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Background/objectives To characterise morphological changes in neovascular age-related macular degeneration (nAMD) during anti-angiogenic therapy and explore relationships with best-corrected visual acuity (BCVA) and development of macular atrophy (MA). Subjects/methods Post-hoc analysis of the phase III HARBOR trial. SD-OCT scans from 1097 treatment-naïve nAMD eyes were analysed. Volumes of intraretinal cystoid fluid (ICF), subretinal hyperreflective material (SHRM), subretinal fluid (SRF), pigment epithelial detachment (PED) and cyst-free retinal volume (CFRV) were measured by deep-learning model. Volumes were analysed by treatment regimen, macular neovascularisation (MNV) subtypes and topographic location. Associations of volumetric features with BCVA and MA development were quantified at month 12/24. Results Differences in feature volume changes by treatment regimens and MNV subtypes were observed. Each additional 100 nanolitre unit (AHNU) of residual ICF, SHRM and CFRV at month 1 in the fovea was associated with deficits of 10.3, 7.3 and 12.2 letters at month 12. Baseline AHNUs of ICF, CFRV and PED were associated with increased odds of MA development at month 12 by 10%, 4% and 3%. While that of SRF was associated with a decrease in odds of 5%. Associations at month 24 were similar to those at month 12. Conclusion Eyes with different MNV subtypes showed distinct trajectories of feature volume response to treatment. Higher baseline volumes of ICF or PED and lower baseline volume of SRF were associated with higher likelihoods of MA development over 24 months. Residual intraretinal fluid, including ICF and CFRV, along with SHRM were predictors of poor visual outcomes.

Treatment decisions for neovascular age-related macular degeneration (nAMD) in the setting of individualised treatment regimens are adapted to disease activity. The main marker of disease activity and trigger for re-treatment with anti-vascular endothelial growth factor (anti-VEGF) agents is the presence of retinal fluid on optical coherence tomography (OCT). Recently, attention has focused on the impact of residual retinal fluid on nAMD management. Based on a literature review and the combined clinical experience of an international group of retinal specialists, this manuscript provides expert guidance on the treatment of nAMD according to fluid status and proposes an algorithm for determining when to administer anti-VEGF treatment according to residual fluid status. We explore the role of residual fluid in treatment decisions and outcomes in nAMD, taking into consideration fluid evaluation and, in particular, distinguishing between fluid in different anatomic compartments and at different stages during the treatment course. Current limitations to identifying and interpreting fluid on OCT, and the assumption that any residual retinal fluid reflects ongoing VEGF activity, are discussed.

AimTo evaluate the impact of fluid volume fluctuations quantified with artificial intelligence in optical coherence tomography scans during the maintenance phase and visual outcomes at 12 and 24 months in a real-world, multicentre, national cohort of treatment-naïve neovascular age-related macular degeneration (nAMD) eyes.MethodsDemographics, visual acuity (VA) and number of injections were collected using the Fight Retinal Blindness tool. Intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), total fluid (TF) and central subfield thickness (CST) were quantified using the RetinAI Discovery tool. Fluctuations were defined as the SD of within-eye quantified values, and eyes were distributed according to SD quartiles for each biomarker.ResultsA total of 452 naïve nAMD eyes were included. Eyes with highest (Q4) versus lowest (Q1) fluid fluctuations showed significantly worse VA change (months 3–12) in IRF −3.91 versus 3.50 letters, PED −4.66 versus 3.29, TF −2.07 versus 2.97 and CST −1.85 versus 2.96 (all p<0.05), but not for SRF 0.66 versus 0.93 (p=0.91). Similar VA outcomes were observed at month 24 for PED −8.41 versus 4.98 (p<0.05), TF −7.38 versus 1.89 (p=0.07) and CST −10.58 versus 3.60 (p<0.05). The median number of injections (months 3–24) was significantly higher in Q4 versus Q1 eyes in IRF 9 versus 8, SRF 10 versus 8 and TF 10 versus 8 (all p<0.05).ConclusionThis multicentre study reports a negative effect in VA outcomes of fluid volume fluctuations during the maintenance phase in specific fluid compartments, suggesting that anatomical and functional treatment response patterns may be fluid-specific.

Background Investigate retinal fluid changes via a novel deep-learning algorithm in real-world patients receiving faricimab for the treatment of neovascular age-related macular degeneration (nAMD). Methods Multicenter, retrospective chart review and optical coherence tomography (OCT) image upload from participating sites was conducted on patients treated with faricimab for nAMD from February 2022 to January 2024. The Notal OCT Analyzer (NOA) algorithm provided intraretinal, subretinal and total retinal fluid for each scan. Results were segregated based on treatment history and fluid compartments, allowing for multiple cross-sections of evaluation. Results A total of 521 eyes were included at baseline. The previous treatments prior to faricimab were aflibercept, ranibizumab, bevacizumab, or treatment-naive for 52.3%, 21.0%, 13.3%, and 11.2% of the eyes, respectively. Of all 521 eyes, 49.9% demonstrated fluid reduction after one injection of faricimab. The mean fluid reduction after one injection was −60.7nL. The proportion of eyes that saw reduction in fluid compared to baseline after second, third, fourth and fifth faricimab injections were 54.4%, 51.9%, 51.4% and 52.2%, respectively. The mean (SD) retreatment interval after second, third, fourth and fifth faricimab injection were 53.4 (34.3), 56.6 (36.0), 57.1 (35.3) and 61.5 (40.2) days, respectively. Conclusion Deep-learning algorithms provide a novel tool for evaluating precise quantification of retinal fluid after treatment of nAMD with faricimab. Faricimab demonstrates reduction of retinal fluid in multiple groups after just one injection and sustains this response after multiple treatments, along with providing increases in treatment intervals between subsequent injections.

Persistent subretinal fluid (PSF) after scleral bucking of rhegmatogenous retinal detachment may delay recovery and affect the final visual quality, but with no effective treatment. This study firstly investigated the safety and efficacy of 577 nm yellow subthreshold micropulse laser (SML) on PSF after scleral bucking surgery. This double-masked randomized clinical trial was conducted from December 2020 to October 2022 at Chongqing Aier Eye Hospital. Participants with PSF last for 1 month after scleral bucking surgery with break closed and retina reattachment were recruitment. These participants were treated by 577 nm yellow SML or sham treatment. Funduscopy, optical coherence tomography (OCT) volume change, best corrected vision acuity (BCVA) and visual field test were evaluated for six mouths follow-up. A total of 24 participants were randomized into SML group or Sham group equally. Compared with Sham group, the OCT volume within 6 mm of macular fovea was significantly less in SML group 6 months after therapy ( P  = 0.048). There were no statistically significant differences of OCT volume at 1, 2 and 3 months from baseline between groups. BCVA of ETDRS letters had no statistically significant difference. Pattern Standard Deviation amelioration ( P  = 0.039) had statistically significance in SML group compared with Sham group. There were no complications in the 2 groups. These preliminary findings suggest that 577 nm yellow SML therapy could accelerate PSF absorption after scleral bucking surgery. Trial registration: Chinese Clinical Trial Registry No. ChiCTR2000037838, 02/09/2020, https://www.chictr.org.cn/showproj.html?proj=51885 .

This study investigated the association between the duration of subretinal fluid (SRF) persistence in affected eyes and baseline chorioretinal structure in unaffected fellow eyes among patients with unilaterally naïve central serous chorioretinopathy (CSC). This retrospective case series comprised 25 healthy control patients and 46 patients with unilaterally naïve CSC, defined as first-episode and untreated within 1 month from symptom onset, who were categorized into prolonged (> 3 months) and nonprolonged (≤ 3 months) groups according to SRF duration in affected eyes from the first visit. Central retinal thickness, outer nuclear layer thickness, central choroidal thickness (CCT), luminal area (LA), stromal area (SA), total choroidal area (TCA), and choroidal vascularity index (CVI) were measured in unaffected fellow eyes at the first visit, and the duration of SRF persistence in affected eyes was recorded. As a result, CCT, SA and TCA were significantly greater, and CVI was significantly lower in the unaffected fellow eyes compared to the healthy control eyes (all p  < 0.05). The optimal model for predicting SRF persistence > 3 months in affected eyes involved CVI ( p  = 0.015) in fellow eyes. Baseline choroidal thickening, mainly in the choroidal stroma of unaffected fellow eyes, was shown to correlate with SRF persistence in the affected eyes in unilateral naïve CSC. This information may be valuable for the identifying cases with a heightened risk of prolonged SRF persistence and for the timely initiation of treatment.

Purpose To evaluate the long-term results of spironolactone in non-resolving central serous chorio-retinopathy (CSCR) and recurrence rates of CSCR. Methods Interventional uncontrolled open-label prospective clinical trial of patients with non-resolving CSCR who were treated with spironolactone 50 mg daily (Spironolacton AL® 50 mg, ALIUD PHARMA) for up to 16 weeks. Follow-up visits were performed at 3, 6, 9, and 12 months. Retreatment criteria for recurrence were: gain in sub-retinal fluid (SRF) of more than 25 % plus/or increase of central retinal thickness (CRT) of more than 50 μm plus visual symptoms compared to last visit. Main outcome measures : 12-month efficacy of upload treatment with spironolactone. Secondary outcome measure was the recurrence rate at 6, 9, and 12 months. Results Of the 21 study eyes treated, 71 % ( n  = 15) showed significant improvement or complete regression on OCT examination over 12 months. Nineteen percent of the patients ( n  = 4) showed a stable course from visit 1 to visit 12. The overall reduction of sub-retinal fluid from visit 1 (156 μm ± 131 SD) to visit 12 (53 μm ± 93 SD) was statistically significant ( p  = 0.003). The change of mean visual acuity (log MAR) from 0.25 (± 0.17 SD) at baseline to 0.17 (± 0.18 SD) at visit 12 was statistically significant, with p  = 0.044. Conclusion Our results confirm a positive effect of spironolactone in non-resolving CSCR in 71 % of cases. Evaluation of recurrence rates and retreatments showed good results in patients who responded to spironolactone primarily. A prospective randomized trial may provide better data about this non-invasive treatment.

Circumscribed choroidal hemangiomas are benign vascular hamartomas without systemic associations. Generally, they are orange-red elevated masses, which are found posterior to the equator. Lesions are usually solitary and unilateral. Overlying subretinal fluid, serous retinal detachment and cystoid macular edema are common findings. Intravenous fluorescein angiography, indocyanine green angiography, ultrasonography, optical coherence tomography and enhanced depth imaging are helpful ancillary tests for diagnosis of circumscribed choroidal hemangiomas. Asymptomatic circumscribed choroidal hemangiomas do not require treatment. For symptomatic lesions with exudative retinal detachment or cystoid macular edema, photodynamic therapy has emerged as the treatment of choice with high rates of tumor regression, subretinal fluid resorption and minimal complications. Lens-sparing external beam radiotherapy, plaque brachytherapy, proton beam therapy, stereotactic radiosurgery, transpupillary thermotherapy, laser photocoagulation and anti-VEGF injections are other treatment modalities.

PurposeTo investigate the incidence of and clinical risk factors for multiple subretinal fluid (SRF) blebs after pars plana vitrectomy (PPV).MethodsThis study examined patients who underwent PPV (25- or 27-gauge) to repair a primary rhegmatogenous retinal detachment (RRD). Clinical characteristics, including age, sex, axial length, symptom duration, and postoperative best-corrected visual acuity (BCVA), were compared between eyes with and without multiple SRF blebs. Intentional drainage retinotomy and cryotherapy use were also performed. Main outcome measures were the effect of these parameters on multiple SRF bleb incidence 1 month after surgery.ResultsA total of 108 eyes of 106 patients (76 men and 32 women; mean age = 58.9 ± 9.0 years) were included. Multiple SRF blebs were observed in 8 eyes (7.4%). Logistic regression analysis showed that creation of intentional drainage retinotomy and 27-gauge PPV are risk factors for the development of multiple SRF blebs. The number and size of blebs spontaneously decreased over time, and SRF had completely resolved in 5 eyes (62.5%) 1 year after surgery.ConclusionMultiple SRF blebs developed even after small gauge vitrectomy. The SRF did not affect postoperative BCVA and gradually absorbed without treatment.

We investigated the characteristics of neovascular age-related macular degeneration (AMD) in which exudation predominantly occurs as a subretinal fluid (SRF) during anti-vascular endothelial growth factor (VEGF) treatment. A total of 509 treatment-naïve neovascular AMD patients treated with anti-VEGF for 24 months were retrospectively analyzed. The baseline characteristics to determine the odds of occurrence of SRF alone were evaluated using multivariate modeling. SRF was the sole manifestation of lesion activity in 209 (40.9%) eyes during follow-up. The visual outcome of eyes with only SRF occurrence during follow-up was comparable to that of eyes without exudative recurrence. In addition, the incidence of macular atrophy was significantly lower in eyes with only SRF occurrence (9.6%, 20 of 208 eyes) than in eyes without exudative recurrence (16.7%, 9 of 54 eyes, P  = 0.018). Multivariate analysis revealed that better best-corrected visual acuity (BCVA) at baseline (odds ratio [OR], 0.306; P  = 0.001), presence of SRF alone at baseline (OR, 5.256; P  < 0.001), lower pigment epithelial detachment (PED) height (less than 100 µm; OR, 4.113; P  = 0.025), and aneurysmal type 1 macular neovascularization (MNV) (OR, 2.594; P  = 0.002) were associated with an increased likelihood of SRF occurrence during follow-up. In conclusion, the eyes with only SRF occurrence during anti-VEGF treatment showed more favorable visual outcomes and a lower incidence of macular atrophy. The baseline characteristics, including better baseline BCVA, presence of SRF alone at baseline, lower PED height, and MNV subtype, might influence the predominant development of SRF during anti-VEGF treatment.