External radiotherapy in macular degeneration: Technique and preliminary subjective response

doi:10.1016/S0360-3016(96)00428-2

International Journal of Radiation OncologyBiologyPhysics

Volume 36, Issue 4, 1 November 1996, Pages 857-860

https://doi.org/10.1016/S0360-3016(96)00428-2 Get rights and content

Abstract

$Purpose$ : This study attempted to assess the toxicity and possible preliminary benefits from teh administration of low-dose external beam irradiation for age-related macular degeneration (ARMD). The premise of the treatment is that radiation induces regression and/or promotes inactivation of the subretinal neovasculature which would result in reabsorption of fluid and blood. This would reduce the risk for further leakage or bleedings, as well as subretinal fibrosis. Consequently, the beneficial effect could be translated into stabilization of visual acuity and prevention of progression of the wet ARMD with the possibility for slight improvement.

$Methods and Materials$ : Allegheny University Department of Radiation Oncology treated 41 patients prospectively from January through October 1995 with low-dose irradiation for wet-type macular degeneration. A total of 39 patients were treated with a total dose of 14.4 Gy in eight fractions of 1.8 Gy/fraction over 10–13 elapsed days. The first two patients were treated with a total dose of 10 Gy in fivefractions of 2 Gy. Patients were evaluated at 2–3 weeks and 2–3 months. Some of the patients (6.7%) had laser treatment in the study eye: 21.9% (9) once, 5% (2) twice, 9.7% (4) thrice or more. Subjective visual acuity and toxicity data were collected on all patients.

$Results$ : At 2–3 weeks after treatment 29 patients (70%) retained their visual acuity without change, 10 (24.5%) stated they had improved vision, adn 2 (4.8%) stated their vision continued to decrease. At 2–3 months after treatment, 27 patients (65.8%) had no change in their vision, 11 (27%) had an improvement in their vision, and 3 (7.2%) had a decrease in visual acuity. Six patients of 41 in the treated group had acute transient side effects.

$Conclusion$ : Our observation in this group of 41 patients support the conclusion that many patients will have improved or stable vision after treatment with low-dose irradiation for age-related wet-type macular degeneration.

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Cited by (54)

Radiation therapy for neovascular age-related macular degeneration
2013, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
Radiation was well tolerated, with cataract developing by 12 months in 1 patient treated with 15 Gy. This landmark paper engendered several additional phase 1/phase 2 studies (Table 1) (31-47). Several drawbacks limit the conclusiveness and generalizability of these early studies.
In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.
Proton Beam Irradiation for Neovascular Age-Related Macular Degeneration
2006, Ophthalmology
To evaluate safety and visual outcomes after proton therapy for subfoveal neovascular age-related macular degeneration (AMD).
Randomized dose-ranging clinical trial.
One hundred sixty-six patients with angiographic evidence of classic choroidal neovascularization resulting from AMD and best-corrected visual acuity of 20/320 or better.
Patients were assigned randomly (1:1) to receive 16-cobalt gray equivalent (CGE) or 24-CGE proton radiation in 2 equal fractions. Visual acuity was measured using standardized protocol refraction. Complete ophthalmological examinations, color fundus photography, and fluorescein angiography were performed before and 3, 6, 12, 18, and 24 months after treatment.
Proportion of eyes losing 3 or more lines of vision from baseline. Kaplan–Meier statistics were used to compare cumulative rates of vision loss between the 2 treatment groups.
At 12 months after treatment, 36 eyes (42%) and 27 eyes (35%) lost 3 or more lines of vision in the 16-CGE and 24-CGE groups, respectively. Rates increased to 62% in the 16-CGE group and 53% in the 24-CGE group by 24 months after treatment (P = 0.40). Radiation complications developed in 15.7% of patients receiving 16 CGE and 14.8% of patients receiving 24 CGE.
No significant differences in rates of visual loss were found between the 2 dose groups. Proton radiation may be useful as an adjuvant therapy or as an alternative for patients who decline or are not appropriate for approved therapies.
Effect of irradiation on neovascularization in rat skinfold chambers: Implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration
2004, International Journal of Radiation Oncology Biology Physics
Citation Excerpt :
In 1993, Chakravarthy et al. (1) reported a study of the use of low-dose radiotherapy for age-related macular degeneration; during a 12-month follow-up period, 63% of the cases showed no subsequent worsening of visual acuity and 77% showed atrophy of the CNV. Additional clinical trials have produced contradictory results: most replicated the original findings (2–8), but others failed to do so (9, 10). Possible explanations of these contradictory results include differences in the stage of disease, in the evaluation of the therapy, and in the evaluation of the CNV.
Wet-type age-related macular degeneration is a refractory eye disease that involves choroidal neovascularization. Randomized controlled trials of low-dose radiotherapy for this disease performed in Japan showed that, at 12 months of follow-up, visual acuity was significantly well preserved and the neovascular membrane size decreased. Because understanding the effect of irradiation on new vascular networks is an important prerequisite for clinical trials, we used a rat skinfold chamber technique to investigate X-ray–induced changes in neovasculature microcirculation.
Neovascularization was induced in rat skinfold chambers via polyvinyl chloride resin plates. Neovessels were irradiated in a single 10-Gy dose, after which, changes in vascular density, blood velocity, tissue blood flow, and interstitial fluid pressure (IFP), were measured.
Vascular density, tissue blood flow, and IFP measurements in resin-induced inflammatory tissue were much higher than those measurements in normal tissue. Although overall blood velocity was low and sluggish or blood-flow stasis occurred in the neovascular network, after a single 10-Gy dose of radiation, the velocity increased, stasis improved markedly, and many dilated vessels narrowed. Thereafter, vascular density, blood flow, and IFP significantly decreased and approached normal values.
These findings may help explain clinical results related to radiotherapy-induced changes in neovascular membranes in age-related macular degeneration. Both vascular morphology and vascular function in inflammatory tissue returned to normal, without vessel destruction, after an appropriate radiation dose.
The age-related macular degeneration radiotherapy trial (AMDRT): One year results from a pilot study
2004, American Journal of Ophthalmology
To assess the short-term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5 × 4 Gy fractions among patients having age-related macular degeneration (AMD).
A multicenter prospective randomized controlled pilot study.
Eighty-eight patients were enrolled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV [N = 41]) or no radiotherapy (sham radiotherapy [N = 22] or observation [N = 25]). Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV not amenable to treatment. Randomization was stratified by lesion type (new or recurrent CNV) and blood (<50% or ≥50% of the lesion [N = 13]). The primary outcome measure was loss of ≥3 lines of visual acuity. Secondary outcome measures were angiographic response and side effects.
At baseline, patient and ocular characteristics were similar between treatment groups. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost ≥3 lines of visual acuity (P = .04; stratified χ² test). At 12 months, 13 radiated eyes (42%) and 9 observed eyes (49%) lost ≥3 visual acuity lines (P = .60). The radiated group demonstrated smaller lesions and less fibrosis than the nonradiated group (P = .05 and .004, respectively) at 12 months. Radiation-induced complications were not observed except for one radiated eye with numerous cotton wool spots and possible radiation retinopathy.
External beam radiation at 5 × 4 Gy may have a modest and short-lived (six month) benefit in preserving visual acuity.
Radiotherapy in age-related macula degeneration
2002, International Journal of Radiation Oncology Biology Physics
$Purpose$ : To ascertain the benefit from radiotherapy in age-related macula degeneration in a single-arm longitudinal study.
$Methods and Materials$ : From 1997 to 1998, 39 patients with occult and 33 patients with classic choroidal neovascularization (CNV) were irradiated with 16 Gy. Fluorescein angiography and measurements of visual acuity were performed before and 3, 6, and 12 months after irradiation.
$Results$ : Complete follow-up data for 1 year were available from 69 patients. The mean patient age was 72 years (range 49–92). Vision decreased in 43, was stable in 18, and improved in 8 cases. The mean vision deteriorated significantly (p = 0.02, Wilcoxon test), particularly within the first 3 months. Patients with occult CNV did significantly better than did those with classic CNV (p = 0.03). The proportion of patients retaining vision ≥0.2 fell from 65% to 42% (p <0.01), for classic and occult CNV from 50% to 23%, and for occult CNV from 77% to 56% (p < 0.02), respectively. CNV size increased in 30 patients and was stable in 38. Neither age (p = 0.17) nor gender (p = 0.21, chi-square test) influenced prognosis. Four patients reported transitional complaints.
$Conclusion$ : Low-dose fractionated radiotherapy with 16 Gy is well tolerated. However, vision and reading ability were not preserved in most patients.
Treatment of age-related macular degeneration
2000, Clinical Eye and Vision Care

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External radiotherapy in macular degeneration: Technique and preliminary subjective response

Abstract

Survey Ophthalmol.

Radiation therapy for subfoveal neovascular membranes in age related macular degeneration. Pilot study

Graefe Arch. Clin. Exp. Ophthalmol.

Radiation therapy for age-related subfoveal choroidal neovascular membranes. A pilot study

Docum. Ophthalmol.

Treatment of age related subfoveal neovascular membranes by teletherapy: A pilot study

Br. J. Ophthalmol.

Treatment of age related subfoveal neovascular membranes by teletherapy

Br. J. Ophthalmol.