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Biomedical subjects

L Zografos

Publications and source records attributed to L Zografos.

At least 37 records · Page 2Linked to original sources

Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study.

OBJECTIVE: To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. DESIGN: Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. SETTING: Four ophthalmic centers in North America and Europe providing retinal care. PARTICIPANTS: Patients with subfoveal CNV caused by age-related macular degeneration. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. RESULTS: The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5), -1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150 J/cm2) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150 J/cm2. Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a significantly better visual acuity outcome (+0.8 line) than eyes in which CNV leakage progressed (-0.8 line). CONCLUSIONS: Photodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in some patients with age-related macular degeneration. Except for nonperfusion of neurosensory retinal vessels at a light dose of 150 J/cm2, no other adverse events were of concern. Randomized clinical trials to investigate whether this new modality can preserve vision in patients with CNV secondary to age-related macular degeneration are justified.

Aged↗

Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study.

OBJECTIVES: To evaluate safety and short-term visual acuity and fluorescein angiographic effects of photodynamic therapy (PDT) after retreatments with verteporfin for choroidal neovascularization (CNV) in age-related macular degeneration (AMD) that demonstrated fluorescein leakage after at least 1 course of PDT. DESIGN: Nonrandomized, multicenter, open-label phase 1 and 2 clinical trial using 2 different retreatment dosage regimens. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of multiple PDT treatments. Two regimens (regimens 2 and 4) for treatment and retreatment were chosen from 5 used in a single-treatment study. Both regimens used a verteporfin dose of 6 mg/m2 infused for 10 minutes. However, regimen 2 used a light dose of 100 J/cm2 applied 20 minutes after the start of the verteporfin infusion, whereas regimen 4 used a light dose of 50, 75, or 100 J/cm2 applied 15 minutes after infusion commenced. Posttreatment evaluations were planned in 31 participants up to 3 months after up to 2 retreatments given at 2- or 4-week intervals after initial PDT treatment. Similar posttreatment evaluations were planned after retreatments in 5 additional participants who were reenrolled some time more than 12 weeks after an initial PDT treatment. RESULTS: The average visual acuity change for the 31 participants who had retreatment within 2 to 4 weeks after the initial treatment and a follow-up examination 16 to 20 weeks after the initial treatment was 0.2 lines (range, -4 to 4 lines) in regimen 2 and -1.0 line (range, -5 to 3 lines) in regimen 4. Similar outcomes were noted in the 5 reenrolled participants. Cessation of fluorescein leakage from classic CNV for at least 1 to 4 weeks could be achieved without loss of visual acuity after at least 2 treatments in 2 (6.5%) of 31 patients. Similar to single-treatment effects, the disappearance of leakage was documented regularly at 1 week after each retreatment. Fluorescein leakage reappeared by 4 to 12 weeks after a retreatment in almost all cases. However, compared with baseline, leakage activity appeared to be reduced after multiple PDT courses. For the 31 patients who had follow-up for 3 months after the last retreatment and had received retreatment 2 to 4 weeks after the initial treatment, progression of CNV beyond the area identified before the retreatment was noted in 10 (48%) of the 21 eyes with classic CNV in regimen 2 and 9 (90%) of 10 eyes in regimen 4. The rate and severity of ocular or systemic adverse events were not increased by multiple applications. CONCLUSIONS: Multiple applications of PDT with verteporfin achieve repetitive, short-term cessation of fluorescein leakage from CNV secondary to AMD, without loss of visual acuity. This strategy can be used in randomized clinical trials investigating the efficacy of verteporfin in PDT for recurrent fluorescein dye leakage from persistent or recurrent CNV, following an initial or subsequent PDT treatment, with maintenance of visual acuity. Retreatments may achieve progressive cessation of leakage and prevent further growth of CNV and subsequent visual loss.

Aged↗

Adenocarcinoma of the nonpigmented ciliary body epithelium: report of a rare case.

Acquired tumours of the nonpigmented ciliary body epithelium are rare. We present herein a case of low-grade adenocarcinoma in order to stress the problems related to the clinical diagnosis. The tumour in our case was circumscribed, localised on the ciliary body, and nonpigmented. The height of the tumour, measured with ultrasound biomicroscopy, was 3.5 mm. The internal reflectivity of the tumor was homogeneous with low attenuation. The tumour was surgically excised with an uneventful iridocyclectomy. Both clinical presentation and preoperative examinations allowed to circumscribe the correct diagnosis which could be confirmed only with histology.

Adenocarcinoma↗

On the role of kerato-epithelin in the pathogenesis of 5q31-linked corneal dystrophies.

PURPOSE: Recently, the authors identified a gene, BIGH3, in which different mutations cause a group of hereditary corneal dystrophies: lattice type I and IIIA (CDLI and CDLIIIA), granular Groenouw type I (CDGGI), Avellino (CDA), and Reis-Bücklers' (CDRB). All these disorders are characterized by the progressive accumulation of corneal deposits with different structural organization. Experiments were conducted to determine the role of kerato-epithelin (KE), the product of BIGH3, in the pathogenesis of the diseases. METHODS: KE-15 and KE-2, two rabbit antisera raised against peptides from the 69-364 and 426 - 682 amino acid regions of KE respectively, were used for immunohistology of the corneas obtained after keratoplasty in six CDLI patients, three CDGGI patients, and one CDA patient. RESULTS: The nonamyloid deposits observed in CDGGI stained intensively with KE-15 and KE-2, whereas the amyloid deposits in all analyzed CDLI corneas reacted to KE-2 but not to KE-15. In the CDA cornea, where amyloid and nonamyloid inclusions were present, positive staining with both antisera was observed. CONCLUSIONS: Pathologic amyloid and nonamyloid deposits observed in CDLI, CDGGI-, and CDA-affected corneas are caused by KE accumulation. Different staining patterns of amyloid and nonamyloid deposits observed with antibodies against the amino and carboxyl termini of KE suggest that two mechanisms of KE misfolding are implicated in the pathogenesis of 5q31-linked corneal dystrophies.

Amyloid↗

Chorioretinal vascular abnormalities associated with angioid streaks and pseudoxanthoma elasticum.

OBJECTIVE: To analyze the retinal and choroidal vascular abnormalities in eyes with angioid streaks (AS) associated with pseudoxanthoma elasticum (PXE). METHODS: Color photographs and fluorescein angiograms of 54 eyes of 27 consecutive patients with AS and PXE were examined retrospectively. RESULTS: Four (7%) of the 54 eyes had a major vascular abnormality at the level of the disc; this took the form of a large vascular loop corresponding to an arteriovenous communication between retina and choroid in 3 eyes (6%) and an anastomosis between 2 retinal arteries in 1 eye (2%). CONCLUSION: Analysis of the vascular network in these eyes showed several vascular abnormalities, among which chorioretinal arteriovenous communications appear to be the most dramatic.

Adult↗

Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples.

BACKGROUND: Conventional photocoagulation of subfoveal choroidal neovascularization (CNV) is often accompanied by visual loss due to thermal damage to adjacent retinal structures. Photodynamic therapy (PDT) allows vascular occlusion by selective photochemical destruction of vascular endothelial cells only. In a pilot study we evaluated the use of PDT in CNV. METHODS: In a clinical phase I/II trial, patients with subfoveal CNV were treated with PDT. Benzoporphyrin derivative monoacid ring A (BPD) was used as sensitizer at a drug dose of 6 mg/m2 or 12 mg/m2. Irradiation was performed via a diode laser emitting at 690 nm coupled into a slit lamp. Safe and maximum tolerated light doses were defined by dose escalation from 25 to 150 J/cm2. Photodynamic effects were documented ophthalmoscopically and angiographically. RESULTS: Sixty-one patients received a single course of BPD-PDT. Preliminary results suggest no damage to retinal structures within the treated area clinically. Retinal perfusion was not altered, while CNV demonstrated immediate absence of fluorescein leakage in the majority of lesions subsequent to PDT. At optimized parameters (6 mg/m2 and 50 J/cm2) complete cessation of leakage from classic CNV occurred in 100% of cases at 1 week and in 50% at week 4. In 70-80% of classic CNV, leakage reappeared at week 12, but markedly less than before treatment. CONCLUSION: PDT allows temporary absence of leakage from CNV with preservation of visual acuity. The long-term prognosis of CNV secondary to age-related macular degeneration treated with repeated courses of PDT is being evaluated in a phase III trial.

Adult↗

Indocyanine green angiographic findings in sympathetic ophthalmia.

PURPOSE: To analyze indocyanine green angiography (ICGA) features in two cases of sympathetic ophthalmia using a standard angiography protocol for posterior uveitis. METHODS: Report on two patients who suffered from penetrating ocular injuries 45 and 8 years before sympathetic ophthalmia was diagnosed and confirmed by histopathological examination of the enucleated eye. In addition to routine examination and fluorescein angiography, initial and follow-up ICGAs were performed. RESULTS: The first patient, with a phthisic right eye following s shotgun injury, consulted 6 months after cataract extraction in his good left eye for progressive visual loss due to a neovascular membrane in a moderately inflamed eye. The second patient consulted 8 years after a perforating injury of his right eye by a metallic foreign body because of recent visual loss and inflammation in his good left eye. ICGA of both patients showed numerous hypofluorescent dark dots visible at the intermediate phase, some becoming isofluorescent at the late phase and resolving after long-term corticosteroid therapy, others remaining hypofluorescent until the late phase. CONCLUSION: The two patterns of hypofluorescent areas, either persisting throughout angiography or fading in the late phase, were interpreted respectively as cicatricial and active lesions. ICGA gave determining additional information on choroidal involvement and on subsequent evolution of lesions.

Adult↗

Proton beam irradiation of choroidal hemangiomas.

PURPOSE: To present a large series of choroidal hemangiomas treated with proton beam irradiation and to describe the treatment outcomes. METHODS: We treated 54 eyes of 53 patients with choroidal hemangioma. The lesions consisted of 48 circumscribed hemangiomas and six diffuse hemangiomas in patients with Sturge-Weber syndrome. The total applied dose was 27.3 Gy in four eyes, 22.7 Gy in three eyes, and 16.4 Gy to 18.2 Gy in 47 eyes. RESULTS: The retina reattached within six months after treatment in all 54 eyes and no recurrence of the secondary retinal detachment occurred within the follow-up period of 6 months to 9 years. Tumors treated with the higher doses regressed faster than tumors treated with the lower doses, but radiation-induced complications of the optic nerve appeared in all four eyes treated with a total dose of 27.3 Gy. Of 31 eyes treated with 16.4 to 18.2 Gy and followed for more than 1 year, 22 had an improvement in their visual acuity, and nine retained the same visual acuity. At the last follow-up examination, the best-corrected visual acuity was 20/20 or better in nine eyes, 20/40 to 20/25 in 13 eyes, 20/100 to 20/50 in six eyes, and 20/200 or less in three eyes. CONCLUSIONS: Proton beam irradiation of choroidal hemangiomas appears to be a valid therapeutic alternative. A total proton dose ranging from 16.4 to 18.2 Gy applied in four daily fractions seems adequate to ensure local control of both tumor and secondary retinal detachment.

Adult↗

Radiotherapy of choroidal metastases.

PURPOSE: This retrospective study was undertaken to clarify the role of high energy external beam radiation therapy (EBRT) and to determine its safety and efficacy on local control and visual acuity in patients suffering from choroidal metastases (CM). MATERIALS AND METHODS: The records of 58 consecutive patients treated with EBRT between 1970 and 1993 were analyzed. The female to male ratio was 2.9 and the median age was 59 years (range 40-81 years). Thirty-six patients (62%) had unilateral CM and 22 patients had bilateral CM. The mean number of lesions per eye was two. Retinal detachment was present in 65% of cases. The primary tumour (PT) was breast carcinoma for 38 patients (75%), lung carcinoma for 10 patients (17%) and gastrointestinal, genitourinary or unknown PT for the remaining 10 patients. The median interval of time between the PT and the CM was 55 months (range 0-228 months). All patients were treated with megavoltage irradiation. The median prescribed dose was 35.5 Gy (range 20-53 Gy) normalized at a 2 Gy per fraction schedule with an alpha/beta value of 10 Gy. Various techniques were used and whenever possible the lens was spared. Ten patients with unilateral disease were treated in both eyes. RESULTS: The tumour response was slow. When assessed after 3 months or more, the complete response rate was 53% with significantly better results for doses higher than 35.5 Gy (72 versus 33%; P = 0.009). Visual acuity was improved or stabilized in 62% of patients, with also significantly better results when doses higher than 35.5 Gy (P = 0.014) were administered. Amongst 26 patients with unilateral CM who had no elective contralateral irradiation, three developed metastasis in the opposite eye versus none of the 10 patients who had bilateral irradiation. Five complications occurred (three cataracts, one retinopathy and one glaucoma). CONCLUSION: Radiation therapy is an efficient and safe palliative treatment for choroidal metastases and it helps the preservation of vision. Thus, there is a major impact on the quality of life in a group of patients with an almost uniformly fatal prognosis. Both tumour response and visual acuity are significantly improved if doses higher than 35.5 Gy are administered. Whenever possible, a lens sparing technique should be used.

Adenocarcinoma↗

Mutation hot spots in 5q31-linked corneal dystrophies.

Mutations in the BIGH3 gene on chromosome 5q31 cause four distinct autosomal dominant diseases of the human cornea: granular (Groenouw type I), Reis-Bücklers, lattice type I, and Avellino corneal dystrophies. All four diseases are characterized by both progressive accumulation of corneal deposits and eventual loss of vision. We have identified a specific recurrent missense mutation for each type of dystrophy, in 10 independently ascertained families. Genotype analysis with microsatellite markers surrounding the BIGH3 locus was performed in these 10 families and in 5 families reported previously. The affected haplotype could be determined in 10 of the 15 families and was different in each family. These data indicate that R555W, R124C, and R124H mutations occurred independently in several ethnic groups and that these mutations do not reflect a putative founder effect. Furthermore, this study confirms the specific importance of the R124 and R555 amino acids in the pathogenesis of autosomal dominant corneal dystrophies linked to 5q.

Chromosome Mapping↗

Morphometric characteristics of traumatic choroidal ruptures associated with neovascularization.

PURPOSE: To define the morphometric characteristics of indirect choroidal ruptures associated with choroidal neovascularization (CNV). METHODS: A total of 79 eyes that had sustained traumatic indirect choroidal ruptures was studied retrospectively. Color pictures of the fundus and fluorescein angiograms were available in all cases, and patients were followed for at least 1 year. Eyes that were free of CNV constituted Group I; eyes that developed CNV constituted Group II. Baseline characteristics of both groups, including age, sex, and visual acuity, were recorded. Distance of indirect choroidal ruptures from the center of the fovea and morphometric characteristics of the ruptures were calculated using image analysis software (Image 1.60; National Institutes of Health, Bethesda, MD). RESULTS: A total of 63 eyes (79.7%) free of CNV was included in Group I and 16 eyes (20.3%) that developed CNV were included in Group II. Morphometric analysis showed a greater distance between the indirect choroidal rupture and the center of the fovea in Group I than in Group II (median, 1480 microm versus 612 microm; P = 0.009). In addition, the length of the rupture was shorter in Group I than in Group II (median, 3054 microm versus 4504 microm; P = 0.03). CONCLUSIONS: Two significant factors associated with the presence of CNV in case of traumatic choroidal rupture were identified and quantified: the proximity of the rupture to the center of the fovea and the length of the rupture. Both should be considered as risk factors for the development of CNV and monitoring should take them into account.

Adolescent↗

Bilateral optic papillitis following mycoplasma pneumoniae pneumonia.

Mycoplasma pneumoniae is an atypical bacterium that can cause a great variety of respiratory infections and be responsible for ocular involvement such as conjunctivitis, anterior uveitis and very rarely optic neuropathy. We report herein an additional case of bilateral optic disc swelling with profound visual loss following Mycoplasma pneumoniae pneumonia and review the world literature on the ocular manifestations associated with this pathogen.

Adult↗

[Clinical study and genetic 3q28 locus linkage in 2 Swiss families with Kjer dominant optic atrophy (OPA1)].

METHODS: We examined 20 patients from 2 unrelated Swiss families to describe their clinical phenotype. In addition, a linkage analysis was performed in an attempt to confirm the reported genetic homogeneity of this condition as well as to refine its genomic localization. RESULTS: Two point analysis provided a cumulative LOD-score of 3.03 with marker D3S 2305. The absence of recombination precluded further refinement of the disease interval. CONCLUSIONS: Our data confirm the genetic homogeneity and the extreme variability of expression, occasionally mimicking low tension glaucoma.

Adolescent↗

Kerato-epithelin mutations in four 5q31-linked corneal dystrophies.

Granular dystrophy Groenouw type I (CDGG1), Reis-Bücklers (CDRB), lattice type I (CDL1) and Avellino (ACD) are four 5q31-linked human autosomal dominant corneal dystrophies. Clinically, they show progressive opacification of the cornea leading to severe visual handicap. The nature of the deposits remains unknown in spite of amyloid aetiology ascribed to the last two. We generated a YAC contig of the linked region and, following cDNA selection, recovered the beta ig-h3 gene. In six affected families we identified missense mutations. All detected mutations occurred at the CpG dinucleotide of two arginine codons: R555W in one CDGG1, R555Q in one CDRB, R124C in two CDL1 and R124H in two ACD families. This suggests, as the last two diseases are characterized by amyloid deposits, that R124 mutated kerato-epithelin (the product of beta ig-h3) forms amyloidogenic intermediates that precipitate in the cornea. Our data establish a common molecular origin for the 5q31-linked corneal dystrophies.

Alternative Splicing↗

Subretinal lesions following a scleral buckling procedure.

Pigment epithelial detachment is usually associated with disorders of the underlying Bruch's membrane and choroid in a context of age-related macular degeneration. In a very few cases, lesions resembling pigment epithelial detachment have been reported after retinal reattachment surgery. We observed an additional case who presented deep lesions several weeks after a scleral buckling procedure for retinal detachment. The lesions, all located posteriorly at the edge of the reattached retina, appeared to be subretinal, well circumscribed and yellowish with a normal overlying retina. All exhibited the typical biomicroscopic features of focal detachment of the retinal pigment epithelium (RPE) but failed to show, throughout the angiogram, the typical fluorescein pooling of the classic pigment epithelial detachment. This suggests that these lesions, though simulating RPE detachments, represent focal pockets of subretinal fluid.

Female↗

Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy.

PURPOSE: Ocular melanoma is characterized by a high rate of liver metastases and is associated with a median survival time less than 5 months. There is no standard treatment available. Treatment strategies have, without success, relied on the experience with metastatic cutaneous melanoma. The only effective treatment is chemoembolization using cisplatin and polyvinyl sponge, which has never become accepted on a large scale. The objective of the study was to establish prospectively the efficacy and toxicity of hepatic intraarterial fotemustine, a third-generation nitrosourea, in patients with liver metastases from ocular melanoma. PATIENTS AND METHODS: Thirty-one patients were subjected to laparotomy to place a totally implantable catheter into the hepatic artery and received fotemustine 100 mg/m2 as a 4-hour infusion, first once a week for four times and then, after a 5-week rest period, every 3 weeks until progression or toxicity. Cox regression models were used to assess the prognostic role of patient survival characteristics. RESULTS: Objective responses were observed in 12 of 30 assessable patients (40%; 95% confidence interval, 22% to 59%). The median duration of response was 11 months and the median overall survival time, 14 months. Lactate dehydrogenase (LDH) appeared to be the strongest prognostic factor for survival. Toxicity was minimal and treatment could be administered on an outpatient basis. CONCLUSION: The results of hepatic arterial chemotherapy with fotemustine produced a high response rate and survival similar to chemoembolization therapy. It involves no major toxicity and preserves the quality of life. To assess further its effectiveness, a randomized study to compare hepatic intraarterial versus intravenous chemotherapy is being planned.

Adult↗