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[Sub-tenon steroid treatment in choroidal neovascularization caused by serpiginous choroiditis. A case report].

CASE REPORT: We present a report of a patient suffering from serpiginous choroiditis complicated by choroidal neovascularization (CNV). Sub-tenon steroid treatment, added to the usual immunosuppressive therapy, resolved the CNV, improving visual acuity in one eye. DISCUSSION: Choroidal neovascularization is a sight-threatening complication of posterior uveitis. Our case suggests that sub-tenon steroid treatment, added to systemic immunosuppressive therapy, may accelerate the CNV resolution in posterior uveitis.

Azathioprine↗

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization associated with multifocal choroiditis.

PURPOSE: Evaluation of visual acuity outcomes of photodynamic therapy with verteporfin for subfoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis. DESIGN: Open-label, prospective, interventional case series. METHODS: Thirteen patients (13 eyes) diagnosed with subfoveal CNV associated with multifocal choroiditis at the Eye Clinics of Trieste and Udine were considered for the study. Inclusion criteria were the presence of subfoveal CNV no larger than 5,400 microm in greatest linear dimension and best-corrected visual acuity, Snellen equivalent, of approximately 20/400 or better. The primary outcome was the number of eyes that had fewer than 8 letters lost (less than approximately 1.5 lines) at the 12-month examination compared with the baseline examination. Secondary outcomes included fluorescein angiographic features such as progression and CNV size. RESULTS: Baseline and final best-corrected visual acuity were 0.52 logarithm of the minimal angle of resolution (20/62(-2) Snellen equivalent) and 0.55 logarithm of the minimal angle of resolution (20/62(-2) Snellen equivalent), respectively. By the 12-month visit, one patient (7.7%) had gained at least 1.5 lines, two patients (15.4%) had lost 1.5 or more lines, and no patient lost 3 or more lines of visual acuity, whereas 10 patients (84.6%) showed less than 1.5-line change. Mean CNV area was 0,69 mm(2) and 0.63 mm(2) at baseline and at the 12-month visit, respectively. By the month 12 examination, patients had received an average of 1.7 treatments. CONCLUSIONS: Photodynamic therapy may be considered a viable therapeutic option for subfoveal CNV associated with multifocal choroiditis at least for a 1-year period. Further studies with longer follow-up are needed to confirm these results.

Adult↗

Photodynamic therapy for juxtafoveal choroidal neovascularization associated with multifocal choroiditis.

PURPOSE: Evaluation of visual acuity outcome of photodynamic therapy (PDT) with verteporfin for juxtafoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis (MC). DESIGN: Open-label, prospective, interventional case series. METHODS: Seven patients (seven eyes) diagnosed with juxtafoveal CNV associated with MC at the Eye Clinic of Trieste were considered. Inclusion criteria were the presence of juxtafoveal CNV no larger than 5400 microm in greatest linear dimension and best-corrected visual acuity (BCVA) (Snellen equivalent) of approximately 20/200 or better. PDT was performed according to the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) study. The primary outcome was the variation in Early Treatment Diabetic Retinopathy Study (ETDRS) charts visual acuity. In particular, the study considered changes of at least eight letters (approximately <1.5 lines of visual acuity loss) at the 12- and 24-month examinations compared with the baseline examination. Secondary outcomes included fluorescein angiographic features such as progression and area of CNV. RESULTS: At both the 12- and 24-month examinations, three patients (43%) gained at least 1.5 lines of visual acuity, three patients (43%) did not show changes in either direction, whereas visual acuity decreased by 1.5 or more lines from baseline in one patient (14%). The median CNV area was 0.3 mm(2) at baseline and 0.24 mm(2) at the 12- and 24-month controls, respectively. CONCLUSIONS: The positive results of the present study and the absence of treatment-related side effects suggest that PDT may be considered a safe and viable therapeutic option for juxtafoveal CNV for a 24-month period. Further studies including a greater number of patients are needed to confirm these preliminary results.

Adult↗

Treatment of subfoveal choroidal neovascularization associated with multifocal choroiditis and panuveitis with photodynamic therapy.

PURPOSE: To study the effects of photodynamic therapy (PDT) using verteporfin on the treatment of patients with subfoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis and panuveitis (MCP), an uncommon disorder with no proven forms of therapy. METHODS: A retrospective chart review of seven consecutive patients with subfoveal CNV secondary to MCP treated with PDT using verteporfin was performed. RESULTS: The mean age of the 7 patients (all myopic women) was 41.4 years. A mean of 1.86 treatments was performed, and the mean follow-up time was 10 months. Four of the seven patients were treated unsuccessfully with corticosteroids before referral for PDT. The mean improvement of visual acuity was 0.86 line; 3 patients (42.8%) had an improvement in visual acuity representing at least a halving of their visual angle, while the other 4 patients remained stable. There were no treatment-related side effects. CONCLUSIONS: Although the follow-up time and the number of patients in this study were limited, the use of PDT was associated with stabilization or improvement of visual acuity in patients with subfoveal CNV secondary to MCP. Further study of this treatment modality is indicated.

Adult↗

The possibility of gene therapy for the treatment of choroidal neovascularization.

PURPOSE: Choroidal neovascularization (CNV) is responsible for most cases of severe visual loss in age-related macular degeneration. Recently, the possibility of gene therapy has been proposed for the treatment of CNV. The purpose of this study was to examine the feasibility of ex vivo and in situ gene therapy approaches for CNV. DESIGN: Experimental study. METHODS: Human retinal pigment epithelial (RPE) cells were transduced with a retroviral vector coding for beta-galactosidase. Transduced cells were grown on type II collagen sheets and transplanted under the retina of 20 rabbits. Animals were observed for 3 to 56 days, and transplanted cells were examined histologically and with X-gal staining. Bovine choroidal endothelial cells (CEC) were transduced with retroviral vectors coding for tissue inhibitor of metalloproteinase-2 (TIMP-2) or control vector. Production of TIMP-2 by transduced cells was determined by immunohistochemical analysis and enzyme-linked immunosorbent assay. Effect of transduction on in vitro proliferation, migration, and tube formation was examined in response to vascular endothelial growth factor (VEGF). Four CNV lesions were induced in one cynomolgus monkey by laser photocoagulation. Two days later, retroviral vector coding for TIMP-2 or control vector was injected into the subretinal space overlying the CNV lesions. The monkey was observed for 12 weeks using fluorescein angiography. RESULTS: Transplantation of transduced RPE cells was technically achieved in 10 of 20 animals. In these animals, RPE cells at the site of transplantation formed a monolayer and expressed beta-galactosidase for 14 days. beta-Galactosidase-positive cells were not identified at 56 days. Choroidal endothelial cells transduced with TIMP-2 secrete TIMP-2 into the media and show decreased migration and tube formation in vitro. In the in vivo monkey model, the control CNV lesions (n = 2) showed prominent leakage, whereas the experimental lesions (n = 2) showed minimal hyperfluorescence. CONCLUSIONS: Retrovirally transduced RPE cells survive in the subretinal space for at least 14 days and continue to express the gene product coded for by the vector. Choroidal endothelial cells retrovirally transduced for TIMP-2 produce TIMP-2 in vitro and show decreased angiogenic responses in vitro in response to VEGF. A preliminary study attempting in situ delivery of TIMP-2 vector to CNV lesions in a monkey eye supports the feasibility of this approach and encourages further study.

Animals↗

Angiotensin II type 1 receptor-mediated inflammation is required for choroidal neovascularization.

BACKGROUND: Choroidal neovascularization (CNV) is a critical pathogenesis in age-related macular degeneration, the most common cause of blindness in the developed countries. The aim of the current study was to determine the involvement of the renin-angiotensin system (RAS) with the development of CNV, using human surgical samples and the murine model of laser-induced CNV. METHODS AND RESULTS: In the human and murine CNV tissues, the vascular endothelium expressed angiotensin II type 1 receptor (AT1-R), AT2-R, and angiotensin II. The CNV volume was significantly suppressed by treatment with an AT1-R blocker telmisartan, but not with an AT2-R blocker. AT1-R signaling blockade with telmisartan inhibited various inflammatory mechanisms including macrophage infiltration and upregulation of VEGF, intercellular adhesion molecule-1 (ICAM-1), MCP-1, and IL-6 in the retinal pigment epithelium-choroid complex. A PPAR-gamma antagonist partially but significantly reversed the suppressive effect of telmisartan on in vivo induction of CNV and in vitro upregulation of ICAM-1 and MCP-1 in endothelial cells and IL-6 in macrophages, showing the dual contribution of PPAR-gamma-agonistic and AT1-R-antagonistic actions in the telmisartan treatment. CONCLUSIONS: AT1-R-mediated inflammation plays a pivotal role in the development of CNV, indicating the possibility of AT1-R blockade as a novel therapeutic strategy to inhibit CNV.

Angiogenesis Inducing Agents↗

Choroidal neovascular membrane.

Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician's viewpoint.

Aged↗

A novel imaging technique for experimental choroidal neovascularization.

PURPOSE: Choroidal neovascularization (CNV) is the end point of several ocular diseases that lead to blindness. The authors developed an imaging technique for visualizing and quantifying morphologic changes associated with experimental laser-induced CNV. METHODS: CNV was induced using laser energy to disrupt Bruch's membrane. Rats were euthanatized immediately after laser injury and at 1, 2, 3, 4, 7, 14, and 60 days. Nonlasered eyes were used as the control. Eyes were enucleated and fixed, and the posterior eye cups were fluorescently labeled with markers for nuclei (DAPI; 4',6'-diamino-2-phenylindole), endothelial cells (isolectin IB4), microglia (CD11b), and filamentous actin (phalloidin). FITC-dextran perfusion was compared with our technique. A confocal microscope was used to evaluate flatmounted specimens. Computer software generated three-dimensional reconstructions for qualitative and quantitative analysis of confocal image stacks. RESULTS: In nonlasered areas, RPE cells were visualized as a uniform hexagonal array. Immediately after laser exposure, a circular area devoid of fluorescent labeling was observed, indicating disruption of the choroid-Bruch's membrane-RPE complex. One day after laser exposure, cellular debris and fragmented nuclei were present, and an autofluorescent ring was visible at the site of Bruch's membrane disruption. The ring correlated with bubble formation and CNV induction. Three days after laser injury, phalloidin-labeled RPE cells and isolectin-labeled endothelial cells increased significantly, reflecting cell proliferation and migration. By day 4, isolectin-positive cells forming vascular tubes were visualized. The volume of CNV vessels increased exponentially during the next 3 days. By 7 days, a well-defined isolectin-labeled CNV network was present, and its volume was preserved for several weeks. CNV volumes calculated on the basis of FITC-dextran perfusion were significantly lower than volumes obtained using lectin-labeled samples. CONCLUSIONS: A novel imaging technique was developed that allows a three-dimensional reconstruction and measurement of laser-induced CNV lesions in rat choroid/RPE flatmounts. This technique provides excellent morphologic detail and facilitates the study of critical early events in CNV, including the rupture of Bruch's membrane and the formation of endothelial clusters before vessel formation. CNV complexes are labeled at an earlier stage and more reproducibly than with FITC-dextran perfusion, providing a more accurate preclinical evaluation of antiangiogenic molecules.

Actins↗

Drug targeting to choroidal neovascularization.

Subfoveal choroidal neovascularization (CNV) causes significant visual loss, especially in patients with age-related macular degeneration (AMD). Several pharmaceutical treatments that use anti-angiogenic agents have been tried to inhibit the activity of CNV experimentally and clinically. In general, however, systemically administered drugs may reach not only targeted tissues but also other tissues, resulting in unwanted side effects. Also, to maintain therapeutic levels of the drugs in targeted tissues, frequent administration for an extended period of time is required. To solve these problems, drug delivery systems targeted to the CNV are being developed. Anatomic characteristics of CNV tissues resemble those of tumor vasculature, exhibiting enhanced permeability and retention effect. Drug targeting to CNV may be feasible in the same manner as it is to tumors. In this review, we describe two approaches of drug targeting to CNV: passive targeting and active targeting.

Animals↗

Present indications for removal of choroidal neovascular membranes.

Subretinal choroidal neovascularization is an important cause of visual loss in adults. Removal of choroidal neovascular membranes using relatively new techniques of subretinal surgery holds promise for improving or stabilizing vision in some patients. A number of factors have been proposed that may affect the outcome of subretinal surgery for choroidal neovascularization, including the degree of involvement of Bruch's membrane, the location of the neovascular complex relative to the retinal pigment epithelium and Bruch's membrane, the location of the ingrowth site, and the etiology of the membranes. Although the surgical techniques are relatively refined, the indications for removal of choroidal neovascular membranes are still under investigation. This article reviews the recent and past literature and summarizes the authors' specific recommendations regarding present indications for removal of choroidal neovascular membranes.

Choroid↗

Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration. Macular Photocoagulation Study Group.

OBJECTIVES: To verify and quantify previously reported risk factors for development of choroidal neovascularization (CNV) in the fellow eye of patients with 1 eye affected with CNV secondary to age-related macular degeneration, to examine the value of characteristics of the pericentral macula in the quantification of risk for developing CNV, and to explore whether the presence of occult CNV in the first eye affects the development of CNV in the fellow eye. DESIGN, PATIENTS, AND SETTING: Follow-up study of fellow eyes of 670 patients enrolled in multicenter, randomized clinical trials of laser photocoagulation of juxtafoveal or subfoveal CNV. MAIN OUTCOME MEASURE: Development of CNV. RESULTS: Three characteristics of the central macula of the fellow eye and 1 systemic factor were associated independently with an increased risk of developing CNV: the presence of 5 or more drusen (relative risk, 2.1; 95% confidence interval, 1.3-3.5), focal hyperpigmentation (relative risk, 2.0; 95% confidence interval, 1.4-2.9), 1 or more large drusen (relative risk, 1.5; 95% confidence interval 1.0-2.2), and definite systemic hypertension (relative risk, 1.7; 95% confidence interval, 1.2-2.4). Estimated 5-year incidence rates ranged from 7% for the subgroup with no risk factors to 87% for the subgroup with all 4 risk factors. Characteristics of the pericentral macula were not strongly associated with the development of CNV. The presence of occult CNV in the first eye affected had no influence on the development of CNV or on the type of CNV in the fellow eye. CONCLUSIONS: The prognosis of the fellow eye is affected strongly by characteristics of its central macula and by systemic hypertension. These factors should be considered when counseling patients with unilateral neovascular age-related macular degeneration and when targeting patients for preventive interventions.

Aged↗

The use of vitreoretinal surgical techniques in subfoveal choroidal neovascularization.

Subfoveal choroidal neovascularization generally carries a poor visual prognosis. This review traces the evolving vitreoretinal surgical techniques for the treatment of this entity. Extensive retinotomies to expose large submacular scars caused frequent complications and poor visual results. More recently, small retinotomy techniques with manipulation of subfoveal membranes behind neurosensory retina have been described. Removal of subfoveal neovascularization with this latter approach is summarized. Visual results are variable. If foveal retinal pigment epithelium can be preserved, excellent central visual function can be regained. In the majority of subfoveal membranes, surgical removal creates retinal pigment epithelium defects, and acuity is limited. These approaches merit further evaluation.

Adult↗

[Confocal scanning laser indocyanine green angiography of classical choroid neovascularization].

"Classic" choroidal neovascularization (CNV) has a relatively uniform appearance in fluorescein angiography. In contrast, indocyanine green (ICG) angiography shows variable features of well-defined CNV. We examined 31 classic CNV patients secondary to age-related macular degeneration using a confocal laser scanning ophthalmoscope (Heidelberg Retina Angiograph) in order to determine ICG characteristics of classic CNV. Vascular patterns (97%), a hypofluorescent rim (84%), a hyperfluorescent margin (42%), late ICG leakage (32%) and "feeder vessels" were identified in variable frequency. Some of the ICG characteristics may correlate with histological features of the membrane and reflect proliferative activity. Extrafoveal "feeder vessels" may be amenable to laser photocoagulation in the presence of subfoveal CNV.

Aged↗