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PubMed1997

[Surgical removal of submacular choroidal neovascular membranes and the results of follow-up].

OBJECTIVE: To explora the long-term effect of surgical removal of submacular neovascular membranes. METHODS: After pars plana vitrectomy, a small retinotomy technique was used to extract submacular choroidal neovascular membranes in the seven eyes of seven cases. Before and after surgery, the visual acuity, best corrected visual acuity, fundus and fundus fluorescein angiography were examined in all eyes and long-term follow-up was carried out. RESULTS: With more than 1 year follow-up, the submacular choroidal neovascular membranes were not noted in six eyes and recurrent in one eye. After surgery, the visual acuity improved differently in six eyes, two eyes of which increased 5 Snellen lines. Only in one eye did the vision decrease with macular organization, and in one eye a secondary epimacular membrane appeared. CONCLUSION: Most of the eyes have their vision improved after the surgical removal of the submacular neovascular membranes. The visual improvement is related to the extent of retinal pigment epithelium and neurosensory retina damaged by the choroidal neovascular membrane scar, and surgical procedure has also some damaging effects on retinal pigment epithelium and neurosensory retina.

Adult↗
PubMed1997

Expression of transforming growth factor-beta mRNA in experimental choroidal neovascularization.

PURPOSE: Transforming growth factor beta (TGF-beta) is a multifunctional cytokine that modulates biological events as diverse as wound healing and angiogenesis and which may be important in the pathogenesis of choroidal neovascularization. We investigated the mRNA expression of TGF-beta isoforms in a model of experimental choroidal neovascularization induced by krypton-laser photocoagulation. METHODS: Rat TGF-beta 1, mouse TGF-beta 2 or TGF-beta 3 cDNAs was inserted into the pBluescript vector to prepare antisense and sense riboprobes. Intense laser burns were applied to the posterior poles of the eyes of pigmented rats according to a protocol described for producing choroidal neovascularization in these animals. At intervals up to 4 weeks after photocoagulation, the eyes were obtained and cut into thin sections. The sections were subjected to in situ hybridization with digoxigenin (DIG)-labeled single-strand riboprobes synthesized from each TGF-beta cDNA. RESULTS: In normal adult rat retinas and choroids, TGF-beta 1 mRNA was found only in cells of the ganglion cell layer, TGF-beta 2 mRNA was found in cells of the ganglion cell layer and choriocapillaris endothelium, whereas TGF-beta 3 mRNA was not detected at all. During the process of neovascularization, TGF-beta 1 and TGF-beta 2 mRNAs (the latter being expressed more prominently) were detected in retinal pigment epithelial cells, fibroblast-like cells and the endothelium of the neovascular region. TGF-beta 2 was the predominant isoform of TGF-beta, and its expression was especially strong in the endothelium of the choroidal neovascularization at 2 weeks. However, TGF-beta mRNAs was decreased in cells 4 weeks after photocoagulation. CONCLUSIONS: Our findings suggest that TGF-beta may act in the retina as a neurotrophic agent, since TGF-beta 1 is normally transcribed in ganglion cells and TGF-beta 2 is also transcribed in ganglion cells and choriocapillaris endothelium. TGF-beta 1 and TGF-beta 2 mRNA expression were increased in photocoagulated lesions from 3 days to 2 weeks after laser treatment. Therefore, it is likely that TGF-beta acts as a mediator of the neovascularization process.

Animals↗
PubMed1994

Symptomatic choroidal neovascularization in blacks.

OBJECTIVE: To acquire descriptive clinical information regarding choroidal neovascularization (CNV) in black Americans. DESIGN: Retrospective review of 1308 fluorescein angiograms obtained during a 4-year interval. Color photographs and clinical records of all black patients with angiographically apparent CNV were subsequently reviewed. SETTING: Retina service of an inner-city county hospital in Atlanta, Ga, serving a predominantly black population. RESULTS: Thirty blacks with CNV (36 of 59 eyes) were identified, 26 (87%) of whom were female. Active, exudative neovascularization was present in at least one eye of 21 patients (70%). Patients were assigned to one of four diagnostic groups for analysis. Group 1 was made up of 13 patients (43%) with age-related macular degeneration with CNV. Women outnumbered men 5.5:1. Choroidal neovascularization was peripapillary in seven (54%) of these 13 patients. Group 2 was made up of six patients (20%) with idiopathic CNV, which was peripapillary in all eyes. Group 3 consisted of three women (10%) with idiopathic polypoidal choroidal vasculopathy. Group 4 was composed of eight patients (27%) with secondary CNV. The CNV was peripapillary in three (33%) of nine eyes, and women outnumbered men 7:1. CONCLUSIONS: The spectrum of neovascular maculopathy in blacks in the current study differed from that typically seen in whites, both clinically and demographically. Clinically, CNV was most commonly juxtapapillary (13 [68%] of 19 patients) and unilateral (12 [92%] of 13 patients) among the age-related macular degeneration and idiopathic groups, while six (20%) of 30 patients (all older than 50 years) had CNV in the absence of drusen or other known predisposing conditions. Disciform-stage CNV in both groups was associated with a greater degree of pigment proliferation than that typically noted in whites. Demographically, female predominance (87% overall) was dramatic compared with prior studies.

Adult↗
PubMed1999

Transpupillary thermotherapy of occult subfoveal choroidal neovascularization in patients with age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy of transpupillary thermotherapy for the treatment of occult subfoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration. DESIGN: A retrospective, noncomparative case series. PARTICIPANTS: Sixteen eyes of 15 consecutive patients who presented with occult subfoveal choroidal neovascularization secondary to age-related macular degeneration. INTERVENTION: After informed consent was obtained, 16 eyes of 15 patients were treated with transpupillary thermotherapy. All patients underwent pretreatment fluorescein angiography and were deemed untreatable by the Macular Photocoagulation Study standard. Transpupillary thermotherapy was delivered using a diode laser at 810 nm. A variable spot size of 1.2 mm, 2.0 mm, or 3.0 mm was used depending on the size of CNV. The diode laser was delivered through a contact lens, and treatment was initiated in one spot for 60 seconds' duration at a power range between 360 and 1000 mW. The end point was an area of no visible color change to a light-gray appearance. MAIN OUTCOME MEASURES: In all eyes, outcome was assessed by Snellen chart visual acuity and clinical examination. In 10 of 16 eyes, preoperative and postoperative fluorescein angiography and optical coherence tomography were available. In the remaining 6 of 16 eyes, exudation was measured by postoperative clinical examination alone. RESULTS: Three eyes (19%) showed a two-or-more-line improvement in visual acuity over a period of 6 to 25 months. Mean follow-up was 13 months. Visual acuity remained stable (no change or one-line improvement) in nine treated eyes (56%). The remaining four eyes (25%) showed a decline (equal to one-line worsening or greater) in visual acuity. Fifteen eyes (94%) demonstrated decreased exudation on fluorescein angiography, optical coherence tomography, and/or clinical examination. CONCLUSIONS: Transpupillary thermotherapy shows no deleterious side effects in treating occult subfoveal choroidal neovascularization. A randomized, prospective study is necessary to evaluate treatment efficacy.

Aged↗
PubMed2002

Influence of photodynamic therapy in choroidal neovascularization on focal retinal function assessed with the multifocal electroretinogram and perimetry.

PURPOSE: To study the influence of photodynamic therapy (PDT) on retinal function in patients with a predominantly classic choroidal neovascular membrane. DESIGN: Comparative observational study. PARTICIPANTS: Sixteen eyes with a choroidal neovascular membrane eligible for PDT were included. METHODS: Visual acuity, multifocal electroretinogram (MF-ERG, Electrodiagnostic Imaging, San Mateo, CA) recordings and visual fields (Octopus d32) were obtained before PDT with Visudyne, Novartis AG, Basel, Switzerland, and at follow-up 2 weeks to 3 months later. MAIN OUTCOME MEASURES: Visual acuity as well as peak-to-peak amplitudes, peak latencies, and focal differences in the scalar product of the two MF-ERG recordings were analyzed. Mean deviation, loss variance, and the absolute difference in sensitivity in the fields obtained were also analyzed. RESULTS: After PDT, mean visual acuity stabilized or improved in 13 eyes. Except for two eyes with a predominantly parafoveolar choroidal neovascular membrane, the MF-ERG contribution from the central 4 degrees was reduced below the normal level. Although it improved slightly after PDT, it remained below the normal range. In the central 7.5 degrees, retinal sensitivity increased by up to 80 dB and within the paracentral 7.5 degrees to 15 degrees, it increased by up to 183 dB in 13 eyes. CONCLUSIONS: Consistent with the results of the treatment of age-related macular degeneration with photodynamic therapy (TAP) study, PDT can lead to stabilization of visual acuity. Improvement in parafoveal function can be demonstrated in the central visual field, as well as in MF-ERG recordings, even in patients whose visual acuity remains stable. Therefore, the MF-ERG and central perimetry may aid the assessment of retinal function in treatment trials of patients with age-related macular degeneration.

Choroidal Neovascularization↗
PubMed2000

Quantitative image analysis of laser-induced choroidal neovascularization in rat.

Rodent models of laser-induced choroidal neovascularization (CNV) are now extensively used to identify angiogenic proteins, determine the role of specific genes with knockout mice, and evaluate the efficacy and safety of anti-angiogenic therapies. CNV is typically evaluated by fluorescein angiography or vascular endothelial cell labeling in histologic sections. The current study examined an alternative method using high molecular weight FITC-dextran (MW 2 x 10(6)) for high resolution angiography in RPE-choroid-sclera flat mounts. At 24 hr after lasering, the lesions appeared as a circular weakly fluorescent area of approximately equal diameter to the laser spot. No FITC-dextran labeled blood vessels were visible in the lesion at day 1. Three days after lasering, 47% of the lesions showed FITC-dextran labeling indicative of CNV. The incidence (71%) and extent of CNV increased by day 6, and by day 10 all lesions were vascularized, and the maximal area was attained. No significant change followed day 10, and the neovascular area remained constant through day 31. The highest rate of blood vessel growth (between 3 and 10 days after laser) correlates with the peak expression of VEGF, bFGF, and their receptors shown in previous studies. Morphologic analysis of flat mounts and histologic sections showed that the neovascular plexus in most lesions originates from deeper choroidal vessels in the center of the lesion, grows towards the neural retina, then branches circumferentially to anastamose with uninjured choriocapillaris. The microvessels in these lesions are broad and flat, similar to normal choriocapillaris. In a separate study, rats were treated daily with the angiostatic corticosteroid dexamethasone (20-500 microg kg(-1)day(-1)), and CNV was examined at day 10 in FITC-dextran labeled flat mounts and histologic sections. Dexamethasone dose-dependently inhibited CNV, and its highest dose inhibited approximately 95% of CNV labeled by FITC-dextran and resulted in lesions with no detectable Factor VIII immunostaining. High resolution angiography with FITC-dextran is reproducible and quantifiable, and it may accelerate the discovery of therapeutic agents that modulate choroidal neovascularization.

Animals↗
PubMed2002

Optic disk drusen, peripapillary choroidal neovascularization, and POEMS syndrome.

PURPOSE: To report the case of a 64-year-old woman with peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, Castleman disease, optic nerve drusen, and peripapillary choroidal neovascularization. METHODS: Interventional case report. Clinical practice. RESULTS: Laser photocoagulation resolved the peripapillary choroidal neovascularization. CONCLUSION: This is the first documented case of optic disk drusen and peripapillary choroidal neovascularization associated with POEMS.

Castleman Disease↗
PubMed1999

The development of choroidal neovascularization in pregnancy.

PURPOSE: To evaluate the possible association between the development of choroidal neovascularization (CNV) and pregnancy. METHODS: A retrospective review was performed of the clinical records of three patients who were pregnant at the time a choroidal neovascular membrane (CNVM) was diagnosed. The clinical presentations and treatment of the CNVM occurring in association with the pregnancies are described. RESULTS: Each patient had a decrease in visual acuity during her pregnancy: one in the first trimester, one in the second trimester, and one in the third trimester. Two patients were diagnosed with CNV related to presumed ocular histoplasmosis syndrome (POHS) and one with an idiopathic CNVM. The two-patients with POHS showed progression of CNV after childbirth. All patients received laser photocoagulation directly to the site of the CNV. The two patients with ocular histoplasmosis experienced recurrence after treatment; one received further photocoagulation treatment, and the other underwent vitrectomy with removal of the CNVM. CONCLUSIONS: Pregnancy and the immediate postpartum period may be associated with development or recurrence of CNV in POHS or idiopathic cases. This may be related to hormonal changes during pregnancy, or the cases described may reflect only a coincidental association. This report discusses possible causal factors and mechanisms.

Adult↗
PubMedDate not supplied

Chorioretinal topography and histopathology in laser-induced choroidal neovascularization.

OBJECTIVE: To investigate the correspondence between topographic mapping of the vitreoretinal and chorioretinal surfaces in vivo and histopathology findings. MATERIALS AND METHODS: Choroidal neovascularization was induced in the retina of a primate by an argon laser. Serial optical section images of the retina were obtained using an optical imaging system based on the Retinal Thickness Analyzer. Topography of the vitreoretinal and chorioretinal surfaces was mapped. The animal was killed and the eyes enucleated for histopathologic examination. RESULTS: In the normal retina, the topography of the vitreoretinal surface showed a depression at the center of the fovea while the chorioretinal surface was relatively flat, corresponding to normal anatomy. In the retina with choroidal neovascularization, the topography of the vitreoretinal surface indicated a smooth elevation while there were irregular elevations in the topography of the chorioretinal surface. Histological sections displayed focal serous retinal detachment, metaplasia of retinal pigment epithelium, and choroidal neovascularization. CONCLUSION: Topographic mapping of the vitreoretinal and chorioretinal surfaces in vivo corresponds with histological findings and shows promise for quantitative evaluation of pathologic alterations caused by chorioretinal diseases.

Animals↗
PubMed2000

Comparison between indocyanine green angiography and outcome of surgical removal of choroidal neovascular membrane in age-related macular degeneration

Purpose: To review the outcome of surgical removal of choroidal neovascular membranes in age-related macular degeneration as classified by indocyanine green angiographic findings.Subjects and Method: Surgery was performed in 42 eyes. They were divided into four types by indocyanine green angiographic findings prior to surgery. Type I comprised 29 eyes showing hyperfluorescence throughout the angiographic phases. Type II comprised 3 eyes showing hyperfluorescence during the early phase only. Type III comprised 5 eyes showing hyperfluorescence in the late phase only. Type IV comprised 5 eyes without hyperfluorescence throughout the angiographic phases. The results were evaluated according to the visual acuity expressed as log MAR before and after surgery.Results: Visual acuity improved significantly in Types I, II, and III after surgery. Visual acuity did not improve in Type IV.Conclusion: The findings of indocyanine green angiography are thought to reflect the histological characteristics of the choroidal neovascular membrane. Neovascular membranes of Type IV may contain a smaller number of vessels and abundant fibrous tissue. Eyes of Type IV will have atrophies in the neurosensory retina, retinal pigment epithelium, and choriocapillaris. Surgical removal of the choroidal neovascular membrane in Type IV is not effective in improving visual acuity.

Journal Article↗
PubMed2005

[Choroidal neovascularization in children--prevalence, diagnostics and treatment].

Choroidal neovascularization (CNV) belongs to the rare retinal disorders in children. Authors present 3 cases of CNV, which were diagnosed in patients between 12-15 years of age (2 females and 1 male). Complete ophthalmological examination including fluorescein angiography, indocyanine angiography and optical coherence tomography were performed in all cases. Laboratory tests to exclude the systemic diseases were also done. CNV in young people maybe a result of high myopia, angioid streaks, ocular histoplasmosis, trauma or it could be idiopathic. In our series, we found idiopathic CNV in 2 eyes and 1 CNV after traumatic choroidal break. Stabilization of visual acuity was achieved after argon laser treatment in 2 cases.

Adolescent↗
PubMed2004

Choroidal neovascularization is provided by bone marrow cells.

Choroidal neovascularization (CNV) is a known cause of age-related macular degeneration (ARMD). Moreover, the most common cause of blindness in the elderly in advanced countries is ARMD with CNV. It has recently been shown that bone marrow cells (BMCs) can differentiate into various cell lineages in vitro and in vivo. Adults maintain a reservoir of hematopoietic stem cells included in BMCs that can enter the circulation to reach various organs in need of regeneration. It has recently been reported that endothelial progenitor cells (EPCs) included in BMCs are associated with neovascularization. We examine the role of BMCs in CNV using a model of CNV in adult mice. Using methods consisting of fractionated irradiation (6.0 Gy x 2) followed by bone marrow transplantation (BMT), adult mice were engrafted with whole BMCs isolated from transgenic mice expressing enhanced green fluorescent protein (EGFP). Three months after BMT, we confirmed that the hematopoietic cells in the recipients had been completely replaced with donor cells. We then carried out laser photocoagulation to induce CNV in chimeric mice (donor cells >95%). Two weeks after the laser photocoagulation, by which time CNV had occurred, immunohistochemical examination was carried out. The vascular wall cells of the CNV expressed both EGFP and CD31. These findings indicate that newly developed blood vessels in the CNV are derived from the BMCs and suggest that the inhibition of EPC mobilization from the bone marrow to the eyes could be a new approach to the fundamental treatment of CNV in ARMD.

Animals↗
PubMed2003

[Molecular mechanism for choroidal neovascularization in age-related macular degeneration].

Choroidal neovascularization (CNV) in age-related macular degeneration (AMD) is the most common cause of severe visual loss in patients over age 60 years in developed countries. While much is unknown about the underlying pathogenesis of CNV, the increased production of vascular endothelial growth factor(VEGF) by retinal pigment epithelium (RPE) is thought to play a central role in the development of this condition. However, recent studies using gene-manipulated mice question the importance of VEGF alone in promoting CNV. Angiogenesis is thought to result from the balance between angiogenesis stimulation and inhibition. A potent antiangiogenic factor recently has been identified in the retina and shown to be secreted by RPE cells. The inhibitor, pigment epithelium-derived factor(PEDF) is considered the key factor associated with avascularity of the cornea, vitreous, and outer retinal layer of the eye. We recently demonstrated that an imbalance between PEDF and VEGF in RPE cells caused by aging and oxidative stress may contribute to the disregulation of endothelial cell proliferation in CNV. In this review, we also discuss the angiogenic role of inflammatory cells in CNV, age-related changes in Bruch's membrane, and the possibility of the development of animal models reflecting CNV in AMD.

Animals↗
PubMed1994

Phthalocyanine photodynamic therapy: new strategy for closure of choroidal neovascularization.

Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photo-chemically active dye employed in photodynamic therapy (PDT). CASPc is a potent generator of singlet oxygen when irradiated with 675 nm light and is also capable of fluorescence, allowing visualization of the dye in tissues. We devised an angiography system using CASPc fluorescence to determine its localization in experimental choroidal neovascularization in monkeys and then investigated the ability of CASPc to produce photochemical closure of neovascularization upon irradiation with 675nm laser light. Fluorescent imaging indicated that CASPc localized angiographically in areas of neovascularization for at least 24 hours. Irradiation with 675 nm laser light 5-30 minutes after CASPc injection produced complete closure of choroidal neovascularization with minimal damage to overlying retina. We conclude that CASPc localizes in neovascular choroidal vessels and that CASPc photodynamic therapy can produce closure of these choroidal vessels.

Aluminum↗
PubMed2004

Histological findings of a surgically excised myopic choroidal neovascular membrane after photodynamic therapy. A case report.

BACKGROUND: The authors describe a myopic choroidal neovascular membrane excised 4 months after photodynamic therapy (PDT). METHODS: A 68-year-old woman with classic choroidal neovascularization (CNV) due to pathologic myopia underwent PDT with verteporfin in the left eye. Four months after treatment a full-thickness macular hole was diagnosed in the same eye and the patient underwent vitrectomy with submacular membranectomy. The subfoveal membrane was studied by light microscopy and immunohistochemical techniques. RESULTS: Light microscopy showed a thin fibrovascular membrane covered by residual retinal pigment epithelium. The membrane contained homogeneous matrix with small collagen bundles, fibroblasts and small blood vessels. The distribution of blood vessels was nonuniform: extravasated red blood cells, macrophages and other inflammatory elements were not present in the fibrous matrix. Endothelial cells were highlighted by CD34 immunostaining and did not show any significant alteration. There was no evidence of inflammatory cells or thrombosis inside vascular lumina. CONCLUSIONS: Histologic examination of the neovascular membrane showed features similar to those of surgically excised myopic CNV without PDT treatment. Our findings suggest that PDT-induced occlusion is temporary. Fluorescein leakage from CNV after a single PDT treatment can be considered as an sign of blood vessel regrowth or recanalization indicating that multiple treatments are necessary.

Aged↗
PubMed1998

Retrospective study on the evolution of visual acuity after external beam radiotherapy (20 Gy, 2 Gy fractions) for subfoveal choroidal neovascular membranes in ARMD.

This is a retrospective study of 104 patients with a total follow-up between 12 and 48 months (mean follow-up of 24 months), in which the effect of External Beam Radiotherapy with a total dose of 20 Gy (2 Gy fractions) on the visual acuity of eyes affected by subfoveal choroidal neovascularization is evaluated. The evolution of the visual acuity of the irradiated eyes is compared with the evolution of the visual acuity of their fellow eyes which were also affected by choroidal neovascularization but were not treated or treated by laser photocoagulation. This study suggests that the effect of radiotherapy, with a total dose of 20 Gy, on the visual acuity of eyes affected by subfoveal choroidal neovascularization, seems to be not better than the natural course of choroidal neovascularization or the evolution after laser therapy.

Adult↗
PubMed2002

Early vascular changes induced by transpupillary thermotherapy of choroidal neovascularization.

OBJECTIVE: To study early direct effects of transpupillary thermotherapy (TTT) on choroidal neovascularization (CNV) and choroid. DESIGN: Retrospective, noncomparative interventional case series. PARTICIPANTS: Sixty-four eyes with subfoveal CNV. INTERVENTION: TTT was delivered using a diode laser at 810 nm through a contact lens. Exposure time was 60 seconds with a power/diameter ratio of 247 mW/mm. The end point was an invisible treatment with no color change at the retina level. MAIN OUTCOME MEASURES: Fluorescein and indocyanine green angiographic findings within 1 hour, and at 1, 2, and 4 weeks after TTT. RESULTS: Fluorescein angiography (FA) and indocyanine green angiography (ICGA) performed within 1 hour after TTT showed increased leakage of CNV and choroidal vessels. Follow-up at 1 and 2 weeks demonstrated a hypofluorescent area corresponding to the laser spot and absence of angiographic leakage seen on FA and ICGA. At 4 weeks after TTT, FA showed mottled hypofluorescence-hyperfluorescence of the TTT-treated area and absence of angiographic leakage. CONCLUSIONS: TTT induces a characteristic dynamic sequence of vascular changes. Treatment with TTT can lead to absence of angiographic (FA and ICGA) leakage for 4 weeks. Determination of the long-term efficacy and visual implications awaits the results of clinical trials.

Adult↗