Indocyanine green angiography in choroidal tuberculomas.
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Biomedical subjects
Publications and source records attributed to C Fardeau.
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Ocular complications of Behçet's disease are considered one of the major criteria upon which the diagnosis is based. The ocular disease is characterized by repeated, explosive ocular inflammatory attacks which can healed spontaneously. During in-between attacks there is little or no evidence of inflammation in the eyes. The anterior segment can be involved alone presenting as a severe anterior uveitis with hypopyon. Posterior pole involvement is often sight threatening presenting as recurrent retinal vaso-occlusive disease. The fundus changes most frequently encountered are hyperhemia of the optic nerve, macular edema, retinal edema, vascular sheathing retinal exudate, and retinal hemorrhages. Complications of the inflammation include retinal and optic disc atrophy, neovascular glaucoma, vitreous hemorrhage, retinal detachment. Treatment is with topical steroids, systemic medications, including corticosteroids, colchicine, and immunosuppressive drugs. These complications are sight threatening and require a close follow up and a collaboration between ophthalmologists and Internal Medicine physicians.
Susac syndrome is an occlusive arteriolar disease that provokes infarcts in the cochlea, retina, and brain of young subjects, mostly women. Its cause is unknown. Some infarcts may be asymptomatic and only revealed by ancillary investigation: 1) audiogram that shows bilateral sensorineural hearing loss predominating on low frequencies, 2) funduscopy and fluorescein retinal angiography demonstrating bilateral distal branch retinal artery occlusions, and 3) brain MRI T2-weighted images disclosing small multifocal hyperintensities in white and gray matter. Treatment options are not codified, ranging from antithrombotic drugs to immunomodulatory therapy. Course is self-limited after an active fluctuating phase. Dementia, blindness, and deafness are rare late sequelae, and half of patients return to normal life.
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Intraocular lymphoma (IOL) is a rare form of non Hodgkin lymphoma (NHL); it has a poor prognosis and is frequently associated with central nervous system (CNS) infiltration. We report the results of a prospective study of 11 patients with IOL who received conventional chemotherapy (CT), followed by salvage high-dose (HD) CT with autologous bone marrow transplantation (ABMT) in five cases. All 11 patients had abnormal funduscopic findings and six had CNS involvement at diagnosis. The diagnosis was based on vitrectomy in 10 cases and cerebral stereotaxic biopsy in one. Pathologic studies showed large-cell NHL in all cases. These large-cell NHL were of the B-cell type in 8 cases and of the T-cell type in two. First-line therapy consisted of a combination of cisplatin 25 mg/m2 as a 24-hour IV infusion on 4 consecutive days, VP-16 40 mg/m2 for 4 days, aracytine 2 g/m2 IV on day 5, and methylprednisolone 500 mg IV daily for 5 days (ESHAP) in 5 cases; alternating courses of ESHAP and HD methotrexate (MTX) in 4 cases; and HD MTX in 2 cases. Three patients underwent ocular and whole-brain radiation therapy. Five refractory patients subsequently received intensive CT with thiotepa 750 mg/m2, busulfan 10 mg/kg and cyclophosphamide 120 mg/kg, followed by ABMT. First-line treatment failed in 10 evaluable cases. One patient died of CNS progression at 12 months. All the patients who underwent intensive CT and ABMT entered CR; two relapsed at 6 months and three are alive in CR 15, 15 and 14 months after ABMT. Six patients are alive with persistent disease at 8, 13, 14, 15, 18 and 24 months. It seems in conclusion that, high-dose thiotepa, busulfan and cyclophosphamide followed by ABMT is effective in some cases of refractory IOL.
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Lesions of the central nervous system result in invasion of peripheral phagocytes and/or in situ activation and proliferation of microglia, depending on the direct or indirect nature of the injury. Neurotoxins which are widely used to induce neurodegeneration have been reported to elicit a pure microglial reaction when administered intraventricularly. However, the mechanical lesion at the injection site, although remote from the lesioned area, could give access to blood-derived cells. Therefore, this study compares the phagocytic reaction occurring after a traumatic lesion of the brain causing a breakdown of the blood-brain barrier (BBB), or after degeneration of the inferior olivary neurons induced by intraperitoneal administration of 3-acetylpyridine, a process that respects the integrity of the BBB as suggested by the results of intravascular injection of Evans blue. The identification of the macrophages at the lesion site used specific binding of the B4 isolectin from Griffonia simplicifolia, preloading of the peripheral monocytes/macrophages with trypan blue, and characteristic morphological features. In traumatically lesioned rats, the lectin-labeled macrophages were mainly large rounded peripheral cells recruited 1-3 days postlesion, whereas in chemically lesioned rats, the cellular reaction appeared 24-36 h postinjection and peaked between 3 and 12 days before undergoing a slow decline. Lectin binding and morphological characteristics indicated that these small cells were reactive microglia. These results confirm that a brain injury leaving the BBB intact involves essentially the recruitment and/or the proliferation of microglia.
The emergence of cross-resistance to various antiviral drugs was investigated both in vivo and in vitro for herpes simplex virus type 1 (HSV1) resistant to idoxuridine (IUdR 0.24%) obtained by seven successive passages (from P0 to P7) in rabbit keratitis treated by IUdR. The viral population obtained at the seventh IUdR passage (P7) showed an activity of the thymidine kinase (TK) reduced to 5.6% of the parental strain (PO); moreover, most of the clones of P7 showed an altered TK phenotype determined by the [125I]iododeoxycytidine (IDC) procedure. In rabbit keratitis, IUdR-resistant viral population P7 showed cross-resistance to bromovinyl desoxyuridine (BVDU) (0.5%) and to acyclovir (ACV) (3%). Under trifluorothymidine (1%) treatment, P7 showed an intermediate sensitivity. HSV1 at P7 remained sensitive to adenine arabinoside (Ara A) (3%) and to dihydroxy-propoxymethylguanine used at high concentration (3%). The in vitro sensitivity determination to various antiviral drugs was investigated by dye-uptake assay for the initial viral population PO and for HSV1 collected under IUdR treatment at the third (P3) and the seventh (P7) passages. Cross-resistance to TK-dependent drugs, such as IDC, BVDU, and ACV were found at P7. P7 remained sensitive to Ara A and to phosphonoformic acids antiviral drugs known not to be dependent on viral TK.
The files of 40 patients operated on for epimacular membranes were reviewed in order to correlate the functional and anatomical results with the presence or absence of internal limiting membrane on histological specimens. Only the eyes with idiopathic membranes were considered for the study. Visual acuity and fluorescein angiography were obtained preoperatively and at the 6 months postoperative visit. The surface of the posterior pole was measured on fluorescein angiogram pre and postoperatively by computerized image analysis. Light microscopy looked for the presence of significant segments of internal limiting membrane. In 28 cases (group 1) long segments of internal limiting membrane were adherent to the epimacular membrane and in 12 cases (group 2) no internal limiting membrane fragments or only small fragments were present. Mean postoperative visual acuity was the same in the two groups; 64% of eyes from group I and 50% from group 2 had visual acuity superior or equal to 0.5 (NS). Image analysis showed that the posterior pole surface area increased by 25% in group 1 but only by 15% in group 2 (p < 0.025). Internal limiting membrane ablation does not preclude good visual recovery and is correlated with improved unfolding of the posterior pole.
During 7 serial passages of Herpes Simplex Virus (HSV1) in rabbit cornea treated with idoxuridine (IUdR) (P1 to P7), the emergence of resistance had been obtained from P3. The reversion towards IUdR sensitivity has been investigated from either viral population P3 or P6 by 6 serial passages in rabbit cornea treated by Vaseline (V1 to V6). From viral population P3, the reversion to IUdR sensitivity has been obtained at V4. In contrast, from viral population P6, the IUdR resistance was conserved from V1 to V6. In vitro, on Vero cells, the effective doses 50% (ED50) and 90% (ED90), determined by dye uptake assay and plaque reduction assay, confirmed the reversibility towards IUdR sensitivity obtained from P3 and the stability of IUdR resistance from P6.
In a controlled clinical trial, 160 eyes underwent "perifoveal" laser photocoagulation. All patients had age-related macular degeneration and subfoveal neovascularization (0.5 to 2.5 disc diameters), without detectable fibrous tissue, and visual acuity from 20/100 to 20/1000. At least 1 year of follow-up has been completed in 127 eyes. Visual acuity was maintained or improved in 12 (20.3%) of 59 untreated eyes vs 28 (41.1%) of 68 treated eyes (P = .04). Reading visual acuity (J4) with the use of low-vision aids was retained in 28 untreated eyes (47.4%) vs 50 treated eyes (73.5%) (P less than .01). Automated static perimetry showed an increased scotomatous area and/or depth with eccentric fixation in all but four patients. A flat atrophic scar was achieved in 53 of 68 treated eyes. Statistical analysis indicated that perifoveal photocoagulation has been effective in the short-term preservation of visual acuity.
The acquisition of drug resistance in vivo was investigated by 7 serial passages (from P0 to P7) of herpes simplex virus (HSV-1) in rabbit cornea treated with either IUdR (idoxuridine), IDC (idoxycytidine), ACV (acyclovir), TFT (trifluridine), or Ara A (adenine arabinoside). Therapeutic failure was acquired gradually: at P3 for IUdR, at P4 for ACV and at P5 for TFT. At P7, viral thymidine kinase (TK) activity was reduced to 5.6% of the parental strain for IUdR, to 7.5% for ACV and to 4.6% for TFT treatment. No signs of clinical unresponsiveness occurred with IDC or Ara A. The in vitro determination of antiviral drug sensitivity performed by the dye-uptake assay on HSV isolates at each passage showed a correlation between the increase in the 50% effective dose (ED50) and the increase of ulcer area grade at each passage under antiviral drug (p less than 0.1). Both IUdR- and TFT-resistant HSV1 developed cross-resistances to TK dependent drugs. However ACV-resistant HSV1 did not show cross-resistance to other antiviral TK dependent drugs. The acquisition of the cross-resistances is discussed, and the practical implications in case of therapeutic failures are suggested.
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AIM: Macular edema is still the main cause of poor visual prognosis in central retinal vein occlusion (CRVO). This study was designed to establish whether grid photocoagulation is effective in the management of this disorder. METHODS: The records of 16 patients who had undergone macular grid photocoagulation for persistent macular edema due to CRVO were reviewed retrospectively. Pre-treatment visual acuity ranged from 20/400 to 20/40, and laser treatment was done six months or more after the onset of the disease. RESULTS: Biomicroscopy and fluorescein angiography showed the improvement or disappearance of macular edema in 14/16 patients (87.5%). Improved visual acuity was observed in eight (50%) and no improvement or reduced vision in the other eight (50%). A poorer prognosis was statistically correlated with older age (p < 0.03), macular ischemia (p < 0.001), foveal avascular zone larger than 1/2 disc diameter (p < 0.05) and pigmentary clumps in the foveal area (p < 0.05). Laser treatment was ineffective for most patients with systemic vascular risk factors and pre-treatment visual acuity below 20/200. CONCLUSION: Macular grid photocoagulation may be effective for drying up, or at least reducing, macular edema due to CRVO and some improvement of vision can be expected in half the cases.