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Correlation between angiographic and pathological findings in experimental choroidal neovascular membranes after transpupillary thermotherapy.

PURPOSE: To evaluate the correlation between angiographic and pathological findings in experimental choroidal neovascular membranes after transpupillary thermotherapy (TTT). METHODS: Experimental subretinal choroidal neovascular membranes were produced in the monkey eye macula by intense photocoagulation. TTT was delivered, targeting the choroidal neovascular membranes, using a diode laser at 810 nm. One week and 4 weeks after TTT, indocyanine green angiography (IA), fluorescein angiography (FA), optical coherence tomography (OCT), and histological examinations were performed. RESULTS: One week after TTT, indocyanine green dye leakage from choroidal neovascular membranes was reduced on IA, and FA showed staining in the late phase. Light microscopic examination showed numerous small-caliber blood vessels and persistent subretinal exudation. Four weeks after TTT, there was no indocyanine green dye leakage on IA, and FA showed staining. OCT showed a decrease in retinal detachment. Light microscopic examination showed fewer blood vessels and subretinal exudation had disappeared. Choroidal neovascular membranes were composed of fibrous tissue. CONCLUSIONS: Changes in angiographic and OCT findings observed after TTT were inferred to be the result of accelerated fibrosis due to TTT and the disappearance of exudation.

Animals↗

Indocyanine green angiographic findings in idiopathic choroidal neovascularization.

PURPOSE: Evaluation of choroidal alterations associated with idiopathic choroidal neovascularization (ICNV) and the possible relation between this affection and Multifocal Choroidopathies (MC). METHODS: The authors analysed, using high definition videoangiography, the choroidal findings in 21 consecutive patients affected by ICNV (7 males and 14 females; 19-46 years; mean age: 31.8 years); with a follow-up at 5-30 months (mean 13 months). Moreover, a retrospective study of 20 cases of ICNV (11 males and 9 females; age: 17-39 years; mean age: 29.3 years) with a follow-up at 6-11 years (mean 8.9), was performed. RESULTS: In 7 eyes, the indocyanine green angiography (ICGA) showed choroidal hypofluorescent spots similar to those observed in MC (in 3 cases even in the fellow unaffected eye), in 2 of them the regression of the spots was observed after steroid therapy. In 2 eyes, the ICGA revealed hyperfluorescent spots; in one of them the complete regression of the spots after oral cyprofloxacine was observed. In 6 patients (10 eyes), choroidal permeability alterations could be visualized (in 4 cases even in the unaffected eye). CONCLUSIONS: The indocyanine green angiographic findings (hypo and hyperfluorescent spots, choroidal permeability alterations) could support the theory of Gass which considers that ICNV is not idiopathic but secondary to a widespread choroidal inflammatory disease. The similarity of the ICGA alterations in ICNV and MC, the observation that cases of ICNV would become MC in the follow-up, could allow the hypothesis of a close connection between these two affections.

Adolescent↗

Choroidal neovascularization following laser in situ keratomileusis.

Two cases of choroidal neovascularization occurring after laser in situ keratomileusis (LASIK) are presented from two separate centers. In the first case, an extrafoveal choroidal neovascular membrane, apparently associated with age-related macular degeneration, occurred 3 months after a LASIK procedure was performed on a 64-year-old man with hyperopia. Argon laser treatment and subsequent photodynamic therapy were performed and resulted in stabilization of vision. The second case involved neovascularization 3 weeks following a LASIK procedure for myopia, apparently associated with the myopia. No treatment was recommended and the vision stabilized at 20/50. Although the cause is not clear, careful preoperative macular evaluation and attention to symptoms that might herald the presence of choroidal neovascularization are recommended for patients undergoing LASIK.

Choroidal Neovascularization↗

Choroidal neovascularization with granulomatous inflammation in ocular histoplasmosis syndrome.

PURPOSE: To report pathologic examination of an excised choroidal neovascular membrane in a patient with ocular histoplasmosis syndrome that demonstrated granulomatous inflammation. METHOD: Case report. A 50-year-old woman with sudden vision loss in her left eye demonstrated clinical and fluorescein angiographic findings characteristic of choroidal neovascularization secondary to ocular histoplasmosis syndrome. RESULTS: Histopathologic examination of the surgically excised choroidal neovascular membrane disclosed granulomatous inflammation. CONCLUSIONS: This case suggests an important role of mononuclear phagocytic cells as primary mediators of angiogenesis or modifiers of choroidal neovascularization. This association of choroidal neovascularization with granulomatous inflammation did not respond to treatment with systemic corticosteroids.

Choroidal Neovascularization↗

Overexpression of vascular endothelial growth factor (VEGF) in the retinal pigment epithelium leads to the development of choroidal neovascularization.

Vascular endothelial growth factor (VEGF) has been strongly implicated in the development of choroidal neovascularization found in age-related macular degeneration. Normally expressed in low levels, this study investigates whether the overexpression of VEGF in the retinal pigment epithelium is sufficient to cause choroidal neovascularization in the rat retina. A recombinant adenovirus vector expressing the rat VEGF(164) cDNA (AdCMV.VEGF) was constructed and injected into the subretinal space. The development of neovascularization was followed by fluorescein angiography, which indicates microvascular hyperpermeability of existing and/or newly forming blood vessels, and histology. VEGF mRNA was found to be overexpressed by retinal pigment epithelial cells and resulted in leaky blood vessels at 10 days postinjection, which was maintained for up to 31 days postinjection. By 80 days postinjection, new blood vessels had originated from the choriocapillaris, grown through the Bruch's membrane to the subretinal space, and disrupted the retinal pigment epithelium. This ultimately led to the formation of choroidal neovascular membranes and the death of overlying photoreceptor cells. By controlling the amount of virus delivered to the subretinal space, we were able to influence the severity and extent of the resulting choroidal neovascularization. These results show that even temporary overexpression of VEGF in retinal pigment epithelial cells is sufficient to induce choroidal neovascularization in the rat eye.

Adenoviridae↗

Laser management of subfoveal choroidal neovascularization in age-related macular degeneration.

Subfoveal choroidal neovascularization in eyes with age-related macular degeneration is associated with a poor natural prognosis. The Macular Photocoagulation Study Group recently has demonstrated that subfoveal photocoagulation in select cases of subfoveal choroidal neovascularization for patients with age-related macular degeneration effectively prevents severe visual acuity loss and reduces the average loss of contrast sensitivity and reading speed associated with this condition. Eligibility criteria and treatment recommendations from the Macular Photocoagulation Study will be reviewed. Results of alternative strategies for laser photocoagulation of such lesions are also discussed; however, the Macular Photocoagulation Study results stand alone in documenting a long-term treatment benefit of photocoagulation for subfoveal choroidal neovascularization.

Aged↗

Subfoveal choroidal neovascularization in punctate inner choroidopathy. Surgical management and pathologic findings.

PURPOSES: To evaluate submacular surgery for the management of subfoveal choroidal neovascularization in punctate inner choroidopathy, to describe the histopathology and ultrastructure of the excised subretinal tissue, and to propose a staging system that characterizes the development of choroidal neovascularization with associated subretinal fibrosis. METHODS: The authors reviewed the records of five patients (6 eyes) with punctate inner choroidopathy who underwent submacular surgery for subfoveal choroidal neovascularization. Surgical specimens were examined using light and transmission electron microscopy. RESULTS: Visual improvement was noted postoperatively in all six eyes, with follow-up ranging from 8 to 36 months (median, 14 months). Recurrences (6 in 4 eyes) were common. Five of the six recurrences required additional procedures: three were managed surgically, two with laser photocoagulation, and one with observation. "Bridging" of separate foci of choroidal neovascularization resulted in stellate or "dumbbell-shaped" areas of subretinal fibrosis in four of six eyes. Histopathologic evaluation of the excised tissue showed endothelial-lined vascular channels, retinal pigment epithelium, lymphocytes, plasma cells, fibrocytes, collagen fragments, and rarely, outer retinal elements. CONCLUSIONS: Subfoveal choroidal neovascularization in punctate inner choroidopathy may be managed with submacular surgery. Recurrences are common and may result in substantial loss of vision. Choroidal neovascular membranes with an accompanying fibrotic reaction are responsible for the stellate or dumbbell-shaped areas of subretinal fibrosis. No beneficial effect was demonstrated using corticosteroid treatment of the choroidal neovascularization.

Adult↗

Photodynamic therapy with verteporfin for choroidal neovascularization in patients with angioid streaks.

PURPOSE: To evaluate safety and efficacy of photodynamic therapy with verteporfin for subfoveal choroidal neovascularization associated with angioid streaks. DESIGN: Prospective interventional case series. METHODS: Eight patients (eight eyes) with subfoveal choroidal neovascularization secondary to angioid streaks were reviewed. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, color photographs, fluorescein angiograms and indocyanine angiograms were used to evaluate the results of photodynamic therapy with verteporfin. Follow up ranged from 6 to 12 months with a mean (+/- SD) of 8.75 (+/- 2.37) months. RESULTS: Photodynamic therapy with verteporfin was well tolerated in patients with choroidal neovascularization related to angioid streaks. No deterioration in visual acuity was observed. Increase in median best-corrected visual acuity was 1.37 lines (SD +/- 1.59 lines, range 1-5 lines) at the last follow up. Two (25%) patients had no improvement of visual acuity. At the last follow up three (37.5%) patients showed no leakage and three (37.5%) patients had minimal leakage from choroidal neovascularization. Photodynamic therapy related ocular complications were not reported in any case. CONCLUSIONS: Photodynamic therapy with verteporfin generally achieved short-term cessation of or decrease of fluorescein leakage from subfoveal choroidal neovascularization without loss of vision in patients with angioid streaks. Further studies with longer follow up are necessary to confirm whether verteporfin therapy is beneficial for subfoveal choroidal neovascularization related to angioid streaks.

Adult↗

[Results of perifoveal argon laser coagulation of subfoveal choroid neovascularization in age related macular degeneration].

BACKGROUND: The treatment of patients with subfoveal choroidal neovascular membrane in age-related macular degeneration is unsatisfactory because only a limited number of patients are eligible. The aim of this study was to prospectively evaluate a new perifoveal treatment technique in patients with subfoveal choroidal neovascular membrane. METHODS: Between April 1992 and January 1994, 385 patients underwent clinical examination and fluorescein angiography. Eligibility criteria were met by 21 (5.5%) patients (22 eyes): well or poorly defined subfoveal choroidal neovascular membrane (< or = 3.5 disc diameters), without fibrosis, with visual acuity < or = 0.25. Visual acuity, morphological findings and complications were studied. The follow-up period was 12-32 months. RESULTS: The visual acuity before laser treatment ranged from counting fingers up to 0.25 (median 0.06). At the end of the follow-up (median 18 months) 28% (6/21) of patients showed a better visual acuity, whereas 44% (9/21) were unchanged and 28% (6/21) had deteriorated compared to visual acuity before treatment. In 71% (15/21) of eyes, resolution of the choroidal neovascular membrane was achieved with development of an atrophic laser scar. CONCLUSION: The visual outcome and the morphological findings after perifoveal laser treatment of subfoveal choroidal neovascular membrane in age-related macular degeneration show it to be an alternative method of treatment with favourable results. Due to inclusion criteria it is suitable only for a limited number of patients.

Aged↗

[Treatment of choroidal neovascularization in degenerative myopia].

Choroidal neovascularization is quite frequent in degenerative myopia. If the neovascularization is near the center, a krypton laser photocoagulation can be effected. If they reach the center, no photocoagulation should be effected. We report here our results in the treatment by krypton laser and describe a simple technic for the determination of the exact position of the foveola, that can be displaced in degenerative myopia.

Adult↗

Clinicopathologic correlations of surgically excised type 1 and type 2 submacular choroidal neovascular membranes.

PURPOSE: To correlate the histologic and clinical classification of type 1 (subretinal pigment epithelium) and type 2 (subsensory retina) choroidal neovascularization. METHODS: Ten eyes of 10 patients with surgically excised choroidal neovascularization that were routinely processed and could be histologically classified as having a type 1 or type 2 configuration were studied. The patients were clinically classified as having type 1 or type 2 choroidal neovascularization according to preoperative fundus appearance of both eyes and patient age. The histologic and clinical classifications were made in a masked fashion, and the results were compared. RESULTS: The histologic classification was type 1 and type 2 for three and seven specimens, respectively. The clinical classification matched the histologic classification in nine of 10 cases. Clinical fundus characteristics that distinguished type 2 choroidal neovascularization included a subretinal pigmented halo or pigmented plaque in the area of the choroidal neovascularization and sharply defined borders. Patients with type 1 membranes were on average older (76 years) than patients with type 2 membranes (53 years). CONCLUSIONS: It is generally possible to clinically ascertain by clinical fundus appearance and age of a patient whether subfoveal choroidal neovascularization represents a type 1 or type 2 configuration.

Adult↗

Expression of vascular endothelial growth factor in experimental choroidal neovascularization.

BACKGROUND: Although the choroidal neovascularization (CNV) is a common pathologic feature of a number of different eye diseases, its pathological mechanisms have not been fully elucidated. We investigated the expression of vascular endothelial growth factor (VEGF) in CNV using an experimental primate model. METHOD: CNV was induced by intense laser photocoagulation in four monkey eyes. Single eyes were enucleated at 1, 3, 7 or 14 days after photocoagulation and examined immunohistochemically for VEGF, macrophage antigen, von Willebrand factor and glial fibrillary acidic protein (GFAP). Expression of VEGF mRNA was examined by in situ hybridization. RESULTS: One day after photocoagulation, the normal structure of the outer portion of the retina and the inner portion of the choroid was destroyed. Three days after photocoagulation, choroidal vascular endothelial cells migrated into the subretinal space through the defect in Bruch's membrane. Increased expression of VEGF was detected in the accumulating macrophages, migrating retinal pigment epithelial (RPE) cells and Müller cells. Maximal expression of VEGF was observed between 3 and 7 days after wounding, and many newly formed vessels extended into the subretinal space 7-14 days after photocoagulation. CONCLUSION: VEGF derived from RPE cells, macrophages and Müller cells may play a role in the formation of CNV.

Animals↗

Combined photodynamic therapy and intravitreal triamcinolone for nonsubfoveal choroidal neovascularization.

PURPOSE: To examine the 12-month results for a group of patients with nonsubfoveal choroidal neovascularization who were treated with combined photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide. METHODS: Patients with nonsubfoveal choroidal neovascularization, which was defined as either juxtafoveal or extrafoveal neovascularization, were treated with PDT immediately followed by an intravitreal injection of 4 mg of triamcinolone acetonide. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. The main outcome measures were visual acuity and the proportion of patients developing subfoveal extension. RESULTS: Of the 15 patients, 9 were women and 6 were men (mean age +/- SD, 80 +/- 7.5 years). The mean baseline visual acuity was almost 20/60 (mean logMAR = 0.46), and 14 of the 15 eyes had juxtafoveal choroidal neovascularization. At 3, 6, and 9 months, the patients had significant improvement in the mean visual acuity (P = 0.002, 0.001, and 0.007, respectively), but at the end of the 12-month follow-up period, the mean visual acuity was slightly worse than 20/40 (mean logMAR = 0.34), which was not statistically significant at an alpha level adjusted for multiple comparisons of .013 (P = .057) as compared with the baseline visual acuity. One patient had subfoveal extension of choroidal neovascularization. The mean number of treatments was 1.9. Three patients (20%) developed an intraocular pressure of >24 mmHg during follow-up, a threshold used to institute pressure reduction therapy. No patient developed endophthalmitis. CONCLUSION: The number of patients in this pilot study was limited; however, the visual acuity response and the low incidence of subfoveal extension suggest that PDT combined with intravitreal triamcinolone for the treatment of nonsubfoveal choroidal neovascularization merits further investigation as a first-line treatment.

Aged↗

Glycoconjugates of choroidal neovascular membranes in age-related macular degeneration.

PURPOSE: Choroidal neovascularization (CNV) is a complication of multiple eye diseases, including age-related macular degeneration, that usually results in irreversible vision loss. It is characterized by proliferation and growth of choroidal blood vessels through Bruch's membrane into the subpigment epithelial and/or subretinal space. The purpose of this study was to characterize the carbohydrate groups associated with CNV by lectin histochemistry. METHODS: Frozen sections from three human eyes with CNV (two fixed eyes and one unfixed eye) were prepared. Sections containing choroidal neovascular membranes were incubated with a battery of biotinylated lectins directed against a number of distinct oligosaccharide moieties. Lectin labeling of the vessels in CNV was visualized with avidin-Texas red. RESULTS: Several carbohydrate groups were preferentially associated with the vascular elements in CNV. Glycoconjugates that react with lectins derived from wheat germ, soybean, and hairy vetch seed (sWGA, SBA, and VVA, respectively) all showed reactivity with CNV vessels that was higher than the labeling of the surrounding matrix. SBA and sWGA also reacted with CNV vessels at low concentrations at which normal retinal and choroidal vessels were largely unlabeled. CONCLUSIONS: Choroidal neovascular membranes possess a distinct set of carbohydrate moieties. These data may be valuable in understanding endothelial cell biology in CNV.

Aged↗

Verteporfin therapy combined with intravitreal triamcinolone in all types of choroidal neovascularization due to age-related macular degeneration.

OBJECTIVE: To evaluate the efficacy and safety of photodynamic therapy with verteporfin combined with intravitreal triamcinolone in choroidal neovascularization secondary to age-related macular degeneration (AMD). DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: One hundred eighty-four patients undergoing treatment for neovascular AMD at one retinal referral center. METHODS: One hundred eighty-four eyes of 184 consecutive patients (63.6% female, 36.4% male) with a mean age of 76.5 years and a follow-up of a median of 38.8 weeks (range, 12-103) were included in a case series. One hundred forty-eight (80.4%) patients had subfoveal choroidal neovascularization, 19 patients (10.3%) had juxtafoveal choroidal neovascularization, and 17 patients (9.2%) had extrafoveal choroidal neovascularization. Verteporfin photodynamic therapy was performed using the recommended standard procedure. A solution containing 25 mg of triamcinolone was injected intravitreally 16 hours after photodynamic therapy in 184 patients. The combined therapy procedure was repeated at the 3-month follow-up visits whenever persistent choroidal neovascularization leakage was documented angiographically. MAIN OUTCOME MEASURES: Mean change in best-refracted visual acuity (VA) between baseline and the last visit, and number of treatments necessary to achieve absence of leakage. RESULTS: Visual acuity improved in the majority of patients (baseline VA, mean 20/125) by a mean increase of 1.22 Snellen lines and 1.43 lines using laser interferometry (P<0.01). The mean number of required treatments was 1.21. Twenty-three eyes (12.5%) required 2 treatments, 6 eyes (3.26%) required 3 treatments, and 1 eye (0.5%) required 4 treatments. The combination treatment including laser and intravitreal steroid administration was well tolerated. Forty-six patients (25%) required glaucoma therapy due to a transient steroid-induced intraocular pressure (IOP) increase. Twelve patients (6.5%) were on topical medication for preexisting glaucoma. Two patients (1%) whose IOP increase could not be controlled with topical therapy required surgery. CONCLUSIONS: Verteporfin photodynamic therapy combined with intravitreal triamcinolone may improve the outcome of standard verteporfin photodynamic therapy in the treatment of choroidal neovascularization secondary to AMD. A significant improvement in VA was observed in a majority of treated patients and was maintained during the maximum follow-up. In addition, retreatment rates were lower than anticipated.

Aged↗

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization secondary to toxoplasmic chorioretinal scar.

BACKGROUND: To assess the effect of photodynamic therapy in the treatment of subfoveal choroidal neovascularization consecutive to a toxoplasmic chorioretinal scar. HISTORY AND SIGNS: Three patients with a previous history of toxoplasmic chorioretinal scar noticed a decrease in visual acuity and metamorphopsia. Fundus examination and fluorescein angiography revealed the presence of subfoveal choroidal neovascularization at the edge of the toxoplasmic chorioretinal scar. THERAPY AND OUTCOME: The first patient, aged 78, was treated by photodynamic therapy followed by three subsequent treatments of feeder vessel by laser photocoagulation. Visual acuity decreased during follow-up in the presence of recurrence of choroidal neovascularization and subretinal fibrosis. The second patient, a 20-year-old lady, was treated with three sessions of photodynamic therapy for a subfoveal choroidal neovascularization related to a toxoplasmic scar. Visual acuity was stabilized on the last follow-up visit at 0.3. The third patient, aged 53, received four treatments with photodynamic therapy at an interval of 3 - 4 months. choroidal neovascularization was stabilized and the last visual acuity was 0.2. CONCLUSIONS: This preliminary report suggests that photodynamic therapy with verteporfine may be an effective therapeutic modality for subfoveal choroidal neovascularization related to a toxoplasmic chorioretinal scar. Further assessment is needed in order to confirm this preliminary findings.

Adult↗

Phosphorothioate oligonucleotides induction into experimental choroidal neovascularization by HVJ-liposome system.

PURPOSE: The purpose of this study was to determine whether the inactivated hemagglutinating virus of Japan (HVJ)-liposome method can induce phosphorothioate oligonucleotides effectively into an experimentally-induced choroidal neovascularization of rats. We also examined whether antisense phosphorothioate oligonucleotides against VEGF could be induced into choroidal neovascularization as a therapeutic agent by the HVJ-liposome method. METHODS: The experiments were conducted on a rat model of choroidal neovascularization. FITC-labeled phosphorothioate oligonucleotides were coencapsulated in liposomes. The liposomes were coated with the envelope of inactivated HVJ and injected into the vitreous cavity following photocoagulation of pigmented rat eyes. The eyes were removed following injection, fixed, frozen and cut into thin sections. Induction of oligonucleotides was observed under a laser confocal scanning microscope for fluorescence and the development of choroidal neovascularization was evaluated histopathologically. RESULTS: Phosphorothioate oligonucleotides were effectively induced into ganglion cells and into the cells of the choroidal neovascularization induced by laser photocoagulation. Highly effective induction of oligos was observed 3 to 14 days after intravitreal injection of HVJ-liposomes after which the level decreased. Antisense oligonucleotides against VEGF were induced specifically into cells in the choroidal neovascularization, however neovascularization was still observed. CONCLUSIONS: Phosphorothioate oligonucleotides can be effectively induced into ganglion cells, and specifically into cells in choroidal neovascularization. Although antisense oligonucleotides against VEGF failed to prevent choroidal neovascularization, the HVJ-liposome method provided a highly effective means of inducing antisense oligos for in vivo antisense therapy.

Animals↗

Laser photocoagulation for choroidal neovascular membrane associated with optic disc drusen.

PURPOSE: To report two cases of choroidal neovascular membrane associated with optic disc drusen which were successfully treated using argon laser photocoagulation. METHODS: Choroidal neovascular complications of optic disc drusen were diagnosed in two of our patients, a 36-year-old woman and a 14-year-old girl. In both cases visual acuity was 20/100 in the affected eye. Fundus examination and angiography revealed a choroidal neovascular membrane. Computer tomography identified bilateral calcified drusen of the optic discs. Photocoagulation of neovascular tissues was immediately performed. RESULTS: Visual acuity improved progressively, reaching 20/20 10 months after treatment in one case and 20/30 in the other. No recurrence was observed during follow-up. CONCLUSION: Early diagnosis and immediate laser photocoagulation of vision-threatening choroidal neovascular membranes associated with optic disc drusen helps stop progression towards the macula and improves longterm visual acuity.

Adolescent↗