Presence Of Intraretinal Fluid Research Articles

Transitioning from Aflibercept to Biosimilar Ranibizumab in Neovascular AMD (The TRANSFORM Trial): A Multicenter Observational Study

Transitioning from Aflibercept to Biosimilar Ranibizumab in Neovascular AMD (The TRANSFORM Trial): A Multicenter Observational Study

NONEXUDATIVE INTRARETINAL FLUID IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.

To describe the occurrence of nonexudative intraretinal fluid (IRF) in intermediate age-related macular degeneration. A retrospective study was designed to include consecutive cases with intermediate age-related macular degeneration associated with IRF. A multimodal imaging approach was used to confirm diagnosis of IRF in intermediate age-related macular degeneration. Multimodal imaging included color fundus photograph, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography. Ten eyes of 10 patients (2 male and 8 female patients, ages 68-80 years) showing IRF in intermediate age-related macular degeneration were included in the study. The mean best-corrected visual acuity was 20/40 Snellen equivalent. Multimodal imaging including fluorescein angiography/indocyanine green angiography and optical coherence tomography demonstrated the absence of macular neovascularization in all cases; optical coherence tomography-angiography did not detect any abnormal flow signal associated with IRF. Seven of 10 patients developed IRF in correspondence of pigment epithelium detachment. Three of 10 patients presented IRF in correspondence of an area of nascent geographic atrophy. Nonexudative intraretinal fluid in intermediate age-related macular degeneration is a novel, distinctive feature that is characterized by the presence of IRF with no evidence of macular neovascular lesions. The authors described different phenotypes of IRF in intermediate age-related macular degeneration. The definite diagnosis of this condition requires further studies with thorough application of multimodal imaging.

Analysis of prognostic and predictive factors in neovascular age-related macular degeneration Kuopio cohort.

The aim of the study was to explore factors affecting the progression of neovascular age-related macular degeneration (nAMD) and identify predictive factors that can estimate the duration of intravitreal treatments. This retrospective real-world study included 421 nAMD patients treated at the Kuopio University Hospital during years 2007-2021. The collected data included background demographics, treatment history, visual acuity and retinal biomarker analysis. Impact of baseline factors on age at diagnosis, treatment duration, received treatment intensity and visual acuity gains were analysed. Heavy smoking and high body mass index (BMI) were associated with an earlier onset, while the use of anticoagulation and anti-aggregation medication were associated with a later onset of nAMD. A low number of injections during the first year of treatment and the presence of intraretinal fluid (IRF) at baseline were associated with shorter treatment duration. Interestingly, when IRF only patients were compared to subretinal fluid (SRF) only patients, IRF patients showed higher occurrences of subretinal drusenoid deposits (43.5% vs. 15%, p = 0.04). In addition, when all patients with IRF were compared to SRF only patients, more hyperreflective foci (HRF) and complete RPE and outer retinal atrophy (cRORA; 20.7% vs. 5%, p = 0.02) were observed in patients with IRF. Our results reveal that heavy smoking and high BMI are accelerating factors for earlier emergence of nAMD, while the presence of IRF results in a fast-progressing disease. More intriguingly, the link between IRF and appearance of subretinal drusenoid deposits, HRF, and increased retinal atrophy was observed.

Clinical and Imaging Biomarkers Associated with Outer Retinal Atrophy Onset in Exudative Age-Related Macular Degeneration: A Real-Word Prospective Study.

Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.

Risk factors for failing sub-Tenon’s triamcinolone acetonide for uveitic macular edema

BackgroundSub-Tenon’s triamcinolone acetonide (STA) is less effective than intravitreal corticosteroids in the treatment of uveitic macular edema (ME), but does have some relative advantages, including substantially lower cost and decreased risk of post-injection ocular hypertension. It would be useful for clinicians to know which eyes may respond well to STA and not necessarily require intravitreal therapy. The objective of this study is to identify risk factors for failing STA for the treatment of uveitic ME.Main bodyA retrospective cohort study was performed. Medical records were reviewed of patients who underwent STA for the treatment of uveitic ME between January 1, 2013, and July 31, 2022, at the University of Colorado Hospital. Uveitic ME was defined by a central subfield thickness (CST) greater than 320 μm or the presence of intra-retinal cystoid spaces on optical coherence tomography (OCT), or by the presence of petaloid macular leakage on fluorescein angiography (FA). Data collected included age, race/ethnicity, sex, history of diabetes mellitus, anatomic classification of uveitis, use of corticosteroids, use of immunomodulatory therapy, presence of intra-retinal fluid on OCT, CST on OCT, and presence of petaloid macular leakage on FA. STA failure was defined as the need for additional therapy within 12 weeks of STA due to persistent or worsening uveitic ME. One hundred eighty eyes from 131 patients were included. Forty-two eyes (23.3%) were considered treatment failures. In univariate and multivariable analysis, higher baseline CST was associated with a higher likelihood of failing STA (OR 1.17 for each 30 μm increase in CST, P = 0.016).ConclusionsSTA, while not as potent as intravitreal corticosteroids for the treatment of uveitic ME, was still an effective therapy, particularly for patients with lower baseline CST. Given its lower side effect profile and cost compared to intravitreal treatments, clinicians could consider STA as an initial treatment for mild uveitic ME.

Analysis of prognostic and predictive factors in Kuopio wet age‐related macular degeneration cohort

Aims/Purpose: Aim of this study was to explore factors affecting wet AMD disease progression and identify predictive factors that can estimate the time of intravitreal treatment duration.Methods: This retrospective real‐world study included 421 wet AMD patients treated at Kuopio University Hospital during years 2007–2021. Collected data included background demographics, treatment history, best‐corrected visual acuity (BCVA) and anatomical changes. Impact of baseline factors to age at diagnosis, treatment duration, received treatment intensity and visual acuity gains was analysed.Results: Heavy smoking and high BMI were associated with an earlier onset of wet AMD. Whereas, use of anti‐coagulation, anti‐aggregation and blood pressure medication were associated with later onset of wet AMD. Low number of injections during the first year and presence of intraretinal fluid (IRF) at baseline were associated with shorter treatment duration. Interestingly, when IRF only patients were compared to subretinal fluid (SRF) only patients, IRF patients showed higher occurrences of subretinal drusenoid deposits (43.5% vs. 15%, p = 0.04). In addition, when all patients with IRF were compared to SRF only patients, more hyperreflective foci (HRFs) and complete RPE and outer retinal atrophy (cRORA, 20.7% vs. 5%, p = 0.02) were observed with IRF patients.Conclusions: Our results raise up number of factors involved in disease progression. They confirm previously described role of heavy smoking, high BMI and IRF as factors, which may accelerate earlier emergence of nAMD or result as fast progressing disease. More intriguingly, our result reveals the link between IRF and appearance of subretinal drusenoid deposits, HRFs and cRORA.

Are intravitreal hyperreflective particles alike in eyes with acute toxoplasma chorioretinitis and non-infectious uveitis?

BackgroundTo compare distinctive features of hyperreflective particles observed on spectral-domain optical coherence tomography (OCT) sections in eyes with acute toxoplasma chorioretinitis (TC) and non-infectious uveitis (NIU). MethodsMedical records and the spectral-domain OCT images of the patients with TC and NIU were retrospectively reviewed. The TC and NIU groups were compared in terms of age, sex, mean OCT image quality, mean central macular thickness (CMT), presence of intraretinal fluid (IRF), presence of subretinal fluid (SRF), number of hyperreflective particles in the posterior vitreous area and mean particle measurement in the posterior vitreous area. ResultsNon-infectious uveitis group included nine patients (60 %) with Behcet's uveitis, five patients (33.3 %) with idiopathic posterior uveitis or panuveitis, and the remaining patient (6.7 %) with HLA-B27 associated uveitis. Comparison of the mean age, sex distribution, mean OCT image quality, mean CMT, presence of IRF, presence of SRF and the mean number of hyperreflective particles in the posterior vitreous area between the two groups showed no statistically significant differences (p = 0.085, p = 0.051, p = 0.748, p = 0.431, p = 0.109, p = 0.080 and p = 0.152, respectively). However, the mean length of the hyperreflective particles in the posterior vitreous area was 27.22 ± 8.60 μm in the TC group, and 21.91 ± 3.58 μm in the NIU group, with a significant difference between the two groups (p = 0.036). ConclusionThis pilot study aimed to assess the hyperreflective particles in the posterior vitreous area using spectral-domain OCT images and image processing software. Despite its limitations, such as the small sample size, limited understanding of the nature of hyperreflective particles, and the absence of differentiation between acute and chronic uveitis, our study points out the potential role of the measurement of the hyperreflective particle length located in the posterior vitreous in differentiating the acute infectious versus non-infectious uveitis as the hyperreflective particles tend to be larger in infectious cases.

Short-Term Outcomes of Faricimab in Patients with Neovascular Age-Related Macular Degeneration on Prior Anti-VEGF Therapy

A subset of patients with neovascular age related macular degeneration (nAMD) experience treatment burden and suboptimal response with anti-vascular endothelial growth factor (anti-VEGF) therapy. The aim of this study was to investigate the effect of switching to a novel bi-specific agent, faricimab, in patients with nAMD currently treated with anti-VEGF. Retrospective, non-comparative cohort study. Patients with nAMD previously treated with anti-VEGF and switched to intravitreal faricimab injection (IFI) at the Cleveland Clinic's Cole Eye Institute. Switching and administration schedule of IFI was at the discretion of the clinician. Visual acuity (VA) and macular optical coherence tomography (OCT) parameters, including central subfield thickness (CST), maximum pigment epithelial detachment (PED) height and presence of subretinal (SRF) or intraretinal fluid (IRF), were assessed at baseline (day of first IFI) and after each IFI. CST and presence of IRF or SRF after at least 3 IFI. 126 eyes of 106 patients were included in the analysis with a mean follow-up time of 24.3±5.2 weeks. Prior to switching to IFI, patients received a mean of either aflibercept (20.0±18.4, mean±SD), bevacizumab (7±8.9), ranibizumab (1.9±8.5), or brolucizumab (0.3±1.6) injections. The most common agent used prior to switching to IFI was aflibercept (n=110, 87%), and the mean treatment interval with any anti-VEGF of 5.6±1.6 weeks prior to switching. CST was reduced from baseline after the first IFI (266.8±64.7 vs 249.8±58.6um, p=0.02) and persisted over the 3 IFIs (p=0.01). PED height was reduced after the 3rd IFI (249.6±179.0 vs 206.9±130.0um, p=0.01). Mean VA (62.9 vs 62.7 approximate EDTRS letters, p=0.42) and interval between injections was similar after the 3rd IFI compared to baseline (6.3 vs 5.7 weeks, p=0.16). Eleven (8.7%) eyes were switched back to their previous anti-VEGF, including 2 (1.6%) eyes from 1 patient with intraocular inflammation requiring cessation of IFI. There were no other adverse events from switching. Switching to faricimab resulted in a reduction in mean CST (-11.6um, p=0.01) and PED height (-44.2um, p=0.01) after 3 injections with stable VA and at a similar treatment interval to prior anti-VEGF therapy.

Efficacy, Safety, and Durability of Brolucizumab: An 8-Month Post-Marketing Surveillance Analysis.

Brolucizumab (Beovu®) is an anti-vascular endothelial growth factor (anti-VEGF) agent approved for the treatment of neovascular age-related macular degeneration (nvAMD). Brolucizumab was marketed for its noninferiority to aflibercept and its potential for greater durability. However, post-marketing utilization has been tempered by safety concerns. We evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world. This was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020. Changes in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events. The majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-naïve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001). Brolucizumab treatment was associated with VA improvement in naïve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee's analysis of HAWK and HARRIER.

The Localization of Intraretinal Cysts Has a Clinical Role on the 2-Year Outcome of Neovascular Age-Related Macular Degeneration

To assess the relationship between ≥ 1 localizations of intraretinal fluid (IRF) within retinal layers and the 2-year outcome in a cohort of neovascular age-related macular degeneration (AMD) eyes. Retrospective case series. Two hundred forty-three eyes of 243 AMD patients affected by type 1 and type 2 macular neovascularization (MNV). We analyzed data considering MNV onset, 1-year, and 2-year timepoints. Optical coherence tomography images were used to classify MNV types, distinguish different types of fluids and assess IRF localization within retinal layers. A subcohort of eyes were also analyzed by OCT angiography. The association between IRF cyst localization and both visual outcome and onset of outer retinal atrophy at 2-year follow-up. Macular neovascularizations were distributed as type 1 (69%) and type 2 (31%). The mean number of intravitreal injections was 7 ± 2 at 1-year follow-up and 5 ± 2 at 2-year follow-up. Baseline best-corrected visual acuity was 0.4 ± 0.3 logarithm of the minimum angle of resolution, improving to 0.3 ± 0.4 at 2-year follow-up (P < 0.01). Outer retinal atrophy occurred in 24% of cases at 1 year and 39% of cases at 2-year follow-up. Intraretinal fluid localizations at the level of IPL-INL and OPL-ONL at baseline were associated with the worst functional and anatomical outcome. Moreover, the presence of IRF at baseline was associated with greater impairment of the intraretinal vascular network. The localization of IRF at the level of IPL-INL and OPL-ONL retinal layers represents a negative prognostic biomarker for the morphologic and functional outcomes of neovascular AMD. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Effect of Intravitreal Aflibercept on Wet Age-Related Macular Degeneration and Evaluation of Risk Factors on Patient’s Response

Purpose: To evaluate the effect of intravitreal Aflibercept injection on wet AMD both functionally and anatomically after loading doses. The secondary aim is to evaluate the effect of risk factors including (gender, age, smoking, hypertension, and diabetes meatus) on the patient’s response. Study Design: Interventional case series. Place and Duration of Study: Al-Haitham Eyes Teaching Hospital in Baghdad, Iraq, from November 2021 and September 2022. Methods: Fifty eyes of 47 patients with treatment naïve wet AMD were selected through convenient sampling. Data were collected for age, gender, smoking, and chronic disease. Clinical examination, best corrected visual acuity (BCVA), optical coherence tomography angiography, and spectral domain optical coherence tomography SD-OCT were performed at baseline and then at 16 weeks, after three one-monthly injections of Aflibercept 2 mg/ 0.05 ml intravitreally. Results: Mean age was 68.23 ± 8.5 years. Mean difference in BCVA was 0.37 ± 0.03 (P = 0.000) and mean difference in central macular thickness was 105.72 ± 45.05 (P value &lt; .0000) at 16 weeks. CNV was associated with intra-retinal fluid in 52% of cases, subretinal fluid in 72%, pigment epithelial detachment in 20%, intraretinal hemorrhage in 6% and subretinal hemorrhage in 4%. Studying associations between the responses of Aflibercept with the general features of the patients as age, gender, chronic diseases and smoking status, revealed no statistically significant difference. Conclusion: This study demonstrates that aflibercept is effective for the treatment of patients with wet AMD both functionally and anatomically after the loading doses. The presence of intraretinal fluid at presentation had a negative effect on the vision.

Tomographic prognostic factors for visual improvement after pars plana vitrectomy for epiretinal membrane

AbstractPurpose: To evaluate postoperative changes and investigate tomographic prognostic factors of visual impairment after vitrectomy for epiretinal membrane (ERM).Methods: A retrospective observational study on patients who underwent pars plana vitrectomy for ERM by a single experimented surgeon. Best corrected visual acuity (BCVA) on the logMAR chart and optical coherence tomography (OCT) features were recorded before surgery and at the last visit. Tomographic parameters analysed were: central foveal thickness (CFT), foveal contour morphology, external limiting membrane (ELM), ellipsoid zone (EZ) and interdigitation zone (IZ) integrity, the presence of intraretinal fluid (IRF), subretinal fluid, disorganization of retinal inner layers (DRIL) and subfoveal deposits. Student's t‐test and Pearson's correlation coefficients were used for statistical analysis. p Values &lt;0.05 were considered statistically significant.Results: Forty‐seven eyes of 43 patients were included. The mean age was 61.7 years (range 13–87). The ERM was idiopathic in 49% and secondary in 51%. The mean BCVA was 1.02 before and 0.5 after surgery and improved significantly (p &lt; 0.001) with a mean gain of 5.2 lines. The postoperative BCVA correlated strongly with the preoperative one (R2 = 0,764, p &lt; 0.001). Tomographic factors associated with worse final BCVA were higher baseline CFT (p = 0.004), abnormal foveal profile (p = 0.02), the presence of IRF (p &lt; 0.001), DRIL (p = 0.01) and subfoveal deposits (p = 0.04). The disruption of ELM, EZ and IZ were as well associated with a poorer visual outcome (p &lt; 0.001, p = 0.03 and p &lt; 0.001 respectively).Conclusions: ERM surgery provides functional and anatomical improvement. Preoperative OCT is an essential tool to evaluate morphological retinal changes and identify prognostic factors for visual recovery.

Multifocal electroretinographic findings in angiographic macular leakage in the setting of intermediate, posterior, or panuveitis

ObjectifÉvaluer les retombées fonctionnelles de l'exsudat maculaire visible à l'angiographie en l'absence de liquide intrarétinien lors de la tomographie par cohérence optique (OCT) dans des yeux présentant une uvéite intermédiaire, une uvéite postérieure ou encore une panuvéite. MéthodesIl s'agit d'une étude rétrospective portant sur des patients qui ont reçu un diagnostic d'uvéite intermédiaire, d'uvéite postérieure ou encore de panuvéite. Ont été inclus les patients qui ont fait l'objet d'une angiographie à la fluorescéine, d'une OCT et d'une électrorétinographie multifocale (ERGmf) selon un échéancier déterminé. Les données démographiques et cliniques comprenaient le type d'inflammation oculaire, la meilleure acuité visuelle corrigée (MAVC) et les résultats de l'OCT, de l'angiographie à la fluorescéine et de l'ERGmf. Les patients ont été répartis en 2 groupes en fonction de la présence d'un exsudat maculaire visible à l'angiographie et d'un œdème maculaire: groupe 1 (aucun œdème maculaire ni exsudat maculaire) et groupe 2 (présence d'un exsudat maculaire sans œdème maculaire). RésultatsAu total, 29 patients (43 yeux) ont été inclus dans l’étude : 13 patients (17 yeux) dans le groupe 1 et 16 patients (26 yeux) dans le groupe 2. On n'a pas noté de différence statistiquement significative entre les 2 groupes au chapitre des paramètres suivants : âge, sexe, cellules de la chambre antérieure, état du cristallin, cellules du vitré, flou vitréen, MAVC ou épaisseur sous-fovéale centrale moyenne. Aucune des mesures obtenues à l'ERGmf, notamment l'amplitude et les temps de culmination des ondes N1 et P1 dans les anneaux 1–5, n'a différé de manière statistiquement significative entre les 2 groupes. Enfin, aucune corrélation n'a pu être établie entre la MAVC ou l’épaisseur sous-fovéale centrale moyenne et l'une ou l'autre des mesures obtenues à l'ERGmf pour les anneaux 1–3. ConclusionsDans des yeux atteints d'uvéite exempts d’œdème maculaire, l'atteinte de la fonction maculaire n'est pas nécessairement pire en présence d'un exsudat maculaire visible à l'angiographie.

Association between structural and functional treatment outcomes in neovascular age-related macular degeneration.

The administration frequency of intravitreal anti-vascular endothelial growth factor (anti-VEGF) in neovascular age-related macular degeneration (AMD) have been widely discussed. The primary objective of the study was to explore the association between anatomical outcomes and changes in functional outcome. This was a retrospective cohort study of patients with newly diagnosed neovascular AMD with a minimum of 12 months of follow-up. Only one eye per patient was included. Patients were treated according to the observe-and-plan or the pro-re-nata regimen. All patients were regularly examined from the time of diagnosis up to 24 months. The effect of intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelium detachment (PED) at any time point on visual acuity (VA) was tested, as well as the long-term effect and the risk of losing VA. Further, the variability of central retinal thickness (CRT) was calculated for each eyes' individual measures during the observation period, excluding the monthly loading phase. The prognostic effect of each factor on VA was estimated by regression analysis. The primary outcome measure was VA, which was correlated with the presence or absence of fluid, seen as IRF, SRF or PED. A total of 504 treatment naïve eyes from 504 patients was included. The presence of IRF was associated with lower VA at all visits (p < 0.001). However, the presence of SRF or PED was not significantly associated with worse VA at any time point during the observation period. Patients in the upper quartile of CRT variance had a greater loss in VA after 12 and 24 months (p < 0.001). In this retrospective cohort study, the presence of intraretinal fluid was associated with poorer visual outcome in neovascular AMD patients treated with anti-VEGF, but the presence of subretinal fluid and PEDs was not. This suggests that IRF is worse than subretinal fluid and PEDs for AMD outcomes and therefore requires the most intensive treatment. Further, we found that patients with the highest CRT variability during the study period had poorer visual outcomes after 12 and 24 months, indicating that stringent control of retinal fluid volume fluctuations is important to prevent visual acuity decline over time.

Efficacy and safety of brolucizumab versus aflibercept in patients with neovascular age-related macular degeneration: a randomized trial in Indian patients

BackgroundThe current standard treatment for neovascular age-related macular degeneration (nAMD) involves intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. The aim of the present study was to compare the effectiveness and safety of two anti-VEGF drugs: brolucizumab and aflibercept, in treatment-naïve nAMD Indian patients over a period of 48 weeks.MethodsA prospective, randomized, single-centre, single-blinded, two-arm comparative study was conducted between March 2021 and February 2022. Of the 114 patients, 56 received intravitreal injections of brolucizumab (6 mg/50 µL) while 58 received aflibercept (2 mg/50 µL). The patients received 03 initial loading doses at 4-week intervals of both the agents and then respective therapies were given as individualized pro re nata (PRN) regimen based on the signs of active macular neovascularization. The functional and anatomical outcomes measured were mean change in best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), presence of intraretinal fluid, subretinal fluid or subretinal hyper-reflective material. Furthermore, the average number of additional injections required after the loading doses, the injection-free interval and safety of both the drugs were also assessed.ResultsBrolucizumab was found to be non-inferior to aflibercept in terms of mean change in BCVA (−0.13 ± 0.21 logMAR vs. −0.10 ± 0.15 logMAR) and reduction in CMT (−112.59 ± 81.23 µm vs. −86.38 ± 71.82 µm). The percentage of eyes with IRF and SHRM was comparable between both the groups while fewer eyes treated with brolucizumab indicated SRF presence than aflibercept after the loading doses. These beneficial effects of brolucizumab were observed with significant (p < 0.0001) lesser number of injections (1.8 ± 1.1 vs. 3.8 ± 1.5) from week 12 to week 48. Moreover, the probability of no injections after the loading doses was significantly higher with brolucizumab compared to aflibercept indicating prolonged injection-free intervals. The average ocular side effects were comparable in the two groups. One adverse event of severe vitritis requiring treatment with oral steroids occurred in Brolucizumab group, while no such event occurred in Aflibercept group.ConclusionThe results of the present study suggest non-inferiority of brolucizumab PRN regimen to aflibercept PRN regimen in treatment naïve nAMD Indian patients while achieving longer inter-injection intervals.Trial registration Clinical Trial Registration of India (CTRI/2021/06/034415). Registered 03 March, 2021, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=54328&EncHid=&userName =

Predominantly Persistent Intraretinal Fluid in the Comparison of Age-related Macular Degeneration Treatments Trials

To describe predominantly persistent intraretinal fluid (PP-IRF) and its association with visual acuity (VA) and retinal anatomic findings at long-term follow-up in eyes treated with pro re nata (PRN) ranibizumab or bevacizumab for neovascular age-related macular degeneration. Cohort within a randomized clinical trial. Participants in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT) assigned to PRN treatment. The presence of intraretinal fluid (IRF) on OCT scans was assessed at baseline and monthly follow-up visits by Duke OCT Reading Center. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2 was defined as the presence of IRF at the baseline and in ≥ 80% of follow-up visits. Among eyes with baseline IRF, the mean VA scores (letters) and changes from the baseline were compared between eyes with and those without PP-IRF. Adjusted mean VA scores and changes from the baseline were also calculated using the linear regression analysis to account for baseline patient features identified as predictors of VA in previous CATT studies. Furthermore, outcomes were adjusted for concomitant predominantly persistent subretinal fluid. Predominantly persistent intraretinal fluid through week 12, year 1, and year 2; VA score and VA change; and scar development at year2. Among 363 eyes with baseline IRF, 108 (29.8%) had PP-IRF through year 1 and 95 (26.1%) had PP-IRF through year 2. When eyes with PP-IRF through year 1 were compared with those without PP-IRF, the mean 1-year VA score was 62.4 and 68.5, respectively (P= 0.002), and was 65.0 and 67.4, respectively (P= 0.13), after adjustment. Predominantly persistent intraretinal fluid through year 2 was associated with worse adjusted 1-year mean VA scores (64.8 vs. 69.2; P= 0.006) and change (4.3 vs. 8.1; P= 0.01) as well as worse adjusted 2-year mean VA scores (63.0 vs. 68.3; P= 0.004) and changes (2.4 vs. 7.1; P= 0.009). Predominantly persistent intraretinal fluid through year 2 was associated with a higher 2-year risk of scar development (adjusted hazard ratio= 1.49; P= 0.03). Approximately one quarter of eyes had PP-IRF through year 2. Predominantly persistent intraretinal fluid through year 1 was associated with worse long-term VA, but the relationship disappeared after adjustment for baseline predictors of VA. Predominantly persistent intraretinal fluid through year 2 was independently associated with worse long-term VA and scar development.

Association Between Visual Acuity and Fluid Compartments with Treat-and-Extend Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis.

IntroductionRecently, there has been growing interest in exploring the relationship between visual acuity and fluid localization in different retinal compartments. This post hoc analysis of the ARIES study explores the relationship between the presence of intraretinal fluid (IRF) and subretinal fluid (SRF), both at baseline and throughout treatment, and best-corrected visual acuity (BCVA) in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in a treat-and-extend regimen.MethodsARIES (NCT02581891) was a multicenter, randomized, phase 3b/4 study comparing the efficacy of two IVT-AFL treat-and-extend regimens over 2 years in patients with treatment-naïve nAMD. This post hoc analysis explores the relationship between the presence of SRF/IRF and absolute BCVA (letter score) at baseline and fixed visits.ResultsIn 210 patients (treat-and-extend treatment arms combined), SRF presence at baseline was associated at every time point with a numerically higher mean BCVA than if absent, with 10 more letters at week 104. IRF presence at baseline was associated at all but one time point with a numerically lower mean BCVA than if absent (week 104, 8-letter difference). Baseline SRF+IRF was associated with lower BCVA (week 104, 7-letter difference) than if only SRF was present, but higher BCVA (week 104, 8-letter difference) than if only IRF was present. Absence of SRF+IRF was not associated with better BCVA at any time point during the study.ConclusionIn ARIES, in patients with nAMD treated with IVT-AFL, the presence of SRF was associated with better visual acuity, whereas IRF was associated with poorer visual acuity. The findings of this post hoc analysis suggest that differentiating IRF from SRF may offer better prognostic value in guiding treatment-extension decisions than the use of combined or “any” IRF and SRF. Prospective trials are needed to validate these results and determine their clinical relevance.Trial registration number (ClinicalTrials.gov)NCT02581891. Association between Visual Acuity and Fluid Compartments with Treat-and-Extend Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis: A Video (MP4 308264 KB)Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00491-1.

Monthly Alternating Injections of Aflibercept and Bevacizumab for Neovascular Age-Related Macular Degeneration.

We investigated the efficacy of monthly alternating injections of aflibercept and bevacizumab (MAAB) for maintenance treatment in patients with neovascular age-related macular degeneration (AMD) who showed improvement with the initial monthly injections but presented with rapid worsening after conversion to bimonthly injections. We included 72 patients with neovascular AMD who showed improvement with loading injections of aflibercept. For maintenance treatment, bevacizumab was administered every alternate month between the bimonthly aflibercept injections in 24 (33.3%) eyes showing worsening (MAAB group). The other eyes were treated with aflibercept (BiA group) bimonthly. Baseline low retinal thickness, thick choroid, and presence of intraretinal fluid were associated with worsening after extending the injection intervals. Visual improvement was lower in the MAAB group than in the BiA group, but the final visual outcomes were comparable. Additional bevacizumab stabilized the early fluctuation of retinal thickness, thus maintaining long-term visual stability without increasing the risk of geographic atrophy or disciform scar until the second year. Previously treated eyes or those with polypoidal choroidal vasculopathy responded less to the initial loading doses and showed worsening under the bimonthly regimen. MAAB was effective in preventing anatomical and functional deterioration when bimonthly aflibercept proved insufficient for the maintenance treatment of neovascular AMD.

InCASEOf scoring system for distinction between pachychoroid-associated macular neovascularization and neovascular age-related macular degeneration in patients older than 50\xa0years

To develop a novel scoring system aiming at guiding the differential diagnosis between macular neovascularization secondary to pachychoroid disease (pMNV) and neovascular age-related macular degeneration (AMD) in patients aged 50 years and older. In this retrospective study performed at University Vita-Salute San Raffaele (Milan, Italy) and Créteil University Eye Clinic (Créteil, France), we enrolled patients 50 years of age and older, visited between January 2017 and January 2019, who were diagnosed with either treatment-naïve pMNV or neovascular AMD. At the time of diagnosis, all patients underwent a comprehensive ophthalmologic evaluation, spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, and optical coherence tomography angiography. Univariate comparison between pMNV and neovascular AMD groups was performed to identify the main clinical predictors for pMNV. The selected predictors were taken into a binomial logistic regression and eventually served as the basis for the development of InCASEOf scoring system. Receiver operating characteristic (ROC) curves were used to study the model performance. Forty-eight right eyes from 48 patients with pMNV and 39 right eyes from 39 patients with neovascular AMD were considered in this study. Age (+ 2 points), sex (+ 2 points), choroidal thickness (+ 2 points), early pachyvessels (+ 2 points), and evidence of MNV at OCTA (+ 3 points) turned out to be predictors for pMNV. Four additional factors significant at univariate analysis were considered: type 2 and type 3 MNVs and presence of intraretinal fluid (− 0.5 points each), and presence of subretinal fluid (+ 0.5 points). InCASEOf scoring system was built with a high score of 11.5 points. The cutoff value of 6.5 showed good accuracy in separating pMNVs from neovascular AMDs. InCASEOf is a straightforward clinical scoring system, accessible to comprehensive ophthalmologists, with the purpose of enabling easy distinction and expert-like diagnosis of pMNV and neovascular AMD in patients aged 50 years or older.

Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration

To find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.