Estimating prognosis for survival after treatment of choroidal melanoma

Choroidal melanoma is fatal in about 50% of patients. This is because of metastatic disease, which usually involves the liver. Kaplan–Meier survival curves based only on tumor size and extent do not give a true indication of prognosis. This is because the survival prognosis of choroidal melanoma correlates not only with clinical stage but also with histologic grade, genetic type, and competing causes of death. We have developed an online tool that predicts survival using all these data also taking normal life-expectancy into account. The estimated prognosis is accurate enough to be relevant to individual patients. Such personalized prognostication improves the well-being of patients having an excellent survival probability, not least because it spares them from unnecessary screening tests. Such screening can be targeted at high-risk patients, so that metastases are detected sooner, thereby enhancing any opportunities for treatment. Concerns about psychological harm have proved exaggerated. At least in Britain, patients want to know their prognosis, even if this is poor. The ability to select patients with a high risk of metastasis improves prospects for randomised studies evaluating systemic adjuvant therapy aimed at preventing or delaying metastatic disease. Furthermore, categorization of tissue samples according to survival prognosis enables laboratory studies to be undertaken without waiting many years for survival to be measured. As a result of advances in histologic and genetic studies, biopsy techniques and statistics, prognostication has become established as a routine procedure in our clinical practice, thereby enhancing the care of patients with uveal melanoma.     

Outcomes of treatment with stereotactic radiosurgery or proton beam therapy for choroidal melanoma

Aim

To present our experience of the use of stereotactic radiosurgery and proton beam therapy to treat posterior uveal melanoma over a 10 year period.

Methods and materials

Case notes of patients treated with stereotactic radiosurgery (SRS), or Proton beam therapy (PBT) for posterior uveal melanoma were reviewed. Data collected included visual acuity at presentation and final review, local control rates, globe retention and complications. We analysed post-operative visual outcomes and if visual outcomes varied with proximity to the optic nerve or fovea.

Results

191 patients were included in the study; 85 and 106 patients received Stereotactic radiosurgery and Proton beam therapy, respectively. Mean follow up period was 39 months in the SRS group and 34 months in the PBT group. Both treatments achieved excellent local control rates with eye retention in 98% of the SRS group and 95% in the PBT group. The stereotactic radiosurgery group showed a poorer visual prognosis with 65% losing more than 3 lines of Snellen acuity compared to 45% in the PBT group. 33% of the SRS group and 54% of proton beam patients had a visual acuity of 6/60 or better.

Conclusions

Stereotactic radiosurgery and proton beam therapy are effective treatments for larger choroidal melanomas or tumours unsuitable for plaque radiotherapy. Our results suggest that patients treated with proton beam therapy retain better vision post-operatively; however, possible confounding factors include age, tumour location and systemic co-morbidities. These factors as well as the patient''s preference should be considered when deciding between these two therapies.     

Intravitreal bevacizumab treatment for radiation macular edema after plaque radiotherapy for choroidal melanoma

PURPOSE: To evaluate the effect of intravitreal bevacizumab treatment on patients with macular edema (ME) due to radiation retinopathy after plaque radiotherapy for choroidal melanoma. METHODS: In this retrospective case series, 10 consecutive patients with ME due to radiation retinopathy after plaque radiotherapy for choroidal melanoma were treated with a single intravitreal injection of bevacizumab. Postinjection best-corrected visual acuity (BCVA) and mean foveal thickness measured by ocular coherence tomography were the primary outcome measures. RESULTS: The mean BCVA at the time of the diagnosis of choroidal melanoma was 20/25 (range, 20/20 to 20/40). The mean radiation dose to the foveola was 4,323 cGy (range, 1,908-7,975 cGy). Radiation ME developed at a mean of 26 months (range, 17-44 months) after plaque radiotherapy. Choroidal melanoma regressed in all patients, and there were no neovascular sequelae. At the time of radiation ME diagnosis, the mean BCVA was 20/100 (range, 20/40 to 20/200). After bevacizumab injection, the mean BCVA was 20/86 at 6 weeks and 20/95 at 4 months. Mean foveal thickness measured by ocular coherence tomography was 482 microm before injection, 284 microm 6 weeks after injection, and 449 mum 4 months after injection. CONCLUSIONS: Intravitreal bevacizumab injection decreases mean foveal thickness while only modestly improving BCVA on a short-term basis in patients with radiation-induced ME.     

Corneal autofluorescence in choroidal melanoma or in choroidal naevus

AIMS: To investigate whether corneal autofluorescence is different in patients with choroidal melanoma or choroidal naevus. METHODS: Corneal autofluorescence was determined by fluorophotometry in both eyes of 32 patients with a unilateral choroidal melanoma, 32 patients with a unilateral choroidal naevus, and 32 age matched healthy controls. The corneal autofluorescence ratio between affected and contralateral eyes of patients or between randomly selected eyes of healthy controls was calculated. RESULTS: Mean corneal autofluorescence ratio of patients with a choroidal melanoma was significantly higher than that of healthy controls (mean ratio: 1.09 (SD 0.15) and 1.00 (0.09), respectively, ANOVA p=0.014), and than that of patients with choroidal naevus (mean ratio 0.96 (0.09), p<0.001). Mean ratios of patients with choroidal naevus and healthy controls were not significantly different (p=0.27). CONCLUSIONS: Corneal autofluorescence ratio of patients with a unilateral choroidal melanoma is increased. This is probably due to an increased flow of glucose through the impaired blood-aqueous barrier in the affected eye, resulting in additional glycation of corneal proteins and hence in increased autofluorescence. The corneal autofluorescence is not increased in patients with a choroidal naevus, because the blood-aqueous barrier is not impaired in the affected eye in these patients. Measurement of corneal autofluorescence is simple, fast, and non-invasive, and might be helpful to distinguish between patients with choroidal melanoma and those with choroidal naevus.     

脉络膜黑色素瘤眼球保留治疗结果初步观察

目的 观察保留眼球的治疗法治疗脉络膜黑色素瘤的临床效果。 方法 回顾分析44例脉络膜黑色素瘤患者44只患眼接受眼球保留治疗的临床资料，观察分析全身转移情况、眼球保留率以及视力预后。患者均为单眼发病，其中，以经瞳孔温热疗法（TTT）作为首选治疗者7只眼，占15.9%；以 106 Ru放射敷贴器近程放射治疗为首选治疗者25只眼，占56.8%；肿瘤切除联合 106 Ru放射敷贴器近程放射治疗者12只眼，占27.3%。治疗后随诊观察时间平均为13.3个月。 结果 44例患者在观察期内均未出现肿瘤全身转移。39例成功保留眼球，占88.6%。6只小肿瘤眼、14只中等大肿瘤眼和24只大肿瘤眼的眼球保留率分别为100%、92.9%和 83.3%。11只眼视力≥0.3，占28.2%；18只眼视力≥0.05~＜0.3，占46.2%；10只眼视力＜0.05，占25.6%。 结论 106 Ru放射敷贴器近程放射治疗和TTT治疗可以有效治疗中、小脉络膜黑色素瘤；部分大肿瘤选择肿瘤切除联合 106 Ru放射敷贴器近程放射治疗，其综合效果是否优于眼球摘除手术尚需进一步观察。 (中华眼底病杂志, 2006, 22: 150-153)     

Enucleation after argon laser photocoagulation for choroidal melanoma

We report the case of a choroidal melanoma 3 disc-diameter in size and 1 mm in thickness located superiorly at 2 disc-diameters from the optic disc. Argon laser photocoagulation was done in 1977. No recurrence was observed for eight years. In 1985, the melanoma suddenly reappeared, invading the posterior pole and causing secondary retinal detachment. The histologic examination after enucleation revealed a spindle-cell melanoma. Considering the fluorescein angiographic findings, we question the effectiveness of argon laser photocoagulation of choroidal melanoma.     

Granulomatous uveitis after treatment of a choroidal melanoma with proton-beam irradiation

Histologic examination of an eye removed 2 years after receiving proton-beam irradiation for a choroidal melanoma revealed residual tumor in the choroid and nonnecrotizing granulomatous inflammation, consistent with the diagnosis of early sympathetic ophthalmia. Sutures that secured four tantulum rings to the sclera did not penetrate the uvea. Sympathetic ophthalmia without evidence of a perforating injury has been described previously after helium ion therapy. The findings in our case further support the hypothesis that there is a risk of developing sympathetic ophthalmia after charged-particle therapy in the absence of a penetrating injury of the uveal tract.     

Laser photocoagulation treatment of choroidal melanoma

Ten cases of choroidal melanoma were treated with Argon and/or Krypton laser photocoagulation in this retrospective study. Each patient received an average of 9.6 laser treatment sessions. Three female and seven male patients were treated and followed for an average of 69.9 months. Clinical regression was observed in seven cases (70%).
Tumour size in these successfully treated cases ranged from 4.5 times 5.0 times 1.5 mm to 7.0 times 7.0 times 3.5 mm. Continued growth occurred in one case (10%), tumour recurrence which failed to respond to additional laser treatment in another (10%), and although a recurrence appeared to respond to additional laser in a third case (the largest tumour in the series 11.0 times 9.0 times 2.5 mm) extraocular extension was found at enucleation (10%).
Complications of laser treatment included cystoid macular oedema (Case 5), branch retinal vein occlusion (Cases 3 and 6), vitreous haemorrhage from neovascularisation at the edge of the scar, optic atrophy and thrombotic glaucoma (Case 8), and macular involvement by laser (Cases 4, 7 and 10). All patients remain alive without any clinical evidence of metastatic disease at the end of the follow-up period.
These results suggest that laser photocoagulation treatment is a useful option in the management of small choroidal melanomas. It avoids the psychological trauma of enucleation, and maintains some vision, without compromising life expectancy.     

Phacoemulsification following treatment of choroidal melanoma

Background: Little is known about the risks, effects and results of phacoemulsification following treatment with different modalities of choroidal melanoma. Methods: In a retrospective study, records were evaluated of 72 patients who underwent cataract surgery after treatment of choroidal melanoma (35 were treated with iodine-125 plaques, 27 with ruthenium-106 plaques, eight by tumor excision, and two with proton beam irradiation). The data were analyzed with respect to complications, effects on postoperative tumor care and visual outcome. Results: Phacoemulsification was performed at a mean interval of 21.5 months after primary tumor therapy. An intraocular lens (IOL) was implanted in 93% of the cases. The mean postoperative follow-up time was 16.2 months. Preoperative problems were rubeosis iridis (30.5%), secondary glaucoma (34.7%) and posterior synechiae (41.6%). Intraoperatively, defects of the posterior capsule occurred in 12.5%. Visual acuity equal to or better than preoperative vision was found in 95.8% of the patients as the best postoperative measurement and in 72.2% at the last follow-up measurement. A deterioration of more than two lines in visual acuity was observed in 4.2% as the best postoperative vision and in 27.8% at the last documented examination. Phacoemulsification was not the cause of deterioration in any of the cases. After cataract surgery, tumor retreatment was necessary in 19.4%. Treatment of radiation retinopathy was performed for the first time in 13.8%. Metastases developed in six patients (8.3%). Conclusion: Phacoemulsification following treatment for choroidal melanoma is both possible and advisable. The majority of patients have enhanced visual acuity. No decrease of vision occurred as a result of cataract extraction. The postoperative care of intraocular tumors and the treatment of radiation retinopathy is improved by timely cataract surgery. Received: 31 January 2000 Revised: 25 July 2000 Accepted: 26 July 2000     

Retinal break and rhegmatogenous retinal detachment after transpupillary thermotherapy as primary or adjunct treatment of choroidal melanoma

OBJECTIVE: To report the development of retinal break or rhegmatogenous retinal detachment (RRD) after transpupillary thermotherapy (TTT) as primary or adjunct treatment of choroidal melanoma. METHODS: In this noncomparative, interventional case series, the authors reviewed medical records of 13 patients who developed retinal break or RRD following TTT. The main outcome measures were clinical features and outcome of treatment of retinal break or RRD following TTT. RESULTS: Of 1574 patients managed on the Oncology Service at Wills Eye Institute with TTT as primary or adjunct treatment of choroidal melanoma, 13 (1%) developed retinal break with or without RRD. The mean patient age at diagnosis of choroidal melanoma was 56 years. Treatment for choroidal melanoma included combined plaque radiotherapy and TTT in 10 patients and TTT alone in 3 patients. The median number of TTT sessions before development of retinal break or RRD was 2. Retinal break or RRD developed at a median of 3 months following the last TTT. All the retinal breaks were located in the TTT-treated area. Retinal breaks were atrophic in 11 eyes and horseshoe shaped in 2 cases. The extent of retinal detachment was none in 1 eye, 1 quadrant or less in 5 eyes, 2 or 3 quadrants in 4 eyes, and 4 quadrants in 3 eyes. Seven patients underwent vitrectomy, one received cryotherapy and laser photocoagulation, and five were observed without treatment. In all eight patients who received treatment for RRD, the retina was attached after a mean follow-up period of 54 months with no intraocular or local extraocular tumor dissemination. CONCLUSIONS: Development of retinal break or RRD is a rare complication of TTT for treatment of choroidal melanoma. The majority of these cases develop within 6 months of TTT and most are caused by atrophic retinal holes in the TTT-treated area.     

Laser treatment for choroidal melanoma: Current concepts

Laser treatment has offered a relatively nonsurgical alternative for eye, life, and vision-sparing treatment of malignant melanoma of the choroid. Historically, the most commonly used forms of lasers were xenon-arc, argon laser, krypton laser, and the more recent transpupillary thermotherapy (TTT) and photodynamic therapy (PDT). Melanomas selected for laser treatment tend to be smaller and visibly accessible, which means these tumors are usually located in the posterior choroid. Laser treatments have been associated with both local tumor destruction and side effects. Unlike radiation therapy, laser treatment has been commonly associated with retinal traction, hemorrhage, chorioretinal neovascularization, and extra scleral tumor extension, as well as higher rates of local treatment failure. In addition, however, laser-treatment has been successfully used to treat tumor-related retinal detachments, radiation retinopathy, and neovascular glaucoma. We review the world's experience of ophthalmic laser treatment for choroidal melanoma, offer safety and efficacy guidelines, as well as a comparison of laser treatment to radiation therapy outcomes.     

Fluorescein angiography in the long-term follow-up of choroidal melanoma after conservative treatment

Three patients showed a growing choroidal melanoma, of them 2 in the only eye. The tumours were treated with Ru106/Rh106 plaques and surrounded by argon or krypton photocoagulation. The patients were followed up for 34-36 months by regular fluorescein angiography. In areas in which the radiation effect was optimal most choroidal and retinal vessels disappeared within 3-6 months. Outside this area occlusion of the vasculature as well as progressing atrophy of the tumour and the overlying retinal pigment epithelium were seen to continue for more than 12 months after treatment. Disappearance of the leaking vessels of the tumour may be the most reliable fluorescein angiographic sign of tumour regression following conservative treatment.     

Choroidal vascular changes after transpupillary thermotherapy for choroidal melanoma

OBJECTIVE: To evaluate choroidal vascular alterations after transpupillary thermotherapy used as the sole treatment for choroidal melanoma. DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: Forty-five eyes of 45 patients affected by malignant choroidal melanoma treated with transpupillary thermotherapy alone with more than 1 year of follow-up. INTERVENTION: Transpupillary thermotherapy was performed through a panfunduscopic contact lens using an 810-nm diode laser. MAIN OUTCOME MEASURES: Dynamic/static fluorescein and indocyanine green angiography were performed at scheduled intervals (24 hours, at 3-month intervals during the first year, and every 6 months thereafter) after transpupillary thermotherapy. Visual acuity, clinical evaluation, fundus photographs, and ultrasonographic examination were also performed. RESULTS: The mean follow-up was 30.5 months (range, 12-54 months). Changes in the choroidal circulation were always confined within the treatment margins (except in one case) and characterized by occlusion of choriocapillaris (100%), patent medium and/or large choroidal vessels (76%), retinochoroidal anastomosis (11%), and progressive choroidal vascular remodeling (42%). Forty-one cases (91%) showed persistent clinical regression, and four cases (9%) recurred; recurrent cases showed retinochoroidal anastomosis. CONCLUSIONS: Transpupillary thermotherapy is suggested as a new single therapeutic modality in the treatment of selected choroidal melanomas, but more precise eligibility criteria and longer follow-up are mandatory. Patent choroidal circulation, choroidal vascular remodeling, and anastomosis after transpupillary thermotherapy might be helpful to detect recurrent tumors.     

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.     

Results of proton beam irradiation for treatment of choroidal melanoma

PURPOSE: To evaluate the results of proton beam irradiation of choroidal melanomas on a large series of patients. PATIENTS AND METHODS: Retrospective analysis of a series of patients treated with proton beam irradiation between 1991 and December 1998. The data were analyzed to evaluate the local tumor control as well as the general progression and metastatic rate of the patients. Statistical analysis served to isolate risk factors for relapse or metastasis. RESULTS: We treated 1062 patients during the study period, with a median follow-up of 38 months. Local control was obtained for 97.1% of the patients. Tumors anterior to the equator were at risk for relapse. The survival rate was 92% at 2 years and 78% at 5 years. 73.1% of the 1062 patients died from metastasis, 6.1% of living patients presented with metastatic disease. The risk factors for death were the initial diameter, the age of the patient, and large tumor volume at diagnosis. Metastasis were essentially hepatic (94.6%). Risk factors for metastasis were: a large tumor volume, a lesion anterior or straddling the equator and the age of the patient. Ocular complications may induce a visual loss of 0.1 and less in 47% of the patients, due to optic nerve head and macular ischemia. 6% of the patients required secondary enucleation due to local complications (neovascular glaucoma). CONCLUSION: Proton beam irradiation of choroidal melanoma allows good tumor control and eye retention. The survival prognosis is associated with the initial volume of the tumor. The functional results may be improved and new therapeutics are needed to treat metastatic disease.