Retinal degeneration associated with congenital transcobalamin II deficiency.
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Biomedical subjects
Publications and source records attributed to G Soubrane.
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Age-related macular degeneration has a natural progression from the precursors (the drusen) towards atrophic or neovascular complications. Choroidal neovascularization is undoubtedly the aspect of the disease that benefits most from new therapeutical approaches. Destructive photocoagulation based on fluorescein angiography has demonstrated since 20 years its efficiency on choroidal neovascularization. The same approach based on indocyanine green (ICG) angiography would increase the number of patients available to therapy. Very recently photodynamic therapy has demonstrated its efficiency to stabilize visual acuity at least at two years in patients with choroidal new vessels predominantly well defined. Other treatment developments are considered, such as refinement of photocoagulation techniques or of surgery. Until now, none has demonstrated its efficiency although they raise justified hopes. The future approaches rely upon the progress of the research both in physiopathology of the disease and on the angiogenic process requiring a constant interaction with all thematics of research. Finally, palliative treatments will be required before heading up to a preventive treatment.
Macular edema is frequently responsible for loss of central vision in patients affected with retinitis pigmentosa (RP). This macular edema can be treated with acetazolamide. Our purpose was to evaluate optical coherence tomography (OCT) examination in the follow-up of macular edema in RP. In addition, we tried to evaluate the minimal efficient dose of acetazolamide, using means other than fundus examination or fluorescein angiography. We report the cases of 5 patients affected with typical retinitis pigmentosa and fundus appearance of macular edema. These patients received oral acetazolamide treatment (500 mg/d). The OCT examinations were performed before and during treatment, which allowed us to demonstrate, quantify and monitor the progression of macular edema during treatment. OCT appears to be a useful tool in the follow-up of patients affected with macular edema and RP. This noninvasive examination contributes to improving our strategy in treating patients.
Age related macular degeneration (AMD) is the main cause of blindness after age 55 in western countries. These last past years, several lines of evidence such as familial aggregation or twin studies suggested a genetic component in AMD. However, the late onset of the disease and the fact that AMD is a polygenic and multifactorial disease are the main limiting factors for linkage studies. Gene candidate strategy allowed the exclusion of several genes (VMD2, RDS, TIMP3) and lead to the implication of two genetic factors: the apoE gene (involved in the transport of lipids) and the ABCR gene (involved in Stargardt macular dystrophy). Concerning the apoE gene, a lower frequency of the epsilon 4 alleles carriers was observed in the exudative AMD population compared with controls, supporting the idea of a role of the apoE gene in exudative AMD with drusen. These results, together with ultrastructural studies, suggest that allele epsilon 4 is a protective factor for drusen and thus for AMD. For the ABCR gene, several studies and a large multicentric study definitively show that some heterozygous mutations are predisposing factors for AMD, in a polygenic and multifactorial model.
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AIMS: To study the effects of intravitreal tissue plasminogen activator (tPA) in recent onset central retinal vein occlusion (CRVO). METHODS: 15 patients with recent onset CRVO (from 1-21 days' duration, mean 8 days) were given 75-100 microg of tPA intravitreally associate with low dose low molecular weight heparin. CRVO was perfused in nine patients and with mild ischaemia not exceeding 100 disc diameters in six patients. Follow up ranged from 5 to 21 months for 14 patients (mean 8 months). Visual acuity measurement, macular threshold (Humphrey perimeter), fluorescein angiography with the scanning laser ophthalmoscope with special emphasis on retinal circulation times, and retinal perfusion were performed at days 0, 1, and 8 and months 1, 3, and 6. RESULTS: Visual acuity was significantly improved on the first day after treatment in only one eye, and decreased transiently in six eyes (40%). Retinal blood velocity was not significantly modified by tPA injection. Retinal ischaemia developed in six eyes (43%), leading to panretinal photocoagulation in five eyes including one with rubeosis iridis. At the end of follow up, visual acuity had improved to 20/30 or better in five eyes (36%), including two with complete recovery; visual acuity was worse than 20/200 in three eyes (28%). No complication of tPA injection was observed. CONCLUSION: Intravitreal tPA treatment for CRVO appears to be simple and safe, but did not significantly modify the course of the occlusion in our patients immediately after treatment. Final visual outcome did not differ significantly from that observed in the natural course of the disease, but final visual acuity seemed to be slightly better. A randomised study is required to determine if intravitreal tPA actually improves visual outcome in CRVO.
PURPOSE: Identification of genetic factors in the pathogenesis of age-related macular degeneration (AMD) is of crucial importance in this common cause of blindness. Mutations in the Stargardt disease gene (ABCR) were previously reported in patients with atrophic forms of AMD. The purpose of this study was to analyze familial segregation of ABCR gene mutations in 52 unrelated multiplex cases of exudative AMD. METHODS: A complete ophthalmological examination including visual acuity measurement, fundus examination, and fluorescein angiography (FA) was performed on each exudative AMD patient. The entire coding sequence of the ABCR gene was analyzed using a combination of single-strand conformation polymorphism and confirmatory sequencing of the exons showing an abnormal pattern of migration. RESULTS: Six heterozygous missense changes were identified. A lack of familial segregation was observed in 4 of 6 codon changes (Arg943Gln, Val1433Ile, Pro1948Leu, and Ser2255Ile). Conversely, 2 codon changes cosegregated with the disease in 2 small families: Pro940Arg and Leu1970Phe. CONCLUSIONS: The authors believe that segregation of the ABCR gene mutations with familial cases of AMD has not yet been shown. The analysis of familial segregation allowed the authors to exclude 4 of 6 codon changes as disease-causing mutations. Furthermore, it was shown here that the ABCR gene may be rarely involved in exudative AMD, with at best 2 of 52 familial cases (4%) related to this susceptibility factor.
BACKGROUND: In pathologic myopia, choroidal neovascularization (CNV) usually occurs in macular region and at the center of the macular staphyloma. CNV has been reported to occur at the borders of an inferior posterior staphyloma in the tilted disc syndrome. We present a case of multiple simultaneous CNVs located at the borders of a myopic macular staphyloma. METHODS: The clinical and angiographic records of a myopic patient who presented several areas of choroidal neovascularization were reviewed. RESULTS: On fundus examination, four gray lesions surrounded by subretinal hemorrhages and covered by a large serous retinal detachment were observed at the borders of a posterior staphyloma. Fluorescein angiography revealed that these four lesions were CNVs extending from the borders of the staphyloma to the macular region. As measured by B-scan ultrasonography, the staphyloma was 4 mm deep. CONCLUSION: This case supports the hypothesis that the borders of staphylomas are sites at risk for the development of CNV in pathologic myopia.
PURPOSE: This study was designed to evaluate B-scan ultrasonography and optical coherence tomography in the pre- and post-operative morphologic evaluation of idiopathic epiretinal macular membranes. METHODS: Fifteen eyes were examined using B-scan ultrasonography and optical coherence tomography before and after surgical excision of the epiretinal macular membranes. RESULTS: Ultrasonography prior to surgery allowed an excellent evaluation of both the peripheral and the posterior vitreous and showed the membrane. The thickening of the retina and the retinal folds were equally visualised by either method. An improved observation of the macular oedema was obtained by the optical coherence tomography as well as the type of membrane adhesion. After surgery, both methods were able to detect membrane remnants. A better visualisation of retinal thickness and cystoid macular oedema was obtained by optical coherence tomography rather than ultrasonography. Serous sub-foveal retinal detachment was only revealed by optical coherence tomography. DISCUSSION: Ultrasonography is indispensable in case of media opacity or of optical inaccessibility of the posterior pole. Moreover, it allows an excellent global analysis of the anterior and posterior vitreous, which is very useful for the surgeon. The membrane is always showed by ultrasonography, but not always by optical coherence tomography in case of diffuse adherence. Both methods can detect the membrane and a cystoid macular edema. However, retinal analysis with the optical coherence tomography is more precise. It can even detect cysts of the macular oedema or serous sub-foveal retinal detachment. CONCLUSION: B-scan ultrasonography and optical coherence tomography give complementary information in pre- and post-operative examination of epiretinal macular membranes.
BACKGROUND: Subfoveal choroidal neovascularization is a main cause of blindness. The new surgical technique of macular translocation conceived by De Juan, with scleral shortening and without a retinotomy, allows to move the fovea away from the neovascular membrane with a low rate of complications. The first results obtained with this technique are presented here, in cases of submacular neovascularization due to age-related macular degeneration (AMD) or degenerative myopia. PATIENTS AND METHODS: The first 10 patients who were operated on with this technique presented with subfoveal neovascularization due to AMD (6 eyes) or myopia (4 eyes). The time period between the beginning of the disease and surgery was less than 3 months. Before and after surgery, a complete examination included fluorescein and ICG angiographies and OCT. RESULTS: Visual acuity improved by 2 lines or more in 6 eyes (60%), was unchanged in 3 eyes (30%) and decreased in 1 eye. The improvement in vision seemed higher in myopia than in ARMD. Conversely, the mean foveal displacement was greater in ARMD than in myopia (1.2 disc diameter and 0.5 respectively). Laser photocoagulation has been performed in all patients after surgery. Main complications were retinal detachment (1 eye) and neovascularization at the site of transretinal injection (1 eye). Mean follow-up was 3 months. COMMENTS: Macular translocation with the technique described by De Juan allowed visual improvement in more than the half of the eyes with subfoveal neovascularization, resulting in a moderate rate of complications. Long term follow-up is necessary to confirm these results.
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PURPOSE: To establish a pure culture of choriocapillary endothelial cells as a model of angiogenesis in vitro. MATERIAL AND METHODS: Bovine choriocapillary endothelial cells (BCEC) were obtained by the method described by Hoffmann et al. (6) using the polystyrene paramagnetic beads coated with Lycopersicon esculentum, which attach specifically to the rest of fucose on the surface of microvascular endothelial cells. The endothelial characteristic of the cultured cells was evaluated by immunocytochemistry using anti von Willebrand factor and anti-CD 31 antibodies. Proliferation and survival of BCEC were tested using haemacytometer of Mallasez. RESULTS: The purity of obtained BCEC culture was confirmed by positive immunocytochemical staining with anti von Willebrand and anti factor CD 31 antibodies in more than 95% of cells. The proliferation of cells in Endothelial Cell Medium resulted in twofold increase of number of cells during 4-day observation period. After reaching the confluence, the cells continued to proliferate with increase of the cell number by 60% during 4-day observation. CONCLUSION: The use of paramagnetic beads coated with specific lectine provide a pure isolation of BCEC, which can be maintained in culture with preservation of their characteristic.
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PURPOSE: To report clinical features and molecular genetic study in three unrelated families in which age-related macular degeneration was observed in grandparents of patients with Stargardt disease. METHODS: A complete ophthalmologic examination including best-corrected visual acuity measurement, fundus examination, and fluorescein angiography was performed on all members of the three families. The entire coding sequence of the ABCR gene was analyzed using a combination of single strand conformation polymorphism and direct sequence analysis of the 50 exons. RESULTS: Compound heterozygous missense mutations were observed in patients with Stargardt disease (Arg212Cys, Argl107Cys, Gly1977Ser, Arg2107His, and le2113Met). Heterozygous missense mutations were observed in the grandparents with age-related macular degeneration (Arg212Cys and Arg1107Cys). CONCLUSIONS: We report phenotype and genotype findings in three unrelated families segregating patients with Stargardt disease and age-related macular degeneration. The hypothesis that the Arg212Cys and Arg1107Cys ABCR gene mutations could be susceptibility factors for age-related macular degeneration is discussed. We speculate that the relatives of patients affected with Stargardt disease who are carriers of heterozygous ABCR gene mutations may have a higher risk of developing age-related macular degeneration.
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BACKGROUND/AIMS: Teletherapy has been proposed as a possible treatment for choroidal neovascular membranes (CNV), secondary to age related macular degeneration (AMD) not amenable to laser photocoagulation. The aim of this prospective study has been to investigate the effect of teletherapy on isolated occult choroidal neovascular membranes of subfoveal location. METHODS: 28 AMD patients presenting with retrofoveal isolated occult CNV demonstrated by fluorescein angiography were treated by external beam radiation. A complete ophthalmological examination, fluorescein angiography, and indocyanine green angiography (ICG) were performed within 15 days before treatment and repeated at follow up. A total dose of 16 Gy was applied in four sessions of 4 Gy using a 4 MeV photon beam. Follow up ranged from 6 to 9 months (mean follow up 6.4 months). RESULTS: Visual acuity was found to be stable in 68% of the cases. The decrease in visual acuity was of 3-6 lines in 18% and of more than 6 lines in 10% of the eyes at last examination. On fluorescein angiography the size of the lesion area was found to be stable in 67%, decreased in 13%, and increased in 20% of the cases. On ICG angiography the size of the CNV was stable in 93% and increased in 7% of the cases. All the eyes experiencing a visual acuity decrease showed either no change or an increase in size of the membrane on fluorescein angiography and/or on ICG. CONCLUSION: According to this study with strict inclusion criteria, external beam radiotherapy seems to have a beneficial effect on the evolution of isolated occult subfoveal CNV.
PURPOSE: To define the natural course of extensive submacular hemorrhage in age-related macular degeneration (AMD). PATIENTS AND METHODS: The clinical charts of 54 patients (60 eyes) older than 55 years with subretinal hemorrhage larger than 1 disk diameter and extending beneath the fovea were retrospectively reviewed. The age of the patient, the use of antihypertensive or anticoagulant medication, visual acuity, biomicroscopic and fluorescein and indocyanine green (in 33 cases) angiographic data were recorded at presentation and during follow-up. RESULTS: At the initial examination, average visual acuity was 20/240 (range from 20/70 to light perception). During follow-up (mean 24 months) visual acuity worsened in 80% of the eyes with a mean final visual acuity of 20/1, 250 (range from 20/100 to light perception). The initial size and thickness of hemorrhage were correlated with initial and final visual acuity. Recurrence of hemorrhage resulted in an important impact on final visual acuity. Anatomic outcome showed fibrous tissue proliferation in 23 eyes (38.3%), atrophic scar in 15 eyes (25%) and occurrence of a retinal pigment epithelium tear in 13 eyes (21.6%). CONCLUSION: The visual outcome in eyes with submacular hemorrhages due to AMD is very poor. Size and thickness of the hemorrhage influenced negatively the natural prognosis. A surgical approach can be considered although it has not yet a widespread use.
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