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PubMed2003

CME review: A cost-utility analysis of laser photocoagulation for extrafoveal choroidal neovascularization.

PURPOSE: The purpose of this study was to perform a reference case (average case), cost-utility analysis of laser photocoagulation for extrafoveal choroidal neovascularization associated with age-related macular degeneration using a model incorporating patient preferences. METHODS: Visual acuity data for patients treated and observed over a 5-year period were obtained from previously reported studies by the Macular Photocoagulation Study Group. The results from this prospective, randomized trial were incorporated in a cost-utility model using time-trade-off utility analysis and decision analysis with Markov modeling according to the recommendations of the Panel on Cost-Effectiveness in Health and Medicine. Expenditures and health care benefits were each discounted at a 3% yearly rate. RESULTS: Laser photocoagulation therapy for extrafoveal choroidal neovascularization in age-related macular degeneration, compared with observation, resulted in a mean gain of 0.0740 quality-adjusted life-year per patient treated. The mean cost of treatment for the average patient totaled 1,715 US dollars. The cost divided by the health care benefit resulted in 23,176 year 2001 US dollars per quality-adjusted life-year gained for this procedure for a reference case. Sensitivity analyses, varying the cost, utility values, and discount parameters, resulted in dollars per quality-adjusted life-year gained ranging from 16,117 to 49,766 US dollars. CONCLUSION: Laser photocoagulation for extrafoveal choroidal neovascularization associated with age-related macular degeneration appears to be cost-effective when compared with interventions across multiple medical specialties.

Choroidal Neovascularization↗
PubMed2003

MMP-2 and MMP-9 synergize in promoting choroidal neovascularization.

Matrix metalloproteinase 2 (MMP-2) and MMP-9 are increased in human choroidal neovascularization (CNV) occurring during the exudative most aggressive form of age-related macular degeneration (AMD), but their precise role and potential interactions remain unclear. To address the question of MMP-2 and MMP-9 functions, mice deficient in the expression of MMP-2 (MMP-2 KO), MMP-9 (MMP-9 KO), and both MMP-2 and MMP-9 (MMP-2,9 KO) with their corresponding wild-type mice (WT) underwent CNV induction by laser-induced rupture of the Bruch's membrane. Both the incidence and the severity of CNV were strongly attenuated in double deficient compared with single gene deficient mice or corresponding WT controls. The reduced neovascularization was accompanied by fibrinogen/fibrin accumulation. Furthermore, overexpression of the endogenous MMP inhibitors TIMP-1 or TIMP-2 (delivered by adenoviral vectors) in WT mice or daily injection of a synthetic and gelatinase selective MMP inhibitor (Ro 26-2853) significantly decreased the pathological reaction. These findings suggest that MMP-2 and MMP-9 may cooperate in the development of AMD and that their selective inhibition represents an alternative strategy for the treatment of choroidal neovascularization.

Animals↗
PubMed1989

Choroidal neovascular membrane and other chorioretinal complications of acquired syphilis.

We reviewed ten patients who had posterior segment complications of acquired syphilis. Five of these patients had a neovascular membrane of the choroid associated with secondary or tertiary syphilis. Vision was stabilized after laser photocoagulation in one patient who had a choroidal neovascular membrane. Five additional patients had ocular manifestations including uveitis, optic neuritis, neuroretinitis, chorioretinitis, retinal hemorrhages, arterial and venous occlusion, vasculitis, and retinitis. Treatment of chorioretinal complications of syphilis with intravenous penicillin, if initiated early in the course of the disease, may result in excellent visual recovery.

Adult↗
PubMed2004

Evaluation of trans-scleral diode laser using diopexy probe for subfoveal choroidal neovascular membrane in age-related macular degeneration.

OBJECTIVE: To evaluate safety and short-term visual and fluorescein angiographic effects of trans-scleral diode laser photocoagulation in patients with subfoveal choroidal neovascularization from age-related macular degeneration (ARMD). BACKGROUND DATA: The visual outcome following treatment of subfoveal choroidal neovascularization in ARMD is still unsatisfactory. Various forms of therapy such as laser treatment, photodynamic therapy, radiation therapy, transpupillary thermotherapy, and surgical excision have been tried with variable results. MATERIALS AND METHODS: Patients with subfoveal choroidal neo-vascularization were treated with trans-scleral diode laser using the diopexy probe under indirect ophthalmoscopic visualization and followed up at 2, 6, and 12 weeks. Standardized protocol refraction, visual acuity testing, reading speed, contrast requirement measurement, ophthalmic examinations, color fundus photographs, and fluorescein angiogram were used to evaluate the results of treatment. RESULTS: Eighteen eyes of 18 patients were included in the study between April 2000 and May 2002. At 12 weeks, 81.5% patients showed stabilization (+/-5 letters) in letter visual acuity score, and one patient showed improvement (gain of more than five letters) in letter visual acuity score. Reading speed levels and contrast requirement were found to be similar to pre-laser level at 3 months followup. At 12 weeks, moderate fluorescein leakage was seen in one eye, minimal leakage was seen in five eyes, absence of leakage was seen in 10 eyes, and progression was seen in two eyes. CONCLUSION: Transcleral diode laser treatment of subfoveal choroidal neovascular membranes in ARMD may be an effective as well as safe alternative in the management of these patients.

Aged↗
PubMed1998

[Choroid neovascularization in senile macular degeneration. 1 hear follow-up after radiotherapy].

UNLABELLED: Choroidal neovascularization (CNV) associated with age-related macular degeneration is the major cause of legal blindness in Europe and the USA in patients aged more than 65 years, but Chakravarthy et al. has reported that radiotherapy has a beneficial effect on visual acuity. METHODS: Since March 1996 we have treated 56 patients in cooperation with the Department of Radiotherapy at the Technical University in Munich. The total dose with external beam radiotherapy was 16 Gy in 8 fractions, delivered through an anterior oblique axis to spare the lens. Before the treatment and 3, 6 and 12 months after therapy, we performed a standardized visual acuity and contrast-sensitivity test (ETDRS, Pelli Robson Chard) and fluorescin angiography 6 and 12 months after therapy. RESULTS: Twenty-five angiograms showed well-defined CNV and 31 not well-defined CNV. Six months after the treatment 15 patients had stable visual acuity within one line. Twenty-seven patients had lost more than one line of visual acuity. There was no difference between well and not well defined CNV's. One year after treatment the visual acuity remained stable within one line in 4 patients, no patient had an increase of two lines or more and 17 patients lost more then 2 lines of vision. We saw no side effects other than sicca symptoms in 3 patients. CONCLUSION: In our opinion, these results do not show that radiation treatment has a real beneficial effect on visual acuity. Further randomized studies are needed to demonstrate the efficiency of this treatment for choroidal neovascularization in AMD.

Aged↗
PubMed1985

Important points in management of patients with choroidal neovascularization.

The efficacy of argon blue-green laser treatment for extrafoveal choroidal neovascularization (CNV) in aging macular degeneration, presumed ocular histoplasmosis syndrome and idiopathic choroidal neovascularization has recently been proven by the Macular Photocoagulation Study. These results are applicable only to eyes managed according to certain principles of therapy and post-treatment follow-up. These include the use of a recent fluorescein angiogram and retrobulbar anesthetic, aiming for complete obliteration of the CNV. Meticulous post-treatment follow-up is critical. This includes daily patient monitoring of the Amsler grid, and prompt examinations if distortion is noted. Excellent quality fluorescein angiography is mandatory. This is repeated frequently and studied promptly. Residual or recurrent extrafoveal CNV requires prompt re-treatment.

Choroid↗
PubMed2001

Staging of idiopathic choroidal neovascularization by optical coherence tomography.

PURPOSE: To assess the clinical course of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography (OCT). METHODS: Thirty-two patients with a clinical diagnosis of ICNV were examined between December 1995 and October 1999. The ages of the patients ranged from 18 to 53 (mean 35.9) years, and the mean period of observation was 5.8 months. Color fundus photography, fluorescein angiography, Indocyanine green angiography, and OCT were performed. The stage of the ICNV was classified as active, intermediate, or cicatricial, based on past history, fundus findings, and fluorescein angiography (FAG). The characteristic OCT images at these three stages were determined. RESULTS: OCT revealed that there were characteristic tomographic images of the choroidal neovascularization (CNV) at each stage. In the active stage, OCT revealed the CNV as a highly reflective, multi-layered area protruding into the subretinal space. In the intermediate stage, the reflectivity of the CNV became stronger and its margin in the subretinal space became smooth. With regression of the ICNV, the lesions consisted of two different areas: a most reflective area corresponding to the fibrotic changes of the CNV (imaged white in OCT images), and a reddish highly reflective area representing a compound protrusion of the CNV. In the cicatricial stage, the ICNV was observed as a moderately high reflective area covered by a dome-shaped highly reflective layer corresponding to the retinal pigment epithelium. CONCLUSION: These findings demonstrated clearly the changes in the OCT images during the development and regression of ICNV. OCT was useful for following the clinical course and understanding the mechanism of the CNV regression.

Adolescent↗
PubMed1996

Indocyanine green-guided laser photocoagulation of focal spots at the edge of plaques of choroidal neovascularization.

OBJECTIVE: To determine whether indocyanine green-guided laser photocoagulation of focal spots at the edge of plaques of neovascularization is beneficial for patients with untreatable occult choroidal neovascularization by fluorescein imaging. PATIENTS: A pilot series of 23 eyes were identified that had untreatable occult choroidal neovascularization secondary to age-related macular degeneration with focal spots at the edge of a plaque of neovascularization on the indocyanine green study. After informed consent was obtained, indocyanine green-guided laser photocoagulation was applied solely to the focal spot at the edge of the plaque. RESULTS: Anatomical success with resolution of the exudative findings was noted in 15 (79%) of 19 eyes at 6 months, 13 (68%) of 19 eyes at 12 months, and six (37.5%) of 16 eyes at 24 months. The median follow-up period was 18 months (range, 3 to 44 months). Visual acuity was stabilized or improved in nine (69%) of 13 successfully treated eyes at 1 year. Of the successfully treated cases at 1 year, nine (69%) of 13 had a final visual acuity of 20/100 or better. CONCLUSIONS: Our preliminary study of indocyanine green-guided laser photocoagulation of focal spots at the edge of plaques of neovascularization suggests that this technique may improve the visual prognosis of these patients with presently untreatable disease. A prospective, randomized, controlled clinical trial is warranted to evaluate this treatment approach.

Aged↗
PubMed1999

Choroidal neovascularization following macular hole surgery.

BACKGROUND: Retinal pigment epitheliopathy, a recognized finding in eyes that have undergone macular hole surgery, may limit visual outcome and predispose to the development of choroidal neovascularization (CNV). This study reports on the features and outcomes of CNV following otherwise successful surgery for idiopathic macular holes. METHODS: Case series including three eyes of two patients who developed CNV following macular hole surgery. RESULTS: Choroidal neovascularization developed 3 to 30 months after macular hole surgery. The CNV was crescent-shaped, surrounding a central area of retinal pigment epithelial mottling that corresponded to the site of the macular hole in all three cases. All neovascular membranes were adjacent to the fovea and were associated with substantial leakage of fluorescein. The macular hole remained closed in all cases. CONCLUSION: Choroidal neovascularization is a rare complication following macular hole surgery. Retinal pigment epitheliopathy and defects in the Bruch's membrane, pre-existing or secondary to surgery, may be predisposing factors.

Aged↗
PubMed2004

Photodynamic therapy of subfoveal and juxtafoveal choroidal neovascularization in ocular histoplasmosis syndrome: a retrospective case series.

PURPOSE: To evaluate the safety and effect on visual acuity of photodynamic therapy (PDT) with verteporfin in patients with subfoveal and juxtafoveal choroidal neovascular membranes from ocular histoplasmosis syndrome (OHS). METHODS: Retrospective case series. The visual outcome of 11 patients with subfoveal (n = 6) and juxtafoveal (n = 5) choroidal neovascularization treated with PDT was reviewed. At 1 to 3 months of follow-up, retreatment with PDT was performed if angiography showed leakage. RESULTS: Within the subfoveal group, 3 patients (50%) had improved vision (two or more lines better than initial vision), 2 patients (33.3%) had no change in vision (within 1 line), and 1 (16.7%) lost four lines of vision. At last follow-up, 3 patients (50%) had vision between 20/20 and 20/40 compared with only 1 patient (16.6%) at the initial visit. Mean follow-up was 13.7 months. Within the juxtafoveal group, 3 patients (60%) had improved vision, 1 patient (20%) had no change in vision, and 1 patient (20%) lost nine lines of vision. At last follow-up, 3 of 5 patients (60%) had vision between 20/20 and 20/40 compared with 2 patients (40%) at the initial visit. Mean follow-up was 10.2 months. No significant adverse effects were reported. CONCLUSION: PDT is a safe and promising option for patients with OHS with choroidal neovascularization that is subfoveal or juxtafoveal.

Adolescent↗
PubMed1998

Surgical removal of non-age-related subfoveal choroidal neovascular membranes.

PURPOSE: To assess anatomical and visual results following the surgical removal of non-age-related subfoveal choroidal neovascular membranes. METHODS: A retrospective study was carried out of 31 consecutive patients undergoing vitrectomy, parafoveal retinotomy and removal of subfoveal choroidal neovascular membranes that were either idiopathic or associated with multifocal choroiditis, high myopia, trauma or angioid streaks. RESULTS: Visual acuity improved or remained the same in 25 eyes (81%) after a mean follow-up of 10.1 months (range 3-37 months). visual acuity improved by more than 2 lines of Snellen acuity in 5 eyes (16%) and decreased by more than 2 lines in 2 eyes (6%). There was no significant association between the final visual outcome and length of symptoms prior to surgery or pre-operative visual acuity. Atrophy of the retinal pigment epithelium and older age were associated with poor outcome. Membranes recurred in 11 eyes (35%), and eyes with subfoveal blood prior to surgery were more likely to have recurrent membranes. CONCLUSIONS: The results of surgical removal of non-age-related subfoveal neovascular membranes have been encouraging, but further studies of long-term outcome and of the natural history of individual conditions are required.

Adolescent↗
PubMed2006

Suppression and regression of choroidal neovascularization by systemic administration of an alpha5beta1 integrin antagonist.

Integrin alpha(5)beta(1) plays an important role in developmental angiogenesis, but its role in various types of pathologic neovascularization has not been completely defined. In this study, we found strong up-regulation of alpha(5)beta(1) in choroidal neovascularization. Implantation of an osmotic pump delivering 1.5 or 10 microg/h ( approximately 1.8 or 12 mg/kg/day) of 3-(2-{1-alkyl-5-[(pyridin-2-ylamino)-methyl]-pyrrolidin-3-yloxy}-acetylamino)-2-(alkylamino)-propionic acid (JSM6427), a selective alpha(5)beta(1) antagonist, caused significant suppression of choroidal neovascularization; the area of neovascularization was reduced by 33 to 40%. When an osmotic pump delivering 10 microg/h of JSM6427 was implanted 7 days after rupture of Bruch's membrane, there was terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining in vascular cells within the neovascularization and significant regression of the neovascularization over the next week. JSM6427 also induced apoptosis of cultured vascular endothelial cells. Fibronectin stimulates phosphorylation of extracellular signal-regulated kinase (ERK) in alpha(5)beta(1)-expressing cells that is blocked by JSM6427. These data suggest that alpha(5)beta(1) plays a role in the development and maintenance of choroidal neovascularization and provides a target for therapeutic intervention.

Administration, Cutaneous↗
PubMed2005

[Treatment of choroidal neovascular membranes].

PURPOSE: The purpose is to present our experience in diagnosis and treatment of choroidal neovascular membranes of various etiology. MATERIAL AND METHODS: This is a retrospective study consisting of 165 patients that were diagnosed with choroidal neovascular membranes (CNM). From this patients, 62 were treated between 2001-2005 for CMN of different etiology: age-related macular degeneration (AMD), myopia, presumed ocular histoplasmosis syndrome, angioid streaks, viteliform dystrophy. The diagnosis was based on the clinical examination (direct and indirect ophthalmoscopy, direct and indirect biomicroscopy) and angiofluorography. The treatment was either PDT for sub-foveolar membranes, or laser coagulation with YAG532 laser for juxta and para-foveolar well defined membranes, or combined treatment for large minimal classic membranes with a well defined juxta para-foveolar component or a component on the feeder vessels. PDT was done with verteporfin (Visudyne, Novartis Pharma AG) activated with a diode laser of 689 nm (Activis, Quantel medical) and the laser coagulation was done with a Visulas YAG 532 Carl Zeiss laser. RESULTS: Results can be evaluated from two points of view: changes in the neovascular membrane (enlargement and activity signs) and the changes in VA. Last researches are based not only on AV but also on the quality life. The membranes are closed with PDT in 90% of the cases in the first week but there are rebounds in almost 100% of the cases at 3 months. This calls for multiple treatments. After two or three treatments the signs of activity (hemorrhage and exudation) drop and 60% of the membranes will close. After laser coagulation the CMN is closed completely in 70% of the patients and in 20% of the cases there is a rebound in the first month and in 30% of the cases the rebound appears in the next 2 years. The visual acuity has improved at 33% of cases, remained the same in 33% of cases and worsened in the rest of the treated eyes. The results are compatible with TAP and VIP results where after 24 months the average VA of those treated with verteporfirin was lower than at the beginning but twice as good compared with placebo. CONCLUSIONS: For four year we had at our disposal methods with which we can improve (33%) the VA in patients with CMN, at some of them we could maintain (33%) the visual acuity and at the rest of the patients, even though the visual acuity is lower, it will be still higher then the one during the natural course of the disease.

Aged↗
PubMed2000

[Correlation of indocyanine green angiography findings and expression of vascular endothelial growth factor in surgically excised age-related macular degeneration-related choroidal neovascular membranes].

PURPOSE: We investigated the relationship between clinical classification by indocyanine green angiography (IA) and pathologic findings including the expression of vascular endothelial growth factor (VEGF) in age-related macular degeneration-related choroidal neovascular membranes. SUBJECT AND METHODS: The subjects were 15 patients with age-related macular degeneration who underwent surgical excision for choroidal neovascular membrane. The patients were classified into 4 types: Type I, hyperfluorescence in both early and late phases (n = 7); Type II, hyperfluorescence in the early phase only (n = 2); Type III, hyperfluorescence in the late phase only (n = 3); and Type IV, no hyperfluorescence in any phase (n = 3). The excised choroidal neovascular membranes were fixed and stained by hematoxylin-eosin and azan. They were also examined by immunohistochemical staining for VEGF. RESULTS: VEGF was expressed markedly in vascular endothelial cells and fibroblast-like cells of interstitial tissue of Types I, II and III. Its expression was weak in Type IV. CONCLUSION: Clinical classification by IA for age-related macular degeneration is consistent with the pathologic findings including the expression of VEGF.

Aging↗
PubMed2000

Multiple choroidal neovascularizations at the border of a myopic posterior macular staphyloma.

BACKGROUND: In pathologic myopia, choroidal neovascularization (CNV) usually occurs in macular region and at the center of the macular staphyloma. CNV has been reported to occur at the borders of an inferior posterior staphyloma in the tilted disc syndrome. We present a case of multiple simultaneous CNVs located at the borders of a myopic macular staphyloma. METHODS: The clinical and angiographic records of a myopic patient who presented several areas of choroidal neovascularization were reviewed. RESULTS: On fundus examination, four gray lesions surrounded by subretinal hemorrhages and covered by a large serous retinal detachment were observed at the borders of a posterior staphyloma. Fluorescein angiography revealed that these four lesions were CNVs extending from the borders of the staphyloma to the macular region. As measured by B-scan ultrasonography, the staphyloma was 4 mm deep. CONCLUSION: This case supports the hypothesis that the borders of staphylomas are sites at risk for the development of CNV in pathologic myopia.

Choroidal Neovascularization↗
PubMed2004

Preventive versus treatment effect of AG3340, a potent matrix metalloproteinase inhibitor in a rat model of choroidal neovascularization.

PURPOSE: AG3340 (prinomastat) is a nonpeptidic, small-molecular-weight, synthetic matrix metalloproteinase inhibitor (MMPI) with selective inhibitory action of MMP-2, MMP-9, MMP-3, and MT-MMP1. We evaluated AG3340 injected intravitreally to treat choroidal neovascularization in a laser induced rat CNV model. METHODS: In the pretreatment group, the drug was injected the same day after induction of choroidal neovascularization by diode laser. In the treatment group, the drug was injected 2 weeks after induction of choroidal neovascularization (CNV). Fluorescein and indocyanine green angiography were performed to evaluate CNV. ERG recordings and histology were performed to assess toxicity and the CNV lesions. RESULTS: When used at the time of CNV induction, 62.8% of lesions in control versus 22.8% of the laser lesions in treated eyes developed CNV (p < 0.0001). The invading fibrovascular complex was thicker in the control eyes than that in the treated eyes. No signs of toxicity were detected. When used to treat established CNV, the percentage of leakage in treated and control eyes were 54.1% and 58.9% respectively (p > 0.05). Prinomastat was effective when given at the time of induction of CNV in the rat model. Administration of prinomastat 2 weeks after laser induction did not show efficacy. CONCLUSION: Prinomastat was active in the earliest stages of experimental CNV. It might be best used in combination with photodynamic therapy to inhibit recurrence of CNV from temporarily closed new vessels.

Animals↗
PubMed2004

[Three-dimensional imaging of photodynamic effects and spontaneous course in choroidal neovascularization].

PURPOSE: Photodynamic therapy (PDT) induces occlusive and regenerative effects in choroidal neovascularization (CNV) and physiological choroid. The process of vascular alteration is documented quantitatively and qualitatively by three-dimensional angiography. METHOD: In a prospective, randomized trial 30 patients with subfoveal CNV due to age-related macular degeneration (AMD) were treated with PDT or placebo. Fluorescence series with 32 tomographic images over a 4-mm depth were analyzed topographically and reproduced in a three-dimensional display. RESULTS: At initial presentation CNV lesions were documented as a well-defined prominence in all patients. In the verteporfin group CNV height continuously decreased with each interval. In the placebo group CNV slightly increased in height during the first 6 months and remained stable at about 90% of the initial prominence at long-term follow-up. After 12 months 44% of the patients in the verteporfin group developed an additional choroidal defect. CONCLUSION: Three-dimensional angiography offers a reliable documentation of CNV progression and regression during PDT. A decrease in CNV size is associated with an increase in choroidal perfusion defects.

Choroidal Neovascularization↗