Experimental therapies for age-related macular degeneration.
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Biomedical subjects
Publications and source records attributed to G Coscas.
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Age-related macular degeneration is the leading cause of non treatable blindness in industrialized countries. The impairment of visual acuity is preceded by the occurrence of "precursors" some of which are the witness of aging and others are the first symptoms of age-related degeneration of the macular retina. The disease involves both eyes with time resulting in a major handicap. Eventually, central visual acuity is destroyed, making reading, writing and recognition of faces impossible. Different clinical types are identified: the atrophic form for which there is at present no possibility of treatment, and the neovascular form in which the destruction of the new vessels with laser photocoagulation is beneficial. However, only an early diagnosis and treatment may allow a preservation of central vision. New possibilities of angiographic diagnosis, new therapeutic approaches (macular surgery or transplantation) based on physiopathogenic research, provide new hopes.
Hereditary retinal dystrophies can be subdivised into central (macular) and peripheral degenerations. Stargardt disease, Best disease, cone dystrophy and retinoschisis, affecting children or young adults, are the 4 commonest macular dystrophies. Retinitis pigmentosa, with primary affects photoreceptors, presents a wide clinical, genetic and molecular heterogeneity. It is certainly the most representative cause of peripheral degeneration. Recent advances in molecular biology allow a more complete clinical definition of these inheritable retinal diseases.
PURPOSE: To analyze indocyanine green angiographic findings of pathologic myopia and compare them with those of fluorescein angiography, with particular reference to the usefulness of indocyanine green angiography in the management of neovascular complications. METHODS: Thirty-two consecutive patients (52 eyes) with pathologic myopia underwent a complete ophthalmologic examination including fluorescein and indocyanine green angiography. RESULTS: Retrobulbar arteries and veins were visualized solely on indocyanine green angiography in 33 (63%) of 52 eyes. Choroidal arteries appeared attenuated and reduced in number. In the area of staphyloma, choroidal veins were less numerous, and in all eyes an absence of the normal choroidal flush caused by the choriocapillaris filling was observed. Subretinal and retinal hemorrhages were present in 28 (54%) of 52 eyes. Choroidal neovascularization was diagnosed in 16 eyes on fluorescein angiography and in 18 eyes on indocyanine green angiography. In seven eyes, indocyanine green angiography disclosed lacquer cracks (without choroidal neovascularization), appearing in the late phases as hypofluorescent lines, as the probable cause of the subretinal and retinal hemorrhages. In only one eye did indocyanine green angiography fail to disclose choroidal neovascularization detectable on fluorescein angiography. In two eyes, neither dye could clarify the origin of the hemorrhages. CONCLUSIONS: Indocyanine green angiography allows identification of retrobulbar arteries and veins, and analysis of the altered choroidal vasculature. Moreover, indocyanine green angiography is a useful diagnostic tool to differentiate lacquer cracks from choroidal neovascularization in retinal and subretinal hemorrhages.
BACKGROUND: The prognosis of retinal vein occlusion is highly unpredictable because nonischemic types may convert into ischemic types within the first months. This study was designed to identify epidemiologic characteristics of the different types of retinal vein occlusion, their visual outcome, and their prognostic factors. METHODS: The authors analyzed prospectively the data from patients who have had retinal vein occlusion with complete medical and biologic examination, including fluorescein angiography, and a 1-year follow-up. RESULTS: One hundred seventy-five retinal vein occlusion eyes consisted of 120 central retinal vein occlusions (CRVO), 7 hemicentral occlusions, and 48 branch occlusions. In initially nonischemic CRVO eyes, retinal ischemia developed in 54%. The study of prognostic factors in the CRVO group showed that older age, male sex, and the number of risk factors (systemic vascular risk factors and glaucoma) were correlated with a poor visual outcome and with the development of retinal ischemia, as well as baseline visual acuity, initial extent of retinal ischemia, and rheologic findings (hematocrit, fibrinogen, and erythrocyte aggregation levels). Logistic regression underlined the prognostic role of sex, the number of risk factors, erythrocyte aggregation, and initial clinical features. Persistent macular edema was shown to be associated with hyperlipidemia and cardiovascular history, and inversely correlated to glaucoma. CONCLUSION: Because clinical characteristics of CRVO may worsen, the authors' results provide a basis to predict visual outcome by taking into account epidemiologic and rheologic findings. A careful follow-up of these patients is recommended.
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A young woman presented with an elevated, retinal yellow-white lesion in mid-periphery of one eye, associated with a dragged disc. Different aetiologies were discussed including retinopathy of prematurity, familial exudative vitreoretinopathy, congenital retinal folds, incontinentia pigmenti, Eales' disease, toxocariasis, combined hamartoma of the retina and the pigment epithelium.
OBJECT: Bone marrow transplantation has improved the prognosis of haematological malignancies, but patients are consequently at considerable risk of developing ocular complications, such as cataracts. MATERIAL AND METHODS: A retrospective case study of 36 eyes (24 patients), with cataract extraction after the transplantation. Surgery was performed at a mean of 4.5 years after transplantation and the average age was 33 years at the time of surgery. The lens changes were all of the posterior subcapsular type. Surgery was indicated for symptoms of dazzling and glare; visual acuity was only moderately decreased (4/10, P6). RESULTS: Cataract surgery required specific measures such to "polish" the posterior lens capsule, since cataract changes were often very adherent. The surgery follow-up was uncomplicated with the exception of five eyes which had an inflammatory reaction (3 cyclitic membrans, 2 "pseudo-endophthalmitis") but which showed complete regression after treatement. The follow-up after surgery varied from 6 months to 4.5 years. Final visual outcome was improved. 82.5% achieved 8/10, and 96.8% achieved P2. Three YAG-laser capsulotomies were performed, mainly for posterior capsulofibrosis. COMMENTS: Cataract surgery after bone marrow transplantation appears to have a good prognosis. Posterior capsule "polishing", though difficult, is possible in most cases. In our study, secondary cataract appears to be less frequent, but, further long-term follow-up is needed to confirm this statement.
PURPOSE: Optic nerve pit is a rare congenital anomaly. In two third of the patients, the severity of the disease is increased by the apparition of a serous macular detachment, which may compromise the visual prognosis. The aim of this study is to propose a therapy appropriate to such complication. METHODS: A prospective study was performed including 10 patients with a serous macular detachment caused by optic nerve pit. All patients underwent intraocular surgery including vitrectomy, peripapillary photocoagulation and intravitreal injection of gas. The mean postoperative follow-up period was 9.5 months. RESULTS: Therapy success was based on anatomical and functional results. Serous macular detachment reattached in 7 patients out of 10 and a recurrence was observed in one case. Visual acuity improved from 0 to 18 lines of the EDTRS chart (mean increase: 6.7 lines). CONCLUSION: These results confirm that intraocular surgery including vitrectomy-photocoagulation-gas injection is a valuable treatment for serous macular detachment associated with optic nerve pit.
OBJECTIVE: To identify specific features of pigment epithelium detachments with limited hyperfluorescent lesions (hot spots). DESIGN: One hundred eighty-two consecutive patients (186 eyes) who had vascularized pigment epithelium detachments and recent onset of symptoms were examined with indocyanine green and fluorescein videoangiography using the scanning laser ophthalmoscope. The choroidal neovascularization complex and macular retinal vessels were studied. The natural history and the effect of laser treatment were evaluated. RESULTS: Fifty-four eyes had hot spots on indocyanine green angiography. In 50 of these 54 eyes, the video analysis showed an anastomosis of one or more retinal vessels, with the choroidal neovascularization within the hot spot. One or two retinal veins or arteries or both filled with both dyes and were seen to enter into the hot spot. Results of indocyanine green-guided photocoagulation of the hot spot in 28 eyes were disappointing. CONCLUSION: Continuous recording of the early phases of fluorescein and indocyanine green angiography allowed identification of chorioretinal anastomoses in vascularized pigment epithelium detachments with hot spots at an early exudative stage of age-related macular degeneration in 50 (26.8%) of 186 eyes. The poor outcome of laser photocoagulation could be related not only to the development of an overlying pigment epithelium detachment, but also to the retinal and choroidal vascularization of the lesion.
BACKGROUND: Congenital microcoria, a bilateral condition of the iris dilatator, is defined as a pupil with a diameter of less than 2 mm when looking at a distant object. Although it is usually a hereditary condition resulting from autosomal dominant transmission with no marked difference between the sexes, it is sometimes sporadic. The ocular abnormalities associated with this condition (myopia, astigmatism, and glaucoma) have never been linked to the malformation. METHOD: Forty-two members of a family were examined: 23 had microcoria and 19 did not. The two groups were studied to identify symptoms of the condition and its associated abnormalities. RESULTS: There was a very strong correlation between microcoria and myopia (Fisher's exact test, P < 0.00001), between microcoria and astigmatism (Fisher's exact test, P < 0.0001), and between microcoria and glaucoma (Fisher's exact test, P = 0.011). CONCLUSIONS: There is a statistical correlation among myopia, glaucoma, and microcoria, and the disorders are associated with the condition in a nonfortuitous way. The functional prognosis for microcoria appears to be extremely poor because of refractive disorders and, particularly, a link between microcoria and glaucoma that is difficult to explain.
A case of central retinal vein occlusion with second development of the same type of retinal vein occlusion in the fellow eye, is reported. The patient was a 68 year-old man with a history of thyroid gland disorder and a cardiac arrhythmia. He presented also with bilateral tilted disc. The first eye occlusion was initially nonischemic, but converted secondarily into an ischemic type and required laser panretinal photocoagulation. The biological assay found the presence of lupus anticoagulant antibodies and rheological findings (major plasma hyperviscosity, increased erythrocyte aggregation, high hematocrit and fibrinogen levels). The patient was given high doses of troxerutin, and aspirin. Central retinal vein occlusion occurred in the fellow eye one year later, a few weeks after the decrease of troxerutin doses. Hemodilution therapy was performed and visual acuity remained unchanged. Unusual risk factors for retinal vein occlusion are discussed. Lupus anticoagulant antibodies may sometimes lead to occlusive vascular phenomenon. Although these antibodies are not commonly found in retinal vascular occlusion, they may constitute a contributory factor. Tilted disc has often been involved in the pathogenesis of central retinal vein occlusion. Finally, abnormal rheological findings, major in this case, are found in more than half of the cases of retinal vein occlusion.
Rheologic abnormalities, observed in type I and type II diabetes, have been implicated in the onset and progression of microangiopathy and of diabetic retinopathy. This theory of pathogenesis, proposed by Farhaeus in 1921, and developed by Little, takes into account complex abnormalities of blood viscosity, platelet and erythrocyte aggregation, fibrinolysis, coagulation and oxygen fixation by hemoglobin. The correction of these abnormalities might delay or prevent the onset or the progression of diabetic microangiopathy, most notably of retinopathy. No study, however, has demonstrated an therapeutic effect of molecules acting on the different rheologic factors. In contrast, strict long-term control of glycemia leads to a partial or complete correction of some of these rheologic abnormalities.
Diabetic retinopathy is the main cause of decreased visual acuity in non-proliferative or proliferative diabetic retinopathy. The frequency of maculopathy rises with age and the duration of diabetes, and now represents the major therapeutic problem following the control of neovascular proliferation through pan-retinal photocoagulation. Oedematous maculopathy, focal or diffuse, and cystoid macular oedema are improved by laser photocoagulation, either focal or grid. Laser photocoagulation is not indicated for predominantly ischaemic maculopathy. The laser treatment should be carried out early in the stage of clinically significant oedema, and applied either focally or in a grid depending on the clinical and angiographic features of the diabetic maculopathy. If pan-retinal photocoagulation is also indicated it should be performed after the focal macular treatment. Laser treatment should always be accompanied by a general medical assessment, emphasising optimal glycemic control and control of associated risk factors, especially arterial hypertension.
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Hemorheologic factors probably play a role in the pathogenesis and prognosis of retinal vein occlusion. Accordingly, we designed a prospective, randomized, double-masked study to evaluate the effect of troxerutin, a rheologic drug, on retinal vein occlusion. Fifty-three patients were included, 27 with central retinal vein occlusion and 26 with branch retinal vein occlusion. They were randomly assigned for treatment with either troxerutin or a placebo. All subjects were similar in age, gender, associated diseases, hemorheologic values, and clinical severity of the retinal vein occlusion. At the end of follow-up, members of the troxerutin-treated group, as compared with the placebo group, showed significant improvement in visual acuity (P = .03), macular threshold (P = .01), retinal circulation times (P = .04), and macular edema (P = .05). Furthermore, they had diminished progression of ischemia (P = .05) and decreased red blood cell aggregability (P = .006) when compared with the controls. These encouraging preliminary results obtained with a rheologic treatment attest to the pathogenic role of blood viscosity in retinal vein occlusion and suggest that a large-scale randomized study should be conducted.