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Biomedical subjects

L Zografos

Publications and source records attributed to L Zografos.

At least 19 recordsLinked to original sources

Diagnosis and current management of retinoblastoma.

Retinoblastoma represents the prototypic model for inherited cancers. The RB1 gene was the first tumor suppressor gene to be identified. It represents the most frequent primary eye cancer in children under 15 years old, habitually occurring in infancy, even in utero, but can be observed in older children or young adults. Many other retinal lesions may also simulate retinoblastoma. The two major presenting signs are leukocoria and strabismus, but other ocular or general signs may be observed. A highly malignant tumor, retinoblastoma can nowadays be cured. The heritable form, however, carries a high risk of second nonocular tumors. Treatment in the early stages of disease holds a good prognosis for survival and salvage of visual function. In very late stages, however, the prognosis for ocular function and even survival is jeopardized.

Cell Division↗

Intra-arterial hepatic fotemustine for the treatment of liver metastases from uveal melanoma: experience in 101 patients.

BACKGROUND: Exclusive liver metastases occur in up to 40% of patients with uveal melanoma associated with a median survival of 2-7 months. Single agent response rates with commonly available chemotherapy are below 10%. We have investigated the use of fotemustine via direct intra-arterial hepatic (i.a.h.) administration in patients with uveal melanoma metastases. PATIENTS AND METHODS: A total of 101 patients from seven centers were treated with i.a.h. fotemustine, administered intra-arterially weekly for a 4-week induction period, and then as a maintenance treatment every 3 weeks until disease progression, unacceptable toxicity or patient refusal. RESULTS: A median of eight fotemustine infusions per patient were delivered (range 1-26). Catheter related complications occurred in 23% of patients; however, this required treatment discontinuation in only 10% of the patients. The overall response rate was 36% with a median overall survival of 15 months and a 2-year survival rate of 29%. LDH, time between diagnosis and treatment start and gender were significant predictors of survival. CONCLUSIONS: Locoregional treatment with fotemustine is well tolerated and seems to improve outcome of this poor prognosis patient population. Median survival rates are among the longest reported and one-third of the patients are still alive at 2 years.

Adult↗

[New trends in corneal surgery. Grafting stem cells and performing lameliar graft].

Epithelial, stromal or endothelial diseases can generate corneal opacity. A lake of corneal epithelial cells leads to corneal opacity and low visual acuity. In these cases, corneal epithelial stem cells from the limbus of the healthy eye or from relatives or other people must be grafted to regenerate corneal epithelium. It is also possible to cultivate corneal stem cells harvested from the sick eye, the healthy eye (autologous culture) or from relatives (allotypic culture). Renewing epithelial cells is not always sufficient to restore corneal transparency. It can also be necessary to replace a part or the entire corneal stroma. We can use today surgical lamellar graft technics to replace only stromal corneal layers involved in the disease we cure.

Corneal Diseases↗

[New therapies in ophthalmology: inhibitors of cytokines and chemokines: new treatment perspectives].

Anti-TNF-alpha (infliximab and etanercept) are potent, selective inhibitors of the inflammatory cascade. They have been widely used in the therapy of rheumatoid arthritis, Crohn's disease and psoriasis. Their efficacy in ophthalmology has been recently proven. The wide use of cytokines inhibitors could also be very useful in the therapy of neovessels in macular degeneration age-related, since the role of inflammation in the proliferation of neovessels has been recently discovered.

Chemokines↗

Lentiviral vector-mediated gene transfer in adult mouse photoreceptors is impaired by the presence of a physical barrier.

Gene transfer offers a substantial promise for the therapy of degenerative ocular diseases. Lentiviral vectors have the ability to efficiently transduce murine photoreceptors during the first days of life, but they are poorly effective on photoreceptors during adulthood. Here, we studied whether a physical barrier was responsible for this impairment. Previous studies have described the capacity of enzymes, such as chondroitinase ABC and neuraminidase X, to modify the structure of the interphotoreceptor matrix (IPM) when subretinally injected. Considering the IPM as a physical barrier that may decrease photoreceptor transduction, we injected different enzymes into the subretinal space of the adult mouse simultaneously with the lentiviral vector preparation, to increase viral transduction by fragilizing the IPM. Subretinal injection of neuraminidase X and chondroitinase ABC induces modifications in the IPM by, respectively, revealing or decreasing peanut agglutinin sites on photoreceptors. The simultaneous subretinal injection of neuraminidase X with a lentiviral vector driving the expression of a reporter gene in the photoreceptors increases the number of transduced cells significantly (around five-fold). After the enzyme treatment, the diffusion of the vector between the pigmented epithelium and the photoreceptors appears to facilitate the lentiviral vector transduction. Such approach targeting the IPM may help to design new strategies to improve gene delivery into the adult photoreceptors.

Animals↗

Idiopathic cyclitic retrolental membrane in children.

BACKGROUND: Cyclitic retrolental membranes (CRM) in children are usually associated with chronic uveitis or genetic syndromes. We report two rare cases of idiopathic CRM. PATIENTS AND METHODS: Two girls aged 9 and 13 years with visual acuities (VA) of 0.05 underwent lensectomy and anterior vitrectomy with dissection of the central part of the retrolental membrane and intraocular lens (IOL) implantation. RESULTS: The clinical evolution was excellent for the 9 year old girl who recovered 1.0 VA after 2 months. Histological examination revealed a fibroelastic tissue of unknown origin without inflammatory components. The 13 year old girl showed VA of 0.6 within 1 month. However, a recurrent CRM developed with retinal detachment and proliferative vitreoretinopathy (PVR). Vitrectomy, complete excision of the CRM and 360 degrees retinotomy with silicon oil tamponade attached the retina with limited visual recovery. Histology showed fibrovascular tissue with inflammatory components infiltrating the CRM. CONCLUSIONS: Idiopathic CRM in children are rare and can be composed of different histological tissues with very different clinical outcomes.

Adolescent↗

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization secondary to toxoplasmic chorioretinal scar.

BACKGROUND: To assess the effect of photodynamic therapy in the treatment of subfoveal choroidal neovascularization consecutive to a toxoplasmic chorioretinal scar. HISTORY AND SIGNS: Three patients with a previous history of toxoplasmic chorioretinal scar noticed a decrease in visual acuity and metamorphopsia. Fundus examination and fluorescein angiography revealed the presence of subfoveal choroidal neovascularization at the edge of the toxoplasmic chorioretinal scar. THERAPY AND OUTCOME: The first patient, aged 78, was treated by photodynamic therapy followed by three subsequent treatments of feeder vessel by laser photocoagulation. Visual acuity decreased during follow-up in the presence of recurrence of choroidal neovascularization and subretinal fibrosis. The second patient, a 20-year-old lady, was treated with three sessions of photodynamic therapy for a subfoveal choroidal neovascularization related to a toxoplasmic scar. Visual acuity was stabilized on the last follow-up visit at 0.3. The third patient, aged 53, received four treatments with photodynamic therapy at an interval of 3 - 4 months. choroidal neovascularization was stabilized and the last visual acuity was 0.2. CONCLUSIONS: This preliminary report suggests that photodynamic therapy with verteporfine may be an effective therapeutic modality for subfoveal choroidal neovascularization related to a toxoplasmic chorioretinal scar. Further assessment is needed in order to confirm this preliminary findings.

Adult↗

[Choroidal melanoma in neurofibromatosis type 2: description of a case].

To the best of our knowledge this is the first description of a choroidal melanoma with documented growth in neurofibromatosis type 2 (NF2). A 20-year-old patient with NF2 presenting deafness due to bilateral acoustic neurinomas and unilateral amaurosis due to a meningioma of the optic nerve developed a pigmented parapapillary choroidal tumor. Despite signs indicating the diagnosis of a melanoma, periodic observation was chosen in order to postpone functional amputation following optic nerve irradiation. The tumor growth was slow during the 5 years that followed, and once progression became rapid, the tumor was treated by accelerated proton beam radiotherapy. One year later, visual acuity diminished due to actinic optic neuropathy and was stabilized at 0.3 for the 2 following years. The tumor presented objective signs of regression, and no sign of metastatic disease was observed. The therapeutic approach in this case provided local control of the tumor while preserving useful visual function.

Adult↗

[Photocoagulation of the retinal feeder vessels of a chorioretinal anastomosis in age-related macular degeneration].

The presence of a chorioretinal anastomosis in the setting of age-related macular degeneration is known as a sign of poor prognosis. No treatment has proven to be effective. We describe a 71-year-old female patient presenting with exudative age-related macular degeneration, a chorioretinal anastomosis with two retinal feeder vessels (arteriole and veinule), a serous retinal pigment epithelium detachment, and a suspected early subretinal neovascular membrane. She was treated with ICG-guided laser photocoagulation directed to the hot spot, with treatment-zone enlargement directed to the retinal feeder vessels and followed up for 6 months. Although a second laser treatment for the reperfused subretinal neovascular membrane was needed, the clinical and angiographic end result was beneficial. Visual acuity improved by two lines, the chorioretinal anastomosis was occluded, and the pigment epithelium reattached. Taking into account the low therapeutic success rate described in the literature, we suggest that the specific treatment of the retinal feeder vessels, which to our knowledge has not been described before, may be a valuable treatment option.

Aged↗

[Centenary of the first radiotherapy treatment of retinoblastoma (Hilgartner, 1903)].

One hundred years ago, Hilgartner used external radiotherapy for the first time in the treatment of retinoblastoma. This first case was published in the Texas Medical Journal in 1903. Immediate results were reported to be excellent but the long-term outcome was not known. The first documented cure of retinoblastoma over a long period of time was a case initially treated by Verhoeff (Boston) in 1917, with histopathological findings provided 71 years later by Marcus et al. at the patient's death. Henry Louis Hilgartner was born in 1868 in Baltimore and died in 1937 at the age of 69. His revolutionary treatment developed from the discovery of X-rays in 1895 by Wilhelm Conrad Röntgen and the parallel discovery of radioactivity by Henri Bequerel and Marie and Pierre Curie. In the sociopolitical context of 1903, Emile Loubet was president of France and this same year saw the Wright brothers' first motorized flight with the first power-driven heavier-than-air machine. The development of radiotherapy in the treatment of retinoblastoma can be divided into three distinct periods: an initial period of trial and error lasting from 1903 to 1928; a second period from 1929 to 1948 covering the introduction of calibrated radon needles up to the advent of external radiotherapy, and a third period, from 1948 to the present day, which can be considered a time of technical improvement and innovation. One hundred years ago, radiotherapy made a triumphant entry on the scene of retinoblastoma management. With our present knowledge of its side effects, we are now trying to remove it.

Baltimore↗

[Sclerochoroidal calcification with subretinal membrane in a patient with high myopia].

BACKGROUND: Sclerochoroidal calcifications are rare and benign lesions. The diagnosis is made upon their fundoscopic and echographic appearance. Because of their possible association with diseases involving disturbances of calcium and phosphate metabolism, these parameters should be investigated as well. CASE REPORT: We present a patient with the classical features of sclerochoroidal calcifications. In fluorescein and indocyanine-green angiographies a presumed subretinal neovascular membrane was observed. CONCLUSION: The diagnosis of sclerochoroidal calcifications should be complemented with angiographic investigations because of a possible association with a subretinal neovascular membrane. In two such cases reported previously in the literature, the neovascular membrane was treated by laser coagulation. In one case, as in ours, no treatment was undertaken. The good prognosis of sclerochoroidal calcifications remained unaltered in all cases.

Adult↗

[New strategies in the management of retinoblastoma].

It was rare that a child survived retinoblastoma at the beginning of the twentieth century. Today the survival rate is in the order of 95% in reference centers, with new strategies improving prognosis step by step. Systematic enucleation used to be the starting point of any true and structured management, until the advent of radiotherapy made it possible not only to save lives but also to retain some useful vision. Early diagnosis has enabled focal therapies such as photocoagulation, cryocoagulation, and radioactive applicators to open up a new era of targeted tumor treatment. However, the onset of nonocular tumors secondary to radiotherapy, the resistance of certain tumors to irradiation, and unsightly cosmetic consequences all justify research into alternative therapeutic strategies. New types of chemotherapy have shown spectacular results and are currently under study: chemoreduction to make large tumors more manageable and enable less aggressive treatment of tumors located in delicate sites, thermochemotherapy using the effect of heat on plasma membrane permeability to antimitotics, and chemotherapy associated with cyclosporine to reduce the multidrug resistance of certain tumors. The aim is to avoid primary enucleation and external beam radiation as far as possible. The future may lie in local chemotherapy, hyperthermia, and dynamic phototherapy, accelerated proton beam radiotherapy also has promising prospects.

Antineoplastic Agents↗

Maximizing local tumor control and survival after proton beam radiotherapy of uveal melanoma.

PURPOSE: This study reports local tumor control and survival after proton beam radiotherapy (PBRT) of uveal melanoma. It identifies the risk factors for local tumor-control failure and for ocular tumor-related death. It presents the improvements implemented to increase the rate of local tumor control, and compares the survival rate of patients with locally controlled tumors to those of patients who had to receive a second treatment. PATIENTS AND METHODS: We have treated 2,435 uveal melanomas with PBRT between March 1984 and December 1998. Data were analyzed as of September 1999. Patients' age ranged from 9 to 89 years; there were 1,188 men and 1,247 women. The largest tumor diameter ranged from 4 to 26 mm, and tumor thickness from 0.9 to 15.6 mm. Median follow-up time was 40 months. RESULTS: Local tumor control probability at 5 years was improved from 90.6 +/- 1.7% for patients treated before 1988, to 96.3 +/- 0.6% for patients treated between 1989 and 1993, and became 98.9 +/- 0.6% for patients treated after 1993. Among 2,435 treated patients, 73 (3%) had to receive a second treatment because of tumor regrowth. Cause-specific survival at 10 years was calculated to 72.6 +/- 1.9% for patients with controlled tumors compared to 47.5 +/- 6.5% for those with recurrent tumors. CONCLUSION: Reduced safety margins, large ciliary body tumors, eyelids within the treatment field, inadequate positioning of tantalum clips, and male gender were identified to be the main factors impairing local tumor control. The improvement of local tumor control rate after 1993 is attributed to changes implemented in the treatment procedure. Our data strongly support that the rate of death by metastases is influenced by local tumor control failure: improvement of the local tumor control rate results in a better survival rate.

Adult↗

Bacterial keratitis: a prospective clinical and microbiological study.

AIM: To define the clinical and microbiological profile of bacterial keratitis at the Jules Gonin Eye Hospital and to test the in vitro bacterial resistance. METHODS: Patients presenting with bacterial keratitis were prospectively followed; clinical features (age, risk factors, visual acuity) and response to therapy were analysed. Bacteriological profile was determined and the sensitivity/resistance of isolated strains were tested towards 12 ocular antibiotics (NCCLS disc diffusion test). RESULTS: 85 consecutive patients (mean age 44.3 (SD 20.7) years) were prospectively enrolled from 1 March 1997 to 30 November 1998. The following risk factors were identified: contact lens wear, 36%; blepharitis, 21%; trauma, 20%; xerophthalmia, 15%; keratopathies, 8%; and eyelid abnormalities, 6%. The most commonly isolated bacteria were Staphylococcus epidermidis, 40%; Staphylococcus aureus, 22%; Streptococcus pneumoniae, 8%; others Streptococcus species, 5%; Pseudomonas, 9%; Moraxella and Serratia marcescens, 5% each; Bacillus, Corynebacterium, Alcaligenes xyloxidans, Morganella morganii, and Haemophilus influenza, 1% each. 1-15% of strains were resistant to fluoroquinolones, 13-22% to aminoglycosides, 37% to cefazolin, 18% to chloramphenicol, 54% to polymyxin B, 51% to fusidic acid, and 45% to bacitracin. Five of the 85 patients (5.8%) had a poor clinical outcome with a visual loss of one or more lines of visual acuity. CONCLUSION: Fluoroquinolones appear to be the therapy of choice for bacterial keratitis, but, based upon these in vitro studies, some strains may be resistant.

Acute Disease↗

A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes.

OBJECTIVE: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. DESIGN: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. PARTICIPANTS: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. RESULTS: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. CONCLUSIONS: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD.

Adult↗

Indocyanine green angiography in Fundus flavimaculatus.

PURPOSE: To describe the characteristic findings of fundus flavimaculatus (Stargardt disease) as seen on indocyanine green angiography. METHODS: Twelve eyes of 6 consecutive patients with fundus flavimaculatus were studied by fundus color photographs, fluorescein angiography and indocyanine green angiography. RESULTS: Indocyanine green angiography allowed visualization of small, clearly demarcated areas in which hypofluorescence increased over time, leading eventually to a large reticular pattern with small areas of normal-appearing choroid encircled by a well-defined network of hypofluorescent curvilinear lesions. These hypofluorescent flecks were present in all 12 eyes but corresponded only partially to the yellow flecks visible on biomicroscopy of the fundus. The peripapillary area was well preserved on indocyanine green angiography and the periphery did not show any visible abnormalities. CONCLUSIONS: The hypofluorescent curvilinear areas visualized on indocyanine green angiography form a reticular pattern that is similar to the polygonal shape of the watershed zones between terminal choroidal arterioles, which supply the choriocapillaris. These dark areas may reflect choriocapillaris defects secondary to lysis of lipofuscin-engorged retinal pigment epithelial cells. The typical lesions of fundus flavimaculatus thus seem to be situated in areas of least vascular supply. Their absence in the peripapillary area, which benefits from anastomotic vascular connections, would support this hypothesis.

Adult↗

Indocyanine green angiographic findings in choroidal hemangiomas: A study of 75 cases.

Indocyanine green (ICG) angiography is a new diagnostic modality that was suggested, in small series, to provide a typical angiographic pattern in cases of choroidal hemangioma. Our study, through an exceptionally large series of 75 patients, assessed in a prospective way whether a typical ICG pattern of choroidal hemangioma exists and what would be its possible variations. The most constant feature is the sequence of the different ICG angiographic phases. The arterial phase demonstrates the filling of intratumoral vessels on a hypofluorescent tumoral background. During the venous phase, the hemangioma reaches a stage of maximal ICG-A fluorescence, with superimposed hyper- and hypofluorescent spots. Sturge-Weber cases have also extratumoral hyperfluorescent spots. The late phase shows a hypofluorescent lesion with residual hyperfluorescent caverns and a well-delineated, but complex border structure.

Choroid↗