Radiotherapy For Age-related Macular Degeneration Research Articles

Radiotherapy for neovascular age-related macular degeneration

Radiotherapy has been proposed as a treatment to prevent new vessel growth in people with neovascular age-related macular degeneration (AMD). The aim of this review was to examine the effects of radiotherapy on neovascular AMD. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) in The Cochrane Library Issue 3, 2010, MEDLINE (January 1950 to March 2010), EMBASE (January 1980 to March 2010), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (March 2010) and ClinicalTrials.gov (http://clinicaltrials.gov) (March 2010). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 23 March 2010. We also wrote to investigators of trials included in the review to ask if they were aware of any other studies. We included all randomised controlled trials in which radiotherapy was compared to another treatment, sham treatment, low dosage irradiation or no treatment in people with choroidal neovascularisation secondary to AMD. Two review authors independently extracted the data. We combined relative risks using a random-effects model. We estimated the percentage of the variability in effect estimates that was due to heterogeneity, rather than sampling error, using I(2). Thirteen trials (n=1154) investigated external beam radiotherapy with dosages ranging from 7.5 to 24 Gy; one additional trial (n=88) used plaque brachytherapy (15Gy at 1.75mm for 54 minutes/12.6 Gy at 4mm for 11 minutes). Most studies found effects (not always significant) that favoured treatment. Overall there was a small statistically significant reduction in risk of visual acuity loss in the treatment group. There was considerable inconsistency between trials and the trials were considered to be at risk of bias, in particular because of the lack of masking of treatment group. Subgroup analyses did not reveal any significant interactions, however, there were small numbers of trials in each subgroup (range three to five). There was some indication that trials with no sham irradiation in the control group reported a greater effect of treatment. The incidence of adverse events was low in all trials; there were no reported cases of radiation retinopathy, optic neuropathy or malignancy. Three trials found non-significant higher rates of cataract progression in the treatment group. This review currently does not provide convincing evidence that radiotherapy is an effective treatment for neovascular AMD. If further trials are to be considered to evaluate radiotherapy in AMD then adequate masking of the control group must be considered.

Radiotherapy for age-related macular degeneration: no more pilot studies please

Age-related macular degeneration (AMD) is a major health problem for the United Kingdom. Currently, AMD accounts for the majority of the 124 000 blind registrations in the over 65 age group. This demonstrates that AMD is also an immensely frustrating condition for patients and their doctors as current treatments are extremely limited both for the atrophic form and for choroidal neovascularization (CNV). CNV while accounting for 10% of the disease, disproportionately causes up to 88% of the legal blindness associated with AMD. Conventional laser treatments for CNV improve vision in only 5% of cases and are suitable only for a minority of patients. Therefore, there is a pressing need for novel and effective therapies. Investment in research makes sense financially as well, as the considerable costs to the NHS in managing visually impaired patients could be significantly reduced with better treatments for CNV. One possible novel therapy for the treatment of CNV associated with AMD is ionising radiation. Radiotherapy seems rational because of its known ability to inactivate rapidly proliferating cells such as the capillary endothelium of CNV. Such cells typically manifest impaired radiation damage repair relative to adjoining slowly proliferating cells. A differential survival response might therefore be exploited with CNV destroyed through DNA breaks that normal tissues have time to repair before undergoing cell division. Although radiation dose fractionation with multiple small treatments over many days is commonly used to reduce normal tissue complications in the treatment of malignancies, since CNV is not a true neoplasm, arguments have been made that there may be no therapeutic advantage to dose fractionation, especially if the volume irradiated can be restricted to the region of macula (it is an axiom of radiotherapy that the probability of complications is proportional to the size of the target volume). In the journal this month, however, a radiotherapy trial is reported which shows no benefit in AMD. Should we therefore abandon this treatment in AMD? The short answer is no, because of the theoretical rationale for why radiotherapy may work and a series of studies which have given enticing hints that it may still be of benefit in AMD. Research into radiotherapy as a treatment modality for AMD started in earnest 10 years ago after Chakravarthy et al demonstrated significant regression in (CNV) following external beam radiotherapy in an animal model and later in a phase I study. Since then a multitude of small pilot studies using standard fractions of 2–3 Gy with a total dose of 10–20 Gy have been published, some showing better maintenance of visual acuity in treated eyes, while others failed to show any benefit. Overall, prior to the study by Hoeller et al there have been 10 randomised control trials (RCT), three nonrandomised trials and eight case series each with over 100 people in the study (see Table 1). Among the above RCTs, three studies demonstrated a significant reduction in visual loss when comparing radiotherapy to very lowdose (effectively sham) radiotherapy or observation. The National Institute for Clinical Excellence recognises the modest benefits from radiotherapy while justifying its restricted usage within ethically approved quality clinical trials in the UK. Part of the challenge with radiotherapy is in finding an appropriate radiation regimen. The difficulty lies in the many different ways and dosage schedules by which ionising radiation can be applied to the eye. The biologically Received: 1 September 2004 Accepted: 1 September 2004 Published online: 22 October 2004 University of Southampton, UK

Idiopathic and radiation-induced ocular telangiectasia: the involvement of the ATM gene.

To investigate whether individuals, with no family history of ataxia telangiectasia (AT), in whom idiopathic or radiation-induced ocular telangiectasia developed are carriers of ATM gene mutations. The ATM cDNA from lymphoblastoid cell lines established from 16 patients with idiopathic retinal or choroidal telangiectasia and 14 patients with radiation-induced telangiectasia after radiotherapy for age-related macular degeneration (AMD) was screened using the restriction endonuclease fingerprinting technique. The frequency of each detected variant was determined in the French population by either a mass spectrometry-based technique or variant-specific endonuclease digestion. Twenty-one ATM missense alterations, at 10 different sites, 8 of which would result in an amino acid substitution at a conserved position in the ATM protein were found. Four were novel changes, three of which were not detected in the 128 French control subjects screened. Eleven of 16 of the individuals with either idiopathic polypoidal choroidal vasculopathy or juxtafoveolar retinal telangiectasis and 6 of 14 individuals that had choroidal telangiectasis after radiotherapy for AMD carried ATM sequence variants. These latter six individuals had a significantly shorter delay time before the presentation of this vasculopathy compared with those individuals who had a wild-type ATM (11.8 +/- 3.4 months vs. 17.5 +/- 4.5 months, P = 0.024). They had also received a lower average dose of X-rays, although this difference did not reach statistical significance (18.7 +/- 3.9 Gy vs. 23.7 +/- 5.6 Gy, P = 0.09). ATM missense variants could confer an AT-like phenotype and influence the formation of retinal and choroidal vascular abnormalities.

Clinicopathological correlation of choroidal neovascularization after external beam radiotherapy in age-related macular degeneration.

To analyze the histopathology of choroidal neovascularization after external beam radiotherapy in age-related macular degeneration. A retrospective non-case-matched comparative histopathologic study. The histoarchitecture of nine surgically removed subretinal specimens from nine patients that had undergone external beam radiotherapy for exudative age-related macular degeneration was studied. Seven patients had received 20 Gy in 10 fractions and two 15 Gy in 5 fractions with an average time interval between radiotherapy and surgical extraction of 14 months (range 3-28). A consecutive series of classic, mixed and occult choroidal neovascular membranes served as controls. Clinical findings. Radiation-associated choroidal neovasculopathy was angiographically suspected in four patients: a coarse net of vessels on fluorescein angiography developing at the border of previously irradiated choroidal neovascularization was observed in three patients; blebs at the margin of a plaque on indocyanine green angiography were observed in two patients. Pathological findings. Diffuse drusen as well as intra-Bruch's fibrovascular tissue was found in all irradiated specimens. In four specimens an edematous vascularized layer was seen between diffuse drusen and normal-appearing intra-Bruch's fibrovascular tissue. This lesion was not found in the control specimens. A particular correlation for the bleb lesion was not recognized. The appearance of an edematous subretinal pigment epithelial vascularized layer between diffuse drusen and normal-appearing fibrovascular tissue in four of nine irradiated membranes may be secondary to previous irradiation. It may correlate with the unusual exudative manifestations observed after external beam radiotherapy.

External beam radiotherapy for age-related macular degeneration causes transient objective changes in tear-film function.

Dry-eye symptoms have been described as possible radiation side effects after external beam radiotherapy for age-related macular degeneration. We therefore investigated tear-film function before and after treatment. Thirty-nine patients with no apparent history of dry-eye symptoms were treated with a 6 MV linear accelerator using a 2x2 cm lateral field angled 10 degrees posteriorly. A total dose of 20 Gy, divided into 10 fractions of 2 Gy and administered 3 times a week, was delivered. Before and 1, 3, and 6 months after radiotherapy, tear secretion was measured by means of tear-film fluorophotometry. The fellow eyes served as controls. At baseline, mean tear secretion as measured by tear-film fluorophotometry was 7.15 microl/min in the eyes receiving radiation and 5.89 microl/min in the control eyes. No statistically significant differences were found between the two eyes at baseline (signed rank test). One month after treatment, again no significant differences could be found between the two eyes; 3 months after radiation, however, tear secretion was significantly lower in the irradiated eyes than in the fellow eyes (P=0.0017). Six months after treatment this effect could no longer be detected. External beam radiotherapy using 20 Gy in 10 fractions and a 2x2 cm lateral field causes a statistically significant difference in tear secretion 3 months after radiation. This effect seems to be transient, as it had disappeared in later follow-up examinations.

Radiotherapy for age-related macular degeneration: is there a benefit for classic CNV?

To evaluate the efficacy of radiotherapy in the treatment of subfoveal classic and occult choroidal neovascularization (CNV) in age-related macular degeneration (AMD) under strict fixation control. Twenty-seven eyes of 27 patients with subfoveal CNV as a result of AMD were treated with a total dose of 20 Gy in 10 fractions (10 well-defined, 17 occult). Fixation monitoring was achieved by installing a TV camera with an attached fixation light 3 cm from the cornea of the eye being treated. Visual acuity and fluorescein angiography were obtained before and 6 months after treatment. Fifteen eyes of 15 patients served as controls (4 well-defined, 11 occult). After 6 months the treated group showed an average decrease in visual acuity of 27%; the control group experienced a decrease of 31%. Membrane size increased by 56% in the treated group and by 28% in the control group. There was no statistically significant difference. Within the subgroup analysis, however, patients with classic CNV suffered significantly less visual loss than in the control group. Radiation therapy under optimized treatment conditions by fixation monitoring failed to control further growth in membrane size in both classic and occult CNV. Regarding visual acuity, however, patients with classic CNV seem to benefit from radiation treatment compared to the natural course.

Radiotherapy for age related macular degeneration causes transient lens transparency changes

AIMEvaluation of potential side effects of photon radiotherapy on the transparency of the lens.METHODSThe anterior segments of 14 phakic eyes from patients suffering from subfoveal neovascularisation as a result of...

Radiotherapy in age-related macular degeneration - results of an analysis of 312

Radiotherapy in age-related macular degeneration - results of an analysis of 312

Ophthalmic plaque radiotherapy for age-related macular degeneration associated with subretinal neovascularization

PURPOSE: To evaluate ophthalmic plaque radiotherapy for the treatment of subretinal neovascularization associated with age-related macular degeneration.METHODS: In a prospective phase I clinical trial, we treated 23 patients (23 eyes) with ophthalmic plaque radiotherapy for subfoveal exudative macular degeneration. Palladium 103 ophthalmic plaque brachytherapy was delivered to a retinal apex dose of 1,250 to 2,362 cGy (rad). Early Treatment Diabetic Retinopathy Study type visual acuity determinations, ophthalmic examinations, and angiography were performed before and after treatment. Clinical evaluations were performed in a nonrandomized and unmasked fashion.RESULTS: Patients were followed up for a mean (±SD) of 19 ± 10.7 months (range, 3 to 37 months). Six months after radiation therapy, three (16%) of 19 eyes had lost 3 or more lines of best-corrected visual acuity; 12 months after radiation therapy, four eyes (31% of 13 eyes), and 24 months after radiation therapy, only two (22% of nine eyes) lost 3 or more lines of visual acuity. No eye suffered sudden irreversible loss of central vision. No radiation retinopathy, optic neuropathy, or cataract could be attributed to radiotherapy within this follow-up period.CONCLUSION: Ophthalmic plaque radiotherapy can be used to treat neovascular age-related macular degeneration. In contrast to external beam radiotherapy, ophthalmic plaque radiotherapy is a unilateral treatment, which allows a larger dose to be delivered to the macula with less irradiation of normal ocular structures. We have found no sight-limiting complications at the doses, dose rates, and follow-up evaluated in this study.

Radiation Therapy in Exudative Age-Related Macular Degeneration

It has been suggested that ionizing radiation at doses relatively safe to the optic nerve and retina exert an inhibitory and occlusive effect on the endothelial proliferation of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). The encouraging results of early studies in preservation or improvement of visual acuity and regression of the CNV gave rise to many clinical trials in different centers. Disparate radiation doses, dose fractions, type and rate of radiation administration have been used to determine the efficacy of radiotherapy in AMD. Conflicting treatment responses have been reported by different centers. Some studies provided evidence of beneficial treatment outcome in AMD, and others could not show any efficacy of ionizing radiation in the visual and morphological evolution of the disease. Data from the literature and our experience indicate that radiotherapy can be effective in regressing the leakage of the CNV in AMD. However, despite treatment visual deterioration continues and new CNV lesions develop. The observation of morphological progression in the disease process might be related to an unfavorable effect of radiation on the pathogenesis of AMD.

2226 Progressive growth of subfoveal choroidal neovascularization after radiotherapy in age-related macular degeneration

2226 Progressive growth of subfoveal choroidal neovascularization after radiotherapy in age-related macular degeneration

Radiotherapy for age-related macular degeneration: Preliminary results of a potentially new treatment

Purpose : Neovascular macular degeneration is the leading cause of severe blindness in North America today. Limited treatments are available for this disease process. A Phase I/II study was performed t determine the toxicity and efficacy of external bea radiotherapy in patients with age-related subfoveal neovascularization. Methods and Materials : Between March 1994 and June 1995, 52 patients with a mean age of 80 (62–92) were enrolled. These patients were either not eligible or were poor candidates for laser photocoagulation, primarily because of the subfoveal location of the neovascularization. Initial visual acuities ranged from 20 out of 32 to finger counting at 3 feet. All patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Patients were treated with a single lateral 4- or 6-MV photon beam, to a dose of 14–15 Gy eight fractions over 10 days. The field size averaged 5 × 3 cm. Results : No significant acute morbidity was noted. All patients underwent ophthalmic examinations and repeat angiography at 1 and 3 months posttreatment and then at 3-month intervals. With a mean follow-up o f 7 months (3–18 months), 41 patients (79%) are within two lines of their pretreatment visual acuity. On angiographic imaging, there was stabilization of subfoveal neovascular membranes in 34 patients (65%). New neovascular membranes have been noted in five patients. Conclusions : It appears that radiotherapy can affect active subretinal neovascularization, but it is unlikely to prevent new neovascular events produced by this chronic disease. Further investigation is warranted.