Subretinal Fluid

BackgroundWith increasing experience using anti-VEGF therapy for the treatment of neovascular age-related macular degeneration (nAMD), ophthalmologists have shifted away from a "one size fits all" to an "individualised" approach based on disease activity with the aim of achieving a fluid-free retina. The FLUID study investigates the non-inferiority of a Treat and Extend (T&E) protocol of 0.5 mg ranibizumab, which allows treatment extension in the presence of incomplete resolution of sub-retinal fluid (SRF) ≤200 μm at the foveal centre relative to a T&E protocol that requires complete resolution of all retinal fluid (i.e., both SRF and intra-retinal fluid [IRF]) in patients with nAMD.Methods/designThis 24 month, randomised, phase IV trial has completed recruitment of treatment-naïve patients randomised 1:1 to ranibizumab "intensive" treatment (complete resolution of IRF and SRF) or ranibizumab "relaxed" treatment (resolution of IRF or >200 μm SRF only at foveal centre). Patients in both arms follow a T&E regimen where extension decisions are based upon assessment of lesion activity: loss of ≥5 letters of visual acuity, new haemorrhage, presence of IRF and SRF on an optical coherence tomography (OCT) scan. The determination of SRF is conducted at a reading centre while the assessment of IRF is physician-determined. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months. Secondary endpoints include the mean change in central retinal thickness (CRT) from baseline to 12 and 24 months, the number of ranibizumab injections administered at 12 and 24 months, and the pharmacogenomic assessment of AMD Gene Consortium-identified single-nucleotide polymorphisms (SNPs) and their association with treatment response. Three hundred and forty seven (347) patients have been recruited by 16 Australian sites within approximately 16 months. A protocol to adjudicate on SRF has been established by the central reading centre and is demonstrating good concordance with investigator assessment.DiscussionThis study will provide important insights into retreatment criteria for managing nAMD using a T&E regimen. The current paper describes the clinical rationale for using a less intensive treatment approach using ranibizumab and details of the treatment protocol.Trial registrationTrial registration numberNCT01972789. Date of registration: 24th October 2013.

Sub-retinal fluid (SRF) has been discussed as a protective factor against macular atrophy in eyes with neovascular age-related macular degeneration (nAMD).To gauge the impact of SRF on macular atrophy, a database of 310 nAMD eyes was screened for eyes manifesting an SRF-only phenotype under treat & extend anti-VEGF treatment, defined as nAMD expressing CNV exudation beyond the three monthly anti-VEGF loading doses by SRF only without any signs of exudative intra-retinal fluid (IRF) for ≥3 years. Incidence of macular atrophy and treatment responses were evaluated on multimodal imaging, including optical coherence tomography (OCT), blue autofluorescence (BAF) and near-infrared (NIR) confocal scanning laser ophthalmoscopy and fluorescence and indocyanine green angiography (FAG/ICGA). In total, 27 eyes (8.7%) of 26 patients with a mean follow-up of 4.2 ± 0.9 (3-5) years met the inclusion criteria. Mean age was 72 ± 6 (range: 61-86) years. The SRF only phenotype was seen from baseline in 14 eyes (52%), and in 13 eyes (48%) after a mean 1.0 ± 1.3 (1-3) injections. In years 1 to 5, mean 7.5, 5.9, 6.1, 6.1 and 7.0 anti-VEGF injections were given (p = 0.33). Cumulative macular atrophy incidence was 11.5% at year 1, 15.4% throughout years 2 to 4, and 22.4% at year 5. In conclusion, eyes manifesting activity by SRF only in treat & extend anti-VEGF regimen for nAMD seem to exhibit rather low rates of macular atrophy during long-term follow-up. SRF might be an indicator of a more benign form of nAMD.

ImportanceAmid an explosion of interest in deep learning in medicine, including within ophthalmology, concerns regarding data privacy, security, and sharing are of increasing importance. A model-to-data approach, in which the model itself is transferred rather than data, can circumvent many of these challenges but has not been previously demonstrated in ophthalmology.ObjectiveTo determine whether a model-to-data deep learning approach (ie, validation of the algorithm without any data transfer) can be applied in ophthalmology.Design, setting, and participantsThis single-center cross-sectional study included patients with active exudative age-related macular degeneration undergoing optical coherence tomography (OCT) at the New England Eye Center from August 1, 2018, to February 28, 2019. Data were primarily analyzed from March 1 to June 20, 2019.Main outcomes and measuresTraining of the deep learning model, using a model-to-data approach, in recognizing intraretinal fluid (IRF) on OCT B-scans.ResultsThe model was trained (learning curve Dice coefficient, >80%) using 400 OCT B-scans from 128 participants (69 female [54%] and 59 male [46%]; mean [SD] age, 77.5 [9.1] years). In comparing the model with manual human grading of IRF pockets, no statistically significant difference in Dice coefficients or intersection over union scores was found (P > .05).Conclusions and relevanceA model-to-data approach to deep learning applied in ophthalmology avoided many of the traditional hurdles in large-scale deep learning, including data sharing, security, and privacy concerns. Although the clinical relevance of these results is limited at this time, this proof-of-concept study suggests that such a paradigm should be further examined in larger-scale, multicenter deep learning studies.

PurposeTo assess the risk of subretinal fluid (SRF) development in the fellow eye of chronic central serous chorioretinopathy (cCSC) patients with unilateral SRF at baseline.MethodsMedical records of 334 presumed cCSC patients were retrospectively reviewed. Multimodal imaging was evaluated, and the available optical coherence tomography (OCT) scans were screened for SRF development in the fellow eye during follow-up.ResultsOf 213 confirmed cCSC cases, 74 (35%) had bilateral SRF at baseline. Among 102 patients with unilateral SRF that met all inclusion criteria, 7/102 (7%) developed SRF in the fellow eye over a mean follow-up of 20.4 months. Retinal pigment epithelial (RPE) alterations in the fellow eye were present at baseline in 7/7 (100%) who developed SRF, compared to 59/95 (62%) in those who did not (p = 0.042). Subfoveal choroidal thickness (SFCT) was higher in the SRF-developing group (482.3 vs. 365.9 μm; p = 0.306), although not significantly. Hyperautofluorescence on fundus autofluorescence (FAF) at baseline occurred in 6/7 (86%) of the SRF-developing group versus 25/91 (28%) who did not (p = 0.004). The ellipsoid zone was interrupted in 5/7 (71%) of SRF-developing patients versus 28/95 (30%) who did not develop SRF (p = 0.005).ConclusionThe risk of SRF development in the fellow eye of cCSC patients with unilateral SRF is relatively low over a follow-up period of almost 2 years. No statistically significant risk factors were identified after correction for multiple testing; however, certain trends were observed.