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Surgical removal of peripapillary choroidal neovascularization associated with age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To describe the results of surgical treatment of peripapillary choroidal neovascularization in age-related macular degeneration as an option to both laser photocoagulation and photodynamic therapy. PATIENTS AND METHODS: Retrospective review of patients with peripapillary choroidal neovascularization secondary to age-related macular degeneration who were not eligible for or refused laser photocoagulation. Patients without the diagnosis of age-related macular degeneration and those who had extension of their neovascularization subfoveally were excluded from the review. RESULTS: Eleven patients total were identified who met the specified inclusion criteria. The male to female ratio was 4:7, with an age range of 63 to 94 years (mean = 78 years). The mean area of involved retina temporal to the optic disc was 5 clock hours, with the distance of the temporal edge of the lesion from the fovea ranging from 100 to 2,000 microm. The mean duration of follow-up was 23 months, with 27% (3 of 11) experiencing recurrent choroidal neovascularization. The preoperative and postoperative visual acuity ranges were both 20/25 to counting fingers. Sixty-four percent (7 of 11) of patients had stable or improved visual acuity postoperatively, with a mean visual acuity change of 1 line visual improvement. CONCLUSION: In cases where photodynamic therapy and laser photocoagulation are not indicated, the surgical treatment of peripapillary choroidal neovascularization secondary to age-related macular degeneration may prove beneficial.

Aged↗

Choroidal ischemia after photodynamic therapy with verteporfin for choroidal neovascularization.

PURPOSE: To report delay in choroidal perfusion suggestive of ischemia after photodynamic therapy (PDT) with verteporfin for choroidal neovascularization (CNV). DESIGN: Observational case series. METHODS: Retrospective review of all patients who developed choroidal ischemia after PDT. RESULTS: This vascular change was found in eight (2.1%) of 373 eyes of patients treated for CNV as a result of age-related macular degeneration (AMD) and in one (0.9%) of 114 eyes treated for pathologic myopia. A decrease of 3 lines of vision was reported to occur one week after treatment in patients with AMD. At the 12-month examination, patients did not exhibit any marked changes in visual acuity. CONCLUSIONS: Choroidal ischemia was an uncommon manifestation owing to the selectivity of verteporfin therapy and the existence of abundant anastomotic vascular connections in the choroid. The low incidence of this vascular event should not preclude counseling PDT in eyes that could benefit greatly from this therapy.

Aged↗

Expression of vascular endothelial growth factor and its receptor (KDR/flk-1) mRNA in experimental choroidal neovascularization.

PURPOSE: Vascular endothelial growth factor (VEGF) is an angiogenic peptide that has been suggested to be important in the pathogenesis of choroidal neovascularization. We investigated the transcription of VEGF and its receptor KDR/flk-1 genes during the development of experimentally induced choroidal neovascularization. METHODS: Rat VEGF or KDR cDNA was inserted in PGEM or pBluescript to prepare antisense or sense riboprobes. Multiple krypton laser burns were applied to the posterior pole of pigmented rat eyes according to a previously described protocol which produces choroidal neovascularization. At intervals of up to 4 weeks after photocoagulation, the eyes were removed and cut into thin sections. The sections were subjected to in situ hybridization with digoxigenin (DIG)-labeled single-strand rat VEGF and KDR cDNA riboprobes. RESULTS: In normal adult rat retinas, VEGF and KDR mRNA expression was mainly observed in the ganglion cell and the inner nuclear layers. During the development of neovascularization, VEGF and KDR mRNAs were detected in retinal pigment epithelial-like cells, fibroblast-like cells and endothelial cells in neovascular lesions. The level of expression was strongest at 1 week after photocoagulation in lasered lesions, and decreased by 4 weeks after photocoagulation. CONCLUSIONS: Our findings demonstrate that expression of VEGF and its receptor KDR may play a role in the formation of experimentally induced choroidal neovascularization. In this study, VEGF and its receptor were co-localized, suggesting that an autocrine and/or paracrine mechanism may be operative.

Animals↗

[Subretinal surgery for choroidal neovascularization].

BACKGROUND: Ten years have passed since subretinal surgery for choroidal neovascularization (CNV) was developed. Many reports regarding the visual outcome after subretinal surgery have been published, which have revealed the role of the subretinal surgery, including long-term visual outcome and surgical complications. METHOD: Reports associated with subretinal surgery published in the past decade were used to clarify the indication for surgery, visual outcome, and surgical complications. RESULTS: The visual prognosis for patients with surgically excited CNV is variable, depending on the underlying disease. Patients with widespread defects of Bruch's membrane and retinal pigment epithelium (RPE), such as age-related macular degeneration, are probably not good candidates for surgery from the standpoint of recovering good visual acuity. On the other hand, patients with focal abnormalities in Bruch's membrane and the RPE, such as presumed ocular histoplasmosis or idiopathic CNV, may be good candidates for surgery. However, it has not been proved that subretinal surgery is superior to photocoagulation or observation. CONCLUSIONS: For the time being, we have to select patients for subretinal surgery on the basis of published reports. The Submacular Surgery Trial now being held in the United States will evaluate the role of subretinal surgery in the management of patients with choroidal neovascularization.

Choroidal Neovascularization↗

[Treatment of macular choroidal neovascular membrane with krypton red laser photocoagulation].

Ten (10) cases of macular choroidal neovascular membrane were treated successfully with krypton red laser (KRL) photocoagulation. The patients were followed up 3-15 months with no recurrence. Choroidal neovascular membranes outside the foveal region carried good visual prognosis, while poor visual outcome accompanied foveal involvement. The authors were encouraged by the efficacy of KRL photocoagulation in the treatment of macular choroidal neovascular membranes. Complications were few; however, the laser parameters, especially the output power, were key points to success.

Adult↗

Health- and vision-related quality of life among patients with ocular histoplasmosis or idiopathic choroidal neovascularization at enrollment in a randomized trial of submacular surgery: Submacular Surgery Trials Report No. 5.

OBJECTIVES: To (1) summarize vision-targeted and general health-related quality-of-life scores at baseline and quantify the effect of the ophthalmic problem, (2) evaluate the strength of relations between visual acuity and interview scores, and (3) compare scores for patients who also had choroidal neovascular lesions in the fellow eye (bilateral cases) with those of patients who had choroidal neovascularization in only the study eye (unilateral cases) at time of enrollment in a randomized trial of surgical removal of subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or of idiopathic origin. DESIGN: Eligible patients had subfoveal choroidal neovascularization (including some classic choroidal neovascularization) and a visual acuity of 20/50 to 20/800 (Snellen equivalent), inclusive, in the eye to be assigned randomly to surgery or observation. Interviews that incorporated the 39-item version of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) and 2 other instruments were conducted by telephone by trained interviewers before patients enrolled and were assigned randomly to surgery or observation. Information from baseline clinical examinations and fluorescein angiograms interpreted centrally by masked readers was used to classify patients as unilateral or bilateral cases and to provide potential explanations for variability of interview responses using linear regression models. RESULTS: The median overall NEI-VFQ score was 75 (interquartile range, 60-84). The median scores on individual subscales ranged from 55 (general vision) to 100 (color vision). The visual acuity of the better-seeing eye accounted for much of the variability in scores on most NEI-VFQ subscales; a 3-line difference in visual acuity was associated with a 10-point or greater difference in scores on 5 subscales after adjustment for other characteristics of patients and eyes. Scores on most scales of all 3 instruments differed between unilateral cases (n = 167) and bilateral cases (n = 58). Even after adjustment for visual acuity and reading speed of the better-seeing eye, age, gender, and scores on the other instruments, scores on the NEI-VFQ near and distance activities subscales differed by almost 13 and 10 points, respectively, between unilateral and bilateral cases. Neither age nor gender was an important independent explanatory variable for NEI-VFQ scores. CONCLUSIONS: Unilateral and bilateral cases had vision-targeted health-related quality-of-life scores worse than those published for a reference population without eye disease. Furthermore, despite younger age, better visual acuity, and better short-term visual prognosis, bilateral cases had NEI-VFQ scores at baseline similar to those published for 2 groups of patients with age-related macular degeneration. Unidentified factors, in addition to the visual acuity of the better-seeing eye, affected patients' perceptions of visual function.

Adolescent↗

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in Vogt-Koyanagi-Harada syndrome.

PURPOSE: To assess the role of photodynamic therapy using verteporfin in the treatment of subfoveal choroidal neovascularization in Vogt-Koyanagi-Harada syndrome. DESIGN: Interventional case report. METHODS: A 9-year-old patient with subfoveal choroidal neovascularization received a single photodynamic therapy with verteporfin session (one eye) and was prospectively followed with fluorescein angiography. RESULTS: A complete regression of the lesion was achieved within 1 week after treatment. Visual acuity improved from 20/800 to 20/320 by 6 months of follow-up. Fluorescein angiography disclosed unexpected retinal pigment epithelium alteration within the treatment area. CONCLUSION: Although regression of the choroidal neovascularization occurred, unpredicted findings involving normal retina in the vicinity of the lesion suggest that further studies are required to assess the clinical value of this treatment for subfoveal choroidal neovascularization in Vogt-Koyanagi-Harada syndrome.

Child↗

[Gene expression patterns of choroidal neovascularization induced by krypton laser photocoagulation].

OBJECTIVE: To explore the gene expression patterns of choroidal neovascularization with gene chip technology. METHODS: Total RNA was isolated from normal choroid and choroid tissues with neovascularization induced by krypton laser photocoagulation in Brown Norway rat. The mRNA was purified and was reversely transcribed to cDNA to prepare for hybridization probes. In choroidal neovascularization, the differentially expressed genes were assayed with gene chips which contained 5705 rat genes. RESULTS: There were 46 genes expressed differentially in choroidal neovascularization. Of these, the expression of 3 genes was upregulated and 43 genes downregulated. These genes were involved in the function of transport, signal, metabolism, development and differentiation of cell adhesion. CONCLUSION: Numerous genes are involved in the development of choroidal neovascularization induced by krypton laser photocoagulation.

Animals↗

Successful photodynamic therapy with verteporfin for recurrent choroidal neovascularization beneath the new fovea after macular translocation surgery with 360-degree retinotomy.

PURPOSE: To report a case of successfully treated recurrent choroidal neovascularization after macular translocation surgery with 360-degree retinotomy by photodynamic therapy with verteporfin. DESIGN: Interventional case report. METHODS: A 76-year-old man developed recurrent choroidal neovascularization at the new fovea after macular translocation surgery with 360-degree retinotomy. RESULTS: Two sessions of photodynamic therapy were applied, which resolved the choroidal neovascularization. Best-corrected visual acuity improved to 20/50 at the 6 and 12 months follow-up. CONCLUSION: Photodynamic therapy may be an option for treatment of recurrent choroidal neovascularization in the new subfoveal region after macular translocation surgery with 360-degree retinotomy.

Aged↗

Macular translocation for subfoveal choroidal neovascularization in age-related macular degeneration: a prospective study.

PURPOSE: To conduct a prospective study of macular translocation in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration. METHODS: In 10 eyes of 10 patients with subfoveal choroidal neovascularization and best-corrected visual acuity ranging from 20/50 to 20/800 (median, 20/111), the fovea was relocated by means of scleral imbrication, intentional retinal detachment with small posterior retinotomies, and partial fluid-air exchange. In two eyes, the choroidal neovascular membranes were removed at the time of macular translocation; in seven eyes they were photocoagulated in the postoperative period; and in one eye the membrane was removed during reoperation to unfold a macular fold. RESULTS: All 10 eyes were followed up for 6 months. The median postoperative foveal displacement was 1286 microm (range, 114 to 1,919 microm). In three eyes (30%), a foveal fold formed postoperatively requiring reoperation, with one of these eyes requiring a second reoperation for a rhegmatogenous retinal detachment. Best-corrected visual acuity improved in four eyes (median, 10.5 letters) and decreased in six eyes (median, 14.5 letters). The median change in visual acuity was a decrease of 5 letters. The final best-corrected visual acuity was 20/80 in two eyes, 20/126 in one eye, 20/160 in four eyes, 20/200 in one eye, 20/250 in one eye, and 20/640 in one eye. CONCLUSIONS: Our initial experience with limited macular translocation suggests that this surgical technique is unpredictable. However, in patients with subfoveal choroidal neovascularization from age-related macular degeneration, it offers the potential for improving visual function and may be associated with less loss of vision than the disease itself, if allowed to progress. Further refinements in surgical indications and technique are needed to make this procedure safer, more predictable, and more beneficial.

Aged↗

Choroidal neovascularization in long-standing case of Vogt-Koyanagi-Harada disease.

The eyes in a case of Vogt-Koyanagi-Harada disease (VKH) with long-standing uveitis for 26 years after the onset were studied histopathologically. It was found that typical granulomatous inflammation was persistent in the uveal tract and the choroidal neovascularization occurred in the peripheral fundus accompanied by proliferation of the retinal pigment epithelial cells (RPE). Some of the new vessels under the pigment epithelium extended into the vitreous. It was concluded that the ocular inflammation of VKH was essentially granulomatous even in this long-standing case. Disappearance of choroidal melanocytes, existence of epithelioid cells containing pigment granules, and accumulation of lymphocytes and plasma cells in the lesion indicated that the inflammation was an autoimmune reaction against uveal melanocytes, although the trigger initiating the disease remains unknown. It was further concluded that the peripheral fundus as well as the peripapillary and macular areas was a predilected site for choroidal neovascularization in chronic uveitis. The choroidal neovascularization may develop in such a way that the uveal inflammation damages the Bruch's membrane and choriocapillaris and consequently causes retinal ischemia, thus stimulating the endothelium of the choriocapillaris and the overlying RPE to proliferate. There is a close relation between choroidal neovascularization and proliferation of RPE. Choroidal neovascularization may cause reactive proliferation of the RPE and vice versa.

Choroid↗

Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group.

OBJECTIVE: To summarize findings from three randomized clinical trials of krypton laser treatment of juxtafoveal neovascular lesions regarding changes in visual acuity during 5 years of follow-up, rates of persistent and recurrent choroidal neovascularization, and status of macular lesions 5 years after enrollment. DESIGN, PATIENTS, AND PRIMARY OUTCOME MEASURES: Follow-up of patients enrolled in three randomized trials of choroidal neovascularization secondary to age-related macular degeneration (AMD), ocular histoplasmosis, or idiopathic causes ended in March 1991. All patients were eligible to complete at least 3 years of follow-up examinations. Data on visual acuity, reading vision, and anatomic outcomes during 5 years of follow-up were available for 276 (92%) of 300 patients with AMD, 236 (92%) of 256 patients with ocular histoplasmosis, and 38 (97%) of 39 patients with idiopathic choroidal neovascularization enrolled 5 or more years earlier who were still living. RESULTS: Among eyes with AMD, the estimated relative risk (RR) of a loss of 6 or more lines of visual acuity from baseline to any examination from 6 months through 5 years after enrollment for untreated eyes in comparison with treated eyes was 1.20 (P = .04). Normotensive patients with AMD realized the greatest benefit from laser treatment (RR, 1.82) and hypertensive patients experienced little or no benefit (RR, 0.93). Untreated eyes with ocular histoplasmosis were at much greater risk of a 6-line decrease in visual acuity from the 1-year through the 5-year examination than were treated eyes (unadjusted RR, 2.60; RR, 4.26 after adjustment for visual acuity and hypertension at baseline; P < .001 for both). The treatment effect for eyes with idiopathic choroidal neovascularization was between the effects for eyes with AMD and eyes with ocular histoplasmosis. CONCLUSIONS: The early beneficial effects of laser treatment on visual acuity persisted for at least 5 years in eyes with all three underlying conditions. Laser treatment of similar eyes with choroidal neovascularization in a juxtafoveal location is recommended for patients with these conditions, with the caveat that hypertensive patients with AMD may fare no better with laser treatment than without treatment.

Aged↗

[Expression of fibroblast growth factor receptor 1 in experimental choroidal neovascularization with in situ hybridization].

Fibroblast growth factor (FGF) is an important factor for neovascularization in vivo. In order to clarify the role of FGF in experimentally produced choroidal neovascularization, we demonstrated mRNA for FGF receptor 1 in situ hybridization. Krypton laser photocoagulation was applied to the posterior retina of colored rats to produce choroidal neovascularization experimentally. These eyes were removed at several different intervals after photocoagulation. Chorioretinal section were used for in situ hybridization. FGF receptor 1 cDNA fragment was used to make antisense and sense probes for in situ hybridization. In normal chorioretinal tissue, staining indicating the existence of FGF receptor 1 mRNA was seen in the ganglion cell layer and inner nuclear layer. After the photocoagulation, the staining was seen in the retinal pigment epithelial cells, melanocytes in the choroid, and choroidal blood vessel wall in the photocoagulated lesions. FGF receptor 1 mRNA was expressed through the development of choroidal neovascularization, and it appears that FGF is necessary for development of choroidal neovascularization. Previous workers showed that the capillary endothelial cells and retinal pigment epithelial cells produce basic FGF in vitro. It seems that FGF effects those cells in an autocrine or paracrine manner in vivo.

Animals↗

Retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization.

PURPOSE: To report a case of retinal pigment epithelial tear after photodynamic therapy for choroidal neovascularization. METHODS: Case report. A 74-year-old woman with exudative age-related macular degeneration and classic subfoveal choroidal neovascularization RE underwent photodynamic therapy with verteporfin. RESULTS: Ophthalmoscopy and fluorescein angiography RE disclosed a retinal pigment epithelial tear in the area of photodynamic therapy. CONCLUSION: This case presents the first report of a retinal pigment epithelial tear after photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in age-related macular degeneration.

Aged↗

[Choroidal neovascularization associated with sympathetic ophthalmia: case report].

A 7-year-old boy with sympathetic ophthalmia secondary to penetrating ocular trauma developed choroidal neovascularization in the macular region of the sympathizing eye. Posterior segment biomicroscopy disclosed a single, round, small, slightly elevated yellow-white lesion temporal to the fovea, linked to the temporal edge of the optic disc by a fibrotic band. On fluorescein angiography the round lesion showed a gradual hyperfluorescence, with late staining and leakage, and was interpreted as a fibrovascular scar from previous choroidal neovascularization. Despite intense immunosuppressive therapy, the patient's final visual acuity was 20/400. Although rarely associated with sympathetic ophthalmia, choroidal neovascularization and its cicatricial stages can occur and compromise the visual prognosis of an already debilitated eye. The best course of treatment for choroidal neovascularization in these types of cases has not yet been determined.

Child↗

Choroidal neovascularization secondary to vitrectomy for idiopathic epiretinal membrane: report of an unusual case.

PURPOSE: Epiretinal membranes (ERM) are a common finding in old patients. Pars plana vitrectomy is effective for removing ERM from the macula, but some postoperative complications are relatively frequent. In the present report, we describe a 73-year-old man in whom extrafoveal choroidal neovascularization developed four months after surgery. METHODS: Choroidal neovascularization was treated by argon laser photocoagulation. RESULTS: Six months after treatment, the choroidal neovascularization was obliterated, with no recurrence of ERM. CONCLUSIONS: Choroidal neovascularization can be an unusual complication of ERM surgery, and should be suspected in case of poor visual outcome or recurrence of symptoms.

Aged↗

Expression of extradomain-B-containing fibronectin in subretinal choroidal neovascular membranes.

PURPOSE: To investigate the presence of the fibronectin isoform containing the extradomain B (B-FN), a marker-protein of angiogenesis, in surgically excised human choroidal neovascular membranes (CNVM) to evaluate whether B-FN could be used as a therapeutic target for specific antibody-photosensitizer immunoconjugates. DESIGN: Laboratory investigation. METHODS: The setting was an institutional practice. The study population consisted of 15 eyes (15 patients) with CNVM undergoing membrane excision (four eyes with age-related macular degeneration, seven with pathologic myopia and four with multifocal choroiditis). The control group consisted of eight eye bank eyes (four subjects) without choroidal neovascularization. Light microscopic immunohistochemistry on cryostat sections of tissues was obtained. B-FN was detected by a human recombinant antibody, CGS-1, and compared with immunostaining for endothelial cells with factor VIII-related antigen. The main outcome measure was the presence of CGS-1 positively stained cells or areas of the extracellular matrix. Staining of CGS-1 was scored on a scale from 0 to 3. RESULTS: Fourteen of 15 neovascular membranes stained strongly with CGS-1 (score 2 or 3). One membrane from a patient with pathologic myopia was negatively stained (score 0). CGS-1 positive staining was detected around endothelial cells and in the extracellular matrix of CNVMs. The retina of eyes without choroidal neovascularization was negative with CGS-1 in all eight donor eyes, while the choroid contained some weakly CGS-1 positive cells (score 0 and 1, respectively). CONCLUSIONS: The extradomain B is abundantly expressed in CNVMs, but its expression is more restricted in eyes harboring no apparent choroidal neovascularization. In the future, B-FN might serve as a target for the delivery of antibody-photosensitizer immunoconjugates to newly developed vessels to enhance the selectivity of photodynamic therapy.

Adult↗

Tissue plasminogen activator-assisted surgical excision of subfoveal choroidal neovascularization in age-related macular degeneration: a randomized, double-masked trial.

OBJECTIVE: To determine whether lysing subretinal fibrin with tissue plasminogen activator (t-PA) before excising subfoveal choroidal neovascularization improves visual acuity in patients with age-related macular degeneration. DESIGN: Randomized, double-masked trial. PARTICIPANTS: Eighty eyes of 80 patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration were studied. INTERVENTION: Each eye underwent pars plana vitrectomy and received a subretinal injection of t-PA or balanced salt solution (BSS) before the neovascular membrane was excised. Preoperative and postoperative protocol refraction, ophthalmic examination, color photography, and fluorescein angiography were performed in all 80 eyes. MAIN OUTCOME MEASURES: Visual acuity and fluorescein angiographic evidence of leakage after 1 year. RESULTS: Visual acuity did not differ between the t-PA group (n = 40) and the BSS group (n = 40), and median best-corrected visual acuity was 20/320 for both groups (P = 0.38). Changes in visual acuity from baseline were also equal, with a median loss of 1 line in each group (P = 0.78). Patients whose initial visual acuity was 20/250 or less were more likely to improve by 2 or more lines (P = 0.01) and less likely to lose 2 or more lines (P < 0.001). Patients with choroidal neovascularization of at least 4 disc areas were more likely to improve by 2 or more lines (P = 0.02) and less likely to lose 2 or more lines (P < 0.001). After 1 year, choroidal neovascularization was present in seven of the t-PA eyes and in eight of the BSS eyes (P = 0.78). CONCLUSIONS: With current surgical techniques, the use of t-PA before surgical excision of subfoveal choroidal neovascularization is of no visual or anatomic benefit to patients with age-related macular degeneration.

Aged↗