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PubMed1999

Long term results of radiotherapy for subfoveal choroidal neovascularisation in age related macular degeneration.

BACKGROUND/AIMS: Radiotherapy has been proposed as an alternative treatment for patients with subfoveal choroidal neovascularisation (CNV) that is untreatable according to macular photocoagulation study guidelines. This prospective study was designed to evaluate whether radiotherapy may affect the functional and anatomical outcome in a large cohort of patients affected by subfoveal CNV, with a follow up period up to 24 months. METHODS: 212 patients (231 eyes) with newly diagnosed subfoveal CNV not amenable to laser therapy were included in this study. Two radiotherapy methods, the lateral beam technique (6 MV, 20 Gy in five fractions) and lateral arc therapy (25 MV, 16 to 20 Gy, in four or five fractions), were used. Comparisons of best corrected visual acuity (VA), fluorescein (FA) and indocyanine green (ICG) angiography, at inclusion and 6, 12, 18, and 24 months after radiotherapy were performed using univariate analysis. RESULTS: A VA improvement of two or more lines was observed in 34% at 12 months, 31% at 18 months, and 32% of the eyes at 24 months. Paired comparisons of CNV areas in FA and ICG showed no significant change between baseline and each visit. However, 12 and 18 months after treatment, 47% of the eyes showed a decrease of 10% or more in CNV size both in ICG and FA. Radiation side effects included radiation retinopathy (eight eyes), optic neuropathy (four eyes), choroidal vasculopathy (five eyes), and branch retinal vein occlusion (three eyes). CONCLUSION: Compared with the natural course of subfoveal CNV, the results of this prospective study suggest that radiotherapy could stabilise visual and anatomical outcome in selected cases.

Aged↗
PubMed2000

Sorsby fundus dystrophy without a mutation in the TIMP-3 gene.

AIMS: To examine a large family with an autosomal dominant fundus dystrophy and to investigate whether or not mutations in TIMP-3 gene were involved. METHODS: A large family of 58 individuals with an autosomal dominant fundus dystrophy was examined ophthalmologically. A DNA linkage analysis in the 22q12.1-q13.2 region was performed. The TIMP-3 gene was screened for mutations in all five exons. RESULTS: In this large family 15 individuals were affected. All other individuals were found to be clinically unaffected. Pisciform flecks in the midperiphery and drusen-like deposits were the most typical ophthalmological finding in this family and were encountered from the fifth decade on. Chorioretinal atrophy and neovascularisation with disciform lesions characterised the disease from the sixth decade on. Linkage analysis using an affected only analysis, showed a maximum positive lod score of 3.94 at theta = 0.0 with marker D22S283. No mutations possibly causing Sorsby fundus dystrophy were found in either the exonic sequences, the promotor region, or the 3'UTR. CONCLUSION: The family in this pedigree has an autosomal dominant fundus dystrophy, which is most probably Sorsby fundus dystrophy. Although, in the linkage analysis, significant positive lod scores were found with the region 22q12.1-q13.2, no causative mutations could be identified in the TIMP-3 gene.

Aged↗
PubMed2001

Preretinal neovascularisation associated with choroidal melanoma.

BACKGROUND: The rare occurrence of iris neovascularisation and choroidal (subretinal) neovascularisation in patients with choroidal melanoma has been reported. However, the occurrence of preretinal neovascularisation (NVE) fed from the retinal circulation in eyes with choroidal melanoma is far less frequently reported. METHODS: Three case reports of choroidal melanoma with the very rare finding of overlying NVE. RESULTS: The three patients had choroidal melanomas, localised serous retinal detachment, and NVE. Two cases showed definite retinal capillary non-perfusion, and one of these two cases demonstrated retinal telangiectasis. One patient's melanoma responded quickly to iodine-125 plaque radiotherapy; however, the retinal neovascularisation persisted and caused vitreous haemorrhage. Localised scatter photocoagulation was successful in causing the complete regression of the neovascularisation. The other two patients had their eyes enucleated (one with planned pre-enucleation external beam radiotherapy). Demonstration of preretinal vessels in one of the cases was possible in histological sections. CONCLUSION: Preretinal neovascularisation may occur as a complication of choroidal melanoma. Possible aetiologies include the release of tumour angiogenic factors, inflammation, chronic retinal detachment with secondary retinal ischaemia, retinal vascular occlusion secondary to retinal vessel invasion by the tumour, or following radiation therapy. Optimal management of the neovascularisation is not known at this time. Supplemental localised scatter photocoagulation may be of benefit in some cases.

Adult↗
PubMedDate not supplied

Human connective tissue growth factor mRNA expression of epiretinal and subretinal fibrovascular membranes: a report of three cases.

PURPOSE: To investigate the correlation between connective tissue growth factor (CTGF) mRNA expression and immunohistochemical characteristics (expression of type I collagen and tenascin) of fibrovascular membranes of proliferative retinal diseases under in vivo conditions. METHODS: CTGF mRNA expression was investigated using in situ hybridization. Expression of type I collagen and tenascin was detected by immunohistochemical staining. RESULTS: CTGF mRNA is produced in transformed retinal pigment epithelial cells and appears also in fibroblast-like cells, which are embedded in epiretinal and subretinal membranes of proliferative retinal diseases as well as in surgically removed subretinal membranes. In all examined membranes, expression of human CTGF mRNA appears in concurrence with the expression of type I collagen and tenascin. CONCLUSIONS: The predominant expression of CTGF mRNA in the development of fibrovascular membranes of proliferative retinal diseases suggests a significant role of CTGF in the pathological course of these ocular disorders.

Aged↗
PubMed1996

Angiogenin levels in the vitreous from patients with proliferative diabetic retinopathy.

The vitreous levels of angiogenin, which is a potent blood vessel-inducing protein, were measured to determine their association with proliferative diabetic retinopathy (PDR). Undiluted vitreous fluid specimens were collected from 30 eyes with PDR at the time of vitrectomy. A sandwich enzyme-liked immunosorbent assay was then used to quantitate the levels of angiogenin. As a control we determined the levels in the specimens from 21 patients with proliferative vitreoretinopathy (PVR) and 4 patients with idiopathic macular epiretinal membrane (IERM). The average angiogenin level in the eyes with PDR was 43.7 ng/ml, and no significant difference was observed among PDR, PVR and their reoperation cases. In the category of IERM, the mean concentration of angiogenin was 2.1 ng/ml, which was significantly lower than that of the PDR and PVR cases. Our study thus demonstrated a significant increase in the vitreous angiogenin levels in eyes with PDR, PVR and those undergoing reoperation for these conditions in comparison to eyes with IERM. We therefore postulated that the elevated angiogenin levels thus reflected a breakdown of the blood-ocular barrier in eyes with PDR and PVR.

Adult↗
PubMed1989

[Vitrectomy in florid proliferative diabetic retinopathy].

In 11 eyes out of 7 patients, vitrectomy was performed for progressive proliferative diabetic retinopathy. The indication for vitrectomy was as follows: (1) macular traction with fibrovascular proliferation on the disk; (2) progressive proliferation with vitreous hemorrhage; (3) fibrovascular proliferation on the disk in spite of intensified scattered photocoagulation. 3 eyes were operated a second time, 1 needed a third vitrectomy after nonresolving hemorrhage. Visual acuity increased after vitrectomy in 9 eyes. In 4 eyes new proliferations on the disk occurred. After an observation period of 1 year, 7 eyes show a stable course.

Adolescent↗
PubMed1990

Characterization of glial involvement in proliferative diabetic retinopathy.

We studied the relationship of glial cells and other supporting tissues associated with newly formed blood vessels in proliferative diabetic retinopathy. Seventeen postmortem, freshly enucleated eyes from diabetic patients and 34 epiretinal and preretinal membranes removed during vitreous surgery for proliferative diabetic retinopathy were analyzed using the peroxidase-antiperoxidase method for light microscopy and protein A/gold labeling of ultrathin cryosections for transmission electron microscopy in addition to routine transmission and scanning electron microscopy. We found that glial cells are commonly and characteristically found in elevated diabetic proliferations and present at the vitreous surface. The newly formed blood vessels, however, were not seen at the edge of elevated epiretinal and preretinal membranes in early and intermediate stages. These results suggest that glial cells may extend beyond the vascularized areas of the proliferative tissue. It is possible that glial cells and their extracellular matrix contribute to the framework leading to the development of new blood vessels.

Cell Membrane↗
PubMed1993

Retinal telangiectasis and proliferation of the retinal vessels in a family.

A 20-year-old woman presented with a marked proliferative retinopathy of the entire central region of the retina in both eyes, with veil-like epiretinal gliovascular membranes and isolated spots of haemorrhaging. The outer region of the retina was unremarkable. Her 49-year-old mother showed perimacular telangiectases in both eyes. The vascular system of both patients were medically sound, and, in particular, the blood pressure, blood sugar and blood picture were normal, with no signs of heart, kidney, lung or liver disease. The first patient had been a heavy smoker for 6 months, and the second did not smoke. The 84-year-old mother of the second patient was blind following bilateral Horton's temporal arteritis.

Adult↗
PubMed2003

Argon laser photocoagulation-induced modification of gene expression in the retina.

PURPOSE: To generate a profile of genes expressed in the retina, RPE, and choroid after laser treatment and to identify genes that may contribute to the beneficial effects of laser photocoagulation in the treatment of angiogenic retinal diseases. METHODS: Argon laser irradiation was delivered to the left eye of normal C57BL/6J mice (n = 30), with the right eye serving as the control in each animal. Three days after laser treatment, mice were culled, eyes enucleated, and the retinas dissected and pooled into respective groups. The total RNA of replicate samples was extracted, and expression profiles were obtained by microarray analysis. Data comparisons between control and treated samples were performed and statistically analyzed. RESULTS: Data revealed that the expression of 265 known genes and expressed sequence tags (ESTs) changed after laser treatment. Of those, 25 were found to be upregulated. These genes represented a number of biological processes, including photoreceptor metabolism, synaptic function, structural proteins, and adhesion molecules. Thus angiotensin II type 2 receptor (Agtr2), a potential candidate in the inhibition of VEGF-induced angiogenesis, was upregulated, whereas potential modulators of endothelial cell function, permeability factors, and VEGF inducers, such as FGF-14, FGF-16, IL-1beta, calcitonin receptor-like receptor (CRLR), and plasminogen activator inhibitor-2 (PAI2), were downregulated. CONCLUSIONS: In this study, genes were identified that both explain and contribute to the beneficial effects of laser photocoagulation in the treatment of angiogenic retinal diseases. The molecular insights into the therapeutic effects of laser photocoagulation may provide a basis for future therapeutic strategies.

Animals↗
PubMed2005

Ocular growth in premature infants conceived by in vitro fertilization versus natural conception.

PURPOSE: To evaluate the possible effect of in vitro fertilization (IVF) on early development of the eye in premature infants. METHODS: Biometric and keratometric values, intraocular pressure, and retinal vascular status were assessed in a cohort of 133 premature infants. These values were compared between premature infants conceived by IVF or naturally, and the relationship between these parameters and postconceptional age and weight at examination were evaluated. RESULTS: The sample consisted of 133 premature infants, 62 (46.6%) born by IVF and 71 (53.4%) by natural conception. Postconceptional age at examination was 28 to 46 weeks. In both groups, axial length, anterior chamber depth, and corneal radius correlated with the postconceptional age and weight at examination and followed a linear growth pattern. Lens thickness changed very slightly. The rate of retinal vascularization correlated with the postconceptional age as well. No correlation was found between intraocular pressure and corrected age or weight at examination. There was no difference between the study and control groups in any of the biometric or keratometric parameters or in intraocular pressure, according to two-way analysis of variance. CONCLUSIONS: IVF apparently does not affect early ocular growth, intraocular pressure, changes in corneal curvature, or retinal vascularization in premature infants. These findings may aid ophthalmologists in assessing ocular dimensions in this patient population.

Biometry↗
PubMed2006

SB-267268, a nonpeptidic antagonist of alpha(v)beta3 and alpha(v)beta5 integrins, reduces angiogenesis and VEGF expression in a mouse model of retinopathy of prematurity.

PURPOSE: To determine whether SB-267268, a nonpeptidic antagonist of the alpha(v)beta3 and alpha(v)beta5 integrins, attenuates angiogenesis in a murine model of retinopathy of prematurity (ROP) and alters the expression of vascular endothelial growth factor (VEGF) and its second receptor (VEGF-R2). METHODS: In receptor binding, SB-267268 exhibited nanomolar potency for human, monkey, and murine alpha(v)beta3 and alpha(v)beta5. SB-267268 inhibited the attachment of alpha(v)beta3-transfected HEK293 cells to microtiter plate wells precoated with RGD-containing matrix proteins, and vitronectin-mediated human and rat aortic smooth-muscle-cell migration. At postnatal day (P)12, C57BL/6 mice were exposed to 80% oxygen for 7 days followed by 7 days in room air (angiogenic period). Between P12 and P17, ROP mice were administered sterile saline (vehicle intraperitoneal [i.p.]) or SB-267268 (60 mg/kg bi-daily, i.p.). Shams were exposed to room air from P0 and administered either vehicle or SB-267268 during P12 to 17. In at least 3 randomly chosen paraffin sections from each eye, the number of blood vessel profiles in the inner retina were counted. In situ hybridization for VEGF and VEGFR-2 was performed on at least 8 randomly chosen paraffin sections from each eye. RESULTS: SB-267268 reduced pathologic angiogenesis in ROP mice by approximately 50% and had no effect on developmental retinal angiogenesis in shams. Both VEGF and VEGFR-2 mRNA were upregulated in the inner retina of ROP mice and reduced with SB-267268. CONCLUSIONS: Nonpeptidic inhibition of alpha(v)beta3 and alpha(v)beta5 integrins is effective in ROP and may be a suitable anti-angiogenic therapy for other ischemic retinal pathologies.

Angiogenesis Inhibitors↗
PubMedDate not supplied

Management of incontinentia pigmenti: a case of monolateral preretinal fibrovascular proliferations adjacent to snail-track degeneration areas.

PURPOSE: To report a case of monolateral preretinal fibrovascularproliferations in a young adult woman, who had suffered from incontinentia pigmenti (IP) during her first month of life. METHODS: Case report. RESULTS: Circumscribed preretinal fibrovascular proliferations, adjacent to a mid-peripheral area of snail track degeneration, were occasionally diagnosed in the left eye of an asymptomatic 18-year-old white female. Careful ocular examination did not reveal any cause of the monolateral vascular abnormalities observed in the posterior segment. A detailed medical history brought to light that the patient has suffered infantile IP, like four other females in her family. The patient did not present any evident malformation of teeth, nails, skeleton or hair. A cytogenetic linkage study documented a chromosomal aberration in the Xq28 band, which confirmed the diagnosis of familial IP (type 2). The fluorescein angiography findings clearly illustrated the minimal retinal involvement in the course of IP. CONCLUSIONS: This case shows that a wide range of etiologies must be considered in patients presenting monolateral preretinal fibrovascular proliferations. To correctly manage these uncommon, inherited or acquired, retinal diseases it is better to do a mid-term follow-up, rather than operate immediately, and this enabled us to observe the natural course of the lesion, while awaiting a definitive diagnosis.

Adolescent↗