Surgical Management of Posterior Uveal Melanoma
Surgical Management of Posterior Uveal Melanoma
Eyes with untreated and treated uveal melanoma frequently have retinal detachments as a result of intrinsic tumor activity or radiation or tumor-related complications. These retinal detachments may be exudative, rhegmatogenous, tractional or a combination. Exudative retinal detachments are very common and represent intrinsic tumor activity, vascular permeability and retinal pigment epithelial dysfunction. These retinal detachments may differentiate a benign nevus from a malignant melanoma, with an estimated incidence of 50–100% in uveal melanomas prior to treatment. Exudative retinal detachments improve with plaque brachytherapy treatment with a natural history of resolution in a mean of 5.6 months and 90% resolution rate at 1 year. With any retinal detachment that persists over time, there is a risk of photoreceptors damage and loss, which may result in permanent and irreversible vision loss. Several strategies have been investigated to speed the resolution of exudative retinal detachments, including surgical and medical techniques. Char et al. reported on 11 patients treated with proton beam irradiation and transpupillary thermotherapy, showing that mean time to resolution of exudative retinal detachment was significantly less as compared to proton irradiation monotherapy (193 days vs 263 days). Use of intravitreal bevacizumab (2.5 mg/0.1 cc) following plaque brachytherapy has shown promise in hastening the resolution of subretinal fluid. When used at the time of plaque removal, Houston et al. showed that the mean time to resolution of exudative retinal detachment in 124 patients was 3.36 months, with 43% resolving by 1 month.
Surgical management of tumor and radiation-related complications has recently been investigated. Potential indications for vitrectomy include exudative detachments, radiation retinopathy and maculopathy, vitreous hemorrhage, tractional and rhegmatogenous retinal detachments. Prior to vitrectomy surgery, the surgeon must ensure tumor inactivity to minimize the risk of intraocular tumor dissemination. As seen in natural history studies of exudative retinal detachments, approximately 10% of patients have persistent subretinal fluid at 1 year or more. Exudative retinal detachments may be associated with active tumor, so it is imperative for the ocular oncologist to observe these tumors and document stability. If the tumor remains stable without any active growth or activity, vitrectomy with drainage of subretinal fluid may be a viable option for visual rehabilitation. Radiation-related complications can manifest as early as 6 months following plaque brachytherapy or anytime thereafter. These early findings are observed using spectral-domain optical coherence tomography, which may identify subtle disease prior to clinically evident changes. The earliest manifestation is radiation maculopathy with macular edema. Anti-VEGF agents and corticosteroids have been shown to be effective in the early treatment of radiation retinopathy and may delay or prevent the progression of radiation effects. For cases intractable to medical therapy, vitrectomy may be considered. Vitrectomy for radiation retinopathy may aid in several ways, including relieving vitreoretinal traction and decreasing the vitreous source of VEGF, a key component in the development of radiation-related complications. Vitreous hemorrhage is another complication that may be amenable to vitrectomy. Vitreous hemorrhage may occur secondary to proliferative radiation retinopathy with neovascularization, tractional forces avulsing a blood vessel, posterior vitreous detachment or tumor-related. For those hemorrhages thought to be tumor-related, careful observation is prudent to determine tumor recurrence or tumor activity. Following plaque brachytherapy, there also appear to be strong vitreoretinal adhesions at the tumor periphery that can exert tractional forces leading to tractional or rhegmatogenous retinal detachments. Vitrectomy can aid in relieving these tractional forces, as well as repair the resultant retinal detachment (Figure 1).
(Enlarge Image)
Figure 1.
A 55-year-old female with a history of posterior uveal melanoma treated with iodine-125 plaque brachytherapy 1 year prior. (A) Patient sustained a vitreous hemorrhage and macula-involving retina detachment. Visual acuity at this time was hand motions. (B) Ultrasound shows previously treated uveal melanoma that shows no growth compared to prior imaging. (C) Patient underwent pars plana vitrectomy, air-fluid exchange, endolaser, silicone oil without complications. No evidence of tumor dissemination, local recurrence or extraocular extension. (D) Visual acuity improved to 20/200, 6 months after positive predictive value. Final visual acuity limited by central retinal atrophy.
Few studies have addressed the surgical management of eyes harboring uveal melanoma, and controversy remains regarding if and when these eyes can be operated. At the heart of the debate is the concern of viable tumor cells disseminating intraocularly or extending extraocularly. Small case reports have shown a low risk for eyes that contain treated tumors; however, in cases with vitreous hemorrhage prior to treatment, there appears to be an increased risk of intraocular dissemination likely secondary to tumor cells being dispersed prior to treatment. Bansal et al. have recently reported on 47 patients receiving vitrectomy for vitreous hemorrhage following posterior uveal melanoma previously treated with plaque brachytherapy. Mean time to vitreous hemorrhage was 22 months (range: 0–137 months), with the mean time from hemorrhage to vitrectomy of 13 months. With an average follow-up of 5 years (range: 0.5–16 years), four out of 47 (9%) cases developed metastasis, and no cases had intraocular tumor dissemination or extraocular extension.
Although not recommended, a small cases series investigated the treatment of exudative retinal detachment with vitrectomy at the time of plaque brachytherapy. Six patients were treated with 25-gauge vitrectomy, transretinal biopsy and subretinal fluid aspiration following plaque placement. Silicone oil tamponade was then inserted by expansion of one of the sclerotomies to 20 gauge. This small case series demonstrated resolution of subretinal fluid that did not recur following silicone oil removal. Although visual acuity was improved in five of six patients (83%), follow-up was limited to a year, which does not allow any conclusions regarding safety, risk of metastasis, tumor dissemination and local tumor control. A larger, retrospective study by Sisk et al. investigated 114 eyes of 111 patients who underwent combined phacoemulsification and suture-less 23-gauge vitrectomy for retinal pathology. A subset of this series (72 patients) also had posterior uveal melanoma treated with plaque brachytherapy that underwent combined vitrectomy following documented tumor inactivity for a minimum of 6 months. Mean follow-up was less than a year (263 days) from surgical intervention. Patients tolerated procedure well, with no severe complications of endophthalmitis or tumor dissemination. Visual acuity improved significantly at 3 months after surgical intervention. Again, follow-up was less than a year, limiting assessment of safety and risk for metastasis, extraocular extension and intraocular dissemination.
Finally, a study by Lonngi et al. reported on a retrospective case series of 102 patients with uveal melanoma treated with iodine-125 plaque brachytherapy who underwent microincisional pars plana vitrectomy. All patients had radiation-related complications, including radiation retinopathy, vasculopathy, retinal detachment (exudative, tractional or rhegmatogenous) or vitreous hemorrhage. All patients underwent 23- or 25-gauge pars plana vitrectomy, with endolaser ablation of the tumor intraoperatively. The mean time to vitrectomy following melanoma treatment was 38.1 months. Mean follow-up after vitrectomy was 19.5 months. At the last follow-up, no cases exhibited tumor recurrence, and there was no intraocular tumor dissemination or extraocular spread. Six patients developed systemic metastasis (5.8%), and one patient died from metastatic disease (0.9%). There were no cases of endophthalmitis. Nine patients (8.8%) developed NVG, but globe salvage was 100%. Mean visual acuity prior to vitrectomy was 20/258, with statistically significant improvements in postoperative visual acuity at all time points. At 12 months, visual acuity had improved to 20/113, with 36.7% gaining two or more lines of vision. Mean visual acuity was ambulatory (better than 5/200) in 90.2% of patients, with 71.4% having better than 20/400 vision, and 36.2% with 20/50 or better vision.
Downsides of vitrectomy for melanoma-related and radiation-related complications include cataract, hypotony, vitreous hemorrhage and endophthalmitis. A dreaded complication of vitrectomy is tumor dissemination intraocularly or extraocularly, which may increase the risk of metastasis. Vitrectomy may also cause iatrogenic retinal breaks and theoretically may decrease the efficacy of intravitreal agents. Finally, long-term data is not available regarding risks and outcomes of surgical intervention, highlighting the need for future research on the use of vitrectomy in eyes with posterior uveal melanoma.
Vitrectomy for Complications
Eyes with untreated and treated uveal melanoma frequently have retinal detachments as a result of intrinsic tumor activity or radiation or tumor-related complications. These retinal detachments may be exudative, rhegmatogenous, tractional or a combination. Exudative retinal detachments are very common and represent intrinsic tumor activity, vascular permeability and retinal pigment epithelial dysfunction. These retinal detachments may differentiate a benign nevus from a malignant melanoma, with an estimated incidence of 50–100% in uveal melanomas prior to treatment. Exudative retinal detachments improve with plaque brachytherapy treatment with a natural history of resolution in a mean of 5.6 months and 90% resolution rate at 1 year. With any retinal detachment that persists over time, there is a risk of photoreceptors damage and loss, which may result in permanent and irreversible vision loss. Several strategies have been investigated to speed the resolution of exudative retinal detachments, including surgical and medical techniques. Char et al. reported on 11 patients treated with proton beam irradiation and transpupillary thermotherapy, showing that mean time to resolution of exudative retinal detachment was significantly less as compared to proton irradiation monotherapy (193 days vs 263 days). Use of intravitreal bevacizumab (2.5 mg/0.1 cc) following plaque brachytherapy has shown promise in hastening the resolution of subretinal fluid. When used at the time of plaque removal, Houston et al. showed that the mean time to resolution of exudative retinal detachment in 124 patients was 3.36 months, with 43% resolving by 1 month.
Surgical management of tumor and radiation-related complications has recently been investigated. Potential indications for vitrectomy include exudative detachments, radiation retinopathy and maculopathy, vitreous hemorrhage, tractional and rhegmatogenous retinal detachments. Prior to vitrectomy surgery, the surgeon must ensure tumor inactivity to minimize the risk of intraocular tumor dissemination. As seen in natural history studies of exudative retinal detachments, approximately 10% of patients have persistent subretinal fluid at 1 year or more. Exudative retinal detachments may be associated with active tumor, so it is imperative for the ocular oncologist to observe these tumors and document stability. If the tumor remains stable without any active growth or activity, vitrectomy with drainage of subretinal fluid may be a viable option for visual rehabilitation. Radiation-related complications can manifest as early as 6 months following plaque brachytherapy or anytime thereafter. These early findings are observed using spectral-domain optical coherence tomography, which may identify subtle disease prior to clinically evident changes. The earliest manifestation is radiation maculopathy with macular edema. Anti-VEGF agents and corticosteroids have been shown to be effective in the early treatment of radiation retinopathy and may delay or prevent the progression of radiation effects. For cases intractable to medical therapy, vitrectomy may be considered. Vitrectomy for radiation retinopathy may aid in several ways, including relieving vitreoretinal traction and decreasing the vitreous source of VEGF, a key component in the development of radiation-related complications. Vitreous hemorrhage is another complication that may be amenable to vitrectomy. Vitreous hemorrhage may occur secondary to proliferative radiation retinopathy with neovascularization, tractional forces avulsing a blood vessel, posterior vitreous detachment or tumor-related. For those hemorrhages thought to be tumor-related, careful observation is prudent to determine tumor recurrence or tumor activity. Following plaque brachytherapy, there also appear to be strong vitreoretinal adhesions at the tumor periphery that can exert tractional forces leading to tractional or rhegmatogenous retinal detachments. Vitrectomy can aid in relieving these tractional forces, as well as repair the resultant retinal detachment (Figure 1).
(Enlarge Image)
Figure 1.
A 55-year-old female with a history of posterior uveal melanoma treated with iodine-125 plaque brachytherapy 1 year prior. (A) Patient sustained a vitreous hemorrhage and macula-involving retina detachment. Visual acuity at this time was hand motions. (B) Ultrasound shows previously treated uveal melanoma that shows no growth compared to prior imaging. (C) Patient underwent pars plana vitrectomy, air-fluid exchange, endolaser, silicone oil without complications. No evidence of tumor dissemination, local recurrence or extraocular extension. (D) Visual acuity improved to 20/200, 6 months after positive predictive value. Final visual acuity limited by central retinal atrophy.
Few studies have addressed the surgical management of eyes harboring uveal melanoma, and controversy remains regarding if and when these eyes can be operated. At the heart of the debate is the concern of viable tumor cells disseminating intraocularly or extending extraocularly. Small case reports have shown a low risk for eyes that contain treated tumors; however, in cases with vitreous hemorrhage prior to treatment, there appears to be an increased risk of intraocular dissemination likely secondary to tumor cells being dispersed prior to treatment. Bansal et al. have recently reported on 47 patients receiving vitrectomy for vitreous hemorrhage following posterior uveal melanoma previously treated with plaque brachytherapy. Mean time to vitreous hemorrhage was 22 months (range: 0–137 months), with the mean time from hemorrhage to vitrectomy of 13 months. With an average follow-up of 5 years (range: 0.5–16 years), four out of 47 (9%) cases developed metastasis, and no cases had intraocular tumor dissemination or extraocular extension.
Although not recommended, a small cases series investigated the treatment of exudative retinal detachment with vitrectomy at the time of plaque brachytherapy. Six patients were treated with 25-gauge vitrectomy, transretinal biopsy and subretinal fluid aspiration following plaque placement. Silicone oil tamponade was then inserted by expansion of one of the sclerotomies to 20 gauge. This small case series demonstrated resolution of subretinal fluid that did not recur following silicone oil removal. Although visual acuity was improved in five of six patients (83%), follow-up was limited to a year, which does not allow any conclusions regarding safety, risk of metastasis, tumor dissemination and local tumor control. A larger, retrospective study by Sisk et al. investigated 114 eyes of 111 patients who underwent combined phacoemulsification and suture-less 23-gauge vitrectomy for retinal pathology. A subset of this series (72 patients) also had posterior uveal melanoma treated with plaque brachytherapy that underwent combined vitrectomy following documented tumor inactivity for a minimum of 6 months. Mean follow-up was less than a year (263 days) from surgical intervention. Patients tolerated procedure well, with no severe complications of endophthalmitis or tumor dissemination. Visual acuity improved significantly at 3 months after surgical intervention. Again, follow-up was less than a year, limiting assessment of safety and risk for metastasis, extraocular extension and intraocular dissemination.
Finally, a study by Lonngi et al. reported on a retrospective case series of 102 patients with uveal melanoma treated with iodine-125 plaque brachytherapy who underwent microincisional pars plana vitrectomy. All patients had radiation-related complications, including radiation retinopathy, vasculopathy, retinal detachment (exudative, tractional or rhegmatogenous) or vitreous hemorrhage. All patients underwent 23- or 25-gauge pars plana vitrectomy, with endolaser ablation of the tumor intraoperatively. The mean time to vitrectomy following melanoma treatment was 38.1 months. Mean follow-up after vitrectomy was 19.5 months. At the last follow-up, no cases exhibited tumor recurrence, and there was no intraocular tumor dissemination or extraocular spread. Six patients developed systemic metastasis (5.8%), and one patient died from metastatic disease (0.9%). There were no cases of endophthalmitis. Nine patients (8.8%) developed NVG, but globe salvage was 100%. Mean visual acuity prior to vitrectomy was 20/258, with statistically significant improvements in postoperative visual acuity at all time points. At 12 months, visual acuity had improved to 20/113, with 36.7% gaining two or more lines of vision. Mean visual acuity was ambulatory (better than 5/200) in 90.2% of patients, with 71.4% having better than 20/400 vision, and 36.2% with 20/50 or better vision.
Downsides of vitrectomy for melanoma-related and radiation-related complications include cataract, hypotony, vitreous hemorrhage and endophthalmitis. A dreaded complication of vitrectomy is tumor dissemination intraocularly or extraocularly, which may increase the risk of metastasis. Vitrectomy may also cause iatrogenic retinal breaks and theoretically may decrease the efficacy of intravitreal agents. Finally, long-term data is not available regarding risks and outcomes of surgical intervention, highlighting the need for future research on the use of vitrectomy in eyes with posterior uveal melanoma.
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