Baseline Central Subfield Thickness Research Articles

Treatment Outcomes of Intravitreal Aflibercept for Uveitic Macular Edema.

To evaluate the efficacy of intravitreal aflibercept for UME (uveitic macular). A retrospective review of records of patients that received aflibercept for UME from January 2017 to August 2022 was conducted. The primary outcomes were mean change in visual acuity (VA) and central subfield thickness (CST) 6 and 12 months from the start of aflibercept treatment. A total of 16 eyes of 12 patients were included. Indications for treatment included eyes that had previously demonstrated a history of elevated intraocular pressure secondary to a steroid response (n = 10) or a history of non-response or partial response to local corticosteroids (n = 6). Fifteen eyes (94%) demonstrated a reduction in CST after their initial injection. At 6-months, mean VA gain was 2.6 ± 7.7 letters (p = 0.24) from a mean VA of 67.8 ± 10.7 letters at baseline and mean CST improved by 97.6 ± 113.5 μm (p = 0.004) from 458.6 ± 123.1 μm at baseline. Fourteen eyes had 12-months of follow up and received a median of 4 injections over 12 visits. The mean VA at 12-months remained stable compared to baseline (mean change of -1.4 ± 12.5 letters (p = 0.87)) while the CST improved by a mean of 90.9 ± 114.6 μm (p = 0.053) compared to baseline. Intravitreal aflibercept injections resulted in reduced central subfield thickness at all time-points. It appears to be an effective treatment alternative for UME, particularly for patients who are not responsive to local corticosteroids or who have contraindications to corticosteroid treatment.

Association of baseline factors with 1-year outcomes in the SB11-ranibizumab equivalence trial: A post hoc analysis

PurposeTo identify baseline factors associated with 1-year outcomes when treating neovascular age-related macular degeneration (nAMD) with ranibizumab biosimilar SB11 or reference ranibizumab (rRBZ), and to compare efficacy of the two products within subgroups judged to be clinically relevant. DesignPost hoc analysis of a prospective, equivalence phase 3 randomized clinical trial (RCT) Methods705 patients with nAMD were randomized 1:1 to receive SB11 or rRBZ for 48 weeks. Pooled and randomized groups were used to identify baseline factors associated with clinical outcomes at Week 52 using multiple linear regression models. Significant factors identified in regression analyses were confirmed in analyses of variance. Subgroup analyses comparing best-corrected visual acuity (BCVA) changes between SB11 and rRBZ were conducted. Results634 (89.9%) participants completed the 52-week visit. Regression analyses showed that younger age, lower BCVA, and smaller total lesion area at baseline were associated with greater BCVA gain at Week 52, while older age, lower BCVA, and thicker central subfield thickness (CST) at baseline were predictors of greater CST reduction in the pooled group. Subgroup analyses demonstrated that BCVA outcomes appeared comparable for the SB11 and rRBZ groups. ConclusionPost hoc analyses of the SB11-rRBZ equivalence study showed that baseline age, BCVA, CST, and total lesion area were prognostic factors for visual or anatomical outcomes of nAMD, while subgroup analyses demonstrated comparable results for SB11 and rRBZ. Collectively, the results appear comparable to similar RCTs of anti-vascular endothelial growth factor reference products for nAMD and strengthen confidence in the biosimilarity of SB11.

Real-world effects of anti-vascular endothelial growth factor injection frequency on visual outcomes in patients with diabetic macular oedema

Background and objectiveAnti-vascular endothelial growth factor (VEGF) injections are often administered less frequently in real-world treatment of diabetic macular oedema (DMO) than what was studied in clinical trials. This study aims to characterise real-world DMO treatment patterns and the effect of treatment intervals on patient outcomes.Study design/patients and methodsThis was a retrospective study of 291 patients with DMO treated with anti-VEGF therapy. 12- and 24-month best visual acuity (BVA) and central subfield thickness (CST) were compared between injection interval groups, which were determined by averaging the two most recent injection intervals. Multiple linear regressions were performed to identify factors associated with injection interval, BVA, and CST.Results48.8% of patients received injections less than or equal to every 8 weeks (≤ q8w), 27.5% between every 8 to 12 weeks (q8–12w), and 23.7% greater than every 12 weeks (> q12w). Baseline CST was similar (p = 0.32), but BVA differed significantly in q8–12w patients (p = 0.0095). BVA and CST at 12 months were similar, but q8–12w patients experienced greater 12-month BVA improvement (7.36 ± 12.4 letters) than > q12w patients (1.26 ± 12.3 letters; p = 0.0056). 24-month BVA and CST changes were similar between groups (p = 0.30 and 0.87). Baseline BVA, HbA1c, and sex were associated with 12-month BVA, and baseline BVA and CST were associated with 12-month CST.ConclusionMany patients experienced improvements in BVA and CST over 12 months of treatment despite receiving less frequent anti-VEGF therapy than recommended in the pivotal trials. The present study showed that extended treatment intervals with bevacizumab were effective in preserving vision of many individuals with high baseline BVA.

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

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

Brolucizumab in age-related macular neovascularization (BRAIN study): Efficacy, optical coherence tomography biomarkers, and safety profile.

Brolucizumab is a new anti-vascular endothelial growth factor (anti-VEGF) in the treatment of neovascular age-related macular degeneration (nAMD) and idiopathic polypoidal choroidal vasculopathy (IPCV). A retrospective, consecutive, interventional study was conducted from a tertiary eye hospital, in which treatment-naïve and treatment-switch patients were included. They underwent an intravitreal injection of brolucizumab. The decision to reinject was made based on the presence of fluid on spectral domain optical coherence tomography (SD-OCT) or worsening of vision at follow-up. Outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), fluid (subretinal/intraretinal/sub-retinal pigment epithelium fluid) levels, and OCT biomarkers and safety analysis. A total of 59 eyes of 50 patients with a total of 132 intravitreal injections were included. There was a statistically significant improvement (P < 0.05) in BCVA from baseline in logMAR treatment-naïve patients (mean BCVA at baseline 0.6 ± 0.41 and 0.37 ± 0.56). The mean baseline CST of all patients significantly reduced from 582.92 ± 233.11 µm at baseline to 474.06 ± 252.89 µm at the final treatment visit. Thirty-eight percent of patients showed complete resolution of SHRM after a single injection. The interval between each subsequent injection increased from a mean of 67 to 96 days in treatment-switch patients and from 47 to 151 days in treatment-naïve patients. Brolucizumab promises reduced number of injections with longer treatment intervals.

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.

Long-Term Outcomes in Early versus Limited Response to Anti-VEGF Treatment for Retinal Vein Occlusion

Macular edema secondary to retinal vein occlusion (RVO) is a sight-threatening condition. Previous studies showed that early responders (ERs) who respond well to anti-VEGF injections within 3 months of treatment have better outcomes, as measured by best visual acuity (BVA) and central subfield thickness (CST) at 12 months postinjection initiation compared with limited early responders (LERs). This study analyzed whether ER eyes continue to respond better than LER eyes over longer periods. This study also aimed to identify baseline comorbidities associated with response status. Retrospective cohort study. Patients aged > 18 years with RVO-related macular edema treated with anti-VEGF injections. Patients were categorized as ERs or LERs. Limited early responder eyes were defined as having CST reduction < 10%, BVA gain < 5 ETDRS letters, or both at 3 months after anti-VEGF initiation. Best visual acuity and CST changes over the 24- and 36-month period after the first anti-VEGF treatment were compared between ERs and LERs. Patient characteristics and systemic comorbidities were identified by chart review. Statistical analysis involved the Levene test, Welch t test, and Welch analysis of variance. Best visual acuity and CST changes over the initial 24-month and 36-month periods after treatment. The 24-month cohort included 68 ERs and 39 LERs, and the 36-month cohort included 58 ERs and 33 LERs. At the 24-month time point, there were significant differences in BVA and CST gains between ERs (+19.8 letters,-221.2 um) and LERs (-2.4 letters,-90.1 um; P < 0.001, P < 0.01). Similarly, at 36 months, there were significant differences in BVA and CST gains between ERs (+17.7 letters,-229.3 um) and LERs (+1.3letters,-128 um; P < 0.001, P < 0.05). After controlling for differences in baseline BVA and CST, only the 24-month change in BVA remained significant (P < 0.001). There were no significant associations between response status and cardiopulmonary, endocrine, and oncologic comorbidities. Early responder eyes with branched retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) have better functional responses to anti-VEGF injections at 24 months compared with LER eyes, even after controlling for baseline differences. Early identification of eyes as ERs or LERs in BRVO and CRVO may predict long-term functional prognoses. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Efficacy of a Modified Treat-and-Extend Aflibercept Regimen for Macular Oedema in Eyes with Central Retinal Vein Occlusion: 2-Year Prospective Study.

This prospective, multicentre, interventional study evaluated the efficacy of a modified treat-and-extend (mTAE) aflibercept regimen as personalized therapy for macular oedema (MO) due to central retinal vein occlusion (CRVO). Fifty eyes were studied from 50 patients who were enrolled between November 2016 and July 2019. All patients received intravitreal aflibercept (IVA) injections on an mTAE regimen for 24 months. Primary outcome measures were best-corrected visual acuity (BCVA) and central subfield thickness (CST) at 12 months. Secondary endpoints were BCVA and CST at 24 months. Mean (standard deviation) baseline BCVA (logMAR) and CST were 0.50 (0.51) and 557 (240) µm, respectively. BCVA and CST showed significant improvements at month 12 (0.19 (0.38) and 275 (98) µm, respectively; both p < 0.0001, paired t-test). BCVA and CST also showed significant improvements at 24 months (0.26 (0.50) and 255 (91) µm, respectively, p = 0.0004 and p < 0.0001, paired t-test). The mean numbers of IVA injections and clinic visits over the 24-month study period were 6.2 (3.0) and 10.3 (1.0), respectively. The mTAE regimen of IVA injections for MO due to CRVO was effective in improving BCVA and decreasing CST at 24 months. The mTAE regimen might be an effective personalized therapy for CRVO.

OCT biomarkers as predictors of visual improvement in diabetic macular edema eyes receiving dexamethasone implants

BackgroundSeveral optical coherence tomography (OCT) biomarkers have been proposed as predictors for functional and anatomical outcomes in Diabetic Macular Edema (DME). This study aims to examine the impact of these OCT features on the visual acuity improvement of patients with DME after long-acting Dexamethasone intravitreal implants (DEX-I) injection. Furthermore, the safety and impact of DEX-I on clinical parameters, including intraocular pressure (IOP) were assessed.MethodsIn this retrospective observational study, we reviewed the medical records of naïve and non-naïve eyes with DME who received at least one DEX-I. The primary endpoint was visual acuity improvement of ≥ 5 ETDRS letters at 1 month and 4 months after treatment. Secondary outcomes were the changes in OCT biomarkers and the impact of DEX-I on IOP at 1 and 4 months of follow-up. Linear panel regression analysis was used to test for differences in central subfield thickness (CST) over time and it was stratified according to biomarkers at baseline. Finally, a logistic regression analysis was used to identify factors predicting visual improvement at 1 and 4 months.ResultsWe included 33 eyes of which 63.6% were at an advanced stage of DME. Overall, CST, cube average thickness (CAT), cube volume (CV), and intraretinal cystoid spaces > 200 μm (ICS) decreased following DEX-I injection (p < 0.001). Additionally, a thicker CST at baseline was observed in eyes with better visual improvement at one month (p = 0.048). After logistic regression analysis, CST was retained as the only predictor for visual improvement at one month (p = 0.044). Furthermore, panel regression analysis identified a relation between subfoveal neuroretinal detachment (SND) at baseline and CST increase at four months. Lastly, only 15.2% of the eyes necessitated topical medication for IOP reduction, with no differences observed when stratifying between naïve and non-naïve eyes.ConclusionOur analyses suggest that a ticker baseline CST may serve as a positive predictor of early visual improvement and SND presence at baseline may be a negative prognostic factor for CST increase 4 months after DEX-I injection. Other well-known biomarkers, such as disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HF), did not demonstrate prognostic value on visual outcomes, at least within the first four months following the injection.

Predictive effect of TCED-HFV grading and imaging biomarkers on anti-VEGF therapy in diabetic macular edema

BackgroundTo evaluate the predictive effect of TCED-HFV grading and imaging biomarkers on anti-vascular endothelial growth factor (anti-VEGF) treatment in diabetic macular edema (DME).Methods81 eyes of 81 DME patients who were treated with anti-VEGF were included in this retrospective cohort study. All patients underwent a comprehensive ophthalmic examination at baseline and follow-up, including best-corrected visual acuity (BCVA), fundus photography, and spectral domain–optical coherence tomography (SD-OCT). Baseline imaging biomarkers were qualitatively and quantitatively graded according to the TCED-HFV classification protocol, and DME was divided into early stage, advanced stage, severe stage, and atrophy stage.ResultsSix months post treatment, central subfield thickness (CST) in 49 eyes (60.5%) had decreased by 10% from baseline, 30 eyes (37.0%) had achieved CST < 300 μm, and 45 eyes (55.6%) had BCVA improved by more than five letters. Multivariate regression analysis revealed that eyes with baseline CST ≥ 390 μm had a higher probability of ≥ 10% reduction in CST from baseline, and eyes with abundant hyperreflective dots (HRD) had a lower probability of 10% reduction in CST (all P < 0.05). Eyes with vitreomacular traction (VMT) or epiretinal membrane (ERM) at baseline were less likely to reach the end point of CST < 300 μm (P < 0.05). BCVA increases of more than five letters were less likely in eyes with baseline BCVA ≥ 69 letters, complete or partial destruction of ellipsoid zone (EZ) at baseline (all P < 0.05). TCED-HFV staging was negatively correlated with BCVA at both baseline and 6 months (Kendall’s tau-b=-0.39 and − 0.55, all P < 0.01). TCED-HFV staging was positively correlated with CST at 6 months (Kendall’s tau-b = 0.19, P = 0.049) and negatively correlated with the reduction of CST (Kendall’s tau-b=-0.32, P < 0.01).ConclusionThe TCED-HFV grading protocol facilitates a comprehensive assessment of DME severity, standardizes the grading of multiple imaging biomarkers, and predicts the anatomical and functional outcomes of anti-VEGF treatment.

DEFINING "STRONG" VERSUS "WEAK" RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR CENTER-INVOLVED DIABETIC MACULAR EDEMA.

To define "strong" versus "weak" antivascular endothelial growth factor (anti-VEGF) treatment response in eyes with center-involved diabetic macular edema (CI-DME). Exploratory analyses of three DRCR Retina Network randomized trials of eyes with CI-DME treated with aflibercept, bevacizumab, or ranibizumab. Thresholds of 5-, 10-, and 15-letter gain defined strong visual acuity (VA) response when baseline VA was 20/25-20/32, 20/40-20/63, or 20/80-20/320, respectively. Thresholds of 50, 100, or 200- µ m reduction defined strong anatomical response when baseline central subfield thickness (CST) was <75, ≥75 to <175, or ≥175- µ m above standard thresholds. Additional thresholds from regression equations were calculated. At 24 weeks, outcomes for strong response were achieved by 476 of 958 eyes (50%) for VA and 505 eyes (53%) for CST. At 104 weeks among the 32% of eyes with strong VA and CST response at 24 weeks, 195 of 281 (69%) maintained strong VA and CST response, whereas 20 (7%) had neither strong VA nor strong CST response. Outcomes rates were similar across protocols and when defined using regression equations. These phenotypes are suitable for efforts to identify predictive biomarkers for response to anti-VEGF therapy for DME and might facilitate comparison of treatment response among diverse cohorts with DME.

Two-Year Outcomes After Variable Duration of Drug Cessation in Patients With Maculopathy Associated With Pentosan Polysulfate Use

Prior retrospective studies have provided limited evidence on disease progression following drug cessation in patients with maculopathy associated with pentosan polysulfate (PPS). To evaluate the 2-year evolution of maculopathy associated with PPS use after drug cessation. This cohort study prospectively evaluated the natural history of patients with maculopathy associated with PPS use. Participants seen at the Emory Eye Center were enrolled between December 1, 2018, and December 1, 2019, and data were collected through November 30, 2021. The main outcomes were changes in visual function and structure. Visual function was assessed annually with refraction and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), mesopic microperimetry, and dark adaptometry. Structural outcomes included presence and extent of complete retinal pigment epithelium and outer retinal atrophy (cRORA), macular central subfield thickness (CST), and subfoveal choroidal thickness (SFCT). Of the 12 participants (23 eyes), 11 (91.7%) were female (1 [8.3%] male), 11 (91.7%) were White (1 [8.3%] Black), and median (IQR) age at enrollment was 58 (47-64) years. Median (IQR) time from PPS discontinuation to initial visit was 0.6 (0.4-1.9) years. Median baseline ETDRS BCVA letter score was 83 (Snellen equivalent, 20/20) (IQR, 80-86.5 [20/25-20/20]), with a median 2-year change of -3 (IQR, -6 to -0.5; P = .08). Four eyes (17.4%) had a letter score decline of 15 or more, all associated with progressive cRORA. Median change in microperimetry average threshold was -3.5 dB (IQR, -4.1 to -2.5 dB; P = .001), and percent reduced threshold was 32.5% (IQR, 20.3%-52.8%; P = .004). Nine eyes (39%) had macular cRORA at baseline, with a median linearized growth rate of 0.23 mm/y (IQR, 0.22-0.25 mm/y). Two eyes (8.7%) without atrophy at baseline developed new-onset cRORA. Median baseline CST was 284 μm (IQR, 253-291 μm), with a median 2-year change of -5 μm (IQR, -13 to 0.5 μm; P = .0497). Median 2-year change in SFCT was 1 μm (IQR, -18 to 16 μm; P = .91). The findings of this cohort study suggest that functional and structural deficits continue to progress in PPS-associated maculopathy even after drug cessation. Additional study is needed to determine whether these findings can be generalized to other patients with PPS-associated maculopathy and whether longer follow-up could determine subsequent disease course.

OUTER FOVEAL DEFECTS IN TYPE-2 MACULAR TELANGIECTASIA.

To report characteristics of outer foveal defects (OFDs) in type-2 macular telangiectasia (MacTel) on spectral domain optical coherence tomography. This was a single-center observational study. From a registry of 745 patients with MacTel, patients with OFDs were characterized. All patients underwent multimodal imaging including color fundus photography, confocal blue reflectance, fundus autofluorescence, and spectral domain optical coherence tomography. Staging of eyes was done using the Gass and Blodi classification. Spectral domain optical coherence tomography characteristics in the central 1 mm of the macula in eyes with OFD are reported. Outer foveal defect was observed in 21 eyes of 15/745 (2%) patients with MacTel. These defects were bilateral in 6/15 (40%) patients and seen in stage 2 MacTel eyes. In order of prevalence, foveal parameters seen in OFD included hyper-reflective dots in outer retina in 19/21 (90%), ellipsoid zone loss in 18/21 (86%) eyes, interdigitation zone loss in 17/21 (81%) eyes, outer retinal hyporeflective cavitation in 14 (67%) eyes, hyporeflective cavitation at foveal pit in 8 (38%) eyes, and loss of external limiting membrane in 1 (5%) eye. The mean baseline length of the foveal ellipsoid zone loss was 240.17 ± 117.249 µm. The mean baseline central subfield thickness was 155.43 ± 17.215 µm. A total of 8/11 eyes (73%) showed an increase in size of OFD on follow-up. Outer foveal defect in MacTel eyes is characterized predominantly by foveal loss of ellipsoid zone and interdigitation zone with relative preservation of external limiting membrane.

Short-term outcomes in patients with center-involving diabetic macular edema after a single dose of intravitreal bevacizumab

BackgroundA significant portion of diabetic macular edema (DME) is refractory to anti-vascular endothelial growth factor (anti-VEGF) agents. This study investigates morphological and functional outcomes to a single intravitreal bevacizumab (IVB) injection in patients with center-involving DME (ciDME) at 4–6 weeks and compares treatment responders and non-responders based on spectral domain optical coherence tomography (SD-OCT) features.MethodsIRB approved observational, retrospective chart review of patients with ciDME, identified by ICD-10 code, who received IVB and underwent baseline and 4–6 weeks follow-up SD-OCT imaging between January 1, 2016 and January 19, 2021. Patients who had received previous treatment with anti-VEGF or intraocular steroids within 1 year were excluded. Variables included best-corrected visual acuity (BCVA), central subfield thickness (CST) and total macular volume (TMV). Eyes were classified as responders if CST reduction was greater than 10%. OCT scans were graded qualitatively by two masked graders using Imagivault software. Paired Student’s t-tests, Wilcoxon signed rank tests and Chi-Square tests were used for analysis.ResultsA total of 334 prospective subjects were identified, and after applying exclusion criteria 52 eyes from 46 patients (mean age 64.22 ± 8.12 years, 58.7% male) were included. Mean BCVA did not significantly change with treatment, 63.9 ETDRS letters (~ 20/50) at baseline and 65.9 ETDRS letters (~ 20/50) post-treatment (p = 0.07). Mean CST decreased from 466 ± 123 μm at baseline to 402 ± 86 μm post-treatment (p < 0.001). 22 (42.3%) of eyes were categorized as responders and 30 (57.7%) as non-responders. Average change in CST from baseline in responders was -164 μm (p < 0.001) and + 9 μm in non-responders (p = 0.47). Vitreomacular adhesion (VMA) was more prevalent in non-responders (28.7% vs. 4.8%, p = 0.03). In addition, cyst location in the inner nuclear layer (INL) was present more frequently in responders (95.5% vs. 73.3%, p = 0.037) as was subretinal fluid (45.5% vs. 13.3%, p = 0.01).ConclusionThe short-term response to a single IVB was sub-optimal with structural but no functional improvements. Greater baseline CST, presence of INL cysts and subretinal fluid may represent factors indicative of a better treatment response.

Anti-Vascular Endothelial Growth Factor Treatment Patterns and Outcomes in Retinal Vein Occlusion in Routine Clinical Practice.

To characterize treatment patterns for retinal vein occlusion (RVO)-related macular edema (ME) in routine clinical practice and its impact on long-term best-corrected visual acuity (BCVA) and central subfield thickness (CST). Retrospective study of 365 eyes with branch RVO (BRVO) or central/hemi-RVO (CRVO/HRVO)-related ME between 2003 and 2020. Regression analysis identified factors associated with maintenance injection interval (MII). Subgroup analysis compared outcomes between different MIIs. 51.3% of BRVO patients received injections ≤q8 weeks, 26.4% received injections q8-12 weeks, and 22.3% received injections >q12 weeks. 45.2% of CRVO/HRVO patients received injections ≤q8 weeks, 32.1% received injections q8-12 weeks, and 22.6% received injections >q12 weeks. Age, diabetes, and baseline CST were found to predict MII. There was no significant difference in BCVA and CST at baseline, 12, or 24 months in all MII groups in BRVO and CRVO/HRVO. There exists a significant heterogeneity in anti-VEGF treatment frequency for RVO-associated ME in routine clinical practice. [Ophthalmic Surg Lasers Imaging Retina 2022;53:626-633.].

Factors Associated with Fluctuations in Central Subfield Thickness in Patients with Diabetic Macular Edema Using Diabetic Retinopathy Clinical Research Protocols T and V

To identify baseline ocular and systemic factors associated with central subfield thickness (CST) fluctuations in patients with diabetic macular edema (DME) using data from Diabetic Retinopathy Clinical Research Protocols T and V. Post hoc analysis of clinical trial databases. Patients in Protocols T and V. The standard deviation (SD) of all recorded CSTs for each patient during each Protocol's study period was calculated. The CST SD (corresponding to CST fluctuations) for each patient was analyzed against baseline ocular and systemic factors using linear regression analyses. Each Protocol was analyzed separately. Factors associated with CST fluctuations. A total of 1197 eyes of 1197 subjects were included. In Protocol T (559 eyes, mean CST SD was 56.4±35.1 microns), using multivariate linear regression analysis, baseline urine albumin/creatine ratio (for every 1000 mg/g, CST point estimate 3.50, 95% confidence interval [CI] 0.58 to 6.43, P= 0.0190), and baseline CST (for every 10 microns, 0.87, 95% CI 0.58 to 1.16, P < 0.0001) were positively associated with CST fluctuations. Baseline visual acuity (for every 10 ETDRS letters,-9.52, 95% CI-11.89 to-7.15, P<0.0001) was negatively associated with CST fluctuations. In Protocol V (638 eyes, mean CST SD 36.6±28.4 microns), gender (female, 2.18, 95% CI 0.30 to 4.06, P= 0.0227), baseline CST (for every 10 microns, 2.51, 95% CI 2.21 to 2.82, P < 0.0001), systolic blood pressure (for every 1 mm of mercury, 0.11, 95% CI 0.01 to 0.21, P= 0.0261), and observation with deferred anti-VEGF injections (5.04, 95% CI 2.51 to 7.58, P<0.0001) were positively associated with CST fluctuations. Type 2 diabetes (-7.37, 95% CI-13.64 to-1.11, P= 0.0209) and prompt anti-VEGF injections (-6.51, 95% CI-9.07 to-3.96, P<0.0001) were negatively associated with CST fluctuations. Worse visual acuity at baseline, baseline renal disease, hypertension, female gender, type 1 diabetes, and delayed anti-VEGF treatment may be associated with increased CSTfluctuations in patients with DME. Addressing these parameters may limit CST fluctuations and help identify patients requiring more frequent monitoring or treatment.

Therapeutic effect of cataract surgery with simultaneous intravitreal injection of aflibercept on diabetic macular edema: An observational study.

This study aimed to investigate the therapeutic effect of cataract surgery along with simultaneous intravitreal injection (IVI) of aflibercept on diabetic macular edema (DME). This cohort study enrolled 106 patients aged >40 years with type 2 diabetes mellitus and DME who received cataract surgery from January 1, 2016, to October 31, 2020. The baseline and mean data of the following parameters were collected: age, sex, glycated hemoglobin level, diabetic retinopathy (DR) grading, previous DR treatments including IVI of anti–vascular endothelial growth factor and pan-retinal photocoagulation, intraocular pressure, use of intraocular pressure-lowering medication, central subfield thickness (CST), and log MAR visual acuity (VA). Patients were categorized into 2 groups based on whether they received aflibercept IVI or not during cataract surgery and were compared using the t test and Fisher exact test for continuous and discrete variables, respectively. Beta coefficient and standard error were calculated using multiple linear regression analysis to identify the explanatory variables predictive of the net change of CST and log MAR VA. There was no difference in the net change in CST (15.24 ± 45.07 μm vs 18.62 ± 33.84 μm, P = .772) and log MAR VA (−0.27 ± 0.29 vs −0.37 ± 0.31, P = .215). Gender, glycated hemoglobin level, aflibercept IVI during cataract surgery, and baseline CST did not interfere with the morphological and functional outcomes of DME in cataract surgery. Older age was significantly and independently associated with a greater net change in log MAR VA. Proliferative DR was significantly and independently associated with a greater net change in CST and log MAR VA. A greater baseline log MAR VA was significantly and independently associated with lower net change in log MAR VA. Simultaneous aflibercept IVI for treating DME may not interfere with the functional and tomographic parameters of cataract surgery relative to cataract surgery alone. Factors influencing the outcomes of patients with DME undergoing cataract surgery are as follows: age, baseline DR staging, and baseline VA. Identifying these factors of DME preoperatively may be an important consideration in preventing it from progressing and for improving the overall visual prognosis.

Time to Resolution of Diabetic Macular Edema after Treatment with Intravitreal Aflibercept Injection or Laser in VISTA and VIVID

To assess the relationship between baseline factors and time to diabetic macular edema (DME) resolution. Post hoc analysis of VISTA and VIVID. Eyes with baseline central subfield thickness (CST) of ≥ 290 μm. Eyes were treated with intravitreal aflibercept injection (IAI) 2 mg (n= 558; every 4 weeks or every 8 weeks after 5 monthly doses) or laser control (n= 274). The effect of baseline factors on the time to DME resolution (CST < 290 μm) was assessed in univariable and multivariable models and further evaluated by the Kaplan-Meier method. Time to and cumulative incidence of DME resolution. Eyes treated with IAI had a 2.5-fold higher DME resolution rate, with median time of 33.0 weeks (95% confidence interval [CI], 28.1-40.0), compared with DME resolution not being achieved in 50% of eyes treated with laser control. Multivariable analysis demonstrated that a lower DME resolution rate was associated with a thicker baseline CST (hazard ratio [HR] [95% CI] per 100-μm CST increase, 0.79 [0.72-0.86]) and better baseline best-corrected visual acuity (BCVA) (HR [95% CI] per 5-letter increase, 0.87 [0.83-0.92]) with IAI. Tertiles of increasing CST (T1CST ≤ 419 μm; T2CST > 419 to ≤ 541; T3CST > 541) were associated with longer median times to DME resolution (20.1, 39.1, and 49.1 weeks, respectively; P < 0.001 for T2CST and T3CST versus T1CST) and lower cumulative incidence of events (HR, 1.0, 0.6, and 0.6, respectively; P < 0.001 for T2CST and T3CST versus T1CST) with IAI. Tertiles of increasing BCVA (T1BCVA ≤ 57 letters; T2BCVA > 57 to ≤ 66; T3BCVA >66) were associated with longer median times to DME resolution (28.4, 31.7, and 44.1 weeks, respectively; P < 0.05 for T3BCVA versus T1BCVA) and lower cumulative incidence of events (HR, 1.0, 0.9, and 0.8, respectively; P < 0.05 for T3BCVA versus T1BCVA) with IAI. No other baseline factor was associated with the time to DME resolution. The median time to DME resolution was 33 weeks among IAI-treated eyes. A thicker baseline CST and better baseline BCVA in the IAI group were associated with a longer time to and a lower rate of DME resolution.

The impact of laboratory findings and optical coherence tomography biomarkers on response to intravitreal anti-VEGF treatment in patients with retinal vein occlusion.

To investigate potential laboratory and imaging biomarkers as treatment response predictors to intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in patients with retinal vein occlusion (RVO). Participants in this prospective study were 53 patients with treatment naïve macular edema secondary to RVO, treated with intravitreal anti-VEGF agents and followed-up for 12months. At baseline, all participants underwent best-corrected visual acuity measurement, dilated fundoscopy, optical coherence tomography and fluorescein angiography (FFA), while full blood count and biochemical analysis of various parameters was also performed. At month 12, treatment response was examined and classified as "favorable" or "non-response". Potential associations between laboratory/imaging biomarkers and treatment response were assessed. Univariate analysis showed that "favorable" response at month 12 after initiation of anti-VEGF treatment was correlated with baseline central subfield thickness (CST) < 464μm (p < 0.001), absence of subretinal fluid (p = 0.004), absence of hyperreflective foci (HF) (p = 0.004), intact ellipsoid zone (EZ) and external limiting membrane (ELM) (p < 0.001 and p = 0.001, respectively), absence of epiretinal membrane (ERM) (p = 0.020) and absence of macular ischemia on FFA (p < 0.001), while increased monocytes-to-lymphocytes ratio was also associated with "favorable" treatment response (p = 0.010). All other laboratory parameters did not reach statistical significance. However, at the multivariate analysis, EZ and ELM status, HF, macular ischemia and monocytes-to-lymphocytes ratio were found to be independent predictors of treatment response. Intact EZ and ELM, absence of HF, absence of macular ischemia and increased monocytes-to-lymphocytes ratio at baseline can predict "favorable" treatment response in patients with treatment naïve macular edema secondary to RVO.

Short-Term Outcomes of Switching Therapy from Bevacizumab Non-Responder to Ranibizumab in Diabetic Macular Edema

Objective: To evaluate the short-term efficacy of ranibizumab therapy in terms of visual function and retinal thickness in patients with diabetic macular edema (DME) who failed to respond to treatment with repeated bevacizumab injections. Additionally, parameters affecting outcomes after switching were investigated. Materials and Methods: The present study was a multicenter, retrospective study of 70 eyes with DME non-responding to bevacizumab. All patients were initially treated with at least three consecutive injections of bevacizumab then switched to at least one injection of ranibizumab. A monthly follow-up after the first ranibizumab injection to the last injection within six months was monitored. Primary outcomes included mean change in best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) changes from baseline. Exploratory outcomes included parameters affecting prognosis after switching. Results: Seventy eyes with DME were included in the present study. The mean change of BCVA (logMAR) was 0.075±0.375 (95% CI 0.014 to 0.164, p=0.098). The mean change of CSFT was 58.85±110.37 μm (95% CI 32.54 to 85.17, p&lt;0.001). Forty-two percent of patients had BCVA improvement and 75.71% had CSFT improvement after switching to ranibizumab. Factors associated with BCVA and CSFT improvement were baseline BCVA, baseline CSFT, and older than 50 years old. Conclusion: Switching to ranibizumab therapy in DME patients unresponsive to repeated bevacizumab injection provides better anatomical outcomes than visual acuity improvement. This will help ophthalmologists better understand the benefits on switching therapy to ranibizumab in terms of visual function and retinal thickness in patients with DME in the real-world setting. Keywords: Diabetes, macular edema; Anti-vascular endothelial growth factor (VEGF); Intravitreal injection; Non-responder; Persistent diabetic macular edema