Radiol Oncol 1999; 33(1): 55-8.
Radiotherapy for choroidal neovascularisation of age-related
macular degeneration
Wolfgang Wagner1, Erik Beeke2, Peter Barsnick2
1 Paracelsus Strahlenklinik, 2 Parace/sus-Klinik, Department of Ophthalmology, Osnabrück, Germany
Age-related macular degeneration caused by choroidal neovascularisation is an increasing problem in ophthalmology. The results of the therapy in the past were poor or associated with a number of side effects. Recently, some reports have shown a beneficial effect of low-dose irradiation. Therefore, we reviewed the data of our patients included in a pilot study to confirm the very preliminary data in literature. Fourty-three patients were irradiated with a linear accelerator (6 MV) at a total dose of 16 Gy. Six months after irradiation, 69% of our patients maintained or improved their visual acuity. We did not observe side effects ar any acute or late sequelae within a median follow-up period of 12 months.
Key words: macular degeneration - radiotherapy, visual acuity
Introduction
Choroidal neovascularisation (CNV) is a major cause of severe loss of visual acuity in the patients with age-related macular degeneration.1 Without therapy, the natura] course of this disease would result in the loss of patient's sight.
In the past, laser photocoagulation was used as treatment method, but was, unfortunately, associated with further decrease in visual acuity.2 In the treatment of CNV, interferon was used systemically, but, so far, the
Received 14 August 1998 Accepted 7 December 1998
Correspondence to: Priv.-Doz. Dr. Wolfgang Wagner, Paracelsus-Strahlenklinik, Liirmannstr. 38/40, 49076 Osnabrück, Germany. Tel: + 49-541-966 4800; Fax: + 49-541-681 137
substance has not proved to be effective, moreover, it may be that it has severe side effects.3
Another approach is the surgical extirpation although the treatment results are not too encouraging.4 Recently, some investigators have reported of a beneficial effect of low-dose irradiation of the subretinal neovas-cular membranes in the CNV.5-13 The preliminary results are encouraging and the number of side effects is small.
Patients and methods
Between September 1996 and July 1998, we treated 43 patients (25 women and 18 men) with radiotherapy for age-related macular degeneration. All patients gave their
56
Wagner W et al. / Irradiation in patienls with macular degeneration
informed consent before irradiation. The median age at the time of treatment was 74 years (range 60-88 years).
The right and the left eye were treated in 18 and 16 patients, respectively. In 9 patients, both eyes were involved. In all cases, the diagnose was set on the basis of visual examination (funduscopy) carried out by the ophthalmologist. All patients were diagnosed as having the exudative variety of macular degeneration. In 21 patients, angiography was used to determine the size of the neovascularisation.
Irradiation was carried out using a linear accelerator of 6 MV photons. A total dose per patient was 16 Gy and was given in normal fractionation with single doses of 2 Gy 5 times a week. When both eyes were involved, opposed portals were used and the dose was specifically adjusted to the middle of the scull. In case of unilateral neovascularisation, a single irradiation field was used. In all cases, we used a lens-sparing technique.
The median follow-up time was 12 months. Each patient was clinically examined before and immediately after the therapy and then every 3 months. All patients included in this study were questioned about their subjective experience of radiotherapy, treatment results and side effects.
Results
After the completion of irradiation, visual acuity improved in 5 patients (11%), in 35 patients (81%), it was the same as before irradiation and was worse in 3 patients.
Six months after the irradiation, 30 patients (69%) maintained their visual acuity while in 9 patients (21%), it was worse. Four patients were lost from the follow-up at the time of investigation.
Objective changes of visual acuity could be observed only to a limited extent (median difference 0.005). In 5 patients, the moist macular degeneration changed to a dry one
Radiol Oncol 1999; 33(1): 55-8.
without affecting the acuity. In 2 patients, the bleeding occurred again 3 and 7 months after the completed irradiation. As to the side effects, we have not observed any acute or late sequelae after irradiation.
In addition to the objective findings, the results of the interviews with the treated patients were the following results: 31 patients (72%) reported that irradiation had a beneficial influence on their acuity and 12 patients felt that irradiation did not improve their sight.
Discussion
Macular degeneration is an increasing problem in ophthalmology. Today, about 5% of the population in their sixties are affected.1 The patients are handicapped by the loss of central vision and, therefore, their ability to read.
Often, both eyes are affected to various degrees and at different times.14 Stage I shows a dry formation of senile membranes. A detachment of the pigment epithelium with retroretinar bleeding occurs within some weeks. In the exudative stage, disci-form lesions are observed. They consist of choroidal neovascularisation and spread into the retroretinal space as a thin layer between the retina and choroid. At this stage, patients often report seeing only shadows. Regression of the exudative changes causes complete atrophy of the central part of the retina. The therapy is stage-dependant.14
In the early dry stage, no special therapy is recommended. The detachment of the pigment epithelium is treated with corticosteri-ods. Laser coagulation could be applied, but causes scars and decreases the acuity. 2,15-17 Neovascular membranes cannot be treated with laser. In these cases, radiotherapy can be applied as alternative treatment. Irradiation seems to be able to stop further progress of the disease.
Proliferating vascular cells have been
Wagner W et al. / Irradiation in patients with macular degeneration
57
known to be relatively sensitive to low doses of radiation. Irradiation may prevent the proliferation of endothelial cells of newly formed subretinal capillaries and induce obliteration of the aberrant new vessels.18 Some data that have appeared so far in the literature confirm the assumption that photon irradiation can be a beneficial tool in treating this disease. Chakravarthy et al. treated macular degeneration with a total dose of 10 or 15 Gy and recorded that the visual acuity was maintained or improved in 78% of all patients.8 Hart and colleagues treated 41 patients with 10, 12 or 15 Gy and found no significant difference in the effect of treatment of 3 different dose regimes.10 Bergking et al.5 evaluated the patients in a study on doses ranging between 8 and 24 Gy. The first group received 8 Gy in a single fraction. In this group, only 30% had stable visual acuity. In the second group, 50% of patients having received a dose of 12 Gy had stable visual acuity after a follow-up of 18 months and in the third group having received a dose of 18 Gy, 40% of patients had stable visual acuity after the same follow-up period. In the group which had received 24 Gy, 80% of all patients had stable visual acuity.
Hence, it is possible that there is a relationship between total doses of irradiation and treatment results. But care should be taken not to exceed a total dose of 25 Gy in order to avoid an increase in side effects.
On the other hand, some data published in literature report of the positive treatment results using proton beam irradiation. Yonemoto et al.13 reported that after a median follow-up of 11.6 months 58% of a total of 21 patients had an improved or stable visual acuity. So far, it has not been proved that, with regard to the treatment results, heavy particles such as protons are superior to normal photon therapy.
In our investigation, we recorded stable visual acuity objectively in 69% of all patients 6 months after irradiation. After interviewing
the patients, it was estimated that the effect of treatment was beneficial in 72% of cases. As no acute or late sequelae and no changes in the number of stable diseases were observed within the median follow-up time of 12 months, we believe that low-dose irradiation can be a good treatment policy of the patients with progressive CNV. Nevertheless, the definitive role of radiotherapy in patients with CNV is still to be defined by a control phase-III study.
References
1.	Bressler NM, Bressler SB, Fine SL. Age-related macular degeneration. Surv Ophthalmol 1988; 32: 375-412.
2.	Macular Photocoagulation Study Group. Laser photocoagulation of subfoveal neovascular lesions in age-related macular degeneration. Results of a rendomized clinical trial. Arch Ophthalmol 1991; 9: 1220-31.
3.	Thoelen A, Menozzi M, Huber C, Messmer E. Treatment of choroidal neovascularization in age-related macular degeneration with interferon alpha-2a: a short term, nonrandomized pilot study. Ger J Ophthalmol 1995; 3: 137-43.
4.	Thomas MA, Dickinson JD, Melberg NS, Ibanez HE, Dhaliwal RS. Visual results after surgical removal of subfoveal choroidal neovascular membranes. Ophthalmology 1994; 8: 1384-96.
5.	Bergink GJ, Deutman AF, von den Broek JE, van Daal WA, van der Maazen RM. Radiation therapy for age-related subfoveal choroidal neovascular membranes. A pilot study. Doc Ophthalmol 1995; 90: 67-74.
6.	Bergink GJ, Deutman AF, van den Broek JF, van Daal WA, van der Maazen RW. Radiation therapy for subfoveal choroidal neovascular membranes in age-related macular degeneration. A pilot study. Graefes Arch Clin Exp Ophthalmol 1994; 10: 591-8.
7.	Bergink GJ, Hoyng CB, van der Maazen RW, Deut-man AF, van Daal WA. Visual acuity and scar size in eyes with age-related subfoveal choroidal neo-vascular lesions, 30 months after radiation therapy. Doc Ophthalmol 1996; 1: 61-75.
8.	Chakravarthy U, Houston RF, Archer DB. Treatment of age-related subfoveal neovascular membranes by teletherapy: a pilot study. Br J Ophthalmol 1993; 5: 265-73.
Radiol Oncol 1999; 33(1): 55-8.
58
Wagner W et al. / Irradiation in patients with macular degeneration	57
14.	Schleicher UM, Andreopoulos D, Wolf S, Schmachtenberg A, Ammon J, Reim M. Radiotherapy of macular degeneration. Experience with two fractionation schemes. Front Radiat Ther Oncol 1997; 30: 253-8.
15.	Coscas G, Soubrane G, Ramahefasolo C, Fardeu C. Perifoveal laser treatment for subfoveal choroidal new vessels in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthaliiioll99l; 9: 1258-65.
16.	Maculai' Photocoagulation Study Group. Laser photocoagulation of subfoveal recurrent neovas-cular lesions in age-related macular degeneration. Results of a randomized clinical trial. Arch Ophthalmol 1991; 9: 1232-41.
17.	Macular Photocoagulation Study Group. Visual outcome after laser photocoagulation for subfoveal choroidal neovascularization secondary to age-related macular degeneration. The influence of initial lesions size and initial visual acuity. Arch Ophthalmol 1994; 4: 480-8
18.	Archer DB, Amoaku WMK, Gardiner TA. Radiation retinopathy - clinical, histopathological, ultrastructural and experimental correlations. Eye 1991; 5: 239-51.
Biol Phys 1996; 4: 867-71.
Radiol Oncol 1999; 33(1): 55-8.
9.	Harino S, Oshima Y, Tsujikawa K, Oh A, Sugimo-to K, Murayama S, et al. Treatment of age-related subfoveal choroidal neovascularization by low-dose external radiation: a preliminary study. Nippon Ganka Gakkai Zasshi 1997; 4: 341-8.
10.	Hart PM, Chakravarthy U, Mac Kenzie G, Archer DB, Houston RF. Teletherapy for subfoveal choroidal neovascularisation of age-related macular degeneration: results of follow-up in a non-randomized study. Br J Ophthalmol 1996; 12: 1046-50.
11.	Matsuhashi H, Takahashi D, Noda Y, Mariya Y, Tarusawa N, Yoshimoto H, et al. Low-dose radiation, therapy for choroidal neovascularization in age-related macular degeneration. Nippon Ganka Gakkai Zasshi 1996; 10: 803-9.
12.	Sasai K, Murata R, Mandai M, Takahashi M, Ogura Y, Ngata Y, et al. Radiation therapy for ocular choroidal neovascularization (phase I/II study): preliminary report. Int J Radiat Oncol Biol Phys 1997; 1: 173-8.
13.	Yonemoto LT, Slater JD, Friedrichsen EJ, Loredo LM, Ing J, Archambeau JO, et al. Phase l/II study of proton beam irradiation for the treatment of subfoveal choroidal neovascularization in age-related macular degeneration: treatment techniques and preliminary results. Int J Radiat Oncol