Age-related macular degeneration: long-term results of radiotherapy for subfoveal neovascular membranes

doi:10.1016/S0002-9394(00)00534-1

American Journal of Ophthalmology

Volume 130, Issue 5, November 2000, Pages 617-635

https://doi.org/10.1016/S0002-9394(00)00534-1 Get rights and content

Abstract

PURPOSE: To study results of 2-year follow-up of radiotherapy for subfoveal choroidal neovascular membrane associated with age-related macular degeneration.

METHODS: In a randomized prospective clinical study, 101 patients received a low-dose radiotherapy or no treatment. In the treatment group, subfoveal choroidal neovascular membranes were treated with 20 Gy of 6-MV photons to the macula of the affected eye.

RESULTS: The overall complete follow-up rate was 84.2% (85/101). No measurable treatment-related morbidity was seen during or after treatment. Mean changes in log of minimal angle of resolution (logMAR) of visual acuity and area of choroidal neovascular membrane for 2-year follow-up were +0.226 ± 0.373 and 143.5 ± 53.1% in the treatment group, and +0.563 ± 0.370 and 190.3 ± 81.4% in the control group; a significant difference was found (P < .0001; P = .0008). In patients with smaller choroidal neovascular membrane (≤1.5 mm²) or better visual acuity (≥60/200) at baseline, the treatment group showed a significantly smaller increase in area of choroidal neovascular membrane and a significantly smaller decrease in LogMAR visual acuity for 2 years, whereas there was no significant difference in patients with larger choroidal neovascular membrane (>1.5 mm²) or poorer visual acuity (<60/200).

CONCLUSIONS: Radiotherapy appeared to have a favorable treatment effect in eyes with subfoveal neovascular membrane associated with AMD. Favorable factors for radiotherapy were a smaller area of choroidal neovascular membrane and better visual acuity.

Section snippets

Patients and methods

One hundred one consecutive patients with subfoveal choroidal neovascular membrane with age-related macular degeneration who fulfilled the indications for radiotherapy were enrolled. Age-related macular degeneration was diagnosed according to the criteria published by the research committee on chorioretinal degenerations supported by the Ministry of Health and Welfare of Japan.37 Age-related macular degeneration was diagnosed on the basis of the results of slit-lamp biomicroscopy with a

Results

Baseline data are summarized in Table 1. Fifty-one eyes of 51 patients and 50 eyes of 50 patients were enrolled in the treatment group and control group, respectively. There was no statistically significant difference in age, gender, area of choroidal neovascular membrane, and visual acuity between the treatment group and control group.

The overall complete follow-up rate was 84.1% (85/101) (Table 1 and Figure 1). There was no significant difference between the two groups; the complete

Discussion

The natural course of the visual acuity in patients with age-related macular degeneration is poor. In our control group of patients without any treatment, mean visual acuity decreased from 0.224 (20/89.3) to 0.061 (20/327.9) after 2-year follow-up. These findings in our untreated patients are almost identical to those reported in the control patients in foveal Macular Photocoagulation Study.2, 3, 4

Although strenuous efforts were made to follow up patients, the overall complete follow-up rate

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Citation Excerpt :
The lack of a coherent control group precluded firm conclusions of statistical significance. These promising results led to 11 phase 3, randomized controlled trials (Table 2) (51-61). Several studies found statistically significant benefits in patients treated with EBRT (52, 53, 55, 56, 61), whereas others found no lasting benefit (51, 54, 57-60).
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.
The Natural History and Prognosis of Neovascular Age-Related Macular Degeneration. A Systematic Review of the Literature and Meta-analysis
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To describe the natural history and progression of visual loss in eyes with untreated neovascular age-related macular degeneration (AMD).
Systematic review and meta-analysis.
Four thousand three hundred sixty-two untreated neovascular AMD patients from published interventional studies.
A systematic review of the literature from 1980 to August 2005 was performed. Studies reporting disease progression outcomes for untreated patients with neovascular AMD were included. Outcome measures were summarized using simple counts and means. Random effects meta-analyses were conducted and tests of heterogeneity were performed where appropriate.
Changes in visual acuity (VA) loss, development of comorbidities, and fellow eye involvement.
Fifty-three primary studies were included. Nearly half of the studies (28) were randomized clinical trials. The quality of the studies was high, with over 80% providing level I or II evidence. Mean baseline VA among study patients was 0.64 logarithm of the minimum angle of resolution (logMAR) (∼20/87 Snellen). The mean VA change in logMAR progressed from 0.1 (1 line lost) at 3 months to 0.3 (2.7 lines lost) after 12 months and 0.4 (4 lines lost) after 24 months. The proportion of patients who developed severe vision loss (>6 lines) from baseline increased from 21.3% at 6 months to 41.9% by 3 years. The proportion of patients with VA worse than logMAR 1.0 (20/200 Snellen) increased from 19.7% at baseline to 75.7% by 3 years. Neovascular AMD developed in the fellow eye in 12.2% of patients by 12 months and in 26.8% by 4 years. Meta-analyses of vision outcome by subtype of neovascular AMD were not possible.
A doubling of the visual angle of presenting VA may be expected to occur in the year after initial presentation in eyes with untreated neovascular AMD. No conclusions can be drawn as to the differences in rates of disease progression by neovascular AMD subtype. The diversity of reporting formats, paucity of long-term natural history data, and heterogeneity among the reported clinical studies impose limits to the clear understanding of long-term prognosis for visual function in neovascular AMD.
The long-term effect of experimental beta-radiation therapy on the human cornea
2007, Contact Lens and Anterior Eye
Radiation treatment of the human eye has been utilized in the United States since the early 1900s. Beta-radiation therapy was generally accepted by the medical community as a treatment option for a wide variety of anterior and posterior segment conditions from 1930 to the early 1950s. By the 1960s, beta-radiation therapy had fallen out of favor due to dangerous side effects; however an updated radiation procedure is now in use in ophthalmology to treat anterior and posterior segment disease.
A 64-year-old Caucasian female presented for a routine eye examination with a history of experimental beta-radiation treatments to the eyes as a teenager. A high astigmatic refractive error was present and best corrected visual acuity was 20/40 OD, 20/30 OS. Slit lamp examination showed severe disruption throughout the lower third of both corneas, appearing densely calcified with inferior vascularization. The left eye had a central descemetocele.
The patient's ocular and visual conditions were relatively stable and required no special treatment as of the writing of this report, decades after her original treatments.
This patient is one example of the long-term effect of beta-radiation treatment on the eye. Ongoing care is needed to monitor the ocular health and vision of these individuals as radiation effects may necessitate observation and/or care throughout the patient's lifetime. Follow-up on more patients who underwent beta-radiation treatment decades ago, should it be possible to do so, would provide further insight into the long-term anterior segment changes that can occur as a result of such treatment.
The Role of Radiation Therapy in Benign Diseases
2006, Hematology/Oncology Clinics of North America
Strontium plaque brachytherapy for exudative age-related macular degeneration: Three-year results of a randomized study
2005, Ophthalmology
Citation Excerpt :
In previous randomized studies on radiotherapy for exudative AMD, different study groups have obtained conflicting results. In studies by Hart et al,16 Valmaggia et al,17 and Kobayashi and Kobayashi,26 a beneficial effect of radiotherapy on at least one parameter of vision was obtained at some point of time. Conversely, in the Radiation Therapy for Age-Related Macular Degeneration14 and Marcus et al15 studies, there was no benefit at all in this treatment modality.
To determine the efficacy of strontium plaque (Sr⁹⁰) brachytherapy for age-related macular degeneration (AMD) with subfoveal choroidal neovascularization (CNV).
Randomized clinical trial.
Eighty-eight eyes of 86 patients with subfoveal CNV secondary to AMD were randomized either to plaque radiotherapy or to observation.
Radiotherapy was given as episcleral brachytherapy using Sr⁹⁰ plaques. Two different plaque types were used. Plaque I had a diameter of 8 mm and delivered a dose of 15 Gy at a depth of 1.75 mm in 54 minutes. With plaque II, the corresponding values were 4 mm, 12.6 Gy, and 11 minutes. The control group was observed without any treatment.
The primary outcome measure was visual acuity at 6, 12, 24, and 36 months. Other outcome variables were contrast sensitivity, fluorescein angiographic, and clinically evaluated changes in the macula.
Eighty-two patients (84 eyes [95%]) completed the 1-year follow-up, and 80 (93%) and 74 (86%) patients completed the 2- and 3-year follow-ups, respectively. At 6 months, visual loss of ≥3 lines occurred in 20% of treated patients and 42% of control patients (P = 0.031). At 12 months, a visual loss of ≥3 lines occurred in 45% (treated) and 56% (controls) (P = 0.325); at 24 months, in 73% and 71% (P = 0.914); and at 36 months, in 80% and 84% of patients (P = 0.591), respectively. Patients irradiated with plaque I had better results: a visual loss of ≥3 lines occurred in 6% at 6 months (P = 0.008, relative to controls), in 18% at 12 months (P = 0.007), in 59% at 24 months (P = 0.348), and in 71% at 36 months (P = 0.212). In patients treated with plaque II, the corresponding values were 29% (P = 0.032), 65% (P = 0.459), 83% (P = 0.317), and 80% (P = 0.687) at 6, 12, 24, and 36 months, respectively.
The short-term clinical course of exudative AMD is affected by Sr⁹⁰ brachytherapy, but by 12 months, there was no treatment benefit.
This article contains additional online-only material available at http://www.ophsource.org/periodicals/ophtha.

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^☆: This study was supported in part by Hyogo Prefecture and Hyogo Medical Society, Hyogo, Japan.

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Original articleAge-related macular degeneration: long-term results of radiotherapy for subfoveal neovascular membranes☆

Abstract

Section snippets

Patients and methods

Results

Discussion

Surv Ophthalmol

Ophthalmology

Ophthalmology

Int J Radiat Oncol Biol Phys

Ophthalmology

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Argon laser photocoagulation for neovascular maculopathythree year results from randomized clinical trials

Arch Ophthalmol

Laser photocoagulation for subfoveal neovascular lesions in age-related macular degeneration

Arch Ophthalmol

Visual outcome after laser photocoagulation for sub-foveal choroidal neovascularization secondary to age-related macular degenerationthe influence of initial lesion size and initial visual acuity

Arch Ophthalmol

Some practical conclusions following a longitudinal study of common macular lesions

Trans Ophthalmol Soc U K

Intravenous infusion of liposomal benzoporphyrin derivate for photodynamic therapy of experimental choroidal neovascularization

Arch Ophthalmol

Clinical experience with the surgical removal of sub-foveal neovascular membranes

Ophthalmology

Retinal separation, retinotomy, and macular relocationa surgical approach for age-related macular degeneration?

Graefes Arch Clin Exp Ophthalmol

Transplantation of fetal pigment epithelium in age-related macular degeneration with subfoveal neovascularization

Graefes Arch Clin Exp Ophthalmol

Treatment of choroidal neovascularization in age-related macular degeneration with interferon alfa-2a and alfa-2b

Br J Ophthalmol

Original article
Age-related macular degeneration: long-term results of radiotherapy for subfoveal neovascular membranes☆