Visual functioning and quality of life in the SubFoveal Radiotherapy Study (SFRADS): SFRADS report 2.

AIMS: To determine whether or not self reported visual functioning and quality of life in patients with choroidal neovascularisation caused by age related macular degeneration (AMD) is better in those treated with 12 Gy external beam radiotherapy in comparison with untreated subjects. METHODS: A multicentre single masked randomised controlled trial of 12 Gy of external beam radiation therapy (EBRT) delivered as 6 x 2 Gy fractions to the macula of an affected eye versus observation. Patients with AMD, aged 60 years or over, in three UK hospital units, who had subfoveal CNV and a visual acuity equal to or better than 6/60 (logMAR 1.0). METHODS: Data from 199 eligible participants who were randomly assigned to 12 Gy teletherapy or observation were available for analysis. Visual function assessment, ophthalmic examination, and fundus fluorescein angiography were undertaken at baseline and at 3, 6, 12, and 24 months after study entry. To assess patient centred outcomes, subjects were asked to complete the Daily Living Tasks Dependent on Vision (DLTV) and the SF-36 questionnaires at baseline, 6, 12, and 24 months after enrolment to the study. Cross sectional and longitudinal analyses were conducted using arm of study as grouping variable. Regression analysis was employed to adjust for the effect of baseline co-variates on outcome at 12 months and 24 months. RESULTS: Both control and treated subjects had significant losses in visual functioning as seen by a progressive decline in mean scores in the four dimensions of the DLTV. There were no statistically significant differences between treatment and control subjects in any of dimensions of the DLTV at 12 months or 24 months after study entry. Regression analysis confirmed that treatment status had no effect on the change in DLTV dimensional scores. CONCLUSIONS: The small benefits noted in clinical measures of vision in treated eyes did not translate into better self reported visual functioning in patients who received treatment when compared with the control arm. These findings have implications for the design of future clinical trials and studies.

Visual outcomes in the subfoveal radiotherapy study: a randomized controlled trial of teletherapy for age-related macular degeneration.

OBJECTIVE: To determine whether teletherapy with 6-mV photons can reduce visual loss in patients with subfoveal choroidal neovascularization in age-related macular degeneration. DESIGN: A multicenter, single-masked, randomized controlled trial of 12 Gy of external beam radiation therapy delivered to the macula of an affected eye vs observation only. SETTING: Three United Kingdom-based hospital units. PARTICIPANTS: Patients with age-related macular degeneration, aged 60 years and older, who had subfoveal choroidal neovascularization and a visual acuity of 20/200 (logMAR 1.0) or better. METHODS: Two hundred three patients were randomly assigned to radiotherapy or observation. Treatment was undertaken at designated radiotherapy centers, and patients assigned to the treatment group received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the data from 199 patients were analyzed. MAIN OUTCOME MEASURES: The primary outcome measure was mean loss of distance visual acuity in the study eye at 12 and 24 months. Other outcome variables analyzed were near visual acuity and contrast sensitivity. The proportions of patients losing 3 or more or 6 or more lines of distance and near acuity and 0.3 or more or 0.6 or more log units of contrast sensitivity at each follow-up were also analyzed. RESULTS: At all time points, mean distance visual acuity was better in the radiotherapy-treated group than in the control group, but the differences did not reach statistical significance. At 24 months, analysis of the proportions of patients with loss of 3 or more (moderate) (P =.08) or 6 or more (severe) (P =.29) lines of distance vision showed that fewer treated patients had severe losses, but there was no statistically significant difference between groups. For near visual acuity, although there was no evidence of treatment benefit at 12 and 24 months, a significant difference in favor of treatment was present at 6 months (P =.048). When analyzed by the proportions of patients losing 3 lines of contrast sensitivity, there was a significant difference in favor of treatment at 24 months (P =.02). No adverse retinal effects were observed during the study, but transient disturbance of the precorneal tear film was noted in treated patients. CONCLUSION: The results of the present trial do not support the routine clinical use of external beam radiation therapy in subjects with subfoveal choroidal neovascularization in age-related macular degeneration.

An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group.

A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.

Choroidal perfusion abnormality with age-related Bruch's membrane change.

Observation of patients with Sorsby's fundus dystrophy has shown that a prolonged choroidal filling phase on fluorescein angiography may indicate the presence of diffuse thickening of Bruch's membrane. We analyzed fluorescein angiography transit photographs in 100 eyes of 100 consecutive patients with age-related changes at the level of Bruch's membrane. Of these, 26 eyes had evidence of a prolonged choroidal filling phase during the initial dye transit. We suggest that this may represent a clinical correlate of diffuse thickening of Bruch's membrane, and that the two features are causally related.

The late stage of serpiginous (geographic) choroiditis.

Serpiginous and geographic choroiditis, one and the same disease, is characterized by episodic involvement of the pigment epithelium and choroid. Each new lesion passes through an acute phase into an atrophic and scarring one. We observed 20 patients, some with long-term follow-up; some had eventual widespread involvement of both posterior poles. There was no basis for the disease, and treatment did not affect its course. In the patients with long-term disease there was widespread atrophy of the choroid and pigment epithelium and variable amounts of pigment clumping and subretinal fibrous tissue deposition. In nine patients discrete peripheral patches of atrophy were also found. In some eyes the atrophy at the posterior pole had become so confluent that the condition could have been mistaken superficially for a primary choroidal dystrophy. The uninvolved areas appeared to be normal. The electroretinogram and electrooculogram were only affected when extensive disease was present.

Evolution of age-related macular degeneration with choroidal perfusion abnormality.

Prolonged choroidal filling on fluorescein angiography in age-related macular degeneration is thought to indicate diffuse thickening of Bruch's membrane. To test the importance of this clinical sign, we reviewed the evolution of disease in eyes of patients with good visual acuity and a readable transit phase of fluorescein angiography at the time of recruitment into a longitudinal study of age-related macular degeneration. Ninety-six eyes satisfied these criteria. Of the 32 eyes with prolonged choroidal filling, 12 (38%) lost two or more lines, of visual acuity by two years, whereas only nine of 64 (14%) eyes with normal choroidal filling did so. The difference was caused by the higher incidence of geographic atrophy in the first group. The proportion of eyes that developed subretinal neovascularization was the same in the two groups, and no pigment epithelial detachments occurred. These findings indicate that this clinical sign has implications concerning visual prognosis in age-related macular degeneration.

Drusen as risk factors in age-related macular disease.

In a study of 150 consecutive patients with age-related macular disease and unilateral visual loss, the drusen in the better eye were analyzed for size, number, density, and fluorescein angiographic appearance, and these characteristics were compared with the type of the lesion causing visual loss in the contralateral eye. In the fellow eye of an eye with avascular detachment of the retinal pigment epithelium, the drusen were more densely packed, larger, and less fluorescent than in the fellow eye of an eye with primary neovascularization. The characteristics of drusen in fellow eyes of those eyes with pigment epithelial detachments and evidence of subpigment epithelial new vessels were intermediate between the other two groups. Because there is significant symmetry of drusen between fellow eyes, these data imply that the characteristics of drusen are important in the determination of the form of the lesion complicating age-related macular disease.

Cortical blindness in cranial arteritis.

A case is presented of cortical blindness in cranial arteritis. A clinical diagnosis at the time of presentation was based on the integrity of the pupillary light reflex and the absence of visually evoked responses. Pathological examination confirmed bilateral occipital infarction. This report stresses the need for recognizing this presentation of cranial arteritis and initiating immediate treatment.

Incidence of aphakic macular oedema. A prospective study.

A prospective angiographic study of 77 aphakic eyes demonstrated cystoid macular oedema in 36 eyes (46-7 per cent) 6 to 7 weeks postoperatively. This subsequently resolved in 16 eyes, improved in eight, and was no better or worse in five (eight patients failed to return for follow-up). Of those patients with cystoid oedema, 16-6 per cent had a visual acuity of less than 6/12 at the time of the original examination; this was reduced to 13-8 per cent at the time of the follow-up study. The mean visual acuity of the group with oedema improved from 6/9 to 6/7-5 between the two examinations compared with 6/6 in the remaining 53-3 per cent without oedema. Preoperative ocular or general disease, specific surgical technique, and vitreous loss were not shown to be associated with macular oedema. However, there was some indication that intraocular inflammation predisposed to macular oedema.

Senile disciform macular degeneration in the second eye.

Development of senile disciform degeneration in the second eye was studied in a group of 104 patients over a period of up to five years. 12 to 15% of these patients develop disciform degeneration in the other eye each year. Patients with large and confluent drusen, especially if combined with accumulation of dye on fluorescein angiogram, were at greatest risk of developing disciform degeneration in the second eye.

Senile disciform macular degeneration: features indicating suitability for photocoagulation.

During a 1-year period 398 new patients were seen with disciform macular degeneration (530 eyes). The lesions were studied retrospectively, and those in which the neovascular tissue did not underlie the fovea, and therefore were treatable, were identified. The following conclusions were drawn: (1) Treatment is possible in most patients with good acuity and few with poor acuity. (2) Treatment is possible in a large proportion of patients with a short history and few with a long history of visual loss. (3) As many as 50% of all patients with senile disciform macular degeneration may be amenable to treatment if seen early enough in the course of their disease. (4) Over one-third of eyes with lesions that are untreated have a visual acuity of 6/60 or better 3 years after the onset of symptoms. (5) If a controlled trial proves that treatment is beneficial, these results emphasise the need for rapid referral and show that these patients will generate a large additional clinical load.

Age-related Bruch's membrane change: a clinical study of the relative role of heredity and environment.

For many years there has been controversy concerning the role of genetic influences in the pathogenesis of age-related macular disease. It is widely believed that the lesions causing visual loss occur in response to age-related changes in Bruch's membrane which are recognised clinically as drusen. In this study the density, size, and confluence of drusen as shown on colour photographs were compared in eyes of 50 spouses and 53 sibling pairs ascertained during a prospective study of age-related macular disease. Concordance between pairs of drusen--number, size, and density-were determined by kappa statistic and chi 2 test for trend. Drusen were absent in one sibling and 26 spouses of patients. There was a trend towards concordance of drusen characteristics between siblings but not between spouses, although the difference achieved 5% significance only for the number and density of drusen in the central macula. The difference of concordance between the probands and spouses and the probands and siblings was significant for all characteristics. These findings support the belief that genetic factors influence age-related changes in Bruch's membrane. They also imply that environmental factors are less important or alternatively that the environmental variation between households included in our study was not great enough to be evident.

Controlled trial of laser photocoagulation of pigment epithelial detachments in the elderly: 4 year review.

Patients who were enrolled in a controlled treatment trial of laser grid photocoagulation for retinal pigment epithelial detachment as part of age-related maculopathy were reviewed 4 years after entry into the trial. The data imply that the original conclusion that this form of treatment did not improve the visual prognosis at 18 months was also justified at 4 years. It has become clear that lesions with evidence of subpigment epithelial new vessels were included in the trial. In a retrospective study the lesions were separated into those in which there was evidence of subretinal neovascularisation and those in which no such evidence existed. A difference was identified in the behaviour of the treated and untreated lesions designated avascular in that the treated eyes had a poorer visual outcome. These cases accounted for the different behaviour between two management groups in the initial study such that the original conclusion that grid photocoagulation of avascular pigment epithelial detachments in the elderly does not improve the visual prognosis is justified.

Detection of subpigment epithelial neovascularisation in cases of retinal pigment epithelial detachments: a review of the Moorfields treatment trial.

The entry angiograms of 42 eyes with detachment of the retinal pigment epithelium in a treatment trial of laser photocoagulation were reviewed in a masked fashion by three observers in order to assess the possible presence of subpigment epithelial neovascularisation. Vascularity or avascularity was designated with reference to a list of clues believed to imply the presence of subpigment epithelial neovascularisation. As a predictor of outcome the initial assessment achieved a sensitivity and specificity of 77% and 82% respectively. Despite notable parity of the degree of sensitivity and specificity among the three observers, full agreement on the initial assessments was reached in only 23 eyes (55%), 10 with vascular and 13 with avascular outcome. Of these, only one eye which developed new vessels after 4 years had an outcome which differed from that predicted by classification of the entry angiograms.