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[Natural course and prognosis of visual acuity in patients of age-related macular degeneration with occult choroidal neovascularization].

OBJECTIVE: To investigate the natural course and the final visual acuity in patients of age-related macular degeneration with choroidal neovascularization. METHODS: Thirty five eyes of 29 patients diagnosed as AMD with occult choroidal neovascularization were studied. The eyes which had laser, radiation therapy or surgical treatment were excluded. Visual acuity, fundus examination, fluorescent angiography (FFA) and perimetry test were performed at the first time visit and 5 years following-up at an interval of 1 to 3 months. The average following-up period of time was 8 years (range from 5 to 16 years) which started in 1985 and ended in 2001. RESULTS: Initial visual acuity 0.1 or less was shown in 10 eyes (28.5%, only hands movement can be seen in 4 of 10 eyes), 23 eyes (65.7%) with visual acuity of 0.1 or less (14 eyes with vision acuity of hands movement) on the last visit. 7 of 35 eyes, the final visual acuity improved more than 2 lines, 12 eyes remained the same and 16 eyes had been lost vision more than two lines. At the baseline examination, 25 eyes had macular hemorrhages and 4 eyes had vitreous hemorrhages. The fundus hemorrhages occurred repeatedly 1 to 4 times in 23 eyes during following-up, the macular hemorrhages was detected in 7 eyes at the last visit. At the initial fundus examination, fibrotic membranes were found in 7 eyes; all 35 eyes had disc form scarring with various size in most recent following-up. CONCLUSION: The natural course of Age-related macular degeneration with choroidal neovascularization is prolonged and the final visual prognosis was poor especially in the cases with recurrent macular hemorrhages.

Age Factors↗

VEGF-TRAP(R1R2) suppresses choroidal neovascularization and VEGF-induced breakdown of the blood-retinal barrier.

Vascular endothelial growth factor (VEGF) plays a central role in the development of retinal neovascularization and diabetic macular edema. There is also evidence suggesting that VEGF is an important stimulator for choroidal neovascularization. In this study, we investigated the effect of a specific inhibitor of VEGF, VEGF-TRAP(R1R2), in models for these disease processes. VEGF-TRAP(R1R2) is a fusion protein, which combines ligand binding elements taken from the extracellular domains of VEGF receptors 1 and 2 fused to the Fc portion of IgG1. Subcutaneous injections or a single intravitreous injection of VEGF-TRAP(R1R2) strongly suppressed choroidal neovascularization in mice with laser-induced rupture of Bruch's membrane. Subcutaneous injection of VEGF-TRAP(R1R2) also significantly inhibited subretinal neovascularization in transgenic mice that express VEGF in photoreceptors. In two models of VEGF-induced breakdown of the blood-retinal barrier (BRB), one in which recombinant VEGF is injected into the vitreous cavity and one in which VEGF expression is induced in the retina in transgenic mice, VEGF-TRAP(R1R2) significantly reduced breakdown of the BRB. These data confirm that VEGF is a critical stimulus for the development of choroidal neovascularization and indicate that VEGF-TRAP(R1R2) may provide a new agent for consideration for treatment of patients with choroidal neovascularization and diabetic macular edema.

Animals↗

Intravitreal triamcinolone acetonide inhibits choroidal neovascularization in a laser-treated rat model.

OBJECTIVE: To determine if intravitreal triamcinolone acetonide (TAAC) inhibits experimental choroidal neovascular membranes induced by laser trauma in a rat model. METHODS: Nineteen anesthetized male Brown Norway rats received a series of 8 krypton red laser lesions per eye (647 nm, 0.05 seconds, 50 microm, and 150 mW in 17 rats, and 200 mW in 2 rats). One eye received an intravitreal injection of triamcinolone acetonide (20 microL, 0.8 mg) and the other eye received an injection of isotonic sodium chloride solution. Fundus and fluorescein angiography examinations occurred just before euthanasia and tissue processing for histopathology on day(s) 0, 1, 3, 7, 14, 21, 28, and 35. RESULTS: From the control eyes that underwent photocoagulation at 150 mW, 57 discrete lesions with definitive fibrovascular proliferations were observed at 21, 28, and 35 days, arising from a total of 72 spots placed (79% yield). From the control eyes that underwent photocoagulation at 200 mW, 11 discrete lesions with definitive fibrovascular proliferations were observed at 28 days, arising from a total of 16 spots placed (69% yield). In the TAAC-treated group, no fibrovascular proliferations were observed in the 72 lesions and in the 16 lesions created with 150 mW and 200 mW, respectively. CONCLUSION: Intravitreal TAAC is a potent inhibitor of fibrovascular proliferations in a rat model of choroidal neovascular membranes induced by laser trauma. CLINICAL RELEVANCE: This study corroborates previous investigations that propose TAAC as a potential treatment for choroidal neovascular membranes in humans.

Animals↗

Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes.

PURPOSE: Matrix metalloproteinases (MMP) are a family of extracellular matrix degrading enzymes associated with the development of neovascularization. To investigate the possible role of these enzymes in choroidal neovascularization, the mRNA expression of MMPs and tissue inhibitors of metalloproteinases (TIMPs) were analyzed in subfoveal fibrovascular membranes from patients with age-related macular degeneration (AMD). METHODS: Surgically removed subfoveal fibrovascular membranes from five eyes were analyzed for the expression of MMP and TIMP mRNA. In situ hybridization anti-sense and sense riboprobes were generated using DNA complementary to human collagenase (MMP-1), 72 kDa gelatinase (MMP-2), stromelysin (MMP-3), 92-kDa gelatinase (MMP-9), TIMP-1, TIMP-2, and TIMP-3. Vascular endothelial cells were detected using immunostaining for von Willebrand factor. RESULTS: MMP-2 and MMP-9 mRNA were detected in all specimens. Most of the membranes also expressed TIMP-1 and TIMP-3 mRNA, and two of the membranes expressed TIMP-2 mRNA. MMP-2, TIMP-1, and TIMP-2 mRNA had a similar overall distribution that was relatively uniform within the vascularized membrane stroma. MMP-2 expression appeared to be localized mainly to the vascular endothelial cells, whereas TIMP-1 and TIMP-3 were detected in other cell types such as fibroblastlike cells. MMP-9 expression was distinctly expressed by cells at the margins of the membranes and often in proximity to a thickened Bruch's membrane-like layer under the retinal pigment epithelial cells. TIMP-3 mRNA was strongly expressed within the retinal pigment epithelial cell layer and also in the stroma of one membrane. None of the membranes showed detectable MMP-1 or MMP-3 expression. CONCLUSIONS: The results support a role for MMPs in the development of choroidal neovascularization in AMD. The localization of MMP-2 and MMP-9 to the areas of new vessel formation and to the enveloping Bruch's-like membrane, respectively, suggests that MMP-2 and MMP-9 may be cooperatively involved in the progressive growth of choroidal neovascular membranes in AMD.

Aged↗

Discrepancy between indocyanine green and fluorescein angiography in occult choroidal neovascularization.

Six eyes without or with minimal evidence of choroidal neovascularization on fluorescein angiography are presented. All six eyes have marked retinal pigment epithelial alterations. Indocyanine green angiography reveals extensive hyperfluorescence, indicative of choroidal neovascularization undermining the macula in these six eyes. It is surprising that three eyes are asymptomatic and two others have a relative good visual acuity. It is suggested that hyperfluorescence observed by indocyanine green angiography without or with minimal late dye diffusion on fluorescein angiography could indicate a slow progression and thus a better prognosis of the maculopathy.

Aged↗

Surgical removal of subfoveal choroidal neovascularization without removal of posterior hyaloid: a consecutive series in younger patients.

PURPOSE: Subfoveal choroidal neovascularization (CNV) remains a common and important cause of visual loss. Previous studies have suggested that submacular surgery may improve or maintain visual acuity, particularly in younger patients. The majority of reported cases included removal of the posterior hyaloid during vitrectomy. The authors present a consecutive series of patients age 55 or younger with subfoveal CNV removal without posterior hyaloid removal. METHODS: Seventeen patients without age-related macular degeneration (ARMD), with subfoveal CNV from choroiditis, presumed ocular histoplasmosis syndrome, myopia, or idiopathic causes, underwent a small retinotomy technique to extract the membranes after vitrectomy without posterior hyaloid removal. RESULTS: Median improvement in visual acuity was from 20/320 to 20/50. Eleven patients (65%) experienced an improvement of three or more lines of Snellen acuity (average 7.5), 4 (23%) were within two lines of preoperative acuity, and 2 (12%) had decreased acuity, with an average follow-up of 12 months (range 3-31). Choroidal neovascularization recurred in six patients (35%). Postoperative retinal detachment, epiretinal proliferation, or macular hole did not occur. CONCLUSIONS: In this series of younger patients with subfoveal CNV not from ARMD, visual acuity was improved in the majority after submacular membrane removal. Omission of removal of the posterior hyaloid did not adversely affect outcome.

Adolescent↗

Optical coherence tomography (OCT) findings in normal retina and laser-induced choroidal neovascularization in rats.

BACKGROUND: To evaluate the optical coherence tomographic (OCT) features of the retina of rats, we compared the OCT images with the histological appearance of normal retinas and retinas with laser-induced choroidal neovascularization. METHODS: Twelve eyes of 12 adult pigmented rats (Brown-Norway) were used. Color fundus photography, fluorescein angiography (FAG), and OCT images of normal retinas and retinas with laser photocoagulation-induced choroidal neovascularization were studied. RESULTS: OCT showed a double-layered structure in the normal sensory retina with a highly reflective layer located in the inner retina and a low reflective layer located in the outer retina. The retinal pigment epithelium (RPE) and choriocapillaris were imaged as a layer with the highest reflection. On the first day after photocoagulation, OCT showed a disruption of the highly reflective layer corresponding to the RPE, and an enhanced reflectivity in the choroid under the lesion. Choroidal neovascularizations (CNVs) which appeared 2 weeks after photocoagulation was seen as a multi-layered, highly reflective area protruding from the RPE into the subretinal space A CNV beneath a subretinal hematoma was difficult to detect because of the low transmission of the scanning light through the hematoma. The histopathological appearance was well correlated with the OCT images. CONCLUSION: The two reflective bands in the OCT images were identified as coming from the inner layers of the retina and from the photoreceptors. The highest reflective band arose from the RPE and choriocapillaris. In the future, OCT combined with FAG or indocyanine-green angiography will be a useful tool for the evaluation of animal studies of choroidal neovascularization and other retinal diseases.

Animals↗

A pilot study of indocyanine green videoangiography-guided laser photocoagulation of occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the use of digital indocyanine green videoangiography in patients with clinical and fluorescein angiographic evidence of "occult" choroidal neovascularization in age-related macular degeneration and to investigate indocyanine green videoangiography-guided laser photocoagulation as a therapeutic approach. METHODS: Three hundred forty-seven consecutive patients with exudative age-related macular degeneration and symptoms and clinical manifestations of occult choroidal neovascularization were studied with indocyanine green videoangiography. Patients were selected for laser treatment, using conventional guidelines, when indocyanine green videoangiography demonstrated a well-delineated area of hyperfluorescence, presumed to be a focal area of choroidal neovascularization. RESULTS: Seventy-nine (23%) of 347 eyes were found to have a localized and definable lesion that was potentially amenable to laser photocoagulation therapy; 44 (56%) of these 79 treated eyes had complete resolution of their exudative manifestations. Visual acuity improvement was noted in 10 (13%) of 79 eyes, and stabilization of vision achieved in 42 eyes (53%). CONCLUSION: Laser photocoagulation treatment guided by indocyanine green videoangiography was shown to produce promising anatomical and visual improvement in a small number of patients with occult choroidal neovascularization secondary to age-related macular degeneration. This pilot study warrants further research to investigate the efficacy and safety of this form of treatment.

Aged↗

Triple therapy of intravitreal triamcinolone, photodynamic therapy, and pegaptanib sodium for choroidal neovascularization.

PURPOSE: To report the six-month results of subfoveal choroidal neovascularization that had been treated with combined therapy of high-dose intravitreal triamcinolone acetonide (HDIVTA), photodynamic therapy (PDT), and pegaptanib sodium injection. DESIGN: Retrospective, interventional case series study. METHODS: Medical files of 16 patients with this treatment were reviewed (22 eyes); 13 eyes had had previous treatment with HDIVTA and PDT; nine eyes were newly diagnosed choroidal neovascularization. Patients were treated with an injection of HDIVTA (10 mg), followed by PDT and pegabtanib sodium injection at two-week intervals. The main outcome variables were visual acuity (VA) and macular thickness by optical coherence tomography (OCT). RESULTS: The mean VA improved 2.2 lines (P = .013 in the new treatment group); the previous treatment group (HDIVTA + PDT) improved only 0.7 lines (P = 0.55, Wilcoxon ranked test). The mean of macular thickness before and after treatment was statistically significant in both groups. CONCLUSION: This combination therapy showed improvement and/or stabilization in VA, particularly when used as first-line therapy.

Aged, 80 and over↗

Confocal scanning laser microscopic findings of excised choroidal neovascular membranes of age-related macular degeneration and their comparison with the clinical features.

PURPOSE: To evaluate the histopathological characteristics of choroidal neovascular membranes excised from eyes of patients with age-related macular degeneration (AMD) and to correlate their characteristics with the clinical features of AMD. METHODS: Choroidal neovascular tissues were excised from 3 patients with AMD and examined by light and confocal scanning laser microscopy. The clinical features were obtained by fundus photography, fluorescein angiography (FA), and indocyanine green angiography (IA) and compared with the histopathological findings. RESULTS: Light microscopy showed the presence around the vascular structures of cells containing pigment. Confocal scanning laser microscopy revealed lipofuscin signals of the retinal pigment epithelium cells around the vascular tissue that was also confirmed by three-dimensional reconstructed views from serial optical sections. Clinical observations of the fundus by IA showed that all 3 cases had areas with hyperfluorescence in early phase on IA. A dark rim was observed around the area of hyperfluorescence in 2 cases, and the dark rim was located within the neovascular membrane. The patterns of fluorescence were heterogeneous in some phases on IA, which reflected the histological heterogeneity of the neovascular membrane. CONCLUSIONS: The retinal pigment epithelium cells appear to play a special role in the induction and regression of the choroidal neovascular membrane associated with age-related macular degeneration.

Aged↗

Photodynamic therapy-treated choroidal neovascular membrane secondary to toxoplasmic retinochoroiditis.

PURPOSE: To report the result of photodynamic therapy with Visudyne (PDT) on a child with choroidal neovascular membrane (CNV) secondary to toxoplasmic retinochoroiditis. METHODS: An 11-year-old child with a unilateral lowering of visual acuity secondary to an extrafoveal choroidal neovascular membrane was submitted to PDT. RESULTS: One week after PDT, the patient's vision had improved from 10/160 to 20/70, with marked improvement in the angiographic findings. The CNV evolved with decreasing of leakage until 45 days after operation, when it regressed to a chorioretinal scar formation, with final vision of 20/25. CONCLUSION: PDT promoted an early recovery of visual acuity in an eye with choroidal neovascularization secondary to toxoplasmic retinochoroiditis.

Antiprotozoal Agents↗

Factors influencing visual acuity after photocoagulation for subfoveal choroidal neovascularization of exudative age-related macular degeneration.

PURPOSE: To evaluate factors influencing visual acuity after laser photocoagulation for subfoveal choroidal neovascularization of exudative age-related macular degeneration. METHODS: Subfoveal choroidal neovascular membranes were photocoagulated. Factors favoring a visual acuity of 20/200 or better were analyzed using Fisher's exact probability test or chi-square test on 28 eyes in which visual acuity was 20/200 or better, and 23 eyes with a visual acuity below 20/200 at the most recent follow-up examination. RESULTS: Factors predicting a postoperative visual acuity of 20/200 or better were (1) distance between one lateral margin of the neovascular membrane and the center of the foveal avascular zone was one-third disc diameter or less, and (2) pretreatment retinal sensitivity at the fixation point was 10 dB or more. CONCLUSION: Good indications for photocoagulation treatment of subfoveal choroidal neovascular membrane were a neovascular membrane margin near the center of the foveal avascular zone and relatively good retinal sensitivity at the fixation point adjacent to the scotoma. These factors predict a visual acuity of 20/200 or better after treatment.

Aged↗

Laser treatment of choroidal neovascular membranes in angioid streaks.

Eight patients with active extrafoveal choroidal neovascular membranes related to angioid streaks were studied. One eye of each of four patients was treated with argon laser. Two patients received bilateral treatment. Four patients received multiple treatments at different times for recurrence of neovascular membranes. Two patients were not treated. The visual acuity of the treated eyes remained the same or improved posttreatment, with one exception. The majority of untreated eyes lost vision. The vast majority of the treated eyes showed a marked improvement in central visual field posttreatment, whereas the untreated eyes remained the same or lost considerably more central visual field. In one to four years after treatment, recurrences of the neovascular membranes occurred in four of the treated eyes demonstrating that these cases must be followed indefinitely. Carefully selected cases appear to benefit from complete obliteration of choroidal neovascularization by argon laser photocoagulation.

Aged↗

Photodynamic therapy with verteporfin in subfoveal choroidal neovascularization secondary to central serous chorioretinopathy.

OBJECTIVE: To examine the efficacy and safety of photodynamic therapy with verteporfin in the treatment of subfoveal choroidal neovascularization secondary to central serous chorioretinopathy (CSC). DESIGN: Prospective interventional, noncomparative case series. METHODS: After the diagnosis of a subfoveal choroidal neovascularization secondary to CSC, 26 eyes of 24 patients were treated with photodynamic therapy with verteporfin. Patients were then followed up every 2 to 3 months, with further treatments performed as deemed necessary through fluorescein angiography. The mean observation was 22.2 months (range, 6-36 months; median, 24 months). RESULTS: There was marked visual improvement, with patients gaining a mean of 1.6 lines after 1 year and a mean of 2.2 lines after 2 years. There was a statistically significant change in visual acuity from baseline to 12 and 24 months (mean difference, -0.16, P =.03; and mean difference, -0.22, P =.02; respectively; t test for both). There was no correlation between patients' age or greatest linear dimension of the lesions and the final outcome (P>.10 for all). No patient experienced any adverse effects. CONCLUSION: Photodynamic therapy with verteporfin resulted in a beneficial outcome in the treatment of subfoveal choroidal neovascularization secondary to CSC, without serious adverse effects in this case series.

Adult↗

Macular infarction after transpupillary thermotherapy for subfoveal choroidal neovascularization in age-related macular degeneration.

PURPOSE: To report the complication of macular infarction after transpupillary thermotherapy (TTT) for the treatment of subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). DESIGN: Interventional case reports. METHODS: Among 107 consecutive patients with subfoveal CNV due to AMD, a 73-year-old woman with recurrent subfoveal classic choroidal neovascularization and a 76-year-old man with subfoveal occult choroidal neovascularization with adjacent areas of geographic retinal pigment epithelium atrophy noted a severe decrease in visual acuity and photopsias within hours of undergoing TTT. RESULTS: Both patients had marked whitening of the macula clinically and closure of the perifoveal capillaries on fluorescein angiography. Immediately after treatment their visual acuity decreased from 20/200 to 6/200 and from 20/400 to 2/200, respectively. Several months later, all exudation had resolved and their visual acuity had stabilized at 20/100 and 20/200, respectively. CONCLUSIONS: Macular infarction is a rare complication that occurred in two of 107 patients undergoing TTT for subfoveal CNV due to AMD. The presence of geographic retinal pigment epithelium atrophy or a previous laser treatment scar in the macular region may predispose patients to this complication.

Aged↗

Choroidal neovascularization in children: report of five cases and literature review.

Choroidal neovascularization is rare in the pediatric population. It has been associated in this age group with a variety of conditions. Increasing ability to treat these neovascular lesions with laser photocoagulation makes early recognition very important for visual preservation. An overview is presented, including an updated list of conditions associated with choroidal neovascularization in children and adolescents. Guidelines to recognition, parent and patient instructions, and the selective use of fluorescein angiography are emphasized. Five illustrative cases are highlighted, including a 10-year-old boy successfully treated with krypton laser photocoagulation near the fovea.

Adolescent↗

[Krypton laser photocoagulation at low power setting for age-related macular degeneration complicated with subfoveal choroidal neovascularization].

OBJECTIVE: To evaluate the efficacy of krypton laser photocoagulation for treatment of age-related macular degeneration (AMD) complicated with mainly subfoveal classic choroidal neovascularization (CNV). METHODS: Seventeen eyes of 17 cases, aged 50 - 74 years (averaged 60.8 years) with mainly subfoveal classic choroidal neovascularization were treated with krypton laser at lower power setting. The treatment was completed in one session. Another course of treatment was given 4 weeks later if there was active leakage demonstrated at the CNV area. Visual acuity, anterior segment and fundus examination, perimetry test, fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed before and after treatment. The follow-up period was 3.5 years on average (1 - 8 years). RESULTS: There was no immediately decrease of visual acuity after treatment. All treated eyes showed absorption of hemorrhages and/or exudates and diminished leakages. Visual acuity was stable in 8 eyes; improved in 6 eyes (>/= 2 lines), and decreased in 3 eyes (</= 2 lines). The central scotoma showed no significant changes after the treatment. Closure of CNV was confirmed on FFA/ICGA and no recurrence was found in 9 cases during 3 years follow-up. CONCLUSION: Krypton laser photocoagulation at low power setting is an effective treatment for AMD with mainly classic subfoveal choroidal neovascularization.

Aged↗

Photodynamic therapy of experimental choroidal neovascularization with a hydrophilic photosensitizer: mono-L-aspartyl chlorin e6.

PURPOSE: To demonstrate the selective localization of the hydrophilic photosensitizer mono-L-aspartyl chlorin e6 (NPe6) in experimental choroidal neovascularization in nonhuman primate eyes. METHODS: Sixty-seven experimental choroidal neovascular lesions (CNV) were created in the fundi of Macaca monkeys using the modified Ryan's model and documented by fluorescein and indocyanine green angiography. To determine the biodistribution of NPe6 and the optimal timing of laser irradiation after dye administration, NPe6 angiography and fluorescence microscopy with NPe6 were performed. Photodynamic therapy (PDT) was performed at various dye doses (0.5-10.0 mg/kg) and laser fluences (7.5-225.0 J/cm2) on the CNV and on 10 areas of normal retina and choroid. Treatment outcomes were assessed by fluorescein and indocyanine green angiography and confirmed by light and electron microscopy. RESULTS: NPe6 fluorescence microscopy demonstrated intense fluorescence of CNV and retinal pigment epithelial cells. Choroidal vessel walls and outer retina adjacent to CNV fluoresced moderately; retinal vessel walls and microcapillaries had trace fluorescence. The fluorescence of CNV lesions on fluorescein angiography became stronger than that of retinal vessels 20-60 minutes after dye injection. Choroidal neovascular lesion closure was achieved with NPe6 PDT without significant damage to the sensory retina. Histology demonstrated necrosis of CNV endothelial cells with minimal damage to surrounding tissues. CONCLUSIONS: NPe6 PDT selectively localizes to experimental CNV in nonhuman primates, resulting in occlusion of CNV with sparing of the neurosensory retina.

Animals↗