Intravitreal Anti-vascular Endothelial Growth Research Articles

Bilateral Anti-VEGF on Same-Day-Investigation on Safety in Retinopathy of Prematurity: A Multicenter Retrospective Study

PurposeTo report incidence of procedure related complications in preterm infants with ROP treated with intravitreal anti vascular endothelial growth factors (anti VEGF) injection in both eyes on same day DesignRetrospective, multicenter case series SubjectsPreterm infants with ROP treated with anti VEGF bilaterally on same day MethodsIntervention: All included infants underwent intravitreal anti VEGF injection in both eyes under aseptic precautions in ophthalmic operation theatre (OT) or neonatal intensive care unit (NICU). Postoperative examination was performed to look for procedure related complications Main Outcome MeasuresIncidence of procedure related complication (Presumed endophthalmitis, intraocular inflammation, lens injury, vitreous hemorrhage, retinal tear) in the study cohort. To study association of indication, type of anti VEGF, type of needle used, setting of procedure, site of injection (distance from limbus) and experience of the treating ophthalmologist with the complications. Results9984 eyes of 4992 infants were analysed. The procedure was most commonly performed in ophthalmic OT (8258, 82.7%) using 29G (4514, 45.2%) needle between 1-1.5 mm (9984, 100%) from limbus. Aggressive retinopathy of prematurity was the most common indication for anti VEGF use (4866, 48.7%) while Bevacizumab was the most commonly used anti VEGF agent (8642, 86.6%). Overall, 26 eyes (0.3%) had procedure related complications. Lens injury (15, 0.15%) and presumed endophthalmitis (7, 0.07%) were most common complications. One eye had culture proven endophthalmitis with Pseudomonas aeruginosa. No case of bilateral endophthalmitis was noted. Endophthalmitis was not associated with setting of procedure or type of anti VEGF used, while risk of lens injury was seven times higher when performed in NICU and 30 times higher when performed by an ophthalmologist with < 1year of experience in injecting anti VEGF in preterm infants. ConclusionsThe incidence of presumed endophthalmitis after bilateral same day anti VEGF in infants with ROP is 0.07%. These infants can be treated in both eyes on same day with the anti VEGFs and needles (29-32G) evaluated in this study, with emphasis on the direction of needle parallel to visual axis. Extra precaution is advocated if the procedure is planned in NICU or by an ophthalmologist with limited experience.

Branch Retinal Vein Occlusion

Branch retinal vein occlusion is common vaso- occlusive disease of retina. Extent of resulting haemorrhage and edema in macular area defines visual acuity. This is a case report of patient with branch retinal vein occlusion with macular edema with no known systemic disease. FDA approved intravitreal anti vascular endothelial growth factor inhibitor was advised as treatment option for the disease.

Analiza zmian parametrów angiografii optycznej koherentnej tomografii wykonanej u pacjentów z zakrzepem naczyń żylnych siatkówki przed leczeniem iniekcjami inhibitora czynnika wzrostu śródbłonka naczyniowego i po leczeniu

Optical coherence tomography angiography is a modern, non-invasive method for assessing hemodynamics in retinal and choroidal vessels. The study presents changes occurring in optical coherence tomography angiography examination in patients with retinal vein occlusion, before and after therapy with intravitreal anti vascular endothelial growth factor injections. Anti vascular endothelial growth factor therapy in patients with retinal vein occlusion reduces the non-perfusion area, improves retinal blood flow, reduces retinal ischemia, reduces cystoid macularedema, and improves visual acuity.

Vascular Tumors and Malformations of the Choroid

Choroidal vascular tumors; it may present as circumscribed and diffuse choroidal hemangiomas and rarely choroidal hemangiopericytoma and phacomatosis pigmentovascularis. Choroidal hemangiomas are benign vascular hamartomatous tumors that occur in two forms: circumscribed and diffuse. The circumscribed form is typically an isolated finding without systemic associations, while the diffuse form generally occurs in association with Sturge–Weber syndrome. Circumscribed choroidal hemangiomas are generally seen as well-circumscribed, round or oval, elevating dome-shaped orange or red masses located posterior to the equator in the fundus, whereas diffuse choroidal hemangiomas have a diffuse red-orange color appearance (tomatoketchup). Although the diagnosis of choroidal hemangioma is better investigated by means of multimodal imaging, indocyanine green angiography and ultrasonography are the most important tests in the differential diagnosis. For circumscribed choroidal hemangiomas with exudative retinal detachment or cystoid macular edema, a variety of treatment modalities are available. Symptomatic patients can be treated with oral propranolol, photodynamic therapy, transpupillary thermotherapy, plaque radiotherapy, external radiotherapy or intravitreal anti-vascular endothelial growth factors.In this review, the pathogenesis, clinical features and treatment methods in choroidal vascular tumors will be discussed.

Efficacy of Intravitreal Anti Vascular Endothelial Growth Factor Injection Compared to Focal Therapy in Pediatric Patients with Coats Disease

Introduction: Coats disease is a retinal vascular disorder that may lead to progressive exudative retinal detachment. The standard regiment of treatment is focal therapy. However, its effectiveness may decrease when more than two quadrants of the retina exhibit vascular abnormalities. Thus, recent studies tried to use anti vascular endothelial growth factor (anti-VEGF) as therapy for the vascular problems. Aims: Comparing the efficacy between anti-VEGF injection and standard therapy regiment such as focal laser therapy. Methods: Literature searching was conducted through PubMed, ScienceDirect, Google Scholar, ProQuest, and SpringerLink. Search terms included "Coats’ Disease" and mesh terms of “Anti- VEGF". The efficacy is assessed based on Best-Corrected Visual Acuity (BCVA) and improvement in fundus manifestations. Results: All of the studies that conducted primary intravitreal anti-VEGF treatment were followed by necessary ablative treatment. These studies, such as by Yang Q and Zheng XX, et al. showed remarkable improvements in both visual acuity and anatomical outcomes. Laser therapy also gained satisfactory result in upgrading clinical stages, even though some complications including subretinal fibrosis, cataract, and vitreous hemorrhage were reported. A comparative study by Ray R, et al. noted that group undergoing anti-VEGF might require longer treatment sessions despite possible benefits. Conclusion: Anti-VEGF agents can be used as neoadjuvant in standard therapy. It did not reduce the time for full treatment, but the resolution of disease was seen in the most severe cases treated with combination therapy.

Bilateral recurrent choroidal neovascularization in AZOOR

AbstractWe present a case of acute zonal occult outer retinopathy (AZOOR) in a 61‐year‐old man who presented associated recurrent choroidal neovascularization as a complication in both eyes; he was managed with several intravitreal anti vascular endothelial growth factor (anti‐VEGF) injections in both eyes as well as with Prednisone and Methotrexate, which in improved the disease control.

Evaluation of blood inflammatory parameters of infants with premature retinopathy treated with intravitreal anti vascular endothelial growth factor

Evaluation of blood inflammatory parameters of infants with premature retinopathy treated with intravitreal anti vascular endothelial growth factor

Impact on visual acuity and psychological outcomes of ranibizumab and subsequent treatment for diabetic macular oedema in Japan (MERCURY)

PurposeThe MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis.MethodsThis was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients’ psychological status using the Hospital Anxiety and Depression Scale (HADS).ResultsThe mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was − 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080).ConclusionMERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

The Risk of Posterior Capsule Rupture during Phacoemulsification Cataract Surgery in Eyes with Previous Intravitreal Anti Vascular Endothelial Growth Factor Injections.

To investigate if previous intravitreal anti vascular endothelial growth factor (VEGF) injections are a predictor for posterior capsule rupture (PCR) during phacoemulsification cataract surgery. National Health Service: Whipps Cross University Hospital Eye Treatment Centre. District General, London, United Kingdom DESIGN:: Single centre, retrospective, electronic medical record (EMR) database study with univariate analysis. EMR (Medisoft) was used to extract data for eyes undergoing phacoemulsification surgery between 01.08.16 to 01.01.18. Patient demographics, indication for intravitreal therapy, treatment type, number of previous intravitreal injections (IVI), diabetic status, surgeon grade and operative complications were included as variables for analysis. Data was available for 4047 cataract operations. Of these, 108 had undergone previous anti-VEGF IVI treatment. Three eyes were noted to have pre-operative PC trauma and were excluded from the final analysis. The logistic regression analysis after exclusion of the eyes with pre-existing damage to the PC confirmed that prior anti-VEGF IVI treatment was associated with an increased risk of PCR when compared to the non IVI group (9.26% vs 1.88%, p<0.0001). There is a dose dependent relationship between the number of anti-VEGF injections and the likelihood of PCR. Previous intravitreal anti-VEGF injections are significantly correlated with an increased risk of surgical PCR despite the absence of visible structural damage to the PC pre-operatively.

A unique case of development of central retinal vein occlusion in diabetic papillopathy

Diabetic papillopathy (DP) is a rare ocular complication of diabetes presenting as acute disc edema. It is characterized by minimal or no visual symptoms and has tendency to resolve spontaneously in most of the patients with no visual sequel. Visual debility, if present, is attributable to diabetic macular edema (DME), advanced diabetic retinopathy or conversion to ischemic optic neuropathy. We report a case of 33 years old female who presented with bilateral papillopathy with best corrected visual acuity (BCVA) of 6/6 in both eyes. She had associated severe non proliferative diabetic retinopathy but noDME. On follow up, thepatient had good metabolic control and clinical improvement in DP, but she developed sudden diminution of vision in left eye as a result of non ischemic central retinal vein occlusion (CRVO) which was characterized by BCVA of 6/36, dilated tortuous veins and DME. No specific cause of non-ischaemicCRVOwas revealed on detailed work up. Structural and functional improvement was seenon monthly intravitrealanti vascular endothelial growth factor(VEGF) administration.Her BCVA post threeinjectionstood at 6/18. This is to report the possibility of development of CRVO in DP and highlight the need for close follow-up of such patients even in presence of strict diabetic control.

Macular edema secondary to malignant Hypertension managed with Intravitreal Bevacizumab

Intravitreal anti VEGF agents are used in a variety of retinal pathologies to decrease the VEGF levels resulting due to breakdown of the blood retinal barrier hence decrease the exudation from vessels which causes macular edema (ME). A 61year old patient presented with sudden decrease in vision in both eyes with a history of systemic malignant hypertension leading to macular edema as documented on optical Coherence Tomography (OCT) in both eyes. The foveal thickness (FT)of 536 and 328 microns (μ) were observed in the right and left eye each. He was advised intravitreal anti vascular endothelial growth factor (VEGF) in both eyes and advised complete systemic evaluation with the physician. Following one month postintravitreal bevacizumab ( IVB) injection in right eye, marked visual improvement was noted with concomitant significant reduction in macular edema in both eyes. Single Bevacizumab injection with control of hypertension in our patient resulted in rapid resolution of the macular edema and early visual recovery. Intravitreal anti VEGF is an effective treatment option in eyes due to hypertensivemaculopathy especially to gain speedy visual recovery. The case gives a unique outlook to the course of ME in the single patient with malignant HTN with or without IVB injection. We believe that anti VEGF injections may result in rapid recovery in vision and minimize the risk of permanent vision loss in eyes with malignant hypertension.

Intravitreal dexamethasone implants versus intravitreal anti-VEGF treatment in treating patients with retinal vein occlusion: a meta-analysis

BackgroundRetinal vein occlusion (RVO) is a common retinal venous disorder that causes vision loss. No specific therapy has been developed. Controversy exists regarding two treatments: intravitreal dexamethasone implants and anti-vascular endothelial growth factor (VEGF). The goal of this study is to compare the effectiveness and safety of dexamethasone implants and anti-VEGF treatment for RVO.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for studies comparing dexamethasone implants with anti-VEGF in patients with RVO. Best-corrected visual acuity (BCVA), central subfield thickness (CST), intraocular pressure changes, conjunctival haemorrhage, reduced VA, and macular oedema were extracted from the final included studies. RevMan 5.3 was used to conduct the quantitative analysis and bias assessment.ResultsFour randomised controlled trials assessing 969 eyes were included. The anti-VEGF treatment showed better BCVA improvement (mean difference [MD] = − 10.59, P < 0.00001) and more CST decrease (MD = − 86.71 μm, P = 0.02) than the dexamethasone implants. However, the dexamethasone implants required fewer injections. As for adverse effects, the dexamethasone implants showed significantly higher intraocular pressure (IOP) and more cataracts than the anti-VEGF treatment. No significant differences were found in conjunctival haemorrhage, reduced VA, and macular oedema.ConclusionsAnti-VEGF treatment showed better functional and anatomical improvement with less risk of IOP elevation and cataract formation compared to dexamethasone implants. Thus, anti-VEGF treatment is the first choice for treating RVO patients.

The Impact of Epiretinal Membrane in Neovascular Age-Related Macular Degeneration Treatment: A Spectral-Domain Optical Coherence Tomography Study

ABSTRACTPurpose: The purpose of this prospective study was to evaluate the impact of epiretinal membrane (ERM) on anatomical and functional results in patients with wet age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth (anti-VEGF) injections. Methods: Participants in the study were 48 patients with either wet AMD alone (AMD group, n = 27) or AMD and ERM (AMD/ERM group, n = 21). All patients received intravitreal anti-VEGF injections (three monthly injections and PRN thereafter) and were followed up for at least 12 months. All participants had best-corrected visual acuity (BCVA) measurement and spectral domain-optical coherence tomography (SD-OCT) at each visit, while fluorescein angiography was performed at baseline and then at the discretion of the physician. Results: There was a statistically significant improvement in BCVA at month 12 compared to baseline in each group (p < 0.001 for both groups), while the two groups did not differ significantly regarding BCVA at the end of the follow-up (p = 0.056). Additionally, there was a statistically significant reduction in CRT in both groups at month 12 (p < 0.001 for AMD group and p = 0.004 for AMD/ERM group) with no statistically significant difference between the groups (p = 0.183). Patients in the AMD group had a lower percentage of subretinal fluid (25.9%) than patients in the AMD/ERM group (52.4%) at the end of the follow-up, while ellipsoid zone disruption was found to be more profound in the AMD/ERM group (38.1%) than in the AMD group (18.5%). Patients in the AMD/ERM group needed more injections (7.1 ± 2.0 injections) than patients in the AMD group (4.8 ± 1.7 injections). Conclusions: Patients in the AMD/ERM group had a higher percentage of subretinal and intraretinal fluid and ellipsoid zone interruption during the follow-up period. Anti-VEGF treatment appeared to have a beneficial effect in both groups, although the AMD/ERM group needed more injections compared to the AMD group.

The impact of epiretinal membrane on neovascular age‐related macular degeneration treatment: A spectral‐domain optical coherence tomography study

PurposeThe purpose of this prospective study was to evaluate the impact of epiretinal membrane (ERM) on anatomical and functional results in patients with wet age‐related macular degeneration (AMD) treated with intravitreal anti‐vascular endothelial growth (anti‐VEGF) injections.MethodsParticipants in the study were 48 patients with either wet AMD alone (n = 27) or AMD and ERM (n = 21). All patients received intravitreal anti‐VEGF injections (3 monthly injections and PRN thereafter) and were followed‐up for at least 12 months. All participants had best corrected visual acuity (BCVA) measurement and optical coherence tomography (OCT) at each visit, while fluorescein angiography was performed at baseline and then at the discretion of the physician. The main outcomes were the change in BCVA and central retinal thickness (CRT) along with the presence of fluid in the two groups.ResultsThere was a statistically significant improvement in BCVA in both groups, while the two groups did not differ significantly regarding BCVA at the end of the follow‐up. Accordingly, there was a statistically significant reduction in CRT in both groups, which did not have any difference in between. Patients with AMD alone presented subretinal fluid in a lower percentage than patients with AMD/ERM at the end of the follow‐up. In addition, patients with coexistence of AMD and ERM needed more injections than patients with AMD alone.ConclusionsPatients with AMD combined with ERM seemed to need more injections for the treatment of AMD, while they presented higher percentage of subretinal fluid at the 12‐month follow‐up, although there was no significant difference in BCVA and CRT in comparison with patients having AMD alone.

Anterior segment changes on ultrasound biomicroscopy after intravitreal anti vascular endothelial growth factor injection

BackgroundIntravitreal injections are standard of care today and have the potential to change the anatomy of the anterior segment of the eye. This research was undertaken to evaluate the changes in anterior segment anatomy after intravitreal anti vascular endothelial growth factor (anti VEGF) injections. MethodsWe conducted a prospective interventional case series at a quaternary care center where patients undergoing intravitreal injection had pre and post injection ultrasound biomicroscopy (UBM) and intraocular pressure (IOP) measurement after intravitreal anti VEGF injection of 0.05ml volume. Results75 eyes of 75 patients as per inclusion criteria were studied. A transient rise in IOP post intravitreal injection was found immediately after the injection. The mean rise from baseline was 17mmHg immediately after injection and IOP returned to normal within 30min in all cases. Angle measurement done as per established techniques revealed no significant changes in the angles and anterior chamber. ConclusionIntravitreal anti VEGF injections had no readily apparent short term concerns. IOP rise was transient and no case was found to have IOP high enough to cause concern for interruption of the optic nerve perfusion or statistically significant narrowing of the anterior chamber angle.

The early effects of intravitreal anti vascular endothelial growth factor agents on intraocular pressure and central corneal thickness.

To investigate the early effects of two intravitreal (IV) anti vascular endothelial growth factor agents (anti-VEGF), bevacizumab and ranibizumab, on intraocular pressure (IOP) and central corneal thickness (CCT) within the first post-injection month. This prospective study comprised 109 eyes of 109 adult cases who had IV bevacizumab or ranibizumab injections because of age-related macular degeneration (ARMD), retinal venous occlusion (RVO), diabetic retinopathy, and macular edema or central serous chorioretinopathy (CSCR). None of the cases had medical histories of any kinds of glaucoma or increased IOP and IV injection before and all of them underwent a detailed ocular examination including measurements of IOP by non-contact tonometer and CCT by ultrasonic pachymeter pre-injection. IOP measurements were repeated at 30min and 1st, 7th, and 30th day after the injection. CCT measurements were repeated at the 7th and 30th post-injectionday. Paired sample t tests were used for the statistical analysis in order to evaluate the significance of changes in IOP and CCT. The mean age of 56 male and 53 female cases was 63.58±11.04years. Fifty-six cases (51.4%) had diabetic retinopathy, 33 cases (30.3%) had ARMD, 11 cases (10.1%) had RVO, and 9 cases (8.3%) had CSCR. Bevacizumab was used in 97 (89%) cases and ranibizumab was used in 12 (11%) cases. The IOP increased significantly 30min after the injection (p<0.001) but significant decreases were observed at the 1st, 7th, and 30th day post-injection (p<0.001). No significant differences were observed in CCT between pre-injection and 7th and 30th post-injection day values (p=0.924 and p=0.589, respectively). Intravitreal bevacizumab and ranibizumab injections can cause hyper acute increase in IOP because of vitreal expansion but this effect is generally reversible in non-glaucomatous cases.

Current status in diabetic macular edema treatments

Diabetes is a serious chronic condition, which increase the risk of cardiovascular diseases, kidney failure and nerve damage leading to amputation. Furthermore the ocular complications include diabetic macular edema, is the leading cause of blindness among adults in the industrialized countries. Today, blindness from diabetic macular edema is largely preventable with timely detection and appropriate interventional therapy. The treatment should include an optimized control of glycemia, arterial tension, lipids and renal status. The photocoagulation laser is currently restricted to focal macular edema in some countries, but due the high cost of intravitreal drugs, the use of laser treatment for focal and diffuse diabetic macular edema (DME), can be valid as gold standard in many countries. The intravitreal anti vascular endothelial growth factor drugs (ranibizumab and bevacizumab), are indicated in the treatment of all types of DME, but the correct protocol for administration should be defined for the different Retina Scientific Societies. The corticosteroids for diffuse DME, has a place in pseudophakic patients, but its complications restricted the use of these drugs for some patients. Finally the intravitreal interface plays an important role and its exploration is mandatory in all DME patients.

Low-fluence PDT better than anti-vascular endothelial growth factor

Sir, It was interesting to read the article “Low-fluence photodynamic therapy” for early onset choroidal neovascular membrane (CNVM) following LASIK by Dr. George J Manayath et al.[1] The authors have to be commended for an excellent work. But I have some reservations that I would like to state. Were there any pathological myopia changes recorded by the refractive surgeon, prior to the refractive surgery? The time lapse between break in Bruch's membrane at the macula and appearance of CNVM is usually quite long. Often many weeks and not just 2 weeks. The break in Bruch's membrane can be induced by the stretch of the microkeratome, for a minute or so (the time the microkeratome suction ring exerts pressure) cannot be deduced from a single case study. I disagree with the author's statement that low fluence PDT is an alternative to intravitreal anti vegf anti-vascular endothelial growth factor (VEGF) injections for the following reasons. The anti vegf VEGF has been shown to be clearly superior to the PDT for the treatment of subfoveal CNVM in Myopia.[2] “The superior functional results of anti-VEGF drugs provide the reason for the first-line status of this treatment modality. Increasing safety data and consistent results of prospective pilot trials have proved photodynamic therapy to be inferior”.[3] Considering the cost of PDT and the ease of intraviteral injection, I would have expected the authors to try intravitreal injection of anti VEGF, rather than the inferior quality of treatment of low fluence PDT. Also statistics extracted from near by Retina Centre (Retina Institute of Karnataka, Bangalore) revealed that the PDT rate that used to be around 50 in 2004 has now come down to less than 6, in 2011, since the ubiquitous use of anti-VEGF. It is to the credit of the authors that they do mention in passing the anti-VEGF treatment for myopic choroidal neovscularization.

Appropriate selection of the managements based on the understanding of diabetic macular edema

Diabetic macular edema (DME) is one of causes leading to visual acuity loss in the diabetic population.In recent years,great progress has been achieved in the treatment for DME.While laser photocoagulation and pars plana vitrectomy remain the standard of care,a new wave of methods,including intravitreal corticosteroid and anti-vascular endothelial growth factor (anti-VEGF) medications,is emerging and shows the preliminary safety and efficacy profile for DME by a number of clinical trials.This article introduce the definition,classification,pathogenesis and the different treatment methods for DME,so to aid ophthalmologists in evaluating the most appropriate and up-todate management options in managing DME.Particular attention is paid to summarize recent peer-reviewed literatures of ranibizumab (Lucentis). Key words: Ranibizumab; Anti-angiogenesis; Corticosteroid; Diabetic macular edema; Diabetic retinopathy

Intravitreal Anti-VEGF Drugs as Adjuvant Therapy in Diabetic Retinopathy Surgery

The use of intravitreal anti vascular endothelial growth factor (anti-VEGF) drugs such as pegaptanib, ranibizumab and bevacizumab has been widely reported to treat complications such as macular edema and rubeosis. During the past few years they have also been used as an adjuvant therapy to reduce intraocular bleeding during vitrectomy in eyes with proliferative diabetic retinopathy as well as to reduce the occurrence of vitreous haemorrhages in vitrectomized eyes and facilitate glaucoma surgery. In this paper we review the use of anti VEGF drugs in the surgical management of diabetic retinopathy related complications.