Subretinal Hyperreflective Material Research Articles

Five-year outcomes of treat and extend regimen using intravitreal aflibercept injection for treatment-naïve age-related macular degeneration.

This study evaluated the long-term outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with aflibercept according to a treat-and-extend (T&E) regimen for up to 5 years. Methods This retrospective study included 112 eyes of 111 patients with nAMD who received aflibercept according to the T&E regimen. The patients received 3 monthly injections of aflibercept followed by a T&E regimen for at least 12 months. Data, including best-corrected visual acuity (BCVA), treatment interval, presence of exudation, central retinal thickness, and central choroidal thickness were analyzed. Of the 112 consecutive eyes, 66 completed the 5-year follow-up. After 5 years of treatment, BCVA (logMAR) was significantly better than baseline (0.29 ± 0.31 at baseline and 0.18 ± 0.23 at 5 years, P < 0.01). A mean of 7.0 ± 1.5 injections in the first year and 4.9 ± 2.2 injections per year thereafter were required. In eyes with subretinal hyperreflective material (SHRM) at baseline, BCVA at baseline and 5 years were significantly worse than in eyes without SHRM at baseline and 5 years. However, the eyes with SHRM required fewer injections and exhibited greater BCVA improvement. This retrospective study demonstrated the effectiveness of the T&E regimen with aflibercept in managing nAMD over a 5-year period, maintaining significant improvements in BCVA.

Clinical and Optical Coherence Tomography Features of Subretinal Fibrin Glue after Glue-Assisted Vitrectomy for Rhegmatogenous Retinal Detachment Repair. GUARD Study – Report 3:

Purpose: To highlight the clinical and optical coherence tomography (OCT) features of subretinal fibrin glue and its resolution over time in patients who have undergone glue- assisted retinopexy for Rhegmatogenous Retinal Detachments (RRD). Methods: A report of 2 cases with subretinal migration of fibrin glue. Both the cases were assessed with clinical examination, serial fundus photos and serial OCT scans through the area of subretinal fibrin immediately after surgery, at 1 week, 2 weeks and at 6 weeks. Results: In both the cases of intraoperative subretinal glue migration during glue-assisted vitrectomy for RRD repair, the subretinal glue had a characteristic appearance and course of evolution. On examination and color photography, the glue had an amorphous whitish appearance with wispy edges. This corresponded to subretinal hyperreflective material (SHRM) on OCT with a layered appearance. By two weeks after surgery, the subretinal glue demonstrated substantial regression on retinal examination and on OCT scans. At 6 weeks visit, the entire glue was noted to be resorbed along with an intact photoreceptor outer segments/Ellipsoid Zone layer Conclusion: In summary, this report describes the clinical and OCT appearance of subretinal migration of fibrin glue. Subretinal fibrin appears whitish on examination and corresponds to layered SHRM without shadowing on OCT. It appears to resorb spontaneously within weeks with apparent recovery of the overlying photoreceptors.

Pathogenesis of Central Serous ChorioRetinopathy and the Link between Choroidal Hyperpermeability and RPE Pump Reversal

Purpose: To describe 6 cases of acute central serous chorioretinopathy (CSCR) and the response to laser treatment, focusing on the underlying pathogenic mechanism. Methods: Multimodal imaging from 6 eyes of 6 patients with acute and recurrent CSCR were reviewed including fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA) and optical coherence tomography (OCT) at baseline and after laser therapy. Results: In 3 out of the 6 cases with acute CSCR, the hyporeflective lucency sign was identified with cross sectional and en face OCT and co-localized with an intense active inkblot retinal pigment epithelium (RPE) leak on FA. The development of this sign was suggestive of active leakage into the subretinal space displacing overlying subretinal hyperreflective material (SHRM) and suggestive of a reversal of RPE pump function. All six cases were treated with focal laser to directly target the intense leakage points with remarkable resolution of the fluid due to destruction of the RPE cells mediating reversal of pump function. Conclusions: Unlike chronic CSCR in which degenerative changes of the RPE lead to oozing of fluid into the subretinal space, in acute forms of CSCR including bullous CSCR, there are focal leaks of the RPE that actively drive fluid into the subretinal space suggestive of RPE pump reversal. We propose that pachychoroid disease causes increased hydrostatic pressure and increased resistance to the RPE pump thereby triggering a reversal in pump function. Understanding this concept can have therapeutic implications.

Effects of Combination Therapy with Intravitreal Ranibizumab and Tissue Plasminogen Activator for Neovascular Age-Related Macular Degeneration.

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm3 to 9.6 mm3, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM.

Early Choriocapillaris Loss in a Porcine Model of RPE Cell Debridement Precedes Pathology That Simulates Advanced Macular Degeneration.

No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling. Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1month, 2months, 3months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2months (n = 3), 3months (n = 2), or 6months (n = 2) after surgery. RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point. Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.

Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

Association Between Quantitative and Qualitative Imaging Biomarkers and Geographic Atrophy Growth Rate

Investigate associations between geographic atrophy (GA) growth rate and multimodal imaging biomarkers and patient demographics in patients with advanced non-neovascular age-related macular degeneration (nnAMD). Prospective cohort study. One hundred twenty-one eyes of 66 patients with advanced nnAMD with GA enrolled in the University of Colorado AMD Registry from August 2014 to June 2021, with follow-up through June 2023. Multimodal images were reviewed by two graders for imaging biomarkers at enrollment. GA growth rate and square-root transformed (SQRT) GA growth rate were measured between enrollment and final visit. Associations between the outcome SQRT GA growth rate and imaging biomarkers, baseline GA lesions characteristics, and patient demographics were evaluated. Average GA growth rate was 1.430 mm2/year and SQRT GA growth rate was 0.268 mm/year over a mean of 3.7 years. SQRT GA growth rate was positively associated with patient age (P = .010) and female sex (0.035), and negatively associated with body mass index (0.041). After adjustment for these demographic factors, SQRT GA growth rate was positively associated with presence of non-exudative subretinal fluid (P < .001), non-exudative subretinal hyperreflective material (P = .037), and incomplete retinal pigment epithelium and outer retina atrophy (P = .022), and negatively associated with subfoveal choroidal thickness (P = .031) and presence of retinal pseudocysts (P = .030). Larger baseline GA size at enrollment was associated with faster GA growth rate (P = .002) but not SQRT GA growth rate. Select patient demographic factors and basic clinically-relevant imaging biomarkers were associated with GA growth rate. These biomarkers may guide patient selection when considering treating GA patients with novel therapeutics.

Validation of a deep learning model for automatic detection and quantification of five OCT critical retinal features associated with neovascular age-related macular degeneration

PurposeTo develop and validate a deep learning model for the segmentation of five retinal biomarkers associated with neovascular age-related macular degeneration (nAMD).Methods300 optical coherence tomography volumes from subject eyes with...

GCN-assisted attention-guided UNet for automated retinal OCT segmentation

With the increase in the aging population of many countries, the prevalence of neovascular age-related macular degeneration (nAMD) is expected to increase. Morphological parameters such as intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), and pigment epithelium detachment (PED) of spectral-domain optical coherence tomography (SD-OCT) images are vital markers for proper treatment of nAMD, especially to get the information of treatment response to determine the proper treatment interval and switching of anti-vascular endothelial growth factor (VEGF) agents. For the precise evaluation of the change in nAMD lesions and patient-specific treatment, quantitative evaluation of the lesions in the OCT volume scans is necessary. However, manual segmentation requires many resources, and the number of studies of automatic segmentation is increasing rapidly. Improving automated segmentation performance in SD-OCT visual results requires long-range contextual inference of spatial information between retinal lesions and layers. This paper proposes a GAGUNet (graph convolution network (GCN)-assisted attention-guided UNet) model with a novel global reasoning module considering these points. The dataset used in the main experiment of this study underwent rigorous review by a retinal specialist from Konkuk University Hospital in Korea, contributing to both data preprocessing and validation to ensure a qualitative assessment. We conducted experiments on the RETOUCH dataset as well to demonstrate the scalability of the proposed model. Overall, our model demonstrates superior performance over the baseline models in both quantitative and qualitative evaluations.

Nonsurgical closure of full thickness macular hole under topical therapy in two eyes with pathologic myopia.

Non-surgical closure of a full-thickness macular hole (FTMH) with eye drops has recently been reported, but there are few similar reports in cases with pathologic myopia. (Case 1) The right eye of a 75-year-old female with an axial length of 28.83 mm had undergone anti-vascular endothelial growth factor (VEGF) treatment for choroidal neovascularization presented with FTMH. Topical betamethasone, bromfenac, and blinzolamide treatments were started, and the FTMH was closed with visual improvement (20/32 to 20/20) after 5 weeks. (Case 2) In the right eye of a 55-year-old male with an axial length of 30.81 mm and lacquer cracks, subretinal hyperreflective material and FTMH developed. The above three drugs were started after anti-VEGF drug injection. Sixteen weeks later, the FTMH was closed with visual improvement (20/63 to 20/20). Nonoperative closure of FTMH has already been reported, but few in eyes with pathologic myopia. Our results suggest that nonoperative closure of FTMH associated with pathologic myopia under eye drops may be possible in some cases.

Comparison of antiangiogenic agents (ranibizumab, aflibercept, bevacizumab and ziv-aflibercept) in the therapeutic response to the exudative form of age-related macular degeneration according to the treat-and-extend protocol- true head-to-head study

PurposeTo evaluate the structural and functional changes in eyes with neovascular age related macular degeneration (nAMD) in a real-world setting, using Treat and Extend protocol (T&E), comparing four antiangiogenic agents.MethodsProspective, observational, case series study performed in 131 patients with the exudative form of nAMD. Patients were randomly assigned into four groups according to the antiangiogenic agent. During the first year, all eyes received at least 3 monthly intravitreal injections of antiangiogenic agents, and afterwards, were submitted to the T&E.ResultsThere was statistically significant difference (p < 0.05) between pre- and post-treatment in the best corrected visual acuity measurements by drug used. Patients who used aflibercept had significantly fewer injections than patients using the other drugs (mean = 9.03). No significant difference was observed between the drugs bevacizumab, ranibizumab and ziv-aflibercept. With regard to biomarkers, patients who used aflibercept and had lower baseline central retinal thickness, absence of hyperreflective foci and no subretinal hyperreflective material had the lowest number of injections.ConclusionResults indicate that over 2 years, Intravitreal aflibercept on T&E provided better visual and anatomical improvements when compared to other drugs used in this study with significantly fewer injections.

Compartmental Exudative Dynamics in Neovascular Age-Related Macular Degeneration: Volumetric Outcomes and Impact of Volatility in a Phase III Clinical Trial

PurposeTo examine retinal feature dynamics in eyes with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (anti-VEGF) therapy and the relationship of these features with visual acuity. DesignPost hoc analysis of the phase 3, randomized, HAWK nAMD clinical trial. ParticipantsParticipants randomized to the brolucizumab 6 mg or aflibercept 2 mg arms of the trial. MethodsSpectral domain optical coherence tomography (OCT) scans collected at 4-week intervals were analyzed using an automated machine learning-enhanced segmentation and feature-extraction platform with manual verification. Quantitative volumetric measures of retinal and exudative features were exported at multiple timepoints over 48 weeks. Volatility of exudative features was calculated as the standard deviation of each feature value during the maintenance phase (week 12–48) of treatment. These features were examined for their associations with anatomic and functional outcomes. Main Outcome MeasuresLongitudinal intraretinal fluid (IRF) and subretinal fluid (SRF) volume, subretinal hyperreflective material (SHRM) volume, ellipsoid zone (EZ) integrity (EZ-retinal pigment epithelium [RPE] volume/thickness), and correlation with best corrected visual acuity (BCVA). ResultsIRF, SRF, and SHRM demonstrated significant volumetric reduction from baseline with anti-VEGF therapy (P<0.001 at each timepoint). EZ integrity measures demonstrated significant improvement from baseline (P<0.001 at each timepoint). Both EZ integrity and SHRM measures significantly correlated with BCVA at all timepoints (EZ-RPE volume: 0.38≤ r ≤0.47; EZ-RPE central subfield thickness: 0.22≤ r ≤0.41; SHRM volume: -0.33≤ r ≤-0.44). Following treatment initiation, correlations of IRF and SRF volume with BCVA were weak or nonsignificant. Eyes with lower volatility of IRF, SRF, and SHRM volumes during the maintenance phase showed greater improvements in EZ integrity (all P<0.01) and greater gains in BCVA (all P<0.01) at week 48 compared to eyes with higher volatility in those exudative parameters. ConclusionsQuantitative measures of SHRM volume and EZ integrity correlated more strongly with BCVA than retinal fluid volumes during treatment. High volatility of exudative parameters, including SRF, during the maintenance phase of treatment was associated with loss of EZ integrity and BCVA.

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...

Hyperreflective material boundary remodelling: A new morphological biomarker of good functional outcomes in neovascular age‐related macular degeneration

Aims/Purpose: To characterize the hyperreflective material (HRM) change over 9‐month follow‐up in treatment‐naïve neovascular age‐related macular degeneration (nAMD) eyes who underwent antiangiogenic treatment.Methods: Spectral‐domain optical coherence tomography images of 207 study eyes enrolled in AVENUE trial were included to analyse HRM features including location, evolvement and boundaries. We looked for the development of a highly hyperreflective band with continuity to the adjacent unaffected retinal pigment epithelium on the inner aspect of persistent HRM, which we termed complete HRM‐BR, if more than 90% of HRM was covered by this feature. Other HRM evolution patterns included complete resolution of subretinal HRM (SHRM) and partial/no remodelling of persistent SHRM. We analysed associations of HRM morphological patterns with vision and intralesional hypertransmission into the choroid (HTC), a proxy for HRM‐associated macular atrophy, at Month 9. Predictive features for complete HRM‐BR were explored.Results: At Month 9, persistent SHRM was present in 57% of the 207 included eyes. Of these, complete HRM‐BR developed in 44.9%, which was associated with greater visual outcome (+4.2 letters vs. −6.1 letter) and less intralesional HTC (20.8% vs. 69.2%) compared to partial/no HRM‐BR at Month 9. These eyes with complete HRM‐BR had similar visual outcome and intralesional HTC development to eyes with resolved SHRM (+2.2 letters; 26.8%). Presence of intralesional HTC (baseline OR 0.06, month 1 OR 0.18, p ≤ 0.01) was associated with lower odds of complete HRM‐BR development by month 9.Conclusions: In nAMD eyes undergoing antiangiogenic therapy, complete HRM‐BR developed frequently when SHRM persisted. It was associated with better visual outcome and less MA compared to eyes with partial/no HRM‐BR, and with similar outcomes compared to those with resolved SHRM. This morphological pattern can be predicted at an early stage by RPE‐related HRM features.

Role of optical coherence tomography angiography in diagnosis and management of inflammatory choroidal neovascular membrane in multifocal choroiditis – A case report

A 32-year-old male presented with decreased vision in the left eye. Fundus examination revealed healed multifocal choroiditis (MFC) and a juxtafoveal subretinal bleed. Optical coherence tomography (OCT) revealed streak subretinal fluid (SRF) and subretinal hyperreflective material (SHRM) at the macula. Fluorescein angiography (FA) showed a small area of faint hyperfluorescence adjacent to a choroiditis scar, amidst background scarring. Optical coherence tomography angiography (OCTA) detected type 2 choroidal neovascular membrane (CNV). A detailed clinical examination with appropriate ancillary imaging helps in detection of inflammatory CNV. OCTA may be superior to FA in detection of these neovascular membranes in certain case scenarios.

Improved Structure and Function in Early-Detected Second-Eye Neovascular Age-Related Macular Degeneration: FASBAT/Early Detection of Neovascular Age-Related Macular Degeneration Report 1

PurposeVisual Acuity (VA) and structural biomarker assessment before and at 24-months after early detection and routine treatment of second eye involvement with neovascular age-related macular degeneration (nAMD) and additional comparison with the first eye affected. DesignProspective, 22-centre observational study of participants with unilateral nAMD in the Early Detection of Neovascular AMD (EDNA) study, co-enrolled into the Observing fibrosis, macular atrophy and subretinal highly reflective material, before and after intervention with anti-VEGF treatment (FASBAT) study for an additional 2-year follow-up. ParticipantsOlder adults (>50 years) with new onset nAMD in the first eye. MethodsAssessment of both eyes with optical coherence tomography (OCT), colour fundus photography (CFP), clinic-measured visual acuity (VA) and quality-of-life (QoL). Main Outcome MeasuresPrevalence of Atrophy, Subretinal Hyperreflective Material (SHRM), Intraretinal fluid (IRF), Subretinal fluid (SRF) and changes in VA over the study duration in both the first and second eyes affected with nAMD. Composite QoL scores over time. ResultsOf 431 participants recruited to the FASBAT study, the second eye converted to nAMD in 100 participants at a mean of 18.9 months. VA was 18 letters better at the time of early diagnosis in the second eye compared with conventional diagnosis in the first eye (72.9 vs 55.6 letters). 24.9-months post-conversion in the second eye, VA was 69.5 letters compared with at a similar matched time point in the first eye (59.7 letters; 18.9 months). A greater proportion of participants had vision >70 letters in the second eye versus the first eye, 24.9-months post-conversion (61 vs 38). Prevalence of SHRM and IRF was lower in the second eye compared with the first eye at 24.9-months post-conversion to nAMD. However, SRF prevalence was greater in the second eye at 24.9-months post-conversion. The development and progression of total area of atrophy appears similar in both eyes. Mean composite QoL scores increased over time, with a significant correlation between VA for the second eye only 24.9 months post-conversion. ConclusionThis study has shown that early detection of exudative AMD in the second eye is associated with reduced prevalence of SHRM and IRF and greater visual acuity which is significantly correlated with maintained quality-of-life.

OCT biomarkers in wet type age related macular degeneration

OCT technology is evolving very quickly, and new retinal biomarkers are continuously described. Optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow‐up of AMD patients, which is widely used to study and guide the clinical approach, as well as to predict and evaluate treatment response.OCT biomarkers in wet type age related macular degeneration can be divided into two different categories.Biomarkers based on the retinal distribution of fluids and, structural biomarkers based on the presence or absence of specific features can be observed in the retinal layers, choroid, or vitreomacular interface.The aim of this review is to describe and analyse various structural OCT‐based biomarkers, which have practical value during both initial assessment and treatment follow‐up of wet type AMD patients.Central retinal thickness has been the most common and one of the first OCT identified biomarkers, today, other qualitative and quantitative biomarkers provide novel insight into disease activity and offer superior prognostic value and better guidance for tailored therapeutic management.The key importance of retinal fluid compartmentalization (intraretinal fluid, subretinal fluid, and subretinal pigment epithelium (RPE) fluid).In the second part, the structural alterations of different retinal layers in various stages of the disease (photoreceptors layer integrity, hyperreflective dots, outer retinal tubulations, subretinal hyperreflective material, and retinal pigment epithelial tears) will be analysed in detail.The last part of the review will focus on how alterations of the vitreoretinal interface (vitreomacular adhesion and traction) and of the choroid (sub‐RPE hyperreflective columns, pre‐choroidal clefts, choroidal caverns, choroidal thickness and choroidal volume, and choroidal vascular index) interact with AMD progression.This up‐to‐date review article provides a comprehensive description on how structural OCT‐based biomarkers provide a valuable tool to monitor the progression of the disease and the treatment response in AMD patients.

Rationale and Design of VOYAGER: Long-term Outcomes of Faricimab and Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Clinical Practice

PurposeTo describe the rationale and design of the VOYAGER (NCT05476926) study, which aims to investigate the safety and effectiveness of faricimab and the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) in routine clinical practice. VOYAGER also aims to understand drivers of real-word treatment outcomes by gaining novel insight into the intersection of treatment regimens, treatment decisions, anatomic outcomes and vision. DesignPrimary data collection, noninterventional, prospective, multinational, multicenter real-world study. ParticipantsAt least 5000 patients initiating or continuing faricimab or PDS for nAMD or DME across 500 sites in 31 countries. MethodsManagement will be per usual care, with no mandated schedule visits or imaging protocol requirements. Using robust methodologies, relevant clinical and ophthalmic data, including visual acuity (VA), and data on treatment clinical setting/regimens/philosophies, presence of anatomical features and safety events will be collected. Routinely collected fundus images will be uploaded to the proprietary Imaging Platform for analysis. An innovative investigator interface will graphically display the patient treatment journey with the aim of optimizing treatment decisions. Main Outcome MeasuresThe primary endpoint is VA change from baseline at 12 months per study cohort (faricimab in nAMD and in DME, PDS in nAMD). Secondary endpoints include VA change over time and according to treatment regimens (fixed, treat-and-extend, pro re nata, other) and number. Exploratory endpoints include VA change in relation to presence/location of anatomical features that impact vision (fluid, central subfield thickness, fibrosis, atrophy, subretinal hyperreflective material, diabetic retinopathy severity, disorganization of retinal inner layers) and according to treatment regimen/philosophies. The impact of regional and practice differences on outcomes will be assessed as will safety (ocular and nonocular adverse events). ResultsRecruitment commenced in November 2022 and will continue until late 2027 allowing for up to 5-years of follow-up. Exploratory interim analyses are planned annually. ConclusionsVOYAGER is an innovative real-world study of retinal diseases that will assess effectiveness and safety of faricimab and PDS in nAMD and DME and identify clinician- and disease-related factors driving treatment outcomes in clinical practices globally to help optimize vision outcomes for patients.

Associations of presenting visual acuity with morphological changes on OCT in neovascular age-related macular degeneration: PRECISE Study Report 2.

To study associations of optical coherence tomography (OCT) features with presenting visual acuity (VA) in treatment naive neovascular age-related macular degeneration (nAMD). Patients with nAMD initiated on aflibercept therapy were recruited from December 2019 to August 2021. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA (VA ≥ 68 ETDRS letters, Snellen ≥ 6/12) and poor VA (VA < 54 letters, Snellen < 6/18) were analysed using Generalised Estimating Equations to account for inter-eye correlation. Of 2274 eyes of 2128 patients enrolled, 2039 eyes of 1901 patients with complete data were analysed. Mean age was 79.4 (SD 7.8) years, female:male 3:2 and mean VA 58.0 (SD 14.5) letters. On multivariable analysis VA < 54 letters was associated with increased central subfield thickness (CST) (OR 1.40 per 100 µm; P < 0.001), foveal intraretinal fluid (OR 2.14; P < 0.001), polypoidal vasculopathy (PCV) relative to Type 1 macular neovascularisation (MNV) (OR 1.66; P = 0.049), presence of foveal subretinal hyperreflective material (SHRM) (OR 1.73; P = 0.002), foveal fibrosis (OR 3.85; P < 0.001), foveal atrophy (OR 5.54; P < 0.001), loss of integrity of the foveal ellipsoid zone (EZ) or external limiting membrane (ELM) relative to their preservation (OR 3.83; P < 0.001) and absence of subretinal drusenoid deposits (SDD) (presence vs absence; OR 0.75; P = 0.04). These features were associated with reduced odds of VA ≥ 68 letters except MNV subtypes and SDD. Presence of baseline fovea-involving atrophy, fibrosis, intraretinal fluid, SHRM, PCV EZ/ELM loss and increased CST determine poor presenting VA. This highlights the need for early detection and treatment prior to structural changes that worsen baseline VA.

Comparative assessment of subretinal hyper-reflective material in patients treated with brolucizumab versus aflibercept in HAWK and HARRIER

PurposePost hoc analysis of the phase III HAWK and HARRIER studies to compare the reductions in subretinal hyper-reflective material (SHRM) thickness following brolucizumab 6 mg or aflibercept 2 mg treatment...