Central Subfield Retinal Thickness Research Articles

Early real-world experience with intravitreal Faricimab for neovascular AMD: FAN study

PurposeThis study presents real-world experiences and clinical outcomes of patients who switched to faricimab after prior treatment with other anti-vascular endothelial growth factor medication for patients with neovascular age-related macular degeneration (nAMD) in 2022. DesignWe evaluated all consecutive patients that received an intravitreal injection (IVI) with faricimab for nAMD and had complete follow-up visits after at least three IVI. MethodsFunctional and structural parameters including best-corrected visual acuity (BCVA, logMAR), foveal centre point (FCP, µm), central subfield retinal thickness (CSRT, µm) and macular volume (mm3) were evaluated after three (n=71) and five (n=57) faricimab injections with complete follow-up visits. ResultsWe included 71 eyes of 63 patients. Mean BCVA at baseline was 0.49 logMAR (0 – 1.6) and did not change significantly after five faricimab injections (p=0.33). Significant reductions were seen for FCP, CSRT and macular volume after the first five consecutive injections when compared to baseline (p<0.0001 respectively). FCP was 388.35 µm (173-924 µm) at baseline and decreased to 279.16 µm (97 – 667) at visit 5. CSRT was 370.68 µm (202 – 1074) and decreased to 307.75 µm (168 – 590) at visit 5. Macular volume was reduced from 2.59 mm3 (1.83 – 4.90) to 2.31 mm3 (1.80 – 3.19) at visit 5. Intraocular inflammation was observed in one eye showing anterior chamber cells that resolved with topical corticosteroid treatment. ConclusionsThe results of the FAN (FAricimab for Neovascular AMD) study indicate that faricimab improves structural outcomes in patients with recalcitrant fluid due to nAMD with no major complications observed.

Factors Affecting Disease Stability After Intravitreal Brolucizumab Injection for Refractory Neovascular Age-Related Macular Degeneration.

The purpose of this study is to identify the factors affecting neovascular age-related macular degeneration (nAMD) disease stability after brolucizumab treatment. We retrospectively analyzed the medical records of 31 patients (31 eyes) with recalcitrant nAMD who were switched to brolucizumab after conventional anti-vascular endothelial growth factor (VEGF) treatment. We divided patients into two groups by treatment extension (TE) period: group 1 with TE < 12weeks (N = 16) and group 2 with TE ≥ 12weeks (N = 15). We compared outcomes between the groups at 2, 4, 8, and 12weeks, including morphological characteristics of choroidal neovascularization (CNV). Logistic regression analysis identified factors associated with TE ≥ 12weeks. Group 2 had a significantly greater proportion of patients with dry macula (subretinal and intraretinal fluids absent) than group 1 (60 vs. 12.5%) at 2weeks (P < 0.05). Best-corrected visual acuity (BCVA) and subfoveal choroidal thickness (SFCT) did not differ significantly between groups at all timepoints. Central subfield retinal thickness (CST) was significantly lower in group 2 at 2 (237.1 vs. 280.8μm; P < 0.05), 4 (224.0 vs. 262.9μm; P < 0.05), and 8weeks (216.8 vs. 331.1μm; P < 0.05). Group 2 had less vessel area (0.63 vs. 1.27 mm2; P < 0.05) and total vessel length (0.22 vs. 0.42mm; P < 0.05). Choriocapillaris flow deficit (CCFd) was significantly lower in group 2 (42.7 vs. 48.2%; P < 0.05). Dry macula at 2weeks (odds ratio [OR] = 8.3; P < 0.05) and a lower CCFd (OR = 0.73; P < 0.05) were associated with TE ≥ 12weeks. Early fluid-free status after switching to brolucizumab and choriocapillary function around CNV were prognostic factors for disease stability in nAMD refractory to anti-VEGF treatment.

Dexamethasone intravitreal implant in diabetic macular oedema refractory to anti-vascular endothelial growth factors: the AUSSIEDEX study

AimTo evaluate effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX) monotherapy in the AUSSIEDEX study non-responder subgroup, defined by diabetic macular oedema (DME) refractory to anti-vascular endothelial growth factor (anti-VEGF)...

Performance of retinal fluid monitoring in OCT imaging by automated deep learning versus human expert grading in neovascular AMD

PurposeTo evaluate the reliability of automated fluid detection in identifying retinal fluid activity in OCT scans of patients treated with anti-VEGF therapy for neovascular age-related macular degeneration by correlating human expert and automated measurements with central retinal subfield thickness (CSFT) and fluid volume values.MethodsWe utilized an automated deep learning approach to quantify macular fluid in SD-OCT volumes (Cirrus, Spectralis, Topcon) from patients of HAWK and HARRIER Studies. Three-dimensional volumes for IRF and SRF were measured at baseline and under therapy in the central millimeter and compared to fluid gradings, CSFT and foveal centerpoint thickness (CPT) values measured by the Vienna Reading Center.Results41.906 SD-OCT volume scans were included into the analysis. Concordance between human expert grading and automated algorithm performance reached AUC values of 0.93/0.85 for IRF and 0.87 for SRF in HARRIER/HAWK in the central millimeter. IRF volumes showed a moderate correlation with CSFT at baseline (HAWK: r = 0.54; HARRIER: r = 0.62) and weaker correlation under therapy (HAWK: r = 0.44; HARRIER: r = 0.34). SRF and CSFT correlations were low at baseline (HAWK: r = 0.29; HARRIER: r = 0.22) and under therapy (HAWK: r = 0.38; HARRIER: r = 0.45). The residual standard error (IRF: 75.90 µm; SRF: 95.26 µm) and marginal residual standard deviations (IRF: 46.35 µm; SRF: 44.19 µm) of fluid volume were high compared to the range of CSFT values.ConclusionDeep learning-based segmentation of retinal fluid performs reliably on OCT images. CSFT values are weak indicators for fluid activity in nAMD. Automated quantification of fluid types, highlight the potential of deep learning-based approaches to objectively monitor anti-VEGF therapy.

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

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

Retinal Neurodegeneration and Visual Acuity Decline in Patients with Chronic Kidney Disease.

Chronic kidney disease (CKD) has been associated with accelerated retinal neurodegeneration. The purpose of this study is to evaluate the association between retinal neurodegeneration and the best-corrected visual acuity (BCVA) decline in patients with CKD. Post hoc analysis of two prospective studies. Patients with CKD stage≥3 were enrolled. Macular thickness, peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular ganglion cell complex (GCC) thickness were measured by optical coherence tomography. Eyes were classified into three groups: Group 1, no GCC defect; Group 2, GCC defect confined to parafoveal area; and Group 3, GCC defects extending beyond the parafoveal area. Each group was matched for age, sex, axial length, lens status, and cataract grading. A total of 120 eyes (40 eyes in each group) from 120 patients (age 63.0±10.3years) were included. The logMAR BCVA was 0.076±0.101, 0.100±0.127, and 0.196±0.191 in Group 1, 2, and 3, respectively. Group 3, but not Group 2, had a significantly worse BCVA than Group 1. In simple linear regression, parafoveal inner retinal thickness, pRNFL thickness, presence of pRNFL defect, GCC thickness, GCC global loss volume, GCC focal loss volume, and GCC defect extending beyond parafoveal area were associated with BCVA. Central subfield retinal thickness (CRT), parafoveal full retinal thickness, and parafoveal outer retinal thickness were not associated with BCVA. In backward stepwise linear regression, age and GCC defects extending beyond the parafoveal area were factors associated with BCVA. Moreover, GCC defect extending beyond parafoveal area was connected with worse BCVA in both phakic and pseudophakic subgroups. GCC defect extending beyond parafoveal area could be an independent biomarker associated with decreased BCVA in patients with CKD. However, macular thinning measured by CRT or parafoveal full retinal thickness might have low discriminative power in determining BCVA.

Morphometric analyses in patients treated with subthreshold laser photocoagulation for central serous chorioretinopathy

Background and objectiveTo analyze changes in selected parameters in optical coherence tomography (OCT) after subthreshold laser coagulation (ST-LP) in patients with central serous chorioretinopathy (CSCR).Materials and methodsFifty-four eyes of 49 patients with CSCR were included in the study. Each patient underwent therapy with ST-LP with a frequency-doubled Neodym-YAG Laser and OCT imaging. In OCT the thickness of the central subfield, cube volume, average cube thickness, volume under the ETDRS grid, and average thickness under the ETDRS grid were collected.ResultsDecreases in total OCT volume and central retinal subfield thickness were statistically significant (p < 0.05). Possible correlations were observed between visual acuity at V3 (3 months after ST-LP) and Baseline and between central retinal subfield thickness at V1 (4 weeks after ST-LP) and visual acuity at BL.ConclusionA decrease in retinal thickness and retinal volume could be shown after ST-LP. Central retinal subfield thickness measured by OCT could be a more sensitive measure than mean retinal thickness or macular volume for early detection of disease recurrence occurring in some patients 3 months after ST-LP.

Preliminary Study of Different Treatment Responses between Bevacizumab, Aflibercept and Dexamethasone Implant According to Renal Function in Diabetic Macular Edema Patients.

Background: The purpose of this study was to investigate the association between responses to intravitreal bevacizumab injection and renal function in diabetic macular edema (DME) patients. Methods: A retrospective study of the medical records of 104 treatment-naïve DME patients who received intravitreal bevacizumab injection (IVBI) was conducted. Based on the estimated glomerular filtration rate (eGFR, mL/min/1.73 m2), the participants were classified into three groups. Intergroup comparisons of the best-corrected visual acuity (BCVA) and central subfield retinal thickness (CST) changes were performed after three-monthly consecutive IVBIs. In the groups with decreased renal function, the response to further treatment with a different drug was investigated. Results: A total of 104 participants were included in the study: 60 participants in the preserved renal function group (eGFR ≥ 60), 25 participants in the moderate chronic kidney disease (CKD) group (30 ≤ eGFR < 60), and 19 participants in the severe CKD group (eGFR < 30). After three-monthly consecutive IVBIs, BCVA (p < 0.001) and CST (p < 0.001) were significantly improved only in the preserved renal function group. Following further treatment of patients with decreased renal function, the treatment results were significantly better in those who were switched to aflibercept or dexamethasone implant than in those who were maintained on IVBI. Conclusions: From this preliminary study, we observed that renal function might affect the response to IVBI treatment in patients with DME. In the case of a poor response to initial IVBI treatment for DME in patients with moderate to severe CKD, our study supports switching to the aflibercept or dexamethasone implant.

The STArgardt Remofuscin Treatment Trial (STARTT): design and baseline characteristics of enrolled Stargardt patients.

Background: This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). Methods: In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF 8). Secondary efficacy variables are best corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic microperimetry (mMP), spectral domain optical coherence tomography (SD-OCT), reading speed on Radner reading charts, and patient-reported visual function as assessed by the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and Functional Reading Independence (FRI) Index. Results: Mean age of participants was 35±11 years with 49 (56%) female. Median qAF 8 value was 438 Units (range 210-729). Median BCVA and LLVA in decimal units were 0.50 (range 0.13-0.80) and 0.20 (range 0.06-0.63), respectively. The median of the mean retinal sensitivity with mMP was 20.4 dB (range 0.0-28.8). SD-OCT showed median central subfield retinal thickness of 142 µm (range 72-265) and median macular volume of 1.65 mm 3 (range 1.13-2.19). Compared to persons without vision impairment, both reading performance and patient-reported visual function were significantly lower (p<0.001, one sample t-test). Mean reading speed was 108±39 words/minute with logRAD-score of 0.45±0.28. Mean VFQ-25 composite score was 72±13. Mean FRI Index score 2.8±0.6. Conclusions: This trial design may serve as reference for future clinical trials as it explores the utility of qAF 8 as primary outcome measure. The baseline data represent the largest, multi-national, STGD1 cohort to date that underwent standardized qAF imaging, reading speed assessment and vision-related quality of life measures which all contribute to the characterization of STGD1. EudraCT registration: 2018-001496-20 (09/05/2019).

The STArgardt Remofuscin Treatment Trial (STARTT): design and baseline characteristics of enrolled Stargardt patients

Background: This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). Methods: In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF8). Secondary efficacy variables are best corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic microperimetry (mMP), spectral domain optical coherence tomography (SD-OCT), reading speed on Radner reading charts, and patient-reported visual function as assessed by the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and Functional Reading Independence (FRI) Index. Results: Mean age of participants was 35±11 years with 49 (56%) female. Median qAF8 value was 438 Units (range 210-729). Median BCVA and LLVA in decimal units were 0.50 (range 0.13-0.80) and 0.20 (range 0.06-0.63), respectively. The median of the mean retinal sensitivity with mMP was 20.4 dB (range 0.0-28.8). SD-OCT showed median central subfield retinal thickness of 142 µm (range 72-265) and median macular volume of 1.65 mm3 (range 1.13-2.19). Compared to persons without vision impairment, both reading performance and patient-reported visual function were significantly lower (p&lt;0.001, one sample t-test). Mean reading speed was 108±39 words/minute with logRAD-score of 0.45±0.28. Mean VFQ-25 composite score was 72±13. Mean FRI Index score 2.8±0.6. Conclusions: This trial design may serve as reference for future clinical trials as it explores the utility of qAF8 as primary outcome measure. The baseline data represent the largest, multi-national, STGD1 cohort to date that underwent standardized qAF imaging, reading speed assessment and vision-related quality of life measures which all contribute to the characterization of STGD1. EudraCT registration: 2018-001496-20 (09/05/2019)

SYSTEMATIC CORRELATION OF CENTRAL SUBFIELD THICKNESS WITH RETINAL FLUID VOLUMES QUANTIFIED BY DEEP LEARNING IN THE MAJOR EXUDATIVE MACULAR DISEASES.

To investigate the correlation of volumetric measurements of intraretinal (IRF) and subretinal fluid obtained by deep learning and central retinal subfield thickness (CSFT) based on optical coherence tomography in retinal vein occlusion, diabetic macular edema, and neovascular age-related macular degeneration. A previously validated deep learning-based approach was used for automated segmentation of IRF and subretinal fluid in spectral domain optical coherence tomography images. Optical coherence tomography volumes of 2.433 patients obtained from multicenter studies were analyzed. Fluid volumes were measured at baseline and under antivascular endothelial growth factor therapy in the central 1, 3, and 6 mm. Patients with neovascular age-related macular degeneration generally demonstrated the weakest association between CSFT and fluid volume measurements in the central 1 mm (0.107-0.569). In patients with diabetic macular edema, IRF correlated moderately with CSFT (0.668-0.797). In patients with retinal vein occlusion, IRF volumes showed a moderate correlation with CSFT (0.603-0.704). The correlation of CSFT and fluid volumes depends on the underlying pathology. Although the amount of central IRF seems to partly drive CSFT in diabetic macular edema and retinal vein occlusion, it has only a limited impact on patients with neovascular age-related macular degeneration. Our findings do not support the use of CSFT as a primary or secondary outcome measure for the quantification of exudative activity or treatment guidance.

Early Macular Thickness Changes after Trabeculectomy and Combined Phaco-Trabeculectomy.

Purpose:To assess postoperative changes in central retinal thickness (RT) following trabeculectomy and combined phaco-trabeculectomy using spectral domain-optical coherence tomography.Methods:In a prospective interventional comparative study, 64 consecutive glaucoma patients who underwent trabeculectomy (32 eyes) or phaco-trabeculectomy (32 eyes) were included. A macular thickness map using the Early Treatment Diabetic Retinopathy Study circles of 1 mm, 3 mm, and 6 mm was the standard to evaluate the 9-subfield thickness preoperatively and again at 1 and 3 months after surgery. Four subfields in each of the 3 mm and 6 mm rings were considered parafoveal and perifoveal regions, respectively.Results:Preoperative measurements were similar in the two groups, except patients in the combined group which were older (P = 0.002). The mean RT in the combined phaco-trabeculectomy group at month 1 was significantly higher than baseline measurements at central subfield retinal thickness (CSRT) (P = 0.01), temporal (P = 0.001), and inferior (P = 0.04) parafoveal and temporal (P = 0.01), superior (P = 0.02), and nasal (P < 0.001) perifoveal quadrants; however, RT changes in the trabeculectomy-only group were not statistically significant at months 1 and 3 (P > 0.05). The increase in the temporal perifoveal RT of the combined phaco-trabeculectomy group persisted at month 3 (P = 0.01), while the RT in other sectors returned to preoperative values. The two treatment groups did not differ in terms of changes in the CSRT over time (P = 0.37). In addition, no difference was observed between the treatment groups regarding the parafoveal RTs at each time points (0.06 ≤ P ≤ 0.29).Conclusions:There was no significant difference in the pattern of changes of CSRT and parafoveal RT between trabeculectomy and combined phaco-trabeculectomy treatment groups up to 3 months after surgery. Some detectable increase in RT in the combined phaco-trabeculectomy will reverse to baseline values 3 months after surgery, except in the temporal perifoveal region.

Foveal Morphology of Normal Fellow Eyes of Patients with Unilateral Macular Hole

To determine the morphology of the fovea in the ophthalmoscopically and tomographically normal fellow eyes of patients with a unilateral idiopathic macular hole (MH) and determine the association between foveal morphological parameters and foveal outer nuclear layer (ONL) thickness. Retrospective observational study. Two hundred three normal fellow eyes of patients with a unilateral MH and 216 normal eyes of 216 healthy subjects. All the eyes were examined using swept-source OCT. A built-in software was used to measure the average retinal and choroidal thickness in the center and in the inner 4 subfields defined in ETDRS. The total retinal thickness, thickness of 3 retinal layers at the fovea and parafovea (0.25 and 0.5 mm nasal and temporal from the fovea), and foveal floor width (FFW) were measured on a scan image of a horizontal line passing through the center of the fovea. We defined the thickness between the internal limiting membrane and outer plexiform layer as inner retinal thickness and the thickness between the external limiting membrane and retinal pigment epithelium as outer retinal thickness. Multiple regression analyses were performed with age, sex, axial length, and the presence of a posterior vitreous detachment as the dependent variables. OCT measurements and correlations between foveal parameters and foveal ONL thickness. The fellow eyes had a thinner central retinal subfield, thinner fovea, thinner ONL at all points except at 0.5 mm nasal, significantly thicker outer retina at all points, and a wider FFW (P= 0.040 to P < 0.0001). The foveal ONL thickness was significantly and positively correlated with the central subfield retinal thickness and foveal thickness and negatively correlated with the FFW (all P < 0.0001). The thinner and deeper fovea and the thinner ONL of the fellow eyes of patients with a unilateral MH make these eyes more susceptible to the formation of an MH.

Dexamethasone intravitreal implant in treatment-naïve diabetic macular oedema: findings from the prospective, multicentre, AUSSIEDEX study

AimTo evaluate the effectiveness of dexamethasone intravitreal implant 0.7 mg (DEX; Ozurdex) monotherapy in the patient subgroup of the AUSSIEDEX study with treatment-naïve diabetic macular oedema (DME).MethodsThe open-label, prospective, phase...

The STArgardt Remofuscin Treatment Trial (STARTT): design and baseline characteristics of enrolled Stargardt patients

Background: This report describes the study design and baseline characteristics of patients with Stargardt disease (STGD1) enrolled in the STArgardt Remofuscin Treatment Trial (STARTT). Methods: In total, 87 patients with genetically confirmed STGD1 were randomized in a double-masked, placebo-controlled proof of concept trial to evaluate the safety and efficacy of 20 milligram oral remofuscin for 24 months. The primary outcome measure is change in mean quantitative autofluorescence value of an 8-segment ring centred on the fovea (qAF8). Secondary efficacy variables are best corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), mesopic microperimetry (mMP), spectral domain optical coherence tomography (SD-OCT), reading speed on Radner reading charts, and patient-reported visual function as assessed by the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and Functional Reading Independence (FRI) Index. Results: Mean age of participants was 35±11 years with 49 (56%) female. Median qAF8 value was 438 Units (range 210-729). Median BCVA and LLVA in decimal units were 0.50 (range 0.13-0.80) and 0.20 (range 0.06-0.63), respectively. The median of the mean retinal sensitivity with mMP was 20.4 dB (range 0.0-28.8). SD-OCT showed median central subfield retinal thickness of 142 µm (range 72-265) and median macular volume of 1.65 mm3 (range 1.13-2.19). Compared to persons without vision impairment, both reading performance and patient-reported visual function were significantly lower (p&lt;0.001, one sample t-test). Mean reading speed was 108±39 words/minute with logRAD-score of 0.45±0.28. Mean VFQ-25 composite score was 72±13. Mean FRI Index score 2.8±0.6. Conclusions: This trial design may serve as reference for future clinical trials as it explores the utility of qAF8 as primary outcome measure. The baseline data represent the largest, multi-national, STGD1 cohort to date that underwent standardized qAF imaging, reading speed assessment and vision-related quality of life measures which all contribute to the characterization of STGD1. EudraCT registration: 2018-001496-20 (09/05/2019)

Analyses of the effects of persistent subretinal fluid on visual/anatomic outcomes according to the type of macular neovascularization during the relaxed treat-and-extend protocol in age-related macular degeneration patients

BackgroundTo analyze the long-term effects of persistent subretinal fluid (SRF) on visual/anatomic outcomes according to the type of macular neovascularization (MNV) during relaxed treat-and-extend regimen with anti-vascular endothelial growth factor (anti-VEGF) agents in age-related macular degeneration (AMD) patients.MethodsPatients with fovea-involving type 1 or type 2 MNV, treated with a relaxed treat-and-extend regimen for 2 years were retrospectively reviewed. Eyes with SRF observed more than three times per year were defined as the ‘persistent SRF (+) group’. To exclude the effects of IRF as much as possible, the eyes with persistent IRF were excluded. The effects of persistent SRF on the best-corrected visual acuity (BCVA), central subfield retinal thickness (CST), and changes in the photoreceptor layer (PRL) thickness and outer retinal bands (external limiting membrane, ellipsoid zone, and cone outer segment tip line) after anti-VEGF injection were analyzed for each MNV type.ResultsSeventy-seven eyes with type 1 MNV (44 eyes with persistent SRF) and 53 eyes with type 2 MNV (18 eyes with persistent SRF) were enrolled. Following a relaxed treat-and-extend regimen with anti-VEGF agents, BCVA and CST improved for each MNV type. In comparison between persistent SRF (+) and persistent SRF (−) group, there were no differences in the amount of change in BCVA and CST between the two groups for each MNV type during 2-year follow-up periods. In addition, there were no differences in the amount of reduction in PRL thickness and state of the outer retinal bands between the two groups for each MNV type.ConclusionsUsing a relaxed treat-and-extend regimen with anti-VEGF agents, persistent SRF did not have additional effects on visual and anatomic outcomes by 2 years, regardless of the MNV type.

Real-life experiences with Brolucizumab in recalcitrant neovascular age-related macular degeneration

Pivotal clinical trials have proven brolucizumab to be apotent intravitreal anti-vascular endothelial growth factor (VEGF) drug in patients with neovascular age-related macular degeneration (nAMD). Therefore, it seems to be apromising drug also in patients with recalcitrant nAMD. This article presents the results of patients who were switched to brolucizumab due to persistent fluid under previous anti-VEGF treatment. In this study 21 eyes were retrospectively analyzed in which treatment was switched to brolucizumab due to persistent intraretinal (IRF), subretinal (SRF) and/or sub-retinal pigment epithelium (sub-RPE fluid) fluid despite long-term anti-VEGF treatment. Functional and spectral domain optical coherence tomography (SD-OCT) data were investigated at diagnosis of nAMD(I), at switch to brolucizumab(II), 4 weeks after upload of brolucizumab(III) and at first reactivation of macular neovascularization (MNV,IV). There were no significant changes in fluid distribution between(I) and(II). After upload of brolucizumab(III) asignificant reduction of central subfield retinal thickness (CSRT, p = 0.0001), SRF (p = 0.004) and sub-RPE fluid (p = 0.04), but no visual acuity improvement (p = 0.56) were observed. Intravitreal brolucizumab treatment can achieve significant reductions particularly of SRF and sub-RPE in patients refractory to previous anti-VEGF treatment. Future studies should further investigate the effects of brolucizumab in patients with recalcitrant nAMD.

Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study

BackgroundBrolucizumab has recently been approved in Europe as a novel treatment for patients with neovascular age-related macular degeneration (nAMD). We report on early experiences with real-world outcomes of switch to...

Intravitreal injections of anti-VEGF agents during COVID-19 pandemic: clinical audit from Tanta University Hospital

BackgroundThe aims of this study were to provide real-life data about the effect of COVID-19 pandemic on the practice of anti-VEGF injections and to evaluate the safety of the modifications in the injection protocol imposed during the ongoing pandemic on the anatomical and functional outcome of patients.MethodsAll patients attending Tanta University hospital for receiving intravitreal anti-VEGF injections were screened. Patients who were previously deferred according to a modified protocol implemented in the hospital in response to the pandemic or who demonstrated deviation from it were included for further analysis.ResultsDuring the audit period, 83 patients attending for anti-VEGF injections were screened, of whom 40 met the abovementioned criteria and were included for analysis. In the deferred subgroup (11 eyes), predeferral mean values of logMAR best corrected visual acuity (BCVA) and central retinal subfield thickness (CST) were 1 ± 0.23 and 444.57 ± 200.1 µm, respectively. There was no significant change when the patients returned for their deferred injections, with the mean BCVA and CST values being 0.8 ± 0.22 and 413.71 ± 237.7 µm, respectively (p = 0.27 and p = 0.12). Moreover, 29 patients encountered a disturbed injection schedule, particularly skipping their injection appointments due to infection fear as found in 18 patients.ConclusionThe COVID-19 pandemic has imposed pressing challenges in maintaining essential health care while ensuring the prevention of spread of infection. Although the modified injection protocol confirmed to be safe for patients, the pandemic caused deflection from the optimum practice in the form of successive skipping of appointments and delays in the processing of patient injection schedules.

Eplerenone versus placebo for chronic central serous chorioretinopathy: the VICI RCT

Background In chronic central serous chorioretinopathy, fluid accumulates in the subretinal space and causes permanent vision loss in ≈ 30% of patients. There is no definitive treatment. Previous research suggests that the mineralocorticoid receptor antagonist eplerenone is effective but it is not licensed for chronic central serous chorioretinopathy. Objectives The objective was to evaluate whether or not eplerenone was safe and superior to placebo for treating chronic central serous chorioretinopathy. We also aimed to set up a biobank of DNA, serum and plasma samples from treatment-naive participants for future research. Design The trial was a parallel, randomised (1 : 1 ratio), multicentre, double-masked, placebo-controlled superiority trial comparing eplerenone plus usual care with placebo plus usual care. Participants were randomly allocated to eplerenone or placebo using a secure online system that returned a unique number corresponding to a bottle of the investigational medicinal product. Participants, clinical care teams, pharmacists, outcome assessors and the trial management group were masked. Setting The trial took place in 22 NHS hospitals in the UK. Participants Eligible participants were patients aged 18–60 years with treatment-naive chronic central serous chorioretinopathy of at least 4 months’ duration, a best corrected visual acuity score of 54–85 letters and no other conditions affecting visual acuity or contraindications to taking eplerenone or placebo. Interventions The intervention was oral eplerenone (25 mg/day for 1 week, increased to 50 mg/day for up to 12 months). Placebo was a lactose-filled capsule that appeared identical to the overencapsulated eplerenone tablets. To maintain blinding, participants in the placebo group followed the same dose escalation schedule as the eplerenone group. Usual care was included in both groups and was administered at the discretion of clinicians. Main outcome measures The primary outcome was best corrected visual acuity score at 12 months. Secondary outcomes were low-luminance visual acuity, central subfield retinal thickness, change in subretinal fluid thickness, systemic and ocular adverse events, macular atrophy of the retinal pigment epithelium, subfoveal choroidal thickness, choroidal permeability, resolution of subretinal fluid, time to recurrence of subretinal fluid, fundus fluorescein angiography phenotype, incidence of chronic central serous chorioretinopathy in the fellow eye, and patient-reported visual function. Results Between 11 January 2017 and 22 February 2018, 57 participants were randomised to eplerenone and 57 to placebo; 57 and 54 participants, respectively, were included in the analysis of the primary outcome. The modelled mean best corrected visual acuity score at 12 months in the eplerenone and placebo groups was 80.4 letters (standard deviation 4.6 letters) and 79.5 letters (standard deviation 4.5 letters), with an estimated difference between groups of 1.73 letters (95% confidence interval –1.12 to 4.57 letters; p = 0.24). Hyperkalaemia occurred in eight participants in each group (14%). No serious adverse events occurred in the eplerenone group; three unrelated serious adverse events occurred in the placebo group. Limitations Limitations included the inability to prevent co-treatments and discontinuation of the investigational medicinal product in the event of resolution or hyperkalaemia. Conclusions Eplerenone was safe but not superior to placebo in improving best corrected visual acuity in people with chronic central serous chorioretinopathy during 12 months of follow-up. In future work, ophthalmologists should investigate alternative treatments for this condition, which remains complicated to treat. Trial registration Current Controlled Trials ISRCTN92746680. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 2. See the NIHR Journals Library website for further project information.