (MNV): MNV-1 (within the subretinal pigment epithelium space) and MNV-2 (within the subretinal space). This retrospective study included 58 eyes from 53 patients with naïve nAMD who received anti-VEGF therapy over a 60-month period. All eyes were treated initially with intravitreal bevacizumab following Pro re nata regimen. Main outcome measures included the following: subfoveal choroidal thickness (SFCT), best corrected visual acuity (BCVA), central macular thickness (CMT), development of subfoveal geographic atrophy (GA), and the number of injections. Thirty-four eyes had MNV-1 (group 1) and 24 eyes had MNV-2 (group 2). SFCT in group 1 vs group 2 was (210 ± 45µm vs 191 ± 52µm, p = 0.01) before treatment and (170 ± 47µm vs 179 ± 48µm, p = 0.24) after 60months. BCVA (log MAR) in group 1 vs group 2 was (0.57 ± 0.18 vs 0.53 ± 0.22, p = 0.47) before treatment and (0.59 ± 0.23 vs 0.69 ± 0.16, p = 0.04) after 60months. CMT in group 1 vs group 2 was (398 ± 154µm vs 382 ± 103µm, p = 0.86) before treatment and (297 ± 68µm vs 283 ± 67µm, p = 0.14) after 60months. The number of injections per eye over a period of 60months was significantly higher in group 1 (34.9 ± 11 vs 29.0 ± 14, p = 0.04). The proportion of eyes with subfoveal GA after 60months was significantly higher in group 2 (13 eyes, 54%) than in group 1 (9 eyes, 25%) (p = 0.03). Over the full 60months of anti-VEGF treatment, eyes with MNV-1 showed a greater reduction in choroidal thickness, better visual acuity, and less development of subfoveal geographic atrophy compared with eyes with MNV-2. The significantly thicker choroid in eyes with MNV type 1 at baseline seems to have a positive impact on long-term outcomes.

Clinical feature of cystoid macular degeneration in central serous chorioretinopathy.

Cystoid macular degeneration (CMD) is a feature of chronic central serous chorioretinopathy (CSCR). Present study intended to analyze the clinical presentation, risk factors, choroidal features, and outcome of CMD in CSCR. This was a retrospective, record-based descriptive study, which included chronic CSCR eyes with CMD. Demographic profile and clinical history were obtained from medical records. Spectralis spectral domain optical coherence tomography (SDOCT; Heidelberg Engineering,Germany) was used for acquiring SDOCT images and for performing fluorescein angiography , indocyanine green angiography , and optical coherence tomography (OCT) angiography. The study included 101 eyes of 69 consecutive patients of CSCR having CMD. The mean age of patients was 56 ± 9.4 years (range 40-79 years), and majority (63, 91.3%) of the patients were male. Prior history of corticosteroid use was present in seven (10.1%) patients. Mean time interval between the first diagnosis of CSCR and appearance of CMD was 55.3 ± 33.9 months. CMD was located away from the fovea in majority of eyes (68, 67.3%). Mean subfoveal choroidal thickness was 396.71 ± 90.5 μm. Subretinal pigment epithelium choroidal neovascularization was noted in four (3.96%) eyes. CMD appears as a late complication of CSCR and is usually present away from the fovea. Such eyes had thickened choroid and fewer cases had associated choroidal neovascularization. Further comparative studies would be needed to validate these findings.

Novel Fractal-Based Sub-RPE Compartment OCT Radiomics Biomarkers Are Associated With Subfoveal Geographic Atrophy in Dry AMD.

The purpose of this study was to quantitatively characterize the shape of the sub-retinal pigment epithelium (sub-RPE, i.e., space bounded by RPE and Bruch's membrane) compartment on SD-OCT using fractal dimension (FD) features and evaluate their impact on risk of subfoveal geographic atrophy (sfGA) progression. This was an IRB-approved retrospective study of 137 subjects with dry age-related macular degeneration (AMD) with subfoveal GA. Based on sfGA status at year five, eyes were categorized as "Progressors" and "Non-progressors". FD analysis allows quantification of the degree of shape complexity and architectural disorder associated with a structure. To characterize the structural irregularities along the sub-RPE surface between the two groups of patients, a total of 15 shape descriptors of FD were extracted from the sub-RPE compartment of baseline OCT scans. The top four features were identified using minimum Redundancy maximum Relevance (mRmR) feature selection method and evaluated with Random Forest (RF) classifier using three-fold cross validation from the training set (N = 90). Classifier performance was subsequently validated on the independent test set (N = 47). Using the top four FD features, a RF classifier yielded an AUC of 0.85 on the independent test set. Mean fractal entropy (p-value = 4.8e-05) was identified as the most significant biomarker; higher values of entropy being associated with greater shape disorder and risk for sfGA progression. FD assessment holds promise for identifying high-risk eyes for GA progression. With further validation, FD features could be potentially used for clinical trial enrichment and assessments for therapeutic response in dry AMD patients.

Drusen and Other Retinal Findings in People With IgA Glomerulonephritis

PurposeRetinal drusen have been described in people with IgA nephropathy. We examined the frequency of drusen in IgA nephropathy, and compared their location and composition with those for drusen in age-related macular degeneration. DesignImmunohistological case series of eyes of patients with IgA nephropathy, and a comparison eye with age-related macular degeneration. MethodsDonor eyes from four individuals (3 male, one female, aged 40 – 80 years) with biopsy-proven IgA nephropathy and kidney failure were examined for the presence of drusen, and location and composition using antibodies for vitronectin, IgA, IgM, IgG, C3 and C1q. Results were compared with those for drusen in macular degeneration without IgA nephropathy. ResultsAll four donors had sparse, sub-retinal pigment epithelium drusen about 55-65 μm diameter, that stained for vitronectin, but not for IgA or complement. All donors had retinal capillaries and choriocapillaris staining for IgA. The youngest donor (F, 40) had rare deposits in the outer nuclear layer that stained for IgA, but not for vitronectin. The oldest donor (M, 82) had large cyst-like spaces in the inner nuclear and plexiform layers, and smaller cysts in the outer nuclear layer, with no staining for IgA or complement. ConclusionsRetinal drusen are uncommon in IgA nephropathy, even with kidney failure. Drusen in IgA nephropathy resemble drusen found in age-related macular degeneration. IgA-staining deposits in the outer nuclear layer were likely due to systemic deposition of IgA and complement activation. The nature of cystic spaces is unknown. Further analysis of the retinae of people with glomerulonephritis is recommended.

Ultrahigh Resolution OCT Markers of Normal Aging and Early Age-related Macular Degeneration.

Ultrahigh resolution spectral domain-OCT (UHR SD-OCT) enables invivo visualization of micrometric structural markers which differentially associate with normal aging versus age-related macular degeneration (AMD). This study explores the hypothesis that UHR SD-OCT can detect and quantify sub-retinal pigment epithelium (RPE) deposits in early AMD, separating AMD pathology from normal aging. Prospective cross-sectional study. A total of 53 nonexudative (dry) AMD eyes from 39 patients, and 63 normal eyes from 39 subjects. Clinical UHR SD-OCT scans were performed using a high-density protocol. Exemplary high-resolution histology and transmission electron microscopy images were obtained from archive donor eyes. Three trained readers evaluated and labeled outer retina morphological features, including the appearance of a hyporeflective split within the RPE-RPE basal lamina (RPE-BL)-Bruch's membrane (BrM) complex on UHR brightness (B)-scans. A semi-automatic segmentation algorithm measured the thickness of the RPE-BL-BrM split/hyporeflective band. Qualitative description of outer retinal morphological changes on UHR SD-OCT B-scans; the proportion of the RPE-BL-BrM complex with visible split (%) and the thickness of the resulting hyporeflective band (μm). In young normal eyes, UHR SD-OCT consistently revealed an RPE-BL-BrM split/hyporeflective band. Its visibility and thickness were less in eyes of advanced age. However, the split/hyporeflective band was again visible in early AMD eyes. Both qualitative reading and quantitative thickness measurements showed significantly elevated visibility and thickness of the RPE-BL-BrM split/hyporeflective in early AMD eyes compared to age-matched controls. Our imaging results strongly support the hypothesis that appearance of the RPE-BL-BrM split/hyporeflective band in older subjects is dominated by the BL deposit, an indicator of early AMD well known from histology. Ultrahigh resolution SD-OCT can be used to investigate physiological aging as well as early AMD pathology in clinical imaging studies. Developing quantifiable markers associated with disease pathogenesis and progression can facilitate drug discovery, as well as reduce clinical trial times. Proprietary or commercial disclosure may be found after the references.

Histology of Type 3 Macular Neovascularization and Microvascular Anomalies in Treated Age-Related Macular Degeneration: A Case Study.

To investigate intraretinal neovascularization and microvascular anomalies by correlating invivo multimodal imaging with corresponding exvivo histology in a single patient. A case study comprising clinical imaging from a community-based practice, and histologic analysis at a university-based research laboratory (clinicopathologic correlation). A White woman in her 90s treated with numerous intravitreal anti-VEGF injections for bilateral type 3 macular neovascularization (MNV) secondary to age-related macular degeneration (AMD). Clinical imaging comprised serial infrared reflectance, eye-tracked spectral-domain OCT, OCT angiography, and fluorescein angiography. Eye tracking, applied to the 2 preserved donor eyes, enabled the correlation of clinical imaging signatures with high-resolution histology and transmission electron microscopy. Histologic/ultrastructural descriptions and diameters of vessels seen in clinical imaging. Six vascular lesions were histologically confirmed (type 3 MNV, n= 3; deep retinal age-related microvascular anomalies [DRAMAs], n= 3). Pyramidal (n= 2) or tangled (n= 1) morphologies of type 3 MNV originated at the deep capillary plexus (DCP) and extended posteriorly to approach without penetrating persistent basal laminar deposit. They did not enter the subretinal pigment epithelium (RPE)-basal laminar space or cross the Bruch membrane. Choroidal contributions were not found. The neovascular complexes included pericytes and nonfenestrated endothelial cells, within a collagenous sheath covered by dysmorphic RPE cells. Deep retinal age-related microvascular anomaly lesions extended posteriorly from the DCP into the Henle fiber and the outer nuclear layers without evidence of atrophy, exudation, or anti-VEGF responsiveness. Two DRAMAs lacked collagenous sheaths. External and internal diameters of type 3 MNV and DRAMA vessels were larger than comparison vessels in the index eyes and in aged normal and intermediate AMD eyes. Type 3 MNV vessels reflect specializations of source capillaries and persist during anti-VEGF therapy. The collagenous sheath of type 3 MNV lesions may provide structural stabilization. If so, vascular characteristics may be useful in disease monitoring in addition to fluid and flow signal detection. Further investigation with longitudinal imaging before exudation onset will help determine if DRAMAs are part of the type 3 MNV progression sequence. Proprietary or commercial disclosure may be found after the references.

Advances in multi-modal non-invasive imaging techniques in the diagnosis and treatment of polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is a disease characterized by subretinal pigment epithelium (RPE) orange-red polypoidal lesions and abnormal branching neovascular networks (BNNs). In recent years, various non-invasive imaging technologies have rapidly developed, especially the emergence of optical coherence tomography angiography (OCTA), multi-spectral imaging, and other technologies, which enable the observation of more features of PCV. In addition, these technologies are faster and less invasive compared to indocyanine green angiography (ICGA). Multi-modal imaging, which combined multiple imaging techniques, provides important references for the diagnosis and treatment of PCV with the assistance of regression models, deep learning, and other algorithms. In this study, we reviewed the non-invasive imaging techniques, multi-modal imaging diagnosis, and multi-scene therapeutic applications of PCV, with the aim of providing a reference for non-invasive multi-modal diagnosis and treatment of PCV.

Screening for biomarkers in age-related macular degeneration

ObjectiveAge-related macular degeneration (AMD) is a significant cause of blindness, initially characterized by the accumulation of sub-Retinal pigment epithelium (RPE) deposits, leading to progressive retinal degeneration and, eventually, irreversible vision loss. This study aimed to elucidate the differential expression of transcriptomic information in AMD and normal human RPE choroidal donor eyes and to investigate whether it could be used as a biomarker for AMD. MethodsRPE choroidal tissue samples (46 Normal samples, 38 AMD samples) were obtained from the GEO (GSE29801) database and screened for differentially expressed genes in normal and AMD patients using GEO2R and R to compare the degree of enrichment of differentially expressed genes in the GO, KEGG pathway. Firstly, we used machine learning models (LASSO, SVM algorithm) to screen disease signature genes and compare the differences between these signature genes in GSVA and immune cell infiltration. Secondly, we also performed a cluster analysis to classify AMD patients. We selected the best classification by weighted gene co-expression network analysis (WGCNA) to screen the key modules and modular genes with the strongest association with AMD. Based on the module genes, four machine models, RF, SVM, XGB, and GLM, were constructed to screen the predictive genes and further construct the AMD clinical prediction model. The accuracy of the column line graphs was evaluated using decision and calibration curves. ResultsFirstly, we identified 15 disease signature genes by lasso and SVM algorithms, which were associated with abnormal glucose metabolism and immune cell infiltration. Secondly, we identified 52 modular signature genes by WGCNA analysis. We found that SVM was the optimal machine learning model for AMD and constructed a clinical prediction model for AMD consisting of 5 predictive genes. ConclusionWe constructed a disease signature genome model and an AMD clinical prediction model by LASSO, WGCNA, and four machine models. The disease signature genes are of great reference significance for AMD etiology research. At the same time, the AMD clinical prediction model provides a reference for early clinical detection of AMD and even becomes a future census tool. In conclusion, our discovery of disease signature genes and AMD clinical prediction models may become promising new targets for the targeted treatment of AMD.

New Concepts for the Diagnosis of Polypoidal Choroidal Vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration (nAMD) that is characterized by a branching neovascular network and polypoidal lesions. It is important to differentiate PCV from typical nAMD as there are differences in treatment response between subtypes. Indocyanine green angiography (ICGA) is the gold standard for diagnosing PCV; however, ICGA is an invasive detection method and impractical for extensive use for regular long-term monitoring. In addition, access to ICGA may be limited in some settings. The purpose of this review is to summarize the utilization of multimodal imaging modalities (color fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and fundus autofluorescence (FAF)) in differentiating PCV from typical nAMD and predicting disease activity and prognosis. In particular, OCT shows tremendous potential in diagnosing PCV. Characteristics such as subretinal pigment epithelium (RPE) ring-like lesion, en face OCT-complex RPE elevation, and sharp-peaked pigment epithelial detachment provide high sensitivity and specificity for differentiating PCV from nAMD. With the use of more practical, non-ICGA imaging modalities, the diagnosis of PCV can be more easily made and treatment tailored as necessary for optimal outcomes.

Establishment and characterization of an iPSC line (UCLi023-A) derived from a Late-Onset Retinal Degeneration patient carrying a founder mutation in C1QTNF5

Late-Onset Retinal Degeneration (L-ORD) is a rare autosomal dominant macular disease, with most cases being caused by a founder mutation in C1QTNF5. Initial symptoms, which generally occur during or after the sixth decade, include abnormal dark adaptation and changes in peripheral vision. Over time, the build-up of sub-retinal pigment epithelium (RPE) deposits leads to macular atrophy and bilateral central vision loss1. Here, we describe the generation of a human induced pluripotent stem cell (iPSC) line from dermal fibroblasts of a 61-year-old L-ORD Caucasian male patient carrying the founder mutation (c.489C>G, p.Ser163Arg), using episomal reprogramming.

Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.

The complement system is crucial for immune surveillance, providing the body's first line of defence against pathogens. However, an imbalance in its regulators can lead to inappropriate overactivation, resulting in diseases such as age-related macular degeneration (AMD), a leading cause of irreversible blindness globally affecting around 200 million people. Complement activation in AMD is believed to begin in the choriocapillaris, but it also plays a critical role in the subretinal and retinal pigment epithelium (RPE) spaces. Bruch's membrane (BrM) acts as a barrier between the retina/RPE and choroid, hindering complement protein diffusion. This impediment increases with age and AMD, leading to compartmentalisation of complement activation. In this review, we comprehensively examine the structure and function of BrM, including its age-related changes visible through in vivo imaging, and the consequences of complement dysfunction on AMD pathogenesis. We also explore the potential and limitations of various delivery routes (systemic, intravitreal, subretinal, and suprachoroidal) for safe and effective delivery of conventional and gene therapy-based complement inhibitors to treat AMD. Further research is needed to understand the diffusion of complement proteins across BrM and optimise therapeutic delivery to the retina.

Ten-Year Incidence of Fibrosis and Risk Factors for Its Development in Neovascular Age-Related Macular Degeneration

To report the incidence and risk factors for fibrosis at 10 years in a large cohort of persons with neovascular age-related macular degeneration (nAMD). Retrospective, multicenter, cohort study. We included 225 naive nAMD eyes that underwent intravitreal anti-vascular endothelial growth factor treatment over 10 years of follow-up at two Italian referral centers. Demographic and clinical data were reviewed at baseline and on an annual basis. Onset of fibrosis was defined by clinically assessing photographs, fundus descriptions, or fluorescein angiograms. Optical coherence tomography (OCT) scans of fibrosis were inspected by an external reading center and graded as subretinal pigment epithelium (RPE), mixed, or subretinal. The mean age at baseline was of 72.1 ± 6.9 years. The incidence rate of fibrosis was estimated to be 8.9 per 100 person-years, with a cumulative incidence of 62.7% at 10 years. Fibrotic lesions were sub-RPE in 46.1%, mixed in 29.8%, and subretinal in 22.7%. Independent factors associated with fibrosis included the following: larger central subfield thickness variation (P < .001), submacular hemorrhages (P=.008), higher number of injections (P=.01), and worse baseline visual acuity (VA) (P=.03). Type 2 macular neovascularization was significantly associated with mixed and subretinal fibrosis. VA significantly declined over 10 years (-16.4 Early Treatment Diabetic Retinopathy Study [ETDRS] letters), particularly in eyes with mixed and subretinal fibrosis (P < .001). We identified a 62.7% cumulative incidence of fibrosis in a large nAMD cohort at 10 years. Fibrosis was more common with frequent reactivations and lower baseline VA; its onset had a significant impact on final VA. This supports the hypothesis that nAMD patients should be promptly treated with proactive regimens.

Brolucizumab for Neovascular Age-Related Macular Degeneration (BEL Study).

This retrospective observational study reports early results on a cohort of neovascular age-related macular degeneration (nAMD) patients switched to brolucizumab, a recently approved anti-vascular endothelial growth factor (anti-VEGF). We evaluated best-corrected visual acuity (BCVA), treatment interval, central subfield retinal thickness (CST) and the presence of intra-retinal (IRF), subretinal (SRF) and/or sub-retinal pigment epithelium (sub-RPE) fluid on optical coherence tomography (OCT). Concurrently, patients were carefully examined for signs of intra-ocular inflammation (IOI) and other adverse events. Seventeen patients (19 eyes) were included. The difference in BCVA at baseline compared to the last examination following brolucizumab injection was not statistically significant (Wilcoxon signed-rank test, p=0.247). Mean CST decrease was -5.16 ±48.28 µm (p=0.647). A morphological improvement in IRF was observed in four eyes, with a complete resolution in 50% (n=2) and a decrease in 50% (n=2). Regarding SRF (total n=15), resolution was seen in 46.67% (n=7), decrease in 26.67% (n=4) and stabilization in 13.33% (n=2). Increase in SRF was observed in 13.33% (n=2). Of 14 eyes with sub-RPE fluid, 7.14% (n=1) demonstrated a resolution, 42.86% (n=6) a decrease, 50% (n=7) a stabilization and none an increase in fluid. Mean treatment interval was increased by 4.08 ±1.40 weeks (p<0.001). Treatment was discontinued in seven eyes (41.18%), including four cases due to IOI. In all four cases, inflammation was mild and resolved under corticosteroid treatment. No cases of vasculitis were observed. This study provides additional data suggesting that brolucizumab is a beneficial alternative for patients refractory to other anti-VEGF therapies. It can provide a morphological reduction in fluid and prolong the treatment interval, while maintaining a stable BCVA and CST. However, as a higher occurrence of IOI is probable, patients should be informed, selected and monitored carefully. Signs of inflammation should be detected early and treated promptly.

Данные о распределении патологической ретинальной жидкости у пациентов с неоваскулярной возрастной макулярной дегенерацией, получавших антиангиогенную терапию в течение 5 лет в условиях реальной клинической практики

Purpose. To analyze the distribution of pathological retinal fluids according to optical coherence tomography (OCT) over time in patients with neovascular age-related macular degeneration (nAMD) who received anti-angiogenic therapy for 5 years. Material and methods. A retrospective analysis of OCT data of patients treated with anti-VEGF therapy (ranibizumab, aflibercept) in the 3+PRN regimen was performed. The study group consisted of 24 patients (79.2 % women, mean age 70.5 years). Results. Best corrected visual acuity increased from the initial 0.31 0.42 0.52 to 0.40 0.50 0.60 (p = 0.00028) by the 60th month. Central retinal thickness decreased from initial 304.0 343.4 382.7 µm to 190.6 209.8 229.1 µm (p &lt; 0.00001). Significant correlation indicators according to Spearman (p &lt; 0.05) were established in relation to an increase in the proportion of patients who had a «dry» retina and cases of subretinal fluid (SRF) resolution. Using the method of proportions, a significant (p &lt; 0.05) increase in the proportion of patients without pathological fluid was determined, as well as a decrease in the percentage of patients with SRF and sub-retinal pigment epithelium fluid, which were achieved in the first year of therapy and maintained until the end of the study, as well as a decrease in the proportion of patients with intraretinal fluid, which achieved a statistical significance (p &lt; 0.05) by the 60th month. Conclusion. One of the indicators confirming the high efficiency of long-term (60 months) anti-VEGF therapy for nAMD was a decrease in the proportion of patients with all compartments of the pathological retinal fluid. Keywords: age-related macular degeneration, anti-VEGF therapy, optical coherence tomography, retinal fluid, biomarkers

Exploring Imaging Characteristics Associated With Disease Activity in Idiopathic Multifocal Choroiditis: A Multimodal Imaging Approach

To identify characteristics on multimodal imaging (MMI) in idiopathic multifocal choroiditis (MFC) that can identify inflammatory activity and distinguish choroidal neovascularization (CNV) activity from inflammatory activity. Prospective cohort study. MMI consisted of spectral-domain optical coherence tomography (angiography) (SD-OCT(A)), fundus autofluorescence, fundus photography, infrared imaging, fluorescein angiography (FA), and indocyanine green angiography (ICGA). MMI characteristics obtained during active and inactive disease were compared within the same lesion. Secondly, MMI characteristics were compared between active inflammatory lesions with and without CNV activity. Fifty patients (110 lesions) were included. In 96 lesions without CNV activity, the mean focal choroidal thickness was increased during the active disease (205 µm) compared to the inactive disease (180 µm) (P ≤ .001). Lesions with inflammatory activity typically demonstrated moderately reflective material located in the sub-retinal pigment epithelium (RPE) and/or in the outer retina with disruption of the ellipsoid zone. During the inactive stage of the disease, the material disappeared or became hyperreflective and indistinguishable from the RPE. During the active stage of the disease, the area of hypoperfusion in the choriocapillaris significantly increased as visualized on both ICGA and SD-OCTA. CNV activity in 14 lesions was associated with subretinal material with a mixed reflectivity and hypotransmission of light to the choroid on SD-OCT and leakage on FA. SD-OCTA identified vascular structures in all active CNV lesions and in 24% of lesions without CNV activity (showing old, quiescent CNV membranes). Inflammatory activity in idiopathic MFC was associated with several MMI characteristics, including focally increased choroidal thickness. These characteristics can guide clinicians in the challenging process of the evaluation of disease activity in idiopathic MFC patients.