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PubMed2001

Topical application of integrin antagonists inhibits proliferative retinopathy.

The expression of alphav-integrins is highly selective for angiogenic endothelial cells; ligation inhibition by cyclic RGD peptides prevents pathological neovascularization in tumor or retinopathy models to a large extent. We have previously demonstrated that proliferative retinopathy in a mouse model of retinopathy of prematurity (ROP model) can be reduced by more than 70%. To minimize systemic side effects and unwanted interference with responsive angiogenesis, we investigated topical application of cyclic RGD-peptides. In preliminary experiments, we could exclude any inhibiting effects of the carrier solution containing EDTA, Na2S, mannitol, hydroxyethyl starch, and benzalconium chloride on the inhibitory effect of cyclic RGD peptides. Retinal presence of small molecular-mass integrin antagonists after topical application was confirmed using fluorescein-labeled cyclic RGD peptide. Topical application of the peptide to the eye inhibited proliferative retinopathy in a dose-dependent fashion with a maximum of almost 50%. These results suggest that small molecular-mass peptide antagonists of alphav-type integrins are efficient in inhibiting proliferative retinopathy by topical application.

Adhesiveness↗
PubMed1998

Vascular endothelial growth factor (VEGF) in endometriosis.

Angiogenesis is likely to be involved in the pathogenesis of endometriosis. According to the transplantation theory, when the exfoliated endometrium is attached to the peritoneal layer, the establishment of a new blood supply is essential for the survival of the endometrial implant and development of endometriosis. From the known angiogenic factors, vascular endothelial growth factor (VEGF) has emerged as a pivotally important regulator of normal angiogenesis and pathological neovascularization. The VEGF protein was evaluated immunohistochemically in the eutopic endometrium of 10 women without endometriosis (group I) at laparoscopy and the eutopic endometrium and peritoneal endometriotic lesions of 43 women with endometriosis (group II). VEGF histological scores were 9.7 +/- 4.3 and 4.0 +/- 2.6 respectively in the epithelium and stroma of the eutopic endometrium of group I women, and 10.3 +/- 2.3 and 3.6 +/- 2.3 respectively in women of group II. In red lesions, the VEGF scores were 11.1 +/- 3.0 in the epithelium and 5.1 +/- 3.0 in the stroma, and in black lesions were 8.6 +/- 2.7 and 1.6 +/- 1.6, respectively. Significantly lower values were observed in black lesions as compared with eutopic endometrium and red lesions, the values of which were similar. Scores were also evaluated according to the phase of the cycle. In eutopic as well as ectopic endometrium, no significant cyclic variations were observed throughout the cycle. However, VEGF content was found to be higher in the eutopic glandular epithelium of women with endometriosis during the late secretory phase, possibly suggesting a more likely tendency to implant. In contrast, significantly higher VEGF content was noted in red lesions as compared with black lesions. During all phases of the cycle, the VEGF content in stromal cells of red lesions was higher than in black lesions. Similarities in VEGF content were observed in the glandular epithelium of the eutopic endometrium of women with endometriosis and red lesions, suggesting that endometriosis probably arises from the peritoneal seeding of viable endometrial cells during retrograde menstruation and that red lesions can be considered as the first stage of implantation. After the attachment phase, the high VEGF levels could provoke an increase in the subperitoneal vascular network and facilitate implantation and viability in the retroperitoneal space. Lower VEGF levels in black lesions explain the decrease in both stromal vascularization, followed by fibrosis and inactivation of the implant.

Adult↗
PubMed2004

Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates angiogenesis.

The 4A11 antigen is a unique cytokine-inducible antigen up-regulated on rheumatoid arthritis (RA) synovial endothelial cells (ECs) compared with normal ECs. Previously, we showed that in soluble form, this antigen, Lewis(y)-6/H-5-2 (Le(y)/H) or its glucose analog, 2-fucosyl lactose (H-2g), induced the expression of EC intercellular adhesion molecule-1 (ICAM-1) and leukocyte-endothelial adhesion through the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway. Currently, we show that H-2g induces release of EC angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), an effect inhibited by decoy nuclear factor kappaB (NFkappaB) oligodeoxynucleotide (ODN). JAK2 and phosphoinositide-3 kinase (PI3K) are 2 upstream kinases of NFkappaB activated by H-2g, as confirmed by an inhibitor of kappa B kinase (IKKbeta) assay. In vitro, H-2g induces vascular sprouting in the rat aortic ring model, whereas blockade of JAK2, PI3K, or NFkappaB inhibits sprouting. Likewise, in the in vivo mouse Matrigel plug angiogenesis assay, chemical inhibitors and antisense or decoy ODNs of JAK2, PI3K, or NFkappaB decrease angiogenesis, confirming the importance of these pathways in H-2g-induced EC signaling. The critical role of Le(y)/H involvement in angiogenesis and its signaling pathways may provide new targets for therapy of diseases characterized by pathologic neovascularization.

ABO Blood-Group System↗
PubMed2006

T2-TrpRS inhibits preretinal neovascularization and enhances physiological vascular regrowth in OIR as assessed by a new method of quantification.

PURPOSE: A carboxyl-terminal fragment of tryptophan tRNA synthetase (T2-TrpRS) has demonstrated potent angiostatic activity during retinal developmental neovascularization in vivo. The effects of T2-TrpRS on pathologic neovascularization were tested and compared with a potent VEGF antagonist using the mouse model of oxygen-induced retinopathy (OIR). METHODS: C57BL/6J mice were transiently exposed to hyperoxic conditions (75% O2) between postnatal day 7 (P7) and P12 and then returned to room air. Retinas were isolated, blood vessels stained with isolectin Griffonia simplicifolia, images of retinal whole-mounts acquired, and the area of vascular obliteration and extent of preretinal neovascularization quantified. This method was compared to the commonly used method of OIR quantification in which the number of pre-inner limiting membrane (ILM) nuclei is counted in serial sections of whole eyes. To assess the angiostatic activity of T2-TrpRS, mice were injected intravitreally at P12 with either T2-TrpRS, a VEGF aptamer, or vehicle (PBS) alone, and the effects on area of obliteration and on preretinal neovascular tuft formation were assessed. RESULTS: Using a modified method of quantification in the mouse OIR model based on images of isolectin-stained retinal wholemounts, we were able to assess reliably and consistently both vascular obliteration and preretinal neovascular tuft formation in the same specimen. T2-TrpRS demonstrated potent angiostatic activity, reducing the appearance of pathologic neovascular tufts by up to 90%. Surprisingly, T2-TrpRS also enhanced physiological revascularization of the obliterated retinal vasculature, reducing these areas by up to 60% compared with PBS-injected eyes. In contrast, the VEGF antagonist, while similarly reducing preretinal neovascular tuft formation, did not enhance revascularization of the obliterated areas. CONCLUSIONS: Use of a rapid, quantifiable method to assess the effect of T2-TrpRS on retinal angiogenesis in the OIR model demonstrates the importance of a quantification system that permits simultaneous analysis of a drug's effect on vascular obliteration as well as on preretinal neovascularization. The results obtained using this method suggest enhanced clinical value for compounds such as T2-TrpRS that not only inhibit pathologic neovascularization, but also facilitate physiological revascularization of ischemic tissue.

Angiostatic Proteins↗
PubMed2006

Twofold illumination photodynamic therapy scheme for subfoveal choroidal neovascularization in pathologic myopia: results from a randomized pilot study.

PURPOSE: To compare the short-term efficacy and safety of standard verteporfin photodynamic therapy (PDT) to modified PDT regimen using a twofold illumination scheme for treating choroidal neovascularization in pathologic myopia. METHODS: Randomized active-controlled clinical trial including 16 patients with subfoveal choroidal neovascularization caused by pathologic myopia and best-corrected visual acuity (BCVA) of 20/320 or better. Patients were randomly assigned (1:1) to standard PDT regimen (50 J/cm; n=8) or twofold illumination PDT scheme (50+50 J/cm; n=8). Comprehensive ophthalmic evaluation including fluorescein angiography was performed at baseline and at weeks 1, 12+/-2, and 24+/-2 following treatment. At week 12 follow-up examination, an additional treatment session with either standard or modified PDT regimens (as assigned at baseline) was applied to areas of fluorescein leakage if present. Changes in BCVA, retreatment rate, and incidence of adverse events were evaluated. RESULTS: All patients completed the 24-week study period. Baseline median BCVA was 20/100 and 20/100 for patients assigned to standard and modified PDT regimens, respectively. At week 24, median improvement in BCVA was significantly greater in patients submitted to twofold illumination PDT scheme (P=0.005; Mann-Whitney U test). Median change from baseline in BCVA (ETDRS lines) was +1.8 (P<0.05; Wilcoxon signed-rank test), +0.4, and +0.5 lines for patients submitted to standard PDT regimen, and +1.8 (P<0.05; Wilcoxon signed-rank test), +1.9 (P<0.05; Wilcoxon signed-rank test), and +2.4 (P<0.05; Wilcoxon signed-rank test) lines for patients submitted to twofold illumination PDT scheme at week 1, 12, and 24 follow-up examinations, respectively. An additional PDT session was performed in 7/8 patients assigned to standard PDT regimen, and in 4/8 patients assigned to modified PDT (P=0.28; Fisher exact test). No PDT-related complications were observed. CONCLUSION: Although the number of patients and length of follow-up in this study was limited, a better visual outcome and diminished retreatment rate were observed in patients assigned to twofold illumination PDT scheme in comparison to those submitted to standard PDT regimen. Larger studies with longer follow-up to look at twofold illumination PDT scheme versus standard one to confirm our preliminary results are warranted.

Adult↗
PubMed2003

Photodynamic therapy of subfoveal recurrences after laser photocoagulation of extrafoveal choroidal neovascularization in pathologic myopia.

BACKGROUND: Photodynamic therapy with verteporfin (Visudyne; Novartis, Bülach, Switzerland) has been proposed for the treatment of subfoveal choroidal neovascularization secondary to pathologic myopia. We retrospectively evaluated the effects of verteporfin therapy of subfoveal recurrences of extrafoveal myopic CNV previously treated with thermal laser photocoagulation. METHODS: Twelve eyes, previously treated with thermal laser photocoagulation for extrafoveal choroidal neovascularization, received photodynamic therapy with verteporfin for subfoveal recurrence of choroidal new vessels. Thirteen eyes that did not receive photodynamic therapy served as control group. Vision and fluorescein angiography outcomes were analyzed on all study visits (every 3 months) through month 12. Visual acuity was measured in Snellen lines. RESULTS: On average, at the month 12 examination the verteporfin-treated group had gained 2 lines and the untreated group had lost 1 line of vision. Eleven eyes of the verteporfin-treated group compared with nine eyes of the untreated group lost fewer than 3 lines of vision, including four eyes versus none improving at least 1 line of vision. CONCLUSION: Photodynamic therapy with verteporfin might increase the chance of stabilizing or improving vision in patients with subfoveal recurrences of extrafoveal myopic CNV previously treated with thermal laser photocoagulation. A prospective, randomized study on larger series of patients is mandatory.

Adult↗
PubMedDate not supplied

Long-term visual outcome of choroidal neovascularization in pathologic myopia: natural history and laser treatment.

UNLABELLED: This retrospective study was designed to help clarify the visual prognosis during long-term follow-up (5-10 years) of myopic choroidal neovascularization (CNV) with and without laser treatment in a referral population. PATIENTS AND METHODS: A group of 50 consecutive non-treated eyes and a group of 50 consecutive treated eyes were selected retrospectively. Inclusion criteria were: fluorescein angiographic documentation of CNV not involving the center of the fovea, visual acuity (VA) > or = 20/200, age less than 60, onset of symptoms < or = 6 months and at least five years of follow-up. The mean decrease in VA in non-treated and treated eyes during the follow-up was analysed on the basis of subgroups with the same initial VA. RESULTS: Considering both groups (100 eyes) at presentation, 89% of CNV spared the center of the fovea but were located in the foveolar area (< 200 microns) and only 11% were extrafoveal (> or = 200 microns). In the natural history group, after five years all CNV involved the center of the fovea and mean VA was 20/160. In the treated group, at the end of the five year follow-up and after one or more laser session, 64% of eyes had a dry scar and mean VA was 20/74. Nevertheless there was a very high rate of recurrences (72%) and at the end of follow-up 36% of treated eyes had a subfoveal recurrence with a mean decrease in VA to 20/154. The difference between the mean decrease in VA of the treated and non-treated groups was statistically significant at two years. At five years (100 eyes), the difference persisted only for eyes with initial VA better than > or = 20/40 (P < 0.05). At eight years (76 eyes) and ten years (24 eyes), this difference was no longer significant. COMMENTS: This study confirms that CNV accompanying degenerative myopia has an extremely poor prognosis. Nevertheless analysis of final VA in both groups suggests that eyes with high initial VA gain more from treatment.

Adult↗
PubMed1989

[Laser treatment of subretinal macular neovascularization in pathologic myopia].

The authors evaluated retrospectively 100 eyes with pathological myopia and a macular subretinal neovascular membranes (SRNV) which was treated with direct laser photocoagulation. Argon green, krypton red and orange dye (590 nm) laser were used to treat, respectively, 19, 63 and 18 eyes. The follow-up period was of 12 months. Mean initial visual acuity was 0.33 and mean final visual acuity was 0.31, with no statistically significative difference between them. One or more recurrence was observed in 44% of the eyes. Recurrences could be treated in 80% of cases. At the end of the follow-up period SRNV had disappeared in 83 eyes and extended into the foveola in the remaining 17.

Adult↗
PubMed2006

[Treatment of subfoveal choroidal neovascularization in pathologic myopia with photodynamic therapy: outcomes at 1 and 2 years of follow-up].

PURPOSE: To evaluate the visual outcome of photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. METHODS: Retrospective and noncomparative analysis of 42 patients with CNV secondary to pathologic myopia recruited between September 2001 and 2003, who were treated with a standard regimen of photodynamic therapy with verteporfin. RESULTS: Forty-two patients were followed up for 12 months; 15 out of 42 completed 24 months of follow-up. Initial visual acuity ranged from 1/10 to 5/10 with a mean of 1.6/10. Twenty-five (56.7%) eyes had stable or improved visual acuity at 12 months with a mean of 2.5/10. In the group of patients who completed 24 months of follow-up, six eyes (39.9%) had stable or improved visual acuity with a mean of 1.6/10 at 1 year and 1.25/10 at 2 years. The average photodynamic therapy treatment required in 1 and 2 years were 1.5 and 2.1, respectively, and they are less than those reported by the Verteporfin in Photodynamic Therapy (VIP) study. CONCLUSION: Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization caused by pathologic myopia maintained a visual benefit at 1 and 2 years.

Adult↗
PubMed2005

Inhibition of pathologic retinal neovascularization by alpha-defensins.

Proliferative retinopathies, such as those complicating prematurity and diabetes, are major causes of blindness. A prominent feature of these retinopathies is excessive neovascularization, which is orchestrated by the hypoxia-induced vascular endothelial growth factor (VEGF) stimulating endothelial cells and the integrin-mediated adhesive interactions of endothelial cells with extracellular matrix components such as fibronectin (FN). Recently, we demonstrated that alpha-defensins interfere with alpha5beta1-FN interactions and dependent endothelial cell functions. Here, alpha-defensins were studied in hypoxia-induced proliferative retinopathy. In vitro, alpha-defensins specifically inhibited alpha5beta1-integrin-dependent migration of bovine retinal endothelial cells (BRECs) to FN, attenuated the VEGF-stimulated increase in endothelial permeability, and blocked BREC proliferation and capillary sprout formation in 3-dimensional fibrin-matrices. An up-regulation of beta1-integrin and FN was observed in the retinal vessels in the mouse model of hypoxia-induced retinal angiogenesis. Systemic and local administration of alpha-defensins reduced retinal neovascularization by 45% and 60%, respectively, and this effect was comparable to the inhibitory effect of alpha5beta1-blocking antibody. alpha-Defensins were detected in human diabetic retinas associated with normal retinal vessels but were absent from proliferative lesions. Together, these data show that alpha-defensins inhibit pathologic retinal neovascularization in vivo and may provide a clinically efficient strategy against proliferative retinopathies.

Animals↗
PubMed2003

Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial--VIP report no. 3.

PURPOSE: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS: Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS: Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS: Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.

Adult↗
PubMed2006

Photodynamic therapy vs limited macular translocation in the management of subfoveal choroidal neovascularization in pathologic myopia: a two-year study.

PURPOSE: To compare the results of limited macular translocation and photodynamic therapy (PDT) in subfoveal choroidal neovascularization (CNV) attributable to pathologic myopia with a 24-month follow-up. DESIGN: Retrospective analysis of nonrandomized interventional clinical study. METHODS: Retrospective review of 66 consecutive patients: 34 myopic eyes with subfoveal neovascularization treated by PDT and 32 operated on with the translocation technique. Translocation was considered principally when the lesion size was adequate (nasal inferior margin of the membrane less than half a disk diameter away from the center of the fovea) with duration of symptoms of less than four months. Main outcome measure was the postoperative change in visual acuity. RESULTS: In the translocation group, mean gain in visual acuity was greater than in the PDT group (+2.8 lines and -1.8 line, respectively, P = .001). In the translocation group, 55% of eyes gained 3 lines or more at two years compared with 10% in the PDT group. Sixty percent of eyes in the translocation group vs 40% in the PDT group had an improvement of at least five letters. Mean foveal displacement after translocation was 906 mum; postoperative complications included retinal detachment (three eyes), macular fold (one eye), and transient diplopia (four eyes). In young patients, the postoperative gain was better in both groups. In the translocation group, mean survival time for choroidal neovascularization recurrence was 40 months for patients younger than 40 years and 20 months for older patients. CONCLUSIONS: Translocation showed better results than PDT at two years. Further studies are required to confirm these findings.

Choroidal Neovascularization↗
PubMed2003

Selective occlusion of subfoveal choroidal neovascularization in pathologic myopia using a new technique of ingrowth site treatment.

PURPOSE: To evaluate the visual and angiographic effects as well as optical coherence tomography findings after a new technique of ingrowth site treatment of subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia with the use of indocyanine green (ICG)-mediated photothrombosis. DESIGN: Interventional, noncomparative case series. METHOD: In the setting of a tertiary referral center, patients with pathologic myopia in whom fluorescein and conventional ICG angiography demonstrated distinct CNV vessels supplying the subfoveal neovascular complex were submitted to focal ingrowth site treatment using a new therapeutic modality termed ICG-mediated photothrombosis. Prospective evaluation including visual acuity assessment, fluorescein and ICG angiography, and optical coherence tomography (OCT) evaluation was performed at weeks 1, 12, 24, and 48 after treatment. RESULTS: Six consecutive patients (six eyes) had treatment using a single session of ICG-mediated photothrombosis at the CNV ingrowth site. Obliteration of the entire neovascular complex was achieved immediately after treatment in all patients. At last follow-up, visual acuity improvement of 1 or more Early Treatment Diabetic Retinopathy Study lines was observed in five of six patients, and fluorescein angiography showed an absence (four eyes) or minimal leakage (two eyes) from CNV. Indocyanine green angiography demonstrated selective obliteration of the neovascular complex. Accordingly, reduction of retinal edema was observed in the OCT evaluation in all patients. There was no significant complication related to the procedure. CONCLUSIONS: The use of lower irradiances of 810- nm continuous light application and intravenous ICG infusion for neovascular ingrowth site photothrombosis induced selective CNV hypoperfusion, as demonstrated by fluorescein and ICG angiography in patients with pathologic myopia. These findings were either consistent with the visual acuity improvement observed in five of six patients or with the partial restoration of the retinal architecture seen in OCT evaluation 12 months after treatment.

Adult↗
PubMed2002

Angiogenic cytokines in cartilage tumors.

Pathologic neovascularization has been described in numerous types of cancers. The angiogenic cytokines vascular endothelial growth factor and basic fibroblast growth factor are thought to be the primary inducers of angiogenesis in these tumors. Hypoxia-inducible transcription factor is a nuclear transcription factor that promotes vascular endothelial growth factor expression. Prior studies have shown pathologic neovascularization in chondrosarcoma, which correlates with pathologic grade of the tumor. Angiogenic and nonangiogenic cartilage tumors were studied for expression of vascular endothelial growth factor, basic fibroblast growth factor and hypoxia-inducible transcription factors by immunohistochemistry and Northern blot analysis. Expression of vascular endothelial growth factor and hypoxia-inducible transcription factor were increased significantly in angiogenic tumors. Fibroblast growth factor expression was similar in angiogenic and nonangiogenic specimens. This may have implications for tumor grading and surgical decision-making, and potential treatment with antiangiogenesis chemotherapeutic agents.

Blotting, Northern↗
PubMed2001

Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial--VIP report no. 1.

OBJECTIVE: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving vision (<8 letter loss) safely in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North AMERICA: PARTICIPANTS: One hundred twenty patients with subfoveal CNV caused by pathologic myopia with a greatest linear dimension no more than 5400 microM and best-corrected visual acuity (Snellen equivalent) of approximately 20/100 or better. INTERVENTION: Patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or placebo (5% dextrose in water; n = 39) administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to give a light dose of 50 J/cm(2) to a round spot size on the retina with a diameter of 1000, microM larger than the greatest linear dimension of the choroidal neovascular lesion. At follow-up examinations every 3 months, retreatment with either verteporfin or placebo (as assigned at baseline) was applied to areas of fluorescein leakage if present. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters (approximately 1.5 lines) of visual acuity lost, adhering to an intent-to-treat analysis. RESULTS: At baseline, more than 90% of each group had evidence of classic CNV (regardless of whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the verteporfin and placebo groups, respectively, had occult CNV (regardless of whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated patients (98%) compared with 36 of the 39 placebo-treated patients (92%) completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters (P < 0.01), including 26 (32%) versus 6 (15%) improving at least five letters (>/=1 line). Seventy (86%) of the verteporfin-treated patients compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters (P = 0.01). Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment. CONCLUSIONS: Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, we recommend ophthalmologists consider verteporfin therapy for treatment of such patients.

Adult↗
PubMed1998

Lacquer cracks following laser treatment of choroidal neovascularization in pathologic myopia.

BACKGROUND: Lacquer cracks are breaks in the retinal pigment epithelial-Bruch's membrane-choriocapillaris complex and are manifestations of pathologic myopia. Progressive posterior segment elongation, uveal scleral thinning, and retinal pigment epithelial degeneration are thought to create a predisposition for crack formation in these eyes. In turn, choroidal neovascularization (CNV) may develop within the cracks to produce disciform scarring of the macula. This study examined lacquer cracks as a possible consequence of laser photocoagulation of CNV. METHODS: From the files of two retinal referral practices, five patients were located in whom lacquer cracks developed or expanded after laser photocoagulation for macular CNV in pathologic myopia. The mean age of the patients was 54.8 years. Four patients were treated with krypton red laser and one with an argon laser. Laser settings were available for only one of the patients. RESULTS: After laser photocoagulation, lacquer cracks were noted to expand in one or two directions from the laser scar between 10 days and 3 months of the treatment. The cracks also served as a pathway for progressive or recurrent neovascularization. CONCLUSIONS: Although lacquer cracks occur spontaneously in pathologic myopia, expansion, elongation, or simple development of a crack may occur as a result of laser photocoagulation of CNV. The new cracks also serve as a potential risk for recurrent neovascularization. This potential adverse complication should be considered in the management of CNV in pathologic myopia with laser treatment.

Adult↗
PubMed2006

Estimation of visual outcome without treatment in patients with subfoveal choroidal neovascularization in pathologic myopia.

OBJECTIVE: To clarify prognostic factors of long-term visual outcome without treatment in patients with myopic choroidal neovascularization (CNV) and estimate a regression equation to predict visual acuity at 5 years after CNV onset. METHODS: Fifty-four eyes of 54 consecutive patients with high myopia and subfoveal CNV who did not receive treatment were identified using clinical records from 1988 to 2004. Photodynamic therapy not approved for myopic CNV in Japan during this period. The association of best-corrected visual acuity (BCVA) at 5 years after CNV onset with patient age, refractive error, axial length, initial BCVA, myopic retinopathy grade, duration of persistent hemorrhage, CNV size at onset, and size of hemorrhage around the CNV was analyzed using Spearman's correlation and multiple linear regression analysis. RESULTS: BCVA at 5 years after onset was significantly associated with patient age, CNV size, and initial BCVA (P<0.05, Spearman's correlation). The regression equation estimating BCVA at 5 years after CNV onset was based on age and initial BCVA (R2=0.43). When subjects were divided into groups according to age (<40 and >or=40 years), CNV size, axial length and duration of persistent hemorrhage influenced BCVA at 5 years in patients under 40 years; while only initial BCVA was an influence in those at least 40 years old. CONCLUSIONS: We developed a linear predictive model to estimate BCVA at 5 years after onset of myopic CNV without treatment based on the identified prognostic factors. This information might be important for managing patients with myopic CNV.

Adult↗
PubMed1999

Pigment epithelium-derived factor: a potent inhibitor of angiogenesis.

In the absence of disease, the vasculature of the mammalian eye is quiescent, in part because of the action of angiogenic inhibitors that prevent vessels from invading the cornea and vitreous. Here, an inhibitor responsible for the avascularity of these ocular compartments is identified as pigment epithelium-derived factor (PEDF), a protein previously shown to have neurotrophic activity. The amount of inhibitory PEDF produced by retinal cells was positively correlated with oxygen concentrations, suggesting that its loss plays a permissive role in ischemia-driven retinal neovascularization. These results suggest that PEDF may be of therapeutic use, especially in retinopathies where pathological neovascularization compromises vision and leads to blindness.

Animals↗