Decrease In Central Subfield Thickness Research Articles

Vitreoretinal Interface Abnormalities in Patients With Retinal Vein Occlusion in a Tertiary Referral Center.

The purpose of this study is to investigate the prevalence of vitreoretinal interface (VRI) disorders in patients with retinal vein occlusion (RVO) and to evaluate the impact of VRI abnormalities on the treatment outcomes of macular edema secondary to RVO using intravitreal aflibercept. Participants in this prospective study were consecutive patients with macular edema secondary to RVO, who received intravitreal aflibercept injections. At baseline, best-corrected visual acuity (BCVA) was assessed, and spectral domain-optical coherence tomography (SD-OCT) was performed to measure central subfield thickness (CST) and to evaluate the presence of VRI disorders, namely, vitreoretinal adhesion (VMA), vitreoretinal traction (VMT), epiretinal membrane (ERM), lamellar macular hole (LMH), and full-thickness macular hole (FTMH). The primary outcomes were the prevalence of various VRI disorders in patients with RVO and the impact of VRI disorders on BCVA and CST after aflibercept treatment in such patients. At baseline, 16.1% of patients had VMA, 3.2% VMT, 18.3% ERM, and 1.1% LMH. There were a statistically significant improvement in BCVA and a decrease in CST in RVO patients over time. There was no statistically significant difference regarding BCVA and CST at baseline and until month 24 after treatment between patients with VRI disorders and those without VRI disorders. However, the mean number of injections during the follow-up period was higher in the group with VRI disorders (9.4±2.1) compared to those without VRI disorders (8.1±0.7, p=0.0002). The prevalence of VRI disorders in patients with RVO was 16.1% for VMA, 3.2% for VMT, 18.3% for ERM, and 1.1% for LMH. VRI disorders were not found to affect the anatomical and visual outcomes after intravitreal aflibercept treatment in patients with RVO, although more intravitreal injections were needed in patients with VRI disorders.

Subthreshold micropulse laser therapy for early postoperative macular thickening following surgical removal of epiretinal membrane

BackgroundThis study aimed to investigate the functional and anatomical outcomes of subthreshold micropulse laser (SMPL) therapy in eyes with early postoperative macular thickening after idiopathic epiretinal membrane (iERM) removal.MethodsThis was a prospective and interventional study. Forty-eight eyes from 48 patients with macular edema at 1 month after iERM removal were randomly divided into two groups. Patients in the SMPL group (n = 24) received SMPL therapy while no special intervention was used for the observation group (n = 24). Baseline demographic data and clinical findings before and at 1 and 3 months after SMPL treatment or observation, including best-corrected visual acuity (BCVA) and the changes in central subfield thickness (CST) and average macular thickness (AMT), were analyzed.ResultsAn improvement in BCVA with a decrease in CST and AMT from baseline to the 3-month follow-ups were observed in both SMPL and observation groups. No significant difference in BCVA was observed between the SMPL group and observation group either in the 1-month (0.26 [0.15, 0.52] vs. 0.26 [0.15, 0.39], P = 0.852) or the 3-month (0.15 [0.10, 0.30] vs. 0.23 [0.15, 0.30], P = 0.329) follow-up. There was a greater reduction in CST in the SMPL group versus observation group between baseline and the 3-month follow-up (-77.8 ± 72.3 μm vs. -45.0 ± 46.9 μm, P = 0.049). The alteration in AMT did not differ between the two groups in either 1-month (-16.5 ± 20.1 μm vs. -19.7 ± 16.3 μm, P = 0.547) or 3-month (-36.9 ± 26.9 μm vs. -34.0 ± 20.1 μm, P = 0.678) follow-up.ConclusionsSMPL therapy led to a significant decrease in CST at the 3-month follow-up while did not significantly improve the visual acuity in patients with postoperative macular thickening following iERM surgery.Trial registrationThe study was registered on Aug 27, 2020 (Trial Registration Number: ChiCTR 2000037227).

Response of Diabetic Macular Edema to Anti-VEGF Medications Correlates with Improvement in Macular Vessel Architecture Measured with OCT Angiography

PurposeImprovement in best corrected visual acuity (BCVA) and central subfield thickness (CST) have been well documented after intravitreal injection of anti-VEGF medications in diabetic macular edema (DME), however their effect on the vasculature of the macula in diabetic retinopathy (DR) remains poorly understood. Our aim was to explore the effect of intravitreal injection of anti-VEGF on parameters of retinal vascular microstructure in DR with optical-coherence tomography angiography (OCT-A). DesignRetrospective study of adult patients with DME that were treated with anti-VEGF intravitreal injections at the University of Illinois at Chicago between 2017-2022. Subjects, Participants, and/or Controls41 eyes from 30 patients with non-proliferative or proliferative DR with a mean age of 58.83 ± 11.71years, mean number of intravitreal injections of 2.8 ± 1.4, and mean follow up of 6.5 ± 1.7 months. Methods, Intervention, or TestingImageJ was employed to measure parameters of retinal vascular microstructure in OCT-A images, which included perfusion density, vessel length-density (VLD), vessel diameter, and FAZ characteristics (area, perimeter, circularity). Student’s T-tests and ANOVA were used to determine statistical significance. Main Outcome MeasuresA primary analysis was performed comparing the mean of each parameter of all patients as a single group at the beginning and end of the study period. A subgroup analysis was then performed after stratifying patients based on visual improvement, change in CST, prior injection history, and number of injections. ResultsEyes demonstrated statistical improvement in BCVA logMAR score and CST after anti-VEGF treatment. Primary analysis showed a reduction in the vessel diameter of the superficial and deep retinal vasculature as well as an increase in the circularity of the FAZ within the superficial retinal vasculature after anti-VEGF treatment. Subgroup analysis revealed that eyes with improvement in BCVA exhibited reduced vessel diameter in the superficial retinal vasculature and that eyes with the largest decrease in CST displayed increased perfusion density and VLD in the deep retinal vasculature. ConclusionsIntravitreal injection of anti-VEGF agents to treat DME improved parameters of retinal vascular microstructure on OCT-A over a period of 3-9 months, and this effect was most pronounced in eyes that experienced improvement in BCVA and CST.

Intravitreal injection of methotrexate in persistent diabetic macular edema: a 6-month study.

Diabetic macular edema (DME) affects approximately 10% of patients with diabetes mellitus. This condition can cause blurred or distorted vision, which significantly affects the quality of life of these patients. We evaluated the therapeutic effects of intravitreal methotrexate (MTX) injections on persistent DME. This prospective interventional case series included patients with confirmed persistent DME that was unresponsive to previous standard treatments. The patients underwent comprehensive eye examinations and macular imaging with optical coherence tomography (OCT). A single intravitreal MTX injection (400 µg MTX in 0.16 mL solution) was administered, followed by patient assessments at 1, 3, and 6 months after injection. Best-corrected distance visual acuity (BCDVA), intraocular pressure (IOP), macular thickness (MT), and central subfield thickness (CST) were measured at baseline and post-injection to evaluate treatment efficacy. We included 33 eyes of 30 patients with a mean (standard deviation [SD], range) age of 62.7 (8.3, 44 to 77) years, of whom 17 (56.7%) were men and 13 (43.3%) were women. All participants had type 2 diabetes mellitus, with a mean (SD, range) duration of 17.0 (6.8, 10 to 31) years. Most participants (n = 27 eyes, 81.8%) had non-proliferative diabetic retinopathy, and six eyes (18.2%) had regressed proliferative diabetic retinopathy. Four eyes (12.1%) had undergone prior macular laser photocoagulation. The mean (SD) number of prior intravitreal bevacizumab injections was 3.4 (0.8), and 29 eyes (87.8%) had received one intravitreal triamcinolone injection. During the study period, a statistically significant difference was observed in CST (P < 0.05); however, no statistically significant differences were observed in BCDVA, MT, or IOP (P > 0.05). Pairwise comparison revealed a significant decrease in CST at 6 months post-injection compared to the baseline value (P < 0.05). During the investigation period, no side effects of MTX, such as macular edema, retinal tears, vitreous hemorrhage, endophthalmitis, or vision loss, were observed. A single intravitreal MTX injection significantly reduced CST in patients with persistent DME, without relevant safety concerns. However, no significant improvement in functional outcomes was observed. Therefore, there is no strong evidence to recommend its use as a treatment for pDME. Further studies, preferably randomized clinical trials with long-term follow-ups, are warranted to assess the long-term efficacy, safety, and potential benefits of intravitreal MTX for the treatment of persistent DME.

Machine Learning to Predict Faricimab Treatment Outcome in Neovascular Age-Related Macular Degeneration

To develop machine learning (ML) models to predict, at baseline, treatment outcomes at month 9 in patients with neovascular age-related macular degeneration (nAMD) receiving faricimab. Retrospective proof of concept study. Patients enrolled in the phase II AVENUE trial (NCT02484690) of faricimab in nAMD. Baseline characteristics and spectral domain-OCT (SD-OCT) image data from 185 faricimab-treated eyes were split into 80% training and 20% test sets at the patient level. Input variables were baseline age, sex, best-corrected visual acuity (BCVA), central subfield thickness (CST), low luminance deficit, treatment arm, and SD-OCT images. A regression problem (BCVA) and a binary classification problem (reduction of CST by 35%) were considered. Overall, 10 models were developed and tested for each problem. Benchmark classical ML models (linear, random forest, extreme gradient boosting) were trained on baseline characteristics; benchmark deep neural networks (DNNs) were trained on baseline SD-OCT B-scans. Baseline characteristics and SD-OCT data were merged using 2 approaches: model stacking (using DNN prediction as an input feature for classical ML models) and model averaging (which averaged predictions from the DNN using SD-OCT volume and from classical ML models using baseline characteristics). Treatment outcomes were defined by 2 target variables: functional (BCVA letter score) and anatomical (percent decrease in CST from baseline) outcomes at month9. The best-performing BCVA regression model with respect to the test coefficient of determination (R2) was the linear model in the model-stacking approach with R2 of 0.31. The best-performing CST classification model with respect to test area under receiver operating characteristics (AUROC) was the benchmark linear model with AUROC of 0.87. A post hoc analysis showed the baseline BCVA and the baseline CST had the most effect in the all-model prediction for BCVA regression and CST classification, respectively. Promising signals for predicting treatment outcomes from baseline characteristics were detected; however, the predictive benefit of baseline images was unclear in this proof-of-concept study. Further testing and validation with larger, independent datasets is required to fully explore the predictive capacity of ML models using baseline imaging data. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Outcomes in patients with retinal vein occlusion with good baseline visual acuity.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) are first-line therapy for macular oedema in retinal vein occlusion (RVO). Appropriate management for RVO with good visual acuity at diagnosis has not been evaluated. The purpose of this study is to analyse the visual and anatomic outcomes from anti-VEGF treatment among RVO patients with good vision at baseline. This retrospective cohort study evaluated patients diagnosed with macular oedema secondary to RVO from January 2012 to February 2021 at a tertiary ophthalmic centre. Patients had a Snellen acuity of 20/32 or better at diagnosis. Three cohorts were compared: patients with no anti-VEGF treatment, delayed anti-VEGF treatment (initial injection >30 days post-diagnosis) and immediate anti-VEGF treatment (initial injection ≤30 days post-diagnosis). Central subfield thickness (CST) and best visual acuity (BVA) were collected at diagnosis and 6-, 12- and 24-month follow-up appointments. Among 131 eyes, mean BVA values among treatment groups did not differ at 6-, 12- or 24-month follow up visits (P = 0.521, 0.426, 0.356, respectively). The percentage of eyes with at least a 5-letter BVA decrease at 24 months was 24.1%, 65.0% and 30.8% in the no treatment, delayed and immediate treatment groups respectively (P = 0.010). There was no significant difference in the percentage of eyes with at least a 10% decrease in CST at 24 months among groups (P = 0.095). Close observation with initiation of treatment in patients with good visual acuity with macular oedema secondary to RVO as indicated has similar outcomes in the setting of routine clinical practice.

Oral minocycline for the treatment of retinitis pigmentosa-associated cystoid macular edema: results of a phase I/II clinical trial.

The etiology of retinitis pigmentosa (RP)-associated cystoid macular edema (CME) has been related to retinal neuroinflammation and microglial activation. Minocycline, a drug FDA-approved for anti-microbial indications, also inhibits microglial activation and expression of inflammatory mediators. This study investigates the safety and efficacy of oral minocycline as primary treatment for RP-associated CME. A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with RP-associated CME. Participants had lead-in assessments prior to the initiation of oral minocycline 100mg twice daily for 12months. Main outcome variables included changes in best-corrected visual acuity (BCVA) and retinal central subfield thickness (CST) measured using spectral domain optical coherence tomography relative to mean of pre-treatment measurements. The study drug was well tolerated and not associated with any severe adverse events. No significant changes in mean BCVA from study baseline were noted in either the study eye (+ 0.7 ± 4.1 letters at 6months, - 1.1 ± 1.7 letters at 12months) or the qualifying fellow eye (- 0.3 ± 3.4 letters at 6months, - 0.3 ± 4.6 letters at 12months) (p > 0.05 for all comparisons). Mean percentage changes in CST from baseline however decreased progressively with treatment (decreases at 6 and 12months: study eyes 3.9 and 9.8%; qualifying fellow eyes 1.4 and 7.7%). Considering all eyes (n = 10), mean percentage CST decrease at 6 and 12months was 2.7 ± 9.5% (p = 0.39) and 8.7 ± 9.5% (p = 0.02) respectively. Oral minocycline administration over 12months was associated with no significant changes in mean BCVA and a small but progressive decrease in mean CST. NCT02140164 (05/2014).

Post-operative visual outcomes based on morphological staging of idiopathic epiretinal membranes on OCT.

To evaluate the recently described optical coherence tomography (OCT) based classification of epiretinal membrane (ERM) and its usefulness in predicting the functional outcome. A retrospective observational review of OCT scans of patients with the diagnosis of idiopathic ERM was carried out from January 2016 to June 2021. All consecutive images diagnosed with any stage of idiopathic ERM and fulfilled the eligibility criteria were included in the analysis. ERM was identified on OCT scans as a thin hyperreflective layer over the inner layers of retina. OCT scans of patients with ERM who underwent vitrectomy, were independently staged as per the new classification by two independent retinal surgeons to form a consensus on stage. Best corrected visual acuity (BCVA) in logMAR scale and central subfield thickness (CST) on pre- and post-operative spectral domain OCT scans were the variables noted for all patients at the time of diagnosis and at 6 and 12mo follow up visit after undergoing intervention. Partial correlation coefficient was computed between BCVA (logMAR) and CST by ERM stage adjusting by baseline measures. Clinical charts of 74 patients with idiopathic ERM were assessed. Clinically significant improvement in BCVA overtime was observed with significant difference in median visual acuity of patients with Stage II-IV ERM with P<0.001. The median CST of all patients with stage II-IV ERM showed similar consistent improvement with P<0.001 from baseline to 12th month. Our results showed not only gain in visual acuity but also shift from baseline to anatomical normalization of CST in stage II. We found a decrease in CST with difference of 166 µm and 151 µm in stage III and stage IV respectively. Our results remained consistent with the hypothesis of improved visual outcomes with all stages of ERM with adjusted moderate linear correlation between visual acuity and CST in stage II-IV (r>0.3). Equally significant visual outcomes of patients with ERM staged II-IV and therefore can be counselled for improved visual acuity after surgical removal of ERM with improvement up to 5 lines on Snellen's chart from the baseline.

Long-term efficacy and safety of RazumabTM (biosimilar ranibizumab) in Indian patients with retinal diseases: results from retrospective REAR RD-2 study

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; To evaluate risk factors associated with retinal diseases and efficacy and safety of Razumab&lt;sup&gt;TM&lt;/sup&gt; (biosimilar ranibizumab) in the management of retinal diseases in Indian patients with wet age-related macular degeneration (wet AMD), diabetic macular edema (DME), retinal vein occlusion (RVO) and myopic choroidal neovascularization (mCNV).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods:&lt;/strong&gt; In the retrospective, observational REAR RD-2 study, all patients with retinal diseases who were treated with biosimilar ranibizumab were included from multiple Indian sites. The demographic parameters, disease characteristics and treatment details were recorded. Efficacy assessments included improvement in best corrected visual acuity (BCVA), and decrease in central subfield thickness (CSFT), intra-retinal fluid (IRF) and sub-retinal fluid (SRF) from baseline to week 48.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; Data of 1422 patients (wet AMD-27.57%; DME-30.7%, RVO-33.47%; mCNV-5.48%), who were treated with biosimilar ranibizumab, was analyzed. The most common age group of patients was 61-70 years (36.6%). The most common ocular risk factor identified was glaucoma (24.90%). A total of 85.72% patients were treatment naïve and 14.28% were previously treated patients. Biosimilar ranibizumab treatment resulted in significant (p&amp;lt;0.05) improvements in the mean BCVA and CSFT, and the proportion of patients with IRF and SRF was significantly reduced throughout the treatment. No new safety concerns with biosimilar ranibizumab were observed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Retinal diseases are more common in the age group of 61-70 years. Glaucoma was the most common ocular risk factor identified for retinal diseases. Long-term treatment with biosimilar ranibizumab was effective and well-tolerated in retinal diseases including wAMD, DME, RVO and mCNV in real-world Indian scenario. &lt;/p&gt;&lt;p&gt;&lt;strong&gt; &lt;/strong&gt;&lt;/p&gt;

Optical coherence tomography angiography analysis of changes in the foveal avascular zone in eyes with diabetic macular edema treated with intravitreal anti-vascular endothelial growth factor

BackgroundTo analyze the changes in foveal avascular zone (FAZ) area, perimeter, and circularity in the superficial (SCP) and deep (DCP) capillary plexuses in eyes with diabetic macular edema (DME) treated with intravitreal anti-VEGF using optical coherence tomography angiography (OCTA).MethodsThis prospective observational study included 56 eyes from 32 patients with DME that received intravitreal anti-VEGF. OCTA images were obtained at baseline and 1, 3, and 6 months of follow-up. The outcome measures were FAZ area, perimeter, and circularity in both the SCP and DCP, as well as central subfield thickness (CST) and best-corrected visual acuity (BCVA).ResultsThe mean number of intravitreal anti-VEGF injections received during the observation period was 4.60 ± 0.82 (range: 3–6). The FAZ area, perimeter, and circularity were statistically unchanged at all observation points in both the SCP (p = 0.772, p = 0.405, p = 0.157, respectively) and the DCP (p = 0.620, p = 0.769, p = 0.481, respectively). Despite having no change in the FAZ parameters, there was still a statistically significant decrease in CST (p < 0.001) as well as a statistically significant increase in BCVA (p = 0.004) during the observation period.ConclusionsThe FAZ area, perimeter, and circularity in the SCP and DCP as measured by OCTA remained stable during the first 6 months of intravitreal anti-VEGF therapy in eyes with DME. While there were no significant changes in the FAZ, treatment with intravitreal anti-VEGF still resulted in decreased CST and improved BCVA.

Correlation of Change in Macular Thickness With Change in Visual Acuity in Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials.

Purpose: To assess the correlation between the change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with diabetic macular edema (DME) treated with fixed-dosing intravitreal aflibercept injection (IAI). Methods: This post hoc analysis of the VISTA and VIVID randomized controlled clinical trials, in which 862 eyes with central-involved DME were randomly assigned to IAI 2 mg every 4 weeks (2q4; 290 eyes), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8; 286 eyes), or macular laser (286 eyes) and followed through 100 weeks. Correlations between the change in CST and change in BCVA from baseline to weeks 12, 52, and 100 were assessed using the Pearson correlation. Results: The respective correlations (r [95% CI]) at weeks 12, 52, and 100 were -0.39 (-0.49 to -0.29), -0.27 (-0.38 to -0.15), and -0.30 (-0.41 to -0.17) in the 2q4 arm and -0.28 (-0.39 to -0.17), -0.29 (-0.41 to -0.17), and -0.33 (-0.44 to -0.20) in the 2q8 arm. Linear regression analysis of the correlation at week 100, adjusted for relevant baseline factors, showed CST changes accounted for 17% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 1.2-letter increase in BCVA (P = .001). Conclusions: Correlations between the change in CST and change in BCVA after 2q4 or 2q8 fixed-dosing IAI for DME were modest. Although a change in CST might be important in determining the need for antivascular endothelial growth factor for DME at follow-up, it was not a good surrogate for VA outcomes.

Correlation between change in central subfield thickness and change in visual acuity in macular edema due to retinal vein occlusion: post hoc analysis of COPERNICUS, GALILEO, and VIBRANT

PurposeAssess correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with macular edema due to retinal vein occlusion (RVO) that received intravitreal aflibercept injections (IAI).MethodsPost hoc analysis of COPERNICUS and GALILEO trials for CRVO and VIBRANT trial for BRVO with relationships determined using Pearson correlation coefficient.ResultsIn COPERNICUS, correlations (r) between change in CST and change in BCVA from baseline at weeks 12, 24, 52, and 100 were −0.36 (95% CI: −0.52, −0.18; P < 0.001), −0.38 (95% CI: −0.53, −0.20; P < 0.001), −0.44 (95% CI: −0.58, −0.27; P < 0.001), and −0.41 (95% CI: −0.56, −0.23; P < 0.001), respectively. CST changes accounted for only 21% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 2.1-letter increase in BCVA (P = 0.003). Similar findings were noted for GALILEO (r, −0.45 to −0.23) and VIBRANT (r, −0.36 to −0.32) trials.ConclusionIn eyes treated with IAI for macular edema due to RVO, correlation between change in CST and change in BCVA was weak to moderate. While change in CST may be helpful in determining the need for anti-VEGF therapy, these findings do not support using changes in CST as a surrogate for changes in visual acuity outcomes.

A Randomized, Controlled Trial of Treat-and-Extend vs. Pro Re Nata Regimen for Neovascular Age-Related Macular Degeneration.

PurposeTo compare the efficacy and safety of conbercept using a treat-and-extend (T&E) regimen vs. a pro re nata (PRN) regimen in Chinese patients with neovascular age-related macular degeneration (nAMD).MethodsThis was a randomized, multicenter, non-inferiority study. After an initial loading phase of three consecutive monthly intravitreal injections of 0.5 mg Conbercept, the patients were treated to PRN or T&E regimen. The prespecified retreatment criteria was defined as a more than 5-letter decrease in BCVA from the previous visit or any evidence of new retinal hemorrhages, or the presence of any IRF and any SRF of more than 200 μm in height at the sub-foveal center. The primary outcome was the mean change in best-corrected visual acuity (BCVA) from baseline to 24 months, with a prespecified non-inferiority limit of −5 letters.ResultsFrom July 2016 through August 2018, 141 participants were allocated and treated (T&E, n = 69; PRN, n = 72). About one fifth of the overall participants were dropped out during the 12-month follow-up (28/141, 19.9%), and about one thirds of the overall participants were lost during the 24-month follow-up (51/141, 36%). At 2 years, mean BCVA letter improvement was + 4.0 in the T&E group vs. + 5.1 in the PRN group, and T&E regimen was not non-inferior to PRN regimen [difference, −1.169 letters; 95% confidence interval (CI): −6.864 ∼ 4.526]. Subgroup analyses also demonstrate the similar results in PCV patients, naive patients and no-naive patients. The mean decrease in central subfield thickness were 180 ± 165 μm in the T&E group and 247 ± 230 μm in the PRN group, respectively. The patients in the PRN group had required significantly fewer injections than those in the T&E group (12.4 vs. 14.6 injections, P = 0.041). The types and rates of adverse events were comparable in the two treatment groups.ConclusionThese findings suggest that the T&E regimen was not non-inferior to the PRN regimen in patients with nAMD in terms of BCVA outcomes through 24 months.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT02802657.

Correlation of Change in Central Subfield Thickness and Change in Visual Acuity in Neovascular AMD: Post Hoc Analysis of VIEW 1 and 2

Determine correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor agents. A post hoc analysis of VIEW 1 and 2 randomized clinical trials. This analysis included participants randomized to ranibizumab 0.5 mg every 4 weeks (Rq4), intravitreal aflibercept injection 2 mg every 4 weeks (2q4), and intravitreal aflibercept injection 2 mg every 8 weeks after 3 monthly doses (2q8) to week 52, followed by capped as-needed (at least every 12 weeks) dosing to week 96. Relationship between changes in CST and BCVA was determined using Pearson correlation coefficient. Of 1815 eyes, 595 were assigned to the Rq4, 613 to 2q4, and 607 to 2q8 arms. Correlations (95% confidence intervals [CI]) at weeks 12, 52, and 96 were -0.08 (95% CI, -0.17 to 0.00), -0.05 (95% CI, -0.14 to 0.04), and -0.15 (95% CI, -0.24 to -0.06) for Rq4; -0.13 (95% CI, -0.21 to -0.04), -0.06 (95% CI, -0.14 to 0.03) and -0.04 (95% CI, -0.13 to 0.05) for 2q4, and -0.04 (95% CI, -0.12 to 0.05), -0.01 (95% CI, -0.09 to 0.08), and -0.01 (95% CI, -0.10 to 0.09) for 2q8. Linear regression analysis adjusted for relevant baseline factors showed CST changes accounted for 11% of BCVA changes. Every 100 μm decrease in CST was associated with a 0.3 letter decrease (P = .25) at week 52 and a 0.14 letter decrease (P = .69) at week 96. Weak or no correlation was found between changes in CST and BCVA with either agent or regimen, suggesting changes in CST should not be used as a surrogate for visual acuity outcomes in neovascular age-related macular degeneration.

Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study.

The present study aimed to determine the efficacy and safety of pro re nata (PRN) intravitreal brolucizumab therapy for neovascular age-related macular degeneration (AMD) without a loading dose in the real-world setting. The PROBE study (Pro Re Nata Brolucizumab for Exudative AMD) is a retrospective, observational, multicentric study that included 27 treatment-naïve patients (27 eyes) with neovascular AMD who received PRN brolucizumab therapy with the treatment interval being at least 8 weeks, should the need for a second consecutive injection arise. The primary outcome measure was changed to best-corrected visual acuity (BCVA) over time. Secondary outcome measures included the determination of change in central subfield thickness (CST) and complications. The mean follow-up was 11.2 ± 1.2 months. The mean baseline and final BCVA were 57.4 ± 4.5 letters and 65.3 ± 3.12 letters, respectively (p = 0.014). The mean gain in letters at the end of follow-up was 7.8 ± 3.5 letters. There was a significant decrease in CST at the end of the follow-up period (p = 0.013). Patients received a mean of 2.2 ± 0.9 injections (in addition to the first mandatory injection) during the follow-up period. There were no adverse events noted. In conclusion, initial PRN brolucizumab for exudative AMD without a loading dose demonstrated significant visual improvement and no adverse events.

Phase 1 Study of THR-687, a Novel, Highly Potent Integrin Antagonist for the Treatment of Diabetic Macular Edema

PurposeTo evaluate the safety and preliminary efficacy of THR-687 in patients with center-involved diabetic macular edema (DME).DesignPhase 1, open-label, multicenter, 3 + 3 dose-escalation study with 3-month follow-up.ParticipantsPatients 18 years of age or older with visual impairment resulting from DME.MethodsSingle intravitreal injection of THR-687 (0.4 mg, 1.0 mg, or 2.5 mg).Main Outcome MeasuresThe primary outcome measure was the incidence of dose-limiting toxicities (DLTs). The secondary outcome measure was the incidence of adverse events (AEs), including the occurrence of laboratory abnormalities. Exploratory outcome measures included changes from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST), assessments of ischemia and leakage on fluorescein angiography, and THR-687 levels in plasma.ResultsTwelve patients were treated: 3 patients received 0.4 mg of THR-687, 3 patients received 1.0 mg of THR-687, and 6 patients received 2.5 mg of THR-687. Most patients were men (9/12 patients). Their mean age was 57.8 years. No DLTs or serious AEs were reported at any of the dose levels tested. Overall, 9 AEs in the study eye were reported for 5 of 12 patients. Of those, 4 AEs in 3 of 12 patients were deemed treatment related by the investigator, all of which were mild, started on the day of the injection, and had resolved within 28 days without treatment. Overall, mean gains from baseline in BCVA were observed at all study visits with a rapid onset (7.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters at day 7) and a durability up to the end of the study (8.3 ETDRS letters at month 3). A mean decrease in CST was observed up to month 1. Overall, the mean BCVA gains and CST decreases were highest at the highest THR-687 dose level tested. THR-687 was undetectable in plasma at 7 days after the injection.ConclusionsAt all dose levels tested, a single intravitreal injection of THR-687 was safe and well tolerated. Preliminary efficacy was observed by a rapid gain in BCVA with 3 months’ durability and a decrease in CST up to 1 month after the injection.

Long-term outcome of neovascular age-related macular degeneration: association between treatment outcome and major risk alleles

AimsTo evaluate the long-term functional and anatomical outcomes of neovascular age-related macular degeneration (nvAMD) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) for up to 10 years, and to identify...

One-year outcomes of Aflibercept for refractory diabetic macular edema in Bevacizumab nonresponders.

Purpose:A sub-population of patients with diabetic macular edema (DME) responds less effectively to off-label use of Bevacizumab. Approval of Aflibercept for DME has offered Bevacizumab nonresponders an alternative therapeutic option. Herein, we investigate the anatomical and functional changes associated with Aflibercept treatment in Bevacizumab nonresponders with chronic DME in a Canadian setting.Methods:A retrospective study of eyes with persistent DME that were switched to Aflibercept due to nonresponse following ≥6 consecutive monthly Bevacizumab injections was performed. Anatomical and functional changes and the predictors of response were assessed using patients' characteristics prior to receiving their first (baseline) and seventh consecutive Aflibercept injections (follow-up).Results:Twenty-four eyes were included, with a mean age of 63.9 ± 10.7 years, an average of 16.8 ± 8.5 Bevacizumab injections prior to switching to Aflibercept, and mean follow-up duration of 11.8 ± 1.7 months following switching to Aflibercept. Best-corrected visual acuity (BCVA) improved significantly from 0.49 ± 0.13 to 0.41 ± 0.11 logMAR (P < 0.001) and central subfield thickness (CST) decreased by 119.4 μm from 409.4 ± 85.8 μm to 290.0 ± 64.5 μm (P < 0.001), with 50% of eyes showing complete anatomical response. Worse BCVA and higher CST at baseline predicted greater vision improvements (P = 0.001 and P = 0.035, respectively) while a larger decrease in CST was associated with greater baseline CST (P = 0.001) and better glycemic control (P = 0.039).Conclusion:Our data from a real-world clinical setting highlight the efficacy of Aflibercept as an alternative therapeutic option for DME recalcitrant to Bevacizumab, with potential additional benefit to those with worse vision, greater CST, and better glycemic control at baseline.

Anatomical and functional outcomes of subthreshold micropulse laser versus intravitreal ranibizumab injection in treatment of diabetic macular edema

BackgroundTo compare the therapeutic effects of subthreshold micropulse laser (SML) versus intravitreal injection of ranibizumab in treatment of diabetic macular edema (DME) both anatomically using optical coherence tomography (OCT) and functionally using best corrected visual acuity (BCVA) and multifocal electroretinogram (mfERG).Methodshis study was an interventional prospective randomized comparative study. The study included 120 eyes classified into 3 groups: Group 1 included 40 eyes of 28 patients treated by SML laser, group 2 included 40 eyes of 32 patients treated by intravitreal injection of ranibizumab, and group 3 (control group for mfERG) included 40 eyes of 20 patients with diabetes mellitus (DM) of more than 10 year duration with no signs of diabetic retinopathy (DR). BCVA measurements, OCT and mfERG were done for the cases before and after interference and were followed up for 6 monthsResultsBy the end of the follow up period, BCVA significantly improved by 31% in group 1 vs 93% in group 2 with a statistically highly significant difference between the two groups (p value < 0.001). There was also a significant decrease in central subfield thickness in both groups with more reduction in group 2 compared with group 1 (p value < 0.001). There was a significant improvement in P1 amplitude of mf-ERG in group 2 (p value < 0.002) with no significant improvement in group 1. There was a significant decrease in P1 implicit time in group 2 (p value < 0.001) while there was no significant decrease in group1.ConclusionsIntravitreal injection of ranibizumab is a superior treatment modality for DME compared with SML regarding both anatomical and functional outcomes.Trial registration: This study has been approved by the local ethical committee of faculty of medicine of Minia University and retrospectively registered at the clinical trial gov. with Identifier: NCT04332133.

Systemic Regulatory T Cells and IL-6 as Prognostic Factors for Anatomical Improvement of Uveitic Macular Edema.

PurposeTo investigate whether systemic immune mediators and circulating regulatory T cells (Tregs) could be prognostic factors for anatomic outcomes in macular edema secondary to non-infectious uveitis (UME).MethodsMulticenter, prospective, observational, 12-month follow-up study of 60 patients with UME. Macular edema was defined as central subfield thickness (CST) > 300 μm measured with spectral domain optical coherence tomography (SD-OCT). Serum samples and peripheral blood mononuclear cells (PBMC) were obtained from venous blood extraction at baseline. Serum levels of IL-1β, IL-6, IL-8, IL-17, MCP-1, TNF-α, IL-10, and VEGF were determined by Luminex. Tregs population, defined as CD3+CD4+FoxP3+ in PBMC, was determined by flow cytometry. Main outcome measure was the predictive association between searched mediators and CST sustained improvement, defined as CST < 300 microns or a 20% CST decrease, at 6 months maintained until 12-months compared to baseline levels.ResultsMultivariate logistic regression analysis showed an association between CST sustained improvement at 12 months follow-up and IL-6 and Tregs baseline levels. Higher IL-6 levels were associated with less events of UME improvement (OR: 0.67, 95% CI (0.45–1.00), P = 0.042), whereas higher levels of Tregs favored such improvement (OR: 1.25, 95% CI: 1.12–2.56, P = 0.049).ConclusionsIncreased levels of Tregs and reduced levels of IL-6 in serum may be prognostic factors of sustained anatomical improvement in UME. These findings could enforce the opportunity to develop more efficient and personalized therapeutic approaches to improve long-term visual prognosis in patients with UME.