anti-VEGF Treatment In Patients Research Articles

The impact of Vitreo-Macular interface abnormalities on the response to Anti-VEGF therapy for centre involving diabetic macular oedema.

The influence of Vitreomacular Interface Abnormalities (VMIA) such as Epiretinal Membrane (ERM) and/or vitreomacular traction (VMT) on the response of patients with Centre Involving Diabetic Macular Edema (CIDME) to standard of care Anti-VEGF medications is under-researched. The aims of this study were: 1) To determine the incidence of VMIA at baseline and 12 months amongst treatment naive patients commencing anti-VEGF treatment 2) To compare the response to Anti-VEGF medications at 3 monthly intervals for 12 months in a large cohort of patients with and without VMIA on their baseline OCT scan. Response was determined in terms of: number of injections, central macular thickness and visual acuity. A retrospective case notes review of treatment naïve patients with newly diagnosed CIDME. Included patients had been commenced on intravitreal Anti-VEGF injections (ranibizumab or aflibercept) at a single centre. Inclusion criteria were: treatment naïve DME patients with a CMT of 400μ or more receiving anti-VEGF treatment with at least 12 months follow up and in whom macular OCT scans and visual acuity (VA) measurements were available within two weeks of baseline, 3, 6, 9 and 12 months. Exclusion criteria included: previous intravitreal therapy, previous vitrectomy, cataract surgery during the follow-up period, concurrent eye conditions affecting vision or CMT. 119 eyes met the inclusion criteria and underwent analysis. Groups were comparable in their baseline demographics. Baseline CMT measurements were comparable at baseline (417μ and 430μ in the No-VMIA and VMIA groups respectively) and improved to approximately 300μ in both groups. From 6 months CMT continued to improve in the no-VMIA while progressively deteriorating in the VMIA group. Change in CMT was statistically different at 12 months between the 2 groups (108μ and 79μ, p= 0.04). There was a mean of 7 injections after 12 months. Our study has shown a 46% incidence of VMIA amongst patients newly diagnosed with centre involving DME undergoing treatment with anti-VEGF injections. We have also demonstrated a significant difference in CMT and VA response to anti-VEGF treatment in patients with and without VMIA. Initial response was similar between the 2 groups up until 6 months. From 6 to 12 months significant differences in treatment response emerged. Differences in clinical response between patients with and without VMIA may help guide further prospective controlled studies and optimise treatment strategies.

Результаты применения анти-VEGF-терапии пациентам с лучевой ретинопатией при увеальной меланоме

Relevance. Radiation retinopathy (RR) in the form of macular edema (ME) is a predictable complication of radiation therapy (RT) in uveal melanoma (UM). ME is the main reason for the decrease in visual acuity (VA) after RT. By reducing visual acuity, ME reduces the quality of life of such patients. To date, there is no standardized algorithm for the treatment of this pathology. In foreign literature, anti-vascular endothelium growth factor (anti-VEGF) are proposed as a solution to the problem, but even here their use is limited by the lack of experience of their introduction in domestic literature, the mode of administration and indications. Purpose. To present results of anti-VEGF treatment in patients with ME against the background of radiation treatment of UM. Material and methods. For the period from 2018 to 2023, at S. Fyodorov Eye Microsurgery Federal State Institution, Moscow, anti-VEGF injection was performed in 70 patients (70 eyes) with ME, which developed against the background of radiation therapy of UM. Of these, 24 (34%) patients were men, 46 (66%) were women. The average age of patients was 54 years (from 14 to 89 years). The average maximum corrected visual acuity (VA) when MO was diagnosed was 0,37 (from 0.001 to 1.0). According to optical coherence tomography, the average value of central macular thickness (CMT) at the time of diagnosis of ME was 411 microns (from 165 to 918), the average value of volume cube (VC) – 11.5 (range from 8 to 15.9). Results. The average VA after anti-VEGF treatment was 0.43 (from 0.001 to 1.0). Based on the data of changes in VA, 22 (32%) patients had stabilization of the process, 30 (43%) showed improvement, 18 (25%) – deterioration. According to optical coherence tomography, the average CMT value after anti-VEGF was 298 microns (from 57 to 688; p<0.001), and the average VC value was 10 (from 3.6 to 13.1;, p<0.001). Conclusion. The first experience of using anti-VEGF in our country has shown its effectiveness in reducing the height of macular edema and improving visual functions, which makes their use in radiation retinopathy expedient. Key words: uveal melanoma, radiation retinopathy, macular edema, anti-vascular endothelial growth factor

Association of PON1, APOE and SDF-1 Gene Polymorphisms with Treatment Response to Intravitreal Anti-VEGF Treatment in Patients with Retinal Vein Occlusion

ABSTRACT Purpose The purpose of this study was to determine whether specific genetic polymorphisms affect the response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with macular oedema secondary to retinal vein occlusion (RVO). Methods Participants in this prospective study were 50 patients with macular oedema secondary to RVO, who were treated with intravitreal ranibizumab or aflibercept, and were followed-up for 12 months after initiation of treatment. Five single nucleotide polymorphisms (SNPs) from three different genes (APOE, PON1, SDF-1) were examined as potential predictors for treatment response to intravitreal anti-VEGF agents. Results Patients with the LL genotype of the PON1 L55M SNP had significantly higher reduction in central subfield thickness (CST) at month 12 after initiation of intravitreal anti-VEGF treatment (101.63 ± 56.80 μm in LL vs. 72.44 ± 39.41 μm in LM vs. 40.25 ± 19.33 μm in MM, p = .026). Patients with the M allele of the PON1 L55M SNP were significantly associated with lower reduction in CST compared to non-carriers (68.29 ± 38.77 μm in LM + MM vs. 101.63 ± 56.80 μm in LL, p = .032). Conclusion PON1 L55M SNP may serve as a promising genetic biomarker for predicting response to intravitreal anti-VEGF treatment in patients with macular oedema due to RVO.

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.

Predictors of response to a lapse in anti-VEGF treatment in patients with macular edema secondary to retinal vein occlusion

BackgroundMacular edema (ME) in the setting of retinal vein occlusions (RVO) is a common cause of vision loss worldwide. Anti-vascular endothelial growth factor (anti-VEGF) injections are the gold standard for ME secondary to RVO. Despite their efficacy, anti-VEGF injections carry significant burdens for patients, resulting in high rates of loss to follow-up and treatment lapses. MethodsA sub-analysis examining the effects of a treatment lapse in RVO patients was conducted. Sixty patients were included and separated into vision-loss and stable-vision groups based on change in vision after a lapse. A logistic regression with age, body mass index (BMI), history of dyslipidemia, and time since diagnosis of RVO as predictors was used to predict whether patients would experience vision loss after a lapse. ResultsThe average lapse was 5.6 months and similar in the vision-loss and stable-vision groups. At baseline, the vision-loss group was older and had a lower BMI (p < 0.05). Age and history of dyslipidemia increased the odds of vision loss by factors of 1.23 (range, 1.10–1.45) and 8.40 (range, 1.62–66.2), respectively. BMI and time since RVO diagnosis decreased the odds of vision loss by factors of 0.83 (range, 0.69–0.95) and 0.95 (range, 0.90–0.99), respectively. The final model had a specificity of 87.5% and a sensitivity of 70.0%. ConclusionsPatients’ responses to treatment lapses for ME secondary to RVO can be predicted with reasonable accuracy using readily available clinical data, particularly age, BMI, time since diagnosis, and history of dyslipidemia. Providers should consider these factors when counselling patients and determining follow-up schedules.

Efficacy οf Wet Age-related Macular Degeneration Treatment οn Reading: A Pilot Study Using Eye-movement Analysis.

Functional vision, as evaluated with silent passage reading speed, improves after anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with wet age-related macular antidegeneration (wAMD), reflecting primarily a concomitant reduction in the number of fixations. Implementing eye movement analysis when reading may better characterize the effectiveness of therapeutic approaches in wAMD. This study aimed to evaluate silent reading performance by means of eye fixation analysis before and after anti-VEGF treatment in wAMD patients. Sixteen wAMD patients who underwent anti-VEGF treatment in one eye and visual acuity (VA) better than 0.5 logMAR served as the AMD group. Twenty adults without ocular pathology served as the control group. Central retinal thickness and near VA were assessed at baseline and 3 to 4 months after their first visit. Reading performance was evaluated using short passages of 0.4-logMAR print size. Eye movements were recorded using EyeLink II video eye tracker. Data analysis included computation of reading speed, fixation duration, number of fixations, and percentage of regressions. Frequency distributions of fixation durations were analyzed with ex-Gaussian fittings. In the AMD group, silent reading speed in the treated eye correlated well with central retinal thickness reduction and improved significantly by an average of 15.9 ± 28.5 words per minute (P = .04). This improvement was accompanied by an average reduction of 0.24 ± 0.38 in fixations per word (P = .03). The corresponding improvement in monocular VA was not statistically significant. Other eye fixation parameters did not change significantly after treatment. No statistically significant differences were found in the control group. Visual acuity tests may underestimate the potential therapeutic effects after anti-VEGF treatment in patients with relatively good acuity who are being treated for wAMD. Evaluating silent reading performance and eye fixation parameters may better characterize the effectiveness of therapeutic approaches in wAMD patients.

Real-World Persistence and Treatment Interval in Patients with Diabetic Macular Edema Treated with Anti-Vascular Endothelial Growth Factors in the USA.

There is little understanding of long-term treatment persistence in patients receiving anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), particularly relating to treatment intervals. The aim of this study was to investigate the association between treatment interval and discontinuation rate after 24months of unilateral anti-VEGF treatment in patients with DME under routine clinical care in the USA. This was a non-interventional, retrospective cohort study to review the health insurance claims of adults with DME linked with the IBM MarketScan® Commercial and Medicare Supplemental databases, who were continuously enrolled in a health plan for at least 6months prior to their first anti-VEGF treatment and for a duration of at least 24months between July 2011 and June 2017. Patients were grouped on the basis of the injection interval they achieved at 24months of treatment. Discontinuation rate beyond 24months and its association with treatment intervals at 24months was estimated using the Kaplan-Meier method and Cox proportional hazards models. The overall discontinuation rate among the 1702 eligible patients from 24 to 60months after treatment initiation was 30%. At 60months, patients were more likely to remain on treatment in shorter (75.3% [4-week interval group]) versus longer treatment interval groups (62.1% [> 12-week interval group], difference = 13.2%, [95% confidence interval (CI) 1.06, 2.06], p = 0.01). Patients on a > 12-week interval were twice as likely to discontinue treatment compared with those on an 8-week interval (hazard ratio = 2.01 [95%CI 1.43, 2.82], p < 0.001). Patients with DME on longer anti-VEGF treatment intervals at 24months consistently had higher discontinuation rates in the following years than those on shorter treatment intervals.

Volumetric fluid analysis of fixed monthly anti-VEGF treatment in patients with neovascular age-related macular degeneration.

To evaluate visual outcomes and changes in fluid after administering monthly anti-vascular endothelial growth factor (VEGF) injections to treat neovascular age-related macular degeneration (nAMD) with subretinal fluid (SRF) and pigment epithelial detachment (PED). This prospective study included eyes with nAMD previously treated with as-needed anti-VEGF injections. The patients were treated with six monthly intravitreal injections of ranibizumab. Quantitative volumetric segmentation analyses of the SRF and PED were performed. The main outcome measures included best-corrected visual acuity (BCVA), and SRF and PED volumes. Twenty eyes of 20 patients were included in this study. At the 6-month follow-up, BCVA and PED volume did not change significantly (P=0.110 and 0.999, respectively) but the mean SRF volume decreased from 0.53±0.82 mm3 at baseline to 0.08±0.23 mm3 (P=0.002). The absorption rate of the SRF volume was negatively correlated with the duration of previous anti-VEGF treatment (P=0.029). Seven of the 20 eyes (35%) showed a fluid-free macula and significant improvement in BCVA (P=0.036) by month 6. Quantifying the SRF can precisely determine the patient's responsiveness to anti-VEGF treatment of nAMD.

VEGF Inhibition in Retinal Vein Occlusion Does Not Associate with Cardiovascular Morbidity or Mortality

Intravitreal treatment with VEGF inhibitors has proven safe in clinical trials, but often on selected patient groups and without statistical power to investigate rare safety events. Data on anti-VEGF treatment in patients with retinal vein occlusion (RVO) are sparsely represented, and studies providing population-based, long-term follow-up are needed to assess the risks in routine clinical practice. We aimed to evaluate the association between treatment with anti-VEGF and the risk of incident cardiovascular disease (CVD) and all-cause mortality in patients with RVO, and whether this association was affected by selected risk factors. A cohort study from January 2012 to December 2018 using Danish nationwide registries linked on an individual level. Patients with RVO (n= 7235), exposed (n= 3508), and unexposed (n= 3727) to anti-VEGF, aged ≥ 40 years, alive, and living in Denmark. Cox proportional hazards analysis evaluating the effect of intravitreal VEGF inhibitory treatment on incident CVD and all-cause mortality. A predefined analysis plan specified primary outcomes as hazard ratios (HRs) of a composite CVD endpoint and all-cause mortality in patients treated with anti-VEGF compared with untreated. Secondary outcomes included cumulative dose analysis, HRs on subgroups of CVD, and stratified analyses evaluating the effect of sex, age, diabetes, intensive treatment, and preexisting CVD on the HRs. We found no increased risk of composite CVD (HR, 1.07; 95% confidence interval [CI], 0.89-1.29) or all-cause mortality (HR, 0.88; 95% CI, 0.77-1.00) in patients with RVO treated with anti-VEGF. In the secondary analyses, we found no dose-response relationship. We found an increased risk of intracranial hemorrhage (HR, 1.66; 95% CI, 1.02-2.71), but no increased risks in remaining subgroups of CVD. We found no increased risk associated with selected predisposing risk factors, and no increased risk in patients with preexisting CVD. Treatment with anti-VEGF in patients with RVO is safe, when evaluated in a nationwide, population-based setting. An increased risk of intracranial hemorrhage might be present, but cannot be reliably quantified and should be further elucidated by larger population-based studies including all indications for anti-VEGF treatment. Proprietary or commercial disclosure may be found after the references.

The Impact of Laboratory Findings and Optical Coherence Tomography Biomarkers on Response to Intravitreal Anti-VEGF Treatment in Patients with Diabetic Macular Edema

ABSTRACT Purpose To investigate potential laboratory and imaging biomarkers as treatment response predictors to intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in patients with diabetic macular edema (DME). Methods The study included 36 treatment naïve patients with DME, treated with intravitreal anti-VEGF agents and followed-up for 12 months. At baseline, all participants underwent best-corrected visual acuity (BCVA) measurement, dilated fundoscopy, optical coherence tomography, color fundus photography and fluorescein angiography, 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. Results Univariate analysis showed that favorable response at month 12 after initiation of anti-VEGF treatment was correlated with baseline central subfield thickness (CST)≤405 μm (p < .001), absence of subretinal fluid (p = .034), absence of exudates (p = .041), absence of disorganization of the inner retinal layers (p = .037), intact ellipsoid zone (EZ) and external limiting membrane (ELM) (p < .001 and p = .002, respectively), absence of epiretinal membrane (ERM) (p = .040) and absence of macular ischemia (p = .042), while increased lipoprotein(a) was associated with no treatment response (p = .025). At the multivariate analysis, CST was found to be independent predictor of treatment response, while EZ, ELM and ERM were found to predict treatment response perfectly and they could not be entered in the model. Conclusion Intact EZ and ELM, absence of ERM and CST≤405 μm at baseline can predict favorable treatment response in patients with treatment naïve DME, while no correlation with baseline laboratory parameters was found.

Association Between Visual Acuity and Residual Retinal Fluid Following Intravitreal Anti–Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration

The association between residual subretinal fluid (SRF) and intraretinal fluid (IRF) and visual acuity following anti-vascular endothelial growth factor (VEGF) treatment is not well understood. To examine the association of residual retinal fluid, SRF, and IRF with visual acuity following anti-VEGF treatment in patients with neovascular age-related macular degeneration (nAMD). A systematic literature search was performed from January 2005 to August 2021 using Ovid MEDLINE, Embase, and the Cochrane Library. Peer-reviewed articles reporting on visual acuity stratified by the presence or absence of any residual SRF, IRF, or any retinal fluid at last study observation after intravitreal bevacizumab, ranibizumab, aflibercept, or brolucizumab in patients with nAMD were included. Studies that were noncomparative, included fewer than 10 eyes, or reported on other anti-VEGF agents were excluded. Two independent reviewers conducted data extraction and synthesis. The Cochrane risk of bias tool 2 and ROBINS-I were used to assess risk of bias and GRADE evaluation was conducted to assess certainty of evidence. Primary outcomes were BCVA at last study observation, change in BCVA from baseline, and retinal thickness at last study observation. In this systematic review and meta-analysis, 11 studies (6 randomized clinical trials [RCTs]) comprising 3092 eyes were included in our analysis. Across all included studies, the BCVA of eyes with residual SRF was better than eyes without SRF (weighted mean difference [WMD], 3.1 letter score; 95% CI, 0.05 to 6.18; P = .05; GRADE, low certainty of evidence; 6 studies; 1931 eyes) but similar in RCTs (WMD, 2.7 letter score; 95% CI, -2.40 to 7.84; P = .30; GRADE, low certainty of evidence; 3 studies; 1406 eyes). The BCVA of eyes with residual IRF was worse than that of eyes without IRF (WMD, -8.2 letter score; 95% CI, -11.79 to -4.50; P < .001; GRADE, low; 7 studies; 2114 eyes). The findings suggest that the presence of residual SRF was associated with slightly better BCVA at last study observation; however, baseline differences in BCVA existed and this conclusion was primarily driven by 1 study. The presence of residual IRF was associated with substantially worse BCVA at last study observation and less improvement of BCVA from baseline. The conclusions are limited by the inclusion of data from observational studies, heterogeneity, and a low certainty of evidence.

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.

Impact of retinal fluid in patients with diabetic macular edema treated with anti-VEGF in routine clinical practice

ObjectifLa présente étude visait à déterminer l'effet du liquide intrarétinien (LIR) et sous-rétinien (LSR) sur les résultats visuels en présence d'un œdème maculaire diabétique (OMD) traité par anti-VEGF (facteur de croissance endothélial vasculaire) en pratique clinique courante. NatureOn a eu recours à un logiciel d'intelligence artificielle doté de capacités d'apprentissage profond pour analyser des images obtenues par tomographie par cohérence optique (OCT, pour optical coherence tomography), qui nous a permis de quantifier le LIR, le LSR et le liquide rétinien total (LRT) au départ de même qu'après 3, 6 et 12 mois. Les variables de prédiction de la meilleure acuité visuelle corrigée (MAVC) ont été évaluées à l'aide de modèles de régression linéaire à effets mixtes. ParticipantsUn total de 220 yeux présentant un OMD (220 patients) au Cole Eye Institute de la Cleveland Clinic. MéthodesÉtude de cohorte non randomisée rétrospective. RésultatsLa MAVC s'est améliorée entre la visite initiale et le suivi à 12 mois (de 63,36 ± 14,72 à 68,49 ± 13,14 lettres selon l’étude ETDRS [Early Treatment Diabetic Retinopathy Study]; p < 0,001). L’épaisseur du sous-champ central s'est également améliorée entre la visite initiale et le suivi à 12 mois (de 411,74 ± 129,7 à 335,94 ± 116,91 mm; p < 0,001). La fréquence des injections par patient était de 8,25 ± 2,5 injections sur une période de 12 mois. Selon le modèle de régression linéaire à effets mixtes, lorsque les volumes du LRT, du LIR et du LSR de la région fovéale se situaient dans le quatrième quartile, on notait une baisse de la MAVC de –8,29 lettres (fourchette : de –10,96 à –5,62 lettres; p < 0,001), de –7,52 lettres (fourchette : de –10,3 à –4,74 lettres; p < 0,001) et de –6,93 lettres (fourchette : de –10,54 à –3,41 lettres; p < 0,001), respectivement. ConclusionsLe quartile le plus élevé des volumes du LRT, du LIR et du LSR s'accompagnait d'une détérioration des résultats visuels après l'administration d'un anti-VEGF pendant 12 mois dans le traitement de l'OMD. D'autres études calibrées pour examiner l'effet de l'anti-VEGF sur la morphologie du liquide rétinien pourront fournir un portrait plus clair du traitement personnalisé de l'OMD.

Consequences of anti-vascular endothelial growth factor treatment lapse in patients with retinal vein occlusion.

Anti-vascular endothelial growth factor (VEGF) treatments are the first-line treatment for Retinal Vein Occlusion (RVO). Although effectiveness and safety of these treatments is well documented, knowledge regarding the effect of lapses in anti-VEGF treatment among RVO patients is lacking. The purpose of this study is to analyse the anatomic and visual outcomes from a lapse in anti-VEGF treatment in patients with RVO. This retrospective case-control study evaluated 136 patients diagnosed with RVO and treated with anti-VEGF between January 2012 and June 2020 at Cole Eye Institute, Cleveland Clinic. Patients were divided into two cohorts: RVO patients with no lapse in anti-VEGF treatment (control group) and RVO patients with a lapse ≥3 months (lapse group). Central subfield thickness (CST) and best corrected visual acuity (BCVA) were collected pre-lapse, the first appointment post-lapse, and at 3-, 6-, and 12-month follow-up appointments. Lapse patients (n = 68) and control patients (n = 68) had similar pre-lapse CST (p = 0.466) and BCVA (p = 0.303). Lapse patients experienced a significant increase in CST after discontinuing anti-VEGF therapy (lapse: 400.6 ± 192.1 µm, control: 333.0 ± 111.1 µm, p = 0.024). This persisted 12 months post-lapse after re-initiation of anti-VEGF agents (lapse: 381.6 ± 161.1 µm, control: 307.5 ± 95.4 µm, p = 0.030). Lapse patients also experienced a decrease in BCVA after lapse (lapse: 54.3 ± 25.1 ETDRS, control: 64.4 ± 17.8 ETDRS, p < 0.001) that recovered after 6 months of anti-VEGF treatment. RVO patients with any lapse of anti-VEGF treatment are at risk for poorer anatomic and visual outcomes. Though BCVA normalizes upon treatment resumption, patients experience a statistically significant increase in CST that does not recover.

Chromatic Full-Field Stimulus Thresholds in Patients with Treatment-Naive Age-Related Macular Degeneration.

PurposeTo evaluate retinal sensitivity using chromatic full-field stimulus thresholds (FST) in patients with treatment naive exudative age-related macular degeneration (e-ARMD) before and during the first intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment.Patients and MethodsAfter general ophthalmological examinations to diagnose patients with e-ARMD the FST, the central foveal thickness (FCt) and the visual acuity were assessed in 20 eyes of 20 patients during this prospective study. Examinations were performed before and during the first treatment series with three intravitreal anti-VEGF injections. Normal values for FST were assessed in 19 eyes of 19 healthy subjects. Results were analyzed using Student’s two-tailed t-test and Pearson’s correlation coefficients between all functional parameters.ResultsAt baseline and before the 1st intravitreal anti-VEGF treatment, a moderately significant negative correlation between VA and FCt was found in the e-ARMD group (p = 0.02, r = −0.45 and p = 0.03, r = −0.45), respectively. After the 2nd intravitreal anti-VEGF injection, no significant correlation between VA and FCt was found (p = 0.12). However, a significant correlation between FCt and blue FST was evident (p = 0.04, r = 0.4). After the 3rd intravitreal anti-VEGF treatment, there was no correlation evident between VA and FCt (p = 0.31) but a high significant correlation between FCt and FST using red (p = 0.01, r = 0.53), green (p = 0.002, r = 0.6) and blue light (p = 0.007, r = 0.66).ConclusionDuring anti-VEGF treatment in patients with e-ARMD, the FST test showed higher significant correlations with the morphology measured by FCt, as it is the case for VA. These findings support that the FST test might serve as a valuable diagnostic tool for monitoring patients with e-ARMD and enhance functional assessment of retinal function under treatment with anti-VEGF.

Efficacy of Anti-Vascular Endothelial Growth Factor Treatment in Neovascular Age-Related Macular Degeneration and Systemic Cardiovascular Risk Factors.

This study evaluates whether the presence of cardiovascular risk factors (CRFs) affects functional and morphological responses to anti–vascular endothelial growth factor (VEGF) therapy in patients with neovascular age-related macular degeneration (nAMD). Retrospective analysis included 98 treatment-naïve eyes followed for at least 12 months. Patients received intravitreal injections of ranibizumab or aflibercept with the dosage and regimen set according to each manufacturer’s recommendations for their product. Parameters evaluated at each follow-up visit included best-corrected visual acuity and central retinal thickness. Additionally, the presence of the following CRFs was evaluated: male sex, age of older than 70 years, history of current or past smoking, systemic arterial hypertension, diabetes mellitus, total hypercholesterolemia, low-density lipoprotein hypercholesterolemia, high-density lipoprotein concentration of 45 mg/dL or less, atherogenic dyslipidemia, family history of cardiovascular disease, and chronic kidney disease. A statistically significant better letter gain in visual acuity (p = 0.012) and greater percentage of responders (p = 0.035)—that is patients in whom best corrected visual acuity was stabilized or improved at 12 months—were noted among patients without a diagnosis of arterial hypertension. A statistically significant better mean visual improvement was also achieved in patients with higher total cholesterol plasma levels (p = 0.004), but this finding was not reflected in the significantly higher percentage of responders. The presence of remaining analyzed risk factors did not substantially affect the results of treatment. Systemic arterial hypertension is an independent factor leading to a poor functional outcome following anti-VEGF therapy in patients with nAMD. Effects of anti-VEGF treatment in patients with high total cholesterol levels should be analyzed in further research.

Imaging Hyperreflective Foci as an Inflammatory Biomarker after Anti-VEGF Treatment in Neovascular Age-Related Macular Degeneration Patients with Optical Coherence Tomography Angiography.

Purpose To investigate the hyperreflective foci (HRF) as an inflammatory biomarker using optical coherence tomography angiography (OCTA) in neovascular age-related macular degeneration (AMD) patients after antivascular endothelial growth factor (anti-VEGF) treatment and its association with the retinal microcapillary density. Methods Twenty-five eyes from 25 patients with neovascular AMD were included in the study. All eyes were imaged with OCTA at baseline (M0) and after 3 consecutive injections (M3; injection performed each month) of anti-VEGF. The number of HRF in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and outer retina was counted. The vascular density of the fovea, parafovea, and the whole macula, as well as the area of the foveal avascular zone (FAZ), was measured. Results The mean interval between baseline and follow-up with OCTA was 93.08 ± 5.00 (range, 85-101) days. Compared with the baseline, the number of HRF significantly decreased in DCP (7.52 ± 3.06 vs. 3.76 ± 1.48, P < 0.01) and outer retina (12.04 ± 4.91 vs. 5.88 ± 3.32, P < 0.01) after treatment. There was no significant difference for HRF number in the SCP, the vascular density (containing foveal, parafoveal, and whole macular), and FAZ area before and after treatments. Conclusion The number of HRF in DCP and outer retina might serve as an inflammatory biomarker in patients with neovascular AMD. The reduced HRF possibly represents the alleviation of inflammation after anti-VEGF treatment in patients with AMD.

The Short-term Effect of a Single Lapse in Anti–Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema Within Routine Clinical Practice

PurposeDiabetic macular edema (DME) is a leading cause of vision loss in diabetics. Anti–vascular endothelial growth factor (VEGF) therapy has been shown to be an effective treatment option for DME, although the injections are costly and require frequent visits, which increases the risk for unintended treatment lapses. The aim of this study is to characterize the effects of an unintended treatment lapse in patients with DME undergoing anti-VEGF therapy.DesignRetrospective, comparative case series.MethodsThis retrospective chart review compared patients seen in a multicenter institutional practice with DME exhibiting an unintended minimum 3-month lapse in anti-VEGF treatment, with a control group of DME patients receiving regular anti-VEGF treatment without lapses. The primary outcome was difference in central subfield thickness (CST) between the control group and the treatment lapse group at 6 months following treatment lapse.ResultsA total of 164 patients were evaluated, 82 patients in the treatment lapse group and 82 patients in the control group. The average age was 65 years, and the average lapse in treatment was 6.2 ± 3.5 months (range 3-24 months). Comparison of data between the lapse and control groups revealed no significant differences in CST (359.9 ± 108.3 μm and 335.4±94.6 μm, respectively, P = .066) or in visual acuity (66.5 ± 14.3 and 68.9 ± 14.5, respectively, P = .136). Limitations included a relatively small sample size, retrospective nature, and only a single lapse being evaluated.ConclusionsAn unintended, single, relatively short-term lapse in anti-VEGF treatment in patients with DME did not appear to result in significant anatomic or visual compromise upon resumption of regular follow-up and treatment.

Relationship Between Final Visual Acuity and Optical Coherence Tomography Findings in Patients with Diabetic Macular Edema Undergoing Anti-VEGF Therapy

Objectives:To identify the prevalence of findings in optical coherence tomography (OCT) sections before intravitreal anti-VEGF treatment in patients with diabetic macular edema (DME), and to evaluate the relationship between these findings and final visual acuity and number of injections.Materials and Methods:This retrospective study included 296 eyes of 191 patients (104 male, 87 female) who started intravitreal ranibizumab treatment after being diagnosed with DME in the retina unit between January 2013 and April 2017 were included the study. Spectral domain OCT findings at the time of presentation such as presence of serous macular detachment (SD), vitreomacular traction (VMT), and epiretinal membrane (ERM) were recorded. In addition, the regularity of the ellipsoid zone (EZ) and inner retinal layers was also studied.Results:The mean central retinal thickness measured in SD-OCT was 449±81 μm before treatment and 350±96 μm after treatment (p<0.001). SD was detected in 155 eyes (52.4%), ERM in 67 eyes (22.6%), and VMT in 9 eyes (3%). Thirty eyes (10.1%) had disorganization of the retinal inner layers (DRIL) and 54 eyes (18.2%) had EZ deterioration. The presence of ERM, EZ irregularity, and DRIL were associated with significantly lower final visual acuity (p<0.0001), while there was no relationship between pre-treatment SD and final visual acuity (p=0.11). Injection number was higher in eyes with SD and ERM compared to those without, but this difference was statistically significant only in the presence of SD (p=0.01 and p=0.59, respectively). There was no difference in injection number according to EZ irregularity or presence of DRIL.Conclusion:The coexistence of SD with DME was associated with increased need for treatment but not with final visual acuity. EZ irregularities, DRIL, and ERM are findings that negatively affect visual acuity.

Risk factors for subretinal fibrosis after anti-VEGF treatment of myopic choroidal neovascularisation

PurposeTo assess the incidence, clinical features and predictive risk factors of subretinal fibrosis after treatment of active myopic choroidal neovascularisation (mCNV) with anti-vascular endothelial growth factor (VEGF).MethodsThis post-hoc analysis of...