Baseline predictors for subretinal fibrosis in neovascular age-related macular degeneration

AbstractTo find baseline predictors for subretinal fibrosis (SF) in neovascular age-related macular degeneration (nAMD). Forty-five eyes of 45 participants with treatment-naïve nAMD were consecutively enrolled and treated according to a standardized treat-and-extend protocol. Spectral-domain optical coherence tomography (OCT), color fundus photography and fluorescein angiography as well as novel imaging modalities polarization-sensitive OCT and OCT angiography (OCTA) were performed to detect SF after 1 year and find baseline predictors for SF development. Baseline OCTA scans were evaluated for quantitative features such as lesion area, vessel area, vessel junctions, vessel length, vessel endpoints and mean lacunarity. Additionally, the type of macular neovascularization, the presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material (SHRM), retinal hemorrhage as well as best-corrected visual acuity (BCVA) were evaluated. After 12 months 8 eyes (18%) developed SF. Eyes with SF had worse baseline BCVA (p = .001) and a higher prevalence of IRF (p = .014) and SHRM at baseline (p = .017). There was no significant difference in any of the evaluated quantitative OCTA parameters (p > .05) between eyes with and without SF. There were no quantitative baseline microvascular predictors for SF in our study. Low baseline BCVA, the presence of IRF and SHRM, however, are easily identifiable baseline parameters indicating increased risk.

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Tolerating subretinal fluid in the treatment of neovascular age-related macular degeneration with intravitreal aflibercept

Therapeutic Advances in Ophthalmology ◽

10.1177/25158414211022874 ◽

2021 ◽

Vol 13 ◽

pp. 251584142110228

Author(s):

Dilan Yildiz ◽

Akin Cakir ◽

Burak Erden ◽

Selim Bolukbasi ◽

Serkan Erdenöz ◽

...

Keyword(s):

Macular Degeneration ◽

Subretinal Fluid ◽

Age Related Macular Degeneration ◽

Age Related ◽

Intensive Treatment Group ◽

Significant Difference ◽

Intravitreal Aflibercept ◽

Treatment Naïve ◽

Change In The Mean ◽

The Mean

Objective: To compare the anatomical and functional outcomes of intensive and relaxed intravitreal aflibercept regimen in the management of neovascular age-related macular degeneration. Methods: The medical records of 50 eyes of 50 patients with treatment-naive neovascular age-related macular degeneration, who underwent intravitreal aflibercept therapy in the Retinal Department of University of Health Sciences Okmeydanı Training and Research Hospital (Istanbul, Turkey), were retrospectively reviewed. The demographic features and best-corrected visual acuities at baseline and at 1st-, 2nd-, 3rd-, 4th-, 6th-, 10th- and 12th- months, optical coherence tomography measurements, presence of intraretinal fluid, subretinal fluid and intraocular pressure values were studied. The patients were divided into two groups: intensive (subretinal fluid intolerant) and relaxed (<200 microns subretinal fluid tolerated) intravitreal aflibercept regimens. Results: The change in the mean best-corrected visual acuities from baseline to 12th month was 13.72 ± 33.97 letters in the intensive treatment group and 8.68 ± 27.22 in the relaxed group. There was no statistically significant difference between the groups ( p = 0.566). Similar proportions of both groups achieved ⩾10 letters gain (%48 vs. %40, respectively; p = 0.755) and ⩾10 letters loss (%20 vs. %24, respectively; p = 0.755). The mean central subfield thickness values decreased statistically significantly in both groups ( p < 0.001). There was no statistically significant difference between the groups (442.40 ± 161.32 to 318.0 ± 63.10 vs. 431.64 ± 151.52 to 303.08 ± 140.91, respectively; p = 0.724). The mean total injection numbers were significantly lower in the relaxed group (6.4 ± 1.65 vs. 4.8 ± 1.45, respectively; p = 0.01). Conclusion: Relaxed intravitreal aflibercept regimen has comparable efficiency and safety outcomes at 12 months with intensive intravitreal aflibercept regimen with fewer injections in the management of neovascular age-related macular degeneration.

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Effect of intravitreal injection of aflibercept on blood coagulation parameters in patients with age-related macular degeneration

Therapeutic Advances in Ophthalmology ◽

10.1177/2515841420903929 ◽

2020 ◽

Vol 12 ◽

pp. 251584142090392

Author(s):

Constantinos D. Georgakopoulos ◽

Olga E. Makri ◽

Athina Pallikari ◽

Konstantinos Kagkelaris ◽

Panagiotis Plotas ◽

...

Keyword(s):

Macular Degeneration ◽

Blood Coagulation ◽

Intravitreal Injection ◽

Age Related Macular Degeneration ◽

Intravitreal Injections ◽

Clinical Effects ◽

Coagulation Parameters ◽

Age Related ◽

Increased Risk ◽

Treatment Naïve

Purpose: Treatment with intravitreal injections of anti-vascular endothelial growth factor agents has been associated with an increased risk of arterial thromboembolic events. The aim of the present pilot study was to assess the effect of a single intravitreal injection of aflibercept on coagulation. Methods: Treatment-naïve patients with age-related macular degeneration ( n = 47), who were scheduled to undergo treatment with intravitreal injections of aflibercept, were enrolled. None of the included patients received any anticoagulation therapy or had a history of a recent arterial thromboembolic event. Blood samples were collected before the first intravitreal injection, and at 7 and 30 days after aflibercept administration. We evaluated coagulation parameters, such as platelet count and plasma fibrinogen and D-dimer levels; functional clotting parameters, such as prothrombin time, international normalized ratio, and activated partial thromboplastin time; and anticoagulant parameters, such as the levels of Proteins S and C. Results: The levels of all of the evaluated biomarkers were within the normal range at baseline and at both the time points throughout the study. No statistically significant changes were observed in any of the measured parameters at 1 week and 1 month after aflibercept administration. Conclusion: A single intravitreal injection of aflibercept in treatment-naïve patients with exudative age-related macular degeneration has no statistically significant effect on blood coagulation parameters for up to 1 month after aflibercept administration. Our results also provide an explorative statistical data, and further studies are required to evaluate any significant clinical effects of aflibercept on blood coagulation parameters. ClinicalTrials.gov ID: NCT03509623.

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Investigation of the Trend of Selecting Anti-Vascular Endothelial Growth Factor Agents for the Initial Treatment of Neovascular Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy

Journal of Clinical Medicine ◽

10.3390/jcm10163580 ◽

2021 ◽

Vol 10 (16) ◽

pp. 3580

Author(s):

Jae-Hui Kim ◽

Jong-Woo Kim ◽

Chul-Gu Kim

Keyword(s):

Macular Degeneration ◽

Initial Treatment ◽

Polypoidal Choroidal Vasculopathy ◽

Age Related Macular Degeneration ◽

Age Related ◽

Significant Difference ◽

Treatment Naïve ◽

Treatment Agent ◽

Type 3 ◽

Choroidal Vasculopathy

BACKGROUND: This study aimed to investigate the trend of selecting ranibizumab and aflibercept for the initial treatment of neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). METHODS: This was a retrospective study that included 460 patients who were diagnosed with treatment-naïve neovascular AMD and PCV and were initially treated with either ranibizumab or aflibercept. The patients were divided into two groups: the ranibizumab group (n = 96) and the aflibercept group (n = 324). The patients’ characteristics and the proportion of the subtypes of macular neovascularization (MNV) were compared between the two groups. RESULTS: Patients in the ranibizumab group were significantly older (mean 74.3 ± 8.4 years) than those in the aflibercept group (mean 70.4 ± 8.8 years; p < 0.001). In the ranibizumab group, the proportions of type 1 or 2 MNV, type 3 MNV, and PCV were 50.0%, 27.1%, and 22.9%, respectively. In the aflibercept group, the proportions were 35.2%, 6.8%, and 58.0%, respectively. There was a significant difference in the proportion of MNV subtypes between the ranibizumab and aflibercept groups (p < 0.001). Ranibizumab was used in 54.2% of patients with type 3 MNVs. However, in patients with PCV, aflibercept was used in 89.5% of patients. CONCLUSIONS: Ranibizumab was preferred as an initial treatment agent in older patients and those with type 3 MNV, whereas aflibercept was highly preferred in patients with PCV. The different characteristics and efficacy of the two agents may have partially contributed to this trend.

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Three-Year Outcomes of Wet Age-Related Macular Degeneration Treatment in Polish Therapeutic Programs

Medicina ◽

10.3390/medicina58010042 ◽

2021 ◽

Vol 58 (1) ◽

pp. 42

Author(s):

Małgorzata Figurska ◽

Marek Rękas

Keyword(s):

Macular Degeneration ◽

Treatment Program ◽

Retinal Thickness ◽

Age Related Macular Degeneration ◽

Central Retinal Thickness ◽

First Year ◽

Regular Treatment ◽

Age Related ◽

Significant Difference ◽

Treatment Naïve

Background and Objectives: Wet age-related macular degeneration (wAMD) is a chronic, progressive disease of the central part of the retina. Standard treatment for wAMD consists of multiple intravitreal injections of anti-vascular endothelial growth factor drugs. The study goal was to evaluate the three-year effectiveness of wAMD treatment with aflibercept and ranibizumab as part of the therapeutic program in routine clinical practice. Materials and Methods: 1430 patients (possessing 1430 wAMD eyes) with median age of 78.0 years (71.0, 83.0) were enrolled in a non-randomized, retrospective, observational, multicenter study; 804 (56.2%) eyes were treatment-naïve. Therapy was carried out in accordance with the guidelines of the treatment program (the fixed or pro re nata regimen). Results: After the first year of treatment, there was a gain of 2.03 (12.15) letters; after the second, 0.94 (13.72) (p ˂ 0.001); and after the third, 0.17 (14.05) (p ˂ 0.001). There was a significant reduction in the central retinal thickness. In the first year, the patients received 7.00 (5.00, 8.00) injections. In the following years, a significantly lower number of injections (4.00 (2.00, 5.00)) was administered. After the first year, there was a significant difference in the distribution of the best corrected visual acuity according to the Early Treatment Diabetic Retinopathy Study protocol, with more frequent values in the ranges > 35 ≤ 70 for this parameter and > 70 letters in the treatment naïve eye subgroup. After the first year, central retinal thickness in treatment-naïve eyes was significantly reduced. Conclusions: Regular treatment of wet age-related macular degeneration as part of the treatment program achieves functional stabilization and significant morphological improvement over a long-term, three-year follow-up, with significantly fewer injections needed after the first year of treatment.

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The Presence of Intra- or Subretinal Fluid during the Loading Phase in the Treatment of Exudative Age-Related Macular Degeneration with Intravitreal Ranibizumab Assessed by Optical Coherence Tomography

Ophthalmologica ◽

10.1159/000430103 ◽

2015 ◽

Vol 234 (2) ◽

pp. 61-66

Author(s):

Andreas Ebneter ◽

Boris Gekkiev ◽

Bhuvan Chanana ◽

Sebastian Wolf ◽

Martin S. Zinkernagel

Keyword(s):

Optical Coherence Tomography ◽

Visual Acuity ◽

Macular Degeneration ◽

Subretinal Fluid ◽

Age Related Macular Degeneration ◽

Optical Coherence ◽

Intravitreal Ranibizumab ◽

Visual Improvement ◽

Age Related ◽

Treatment Naïve

Purpose: To assess intra- and subretinal fluid during the loading phase with intravitreal ranibizumab in exudative age-related macular degeneration and to quantify the accuracy of crosshair scan spectral-domain optical coherence tomography with regard to retinal fluid. Methods: This is a retrospective study of 31 treatment-naive patients who received 3 monthly intravitreal ranibizumab injections. Visual acuity and the presence of retinal fluid were assessed at each visit using volume and crosshair scan protocols. Results: Visual acuity improved and central retinal thickness decreased significantly during the loading phase. However, retinal fluid persisted in two thirds of the patients. The accuracy of the crosshair scan to detect fluid was 93%. Conclusions: A substantial proportion of eyes had persistent fluid after 3 months of ranibizumab injections. However, visual improvement was independent of residual fluid. Message: Crosshair scans detect relevant collections of retinal fluid accurately and may be sufficient in daily clinical practice.

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One-year outcome of intravitreal ziv-aflibercept therapy for non-responsive neovascular age-related macular degeneration

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-310318 ◽

2017 ◽

Vol 102 (1) ◽

pp. 91-96 ◽

Cited By ~ 8

Author(s):

Imoro Zeba Braimah ◽

Komal Agarwal ◽

Ahmad Mansour ◽

Jay Chhablani

Keyword(s):

Adverse Events ◽

Macular Degeneration ◽

Retinal Pigment ◽

Subretinal Fluid ◽

Age Related Macular Degeneration ◽

Secondary Outcome ◽

Free Interval ◽

Age Related ◽

Significant Difference ◽

The Mean

AimTo evaluate 12-month outcome of intravitreal ziv-aflibercept (IVZ) therapy in eyes with neovascular age-related macular degeneration (nAMD) that are non-responsive to bevacizumab and ranibizumab.MethodsThis retrospective study included 16 eyes (14 patients) with nAMD who were on prior treatment with bevacizumab and ranibizumab and were treated with as-needed IVZ (1.25 mg/0.05 mL) for 12 months. The primary outcome measure was the mean change in best corrected visual acuity (BCVA) and secondary outcome measures included mean change in central macular thickness (CMT), retinal pigment epithelial detachment (RPED) heights, longest treatment free interval, presence of subretinal fluid (SRF) and intraretinal fluid (IRF) and adverse events.ResultsThere was no change in the mean logarithm of minimum angle of resolution (logMAR) BCVA at baseline and following treatment with IVZ therapy (p=0.978). The mean number of IVZ injections during 12 months was 5.9±3.3, and the mean number of antivascular endothelial growth factors (VEGFs) injections prior to switching to IVZ was 8.4±4.7. The mean treatment free interval was longer during IVZ therapy (114.4±67.1 days) compared with 76.3±54.6 days before IVZ therapy (p=0.03). Five (31.25%) eyes had visual gains of at least 0.1 logMAR, 3 (18.75%) eyes had stable BCVA (within 0.1 logMAR) and 8 (50%) eyes had BCVA decline of at least 0.1 logMAR. There was no significant difference in the mean CMT, RPED heights and presence of IRF and SRF at 12 months compared with baseline. No adverse events were noted.ConclusionIVZ increased the treatment free interval in non-responders but no significant change in visual and anatomic outcomes.

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Visual and anatomical outcomes associated with treat-and-extend administration of intravitreal aflibercept for neovascular age-related macular degeneration

International Journal of Retina and Vitreous ◽

10.1186/s40942-021-00326-4 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Mohamed Kamel Soliman ◽

Nicolas Tuli ◽

Thomas K. Lee ◽

William A. Britton ◽

Raman Tuli

Keyword(s):

Macular Degeneration ◽

Subretinal Fluid ◽

Retrospective Chart Review ◽

Age Related Macular Degeneration ◽

Treat And Extend ◽

Age Related ◽

Intravitreal Aflibercept ◽

Treatment Naïve ◽

The Mean ◽

Anatomical Outcomes

Abstract Purpose To investigate the visual and anatomical outcomes associated with treat-and-extend (TAE) regimen of intravitreal (IVT) aflibercept in eyes with treatment naïve neovascular age-related macular degeneration (nvAMD). Methods A retrospective chart review of eyes that underwent IVT aflibercept injections for nvAMD between May 2014 and March 2018 was performed. The primary outcome was the change in best corrected visual acuity (BCVA) at 12 months. Secondary outcomes included the change in central retinal thickness (CRT), subretinal fluid (SRF) and intraretinal fluid (IRF). Results Data from 213 eyes of 213 patients (138 female, 65%) met the inclusion criteria. The mean (SD) age of the patients was 80.4 (± 9.2) years. The mean baseline BCVA (0.92 ± 0.50 logMAR, improved by 0.20 (± 0.40) logMAR units at 12 months (p < 0.001). Seventy-two (34%) eyes gained ≥ 0.3 logMAR and 47 (22%) eyes achieved BCVA ≤ 0.3 logMAR at 12 months. Baseline BCVA, patient age, and the number of aflibercept injections received were predictors of the change in BCVA at 12 months. Mean CRT improved from 347 (± 117) µm at baseline to 246 (± 55) µm at 12 months (p < 0.001). The percentage of eyes with SRF and IRF on SD-OCT declined from 63 to 21% and from 60 to 26% at 12 months, respectively. Conclusion A TAE regimen of IVT aflibercept in treatment naïve nvAMD is associated with good visual and anatomical outcomes in routine clinical practice. Resolution of exudation occurred in about half of nvAMD cases at 12 months. Individualized administration of IVT aflibercept may reduce injection burden.

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Elevated Levels of Serum IL-17A Secondary to Repeated Intravitreal Injections of Aflibercept in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration

Applied Sciences ◽

10.3390/app10124109 ◽

2020 ◽

Vol 10 (12) ◽

pp. 4109

Author(s):

Małgorzata Seredyka-Burduk ◽

Michał Wiciński ◽

Sławomir Liberski ◽

Daria Marczak ◽

Magdalena Pol ◽

...

Keyword(s):

Growth Factor ◽

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Intravitreal Injections ◽

Monocyte Chemoattractant Protein 1 ◽

The Third ◽

Initial Loading ◽

Age Related ◽

Significant Difference ◽

Treatment Naïve

We evaluated the effect of three monthly intravitreal injections of aflibercept on the serum concentration of interleukin 17A (IL-17A), monocyte chemoattractant protein 1 (MCP-1/CCL2), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in treatment-naive patients with neovascular age-related macular degeneration (nAMD). Twenty-two eyes of twenty-two patients with nAMD scheduled for the initial loading phase of intravitreal aflibercept (2 mg/0.05 mL) were included. Serum VEGF, PlGF, MCP-1/CCL2 and IL-17A levels were determined four times in each individual—just before the first injection, 2–3 days after the first injection, just before the third injection, and then 2–3 days after the third aflibercept injection. A statistically significant difference was found between the serum PlGF and IL-17A levels measured before the first injection and after the initial loading phase, with a mean value (MV) of 440.884 vs. 302.151 (p = 0.023) for PlGF and MV = 139.088 pg/mL vs. 151.233 pg/mL (p = 0.016) for IL-17A, respectively. There were no statistically significant differences for VEGF and MCP-1/CCL2 between any of the compared measurements. We reveal that repeated injections of aflibercept promote an increase in serum IL-17A concentration, which may lead to a systemic inflammatory response mediated by IL-17A, but not by MCP-1.

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Genetic Risk Evaluation in Wet Age-Related Macular Degeneration Treatment Response

Ophthalmologica ◽

10.1159/000446819 ◽

2016 ◽

Vol 236 (2) ◽

pp. 88-94 ◽

Cited By ~ 3

Author(s):

Varun Chaudhary ◽

Michael Brent ◽

Wai-Ching Lam ◽

Robert Devenyi ◽

Joshua Teichman ◽

...

Keyword(s):

Macular Degeneration ◽

Treatment Response ◽

Age Related Macular Degeneration ◽

Patient Treatment ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Age Related ◽

Increased Risk ◽

Treatment Naïve

Objective: To evaluate the pharmacogenetic relationship between CFH haplotypes and single nucleotide polymorphisms (SNPs) with response to ranibizumab treatment for neovascular age-related macular degeneration (nAMD). Patients and Methods: This was a prospective cohort study involving 70 treatment-naive nAMD patients. Patients were genotyped for CFH haplotypes and SNPs in the C3, ARMS2, and mtDNA genes. Visual acuity and central macular thickness were assessed at baseline and during 6 monthly follow-up visits. Multivariate logistic regression was used to determine the association between genotypes and a gain of ≥15 letters at the 6-month endpoint after adjusting for potential confounders. Results:CFH haplotypes were associated with a gain of ≥15 letters at the 6-month endpoint (p = 0.046). Patients expressing protective haplotypes were more likely to achieve a gain of ≥15 letters relative to the greatly increased risk haplotypes [OR 6.58 (95% CI: 1.37, 31.59)]. Conclusion:CFH is implicated in nAMD patient treatment response to ranibizumab.

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Fluorescein angiographic characteristic in predominantly classic and occult types of neovascular age-related macular degeneration treated with ranibizumab

Therapeutic Advances in Ophthalmology ◽

10.1177/25158414211005305 ◽

2021 ◽

Vol 13 ◽

pp. 251584142110053

Author(s):

Cemal Çavdarlı ◽

Sebile Çomçalı ◽

Pınar Topcu Yılmaz ◽

Mehmet Numan Alp

Keyword(s):

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Clinical Aspects ◽

Fundus Fluorescein Angiography ◽

Intravitreal Ranibizumab ◽

Age Related ◽

Significant Difference ◽

Treatment Naïve ◽

The Mean ◽

Fluorescein Angiographic

Background and purpose: Randomised-controlled clinical trials (the ANCHOR and MARINA) examined the intravitreal anti-vascular endothelial growth factor (anti-VEGF) efficacy for eyes having fluorescein angiographic classic and occult (OCC) neovascular lesions. No significant difference in the treatment response between the lesion types was observed. Fundus fluorescein angiography and optical coherence tomography (OCT) are complementary devices that provide information about neovascular age-related macular degeneration (n-AMD). The aim of this retrospective study was to compare the clinical aspects of fluorescein angiographic characteristics in predominantly classic (PDC) and OCC subtypes of n-AMD treated with intravitreal ranibizumab. Methods: Treatment-naive fluorescein angiographic OCC-n-AMD and PDC-n-AMD patients, who received monthly intravitreal ranibizumab for 3 months after baseline, and were followed-up with pro re nata injections between March 2013 and February 2018, were included. Means of the visual acuity (VA), central macular thickness (CMT), and intravitreal injection and visit numbers of the groups were compared throughout 24 months. Results: We included 41 eyes of PDC-n-AMD patients and 36 eyes of OCC-n-AMD patients. The mean ages were 74.5 ± 10.6 and 71.9 ± 9.4, respectively. The baseline, and 3-, 6-, 12-, 18-, and 24-month VA results of the OCC group were significantly better than those in the PDC. However, VA gain in the PDC group at 3, 6, and 12 months was significantly higher than that in the OCC group. The mean of baseline CMT of the PDC (353 ± 118 µm) was significantly higher than that in the OCC group (293 ± 64 µm). No significant differences in terms of the number of visits or injections, or CMT change from the baseline values between groups were observed. Conclusion: The OCC-n-AMD patients had better baseline and follow-up VA and CMT means than the PDC-n-AMD patients. However, the PDC-n-AMD patients are expected to benefit more than the OCC-n-AMD patients in terms of VA gains.

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