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Bertil Damato

Publications and source records attributed to Bertil Damato.

At least 19 recordsLinked to original sources

Transscleral local resection versus iodine brachytherapy for uveal melanomas that are large because of tumour height.

BACKGROUND: To compare visual outcome and ocular complications of transscleral local resection (TSR) with those of iodine-125 plaque brachytherapy (IBT) for uveal melanomas categorised as large because of tumour height. METHODS: Retrospective study of 87 patients with a uveal melanoma <or=16 mm by largest basal diameter (median, 12.6 vs 14.0 mm for TSR and IBT, respectively) and large by height (median, 11.0 vs 10.6 mm) by the Collaborative Ocular Melanoma Study (COMS) criteria. Thirty-three patients underwent TSR in the United Kingdom and 54 underwent IBT in Finland. Loss of 20/65 and 20/400 vision, local tumour recurrence, cataract, iris neovascularization, glaucoma, maculopathy, optic neuropathy, persistent retinal detachment, and vitreous haemorrhage were analysed using competing risks and logistic regression to control for confounders. RESULTS: All patients save one managed with TSR lost 20/70 vision within 3 years. The 2-year cumulative incidence of losing 20/400 vision was 60% (95% CI, 35-75) for TSR and 75% (95% CI, 59-86) for IBT. The 5-year incidence of local tumour recurrence was 41% (95% CI, 17-63) after TSR and 7% (95% CI, 2-17) after IBT. Glaucoma and optic neuropathy were rare after TSR. Cataract, maculopathy, retinal detachment, and vitreous haemorrhage were common after either treatment. The number of patients needed to treat with TSR instead of IBT was four for one additional patient to benefit by avoiding loss of visual acuity 20/400 for at least 2 years, and the corresponding number was three for one additional patient to experience a local recurrence from TSR. CONCLUSIONS: If TSR is further evaluated as an alternative to IBT in avoiding blindness of an eye with a ciliochoroidal melanoma categorised as large by COMS criteria because of its height, special emphasis must be given to increased risk of local tumour recurrence.

Aged↗

Expression of p53-induced apoptosis effector PERP in primary uveal melanomas: downregulation is associated with aggressive type.

Expression of PERP (p53 apoptosis effector related to PMP-22) was investigated in primary uveal melanomas and its variation was analyzed in relation to clinico-pathological and cytogenetical characteristics of these tumors. The transcriptional level of PERP gene was measured by quantitative real-time RT-PCR in 26 uveal melanomas with known chromosomes 3 and 8 status. PERP protein levels were assessed by Western blot analysis of 22 fresh-frozen tumors and by immunohistochemical analysis of 16 paraffin-embedded tumor specimens. Differential expression of PERP was identified in primary choroidal melanoma specimens, both at transcriptional and protein level. Reduced PERP mRNA level was significantly associated with monosomy 3 (two-way ANOVA and t-test, p=0.004) but not with gains in chromosome 8. Transcriptional downregulation of PERP did not present a statistically significant association with ciliary body involvement, size, PAS-positive loops or cell type. Immunoblotting and immunohistochemistry further demonstrated significantly reduced PERP protein level in monosomy 3 melanomas, as compared with disomy 3 tumors. The altered expression of PERP highlighted this apoptosis-specific target of p53 as a possible contributor to apoptosis in uveal melanoma with PERP downregulation being particularly relevant to the aggressive (monosomy 3) type of uveal melanoma. As PERP is a novel type of p53 effector that is likely to stimulate apoptosis through a mechanism distinct from that of Bcl-2-related mitochondrial effectors, further elucidation of its role in uveal melanoma pathogenesis will assist in the design of novel therapeutic approaches aimed at increasing the rate of apoptosis in this tumor.

Adult↗

Screening options for diabetic retinopathy.

PURPOSE OF REVIEW: This review assesses the current status of the different methods used in screening for diabetic retinopathy. This update is particularly timely because the incidence of diabetes is rising rapidly and the number of patients with vision-threatening diabetic retinopathy is increasing. RECENT FINDINGS: We evaluate the different methods used and their results in improving the delivery of eye care to patients with diabetic retinopathy. In populations with poor access to ophthalmic care, screening techniques such as the nonmydriatic camera used in offices of primary care physicians may be useful in identifying lesions of diabetic retinopathy requiring treatment. One of the limitations is the lack of dilation and cataract formation, which may result in ungradable photographs. Patients with treatable lesions as well as those with ungradable photographs should be referred for comprehensive ocular examination. SUMMARY: Screening techniques do not replace the eye examination. Ophthalmologists can play an important role in diabetic care apart from treating eye disease. Counseling can be provided to patients regarding the importance of blood glucose and blood pressure control and may motivate patients to achieve strict glucose and blood pressure control.

Diabetic Retinopathy↗

Choroidal neovascular membrane in a series of cases of malignant melanoma of the choroid.

PURPOSE: To examine a series of choroidal melanoma specimens to determine the frequency of overlying choroidal neovascularization (CNV) and to ascertain whether CNV over choroidal malignant melanoma is associated with any particular histological tumour characteristics. METHODS: We carried out a retrospective histological analysis of globes containing choroidal melanomas for evidence of choroidal neovascular membranes. RESULTS: Microscopic evidence of choroidal neovascular membranes was evident in 6% of cases. Choroidal neovascularization was not associated with any particular histological tumour characteristic. CONCLUSION: Choroidal neovascularization over choroidal malignant melanoma is not an infrequent occurrence and possibly appears as frequently as CNV over choroidal naevi. The presence of a choroidal neovascular membrane over a pigmented fundal lesion should not be taken as reassurance that the lesion is benign.

Aged↗

Treatment of primary intraocular melanoma.

The treatment of intraocular melanoma has evolved recently. Enucleation has been superseded largely by brachytherapy, proton beam radiotherapy, stereotactic irradiation, trans-scleral local resection, transretinal resection and diode laser phototherapy. Many patients develop metastatic disease, which usually involves the liver and occurs hematogenously. Disseminated disease rarely responds to therapy, and is usually fatal within 1 year of the onset of symptoms. Uveal melanomas develop characteristic chromosomal abnormalities, such as loss of chromosome 3. This is associated with a reduction in the 5-year survival from approximately 95% to less than 50%.

Antineoplastic Agents↗

Local tumor control after 106Ru brachytherapy of choroidal melanoma.

PURPOSE: To report on local tumor control after (106)Ru brachytherapy for choroidal melanoma. METHODS AND MATERIALS: A total of 458 patients with choroidal melanoma were treated at a single institution between January 1993 and December 2001. The tumors had a median longest basal dimension of 10.6 mm and a median height of 3.2 mm. The brachytherapy was administered using a 15- or 20-mm plaque. For posterior tumors, the plaque was positioned eccentrically with its posterior edge aligned with the posterior tumor margin to reduce the radiation dose to the optic disk and fovea. A minimal scleral dose sufficient to cause visible choroidal atrophy provided a permanent ophthalmoscopic record of the distribution of choroidal irradiation. If radiotherapy to the posterior tumor was uncertain, adjunctive transpupillary thermotherapy was administered 6 months postoperatively. RESULTS: The actuarial rates of tumor recurrence were 1%, 2%, and 3% at 2, 5, and 7 years, respectively. Local tumor recurrence correlated with the longest basal tumor dimension (Cox univariate analysis, p = 0.02, risk ratio 1.41, 95% confidence interval 1.06-1.88). Seven of the nine eyes with recurrent tumor were salvaged with additional conservative therapy. CONCLUSION: The low rate of local tumor recurrence suggests that ruthenium plaque radiotherapy is effective with good case selection and if special measures are taken to ensure that the plaque is positioned correctly.

Adult↗

Visual acuity after Ruthenium(106) brachytherapy of choroidal melanomas.

PURPOSE: To report on conservation of visual acuity after Ruthenium(106) (Ru-106) brachytherapy of choroidal melanoma. METHODS AND MATERIALS: This study was a noncomparative interventional case series of 458 patients with choroidal melanoma treated at a single center between January 1993 and December 2001. The intervention consisted of Ru-106 brachytherapy delivering minimum scleral and apex doses of 300 Gy and 80 Gy, respectively, using a 15-mm or 20-mm plaque. For discrete, posterior tumors, the plaque was positioned eccentrically with its posterior edge aligned with the posterior tumor margin. To ensure correct plaque positioning, any overlying extraocular muscles were dis-inserted, and the locations of both tumor and plaque edges were confirmed by transillumination and indentation. The main outcome measures were conservation of vision of 20/40 or better, 20/200 or better, and Counting Fingers or better, according to baseline variables. RESULTS: The actuarial rate of conservation of 20/40 or better was 55% at 9 years, loss of such vision correlating with posterior tumor extension (p < 0.001), temporal tumor location (p = 0.001), increased tumor height (p = 0.01), and older age (p < 0.01) (Cox multivariate analysis). Similar analyses showed conservation of 20/200 or better in 57% of eyes at 9 years, loss correlating with reduced initial visual acuity (p < 0.001), posterior tumor extension (p < 0.001), and temporal tumor location (p = 0.006). Counting Fingers or better vision was conserved in 83% of patients at 9 years, loss correlating with increased tumor height (p < 0.0001). Local tumor recurrence occurred in 9 patients (actuarial rate, 3% at 9 years). CONCLUSION: Ruthenium(106) brachytherapy of posterior choroidal melanoma achieves good conservation of vision if the tumor does not extend close to the optic nerve or fovea.

Adult↗

Proton beam radiotherapy of iris melanoma.

PURPOSE: To report on outcomes after proton beam radiotherapy of iris melanoma. METHODS AND MATERIALS: Between 1993 and 2004, 88 patients with iris melanoma received proton beam radiotherapy, with 53.1 Gy in 4 fractions. RESULTS: The patients had a mean age of 52 years and a median follow-up of 2.7 years. The tumors had a median diameter of 4.3 mm, involving more than 2 clock hours of iris in 32% of patients and more than 2 hours of angle in 27%. The ciliary body was involved in 20%. Cataract was present in 13 patients before treatment and subsequently developed in another 18. Cataract had a 4-year rate of 63% and by Cox analysis was related to age (p = 0.05), initial visual loss (p < 0.0001), iris involvement (p < 0.0001), and tumor thickness (p < 0.0001). Glaucoma was present before treatment in 13 patients and developed after treatment in another 3. Three eyes were enucleated, all because of recurrence, which had an actuarial 4-year rate of 3.3% (95% CI 0-8.0%). CONCLUSIONS: Proton beam radiotherapy of iris melanoma is well tolerated, the main problems being radiation-cataract, which was treatable, and preexisting glaucoma, which in several patients was difficult to control.

Adult↗

Proton beam radiotherapy of choroidal melanoma: the Liverpool-Clatterbridge experience.

PURPOSE: To report on outcomes after proton beam radiotherapy of choroidal melanoma using a 62-MeV cyclotron in patients considered unsuitable for other forms of conservative therapy. METHODS AND MATERIALS: A total of 349 patients with choroidal melanoma referred to the Liverpool Ocular Oncology Centre underwent proton beam radiotherapy at Clatterbridge Centre for Oncology (CCO) between January 1993 and December 2003. Four daily fractions of proton beam radiotherapy were delivered, with a total dose of 53.1 proton Gy, and with lateral and distal safety margins of 2.5 mm. Outcomes measured were local tumor recurrence; ocular conservation; vision; and metastatic death according to age, gender, eye, visual acuity, location of anterior and posterior tumor margins, quadrant, longest basal tumor dimension, tumor height, extraocular extension, and retinal invasion. RESULTS: The 5-year actuarial rates were 3.5% for local tumor recurrence, 9.4% for enucleation, 79.1% for conservation of vision of counting fingers or better, 61.1% for conservation of vision of 20/200 or better, 44.8% for conservation of vision of 20/40 or better, and 10.0% for death from metastasis. CONCLUSION: Proton beam radiotherapy with a 62 MeV cyclotron achieves high rates of local tumor control and ocular conservation, with visual outcome depending on tumor size and location.

Adult↗

Uveal melanoma: resection techniques.

This article describes surgical methods for resecting uveal melanoma, emphasizing techniques for preventing complications. Outcomes of surgery and the indications, contraindications, and controversies of resecting uveal melanoma are discussed.

Anesthesia↗

Differential expression of angioregulatory matricellular proteins in posterior uveal melanoma.

Metastases from uveal melanoma, the most common primary malignant eye tumour in adults, develop solely via their vascular bed due to the absence of intraocular lymphatics. The present study investigated the expression in this tumour of three matricellular proteins--Secreted Protein Acidic and Rich in Cysteine (SPARC), thrombospondin 1 (TSP1) and thrombospondin 2 (TSP2)--with putative contrasting roles in the regulation of angiogenesis. Immunohistochemical analysis of the three proteins was carried out in paraffin-embedded specimens from 27 posterior uveal melanomas and was corroborated with Western blot analysis of fresh-frozen samples from seven of the tumours. SPARC immunoreactivity was detected in all specimens and defined two categories of tumour: SPARC-rich (21 of 27 specimens) and SPARC-patchy (six of 27 specimens) uveal melanomas. SPARC-rich tumours had a significantly higher proportion of specimen area occupied by blood vessels (P=0.04) and showed a positive association with the presence of epithelioid-type tumoral cells (P=0.101). TSP1 was not detected by either of the methods in any of the tumours analysed. Some immunopositivity for TSP2 was detected in tumour cells in approximately 40% of specimens, but was not associated with survival, tumour vascularity or any other histopathological indices of survival. The pattern of expression of these matricellular proteins in uveal melanoma is consistent with a cooperative mechanism for establishing an enhanced environment favourable to angiogenesis. Interventions inducing TSP1 expression and/or inhibiting SPARC expression may be candidates for therapies directed towards the inhibition of angiogenesis in posterior uveal melanoma.

Adult↗

Conservation of eyes with choroidal melanoma by a multimodality approach to treatment: an audit of 1632 patients.

OBJECTIVE: To report on conservation of eyes with choroidal melanoma with a multimodality approach to treatment. DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: All 1632 patients with choroidal melanoma treated at a single center between 1993 and 2002. INTERVENTION: Primary enucleation (35%), brachytherapy (31.3%), proton beam radiotherapy (16.7%), transscleral local resection (11.0%), endoresection (3.7%), transpupillary thermotherapy (2.5%), and photocoagulation (0.1%). MAIN OUTCOME MEASURES: Primary and secondary enucleation. RESULTS: Logistic regression showed the main predictive factors for primary enucleation to be: age more than 60 years (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.8%-3.2%); reduced visual acuity (OR, 2.5; 95% CI, 1.9%-3.2%); posterior extension close to or involving the optic disc and fovea (OR, 1.7; 95% CI, 1.2%-2.4%); circumferential spread around the ciliary body, iris, or angle (OR, 3.1; 95% CI, 1.8%-5.5%); basal tumor diameter (OR, 3.5; 95% CI, 2.4%-5.0%); and tumor height (OR, 6.3; 95% CI, 4.5%-8.9%). After conservative treatment, the actuarial rate of secondary enucleation was 11.1% at 5 years (95% CI, 8.6%-13.6%). Cox multivariate analysis indicated the factors independently predicting secondary enucleation as: nasal/midline tumor location (risk ratio [RR], 2.6; 95% CI, 1.6%-4.4%); disc involvement (RR, 2.2; 95% CI, 1.2%-4.1%); tumor diameter (RR, 1.2; 95% CI, 1.0%-1.5%); and tumor thickness (RR, 1.8; 95% CI, 1.5%-2.1%). CONCLUSIONS: With a multimodality approach to treatment, 65% of patients underwent conservative treatment, and of them, 89% retained their eye at 5 years, with success depending on tumor diameter, tumor thickness, disc involvement, and coronal location.

Adolescent↗

Developments in the management of uveal melanoma.

Uveal melanomas threaten visual loss, enucleation, and death from metastatic disease. Most patients present because of symptoms, but failures of detection and diagnosis still occur commonly. Treatments aimed at avoiding enucleation include: plaque, proton beam or stereotactic radiotherapy; trans-scleral or trans-retinal local resection; and transpupillary thermotherapy. Increasingly, different modalities are being used in combination. The ocular outcomes are related to tumour size, location, spread and cell type. Metastatic disease occurs in many patients and is related to factors such as tumour dimensions, ciliary body involvement, cell type, extravascular matrix patterns and cytogenetics. Abnormalities related to chromosomes 3, 6 and 8 are strongly related to tumour behaviour, for the first time enabling survival probability to be estimated with a high degree of reliability in an individual patient. This enables high-risk individuals to be targeted for screening while providing reassurance to those with a minimal chance of developing metastatic disease. Such targeting would allow selection of patients for adjuvant systemic therapy, should a suitable treatment become available, and would also facilitate the evaluation of such treatment by increasing the statistical power of any randomized prospective study. The high mortality in patients with monosomy 3 melanoma suggests that in these patients ocular treatment is only palliative. Cytogenetic studies suggest that some melanomas may never develop any metastatic potential and if these impressions are confirmed by further studies, then in these patients the main priority of treatment would be to conserve vision.

Antineoplastic Agents↗

Transscleral resection versus iodine brachytherapy for choroidal malignant melanomas 6 millimeters or more in thickness: a matched case-control study.

OBJECTIVE: To assess differences in treatment outcome after transscleral resection (TSR) and iodine brachytherapy (IBT) of choroidal melanomas too thick for ruthenium brachytherapy. DESIGN: Matched case-control study. SETTING: Two national ocular oncology services. PARTICIPANTS: Forty-nine pairs of patients with choroidal melanoma 6 mm thick or more (range = 6-14), treated within 3 years of each other by either TSR or IBT, and retrospectively matched by age, visual acuity at diagnosis, largest basal tumor diameter, and posterior extension of the tumor. INTERVENTION: Iodine brachytherapy in Finland or TSR in United Kingdom. Prospectively collected time-to-event data were compared with parametric Weibull regression, adjusting for matching. MAIN OUTCOME MEASURES: Tumor control, complications, and visual acuity. RESULTS: Risk of local recurrence after IBT was smaller than that after TSR (hazard ratio [HR] = 0.02, 95% confidence interval [CI] = 0.01-0.11, P<0.001, Weibull regression adjusted for matching), but the 8-year all-cause and melanoma-specific (HR = 0.81, 95% CI = 0.30-2.22, P = 0.69) survivals did not differ. The risks of cataract (HR = 2.05, 95% CI = 1.08-3.89, P = 0.029), maculopathy (HR = 2.28, 95% CI = 0.96-5.43, P = 0.062), and vitreous hemorrhage (HR = 2.30, 95% CI = 0.95-5.57, P = 0.064) were higher after IBT. Rubeosis, neovascular glaucoma, and optic neuropathy developed only after IBT. Risk of retinal detachment, exudative after IBT and rhegmatogenous after TSR (HR = 0.84, 95% CI = 0.40-1.75, P = 0.63), and risk of losing 20/60 vision (HR = 1.37, 95% CI 0.76-2.45, P = 0.29) were comparable between the groups, but risk of losing 20/200 vision was higher after IBT (HR = 2.38, 95% CI = 1.48-3.83, P<0.001). No overall difference in quality of life was found. CONCLUSIONS: This study suggests that TSR preserves 20/200 vision better than IBT and avoids some of its major complications, but increases the risk of local recurrence. About 350 patients would need to be randomized to prove that TRS preserves 20/60 vision better than IBT.

Adult↗