Regression Of Choroidal Neovascularization Research Articles

Two macular holes due to choroidal neovascularization after pars plana vitrectomy with internal limiting membrane peeling

Introduction: To present a case of two macular holes (MHs) with myopic choroidal neovascularization (CNV) lesion. Case Presentation: A single case was evaluated. A 72-year-old woman presented with two small MHs in her left eye. One year ago, she had undergone vitrectomy for myopic foveal schisis, and a significant reduction of the schisis and a CNV lesion was observed after surgery. On examination, OCT (optical coherence tomography) showed the atrophic CNV and two MHs were located upper and lower close to the edge of the CNV. A PPV (pars plana vitrectomy) with two free ILM (internal limiting membrane) flaps implant was performed in her left eye. At 3 months after surgery, the two macular holes were both closed and the BCVA (best corrected visual acuity) was improved. Conclusions: Two MHs secondary to the regression of CNV after primary PPV combined with complete ILM peeling in eyes with macular schisis.

The effect of fibroblast growth factor 2 on neovascular vessels depends on the stage of angiogenesis

ObjectiveThe exact relationship between fibroblast growth factor 2 (FGF2) and choroidal neovascularization (CNV) remains unclear. In this study, using optical coherence tomography angiography (OCTA) and FGF2-tg mice which are transgenic mice with a rhodopsin promoter/FGF2 gene fusion, we aimed to investigate the dynamics of FGF2's role in angiogenesis over time. MethodsWe developed laser-induced CNV models of FGF2-tg and wild-type (WT) mice and then separated them into two groups using different laser photocoagulation (PC) conditions. The first group received 3 intense PC shots (1st PC) altogether (one-time PC group), while the other group received 3 intense PC shots (1st PC) followed by 6 additional weak PC shots (2 nd PC) on the 7th day after 1st PC (two-times PC group). ResultsUsing OCTA to observe vessel changes within the same individual over time, there was no difference in the timing of vessel transition from the CNV development phase to the CNV regression phase between FGF2-tg and WT mice in the one-time PC group. In contrast, the neovascular vessels in the two-times PC group of FGF2-tg mice were maintained at least 28 days post-2nd PC without regression. In addition, mature vessels surrounded by PDGFRβ positive pericytes and α-SMA positive smooth muscle cells were observed. Real-time qPCR showed a substantial increase in apelin mRNA expression in the one-time PC group of FGF2-tg, rather than VEGF-A (p < 0.05, n = 5 or 6). Moreover, the expression levels of PDGFRβ, apelin, and Ang1 were significantly higher in FGF2-tg mice of two-times PC group than in WT mice (p < 0.05, n = 5 or 6). ConclusionsFGF2 not only promotes neovascularization via the apelin/APJ system, which is independent of VEGF signaling pathway, but also helps maintain and stabilize pre-existing neovascular vessels by stimulating PDGFRβ and Ang1. The effect of FGF2 on the neovascular vessels depends on the stage of angiogenesis.

Clinical case of bilateral rapidly progressive osteoma of the choroid

Choroidal osteoma is a benign neoplasm characterized by the appearance of mature bone tissues at the level of the choroid and unilateral development. This study highlights a clinical case of bilateral rapidly progressing osteoma of the choroid in a child, which was complicated by tumor decalcification and choroidal neovascularization. A 14-year-old male teen has been under observation in the S. Fyodorov Eye Microsurgery Federal State Institution, Saint-Petersburg branch since 2019, for bilateral choroidal osteoma. At the initial visit, a yellow-orange lesion with clear boundaries was noted in the left eye, localized at the level of the choroid and parapapillary, and had a trabecular bone structure. Based on the clinical picture and data from instrumental studies (ultrasound and optical coherence tomography), he was diagnosed with choroidal osteoma. During observation, a similar lesion appeared in the right eye, and its relatively rapid growth was observed in both eyes. Owing to the absence of zones of decalcification and neovascularization, further follow-up was initiated. However, in the presence of zones of decalcification of the bone tissue and newly formed vessels of the choroid, a threefold intravitreal injection of an angiogenesis inhibitor was performed. Consequently, regression of choroidal neovascularization was observed. Speculatively, the main reason for the atypical disease course in this teenager is the specificity of bone tissue development in childhood and adolescence.

CRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization

The CRISPR/Cas9 system easily edits target genes in various organisms and is used to treat human diseases. In most therapeutic CRISPR studies, ubiquitously expressed promoters, such as CMV, CAG, and EF1α, are used; however, gene editing is sometimes necessary only in specific cell types relevant to the disease. Therefore, we aimed to develop a retinal pigment epithelium (RPE)-specific CRISPR/Cas9 system. We developed a CRISPR/Cas9 system that operates only in retinal pigment epithelium (RPE) by expressing Cas9 under the RPE-specific vitelliform macular dystrophy 2 promoter (pVMD2). This RPE-specific CRISPR/pVMD2-Cas9 system was tested in human retinal organoid and mouse model. We confirmed that this system works specifically in the RPE of human retinal organoids and mouse retina. In addition, the RPE-specific Vegfa ablation using the novel CRISPR-pVMD2-Cas9 system caused regression of choroidal neovascularization (CNV) without unwanted knock-out in the neural retina in laser-induced CNV mice, which is a widely used animal model of neovascular age-related macular degeneration. RPE-specific Vegfa knock-out (KO) and ubiquitous Vegfa KO were comparable in the efficient regression of CNV. The promoter substituted, cell type-specific CRISPR/Cas9 systems can be used in specific ‘target cell’ therapy, which edits genes while reducing unwanted off- ‘target cell’ effects.

Persistence of vascular empty sleeves in choroidal neovascularization after VEGF therapy in both animal models and humans.

Choroidal neovascularization (CNV) often recurs during anti-vascular endothelial growth factor (VEGF) therapy; however, little is known about the mechanism of vascular regrowth. Vascular regrowth along the empty sleeves of basement membranes was proposed as a mechanism for recurrence after the reversal of VEGF inhibition in tumors. This study investigated whether the proposed mechanism is involved in CNV during VEGF therapy. We made two observations using a mice model, as well as patients with CNV. Laser-induced CNV mice were used to examine the vascular empty sleeves of the basement membrane and CNV with the immunohistochemistry of type IV collagen and CD31, respectively. A retrospective cohort study included 17 eyes from 17 patients with CNV treated with anti-VEGF treatment. Vascular regrowth during anti-VEGF treatment was assessed using optical coherence tomography angiography (OCTA). In the CNV mouse model, the CD31+ vascular endothelium area was decreased during anti-VEGF treatment compared with the IgG control (33516.7 ± 10864.7 vs. 10745.9 ± 5755.9 μm2, P < 0.05), whereas a significant difference was not observed in the area of type IV collagen+ vascular empty sleeve after the treatment compared with the control (29135.0 ± 7432.9 vs. 24592.0 ± 5935.3 μm2, P = 0.7). The proportions of CD31+ to type IV collagen+ areas were significantly decreased after the treatment (38.7 ± 7.4% vs. 17.1 ± 5.4%, P < 0.05). In the OCTA observations, the follow-up period in the retrospective cohort study was 58.2 ± 23.4months. CNV regrowth was observed in 682 neovessels of the 17 eyes. In group 1, CNV regression and regrowth are in the same form (129 neovessels, 18.9%). In group 2, CNV regression and regrowth are in a different form (170 neovessels, 24.9%). In group 3, CNV regrowth is with a different form without the regression (383 neovessels, 56.2%). Parts of CNV regrowth may occur along the vascular empty sleeve, which remain after anti-VEGF treatment.

Age differential response to bevacizumab therapy in choroidal neovascularization in rabbits

Choroidal neovascularization (CNV) in young rabbits has been shown to have a rapid, robust response after treatment with bevacizumab, an anti-vascular endothelial growth factor (VEGF) medication. This investigation evaluates an age differential response to bevacizumab in older populations of rabbits using multimodal high resolution molecular imaging. Young (4 months old) and life span (14 months old) rabbits were given subretinal injections of Matrigel and VEGF to produce CNV. All CNV rabbit models were then treated with a bevacizumab intravitreal injection. Rabbits were then monitored longitudinally using photoacoustic microscopy (PAM), optical coherence tomography (OCT), color photography, and fluorescence imaging. Chain-like gold nanoparticle clusters (CGNP) conjugated with tripeptide arginylglycylaspartic acid (RGD) was injected intravenously for molecular imaging. Robust CNV developed in both young and old rabbits. After intravitreal bevacizumab injection, fluorescence signals were markedly decreased 90.13% in the young group. In contrast, old rabbit CNV area decreased by only 10.56% post-bevacizumab treatment. OCT images confirmed a rapid decrease of CNV in the young group. CGNPs demonstrated high PAM signal in old rabbits and minimal PAM signal in young rabbits after bevacizumab, indicating CNV regression. There is a significant difference in response to intravitreal bevacizumab treatment between young and old rabbits with CNV which can be monitored with multimodal molecular imaging. Old rabbits demonstrate significant persistent disease activity. This represents the first large eye model of persistent disease activity of CNV and could serve as the foundation for future investigations into the mechanism of persistent disease activity and the development of novel therapies.

Acute Syphilitic Posterior Placoid Chorioretinitis With Subfoveal Choroidal Neovascularization Managed With Anti-VEGF Therapy.

We describe the development and management of choroidal neovascularization (CNV) in a patient with acute syphilitic posterior placoid chorioretinitis (ASPPC). A retrospective case review is presented. A 66-year-old man presented with unilateral blurry vision. He had a history of systemic syphilis infection twice, the last diagnosed 15 years before presentation and treated with intravenous ceftriaxone, resulting in seroreversion of an initially positive rapid plasma reagin (RPR). Examination revealed ASPPC with subfoveal CNV. Repeat testing revealed an RPR titer of 1:16 384. He was treated with 6 monthly intravitreal injections of bevacizumab and systemic antibiotics, resulting in resolution of his ASPPC and regression of his CNV. CNV is a rare complication of ASPPC. Multimodal imaging can be useful to suggest the diagnosis, and prompt treatment with systemic antibiotics and intravitreal anti-vascular endothelial growth factor agents can lead to resolution of ASPPC and regression of CNV, respectively.

Antiangiogenic Nanomicelles for the Topical Delivery of Aflibercept to Treat Retinal Neovascular Disease.

The traditional intravitreal injection delivery of antivascular endothelial growth factor (anti-VEGF) to the posterior segment of the eye for treatment of retinal diseases is invasive and associated with sight-threatening complications. To avoid such complications, there has been significant interest in developing polymers for topical drug delivery to the retina. This study reports a nanomicelle drug delivery system made of a copolymer EPC (nEPCs), which is capable of delivering aflibercept to the posterior segment topically through corneal-scleral routes. EPC is composed of poly(ethylene glycol) (PEG), poly(propylene glycol) (PPG), and polycaprolactone (PCL) segments. In this study, aflibercept-loaded nEPCs (nEPCs + A) are capable of penetrating the cornea in ex vivo porcine eye models and deliver a clinically significant amount of aflibercept to the retina in laser-induced choroidal neovascularization (CNV) murine models, causing CNV regression. nEPCs + A also demonstrate biocompatibility in vitro and in vivo. Interestingly, this study also suggests that nEPCs have intrinsic antiangiogenic properties. The ability to deliver anti-VEGF drugs and the intrinsic antiangiogenic properties of nEPCs may result in synergistic effects, which can be harnessed for effective therapeutics. nEPCs may be a promising topical anti-VEGF delivery platform for the treatment of retinal diseases.

Pediatric choroidal neovascularization: Etiology and treatment outcomes with anti-vascular endothelial growth factors.

To describe the etiology and treatment outcomes of choroidal neovascularization (CNV) in a pediatric population with intravitreal anti-vascular endothelial growth factors (VEGF). Retrospective single center interventional case series. A total of 26 eyes of 23 consecutive pediatric patients with CNV of various etiologies were treated with intravitreal injection of anti-VEGF agents. There were 15 males (65.2%) and eight females (34.8%), diagnosed with CNV during the study period. The mean age at presentation with CNV was 11.7 ± 3.3 years, (range 4-16 years) and the mean follow was 28.1 ± 18 months, (range 8-72 months). Inflammatory CNV was the most common etiology. The mean best corrected visual acuity (BCVA) and mean central macular thickness (CMT) at presentation, were logMAR 0.8 ± 0.3 and 367.6 ± 134.8 µm respectively. At the final visit, CNV in all eyes remained regressed with significant improvement in mean BCVA to logMAR 0.4 ± 0.4 (p < 0.0001) and mean CMT to 242.5 ± 82.4 µm (p < 0.0001). A mean of two intravitreal injections per eye was required for CNV regression. Intravitreal anti-VEGF therapy for pediatric CNV is an effective treatment in majority of affected eyes.

Choroidal neovascularization in 111 eyes of children and adolescents.

To describe the clinical features, management, and outcomes of choroidal neovascularization (CNV) in children less than 18years of age. This was a retrospective, case control study of 111 eyes of 96 patients. CNV was clinically diagnosed in all patients. Eyes were classified as those that were observed (Controls; Group 1) or those that had treatment (Cases; Group 2). CNV was categorized as regressed, persistent, or recurrent in order to evaluate the anatomical outcomes. Of 96 patients, 68(71%) were male. Mean presenting age was 11.4 ± 3.4years (median = 11years, range = 1-17years). CNV was bilateral in 15(16%) patients. Of 111 eyes, 38 eyes had treatment (Cases) and 73 eyes did not (Natural history group or Controls). Subfoveal CNV was seen in majority of cases (59%). Most common etiology was post-inflammatory (38%), followed by trauma (16%). Eyes were classified as those that were observed (controls; Group 1) or those that had treatment (cases; Group 2). In group 1, spontaneous regression of CNV was seen in 26(36%) eyes and there was no recurrence in this group. In group 2 following treatment, 25(66%) of 38 eyes achieved complete regression at mean 4.9months and was persistent in 5 eyes. CNV recurrence was seen in 10 eyes with the mean time to first recurrence being 9months. At presentation, mean best-corrected visual acuity (BCVA) of eyes with subfoveal CNV was logMAR 0.99 that improved to logMAR 0.63 with treatment. Mean follow-up was 17months. CNV results in significant visual decline in children; most commonly of post-inflammatory etiology. Treatment achieves high regression rates, albeit with limited visual improvement.

Activated Protein C (APC) and 3K3A-APC-Induced Regression of Choroidal Neovascularization (CNV) Is Accompanied by Vascular Endothelial Growth Factor (VEGF) Reduction.

The activated protein C (APC) ability to inhibit choroidal neovascularization (CNV) growth and leakage was recently shown in a murine model. A modified APC, 3K3A-APC, was designed to reduce anticoagulant activity while maintaining full cytoprotective properties, thus diminishing bleeding risk. We aimed to study the ability of 3K3A-APC to induce regression of CNV and evaluate vascular endothelial growth factor (VEGF) role in APC’s activities in the retina. CNV was induced by laser photocoagulation on C57BL/6J mice. APC and 3K3A-APC were injected intravitreally after verification of CNV presence. CNV volume and vascular penetration were evaluated on retinal pigmented epithelium (RPE)-choroid flatmount by fluorescein isothiocyanate (FITC)-dextran imaging. VEGF levels were measured using immunofluorescence anti-VEGF staining. We found that 3K3A-APC induced regression of pre-existing CNV. VEGF levels, measured in the CNV lesion sites, significantly decreased upon APC and 3K3A-APC treatment. Reduction in VEGF was sustained 14 days post a single APC injection. As 3K3A-APC retained APCs’ activities, we conclude that the anticoagulant properties of APC are not mandatory for APC activities in the retina and that VEGF reduction may contribute to the protective effects of APC and 3K3A-APC. Our results highlight the potential use of 3K3A-APC as a novel treatment for CNV and other ocular pathologies.

Choroidal Neovascularization Associated with Morning Glory Syndrome: A Case Report

Morning glory syndrome (MGS) is a congenital optic disc anomaly caused by abnormal closure of the embryonic fissure. Retinal detachment is commonly associated with MGS, though the association of choroidal neovascularization (CNV) with MGS is rare. Herein, we report a case of CNV associated with MGS, which was successfully treated with a single intravitreal injection of bevacizumab. A 32-year-old Japanese woman consulted at our clinic for blurred vision in her left eye for five days. Her best-corrected decimal visual acuity (BCVA) was 1.5 (S-1.0) OS. The fundus examination revealed subretinal hemorrhage associated with MGS in the temporal margin of the optic disc. As she was pregnant, we planned to continue follow-up without further invasive testing and treatment; however, her visit to the hospital was interrupted. Ten months later, she returned with complaints of poor vision and central scotoma in her left eye for six months. The BCVA was 0.5 (S-1.0/C-1.0/45°) OS. The fundus examination showed that subretinal hemorrhage increased, and the subretinal fluid extended below the fovea. Multimodal imaging revealed type 2 CNV on the temporal and nasal disc margins. After she received an intravitreal injection of bevacizumab (1.25 mg), rapid absorption of subretinal fluid and regression of CNV were observed. The BCVA improved to 1.5 (S-0.5/C-0.75/35°) OS. No recurrence of CNV was observed for 26 months after the injection. During the follow-up of MGS cases, we should pay attention, not only to retinal detachment, but also to the occurrence of CNV around the disc margins.

Activated protein C induces suppression and regression of choroidal neovascularization– A murine model

Activated protein C (APC) exerts diverse cell signaling pathways which results in multiple distinct cytoprotective actions. These include anti-apoptotic and anti-inflammatory activities and stabilization of endothelial and epithelial barriers. We studied the ability of APC to inhibit the leakage and the growth of newly formed as well as pre-existing choroidal neovascularization (CNV) and examined the ability of APC to stabilize the Retinal Pigmented Epithelium (RPE). We explored the contribution of Tie2 receptor to the protective effects of APC.CNV was induced by laser photocoagulation in C57BL/6J mice. APC was injected intravitreally immediately or 7 days after CNV induction. Neovascularization was evaluated on RPE-choroidal flatmounts using FITC-dextran perfusion and CD31 immunofluorescence. CNV leakage was measured by fluorescein angiography (FA). The ability of APC to stabilize the RPE barrier was evaluated in-vitro by dextran permeability and zonula occludens 1 (ZO1) immunostaining. Tie2 blocking was induced in-vivo by intraperitoneal injection of Tie2 kinase inhibitor and in-vitro by incubation with anti Tie2 antibodies.APC treatment dramatically inhibited the generation of newly formed CNV leakage sites and reversed leakage in 85% of the pre-existing CNV leaking sites. In RPE cell culture, APC induced translocation of ZO1 to the cell membrane, accompanied by reduction in permeability of the monolayer. Inhibition of Tie2 significantly decreased APC protective activities in both the mouse model and the RPE cell culture.Our results show that APC treatment significantly inhibits the leakage and growth of newly formed, as well as pre-existing CNV, and its protective activities are partially mediated via the Tie2 receptor.The data suggest that APC should be further investigated as a possible effective treatment for CNV.

Treatment of idiopathic choroidal neovascular membrane with ranibizumab - our experience.

To evaluate the anatomical and functional outcome of ranibizumab therapy in patients with idiopathic choroidal neovascularization (CNV). File and Methodology: The group consists of 6 patients. Patients were older 18 years but they were under 50 years of age. The monitoring period lasted 12 months. We confirmed active idiopathic CNV in subfoveal position with fluorescein angiography (FAg) and optical coherence tomography (OCT). The activity of idiopathic CNV we demonstrated with leakage of dye by FAg examination. The presence of serous retinal pigment epithelium detachment and / or subretinal fluid and / or intraretinal edema in the form of intraretinal cysts demonstrated activity of CNV on OCT scans. Adecrease of the visual acuity under 85 letters was observed at the ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity chart. After the initial administration of ranibizumab apro re nata regimen was used. We indicated repeated injection of ranibizumab in patients with signs of activity of idiopathic CNV on OCT scans or by FAg. Also we indicated repeated injection of ranibizumab in patients with new loss of visual acuity on the ETDRS visual acuity chart connected with signs of activity of CNV on OCT scans or by FAg. On average, we observed the gain of +11 letters on the ETDRS visual acuity chart after 12 months of the follow-up period. On average we observed reduction of central macular thickness -233&#956;m. At the 12th month of follow-up we observed in all patients of our group only inactive scar without exudation. No serous retinal pigment eithelium detachment, subretinal fluid or intraretinal cysts were observed. Only 3 injections of ranibizumab were administered on average to each patient during the 12 months of the follow-up period. In our study, we observed the positive effect of ranibizumab on the course of idiopathic CNV. With ranibizumab treatment we achieved regression of CNV with resorption of macular edema in all patients of our group. With the disappearance of the activity of idiopathic CNV ranibizumab gives real hope to improve visual acuity.

The involvement of NK1 and Y2 receptor in the development of laser-induced CNVs in C57Bl/6N mice

Purposeto explore whether the NK1 and Y2 receptors are involved in the pathogenesis of laser-induced CNV (choroidal neovascularization) in C57Bl/6N mice. MethodsCNV was induced by laser damage of Bruch's membrane and the CNV volume was determined by OCT and/or flatmount preparation. First, the development of the CNV volume over time was evaluated. Second, the CNV development in NK1- and Y2 KO mice was analyzed. Third, the effect on the development as well as the regression of CNV by intravitreal injections of the NK1 antagonist SR140333 and the Y2 antagonist BIIEO246 separately and each in combination with Eylea®, was investigated. Furthermore, flatmount CNV volume measurements were correlated to volumes obtained by the in vivo OCT technique. ResultsCNV volume peak was observed at day 4 after laser treatment. Compared to wild type mice, NK1 and Y2 KO mice showed significantly smaller CNV volumes. Eylea® and the Y2 antagonist significantly reduced the volume of the developing CNV. In contrast to Eylea® there was no effect of either antagonist on the regression of CNV, additionally no additive effect upon combined Eylea®/antagonist treatment was observed. There was a strong positive correlation between CNV volumes obtained by OCT and flatmount. ConclusionNK1 and Y2 receptors mediate the development of laser-induced CNVs in mice. They seem to play an important role at the developmental stage of CNVs, whereas VEGF via VEGF receptor may be an important mediator throughout the CNV existence. In vivo OCT correlates with flatmount CNV volume, representing a useful tool for in vivo evaluations of CNV over time.

Automatic versus Manual Segmentation of Choroidal Neovascularization Lesions Using Optical Coherence Tomography

1.1.Purpose: To measure and quantify choroidal neovascularization (CNV) lesion size in classic lesions visualized on Spectral Domain-Optical Coherence Tomography (SD-OCT) using automated segmentation analysis and confirm whether further refinement improves the accuracy of disease regression after loading dose Anti-VEGF injections. 1.2.Methodology: A retrospective study of 10 macular degeneration patients diagnosed with CNV. Blinded observers, trained to detect changes on OCT, delineated boundaries of CNV lesions using SD-OCT (Topcon 2000) with automated software and then modified segmentation manually before and after loading dose Ranbizumab injections. Automated measurements were then compared to manual segmentation values. Statistical analysis was performed, taking into account inter-observer variability. 1.3.Results: Automatic and manual segmentation measurements are similar in 1) retinal area and fovea center values both pre-and post-injection; and 2) retinal volume post-injection. Retinal volume pre-injection is 1) similar between the two blinded observers; 2) varies between automatic measurements and observers in some patients; and 3) underestimated for all patients in the automatic measurements. Overall, automatic segmentation detects a general reduction in CNV lesion size following loading dose injections. 1.4.Conclusion: SD-OCT automated segmentation software detects CNV lesions and reports size reduction after the third anti-VEGF injection. SD-OCT automatic segmentation using Topcon segmentation analysis in this small cohort is an accurate diagnostic tool to measure CNV surface area and volume as a biomarker of CNV regression.

Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration.

Choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF) has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®), initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD.

Retinal pigment epithelial cell proliferation.

The human retinal pigment epithelium forms early in development and subsequently remains dormant, undergoing minimal proliferation throughout normal life. Retinal pigment epithelium proliferation, however, can be activated in disease states or by removing retinal pigment epithelial cells into culture. We review the conditions that control retinal pigment epithelial proliferation in culture, in animal models and in human disease and interpret retinal pigment epithelium proliferation in context of the recently discovered retinal pigment epithelium stem cell that is responsible for most invitro retinal pigment epithelial proliferation. Retinal pigment epithelial proliferation-mediated wound repair that occurs in selected macular diseases is contrasted with retinal pigment epithelial proliferation-mediated fibroblastic scar formation that underlies proliferative vitreoretinopathy. We discuss the role of retinal pigment epithelial proliferation in age-related macular degeneration which is reparative in some cases and destructive in others. Macular retinal pigment epithelium wound repair and regression of choroidal neovascularization are more pronounced in younger than older patients. We discuss the possibility that the limited retinal pigment epithelial proliferation and latent wound repair in older age-related macular degeneration patients can be stimulated to promote disease regression in age-related macular degeneration.

Treatment of vascular activity secondary to atypical choroidal nevus using intravitreal bevacizumab.

ObjectiveTo report the optical coherence tomography (OCT) findings of 27 eyes treated with intravitreal bevacizumab for intraretinal and subretinal vascular activity associated with atypical choroidal nevi.MethodsThis was an Internal Review Board-approved retrospective review of 27 eyes of 27 patients with choroidal nevus treated for secondary vascular activity with intravitreal injections of bevacizumab, performed by a single surgeon (TGM) at the Bascom Palmer Eye Institute. All patients were rigorously evaluated before the procedure and followed thereafter with ophthalmic examinations, refractive analysis, fundus photos, optical coherence tomography (OCT), and ocular echography. Patient demographics, tumor characteristics, dates of bevacizumab injections, and spectral-domain (SD)-OCT findings at each injection were recorded. Macular edema was graded as per SD-OCT findings for the initial and final visit.ResultsThe mean age was 66.6 years (range, 40–86 years), with ten males and 17 females. Mean, median, and range baseline best corrected visual acuity (BCVA) were 20/53, 20/40, and 20/20–4/200, respectively. After a mean follow up of 29 months, the final BCVA mean, median, and range were 20/50, 20/40, and 20/20–20/400, respectively. The final BCVA ranged from 20/20 to 20/25 in nine eyes, while only six eyes had an initial BCVA within the same range. All patients demonstrated OCT findings of vascular activity suggestive of choroidal neovascularization (CNV). Initial SD-OCT findings included intraretinal cysts in eleven eyes, intraretinal fluid in six eyes, subretinal fluid in 14 eyes, pigment epithelial detachment in six eyes, epiretinal membrane in five eyes, and subretinal neovascularization in 14 eyes. On fundus photos, four eyes presented retinal hemorrhage. A mean of eight (range of 1–31) intravitreal bevacizumab (1.25 mg/0.05 cc) injections were given in all cases. A total of 37% (10/27) of eyes had complete or partial regression of vascular activity. The mean initial OCT classification for macular edema was 3 and a mean grade of 3 was maintained at the final follow-up OCT. All 27 choroidal nevi remained stable, and there were no adverse effects from the bevacizumab injections.ConclusionTo our knowledge, this is the largest published case series of eyes treated with intravitreal bevacizumab for vascular activity associated with choroidal nevus. Intravitreal bevacizumab seems to be effective in the treatment of CNV secondary to choroidal nevus, and OCT can be a useful tool in the follow up of these patients, to assess the regression of CNV and to monitor macular edema.

Intravitreal Bevacizumab Injection for the Treatment of Choroidal Neovascularization Secondary to Candida Chorioretinitis

Purpose: To report a case of choroidal neovascularization (CNV) secondary to candida chorioretinitis initially treated with an intravitreal bevacizumab injection. Case summary: A 50-year-old female presented at our clinic with decreased vision and metamorphopsia in her left eye of 5 days duration. She received an anti-fungal treatment 2 months prior due to the presence of endogenous candida choroiditis in both eyes. Fluorescein angiography and optical coherence tomography (OCT) revealed juxtafoveal CNV in her left eye. Three monthly intravitreal injections of bevacizumab were administered as the initial loading dosage. Her visual symptoms improved and CNV regression was observed on OCT. No recurrence or complications were observed during the 6 month follow-up. Conclusions: Based on the present study results we suggest that intravitreal bevacizumab injection can be used to effectively treat CNV and improve visual symptoms during the treatment of juxtafoveal CNV associated with candida choroiditis. J Korean Ophthalmol Soc 2014;55(7):1106-1110