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Consequences of verteporfin photodynamic therapy on choroidal neovascular membranes.

OBJECTIVE: To examine the impact of photodynamic therapy (PDT) on angiogenesis in human choroidal neovascular membranes with respect to vascular endothelial growth factor (VEGF) expression, proliferation, and vascularization. METHODS: Retrospective review of an interventional case series of 50 patients (50 eyes) who underwent removal of choroidal neovascular membranes. Choroidal neovascularization was secondary to age-related macular degeneration. Twenty patients were treated with PDT 3 to 655 days before surgery. Choroidal neovascular membranes were stained for CD34, CD105, Ki-67, cytokeratin 18, and VEGF. Thirty choroidal neovascular membranes secondary to age-related macular degeneration without previous treatment were used as controls. RESULTS: Specimens without pretreatment disclosed varying degrees of vascularization, proliferative activity, and VEGF expression by different cells. Specimens treated with PDT 3 days earlier showed mostly occluded vessels, damaged endothelial cells, and low proliferative activity. In contrast, specimens excised at later time points after PDT were highly vascularized and proliferating. This chronology was associated with an impressive VEGF immunoreactivity unique to retinal pigment epithelial cells shortly after PDT that also shifted to other cells at later time points. CONCLUSIONS: Photodynamic therapy induces selective vascular damage in choroidal neovascular membranes. The effectiveness and selectivity of this treatment, however, seem to be jeopardized by a rebound effect initiated by enhanced VEGF expression in retinal pigment epithelial cells.

Aged↗

Laser photocoagulation of choroidal neovascularization in angioid streaks.

PURPOSE: To determine if laser photocoagulation of macular choroidal neovascularization in angioid streaks may be effective in preventing severe loss of vision. METHODS: Sixty-six consecutive eyes of 52 patients with extrafoveal, well-defined choroidal neovascularization secondary to angioid streaks who underwent direct laser photocoagulation were followed for 3-108 months (mean, 34.5 months; median, 20 months). RESULTS: Pretreatment mean visual acuity was 20/40 (range, 20/200-20/20), postlaser outcome was a visual acuity of 20/50 at 3 months, 20/50 at 6 months, 20/80 at 1 year, 20/80 at 2 years, 20/100 at 3 years, 20/125 at 4 years, 20/125 at 5 years, 20/100 at 6 years, and 20/80 at 7 years. During the first year after treatment there was a significant decrease in visual acuity (P < 0.01), but no significant change thereafter. Choroidal neovascularization recurred one or more times in 77% of the eyes, but by the final examination choroidal neovascularization had been eliminated completely in 31 eyes (47%). Fellow eyes with naturally progressed choroidal neovascularization were considered control eyes. Final visual acuity in treated eyes was definitely better than that in untreated eyes (P < 0.01). CONCLUSIONS: This is the largest series of eyes treated by laser photocoagulation for angioid streaks and choroidal neovascularization ever reported. Laser photocoagulation of choroidal neovascularization in angioid streaks may end the choroidal neovascularization and help stabilize visual acuity or slow down visual loss. Considering the very high frequency of recurrences (77% of the eyes studied), an intense clinical and fluorangiographic follow-up period is strongly recommended, mainly for the first 3 months after treatment.

Adult↗

Scanning laser ophthalmoscope fundus perimetry after surgery for choroidal neovascularization.

PURPOSE: Submacular surgery is under investigation for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration, ocular histoplasmosis syndrome, and other causes. The aims of this study were to determine whether the macular area from which choroidal neovascularization was removed surgically remained functional and whether there was any qualitative difference between eyes with different disease conditions or between eyes of younger and older patients. METHODS: Our study included 19 patients (19 eyes) with choroidal neovascularization, seven cases caused by age-related macular degeneration and 12 caused by ocular histoplasmosis syndrome, pathologic myopia, or idiopathic causes. All tests were performed at least 6 months after surgical removal of choroidal neovascularization. All patients underwent fundus perimetry with the scanning laser ophthalmoscope for evaluation of dense and relative scotomas and fixation site. RESULTS: After submacular surgery in 19 patients, 10 patients (one with age-related macular degeneration and nine with pathologic myopia, ocular histoplasmosis syndrome, or an idiopathic cause of choroidal neovascularization) fixated within an area that ophthalmoscopically and angiographically was an area of retinal pigment epithelial disturbance occupied by choroidal neovascularization preoperatively. Of 12 patients without age-related macular degeneration, seven of eight patients younger than 50 years of age compared with two of four patients 50 years or older fixated within the area of retinal pigment epithelial disturbance. CONCLUSIONS: Our data suggest that in patients without age-related macular degeneration who undergo submacular surgery, the surgically disturbed area previously occupied by choroidal neovascularization can remain functional postoperatively. Furthermore, occasionally a patient with age-related macular degeneration undergoing submacular surgery still can fixate in the area from which the choroidal neovascularization was removed.

Adolescent↗

[Occurrence of choroidal neovascularization following photocoagulation treatment for central serous retinopathy].

Occurrence of choroidal neovascularization following laser photocoagulation treatment for central serous retinopathy (CSR) has been reported. We reviewed all the cases of photocoagulation treatment for CSR in our clinic during the past 25 years (1968-1993). Among 1,824 CSR-affected eyes which were treated, choroidal neovascularization occurred in 19 at the site of photocoagulation. In a careful reevaluation of pretreatment fluorescein angiograms, small choroidal neovascularizations were detected in 5 eyes, in which cases the diagnosis of CSR was incorrect. In 3 eyes, choroidal neovascularization was suspected and might have been masked. In the remaining 11 eyes, choroidal neovascularization was not seen. Our survey indicates that, in central serous retinopathy, when the age of the patient is over 50 years, and leakage is weak and parafoveal, choroidal neovascularization may be masked. Laser photocoagulation for these eyes should be conservative with careful, long-term observation.

Adult↗

Experimental studies of indocyanine green dye-enhanced photocoagulation of choroidal neovascularization feeder vessels.

PURPOSE: To report a model of choroidal neovascularization feeder vessels that reconciles current histologic, angiographic, and clinical data, and to report experimental studies that investigate the potential of indocyanine-green-dye-enhanced photocoagulation to improve feeder-vessel treatment. METHODS: A model of choroidal neovascularization feeder vessels was conceived to account for current histologic and angiographic data. Based on that model, experimental studies of the efficacy of indocyanine green-dye-enhanced photocoagulation were performed, using pigmented rabbit eyes as a model system. A Zeiss fundus camera was modified to permit visualization of choroidal blood flow by high-speed indocyanine green angiography and to permit simultaneous delivery of 810-nm-wavelength diode laser photocoagulation pulses to specific choroidal vascular targets during indocyanine green-dye bolus transit. RESULTS: Choroidal neovascularization feeder vessels appear to originate in the Sattler layer (that is, that portion of the choroidal vasculature consisting of medium-diameter vessels) and enter the choriocapillaris in close proximity to the small capillary-like vessels that penetrate Bruch membrane and communicate with the choroidal neovascularization. The rabbit eye experiments demonstrated that the presence of high indocyanine green dye concentration in circulating blood enhances uptake of near-infrared laser energy (three eyes); injection of sequential indocyanine green dye boluses results in gradually decreased efficiency of dye-enhanced photocoagulation (two eyes); and by application of laser energy during the initial transit of small-volume, high-concentration indocyanine green dye boluses, dye-enhanced photocoagulation of large diameter choroidal arteries can be accomplished with relatively little concomitant retinal tissue damage (three eyes). CONCLUSIONS: Although future trials will be necessary to substantiate these initial findings in the clinical arena, it appears that the efficiency of choroidal neovascularization feeder-vessel photocoagulation may be enhanced, while minimizing concomitant damage to overlying retinal tissue, by delivery of 810-nm wavelength laser energy immediately upon arrival of a high-concentration indocyanine green dye bolus in a targeted feeder vessel. However, molecules of dye adhering to vessel walls or lying in tissue interstitial spaces appear to divert laser energy from the photocoagulation process, so efficiency of indocyanine green dye-enhanced photocoagulation gradually diminishes as the number of injected dye boluses increases.

Animals↗

Atypical choroidal neovascularization in radiation retinopathy.

PURPOSE: To report atypical choroidal neovascularization associated with radiation retinopathy. DESIGN: Case report. METHODS: The patient was examined with ophthalmoscopy, fluorescein angiography, and indocyanine green angiography. RESULTS: A 32-year-old woman presented with an accelerated course of radiation retinopathy with macular edema, capillary telangiectasis, subretinal fluid, and lipid during and after pregnancy. Indocyanine green, but not fluorescein angiography, demonstrated an unusual area of choroidal neovascularization with prominent saccular dilations adjacent to a large zone of poor choroidal perfusion. Laser photocoagulation of the choroidal neovascularization resulted in an angiographic closure with absorption of the subretinal fluid and improvement of visual acuity. CONCLUSIONS: Choroidal neovascularization may be associated with radiation retinopathy and, when present, may require indocyanine green angiography for its diagnosis.

Adult↗

Expression of transforming growth factor-beta receptors in normal rat retina and experimental choroidal neovascularization.

PURPOSE: Transforming growth factor-beta (TGF-beta) plays an important role in the development of choroidal neovascularization. TGF-beta transduces signals through the mediation of type I and type II receptors. We investigated the expression of TGF-beta receptors in a normal rat retina and a model of experimentally induced choroidal neovascularization. METHODS: Choroidal neovascularization was induced by laser photocoagulation in rat eyes. The expression of TGF-beta receptors was determined using immunohistochemical and in situ hybridization methods. RESULTS: In normal adult rat retinas, immunoreactivity and mRNA expression of TGF-beta receptor type I (TbetaRI) and TGF-beta receptor type II (TbetaRII) were found in the ganglion cells. During the process of neovascularization, immunoreactivity and mRNA expression of TbetaRI and TbetaRII were widely distributed in laser lesions soon after photocoagulation; thereafter, these receptors were specifically detected in the endothelial cells of choroidal neovascularization. CONCLUSIONS: The expression of TGF-beta receptors in normal rat retinas suggests that TGF-beta plays an important role in the homeostasis of normal retina. The upregulation of TGF-beta receptors in choroidal neovascularization strongly suggests that TGF-beta is most likely transduced through specific receptors and plays an important role in the development of choroidal neovascularization.

Animals↗

Clinicopathological correlation in exudative age-related macular degeneration: recurrent choroidal neovascularization.

PURPOSE: To report the pathology of surgically removed submacular tissue in recurrent choroidal neovascularization after laser photocoagulation of classic choroidal neovascularization in age-related macular degeneration. METHODS: A recurrent subfoveal choroidal neovascular membrane was surgically removed in two patients. The recurrence was identified as a classic membrane on fluorescein angiography at the foveal border of the laser scar. A net was visualized in the early venous phase of the indocyanine green angiogram, with associated late hyperfluorescence. Both patients had undergone laser photocoagulation for a classic interpapillomacular choroidal neovascular membrane about 1 1/2 years earlier. The specimens were serially sectioned and stained with hematoxylin-eosin, periodic acid-Schiff, Masson trichrome and phosphotungstic acid-hematoxylin. RESULTS: The two specimens consisted of subretinal fibrovascular tissue with fibrin exudation. Fibrovascular tissue bordered subretinal fibrous tissue adherent to Bruch's membrane and remnants of the choroid in one patient. The fibrovascular portion most likely corresponded to the recurrence, whereas the fibrous portion represented the original membrane, being obliterated after photocoagulation. Some peripapillary tissue was additionally removed in the other patient. The latter lesion was invisible on fluorescein angiography but stained in the late phase of indocyanine green angiography and corresponded histopathologically to poorly vascularized intra-Bruch's fibrovascular tissue. Granular deposits, periodic acid-Schiff positive and metachromatically purple on Masson trichrome stain, representing diffuse drusen (basal laminar/linear deposits), were identified in the three specimens. CONCLUSION: A subretinal fibrovascular membrane corresponded with the classic recurrent choroidal neovascularization.

Aged↗

Choroidal neovascularization in younger patients.

Choroidal neovascularization (CNV) is the most common cause of legal blindness in older adults in the United States. The most common cause for CNV in this age group is age-related macular degeneration, a condition manifesting with drusen (particularly soft drusen) and pigmentary alterations in the macular region. CNV can occur in younger people (< 50 years), who usually do not have conspicuous drusen or pigmentary abnormalities. In this age group CNV may occur as a secondary manifestation of many inherited and acquired conditions such as angioid streaks, high myopia, trauma, choroidal tumors, familial macular dystrophies, and inflammatory retinochoroidopathies. Occasionally, CNV in young people has no apparent antecedent cause, and these cases are termed "idiopathic CNV." This review examines the common reasons for CNV in young adults, with reference to some of the older literature as well as to recently published papers.

Adult↗

Selective use of indocyanine green angiography for occult choroidal neovascularization.

PURPOSE: Indocyanine green angiography is useful in situations where fluorescein angiography shows occult choroidal neovascularization or pigment epithelial detachment. We sought to determine how often the selective application of indocyanine green angiography results in useful information for eyes with occult choroidal neovascularization. METHODS: We reviewed 153 consecutive indocyanine green angiograms and identified 77 in which corresponding fluorescein angiograms showed occult choroidal neovascularization or pigment epithelial detachment. We examined the indocyanine green angiograms to detect areas of hyperfluorescence and to classify the margins of hyperfluorescence as well demarcated or poorly demarcated. RESULTS: Of 77 eyes, 42 (55%) eyes had occult choroidal neovascularization by fluorescein angiography, seven (9%) eyes had both classic and occult choroidal neovascularization by fluorescein angiography, and 28 (36%) eyes had pigment epithelial detachments. Of 42 eyes with occult choroidal neovascularization by fluorescein angiography, 21 (50%) had well-demarcated margins, 13 (31%) had poorly demarcated margins, and eight (19%) had no detectable hyperfluorescence by indocyanine green angiography. Of seven eyes with both classic and occult choroidal neovascularization by fluorescein angiography, two had both poorly demarcated and well-demarcated borders, two had only poorly demarcated borders, and three had well-demarcated borders by indocyanine green. The indocyanine green angiogram showed 23 (82%) of 28 pigment epithelial detachments to have well-demarcated borders of hyperfluorescence; 13 (57%) of 23 were treated. CONCLUSION: Indocyanine green angiography adds clinically useful information to fluorescein angiography by demonstrating well-demarcated areas of hyperfluorescence in 50% of eyes selected because of diagnosis of occult choroidal neovascularization and in 82% of eyes selected because of pigment epithelial detachment.

Choroid↗

Comparison of 2D reconstructions of surgically excised subfoveal choroidal neovascularization with fluorescein angiographic features: SST report No. 15.

OBJECTIVES: To compare topographic features of surgically excised subfoveal choroidal neovascularization with preoperative and postoperative fluorescein angiographic features from Submacular Surgery Trials (SST) patients, and to compare histological and angiographic features with preoperative and postoperative visual acuities (VAs). METHODS: Patients enrolled in the SST Groups N, B, and H trials between October 1999 and September 2001 and assigned to the surgery arm had surgically removed choroidal neovascularization sent to the SST Pathology Center. Grossly intact specimens were sectioned serially for 2-dimensional reconstruction and were assigned to growth pattern groups based on topographic mapping of the location of cellular components relative to the retinal pigment epithelium (RPE): sub-RPE, subretinal, combined, or indeterminate. These features were compared with preoperative fluorescein angiographic features. The histological choroidal neovascularization growth pattern was compared with preoperative VAs. RESULTS: Two-dimensional reconstructions of surgically excised choroidal neovascularization could not be matched point for point to fluorescein angiographic features. Among the 52 specimens selected, the growth pattern could be determined by 2-dimensional reconstruction in 34 instances (65%), including 28 (80%) of 35 Group N specimens, 2 (40%) of 5 Group B specimens, and 4 (33%) of 12 Group H specimens. Among the choroidal neovascularization growth patterns that could be determined from specimens submitted, the majority of Group N specimens were combined, and the majority of Group H specimens were subretinal. In most instances for Group B specimens, the growth pattern was indeterminate. The postoperative abnormalities on fluorescein angiography were generally larger than measurements of excised specimens. The subretinal growth pattern was associated with the smallest decrease in 3-month postoperative average VA. CONCLUSIONS: Among the 52 specimens from the SST with adequate tissue to try to evaluate the growth pattern of the neovascular lesion, 34 had patterns that could be determined. The subretinal growth pattern tended to correspond with lesions that were classic choroidal neovascularization without occult choroidal neovascularization on fluorescein angiography. The most favorable visual outcome occurred if the choroidal neovascularization had a subretinal growth pattern. The combined growth pattern tended to correspond with lesions on fluorescein angiography that had both classic choroidal neovascularization and occult choroidal neovascularization. The conclusions must be viewed within the context that 18 (35%) of the 52 participants could not be characterized for histologic growth pattern.

Adult↗

Correlation of CD105 and vascular endothelial growth factor in laser-induced choroidal neovascularization in rats.

PURPOSE: Choroidal neovascularization (CNV) plays an important role in pathogenesis of age-related macular degeneration (AMD), ocular histoplasmosis syndrome (OHS) and so on. However, mechanisms of CNV formation are not fully understood. The aim of this study is to investigate the correlation between expressions of CD105 and vascular endothelial growth factor (VEGF) in experimental laser-induced CNV in rats. METHODS: CNV model was established by 532 nm laser photocoagulation in Brown-Norway rats. The expression of CD105 and VEGF in CNV was observed by immunohistochemistry at 3, 7, 14, 21, 28 and 56 days after laser photocoagulation. The image analysis was performed with the professional software of Image-Pro Plus. RESULTS: Fluorescein angiography showed fluorescein leakage in CNV from days 7 to 56 after photocoagulation. VEGF expression was mainly observed in vascular endothelial cells, ganglion cells, inner nuclear layers and retinal pigment epithelial cells in normal retina and vascular endothelial cells in normal choroid of the rats. On day 3 after photocoagulation, VEGF began to express in laser-induced lesions. VEGF was strongly expressed in CNV after 7 days (P < 0.05) and decreased after 14 days (P > 0.05). CD105 was initially presented in CNV at 7 days and obviously expressed at 14 days after photocoagulation (P < 0.05). Four weeks later, when angiogenesis tended toward inactive status, expression of CD105 was markedly decreased (P>0.05). There was notablely direct correlation between CD105-positive-microvessel density and positively semiquantitative scoring of VEGF in the CNV (r = 0.989, P < 0.01). CONCLUSIONS: There is direct correlation between the expression of CD105 and VEGF in the laser-induced CNV in rat. It suggests that CD105 and VEGF might participate in the new blood vessel formation and promote the growth of CNV.

Animals↗

Choroidal neovascularization.

PURPOSE: To review clinicopathologic findings of choroidal neovascularization (CNV) in a historical framework with emphasis on pathobiology and correlation with treatment. DESIGN: Selective literature review combined with authors' experience. RESULTS: Choroidal neovascularization represents a stereotypic, nonspecific response to a specific stimulus. Although CNV differs among patients, the general growth patterns are subretinal pigment epithelium (type 1), subretinal (type 2), or combined. Choroidal neovascularization occurs over time in dynamic stages of initiation, active and involutional. Treatments are now being designed based on modern understanding of CNV growth. CONCLUSIONS: Progress continues to be made concerning understanding the pathobiology and treatment of CNV.

Choroidal Neovascularization↗

Oral fluorescein angiography in patients with choroidal neovascularization and macular degeneration.

OBJECTIVE: To evaluate image quality of oral fluorescein angiography in patients with age-related macular degeneration and choroidal neovascularization. MATERIALS AND METHODS: Twenty four patients with proven choroidal neovascularization were examined in a prospective observational case series. Confocal oral and intravenous fluorescein angiography were performed using the Heidelberg Retina Angiograph. Oral and intravenous image quality were compared in a masked fashion. RESULTS: Choroidal neovascularization could be diagnosed in all patients using intravenous angiograms. Oral fluorescein angiography accurately detected the presence or absence of choroidal neovascularization in all patients and could determine the classification of choroidal neovascularization, location, and extent and borders in 20 (83.3%) of 24 patients. Early, mid, and late phases of oral angiograms occurred at 8, 15, and 26 minutes, respectively. CONCLUSION: Oral fluorescein angiography using the confocal Heidelberg Retina Angiograph allowed detection of choroidal neovascularization in all patients in this study. Visualization of extent and type of choroidal neovascularization was possible in most eyes with choroidal neovascularization. These findings suggest oral angiography is an excellent screening tool for choroidal neovascularization and allows guidance of treatment in the majority of cases.

Administration, Oral↗

Subretinal endophotocoagulation in the treatment of choroidal neovascularization.

The development of subfoveal choroidal neovascularization is a major cause of visual loss in age-related macular degeneration and other disorders of the retinal pigment epithelium-Bruch's membrane complex. We designed a new subretinal laser delivery system and used it to treat subfoveal neovascular membranes in three eyes with age-related macular degeneration. Preoperative visual acuities were 20/200, 20/80, and 20/300, respectively. With a mean follow-up of seven months, postoperative visual acuities were 20/80, 20/400, and 20/300, respectively. One eye developed recurrent neovascularization, which was adequately treated with slit lamp-delivered laser photocoagulation. Another eye continued to lose visual acuity because of progressive atrophy of the retinal pigment epithelium. Although ablation of choroidal neovascular membranes was possible with this technique, visual results were disappointing, probably because of damage of the underlying retinal pigment epithelium and choriocapillaris.

Aged↗

Theoretical investigation of the role of choriocapillaris blood flow in treatment of subfoveal choroidal neovascularization associated with age-related macular degeneration.

PURPOSE: To investigate the relationship between choriocapillaris blood flow and blood flow through an overlying choroidal neovascularization, as it relates to photocoagulation-induced changes in the choriocapillaris circulation. METHODS: A theoretical model that simulates the blood flow in the choriocapillaris and choroidal neovascularization of the human eye was developed, based on histologically determined vascular geometry and experimentally measured blood pressure gradients. The choriocapillaris blood pressure and blood flow were examined before and after simulated photocoagulation of various Sattler layer vessels entering the choriocapillaris in the vicinity of the choroidal neovascularization. (The Sattler layer is the inner layer of medium-sized choroidal vessels that includes both arterioles and venules that supply the choriocapillaris.) RESULTS: The theoretical model showed that both partial and complete occlusion of either Sattler arteriole or venous vessels in the vicinity of the capillary-like vessels connecting a choroidal neovascularization to the underlying choriocapillaris results in significant choroidal neovascularization blood flow reduction. These theoretical results are similar to clinically observed changes induced by laser photocoagulation of feeder vessels. (In this discussion, the term "feeder vessels" refers to those vessels in an indocyanine green angiogram image that appear to supply blood to a choroidal neovascularization; these vessels appear to be Sattler layer vessels, rather than the histologically demonstrated short, capillary-like vessels that form choriocapillaris-choroidal neovascularization communications.) CONCLUSIONS: Reduction of choriocapillaris blood flow underlying a choroidal neovascularization may be sufficient to reduce the blood flow rate in the choroidal neovascularization and thereby reduce the associated retinal edema. The results also suggest that reduction of choriocapillaris blood flow may be the common hemodynamic event associated with the successful application of several currently practiced methods of choroidal neovascularization treatment, including feeder vessel photocoagulation, photodynamic therapy, transpupillary thermotherapy, and prophylactic drusen photocoagulation. Ultimately, this model may be useful in determining optimal placement of laser photocoagulation burns to achieve a desirable perturbation in choroidal blood flow distribution and thereby reduce choroidal neovascularization blood flow to the extent necessary to obliterate associated retinal edema.

Blood Flow Velocity↗

A role for connective tissue growth factor in the pathogenesis of choroidal neovascularization.

OBJECTIVE: To evaluate the expression of connective tissue growth factor (CTGF) in choroidal neovascular membranes from patients with age-related macular degeneration and the effect of CTGF on choroidal endothelial cell (CEC) function. METHODS: Using immunohistochemical methods, we analyzed CTGF expression in 13 surgically excised choroidal neovascular membranes related to age-related macular degeneration. The expression of CTGF in retinal pigment epithelial and CEC cultures was determined by means of reverse transcriptase polymerase chain reaction and Western blot, and its regulation by vascular endothelial growth factor and transforming growth factor beta was determined. The effects of CTGF on bovine CEC proliferation, attachment, migration, and tube formation were measured. RESULTS: Vascularized human choroidal neovascular membranes showed strong CTGF immunoreactivity. Double staining disclosed colocalization of CTGF with retinal pigment epithelial cells and CECs. The CTGF induced a significant increase in attachment and migration of CECs; however, it did not stimulate CEC proliferation. The CTGF protein was up-regulated in retinal pigment epithelial cells and CECs by stimulation with transforming growth factor beta and vascular endothelial growth factor, respectively. CONCLUSIONS: The expression of CTGF in choroidal neovascular membranes, its regulation by angiogenic growth factors, and its proangiogenic effects on CEC function suggest that CTGF may play a role in the pathogenesis of choroidal neovascularization. Clinical Relevance Multiple growth factors are involved in the pathogenesis of choroidal neovascularization in age-related macular degeneration.

Aged↗

Targeted disruption of the FGF2 gene does not prevent choroidal neovascularization in a murine model.

Choroidal neovascularization (CNV) is the major cause of severe visual loss in patients with age-related macular degeneration. Laser treatment is helpful for a minority of patients with CNV, and development of new treatments is hampered by a poor understanding of the molecular signals involved. Several lines of evidence have suggested that basic fibroblast growth factor (FGF2) plays a role in stimulating CNV. In this study, we tested this hypothesis using mice with targeted disruption of the FGF2 gene in a newly developed murine model of laser-induced CNV. One week after krypton laser photocoagulation in C57BL/6J mice, 34 of 60 burns (57%) showed fluorescein leakage and 13 of 16 (81%) showed histopathological evidence of CNV. At 2 weeks, CNV was detected in 9 of 10 burns (90%) in which a bubble had been observed at the time of the laser treatment. Electron microscopy showed fenestrated vessels with large lumens within choroidal neovascular lesions. Two weeks after laser-induced rupture of Bruch's membrane, 27 of 36 burns (75%) contained CNV in FGF2-deficient mice compared with 26 of 30 (87%) in wild-type control mice, a difference that is not statistically significant. This study demonstrates that FGF2 is not required for the development of CNV after laser-induced rupture of Bruch's membrane and provides a new model to investigate molecular mechanisms and anti-angiogenic therapy in CNV.

Animals↗