Cidofovir ocular toxicity is related to previous ocular history.
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
E Frau
Publications and source records attributed to E Frau.
Acyclovir-resistant bilateral keratitis associated with mutations in the HSV-1 thymidine kinase gene.
PURPOSE: To evaluate the contribution of molecular methods for the diagnosis of an acyclovir-resistant HSV-1 bilateral keratitis in an AIDS patient and to report a new point mutation in the nucleotide sequence of the thymidine kinase (tk) gene involved. METHODS: A 31 year old HIV-positive female presented with severe, active, bilateral and sight-threatening keratitis of 6 months duration, which was treated unsuccessfully with acyclovir. After corneal biopsy, samples were analysed by standard virological procedures, in situ hybridization, and PCR. The tk gene was cloned and subsequently sequenced. RESULTS: Conventional virological methods remained inconclusive. However, in situ hybridization and PCR rapidly confirmed the diagnosis of HSV-1 keratitis. The tk gene sequence revealed the presence of five variations previously described in two reference strains, but also a new point mutation at nucleotide position 431 which leads to an amino-acid change at position 144 that supported the hypothesis of a putatively altered functional form of the enzyme. Intravenous foscarnet treatment in an induction regimen was effective and cicatrization occurred within 3 weeks. CONCLUSIONS: PCR and in situ hybridization are effective and powerful techniques when other virological procedures are non-contributive, particularly in immunocompromised patients previously treated with antiviral drugs. The new point mutation identified in the tk gene may be associated with resistance to acyclovir.
AIDS-Related Opportunistic Infections↗
Neuronal pathways for the propagation of herpes simplex virus type 1 from one retina to the other in a murine model.
Herpetic retinitis in humans is characterized by a high frequency of bilateral localization. In order to determine the possible mechanisms leading to bilateral retinitis, we studied the pathways by which herpes simplex virus type 1 (HSV-1) is propagated from one retina to the other after intravitreal injection in mice. HSV-1 strain SC16 (90 p.f.u.) was injected into the vitreous body of the left eye of BALB/c mice. Animals were sacrificed 1, 2, 3, 4 and 5 days post-inoculation (p.i.). Histological sections were studied by immunochemical staining. Primary retinitis in the inoculated eye (beginning 1 day p.i.) was followed by contralateral retinitis (in the uninoculated eye) starting at 3 days p.i. Infected neurons of central visual pathway nuclei (lateral geniculate nuclei, suprachiasmatic nuclei and pretectal areas) were detected at 4 days p.i. Iris and ciliary body infection was minimal early on, but became extensive thereafter and was accompanied by the infection of connected sympathetic and parasympathetic pathways. The pattern of virus propagation over time suggests that the onset of contralateral retinitis was mediated by local (non-synaptic) transfer in the optic chiasm from infected to uninfected axons of the optic nerves. Later, retinopetal transneuronal propagation of the virus from visual pathways may have contributed to increase the severity of contralateral retinitis.
Animals↗
[Familial amyloid polyneuropathy type I complicated by chronic glaucoma: 3 cases].
PURPOSE: We report 3 cases of familial amyloid polyneuropathy type I (FAP) with amyloid infiltration of the vitreum and glaucoma. PATIENTS AND METHODS: We reviewed the records of three patients, 2 females and one male, aged 41, 47 and 83 years respectively. The 3 patients had familial amyloid polyneuropathy type I with vitreous infiltration and open angle glaucoma. The two women underwent a liver graft four years earlier. Vitrectomy allowed confirmation of the diagnosis in the 83-year-old patient. Two patients underwent trabeculectomy, histological analysis of the iris and the trabeculum was obtained for one patient. RESULTS: The tree patients presented a polyneuropathy, vitreous infiltration and open angle glaucoma. Results of light microscopy of the iris and the trabeculum showed amyloid deposits in the iris and the trabecular meshworks. CONCLUSION: Familial amyloid polyneuropathy is a hereditary disease which may have a wide range of ocular manifestations. Glaucoma is among the most serious complications of familial amyloid polyneuropathy.
Adult↗
[Optic neuropathy after proton-beam therapy for malignant choroidal melanoma].
Proton-beam irradiation is a conservative therapy commonly used for the treatment of uveal malignant melanomas. Some adverse effects such as optic neuropathy can compromise the visual outcome. We were interested in determining the risk factors for radiation papillopathy. Since there is currently no effective therapy, this is an interesting way to improve prevention of optic neuropathy. Six hundred sixty-two eyes had more than 24 month follow-up after proton-beam irradiation for uveal melanoma. In five hundred twenty-two cases, the clinical examination of the optic nerve head by ophthalmoscopy was possible. One-hundred eleven optic discs were pathologic, whereas 411 remained disease-free. Retrospective study of these two groups allowed to quantify the risk factors for optic neuropathy. The irradiation of more than 2mm of optic nerve at 30 Grays-equivalents appeared to be the major risk factor for optic neuropathy. For a given irradiation dose, the observed pattern of clinical responses was heterogeneous. These results are discussed and compared to the previous published reports. Visual results and life prognosis are also discussed, considering the optic nerve head status. Proton-beam therapy can preserve the optic nerve when the tumor location allows to keep it away from the irradiation-field. Patients must be informed about the risk of optic neuropathy after proton-beam irradiation.
Choroid Neoplasms↗
Neuronal propagation of HSV1 from the oral mucosa to the eye.
PURPOSE: To identify possible neuronal pathways leading to herpetic ocular disease after primary oral infection in mice. METHODS: The SC16 strain of herpes simplex virus (HSV)-1 (10(6) plaque-forming units) was injected into the mucocutaneous border of the left upper lip. Animals were killed 2 to 10 days postinoculation (DPI). Spread of the virus in neural structures was studied by immunochemistry. RESULTS: HSV1 first replicated at the site of inoculation and then at the superior cervical ganglion (at 2 DPI). The trigeminal ganglion and the facial nerve fibers were infected by 4 DPI. Infection of the ciliary body and iris occurred at 6 DPI, together with several brain stem nuclei belonging to the autonomic or sensory pathways. Between 8 and 10 DPI, the neural infection gradually cleared up, except for the ipsilateral sympathetic ganglion, and ipsilateral keratitis appeared in some animals. CONCLUSIONS: The pattern of viral dissemination in this mouse model suggests that infection of iris and ciliary body results from transfer of virus in the superior cervical ganglion from sympathetic neurons innervating the lip to neighboring neurons innervating the anterior uvea. Later, zosteriform spread of virus from the trigeminal system may have contributed to the clinical and histologic findings.
Animals↗
Cytomegalovirus retinitis in advanced HIV-infected patients treated with protease inhibitors: incidence and outcome over 2 years.
We prospectively studied the incidence of cytomegalovirus (CMV) retinitis in 93 patients treated with highly active antiretroviral therapy (HAART) containing a protease inhibitor (PI), during a median follow-up period of 24 months. The median initial CD4+ count was 22 cells/microl (range, 1-311 cells/microl), and the median plasma HIV viral load was 5.1 log10 copies/ml (range, 2.4-6.4 log10 copies/ml). The fundus was examined monthly in patients with a history of CMV retinitis or an initial CD4+ count <50 cells/microl and every 3 months in the other patients. Of patients with previously controlled CMV retinitis, 1 of 7 relapsed. In addition, 6 of 59 patients with a CD4+ count <50 cells/microl and no history of CMV retinitis before starting PI therapy developed CMV retinitis. Of them, 3 had at least one relapse during follow-up. CD4+ counts were <40 cells/microl at the time of primary or recurrent CMV retinitis, except in two cases (147 cells/microl and 203 cells/microl). In conclusion, the incidence of CMV retinitis was 0.091 per patient-year among study subjects with advanced HIV infection who were receiving HAART (95% confidence interval [CI], 0.037-0.145). The time to progression of CMV retinitis (mean, 215 days; 95% CI, 113-317 days) was longer than reported before widespread use of PIs.
AIDS-Related Opportunistic Infections↗
Phacoemulsification combined with silicone oil removal through posterior capsulorhexis.
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Adolescent↗
[Hemangioma of the choroid with extra-scleral extension].
We report a case of atypical circumscribed choroidal hemangioma with retinal detachment in a 41-year-old man referred with the diagnosis of Harada disease. B. Scan ultrasonography showed an hyperechogenic area extended through the sclera. Careful examination of the fundus showed a small peripapillary orange mass and an inferior retinal detachment. Surgical exploration revealed an extrascleral hemangioma. Proton beam irradiation was followed by retinal reattachment within three months. No recurrence has been observed 18 months after treatment.
Adult↗
A preliminary comparative treatment planning study for radiotherapy of age-related maculopathy.
PURPOSE: We present a comparative planning of different approaches for external radiotherapy in age-related maculopathies. MATERIALS AND METHODS: Calculated dose distributions and dose-volume histograms for (a) bilateral irradiation with 6 MV photons, (b) a single lateral-oblique beam using either photons, electrons or protons and (c) an anterior circular proton beam. RESULTS: For lateral photon or electron beams the dose to the lens is usually lower than 10% of the dose to the macula. The entrance doses for bilateral photon beams are about 50% which increase up to 100% at the orbital bone. About 5 mm of optic nerves are irradiated at the maximal dose while the optic chiasma is spared. A single photon beam gives 50% of the dose to the fellow eye. The electron beam spares the fellow eye but gives a rather inhomogeneous dose to the target volume. For a lateral proton beam, 4 mm of optic nerve receives 90% of the dose, the skin dose is at least 70% of the dose to the macula and the lens and the fellow eye are spared. An anterior proton beam gives 90% of the dose to 1 mm of optic nerve and the 50% isodose approaches the periphery of the lens. CONCLUSION: Doses to the critical structures can be dramatically diminished for all the techniques by reducing the beam size, but only if very precise set-up techniques are used. Proton beams are an attractive solution, but the impact of such a choice on the use of proton facilities and on the national health system should be carefully evaluated, as well as the risk of radio-induced secondary neoplasias.
Humans↗
T-cell clonal expansion in patients with B-cell lymphoproliferative disorders.
We investigated whether T-cell clonal expansion could be found in the blood of 14 untreated patients with B-cell lymphoproliferative disorders [5 B-chronic lymphocytic leukemia (CLL), 4 myelomas, 5 non-Hodgkin lymphoma (NHL)]. The putative presence of T-cell clonotypes was analyzed with a polymerase chain reaction-based method determining V-D-J junction size patterns in 24 T-cell receptor (TCR) V beta subfamilies. This high-resolution method, analyzing CDR3 sizes of TCR transcripts, was used in conjunction with cytometric analysis of the corresponding T-cell subpopulations with 18 TCR V beta-specific monoclonal antibody. We found multiple dominant T-cell clonotypes in the blood of most patients with B-CLL or myeloma as well of a patient with stage IV NHL. In some cases, T-cell clonal expansion was so dominant that the percentage of these clonal T-cell subpopulations in blood represented more than the mean +2 SD value determined in a series of healthy controls. We conclude that a systemic antigen-specific (i.e., leading to clonotypic expansion) immune reaction involving few TCR clonotypes is a hallmark of disseminated B-cell malignancies. The nature of the putative antigens recognized is not known presently. Nonetheless, such insights into the T-cell repertoire of these patients may help to reassess the potential of immunotherapeutic strategies in B-cell malignancies.
Adult↗
Silicone oil removal combined with macular pucker dissection: a retrospective review of 14 cases.
PURPOSE: Silicone oil must be removed from the eye to avoid late complications after the surgical management of proliferative vitreoretinopathy (PVR). Macular pucker, frequently observed after retinal detachment surgery, is responsible for visual impairment. The safety of a procedure combining epimacular membrane peeling and silicone oil removal was retrospectively evaluated. METHODS: Fourteen eyes that had previously undergone vitrectomy and silicone oil tamponade for rhegmatogenous retinal detachment with severe PVR, penetrating or blunt trauma, and intraocular foreign bodies were included. Silicone oil tamponade was maintained for a mean period of 30 weeks (range, 12-108 weeks). The removal of silicone oil was combined with the peeling of an epimacular membrane. RESULTS: Mean follow-up after silicone oil removal was 86 weeks (range, 13-234 weeks). The final retinal reattachment rate was 78%. Macular pucker recurred in one eye after a 24-month period. Best-corrected visual acuity improved two lines or more in eight eyes (57%) and reached 20/200 or better in eight eyes (57%) at last follow-up. CONCLUSION: Macular pucker dissection and silicone oil removal can be safely combined. This single procedure can obviate the need for further surgery in eyes that have already undergone multiple operations and allows good visual recovery.
Adolescent↗
[Incidence and evaluation of viral retinitis in patients infected with the HIV virus and treated with HIV protease inhibitors].
BACKGROUND: Since the beginning of the use of HIV-Protease Inhibitors (PI) to treat HIV-infected patients, a decrease of the incidence of extraocular opportunistic infections has been observed. We studied the incidence of CMV-retinitis in patients treated with a highly active antitetroviral therapy (HAART) containing PI over a mean follow-up of 12 months. METHODS: Ninety-three HIV-infected patients treated with HAART containing PI were included. The mean initial CD4+ cell-count was 54/microliter (median: 22/microliter), and the mean plasma HIV-load was 5.46 log 10 RNA-copies/ml. Fundus examination was performed each month in case of a previously treated and controlled CMV-retinitis or if initial CD4 cells were below 50/microliter. In other patients, fundus examination was performed every 3 months. The mean follow-up was 362 days. RESULTS: Among the 7 patients with a previously treated and controlled CMV-retinitis, one experienced a progression during the study (after 163 days of PI). Among the 59 patients with CD4 cells below 50/microliter and without previous CMV-retinitis before the beginning of PI, 5 experienced a CMV-retinitis (mean delay after the onset of HAART: 141 days), including 2 with relapse. When retinitis occurred, CD4 cells were below 32/microliter except in one case (147/microliter). CONCLUSIONS: Compared to previously published reports, this study showed an increase of the time to progression of previously treated and controlled CMV-retinitis in patients treated with PI. Considering deeply immunocompromised patients (less than 50 CD4-cells/microliter), the risk of suffering from CMV-retinitis was 8.5% after 12 months of PI treatment. Longer follow-up remains necessary to confirm these results.
AIDS-Related Opportunistic Infections↗
Efficacy of proton therapy in circumscribed choroidal hemangiomas associated with serious retinal detachment.
OBJECTIVE: The purpose of the study is to evaluate the efficacy and safety of proton therapy in complicated circumscribed choroidal hemangiomas. DESIGN: The study design was a retrospective review. PARTICIPANTS: Studied were 13 patients (13 eyes) who had circumscribed choroidal hemangioma associated with serous retinal detachment. Of these, four eyes previously underwent laser unsuccessfully. INTERVENTION: Proton therapy including a total dose of 30 Cobalt-Gray-Equivalent was administered to each eye. MAIN OUTCOME MEASURES: Patients were controlled for initial and final best-corrected visual acuity, slit-lamp examination, intraocular pressure, fundus examination, fluorescein angiography, and tumor thickness on B-scan ultrasonography. RESULTS: The mean follow-up period was 26 months (range, 9-48 months). Retinal reattachment was obtained in all cases after a mean period of 52 days. The tumor height decreased in all cases. Visual acuity improved to two lines or more in eight eyes (62%) and reached 20/200 or more in nine eyes (69%). No radiation complication was detected during follow-up. CONCLUSIONS: Proton radiation seems to be effective and safe in the management of choroidal hemangioma associated with serous retinal detachment. It may be useful when photocoagulation can not be performed.
Adult↗
[Initial results of proton therapy in choroidal melanoma at the d'Orsey Center for Proton Therapy; the first 464 cases].
PURPOSE: Retrospective analysis of the treatment of choroidal melanoma with protontherapy at the Centre de protonthérapie d'Orsay, France. PATIENTS AND METHODS: Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by protontherapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow-up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. RESULTS: Univariate analysis showed that the actuarial local recurrence rate was 5%, the 3-year survival rate 88%, and the overall metastasic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. CONCLUSION: Protontherapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor.
Choroid Neoplasms↗
[A case of atypical exsudative retinal detachment and its treatment].
A 32 year-old woman with bilateral retinal detachment was observed for 18 months after the onset of symptoms. Because of probable systemic lupus erythematosus and a partial response to corticosteroid treatment she received, monthly, cyclophosphamide intravenously. The mechanism of this choroidopathy and its surgical management is discussed in light of data found in the literature.
Adult↗
[Subconjunctival adipose hernias of the orbit].
Clinical report of three cases of subconjunctival fat prolapse. Differential diagnoses are discussed. Subconjunctival orbital fat prolapse is a benign entity with a fat herniation through defective Tenon's capsule.
Adipose Tissue↗
[Retinal detachment secondary to CMV retinitis].
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AIDS-Related Opportunistic Infections↗