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1. The recent ability to isolate stem cells and study their specific capacity of self-renewal with the formation of different cell types has opened up exciting vistas to help the repair of damaged tissue and even the formation of new tissue. In the present review, we deal with the characteristics and sources that stem cells can be derived and cultured from. 2. We focus on the role that stem cell-derived vascular cells or endothelial progenitor cells (EPC) may play in (re)vascularization of ischaemic and engineered tissues. This so-called vasculogenesis resembles the embryological process in which 'haemangioblasts' differentiate in blood cells, as well as in primitive vessels. Although also derived from the blood-forming bone marrow, in adult life vasculogenic stem cells contribute only little to the regular vascular repair mechanisms: namely (i) angiogenesis (outgrowth of vessels from existing vessels); and (ii) arteriogenesis (monocyte-aided increase in the calibre of existing arteriolar collaterals). 3. Most attempts to increase vascular repair by stem cells involve the use of growth factors, which mobilize stem cells from bone marrow into the blood, sometimes combined with isolation and reinfusion of these cells after ex vivo expansion and differentiation into EPC. 4. Clear improved perfusion of ischaemic sites and new vasculature has been observed in vivo mostly in animal models. Specific homing or administration of these cells and regulated and quantitative expansion and (final) differentiation at these vascular (repair) sites are less studied, but are paramount for efficacy and safety. 5. In conclusion, the use of embryonic stem cells will still encounter ethical objections. Moreover, special attention and measures are needed to cope with the allogeneic barriers that these cells usually encounter. In general, the long and complicated ex vivo cultures to obtain sufficient offspring from the very small numbers of stem cells that can be obtained as starting material will be costly and cumbersome. Both basic research on conceptual matters and cost-effective development of the product itself will have to go a long way before the clinical use of some volume can be expected.

In the pre-natal period, hemangioblasts derived from the human ventral aorta give rise to cellular elements involved in both hematopoiesis and vasculogenesis, resulting in formation of the primitive capillary network. Endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts are also present in human adult bone marrow, and can be used to induce infarct bed vasculogenesis and angiogenesis after experimental myocardial infarction. The neovascularization results in decreased apoptosis of hypertrophied myocytes in the peri-infarct region, long-term salvage and survival of viable myocardium, reduction in collagen deposition, and sustained improvement in cardiac function. Autologous angioblasts may also be useful in cellular therapy strategies aiming to regenerate myocardial tissue after established heart failure. It is likely that protocols using cardiomyocyte/mesenchymal stem cells will require balanced co-administration of angioblasts to provide vascular structures for supply of oxygen and nutrients to both the chronically ischemic, endogenous myocardium and to the newly-implanted cardiomyocytes. Future studies will need to address the timing, relative concentrations, source and route of delivery of each of these cellular populations in animal models of acute and chronic myocardial ischemia.

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.

Aortopulmonary paraganglioma is a rare tumor of the mediastinum. The only effective treatment is complete resection, which may pose a surgical challenge because of its proximity to the heart, great vessels, and trachea, often rendering a complete resection difficult to achieve. We report a case in which the tumor was excised under cardiopulmonary bypass and resulted in massive bleeding only controlled by means of packing the pleural cavity during 48 hours, known as damage control strategy. The patient survived and has been disease-free for 2 years.

Diabetic retinopathy remains one of the major causes of acquired blindness in developed nations. This is true despite the development of laser treatment, which can prevent blindness in the majority of those who develop macular oedema (ME) or proliferative diabetic retinopathy (PDR). ME is manifest by retinal vascular leakage and thickening of the retina. The hallmark of PDR is neovascularisation (NV)--abnormal angiogenesis that may ultimately cause severe vitreous cavity bleeding and/or retinal detachment. Pharmacologic therapy aimed specifically at preventing vascular leakage and NV would be a welcome addition to the armamentarium. PDR and ME could be prevented by improved metabolic control or by pharmacologically blunting the biochemical consequences of hyperglycaemia (e.g., with aldose reductase inhibitors, inhibitors of non-enzymatic glycation or by protein kinase C [PKC] inhibition). The angiogenesis in PDR could be treated via growth factor (e.g., vascular endothelial growth factor [VEGF], insulin like growth factor-1 [IGF-1]) blockade, integrin (e.g., alpha-v beta-3) blockade, extracellular matrix alteration (e.g., with steroid compounds) or interference with intracellular signal transduction pathways (e.g., PKC and mitogen activated protein kinase [MAPK] pathway proteins). Some of these antiangiogenic agents may also prove useful for treating or preventing ME. Numerous potentially useful antiangiogenic compounds are in development; two drugs are presently in clinical trials for treatment of the preproliferative stage of PDR, while two are in clinical trials for treatment of ME.

The aim of this study was to compare the efficacy of CO(2) angiography with that of iodinated contrast angiography for vascular mapping prior to partial nephrectomy for presumed renal cell carcinoma. 13 consecutive patients were studied and all patients underwent selective renal angiography using both CO(2) and iodinated contrast medium. Digitally subtracted images were acquired and compared. Seven male and six female patients, with a median age of 58 years (range 46-74 years), were examined. On comparing images the main renal artery was visualized in all cases with both contrast agents. The segmental vessels were seen in 7 of 13 CO(2) studies and 12 of 13 iodinated contrast studies. CO(2) was also inferior in the depiction of tumour circulation, showing it in 4 of 13 cases compared with 9 of 13 cases using iodinated contrast. It therefore appears that CO(2) angiography offers no diagnostic advantage and is also inferior to iodinated contrast angiography in the pre-operative vascular mapping of renal tumours.

Objective: To establish a role for vascular endothelial growth factor (VEGF) during the onset and clinical course of neovascularization of the iris (NVI) in ischemic central retinal vein occlusion., Methods: Sixteen patients with ischemic central retinal vein occlusion were followed up for 12 months by clinical examination, retinal and iris angiography, and serial anterior chamber sampling of aqueous humor. Aqueous VEGF level was determined by enzyme-linked immunoassay, and permeability changes were estimated by capillary zone electrophoretic assessment of aqueous albumin., Results: A correlation was found between aqueous VEGF concentrations and the onset, persistence, and regression of NVI; extent of retinal capillary nonperfusion; and vascular permeability. The NVI occurred when aqueous VEGF concentrations were 849 to 1569 pg/mL and regressed fully when they fell below 550 pg/mL. Aqueous concentrations of serum albumin, a marker of increased permeability, correlated with increased VEGF. Placental growth factor was found at low levels only when VEGF levels exceeded 330 pg/mL. The NVI remained VEGF-dependent during the course of the disease, regressing only if VEGF concentrations were reduced after laser ablation of hypoxic retina., Conclusions: The close temporal correlation between aqueous VEGF levels and the course of neovascularization and permeability in human ischemic central retinal vein occlusion indicates that increased aqueous VEGF level may predict the need for treatment, and that anti-VEGF therapy at an early stage of ischemic central retinal vein occlusion may be therapeutically beneficial.

Objective: To evaluate visual outcomes following macular translocation with 360 degrees peripheral retinectomy in patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration., Methods: In a prospective study, 15 consecutive patients with large subfoveal choroidal neovascularization underwent macular translocation with 360 degrees peripheral retinectomy and silicone oil tamponade. Preoperative and postoperative photographs and fluorescein angiograms were obtained to evaluate lesion size and characteristics and translocation results. Standardized near and distance visual acuity and reading speed were measured preoperatively and 6 and 12 months postoperatively., Main Outcome Measures: Changes in and final levels of near and distance visual acuity and reading speed., Results: Median lesion size was 9 Macular Photocoagulation Study disc areas (range, 4-16 disc areas). In all patients, the fovea was successfully translocated off the subfoveal lesion. The median near visual acuity logMAR score (logarithm of the minimum angle of resolution) improved significantly from 0.54 units to 0.40 units (Snellen equivalent, 20/70 to 20/50; P =.02) at the 6-month follow-up and stabilized at 0.54 (12 months postoperatively; Snellen equivalent, 20/70). Seven (54%) of 13 patients and 7 (58%) of 12 patients achieved reading speeds of 70 words/min or greater at the 6-month and 12-month postoperative visits, respectively. Median preoperative distance visual acuity (20/100) was maintained at both the 6-month and 12-month examinations. No postoperative retinal detachments occurred in this series., Conclusion: Macular translocation with 360 degrees peripheral retinectomy and silicone oil tamponade stabilizes and can sometimes improve near and distance visual acuity and reading speed in patients with vision loss from subfoveal neovascular age-related macular degeneration.

Meningioangiomatosis is regarded as a rare, benign, hamartomatous malformation. Histopathologically, the lesion is characterized by circumscribed transcortical and leptomeningeal meningovascular proliferation with focal calcifications. It may be classified into cases with predominant cellular or vascular features and may occur in association with neurofibromatosis, mostly of type 2, but sporadic cases are more frequently reported. Sporadic cases often present initially with seizures and can be treated surgically. However, a certain percentage of patients will need ongoing anticonvulsive therapy. The lesions are seldom associated with an overlying meningioma. These are usually benign lesions that must be strictly separated from an invasive anaplastic meningioma, which would warrant an adjuvant therapy. We report on a 4-year-old girl who presented with spontaneous, predominantly cellular meningioangiomatosis with associated fibrous meningioma. Focal immunopositivity of the meningioangiomatosis for CD34 was helpful in ruling out an invasive meningioma.

Surgical treatment of age-related macular degeneration has been developed since 1991 when the limitations of photocoagulation were demonstrated: it is suitable for few patients, high recurrence rate, and immediate loss of visual acuity for subfoveal membranes. This article will review the different procedures: surgical excision, macular translocation, and macular rotation. We will attempt to clarify the surgical indications, taking into account of the early results of dynamic phototherapy. However, because of the lack of comparative studies, there is no definitive consensus regarding surgery for age-related macular degeneration.

Purpose: To describe a rare manifestation of sarcoidosis., Methods: Case report of a patient with histologically proven sarcoidosis, who developed peripapillary choroidal neovascularisation in the absence of uveitis or optic nerve disease., Results: Oral corticosteroids achieved reduction in the size of the peripapillary choroidal neovascularisation. Laser treatment was effective in treating the remaining peripapillary choroidal neovascularisation, resulting in improvement of visual acuity., Conclusions: Isolated peripapillary choroidal neovascularisation is a previously unreported complication of sarcoidosis. A combination of oral corticosteroids and laser can be successful in treating this type of lesion, thereby preventing permanent visual loss.

Objective: Pulmonary arteriovenous malformations may cause progressive cyanosis after cavopulmonary anastomosis and may develop as a result of abnormal angiogenesis. We used immunohistochemistry to determine whether angiogenic proteins are increased in the lungs of children after cavopulmonary anastomosis., Methods: Lung specimens were obtained from 13 children after cavopulmonary anastomosis and from 6 control subjects. Specimens were stained with antibodies against vascular endothelial growth factor and its receptor (flk-1/KDR), basic fibroblast growth factor, alpha-smooth muscle actin, CD31, collagen IV, fibronectin, and proliferating cell nuclear antigen. Staining was graded on a scale of 0 to 3. Vessels positive for proliferating cell nuclear antigen were counted in 10 fields per specimen, and the results were averaged., Results: After cavopulmonary anastomosis, patients demonstrated increased staining for vascular endothelial growth factor (P =.03) and its receptor (P =.03) and decreased staining for CD31 (P =.004). Proliferating cell nuclear antigen staining in patients was equivalent to that for control subjects (P =.9)., Conclusions: Lung biopsy specimens from children after cavopulmonary anastomosis demonstrate increased expression of vascular endothelial growth factor and its receptor. These data confirm earlier findings that blood vessels forming after cavopulmonary anastomosis may have reduced intercellular junctions (decreased CD31 staining). Despite the increased numbers of pulmonary vessels that are present in these patients, these vessels are not highly proliferative (proliferating cell nuclear antigen staining equivalent to that of control subjects). These results suggest that vascular endothelial growth factor may be a mediator of angiogenesis in the lungs of children after cavopulmonary anastomosis; however, other factors, such as vascular dilation and remodeling, may also be important.

Anastomotic intimal hyperplasia and surface thrombogenicity are the main reasons for the high failure rate of prosthetic small-diameter vascular grafts. While anastomotic intimal hyperplasia is a multifactorial event, ongoing surface thrombogenicity is primarily caused by the lack of an endothelium, even after years of clinical implantation. After decades of poorly performing synthetic artery-grafts, tissue engineering has emerged as a promising approach to generate biologically functional bio-synthetic hybrid grafts mimicking native arteries regarding the presence of an endothelial lining on the blood surface. "In vitro endothelialization" represented the first generation of such tissue-engineered vascular grafts, utilising cell culture techniques for the creation of a confluent autologous endothelium on ePTFE grafts. The clinical long-term results with this method in almost 200 patients are highly encouraging, showing patencies equal to vein grafts. Since "in vitro endothelialization" requires cell culture facilities, it will always be confined to large centres. Therefore, research of the 1990s turned to the development of spontaneously endothelializing implants, to make tissue-engineered grafts amenable to the entire vascular-surgical community. Apart from scaffold designs allowing transmural ingrowth, biological signalling through a facilitating ingrowth matrix holds a key to spontaneous endothelialization. In biological signalling, the increasingly deeper understanding of bio-active molecules and the discovery of domains and peptide sequences during the 1980s created the expectation in the 1990s that peptide signalling may be all that is needed. This present review highlights the possible problems associated with such a reductionist approach. Using the fibronectin molecule, we demonstrated that domains may be more suitable modules in tissue engineering than peptide sequences., (Copyright 2001 Wiley-Liss, Inc.)

A meticulous dissection of the sapheno-femoral junction (SFJ) at the time of primary surgery is regarded as best protection against the development of recurrences from this area. However, despite correct ligation of the junction recurrences may occur. In a prospective randomised trial, which has been started in 1998, we want to find out, whether this regrowth might be inhibited by the use of different ligation technics of the SFJ: Group 1: Ligation of the SFJ with resorbable Vicryl Group 2: Ligation with Vicryl and continuous non-resorbable stitching over (Prolene) the saphenous stump which precludes contact between free stump endothelium and the surrounding subcutaneous tissue Group 3: Non-resorbable ligation of the SFJ (Ethibond) Group 4: Ethibond ligation with Prolene stitching over the saphenous stump. The first follow-up examinations, which have been done by color-dupley-scan are presented. In each group about n = 100 groins could be examined. We found slight inguinal insufficiency due to a small branch of the femoral vein in group one: n = 10; group two: n = 6; group three: n = 3; group four: n = 1. Our hypothesis that the use of the suture material or the free lying stump endothelium might be influencing the development of the neovascularisation, seems to be supported by these results. We found the lowest rate of postoperative inguinal refluxes in the Ethibond-Prolene group, where the contact between free stump endothelium and the surrounding subcutaneous tissue is precluded. However, definite reliable data will be presented not before the third follow-up (24 months after the operation).

Mediastinal goiter is a well known benign disease, usually resectable through a cervical approach with minimal morbidity and mortality. Only occasionally a median sternotomy or a lateral thoracotomy may be required. The present case is worthy of presentation because of the exceptional dimension of the disease and the surgical challenge that it presented. In a 72-year-old woman a large intrathoracic goiter of the right thorax caused a severe dyspnoea due to an important contralateral mediastinal shift with compression of the lung, superior vena cava system and trachea. At surgical exploration, through a cervico-sternotomic approach, the mediastinal structures dislocation and the strong adherences between the anomalous neovascularized capsula of the mass and the surrounding structures, complicated the surgical dissection. An accidental lesion of the innominate artery required its reimplantation on the ascending aorta. An immense mass, was finally removed and pathological examination revealed a rare case of neovascularized, pseudosarcomatoid capsula among a benign hyperplastic proliferation. In spite of its benign nature, a giant goiter caused a life-threatening compression of the respiratory tract and lung parenchyma in this patient. The dimension of the lesions, the mediastinal anatomy alterations and the severe intraoperative haemorrhage represented major technical difficulties during surgical resection.

Aim: A pilot study of the feasibility of using dye laser thermotherapy (LTT) at a subcoagulation temperature to occlude newly formed vessels in patients with age related macular degeneration (AMD)., Methods: Choroidal neovascularisation (CNV) in 24 eyes with exudative AMD was treated with a continuous wave yellow laser at 578 nm. Parameters were an exposure time of 2 or 5 seconds, a spot size of 750 or 1000 microm, and a laser power of 100-200 mW. The clinical end point was a greyish discoloration at the treatment site. The effect of thermotherapy was documented by ophthalmoscopic and fluorescein angiographic examination. The follow up after LTT was 4-16 months, mean 5 months., Results: LTT resulted in total occlusion of newly formed vessels in 15 eyes (62.5%). Neovascular outgrowth within 6 weeks and recurrences 2-4 months after LTT were observed, each in three eyes. In six of the nine eyes with occlusion of CNV without recurrence the choriocapillaris remained perfused; in two eyes only the large choroidal vessels remained perfused. In six eyes pigmentary changes were the only ophthalmoscopic and fluorescein angiographic signs of treatment. The effect of LTT is rather unpredictable., Conclusion: CNV in AMD can effectively be treated by yellow dye laser thermotherapy with preservation of choroidal perfusion. The technique requires dosimetric adaptation.

We report the case of a 39-year old man who presented with central serous chorioretinopathy. Two months after diagnosis, argon laser photocoagulation was performed. One month later, the patient noticed distortion and a reduction in vision revealing a subretinal neovascularization above the fovea next to the laser scar. The patient underwent surgical extraction of the neovascular membrane and recovered a visual acuity of 20/30. This case report shows a complication of laser treatment of central serous chorioretinopathy and underlines the diagnostic difficulties of this disease and its treatment modalities. The surgical excision, the first reported in this etiology, led to good visual recovery, as is usually observed in young patients operated on for neovascular membrane.

New molecular factors have been characterized that are associated with the prognosis of prostate carcinoma patients, including p53 status and angiogenesis. We reported recently that mutant p53 (mp53) was associated with decreased expression of an endogenous inhibitor of angiogenesis, thrombospondin-1 (TSP-1), and increased microvessel density in melanoma and breast cancer. In this study, we performed a similar analysis on primary prostate carcinoma to determine whether these factors were associated with each other or patient outcomes. Paraffin-embedded specimens of 98 cases of primary prostate carcinoma were obtained and examined to confirm tissue diagnosis and Gleason scores. Carcinoma-specific levels of p53, TSP-1, and tumor angiogenesis were determined using semiquantitative immunohistochemistry (IHC) methods. Acquisition of mp53 was significantly associated with decreased TSP-1 (P = 0.002) and increased angiogenesis (P < 0.0001). An angiogenesis index integrating mp53, TSP-1, and angiogenesis (CD31) scores was found to be an independent predictor of survival in univariate and multivariate analyses that included Gleason score, clinical stage, and patient age. Further validation of the angiogenesis index in prostate carcinoma may provide a new tool to stratify patient risk.

Aim: To investigate the prevalence and the outcome of management of fibrovascular ingrowth (FVI) in eyes undergoing vitreous cavity washout (VCWO) following vitrectomy for diabetic retinopathy., Method: FVI was searched for at VCWO for in 19 consecutive eyes with proliferative diabetic retinopathy undergoing vitreous surgery for recurrent vitreous cavity haemorrhage over an 18 month period; the findings were correlated with the presence or absence of associated sclerotomy vessels externally. Eyes with richly vascularised ingrowths from the pars plana entry sites, as well as eyes with less extensive ingrowths but extensive retinal ablation applied at previous surgery for recurrent haemorrhage, underwent lensectomy and ciliary membrane dissection in addition to extensive retinopexy (n=6). Less severe cases received peripheral laser and cryotherapy only. The outcome of repeat surgery was studied prospectively in the 11 eyes with FVI., Results: 11 of the 19 eyes had a definite FVI from one or more of the original pars plana sclerotomies. In six of 11 eyes with FVI a large external episcleral vessel was present entering the original sclerotomy sites at which ingrowth was found peroperatively, but such sclerotomy vessels were also present in three of eight eyes with no FVI detected on the internal aspect of the sclerotomy. Two patients were lost to follow up and the remaining nine patients with FVI had no further vitreous cavity haemorrhage during initial follow up of 2-5 months., Conclusions: FVI has until now been considered an infrequent occurrence following vitrectomy for diabetic retinopathy. These findings would suggest that it is not uncommon and careful examination of the sclerotomy sites should be undertaken in all cases with recurrent haemorrhage and if FVI is found this should be treated appropriately.

Chronic subdural hematoma (CSH) is generally a disease affecting the elderly and infants. In infants, the process is particularly confusing and frequently misunderstood. In the pediatric population, CSH is just one of a group of sometimes related conditions known as extracerebral fluid collections. In the past, extracerebral fluid collections, in general, and CSHs, in particular, have been inaccurately or incompletely described. Modern neuroimaging techniques, however, have greatly advanced our understanding of these conditions. Surprisingly little literature exists on the subject, and publications before the advent of modern computed tomography and magnetic resonance imaging should be interpreted with caution.

Although the pathophysiology of the development, propagation, and recurrence of current subdural hematoma remains debatable, fundamental management strategies may be formulated to optimize outcomes. Effective drainage by whatever surgical means, removal of offending membranes when appropriate, and maximization of postoperative physiologic parameters are based on the best available current pathophysiologic information.

Purpose: Solid and necrotic brain tumors respond to radiosurgery, although necrotic lesions often contain a significant proportion of hypoxic cells which cannot become reoxygenated during the short overall treatment time of single dose application. In addition to the direct cytotoxic action, delayed vascular occlusion followed by ischemic tumor cell death could contribute to the effect of radiosurgery., Materials and Methods: In order to determine the impact of the two possible effects on tumor response, a 3-dimensional computer simulation was developed and fitted to response data obtained from 90 patients who were treated by LINAC radiosurgery for 1-3 brain metastases with median marginal doses of 20 Gy. Complete response rates were as follows: small, solid lesions (diameter 0.4-1 cm), 52% (12/23); large solid lesions (1.1-5.2 cm), 28% (17/60); large necrotic lesions, 12% (6/50). The 3-dimensional computer model simulated the growth of small solid and large, solid or necrotic tumors situated in a vascularized stroma. Oxygen supply, tumor cell division (cell cycle time 5 days), neovascularization, tumor cell kill by single dose irradiation (linear-quadratic model, alpha/beta=10 Gy, oxygen enhancement ratio 3.0) and time-dependent vascular occlusion (alpha/beta=3 Gy) were modeled by Monte-Carlo simulation techniques., Results: In the presence of neovascularization, solid tumors with a hypoxic fraction of 1-2% developed. Without neoangiogenesis, central necrosis occurred, and tumors had a hypoxic fraction of 20-25%. Assuming a pure cytotoxic effect of radiosurgery, neither the dose-response relationship for the solid lesions of different size nor that for the large lesions with solid or necrotic appearance could be reproduced for any given level of radiosensitivity. This was only possible by introducing a vascular effect that led to the occlusion of >/=99% of the vessels at the border of the target volume within 1 year after irradiation. In the presence of the vascular effect, the apparent radiosensitivity of the tumor cells was increased by 50-100%. Calculations of the dose-equivalent for the vascular effect show that it contributes 19-33% of the overall effect of single dose radiosurgery., Conclusion: This simulation study suggests that the therapeutic effect of single radiosurgery in malignant brain tumors cannot be understood without the consideration of vascular effects. The computer model might serve as a basis for exploring new treatment modalities that modify both cytotoxic and vascular effects of radiosurgery.

Objective: The standard categorization of arteriovenous malformations (AVMs) involves the Spetzler-Martin grading system, which uses a simple analysis of size, location (superficial or deep), and the presence of deep or superficial drainage. Hemodynamic risk factors are also thought to play important roles in the pathogenesis of these lesions and to be associated with the intracranial hemorrhage (ICH) rate. The actual hemodynamic factors for AVMs cannot be easily measured, but angioarchitectural features can be assessed and used as surrogate parameters., Methods: The AVM angioarchitectural features for 662 patients were analyzed, and their associations with ICH as a presenting sign were studied. A cross-sectional analysis was used to qualify the strength of associations among clinical features, angioarchitectural characteristics, and ICH before treatment., Results: The multivariate analysis indicated that arterial stenosis and arterial ectasia were associated with lower ICH rates, whereas venous stenosis increased the rate of ICH. The presence of angiogenesis modified the effects of arterial and venous stenosis. Furthermore, the effect of venous stenosis depended on the location of the nidus. The presented data do not support a direct positive association between associated aneurysms and ICH., Conclusion: Certain angiographic features seem to have prognostic potential with respect to the occurrence of ICH among patients with AVMs. A discriminatory prognostic index is proposed; its relevance must be proven in a future prospective study.

Purpose: The aim of this study was to evaluate the direct effect of surgical treatment of subfoveolar neovascular membranes in age related macular degeneration to macular functions., Patients and Methods: Thirteen eyes of 13 patients were included in this study. Macular function was assayed by visual acuity and central visual field using the Octopus perimeter before surgery and in the first three post operative months. Pre and post operative fluorescein angiography frames were digitalized and the size of each lesions were compared., Results: After a 3 months follow up, visual acuity remained stable or improved in 66% of the patients. However, visual acuity was better than 0.1 in 15% of the patients. Central visual field comparison disclosed a significant worsening of the retinal sensitivity in the 3 degree field surrounding the central point. On fluorescein frames, submacular scar was 141% of the size of the neovascular membrane. After a mean follow up of 6.9 months (range 3-14), one case of recurrence occurred. A cataract was observed in 85% of the phakic patients followed for more than six months., Conclusion: After a short term follow up, surgery can stabilise visual acuity, even though it remains poor. A worsening of the scotoma in the 3 degrees surrounding the central point is observed. However, patients noticed a subjective visual improvement in 62% of the case.

Purpose: Age related macular degeneration (AMD) is the most common cause of legal blindness in the Western world in people over 50 years of age. The most severe visual loss occurs in patients with AMD complicated by choroidal neovascular membranes (CNV). Indocyanine green angiography (ICG) account for visualization in up to 60% of the cases that are classified as occult on fluorescein angiography (up to 70% of the cases). ICG-guided laser photocoagulation of CNV is currently a mater of debate. We conducted a pilot study to determine wether it could be beneficial for patients presenting with occult CNV on fluorescein angiography., Material and Methods: Twenty consecutive patients (20 eyes) with occult CNV in AMD were included. All showed occult CNV on fluorescein angiography and a well defined juxta- or extrafoveal hot spot or plaque hyperfluorescence on ICG. Fibrovascular retinal pigment epithelial detachments were excluded. The patients had serial controls, including fluorescein angiography and ICG, at 15 days, 1, 2, 3, 6, 9 and 12 months after photocoagulation., Results: At the end of follow-up visual acuity (VA) was stable (within +/- 3 lines) compared to the initial one in 80% (16) of the cases. A complete resolution of exudative signs was observed in 75% (15) of the cases., Conclusions: ICG-guided laser photocoagulation of occult CNV in AMD account for better visual acuity than natural course of the disease at 12 months follow-up. However, a prospective randomized clinical trial is warranted to evaluate definitively this treatment approach.

Background and Purpose: The techniques of preoperative embolization of hypervascular spinal tumors, which has been known to be helpful for completing tumor resection, have not been described in detail. The purpose of this study was to analyze the technique and to evaluate the safety and value of preoperative transarterial embolization of hypervascular spinal tumors., Methods: Eighteen patients with hypervascular spinal tumors underwent transarterial embolization before surgery. The lesions were located between the upper cervical and lower lumbar spine: C1-T1 (n = 6), T5-L3 (n = 11), and L5 (n = 1); they arose intradurally in six patients and extradurally in 12. Thirty-one arteries were embolized with polyvinyl alcohol (PVA) particles (150-500 microm), and, in 18 of these, pieces of gelatin sponge were added for proximal pedicular embolization. The criteria for judging the effectiveness of embolization were completeness of tumor removal and estimated blood loss during surgery., Results: Tumor embolization was total in eight patients, nearly total in seven, subtotal in one, and partial in two. There were no symptomatic complications associated with embolization. Tumors were totally removed in 17 patients and nearly totally removed in one. The average estimated blood loss during surgery was 1100 mL (range, 200-6000 mL) for all 18 patients, and 1540 mL in patients with extradural tumors., Conclusion: Preoperative embolization of hypervascular spinal tumors is safe and effective. It can make complete resection of a tumor possible and can make an unresectable tumor resectable. Superselection or flow control is necessary to achieve effective devascularization and to avoid complications.

Objective: To investigate the therapeutic effect of surgical removal of subfoveal neovascular membrane with vitrectomy in treatment of age-related macular degeneration., Methods: 30 patients (30 eyes) with the macular degeneration were selected. The duration of the disease was limited less than 2 years and the size of the neovascular membrane was limited to

Purpose: To investigate a patient with talc retinopathy who developed macular fibrosis with resultant visual loss., Methods: A 64-year-old intravenous drug abuser was evaluated for bilateral peripheral retinal neovascularization. He admitted to abusing oral methylphenidate intravenously. Funduscopy showed numerous intravascular talc particles in the macular area of both eyes. Over a period of next 4 years, visually significant macular fibrosis gradually developed in both eyes, the left eye more than the right eye., Results: Fluorescein angiography confirmed the presence of bilateral peripheral retinal neovascularization with adjacent areas of ischemic retina. The patient was treated with peripheral laser treatment to the ischemic retina with resultant regression of peripheral retinal neovascularization. Bilateral macular fibrosis accounted for the reduced vision in our patient., Conclusion: Talc retinopathy can be associated with macular fibrosis with resultant visual loss.

Beside the immediate success of surgery and of embolization of angiodysplasias, certain number of patients return to medical consultation, because recanalization of the arteriovenous fistulae after their resection or obturation. From the presentation of two clinical cases of thoracic angiodysplasia: one of them slender, and threatening the other, the authors point out the complications and recurrence after surgical resection or arterial embolization. The recurrence takes place even when only one artery remains permeable after resection or embolization of the fistula. There are cases where the affected limb has to be amputated. However, angiodysplasia shows itself in the stump of the amputee limb. Uncontrolled angio-genesis is the natural history or postoperatory evolution of angiodysplasias, probably originated by an erroneous genetic program, which persist in spite of resection of the vascular malformation, causing a therapeutic failure.

Plexiform vascularisation of a retropharyngeal lymph node is described in an adult cat. The cat presented with a chronic history of inspiratory stridor and a slowly growing mass in the cranial cervical area. Clinical signs resolved after excision of the affected node. This appears to be the first clinical report of plexiform vascularisation of a retropharyngeal lymph node and its treatment in a cat.

The effect of photothermal vascular targeting, alone and in combination with antiangiogenic therapy, was evaluated using tumors produced in mice by transplantation of KB cells. Tumor growth inhibition and regression followed vascular damage produced by pulsed dye laser (PDL) radiation. Administration of the antiangiogenic agent all-trans-retinoic acid (RA) was associated with smaller average tumor volumes in the presence and absence of PDL irradiation, but this effect was not statistically significant. The ability of PDL photothermal vascular targeting to cause regression of tumors without harming normal tissue may be a consequence of preferential damage to supplying vessels at the tumor periphery.

Purpose: To study the fluorescein angiographic appearance of the extreme peripheral retina in patients with proliferative diabetic retinopathy with rubeosis iridis., Methods: Using a modified endoscope, fluorescein angiography was performed prospectively during pars plana vitrectomy on 14 eyes of 12 patients with proliferative diabetic retinopathy who had or developed postoperative rubeosis. These findings were compared with those obtained from 41 eyes of 35 patients without rubeosis., Results: A fibrovascular ridge was observed at the ora serrata in 11 of 12 eyes (92%) with rubeosis but in only 15 of 35 (43%) eyes without rubeosis. Seven of 12 (58%) eyes with rubeosis showed the continuous type of fibrovascular ridge, whereas only 5 of 35 (14%) eyes without rubeosis showed the continuous type. A broom-shaped continuous fibrovascular ridge was observed only in eyes with rubeosis., Conclusions: Many eyes with proliferative diabetic retinopathy showed unusual findings in the extreme retinal periphery, which were more frequent in the eyes with rubeosis iridis. Fluorescein angiography of this region may provide valuable information for possible anterior neovascularization.

Background: There are conflicting reports on the value of cyclocryotherapy and it seems that the success rate is depending on glaucoma conditions, the period of follow-up and the technique. This retrospective study was carried out to assess the efficacy and complication rate of cyclocryosurgery for advanced glaucoma with and without neovascularization., Patients and Methods: We induced 76 eyes of 75 patients with inadequately controlled glaucoma, which underwent cyclocryotherapy during the period of 1993 and 1996 (treatment time 60 seconds with -80 degrees C, 6-12 applications (mean 9.8 +/- 2.3), 180-360 degree (median 270 degree), diameter of the probe tip 2.5 mm, 1-2 mm distance from the limbus). Depending on the etiology we distinguished between neovascular (NVG) and non-neovascular glaucoma (nNVG). Pre- and postoperative data from all patients were studied retrospectively, for follow-up after 12-36 months patients were examined., Results: Intraocular pressure (IOP) decreased in all patients from 44.7 +/- 12.6 mm Hg preoperatively to 15.6 +/- 6.5 mm Hg postoperatively after a follow-up of 12-36 months. In 88.2% IOP was lowered to < or = 25 mm Hg. NVG showed a mean IOP reduction from 49.1 +/- 12.5 mm Hg before cyclocryotherapy to 15.6 +/- 5.0 mm Hg at follow-up. In the nNVG group IOP was 40.5 +/- 11.3 mm Hg and 15.7 +/- 7.6 mm Hg after cyclocryotherapy. Pressure was controlled (< or = 25 mm Hg) for 83.8% of NVG and 92.3% of nNVG. A cyclocryotherapy-induced intense inflammation was seen more frequent in NVG (43.2%) than in nNVG (17.9%). 2 patients with NVG and 3 with nNVG developed phthisis postoperatively (total 6.7%)., Conclusions: Cyclocryosurgery is an effective method to reduce IOP in advanced, refractory glaucoma, when other methods have failed. The risk/success rate seems to be acceptable.

Objective: This study aimed to report the visual outcome of surgical removal of extensive peripapillary choroidal neovascularization (CNV) due to presumed ocular histoplasmosis syndrome (POHS)., Design: Retrospective review of the records of all patients seen at the Barnes Retina Institute who underwent surgical removal of extensive peripapillary CNV associated with POHS and who had at least 12 months of follow-up., Participants: Seventeen consecutive eyes (in 14 patients) undergoing surgical removal of extensive peripapillary CNV associated with POHS were studied., Intervention: Pars plana vitrectomy and surgical removal of CNV were performed., Main Outcome Measurements: Best-corrected Snellen visual acuity, funduscopic examination, and intravenous fluorescein angiography were obtained before surgery and at regular intervals after surgery., Results: In 14 of 17 eyes, the peripapillary CNV was subfoveal, and in 3 eyes, it was extrafoveal. All three eyes with extrafoveal CNV were not eligible for laser treatment according to Macular Photocoagulation Study guidelines because treatment would have spared less than 1.5 contiguous clock-hours of retina temporal to the optic disc. Follow-up ranged from 17 to 57 months, with a median of 32 months. In eyes with subfoveal CNV, best-corrected preoperative Snellen visual acuity ranged from 20/25 to counting fingers at 2 feet with a median of 20/200, and best-corrected final Snellen visual acuity ranged from 20/25 to 20/200 with a median of 20/40. In 7 (50%) of 14 eyes, a final Snellen acuity of 20/40 or better was achieved, and in all cases except 1, visual acuity improved or did not change with surgery. In the three eyes with extrafoveal CNV, best-corrected preoperative Snellen visual acuity ranged from 20/20 to 20/400 with a median of 20/200, and best-corrected final Snellen visual acuity was 20/20 in all cases. In addition, visual acuity improved with surgery., Conclusions: The data from this small retrospective study suggest that surgical removal may provide visual benefit in selected cases of extensive peripapillary CNV due to POHS.

Purpose: To report clinical features and surgical management of neovascular complications associated with rubeosis iridis and peripheral retinal detachment after retinal detachment surgery in nondiabetic patients., Methods: Seven consecutive eyes of seven nondiabetic patients who developed neovascular complications associated with rubeosis iridis and peripheral retinal detachment after scleral buckling and vitrectomy procedures were retrospectively reviewed. None of the eyes had clinical evidence of anterior segment ischemia or retinal vascular disease, but each eye developed rubeosis iridis and neovascular complications., Results: Of the seven eyes with rubeosis iridis and peripheral retinal detachment, six developed recurrent or progressive vitreous hemorrhage, and three developed progressive neovascular glaucoma. Four eyes underwent a revision procedure to repair the peripheral retinal detachment, and anterior proliferative vitreoretinopathy was found in each of these cases. Rubeosis iridis regressed in all three eyes in which surgery resulted in complete reattachment of the retina. In one eye with persistent peripheral retinal detachment and in the three remaining eyes that did not undergo revision surgery, rubeosis iridis persisted and was associated with long-term neovascular complications. Final corrected visual acuity was 20/70 to 20/400 in three eyes with total retinal reattachment and no light perception to hand motions in four eyes with persistent peripheral retinal detachment and rubeosis iridis., Conclusion: Visually significant neovascular complications may occur in eyes that develop rubeosis iridis associated with peripheral retinal detachment after retinal detachment surgery in nondiabetic patients. Successful repair of the peripheral retinal detachment may induce regression of rubeosis iridis, reduce associated complications, and improve the long-term prognosis of these eyes.

Objective: To present the cases of two patients with laser-induced iatrogenic subfoveal choroidal neovascular membranes (CNVMs) who underwent surgical removal of the membranes with favorable outcomes., Design: Interventional case reports., Participants: Two patients with iatrogenic subfoveal CNVM. One case developed after laser treatment for macular edema due to branch retinal vein occlusion, and the second case developed after focal laser photocoagulation for diabetic retinopathy., Intervention: Surgical removal by pars plana vitrectomy., Main Outcome Measures: Visual acuity, scotoma, retinal examination with fundus photography, and fluorescein angiography before surgery and during the postoperative period., Results: Both patients underwent surgical removal after progression of the membrane with severe visual loss of 20/200 was noted. At present follow-up, there is a significant improvement in visual acuity and a reduction in the size of the scotoma. No recurrence of CNVM is noted., Conclusion: Both patients with laser-induced iatrogenic subfoveal CNVM achieved a good visual outcome after surgical removal of the membrane. The reasons for a good surgical result are thought to be twofold. First, the origin of the CNVM is extrafoveal at the site of laser application. The chance for foveal cone cell damage during the surgery is reduced. Second, the degree of cellular destruction in iatrogenic CNVM is usually focal without extensive retinal photoreceptor cell and retinal pigment epithelial damage. Therefore, a better chance of postoperative visual recovery is anticipated.

Purpose: To determine whether choroidal neovascularization excision causes mechanical damage to the neurosensory retina, retinal pigment epithelium, or choriocapillaris., Methods: Prospectively, 18 eyes of 18 consecutive patients who underwent choroidal neovascularization excision were observed. Preoperatively and postoperatively, the integrity of the choriocapillaris circulation in the pathway of choroidal neovascularization extraction was studied by fluorescein and indocyanine green angiography. Using static scanning laser ophthalmoscope microperimetry, the presence of iatrogenic scotomas that developed postoperatively in the pathway of choroidal neovascularization extraction was also investigated., Results: Postoperatively, a choriocapillaris defect was detected in 17 (94.4%) of 18 cases. In 15 cases (83.3%), the choriocapillaris defect had a clear relationship to the pathway of choroidal neovascularization extraction. Postoperatively, a scotoma was present in 16 (88.9%) of 18 cases. In 14 cases (77.8%), the location of the scotoma had a clear relationship to the pathway of choroidal neovascularization extraction., Conclusion: Surgical excision of choroidal neovascularization leads to severe damage of the choroid and retina in the pathway of the extracted choroidal neovascularization. The injury involves the neurosensory retina, retinal pigment epithelium, and choriocapillaris.

Objective: To describe the comparative impact of current and preventive treatments on incidence of choroidal neovascularization (CNV) and severe vision loss in patients with bilateral soft drusen (BSD)., Design: Stochastic model., Setting: US population., Patients: Prevalence cohort of white patients 43 years or older with BSD., Interventions: Application of prophylaxis of 10% to 50% efficacy to 1 or both eyes of patients with BSD, application of laser photocoagulation to eligible CNV lesions, or both., Main Outcome Measures: Proportion of patients with BSD after 10 years with unilateral and bilateral CNV and resultant unilateral and bilateral vision loss to visual acuity of 20/200 or worse., Results: The natural history of patients with BSD generated by the model shows that 12.40% of these patients develop either unilateral or bilateral CNV within 10 years of their entry into the BSD prevalence cohort. Bilateral disease occurs in 3.86% of patients with BSD within 10 years. The proportion of patients with BSD becoming legally blind from CNV within 10 years is 2.54% if no treatment is performed. Current laser treatment for CNV decreases the proportion with legal blindness within 10 years to 2.24%. The addition of a preventive treatment of 10% efficacy applied bilaterally to the current laser treatment regimen decreases the proportion with legal blindness to 1.86%; a 25% effective preventive treatment decreases it to 1.34%. Comparatively, preventive treatment of 10% and 25% efficacy given to the fellow eye only after the first eye has developed CNV decreases the proportion of legally blind patients at 10 years only to 2.06% and 1.77%, respectively. All outcomes vary with sex and age at entry into the BSD cohort., Conclusions: Patients with BSD face a 12.40% risk of developing CNV within 10 years. The addition of even a modest (10% effective) bilateral preventive treatment to the current regimen for CNV would more than double the prevention of legal blindness in the BSD population relative to current laser treatment; a preventive treatment of 33% efficacy more than halves the rate of legal blindness caused by CNV. Preventive treatment given to the fellow eye only after the first develops CNV has substantially less impact.

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

Unlabelled: The surgical removal of choroidal neovascularization (CNV) in age-related macular degeneration (AMD) causes a retinal pigment epithelial defect (RPED) corresponding to the area of diffuse RPE damage. We describe angiographic features of recurrent CNV in AMD after surgical membranectomy in order to elucidate the nature of persistence and recurrence., Methods: After digitalization of the pre- and postoperative fluorescein angiographic images of eight patients with recurrent CNV in AMD we determined the morphology (well or ill-defined) and the area of the CNV and of the subretinal hemorrhage preoperatively and of the recurrent CNV and of the RPE defect postoperatively., Results: The nature of recurrences showed differences between preoperatively well- and ill-defined CNV. Four preoperatively well-defined CNV with surrounding subretinal hemorrhage showed recurrences in the entire area of the preoperative CNV excluding the retinotomy 8-9 weeks postoperatively. Four preoperatively ill-defined CNV with subretinal hemorrhage developed marginal recurrences at the rim of the RPED. There was no background fluorescence in the area of the RPED., Conclusion: The nature of recurrences extending over the entire area of the preoperatively well-defined CNV without loss of background fluorescence only a few weeks after surgical removal of well-defined CNV suggests partial persistence. The removal of the subretinal well-defined CNV could leave sub-RPE parts in locations that preoperatively cannot be visualized angiographically. The marginal recurrence of preoperatively ill-defined CNV weeks to months postoperatively shows angiographic similarities to recurrent CNV after laser coagulation.

Subretinal choroidal neovascularization is an important cause of visual loss in adults. Removal of choroidal neovascular membranes using relatively new techniques of subretinal surgery holds promise for improving or stabilizing vision in some patients. A number of factors have been proposed that may affect the outcome of subretinal surgery for choroidal neovascularization, including the degree of involvement of Bruch's membrane, the location of the neovascular complex relative to the retinal pigment epithelium and Bruch's membrane, the location of the ingrowth site, and the etiology of the membranes. Although the surgical techniques are relatively refined, the indications for removal of choroidal neovascular membranes are still under investigation. This article reviews the recent and past literature and summarizes the authors' specific recommendations regarding present indications for removal of choroidal neovascular membranes.

Objective: To study the histologic and ultrastructural features of surgically excised choroidal neovascularization (CNV) from patients who had undergone submacular surgery., Materials and Methods: Voluntarily submitted surgically excised CNV specimens from a subset of specimens obtained by the Submacular Surgery Trials Research Group between January 1, 1994, and December 31, 1996, were available for this study. The specimens were routinely processed for transmission electron microscopic examination. The largest horizontal and vertical dimensions, cellular and extracellular constituents, and relationship of the CNV to the neurosensory retina and retinal pigment epithelium (RPE) were recorded., Results: Seventy-eight surgical specimens were obtained from 160 patients treated surgically in Submacular Surgery Trials centers. Sixty-one (78%) were from patients with age-related macular degeneration (ARMD) and 17 (22%) were from patients with ocular histoplasmosis syndrome or idiopathic causes (hereafter referred to as the non-ARMD group). The histologic diagnosis was fibrovascular tissue, fibrocellular tissue, or hemorrhage in all cases. Vascular endothelium and RPE were the most common constituents of the CNV. Basal laminar deposit was only present in CNV from patients with ARMD. Age-related macular degeneration specimens were larger (mean +/- SD, 2042 [+/- 1175] x 320 [+/- 185] microm vs 1498 [+/- 792] x 227 [+/- 166] microm) and were more likely to have a sub-RPE (beneath the RPE) component than non-ARMD specimens., Conclusions: All evaluated surgically excised CNV specimens in this study from patients enrolled in the Submacular Surgery Trials consisted of fibrovascular tissue, fibrocellular tissue, or hemorrhage. Surgically excised CNV associated with ARMD in this series was larger and often was located beneath the RPE compared with non-ARMD CNV, although fewer than half of all the specimens could be oriented by topographic relationship to the RPE.