scholarly journals Anti-vascular Endothelial Growth Factor Pharmacotherapy in the Treatment of Subretinal Choroidal Neovascularization

2012 ◽  
Vol 05 (02) ◽  
pp. 107
Author(s):  
Yoreh Barak ◽  
Mark A Ihnen ◽  
Shlomit Schaal ◽  
◽  
◽  
...  

Vascular endothelial growth factor (VEGF) plays a pivotal role in stimulating the growth of pathologic subretinal choroidal neovascularization (CNV). The increased production of VEGF and subsequent CNV formation can occur in degenerative, inflammatory, and vascular diseases of the retina and choroid, often leading to severe visual impairment. Anti-VEGF agents which are readily available today are much better, more potent, and longer acting in comparison with previous treatment modalities, and therefore have dramatically improved the prognosis of patients with CNV. There are four intravitreal anti-VEGF pharmacotherapies proven by large prospective, multicenter, randomized trials to be effective in the treatment of age-related macular degeneration (AMD)-related CNV: pegaptanib (Macugen®, Eyetech Pharmaceuticals, Palm Beach Gardens, FL), ranibizumab (Lucentis®, Genentech, Inc., South San Francisco, CA), bevacizumab (Avastin®, Genentech, Inc., South San Francisco, CA), and VEGF Trap-Eye (Eylea® Regeneron, Tarrytown, NY). However, there are still many challenges and unanswered questions regarding the optimal anti-VEGF pharmacotherapy agent, the best clinical treatment regimen, the most effective dosage, the optimal injection frequency, and the duration of treatment. The heavy burden of frequent injections on the elderly patient population and physicians begs for a simpler way of drug administration or development of more potent compounds.

2012 ◽  
Vol 06 (05) ◽  
pp. 296
Author(s):  
Yoreh Barak ◽  
Mark A Ihnen ◽  
Shlomit Schaal ◽  
◽  
◽  
...  

Vascular endothelial growth factor (VEGF) plays a pivotal role in stimulating the growth of pathological subretinal choroidal neovascularisation (CNV). The increased production of VEGF and subsequent CNV formation can occur in degenerative, inflammatory and vascular diseases of the retina and choroid, often leading to severe visual impairment. Anti-VEGF agents which are readily available today are much better, more potent and longer acting in comparison with previous treatment modalities and therefore have dramatically improved the prognosis of patients with CNV. There are four intravitreal anti-VEGF pharmacotherapies proven by large prospective, multicentre, randomised trials to be effective in the treatment of age-related macular degeneration (AMD)-related CNV: pegaptanib (Macugen®, Eyetech Pharmaceuticals, Palm Beach Gardens, FL), ranibizumab (Lucentis®, Genentech, Inc., South San Francisco, CA), bevacizumab (Avastin®, Genentech, Inc., South San Francisco, CA) and VEGF Trap-Eye (Eylea® Regeneron, Tarrytown, NY). However, there are still many challenges and unanswered questions regarding the optimal anti-VEGF pharmacotherapy agent, the best clinical treatment regimen, the most effective dosage, the optimal injection frequency and the duration of treatment. The heavy burden of frequent injections on the elderly patient population and physicians begs for a simpler way of drug administration or development of more potent compounds.


2016 ◽  
Vol 235 (4) ◽  
pp. 225-232 ◽  
Author(s):  
Tomoaki Shiba ◽  
Mao Takahashi ◽  
Izumi Yoshida ◽  
Hikari Taniguchi ◽  
Tadashi Matsumoto ◽  
...  

Purpose: The aim of this study was to determine whether multiple intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs for age-related macular degeneration (AMD) exacerbate systemic arteriosclerosis, using the cardio-ankle vascular index (CAVI) and intima-media thickness (IMT). Methods: We analyzed the data of 45 AMD patients who received intravitreal injections of anti-VEGF drugs (ranibizumab and/or aflibercept) and underwent systemic evaluations at baseline and after treatment. Reevaluation was conducted at ≥12 months from the initial treatment. Results: The total number of intravitreal injections of overall anti-VEGF drugs was significantly correlated with Δserum cystatin C. The cumulative number of aflibercept injections was identified as an independent protective factor for ΔCAVI. An increase in the cumulative number of intravitreal injections of overall anti-VEGF drugs was identified as a protective factor for Δmean IMT. Conclusion: Repeated intravitreal injections of an anti-VEGF drug for AMD may lead to morphological and functional changes in large arteries.


2017 ◽  
Vol 102 (7) ◽  
pp. 959-965 ◽  
Author(s):  
Maria Kataja ◽  
Pekko Hujanen ◽  
Heini Huhtala ◽  
Kai Kaarniranta ◽  
Anja Tuulonen ◽  
...  

AimsTo evaluate outcome of anti-vascular endothelial growth factor (VEGF) therapy for the treatment of neovascular age-related macular degeneration (nAMD) in the real-life setting and to compare incidence of ocular serious adverse events (SAE) after injections administered by nurses and physicians.MethodsRetrospective, single-centre study. Medical records of patients receiving anti-VEGF treatment for nAMD between 2008 and 2013 with three-loading-dose regimen were evaluated. Outcome measures were baseline visual acuity (VA), change in VA, number of intravitreal injections, incidence of ocular SAE and patients’ baseline characteristics affecting VA change. In addition, the number of injections per 1000 citizens living in the serving area and per individuals over 65 years old were estimated.Results1349 eyes in 1117 patients received a total of 11 562 intravitreal anti-VEGF injections. Twenty-one per cent of patients received treatment for both eyes. The mean baseline Snellen VA was 0.32. The mean change of VA from baseline was +2, +2 and ±0 Early Treatment Diabetic Retinopathy Study letters and the mean numbers of injections were 5.7, 4.7 and 4.9 at years 1, 2 and 3, respectively. There was a negative correlation between baseline VA and change of VA. Incidence of endophthalmitis was 0.086%. No difference in the incidence of ocular SAE was identified between injections given by nurses or by physicians. The number of intravitreal injections per all citizens was 9 per 1000 inhabitants and 45 per 1000 inhabitants over 65 years.ConclusionThe VA was maintained at the baseline level (±0 letters) with the mean of 15.3 anti-VEGF injections in real-world clinical practice during 3-year follow-up.


10.36469/9887 ◽  
2014 ◽  
Vol 2 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Tomohiro Iida ◽  
Aya Narimatsu ◽  
Kenji Adachi ◽  
Edward CY Wang

Purpose: To identify outpatient treatment patterns of patients with exudative age-related macular degeneration (AMD) who received approved anti–vascular endothelial growth factor (VEGF) therapy, using real-world data from hospitals in Japan. Methods: A hospital claims database was retrospectively reviewed for patients diagnosed with exudative AMD who were treated with anti-VEGF therapy in the outpatient setting between January 2010 and December 2012. Within a treatment period of at least 12 months, the frequency of anti-VEGF injections and AMD-related visits, and time intervals between AMD-related visits and anti-VEGF injections were captured for patients who had neither cataracts nor glaucoma. “Loading dose regimen” was defined as the first 2 or 3 monthly doses and “PRN maintenance regimen” (where PRN=pro re nata) was defined as the entire period of time after the loading doses had been administered. Results: Claims data were collected from a total of 219 patients from 13 of 126 hospitals: 217 treated with ranibizumab (8 received pegaptanib as well), 2 with aflibercept. Of these, 68 patients were treated for at least 12 months (all with ranibizumab PRN), and 29 had neither cataracts nor glaucoma and were included in the treatment pattern analysis. These 29 patients received a mean of 3.8 injections in the first 12 months and another 2.5 injections in the second 12 months of treatment. The average number of all outpatient visits was 16.1 in the first 12 months and 13.7 in the second 12 months, and an average of 11.6 days elapsed between injections and the previous outpatient monitoring visits using a PRN schedule. Conclusion: In a real-world setting in Japan, anti-VEGF PRN injections are administered less frequently than in clinical trials, and with time between monitoring and re-injection visits. Nonetheless, patients still visit the hospital frequently, which can significantly burden patients, caregivers, and healthcare providers.


2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Zhang ◽  
Sheng Gao ◽  
Xun Li ◽  
Xi Huang ◽  
Yi Zhang ◽  
...  

Background: We aimed to evaluate the comparative efficacy and safety of anti–vascular endothelial growth factor (anti-VEGF) monotherapy to identify its utilization and prioritization in patients with neovascular age-related macular degeneration (nAMD).Methods: Eligible studies included randomized controlled trials comparing the recommended anti-VEGF agents (ranibizumab, bevacizumab, aflibercept, brolucizumab, and conbercept) under various therapeutic regimens. Outcomes of interest included the mean change in best-corrected visual acuity (BCVA), serious adverse events, the proportion of patients who gained ≥15 letters or lost <15 letters in BCVA, the mean change in central retinal thickness, and the number of injections within 12 months.Results: Twenty-seven trials including 10,484 participants and eighteen treatments were identified in the network meta-analysis. The aflibercept 2 mg bimonthly, ranibizumab 0.5 mg T&E, and brolucizumab 6 mg q12w/q8w regimens had better visual efficacy. Brolucizumab had absolute superiority in anatomical outcomes and a relative advantage of safety, as well as good performance of aflibercept 2 mg T&E. The proactive regimens had slightly better efficacy but a slightly increased number of injections versus the reactive regimen. Bevacizumab had a statistically non-significant trend toward a lower degree of efficacy and safety.Conclusion: The visual efficacy of four individual anti-VEGF drugs is comparable. Several statistically significant differences were observed considering special anti-VEGF regimens, suggesting that brolucizumab 6 mg q12w/q8w, aflibercept 2 mg bimonthly or T&E, and ranibizumab 0.5 mg T&E are the ideal anti-VEGF regimens for nAMD patients. In the current landscape, based on the premise of equivalent efficacy and safety, the optimal choice of anti-VEGF monotherapies seems mandatory to obtain maximal benefit.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247161
Author(s):  
Ameay V. Naravane ◽  
Rusdeep Mundae ◽  
Yujia Zhou ◽  
Christopher Santilli ◽  
Frederik J. G. M. van Kuijk ◽  
...  

Regularly scheduled intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are essential to maintaining and/or improving many ocular conditions including: neovascular age-related macular degeneration (nAMD), diabetic retinopathy, and retinal vein occlusions with macular edema (RVO). This study aims to assess the effect of unintended delays in anti-VEGF treatment during the first wave of the COVID-19 pandemic. This retrospective case series identified patients receiving regularly scheduled anti-VEGF intravitreal injections based on current procedural terminology (CPT) code at two practices in Minnesota. Diagnoses were limited to nAMD, diabetic macular edema (DME), proliferative diabetic retinopathy, and RVO. Patients were divided into two groups based on whether they maintained or delayed their follow-up visit by more than two weeks beyond the recommended treatment interval during the COVID-19 lockdown. The ‘COVID-19 lockdown’ was defined as the period after March, 28th, 2020, when a lockdown was declared in Minnesota. We then compared the visual acuity and structural changes to the retina using ocular coherence tomography (OCT) to assess whether delayed treatment resulted in worse visual outcomes. A total of 167 eyes from 117 patients met criteria for inclusion in this study. In the delayed group, the average BCVA at the pre- and post-lockdown visits were 0.614 and 0.715 (logMAR) respectively (p = 0.007). Central subfield thickness (CST) increased from 341 to 447 in the DME delayed group (p = 0.03) while the CST increased from 301 to 314 (p = 0.4) in the nAMD delayed group. The results of this pilot study suggests that treatment delays may have a negative impact on the visual and anatomic outcomes of patients with nAMD and DME. Future studies with larger sample sizes are required for further investigation.


2019 ◽  
Vol 45 (1) ◽  
pp. 1
Author(s):  
Tjahjono D Gondhowiardjo

Secara global telah diterima bahwa perkembangan kemampuan ekonomi suatu Negara, berjalan parallel dengan peningkatan usia harapan hidup masyarakat-nya. Saat ini, usia harapan hidup penduduk Indonesia, berkisar antara 69 tahun (pria) dan 72 tahun (wanita). Kondisi demograpik ini secara tidak langsung akan terkait dengan pergeseran distribusi pola penyakit, terutama pergeseran pola penyakit berdasarkan infeksi menjadi pola penyakit/keadaan degeneratif yang terkait dengan gaya hidup. Hal itu dapat terlihat pada edisi ini, yang di-dominasi oleh makalah segment posterior yang terkait dengan peningkatan usia harapan hidup dan degenerasi (age related macular degeneration), atau kondisi yang secara tidak langsung merupakan refleksi gaya hidup (Diabetes Mellitus atau kualitas viskositas darah).  Kondisi tsb memperlihatkan bahwa, walaupun jaringan bolamata bersifat sangat spesifik  dan merupakan suatu kompartemen yang relatif terpisah dengan adanya sawar darah-bolamata, namun tetap terkait dengan berbagai kondisi sistemik; sehingga bolamata dapat menjadi “jendela” kondisi sistemik. Pergeseran pola penyebab kebutaan ke sisi segmen posterior, menuntut peningkatkan peralatan diagnostik digital dan peralatan intervensi yang lebih canggih, seperti foto-koagulasi laser, vitrektomi dan penggunaan berbagai jenis gas, yang tentunya menuntut keterampilan khusus baik bagi operator maupun paramedis-nya; serta pengobatan anti vascular endothelial growth factor (anti VEGF) secara serial yang relatif mahal, sebagaimana ketiga makalah yang ditampilkan.  Pergeseran pola penyakit tsb, secara tidak langsung menuntut kita, baik sebagai insititusi pelayanan ataupun pendidikan, maupun sebagai individu untuk ikut menyesuaikan diri, terutama dalam mengembangkan pola fikir untuk selalu dapat memberikan yang terbaik bagi pasien-pasien kita.  Namun sayangnya, tanpa sadar kita telah membuat dinding-dinding pembatas yang cenderung membatasi upaya pencapaian tujuan;  dan yang relatif dibuat tanpa mempertimbangkan situasi dan kondisi lokal.  Berbagai batasan tsb, baik yang terjadi secara internal, maupun external telah membelenggu kita terhadap kemungkinan menumbuhkan daya inovasi maupun kreativitas untuk pengembangan keilmuan demi kemaslahatan masyarakat.   Pada era jaminan kesehatan saat ini, pengobatan anti VEGF awalnya mendapat pembiayaan, namun kemudian di hentikan karena pembiayaan terhadap upaya pencegahan kebutaan yang dianggap terlalu tinggi. Hal itu terjadi, antara lain karena penolakan terhadap bukti ilmiah yang menyatakan bahwa sekalipun preparat anti VEGF dengan harga yang lebih murah, terdaftar untuk kondisi lain; namun terbukti tidak ada perbedaan effektivitas dibandingkan dengan jenis obat yang spesifik untuk kelainan mata yang lebih mahal. Selain itu, karena pengabaian pernyataan Badan Kesehatan Dunia yang menyatakan bahwa obat tsb termasuk obat essential untuk pencegahan kebutaan.  Penghentian pendanaan itu, merupakan ironi karena di berbagai Negara tetangga dengan pendapatan domestik yang lebih tinggi, justru memperbolehkan penggunaan obat tsb. Di berbagai Negara maju, dasar penentuan prioritas pendanaan pemerintah dibuat berdasarkan kajian biaya penatalaksaan / tindakan langsung, serta kerugian akibat terjadi pengabaian karena hilangnya potensi individu, keluarga dan masyarakat, baik dalam sisi sosial dan ekonomi bagi Negara (health technology assessment / HTA), berjalan lurus dengan besaran nilai prevalensi, dan Year of Lost Life due to Disability (YLD) serta (disability of activity loss / DALY) akibat suatu kondisi / penyakit.  Nilai YLD dan DALY menampilkan besaran kehilangan produktivitas individu, akibat  suatu penyakit dan dampaknya pada besaran biaya kesehatan yang harus ditanggung; data tersebut dibandingkan dengan nilai serupa untuk penyakit/keadaan lain, seperti stroke, gangguan kardio-vaskular, berbagai jenis kanker dll.


Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 438 ◽  
Author(s):  
Emmi Kokki ◽  
Tommi Karttunen ◽  
Venla Olsson ◽  
Kati Kinnunen ◽  
Seppo Ylä-Herttuala

Vascular endothelial growth factor (VEGF) expression induces age-related macular degeneration (AMD), which is a common vision-threatening disease due to choroidal neovascularization and a fibrovascular membrane. We describe a mouse model of neovascular AMD with the local expression of human VEGF-A165 in the eye. We use a transgenic mouse in which human VEGF-A165 has been silenced with the loxP-STOP fragment. The choroidal neovascularization and human VEGF-A165 expression in the mouse are induced by subretinal adenoviral Cre gene delivery. Cre gene transfer is compared with adenoviral LacZ gene transfer control. We characterize the AMD phenotype and changes in the vasculature by using fluorescein angiography, optical coherence tomography, and immunohistochemistry. At early time points, mice exhibit increases in retinal thickness (348 ± 114 µm vs. 231 ± 32 µm) and choroidal neovascularization area (12000 ± 15174 µm2 vs. 2169 ± 3495 µm2) compared with the control. At later time points, choroidal neovascularization develops into subretinal fibrovascular membrane. Human VEGF-A165 expression lasts several weeks. In conclusion, the retinas display vascular abnormalities consistent with choroidal neovascularization. Together with immunohistochemical findings, these changes resemble clinical AMD-like ocular pathologies. We conclude that this mouse model of Cre-induced choroidal neovascularization is useful for mimicking the pathogenesis of AMD, studying the effects of human VEGF-A165 in the retina, and evaluating anti-VEGF treatments for choroidal neovascularization.


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