Ординатура / Офтальмология / Английские материалы / Retinal Vascular Disease_Joussen, Gardner, Kirchhof_2007

B. Damato

23 III

Core Messages

Vasculopathy can develop after different forms of treatment for uveal melanoma

After radiotherapy, macular edema and hard exudates can be caused by macular vasculopathy, extramacular retinopathy, or exudation from the irradiated tumor

Maculopathy caused by exudation from persistent irradiated tumor can be treated by administering transpupillary thermotherapy to the tumor or by removing the tumor

After radiotherapy of a large choroidal melano-

23.1 Uveal Melanoma

Essentials

Most uveal melanomas arise in choroid and almost 50 % of these extend close to optic nerve or fovea

Treatment of choroidal melanoma is by radiotherapy, phototherapy, local resection or enucleation, individually or in combination

ma, severe exudative retinal detachment, rubeosis iridis and neovascular glaucoma can be treated by excising the irradiated tumor Photocoagulation of a choroidal melanoma can induce aggressive disk and retinal neovascularization if the major retinal vessels are occluded, as well as choroidal new vessels if Bruch’s membrane is ruptured

Choroidal new vessels can develop from a surgical coloboma of the choroid, to cause disciform macular degeneration

Uveal melanomas present in adulthood, their incidence peaking at around the age of 60 years [4]. More than 90 % of uveal melanomas arise in choroid, about 40 % extending close to optic disk or fovea. These tumors tend to cause visual loss from retinal pigment epithelial disease, macular edema, and exudative retinal detachment (Fig. 23.1). In advanced cases, the presence of a large intraocular tumor and extensive retinal detachment can result in rubeosis, neovascular glaucoma, phthisis, and a blind and painful eye. Approximately 50 % of

patients develop metastatic disease, which usually involves the liver and which is usually fatal within a few months.

Treatment of uveal melanoma by enucleation has largely been superseded by a variety of methods aimed at conserving the eye with as much vision as possible [5]. Such “conservative” therapies consist of: (a) radiotherapy, which includes brachytherapy, proton beam radiotherapy, and stereotactic radiotherapy; (b) phototherapy, such as photocoagulation, transpupillary thermotherapy, and photodynamic therapy; and (c) tumor resection, performed by the transscleral or transretinal routes. Several of these treatments induce vascular changes in the tumor as well as in adjacent ocular tissues and these effects can cause visual loss.

The aims of this chapter are to describe vasculopathies caused by the different forms of treatment of uveal melanoma and to discuss their treatment.

23.2 Radiotherapy

23.2.1 Radiotherapy Techniques

In most centers, the first choice of treatment is brachytherapy, usually administered with a radioactive plaque containing ruthenium-106 or iodine125. Less commonly used plaques include the binuclide plaque containing both ruthenium and iodine, palladium, iridium, and strontium [11, 12, 16, 18]. Proton beam radiotherapy is available in only a small number of centers around the world. Some oncologists use this treatment for all choroidal melanomas; others reserve it for tumors that cannot adequately be treated with brachytherapy, because of large size or close proximity to optic disk or fovea [14].

Stereotactic radiotherapy is generally used as an alternative to proton beam radiotherapy in centers where a cyclotron unit is not available [10].

23.2.2 Radiation Vasculopathy

Ionizing radiation displaces electrons from water molecules, producing toxic free radicals, and from DNA and membranes, which are damaged reparably or irreversibly. Irradiated cells can die rapidly by apoptosis or they can lose their reproductive capacity, continuing to function normally until they reach the end of their normal life-span, becoming senes-

cent or dying when trying to divide. III 23 Radiation causes both acute and chronic effects.

The acute effects are caused by breakdown of cell membranes, which result in optic disk swelling, macular edema, and exudative retinal detachment. These can resolve or may be followed by atrophy of the optic nerve, retina, retinal pigment epithelium and choroid. Chronic effects in the posterior segment of the eye are dominated by vascular degeneration, because of the relatively low cell turnover of cells in the retina and optic nerve. Gradual depletion of vascular endothelial cells and pericytes results in progressive circulatory decompensation, causing exudation, hemorrhage, occlusion, ischemia and neovascularization. These are manifest clinically as retinal telangiectasia, microaneurysms, macular edema, hard exudates, retinal hemorrhages, capillary closure, cotton wool spots, optic disk swelling, retinal and disk neovascularization, rubeosis, vitreous hemorrhage and neovascular glaucoma.

Visual loss after radiotherapy can be caused: (a) directly by cell death and vasculopathy in the optic nerve (Fig. 23.2) or macula (Fig. 23.3); or (b) indirectly, from exudation or hemorrhage arising from vasculopathy in another part of the eye, far from

Essentials

Radiation retinopathy may be primary, as a result of retinal irradiation, or secondary, caused by the persistence of irradiated tumor in the eye

Secondary radiation retinopathy can be treated by administering transpupillary thermotherapy to the irradiated tumor or by resecting the tumor

a

Fig. 23.2. Optic neuropathy after proton beam radiotherapy of a superonasal, juxtapapillary choroidal melanoma in the right eye: a exudative phase, 16 months after radiotherapy, with disk swelling and hard exudates

b

Fig. 23.2. b ischemic phase, 48 months after radiotherapy, with disk neovascularization and vitreous hemorrhage

Fig. 23.5. Extensive radiation retinopathy after proton beam radiotherapy of an inferior choroidal melanoma in a 32-year- old, female, diabetic patient. Despite aggressive panretinal photocoagulation, enucleation was eventually necessary

Fig. 23.3. Macular atrophy after ruthenium plaque radiotherapy of a posterior choroidal melanoma in the left eye

Fig. 23.4. Macular hard exudates from a temporal choroidal melanoma after proton beam radiotherapy

these structures (Fig. 23.4). The indirect effects of radiation diminish when there is complete vascular obliteration and atrophy of the irradiated tissues, because exudation ceases and because the ischemic stimulus to neovascularization is no longer present. This is why a low dose of radiation to a large part of the eye (e.g., from external beam radiotherapy of an intracranial tumor) can cause more ocular morbidity and visual loss than a high dose of radiation to a small area (e.g., brachytherapy of a choroidal melanoma). Irrespective of the type of radiation, ocular morbidity is more severe in the presence of diabetes (Fig. 23.5) or with concurrent chemotherapy.

23.2.3 Treatment of Radiation Vasculopathy

With iodine-125 brachytherapy, direct radiation damage to optic nerve and macula can be avoided by collimation (Fig. 23.6) [1]. With ruthenium-106 brachytherapy, such collateral damage can be prevented by positioning the plaque eccentrically, with its posterior edge aligned with the posterior tumor margin, using side-scatter of radiation to achieve the required safety margin (Fig. 23.7). This approach has improved conservation of vision, without any increase in local tumor recurrence rates (Fig. 23.8) [8, 9]. With proton beam radiotherapy, irradiation of optic nerve and macula is reduced by creating a notch in the beam (Fig. 23.9).

Direct radiation damage to optic nerve and macula is untreatable. In mild cases, spontaneous improvement can sometimes occur (Fig. 23.10). There is scope for investigating agents such as intraocular steroids (Fig. 23.11), and in the future radioprotective agents [17].

23.3 Phototherapy

23.3.1 Phototherapy Techniques

Photocoagulation heats the target tissue to approximately 60 °C so that cellular proteins are coagulated. Transpupillary themotherapy heats the tumor by only a few degrees and is regarded as being safer and more effective than photocoagulation, which it supersedes [15]. There are anecdotal reports of photodynamic therapy of choroidal melanoma, but further evaluation is needed to determine the efficacy of this treatment [2].

23.3.2 Vasculopathy After Phototherapy

Photocoagulation obliterates not only all the tumor vasculature but also any overlying retinal vessels. Severe retinal ischemia caused by occlusion of the major retinal vessels can cause disk and retinal neovascularization. Furthermore, any breaks in Bruch’s membrane can allow choroidal new vessels to develop (Fig. 23.16) [13]. These can be aggressive, growing as far forward as the lens (Fig. 23.17). As with radiation-induced neovascularization, any new vessels caused by phototherapy behave more aggressively if the patient suffers from diabetes mellitus. Neovascular complications are rarer with transpupillary thermotherapy than with photocoagulation.

Fig. 23.16. Choroidal neovascularization with subhyaloid hemorrhage after photocoagulation of a choroidal melanoma in the left eye of a 50-year-old man

Fig. 23.17. Subluxation of the lens from traction by a choroidal fibrovascular membrane arising after photocoagulation of a superior, juxtapapillary choroidal melanoma in the right eye of a 70-year-old man. Neovascular glaucoma had also developed

a

23.3.3 Treatment of Vasculopathy After

Phototherapy

23.4 Local Resection

23.4.1 Local Resection Techniques

Transscleral local resection involves the en bloc excision of the intact tumor, together with the deep scleral lamella to which it is attached, if possible without damaging the adjacent retina [7]. Endoresection is performed transvitreally, either through a hole in the retina over the tumor or after raising a retinal flap [6]. These operations are difficult and controversial and are therefore performed as primary procedures only by a few surgeons and for tumors considered unsuitable for radiotherapy. An alternative approach is to perform endoresection after radiotherapy [3].

23.4.2 Vasculopathy After Local Resection

After both types of local resection, choroidal new vessels can develop from the surgical margins. These vessels are subclinical if they grow into the surgical coloboma (Fig. 23.18). When the surgical excision extends far posteriorly, there is a tendency for any choroidal vessels to grow towards the fovea, resulting in a disciform scar, this condition arising both after transscleral resection (Fig. 23.19) and after transretinal resection (Fig. 23.20). Such disciform macular

b

Fig. 23.21. Choroidal neovascular membrane arising from an iatrogenic choroidal tear following transscleral local resection of a choroidal melanoma in the left eye of a 46-year-old woman

degeneration can occur also as a result of an iatrogenic choroidal tear (Fig. 23.21).

23.4.3Treatment of Vasculopathy After Local Resection

The treatment of choroidal new vessels threatening vision after local resection is the same as for agerelated macular degeneration.

23.5 Conclusion

Vasculopathy is a common cause of visual loss after treatment of choroidal melanoma, resulting in ischemia and exudation. After radiotherapy, maculopathy and optic neuropathy can be the result of direct irradiation or can arise indirectly, because of exudation from irradiated retina or tumor as well as from neo-

vascular complications. Phototherapy can induce retinal or disk neovascularization by obliterating large retinal vessels and, furthermore, choroidal neovascularization can occur if Bruch’s membrane is ruptured. After transretinal or transscleral local resection, choroidal neovascularization can develop harmlessly into the coloboma or can extend posteriorly to cause a macular disciform scar. The principles of treating these neovascular and exudative complications are the same as for other diseases; however, when irradiated tumor is the cause of retinopathy, then phototherapy or excision of the residual tumor can be effective.

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