age-related macular degeneration: long-term results of radiotherapy for subfoveal neovascular...

Age-related Macular Degeneration: Long-termResults of Radiotherapy for Subfoveal

Neovascular Membranes

HIROSHI KOBAYASHI, MD, PHD, AND KAORI KOBAYASHI, MD, PHD

● PURPOSE: To study results of 2-year follow-up ofradiotherapy for subfoveal choroidal neovascular mem-brane associated with age-related macular degeneration.● METHODS: In a randomized prospective clinical study,101 patients received a low-dose radiotherapy or notreatment. In the treatment group, subfoveal choroidalneovascular membranes were treated with 20 Gy of6-MV photons to the macula of the affected eye.● RESULTS: The overall complete follow-up rate was84.2% (85/101). No measurable treatment-related mor-bidity was seen during or after treatment. Mean changesin log of minimal angle of resolution (logMAR) of visualacuity and area of choroidal neovascular membrane for2-year follow-up were 10.226 6 0.373 and 143.5 653.1% in the treatment group, and 10.563 6 0.370 and190.3 6 81.4% in the control group; a significantdifference was found (P < .0001; P 5 .0008). Inpatients with smaller choroidal neovascular membrane(<1.5 mm2) or better visual acuity (>60/200) at base-line, the treatment group showed a significantly smallerincrease in area of choroidal neovascular membrane anda significantly smaller decrease in LogMAR visual acuityfor 2 years, whereas there was no significant difference inpatients with larger choroidal neovascular membrane(>1.5 mm2) or poorer visual acuity (<60/200).● CONCLUSIONS: Radiotherapy appeared to have a fa-vorable treatment effect in eyes with subfoveal neovas-cular membrane associated with AMD. Favorable factorsfor radiotherapy were a smaller area of choroidal neovas-cular membrane and better visual acuity. (Am J Oph-

thalmol 2000;130:617–635. © 2000 by ElsevierScience Inc. All rights reserved.)

T HE NATURAL COURSE OF VISUAL ACUITY IN PA-

tients with age-related macular degeneration ispoor.1 In Japan and other developed countries,

age-related macular degeneration is a leading cause ofblindness in aged people. Subfoveal choroidal neovascularmembrane, with an initial visual acuity of 0.1 (20/200) orbetter, is accompanied in at least 70% of eyes by visualacuity of 0.1 or worse after 21 months of follow-up.1 Laserphotocoagulation remains the main treatment for choroi-dal neovascular membranes.2–4 In the long term, lasertreatment of subfoveal membranes results in better-pre-served central visual function in treated patients whencompared with no treatment.5 However, laser photocoag-ulation leads to a substantial and immediate loss of vision.The majority of subfoveal choroidal neovascular mem-branes are not suitable for the laser treatment, according tothe Macular Photocoagulation Study criteria, because thelesion may be ill defined, occult, and large.4

Various other treatments have been tried, with verylimited success. These include alternative laser techniquessuch as grid laser therapy, photodynamic therapy,6,7 sub-macular surgery,8,9 macular translocation,10 macular trans-plantation,11 and antiangiogenic drug therapies such asinterferon alpha and thalidomide.12–14

Several investigators reported the outcomes of low-doseexternal beam radiotherapy in exudative age-related mac-ular degeneration.15–32 The majority of these reports indi-cated that the radiotherapy allowed visual acuity to bemaintained and removed the risk of rapid visual loss. Fourof the studies found no beneficial effect.27,28,30,32 In all butthe study by Hart and associates,16 the follow-up durationwas 12 months or less. Although a rapid loss of visionoccurs in patients with a subfoveal choroidal neovascularmembrane, a substantial number of patients may havemaintained vision during a protracted and variable period.The relatively short follow-up may overestimate the ben-eficial effects of radiotherapy. Many studies have includedpatients with occult choroidal neovascular membrane

Accepted for publication Apr 13, 2000.From the Department of Ophthalmology, Amagasaki Hospital, Hyogo,

Japan (Dr H. Kobayashi); Department of Ophthalmology and VisionScience, Kyoto University Graduate School of Medicine, Kyoto, Japan(Dr H. Kobayashi); and Department of Ophthalmology, Osaka Red CrossHospital, Osaka, Japan (Dr K. Kobayashi).

This study was supported in part by Hyogo Prefecture and HyogoMedical Society, Hyogo, Japan.

Reprint requests to Hiroshi Kobayashi, MD, PhD, Department ofOphthalmology, Saga Medical School, Saga, Japan; fax: (81) 952-33-3696; e-mail: [email protected]

© 2000 BY ELSEVIER SCIENCE INC. ALL RIGHTS RESERVED.0002-9394/00/$20.00 617PII S0002-9394(00)00534-1

only. Occult choroidal neovascular membrane appears tohave a slower rate of development of severe visual loss thanclassic choroidal neovascular membrane and mixedtype.33–36 The good outcome with radiotherapy reported inthese studies may have reflected the slow natural course ofthe disease process. There were three randomized prospectivetrials.30–32 Bergink and associates28 reported the beneficialeffect of radiotherapy for subfoveal choroidal neovascularmembrane, whereas Holz and associates30 and Finger andassociates31 showed no favorable treatment effect. In thesestudies, the follow-up was relatively short. Therefore, arandomized prospective study and long-term follow-up arerequired to assess the effect of the radiotherapy for age-relatedmacular degeneration.

In this study, we report a randomized study for radio-therapy for subfoveal choroidal neovascular membraneassociated with age-related macular degeneration and2-year follow-up. We also evaluate factors influencinglong-term posttreatment area of choroidal neovascularmembranes and visual acuity and their changes throughoutthe follow-up.

PATIENTS AND METHODS

ONE HUNDRED ONE CONSECUTIVE PATIENTS WITH SUBFO-

veal choroidal neovascular membrane with age-relatedmacular degeneration who fulfilled the indications forradiotherapy were enrolled. Age-related macular degener-ation was diagnosed according to the criteria published bythe research committee on chorioretinal degenerationssupported by the Ministry of Health and Welfare ofJapan.37 Age-related macular degeneration was diagnosedon the basis of the results of slit-lamp biomicroscopy witha precorneal lens, indirect ophthalmoscopy, and fluores-cein angiography. Indications for radiotherapy were (1)unsuitability for laser photocoagulation under the MacularPhotocoagulation Study criteria, (2) newly formed orexacerbated choroidal neovascular membranes (eg, within3 months), (3) visual acuity of 0.5 (25/50) or worse, and(4) age of 60 years of more, according to previous reportsby Chakraverthy and associates.15,16 Any patient withpreexisting ocular disease (ie, glaucoma, severe myopia,chronic inflammatory disease, or neoplastic disorders) wereexcluded, as were those with systemic disorders (diabetes,uncontrolled hypertension) or a known life-threateningdisease at enrollment into the study. The study protocoland consent forms were approved by the Human SubjectsCommittee of Amagasaki Hospital. Patients were informedof the purpose of the study and provided their signedconsent to participate.

One eye of each of the 101 patients was prospectivelyramdomized to receive radiotherapy or no treatment. Forcases in which we believed that both eyes of a patient wereeligible, the patient and we made a subjective judgment asto which eye would be enrolled in the study. Within 24

hours after enrollment, the patients were randomized bymeans of computer-generated numbers; patients assigned 0received low-dose radiotherapy and those assigned 1 re-ceived no treatment. The treating physician (H.K.) wasunaware of the patients’ randomization state. Fifty-onepatients underwent radiotherapy, and the remaining 50patients who did not undergo radiotherapy were followedup as a randomized group. Treatment began within a weekafter random assignments.

All recruited patients were subjected to a detailedophthalmic examination, including slit-lamp biomicros-copy and confocal scanning laser tomography. Fully cor-rected visual acuity was measured by means of the EarlyDiabetic Retinopathy Treatment Study chart, and thelogarithm of the minimum angle of resolution (logMAR)was calculated and used for all statistical analysis. Pretreat-ment fluorescein and indocyanine green angiograms wereobtained within 1 week of the start of radiotherapy.Radiotherapy was carried out as described as below. Afterradiotherapy, the patients were examined at 2 weeks, 1, 2,3, 6, 9, 12, 18, and 24 months, and then every 6 months.Visual function was assessed at every visit, and angiogra-phy was scheduled for the visits at 1, 3, 6, 12, 18, and 24months. An increase or decrease in visual acuity wasdefined as a change of greater than 0.2 in logMAR visualacuity. Safety was evaluated by determining the incidenceof radiotherapy-related complications and adverse reac-tions for both treatment and control groups. The patientswere regularly questioned and examined for side effects.We reviewed photographs for radiation retinopathy andneuropathy. The control group received the same fol-low-up as the treatment group. Assessment of outcomes,including visual acuity, angiographic interpretation, andassessment of complications and adverse events, was per-formed in a masked fashion. To detect adverse events, allpatients were examined by the same examiner (H.K.) toavoid interobserver variation. For assessment of cataract,nuclear sclerosis was assessed as described by Emery andassociates.38 Anterior and posterior subcapsular cataractand cortical opacity were scored according to Hecken-lively.39

Radiotherapy was carried out as described by Chakra-verthy and associates.15 In brief, the patient was fitted witha custom-made beam direction shell, and a high-definitioncomputed tomographic scan was performed. Cursor mea-surements were made from surface markers placed on theshell at the temporal region, and the position of theposterior pole of the eye was plotted from these measure-ments. Computer-generated isodose curves for a single6-MV photon beam, given to 90% of the maximum dose,were superimposed onto the computed tomographic im-ages. The 90% isodose curve encompassed the macula andoptic disk, with less than 50% of the maximum dose fallingon the posterior lens. A total of 20 Gy was used in 10divided doses over 14 days. All eyes were irradiatedthrough a single lateral port.

AMERICAN JOURNAL OF OPHTHALMOLOGY618 NOVEMBER 2000

Area of choroidal neovascular membrane was defined asthe area of hyperfluorescence on the angiogram. Measure-ments of the choroidal neovascular membrane includedonly choroidal neovascular membrane, but not contiguousblood, fibrosis, or atrophy. Subretinal blood was consideredto be present if blood was under the retina in a locationimmediately contiguous with the area of choroidal neovas-cular membrane or within a serosanguineous detachmentof the retina contiguous with the area of choroidal neo-vascular membrane. Fundus angiograms were obtainedwith a high-resolution digital fundus imaging system basedon a Canon UVi fundus camera (Canon, Tokyo, Japan). Ineach angiogram, one picture was selected that showed theextent of the choroidal neovascular membrane and theoptic disk. The image was analyzed with UTHSCSAImage Tool 32-bit image analysis program (developed atthe University of Texas Health Science Center at SanAntonio).27 After sharpening and contrast-enhancing im-age filters were applied, the outline of the membrane wasdrawn on the image manually and the membrane surfacewas calculated. The outline of the optic disk was simulta-neously drawn and saved. To calculate for magnificationerrors, the disk/choroidal neovascular membrane ratio wascalculated for each image. The initial (pretreatment) sizeof the choroidal neovascular membrane was set to 100%,and all posttreatment measurements were normalized rel-ative to the initial size. When repeated measurement wasdone on the same picture, statistical analysis of thereproducibility of this measuring method showed a highcorrelation coefficient of 0.995. A change of less than 20%was considered as unchanged.

The Heidelberg Retina Tomograph (Heidelberg Engi-neering, Heidelberg, Germany), a confocal scanning diodelaser (670-nm) retinal tomograph, was used to scan andanalyze the macular area of both eyes; the other eye wasused as a control if it was an unaffected eye. The topo-graphic images are a series of 32 optical images, which aretaken along the z-axis at height planes of 50 mm to 80 mmeach over a 2-mm scan depth. Each two-dimensionaltransverse image consists of 256 3 256 pixels scannedalong the x- and y-axes, with a scanning angle of 10 to 20degrees. The image acquisition time is 1.6 seconds. Thetechnology of the laser scanner relies on an extremelyshallow depth of field; thus, the Heidelberg Retina Tomo-graph records only the image at the focal plane, disregard-ing any information outside the focal plane. The resolutionis 40 mm along the z-axis and 10 mm along the x- andy-axes, as reported by Menezes and associates.40

In present study, the scan angle was 10 to 20 degrees ofthe retina; the fovea was the center of the scanned region.Scanning was performed with a scan depth of 1.5 to 4.0mm. Heidelberg Retina Tomograph examinations wereperformed in a masked fashion. All examinations wereperformed by the same observer to avoid interobservervariation. Measurements were repeated five times to con-firm reproducibility and to eliminate artifacts. Fluctuations

were minimized by using the average of the five valuesobtained.

We measured the following Heidelberg Retina Tomo-graph parameters: area of the neurosensory elevation,measured in square millimeters; volume of the neurosen-sory elevation, measured in cubic millimeters; and maxi-mum height of the neurosensory elevation, measured inmillimeters.41–43

Values are presented as the mean 6 SD and the range,or as frequencies. This method was chosen as an appropri-ate way to express the incidence of particular outcomes bybroad categories of patients. For all 2 3 2 comparisons, theFisher exact test was used. Other comparisons of frequencydistributions were performed by means of the chi-squaretest for independence. Unless otherwise specified, datawere analyzed by paired, two-sided t tests. A level of P ,.05 was accepted as statistically significant. In multiplecomparisons, the Bonferroni procedure was used in select-ing the P value considered as the threshold for significance.

For the pairing of both groups, age, gender, visual acuity,area and type of choroidal neovascular membrane, andarea, volume, and maximal height of neurosensory eleva-tion at baseline were used for matching. We studiedcorrelations between the paired observation. If these ob-servations were correlated, the F test was used to studytwo-population variances.

Stepwise regression analysis was used to evaluatewhether possible baseline factors, including age, gender,visual acuity, type and size of CNVM, area, volume, andmaximal height of neurosensory elevation, would predictvisual acuity and area of CNVM at 2 years after the startof the follow-up.

Hayashi’s quantification of qualitative data was used toquantify types of choroidal neovascular membrane; classictype, mixed type, and occult type were designated 0, 1, and2, respectively.44,45

RESULTS

BASELINE DATA ARE SUMMARIZED IN TABLE 1. FIFTY-ONE

eyes of 51 patients and 50 eyes of 50 patients were enrolledin the treatment group and control group, respectively.There was no statistically significant difference in age,gender, area of choroidal neovascular membrane, andvisual acuity between the treatment group and controlgroup.

The overall complete follow-up rate was 84.1% (85/101)(Table 1 and Figure 1). There was no significant differencebetween the two groups; the complete follow-up rate was88.2% (45/51) and 80.0% (40/50) in the treatment groupand control group, respectively. Six treated patients and 10untreated patients were not evaluated, because five pa-tients died with intercurrent disease, six patients were tooill or frail to attend, and it was not possible to contact fivepatients.

AGE-RELATED MACULAR DEGENERATIONVOL. 130, NO. 5 619

TABLE 1. Demographics of Patient Groups

Treatment Group Control Group

Total no. of subjects enrolled 51 50

Gender

Male 19 (37.3%) 17 (34.0%)

Female 32 (62.7%) 33 (66.0%)

Eye

RE 27 (52.9%) 27 (54.0%)

LE 24 (47.1%) 23 (46.0%)

Total no. of subjects with complete follow-up (rate) 45/51 (88.2%) 40/50 (80.0%)

Gender

Male 17 (37.8%) 15 (37.5%)

Female 28 (62.2%) 25 (62.5%)

Eye

RE 24 (53.3%) 21 (52.5%)

LE 21 (46.7%) 19 (47.5%)

Age (yrs)

60–69 16 (35.6%) 14 (35.0%)

70–79 24 (53.3%) 21 (52.5%)

80–89 5 (11.1%) 5 (12.5%)

Mean 6 SD 71.467 6 6.525 71.821 6 6.270

Range 60–89 60–89

Type of CNVM

Classic 28 (62.2%) 23 (57.5%)

Occult 6 (13.3%) 7 (17.5%)

Mixed 11 (24.4%) 10 (25.0%)

Area of CNVM (mm2)

0–0.500 8 (15.7%) 8 (20.0%)

0.501–1.000 5 (11.1%) 4 (10.0%)

1.001–1.500 5 (11.1%) 1 (2.5%)

1.501–2.500 3 (6.7%) 7 (17.5%)

2.501–5.000 4 (8.9%) 4 (10.0%)

5.001–7.500 5 (11.1%) 4 (10.0%)

7.501–10.000 4 (8.9%) 2 (5.0%)

10.001–15.000 6 (13.3%) 6 (15.0%)

15.001–20.000 3 (6.7%) 3 (7.5%)

.20.001 2 (4.4%) 1 (2.5%)

Mean 6 SD 6.064 6 6.682 6.125 6 5.870

Range 0.221–25.044 0.213–25.641

Neurosensory elevation

Area (mm2)

0–1.000 3 (6.7%) 4 (10.0%)

1.001–2.500 6 (13.3%) 4 (10.0%)

2.501–5.000 9 (20.0%) 8 (20.0%)

5.001–10.000 12 (26.7%) 10 (25.0%)

10.001–20.000 11 (24.4%) 12 (30.0%)

.20.000 4 (8.9%) 2 (5.0%)

Mean 6 SD 9.689 6 7.522 9.229 6 6.563

Range 0.554–30.564 0.366–29.418

Volume (mm3)

0–0.250 6 (13.3%) 4 (10.0%)

0.251–0.500 7 (15.6%) 7 (17.5%)

0.501–1.000 7 (15.6%) 5 (12.5%)

1.001–2.000 8 (17.8%) 10 (25.0%)

2.001–4.000 12 (26.7%) 10 (25.0%)

.4.001 5 (11.1%) 4 (10.0%)

Continued on next page


At baseline, mean best-corrected visual acuity was 0.203(20/98.5) and 0.224 (20/89.3) in the treatment and con-trol group, respectively (Table 1). Baseline best-correctedvisual acuity was slightly poorer in the treatment groupthan the control group, but this difference was not statis-tically significant. Mean area of choroidal neovascularmembrane at baseline was 6.064 6 6.682 mm2 in thetreatment group and 6.125 6 5.870 mm2 in the controlgroup (Table 1). The angiograms of 28 treated patients and23 control patients showed only classic choroidal neovas-cularization (early, well-defined leakage occurring within30 seconds of dye injection). The angiograms of six treatedpatients and seven control patients showed only lateleakage of intermediate origin indicative of occult neovas-cularization. In addition, 11 treated patients and 10 con-trol patients showed both early and late leakage (mixedtype). No difference was found in the type and area ofchoroidal neovascular membrane between the two groups.The area, volume, and maximal height of sensory elevationwere greater in the treatment group than those in thecontrol group, but these differences were not significant.

Throughout the duration of the study, patients weremonitored for any possible adverse side effects that couldbe attributed to radiotherapy. There was no significantacute morbidity for the treatment group. Two patientscomplained of transient conjunctival injection that re-solved within 2 weeks, and thereafter they remainedasymptomatic. Cataract formation was observed in onepatient in the treatment group, 3 months after the treat-ment. The posterior subcapsular cataract progressed from11 to 13. No significant progression of cortical andnuclear lens opacities was observed. Radiation-induced

FIGURE 1. Profile of patients randomized, receiving radiother-apy, and completing follow-up through 24 months.

TABLE 1. (Continued) Demographics of Patient Groups

Treatment Group Control Group

Mean 6 SD 1.667 6 1.397 1.646 6 1.466

Range 0.138–4.798 0.148–4.823

Maximal height (mm)

0–0.250 12 (26.7%) 10 (25.0%)

0.251–0.500 21 (46.7%) 19 (47.5%)

0.501–0.750 10 (22.2%) 9 (22.5%)

.0.750 2 (4.4%) 2 (5.0%)

Mean 6 SD 0.381 6 0.168 0.369 6 0.159

Range 0.135–0.787 0.146–1.154)

Best-corrected visual acuity

0.3–0.5 (20/66.7–20/40) 22 (46.7%) 20 (50.0%)

0.1–0.2 (20/200–20/100) 20 (44.4%) 15 (37.5%)

0.05–0.09 (20/400–20/222) 2 (4.4%) 5 (12.5%)

0.01–0.04 (20/2,000–20/500) 1 (2.2%) 0 (0.0%)

Mean 0.203 (20/98.5) 0.224 (20/89.3)

Range 0.04–0.5 0.05–0.5

Mean 6 SD (logMAR) 0.693 6 0.306 0.650 6 0.352

LogMar 5 logarithm of the minimal angle of resolution; CNVM 5 choroidal neovascular membrane.


TABLE 2. Changes of Area of CNVM

Treatment Group Control Group P Value

No. of patients 45 39

Duration of follow-up (mos)

Mean 6 SD 27.3 6 4.8 28.7 6 5.0 —

Range 24–34 24–36

Area of CNVM (mm2)

Baseline

Mean 6 SD 6.064 6 6.682 6.125 6 5.870 —

Range 0.221–25.044 0.213–25.641

3 mos

Mean 6 SD 6.584 6 7.097 6.656 6 7.332 —

Range 0.245–32.983 0.235–34.244

6 mos

Mean 6 SD 7.221 6 7.535 7.183 6 7.747 —

Range 0.238–36.747 0.378–38.759

12 mos

Mean 6 SD 8.305 6 9.967 8.172 6 7.674 —

Range 0.233–43.451 0.476–31.538

24 mos

Mean 6 SD 10.534 6 13.292 10.330 6 9.516 —

Range 0.222–51.544 0.568–36.410

Change of area of CNVM

3 mos

Mean 6 SD 107.6% 6 18.4% 116.28% 6 20.3% .0438

Range 58%–148% 93%–187%

6 mos

Mean 6 SD 116.7% 6 24.8% 127.3 6 32.1% —

Range 58%–169% 94%–209%

12 mos

Mean 6 SD 122.3% 6 35.8% 143.2 6 41.1% .0147

Range 56%–188% 103%–331%

24 mos

Mean 6 SD 143.5% 6 53.1% 190.3 6 81.4% .0008

Range 52%–258% 112%–412%

Eyes with change of area

of CNVM for 2 yrs

,80% 8 (17.8%) 0 (0%)

81%–100% 1 (2.2%) 0 (0%)

101%–120% 6 (13.3%) 4 (10.3%)

121%–150% 8 (17.8%) 11 (28.2%)

151%–200% 14 (31.1%) 14 (35.9%)

201%–300% 8 (17.8%) 7 (17.9%)

.300% 0 (0%) 3 (7.7%)

Area of CNVM 2 yrs after

start of follow-up (mm2)

0–0.500 5 (11.1%) 4 (10.3%)

0.501–1.000 9 (20.0%) 6 (15.4%)

1.001–1.500 4 (8.9%) 3 (7.7%)

1.501–2.500 2 (4.4%) 3 (7.7%)

2.501–5.000 3 (6.7%) 4 (10.3%)

5.001–7.500 3 (6.7%) 4 (10.3%)

7.501–10.000 2 (4.4%) 3 (7.7%)

10.001–15.000 3 (6.7%) 4 (10.3%)

15.001–20.000 6 (13.3%) 3 (7.7%)

.20.000 8 (17.8%) 5 (12.8%)

CNVM 5 choroidal neovascular membrane.


retinal vasculopathy (microvascular abnormalities, leak-age, and cotton-wool spots) or optic neuropathy (diskpallor) were not observed clinically. Angiograms werescrutinized for evidence of retinal microvascular abnormal-ities, and none was found. In the control group, nocomplication or adverse reaction was found.

In the control group, area of choroidal neovascularmembrane of one patient was not evaluated because ofvitreous hemorrhage. Mean area of choroidal neovascularmembrane before and 2 years after the start of thefollow-up was 6.064 6 6.682 mm2 and 10.534 6 13.292mm2 in the treatment group and 6.125 6 5.870 mm2 and10.330 6 9.516 mm2 in the control group (Table 2). Meanchanges in area of choroidal neovascular membrane for 1

and 2 years were 122.3% 6 35.8% and 143.5% 6 53.1%in the treatment group and 143.2% 6 41.1% and 190.3%6 81.4% in the control group. The increase in the size ofchoroidal neovascular membrane for 1 and 2 years in thetreatment group was significantly smaller than that in thecontrol group (P 5 .0147; P 5 .0008).

In the control group, no patient showed regression ofthe choroidal neovascular membrane. Of 45 patients in thetreatment group, eight (17.8%) showed significant regres-sion and seven (15.6%) showed a stable fluorescein angio-graphic appearance at 2 years after radiotherapy (Table 2).

In the treated eyes, mean best-corrected visual acuitybefore and 1 and 2 years after radiotherapy was 0.203(20/98.5), 0.143 (20/139.9), and 0.119 (20/168.1), respec-

TABLE 3. Change in Best-corrected Visual Acuity

Treatment Group

(N 5 45)

Control Group

(N 5 40) P Value


Baseline

Mean 0.203 (20/98.5) 0.224 (20/89.3)

Range 0.04–0.5 0.05–0.5

LogMAR (mean 6 SD) 0.693 6 0.306 0.650 6 0.352 —

3 mos

Mean 0.190 (20/105.2) 0.190 (20/105.2)

Range 0.02–0.6 0.03–0.4

LogMAR (mean 6 SD) 0.722 6 0.362 0.721 6 0.364 —

6 mos

Mean 0.175 (20/114.2) 0.138 (20/144.9)

Range 0.02–0.8 0.03–0.4

LogMAR (mean 6 SD) 0.756 6 0.404 0.857 6 0.373 —

12 mos

Mean 0.143 (20/139.9) 0.098 (20/204.1)

Range 0.01–0.8 0.02–0.4

LogMAR (mean 6 SD) 0.844 6 0.413 1.010 6 0.352 .0500

24 mos

Mean 0.119 (20/168.1) 0.061 (20/327.9)

Range 0.01–0.8 0.01–0.3

LogMar (mean 6 SD) 0.926 6 0.461 1.212 6 0.393 .0030

Change in LogMAR best-

corrected visual acuity

after start of follow-up

3 mos

Mean 6 SD 10.029 6 0.062 10.064 6 0.087 .0342

Range 20.602–10.523 20.477–10.699

6 mos

Mean 6 SD 10.063 6 0.161 10.200 6 0.131 ,.0001

Range 21.699–10.824 0–11.222

12 mos

Mean 6 SD 10.164 6 0.291 10.360 6 0.293 ,.0001

Range 20.301–11 20.301–1.222

24 mos

Mean 6 SD 10.226 6 0.373 10.563 6 0.370 ,.0001

Range 20.699–11.097 20.204–1.699



tively (Table 3). In the control eyes, best-corrected visualacuity before and 1 and 2 years after the start of follow-upwas 0.224 (20/89.3), 0.098 (20/204.1), and 0.061 (20/327.9). A change in logMAR visual acuity for 6, 12, and24 months was 10.063 6 0.161, 10.164 6 0.291, and10.226 6 0.373 in the treatment group, and 10.200 60.131, 10.360 6 0.293, and 10.563 6 0.370 in thecontrol group. A significant difference was found for afollow-up of 6, 12, and 24 months (P , .0001; P , .0001;P , .0001).

In the treatment group, multiple regression analysisshowed the strongest correlation between best-correctedvisual acuity at 2 years after radiotherapy and a combina-tion of pretreatment best-corrected visual acuity and typeof choroidal neovascular membrane, indicating that pa-tients with better visual acuity at baseline and those withoccult choroidal neovascular membrane showed bettervisual acuity after 2-year follow-up (Table 4). The changein best-corrected visual acuity for 2 years was the mostsignificantly correlated with pretreatment type of choroidalneovascular membrane, as shown in Table 4. This corre-lation showed that patients with ocult choroidal neovas-cular membrane showed a smaller decrease in visual acuitythan those with mixed and classic choroidal neovascularmembrane. Area of choroidal neovascular membrane at 2years after radiotherapy and its change for 2 years showedthe strongest correlation with the combination of pretreat-ment type and area of choroidal neovascular membrane.

Patients with smaller choroidal neovascular membrane atbaseline showed a smaller increase in area of choroidalneovascular membrane for 2 years and a smaller area ofchoroidal neovascular membrane at 2 years. In the controlgroup, best-corrected visual acuity at 2 years after the startof the follow-up and its change showed a strongest corre-lation with pretreatment best-corrected visual acuity. Thecorrelation showed that patients with better visual acuityat baseline had a smaller decrease in visual acuity for 2-yearfollow-up and a better visual acuity at 2 years.

We divided patients into two subgroups based on thearea of choroidal neovascular membrane at baseline: thesmall choroidal neovascular membrane group (#1.5 mm2)and large choroidal neovascular membrane group (.1.5mm2) (Table 5). In the small and large choroidal neovas-cular membrane groups, there was no difference in age,gender, area of choroidal neovascular membrane, andbest-corrected visual acuity at baseline between the treat-ment and control groups (Table 5). In the small choroidalneovascular membrane group, the change in area of cho-roidal neovascular membrane for 1 and 2 years was 98.9%6 35.8% and 111.0% 6 58.7% in the treatment group and160.6% 6 60.9% and 226.7% 6 109.2% in the controlgroup. The change in logMAR best-corrected visual acuityfor 1- and 2-year follow-up was 10.093 6 0.316 and10.185 6 0.417 in the treatment group and 10.499 60.302 and 10.769 6 0.364 in the control group. Thetreatment group showed a significantly smaller increase in

TABLE 3. (Continued) Change in Best-corrected Visual Acuity

Treatment Group

(N 5 45)

Control Group

(N 5 40) P Value

Eyes with change in best-

corrected visual acuity for

2 yrs (no. [%])

,20.4 1 (2.2) 0 (0)

20.201–20.4 5 (11.1) 1 (2.5)

20.2–10.2 16 (35.6) 4 (10.0)

10.201–10.4 11 (24.4) 9 (22.5)

10.401–0.6 2 (4.4) 9 (22.5)

.10.601 10 (22.2) 17 (42.5)


at 2 yrs after start of

follow-up (no. [%])

.0.6 (20/33.3) 8 (17.8) 0 (0)

0.3–0.5 7 (15.6) 4 (10.0)

(20/66.7–20/40)

0.1–0.2 9 (20.0) 10 (25.0)

(20/200–20/100)

0.06–0.09 16 (35.5) 15 (37.5)

(20/333.3–20/222.2)

0.01–0.05 5 (11.1) 11 (27.5)

(20/2,000–20/400)

LogMAR 5 logarithm of the minimal angle of resolution.


the area of choroidal neovascular membrane (P 5 .0014;P , .0001) and a significantly smaller decrease in logMARbest-corrected visual acuity (P , .0001; P , .0001). In thelarge choroidal neovascular membrane group, the changein area of choroidal neovascular membrane for 1 and 2years was 137.9% 6 26.3% and 165.1% 6 36.0% in theradiotherapy group, and 134.5% 6 23.4% and 172.1% 657.5% in the control group. The change in logMARbest-corrected visual acuity was 10.212 6 0.269 and10.287 6 0.342 in the treatment group, and 10.291 60.272 and 10.397 6 0.346 in the control group. There wasno significant difference between the two groups.

The treatment group and control group were dividedinto two subgroups according to baseline best-correctedvisual acuity: good visual acuity ($0.3 [20/66.7]) and poorvisual acuity (,0.3 [20/66.7]) (Table 6). In the good visualacuity group, there was no significant difference in age,area of choroidal neovascular membrane, and visual acuityat baseline between the treatment and control groups. Thechange in area of choroidal neovascular membrane for 1and 2 years was 108.7% 6 37.4% and 124.7% 6 59.0% in

the treatment group, and 152.4% 6 51.3% and 212.7% 697.7% in the control group; there was a significant differ-ence for both durations (P 5 .0029; P 5 .0009). Thetreatment group showed a significantly smaller decrease invisual acuity for 1 and 2 years (P 5 .0047; P 5 .0023).

In the poor visual acuity group, no significant differencewas found in baseline age, area of choroidal neovascularmembrane, and visual acuity between the two groups. Theincreases in area of choroidal neovascular membrane for 1and 2 years in the treatment group (135.3% 6 29.3% and161.5% 6 40.3%) were comparable to those in the controlgroup (133.5% 6 24.4% and 166.7% 6 52.5%). Thetreatment group showed a decrease in visual acuity similarto that of the control group.

Table 7 summarizes changes of area of choroidal neo-vascular membrane and best-corrected visual acuity for theclassic, mixed, and occult types. In the treatment group,the change in area of choroidal neovascular membrane for2-year follow-up was 220.4% 6 91.4% for the classic type,144.6% 6 42.9% for the mixed type, and 105.8% 6 35.7%for the occult type. The decrease in logMAR visual acuity

TABLE 4. Multiple Regression Analysis of Predictors of Visual Acuity and Area of CNVM 2Years After Start of Follow-up, and Their Changes

Variable Entered r F Test Correlation Equation

Treatment Group (N 5 45)

B-CVA 0.614 25.469 [LogMAR postTx B-CVA] 5 20.288 1 0.971

3 [LogMAR preTx B-CVA]

0.768 29.490 [LogMAR of postTx B-CVA] 5 20.572

1 0.264 3 [type of CNVM] 1 0.864 3 log

[LogMAR preTx VA]

Change in B-CVA 0.574 20.684 [Change of logMAR B-CVA] 5 10.472

2 0.257 3 [LogMAR preTx B-CVA]

Area of CNVM 0.979 983.622 [PostTx CNVM area (mm2)] 5 21.26 1 1.949

3 [type of CNVM]

0.982 555.146 [PostTx area of CNVM (mm2)] 5 20.112

2 1.19 3 [type of CNVM] 1 1.915

3 [preTx area of CNVM (mm2)]

Change in area of

CNVM (%)

0.578 21.047 [Change of area of CNVM (%)] 5 140.58

2 24.158 3 [type of CNVM]

0.642 14.349 [Change of CNVM area (%)] 5 129.357

2 21.488 3 [type of CNVM] 1 1.509

3 [preTx area of CNVM (mm2)]

Control Group (N 5 39)

B-CVA 0.465 9.933 [LogMar postTx B-CVA] 5 20.959 1 0.549

3 [LogMAR preTx B-CVA]

Change in B-CVA 0.397 6.725 [Change of logMAR B-CVA] 5 10.959

1 0.451 3 [LogMAR preTx B-CVA]

Area of CNVM 0.947 311.414 [PostTx area of CNVM (mm2)] 5 0.866

1 1.579 3 [preTx area of CNVM (mm2)]

Change in area of

CNVM

— — —

PreTx 5 pretreatment; postTx 5 posttreatment; B-CVA 5 best-corrected visual acuity; LogMAR 5

logarithm of the minimal angle of resolution; CNVM 5 choroidal neovascular membrane.


TABLE 5. Comparison of Changes in Area of CNVM and Best-corrected Visual AcuityBetween Small and Large CNVM Groups


Small CNVM (Area , 1.5 mm2)


Age (yrs)

Mean 6 SD 69.056 6 6.226 70.077 6 5.057 —

Range 60–84 60–76

Area of CNVM (mm2)*

Baseline

Mean 6 SD 0.657 6 0.419 0.758 6 0.479 —

Range 0.221–1.438 0.213–1.448

1 yr

Mean 6 SD 0.607 6 0.368 1.097 6 0.639 .0114

Range 0.233–1.510 0.476–2.107

2 yrs

Mean 6 SD 0.652 6 0.385 1.427 6 0.811 .0013

Range 0.222–1.553 0.568–2.693

Change in area of CNVM (%)

1 yr

Mean 6 SD 98.9 6 35.8 160.6 6 60.9 .0014

Range 56–165 103–311

2 yrs

Mean 6 SD 111.0 6 58.7 226.7 6 109.2 ,.0001

Range 52–258 112–412

Eyes with change in area of CNVM for

2 yrs (no. [%])

,80% 8 (44.4) 0 (0)

80%–120% 5 (27.8) 2 (15.4)

.120% 5 (27.8) 11 (84.6)


Baseline

Mean 0.375 (20/5.3) 0.463 (20/43.1)

Range 0.15–0.5 0.3–0.5

LogMAR 0.425 6 0.141 0.334 6 0.176 —

1 yr

Mean 0.303 (20/66.0) 0.147 (20/136.1)

Range 0.08–0.8 0.03–0.5

LogMAR 0.519 6 0.329 0.834 6 0.304 .0111

2 yrs

Mean 0.245 (20/81.6) 0.079 (20/253.2)

Range 0.04–0.8 0.01–0.5

LogMAR 0.610 6 0.420 1.103 6 0.360 .0019

Change in LogMAR best-corrected

visual acuity (mean 6 SD)

1 yr 10.093 6 0.316 10.499 6 0.302 ,.0001

2 yrs 10.185 6 0.417 10.769 6 0.364 ,.0001

Eyes with change in LogMAR visual

acuity for 2 yrs (no. [%])

,20.2 5 (27.8) 0 (0)

20.2–10.2 6 (33.3) 2 (15.4)

.10.2 7 (38.9) 11 (84.6)

Large CNVM (Area . 1.5 mm2)

No. of patients 27 27*

Age (yrs)



for 2 years was 10.606 6 0.385 for the classic type,10.207 6 0.388 for the mixed type, and 10.066 6 0.205for the occult type. There was a significant difference in

changes in area of choroidal neovascular membrane andlogMAR visual acuity between the classic and mixed types(area of choroidal neovascular membrane, P 5 .0130;

TABLE 5. (Continued) Comparison of Changes in Area of CNVM and Best-corrected VisualAcuity Between Small and Large CNVM Groups


Mean 6 SD 73.074 6 6.324 72.629 6 6.716 —

Range 60–86 60–89

Area of CNVM (mm2)

Baseline

Mean 6 SD 9.669 6 6.458 8.800 6 5.469 —

Range 1.567–25.644 1.883–25.641

1 yr

Mean 6 SD 12.445 6 7.926 11.700 6 7.103 —

Range 2.076–43.451 2.542–31.538

2 yrs

Mean 6 SD 17.307 6 13.882 14.771 6 8.706 —

Range 1.614–51.544 2.749–36.410


1 yr

Mean 6 SD 137.9 6 26.3 134.5 6 23.4 —

Range 102–188 105–203

2 yrs

Mean 6 SD 165.1 6 36.0 172.1 6 57.5 —

Range 103–256 115–356

Eyes with change in area of CNVM for

2 yrs (no. [%])

,80% 0 (0.0) 0 (0.0)

80%–120% 2 (7.4) 2 (7.7)

.120% 25 (92.6) 24 (92.3)


Baseline

Mean 0.141 (20/141.8) 0.156 (20/128.2)

Range 0.04–0.5 0.05–0.5

LogMAR 0.850 6 0.257 0.807 6 0.328 —

1 yr

Mean 0.087 (20/229.9) 0.080 (20/250.0)

Range 0.01–0.4 0.02–0.4

LogMAR 1.062 6 0.308 1.098 6 0.346 —

2 yrs

Mean 0.073 (20/274.0) 0.055 (20/363.6)

Range 0.01–0.5 0.01–0.3

LogMAR 1.137 6 0.360 1.260 6 0.415 —



1 yr 10.212 6 0.269 10.291 6 0.272 —

2 yrs 10.287 6 0.342 10.397 6 0.346 —

Eyes with change in LogMAR visual

acuity for 2 yrs (no. [%])

,20.2 1 (3.7) 1 (3.7)

20.2–10.2 10 (37.0) 2 (7.4)

.10.2 16 (59.3) 24 (88.9)

CNVM 5 choroidal neovascular membrane; LogMAR 5 logarithm of the minimal angle of

resolution.

*Area of CNVM of one patient was not evaluated because of vitreous hemorrhage.


TABLE 6. Comparison of Changes in Area of CNVM and Best-corrected Visual AcuityBetween the Good and Poor Visual Acuity Groups


Good Best-corrected Visual Acuity ($0.3 [20/66.7])


Age (yrs)

Mean 6 SD 69.318 6 5.979 70.900 6 5.839 —

Range 60–84 60–84

Area of CNVM (mm2)

Baseline

Mean 6 SD 2.035 6 3.105 2.499 6 3.118 —

Range 0.221–12.331 0.213–10.211

1 yr

Mean 6 SD 2.580 6 4.192 3.614 6 4.814 —

Range 0.233–13.895 0.476–16.644

2 yrs

Mean 6 SD 3.104 6 5.284 5.130 6 7.495 —

Range 0.222–18.003 0.568–23.528


1 yr

Mean 6 SD 108.7 6 37.4 152.4 6 51.3 .0029

Range 56–156 103–311

2 yrs

Mean 6 SD 124.7 6 59.0 212.7 6 97.7 .0009

Range 52–258 112–412

Eyes with change in area of CNVM

for 2 yrs (no. [%])

,80% 7 (31.8) 0 (0.0)

80%–120% 6 (27.2) 2 (10.0)

.120% 9 (40.9) 18 (90.0)


Baseline

Mean 0.392 (20/51.0) 0.457 (20/43.8)

Range 0.3–0.5 0.3–0.5

LogMar 0.406 6 0.084 0.340 6 0.082 .0140

1 yr

Mean 0.265 (20/75.5) 0.156 (20/128.2)

Range 0.06–0.8 0.03–0.4

LogMAR 0.576 6 0.340 0.808 6 0.322 .0290

2 yrs

Mean 0.205 (20/97.6) 0.092 (20/217.4)

Range 0.04–0.8 0.01–0.5

LogMar 0.689 6 0.427 1.037 6 0.422 .0114



1 yr 10.171 6 0.330 10.468 6 0.310 .0047

2 yrs 10.283 6 0.410 10.697 6 0.411 .0023

Eyes with change in LogMAR

visual acuity for 2 yrs (no. [%])

,20.2 5 (22.7) 0 (0.0)

20.2–10.2 7 (31.8) 2 (10.0)

.10.2 10 (45.5) 18 (90.0)

Poor Best-corrected Visual Acuity (,0.3 [20/66.7])


Age (yrs)



logMAR, P 5 .0304) and the classic and occult types (areaof choroidal neovascular membrane, P 5 .0054; logMAR,P 5 .0018).

In all subgroups, there was no significant difference inage, area of choroidal neovascular membrane, and visualacuity at baseline between the treatment and control

TABLE 6. (Continued) Comparison of Changes in Area of CNVM and Best-corrected VisualAcuity Between the Good and Poor Visual Acuity Groups


Mean 6 SD 73.522 6 6.480 72.789 6 6.713 —

Range 60–86 60–89

Area of CNVM (mm2)*

Baseline

Mean 6 SD 9.918 6 6.952 9.930 6 5.7169 —

Range 0.352–25.644 3.452–25.641

1 yr

Mean 6 SD 13.782 6 10.853 12.957 6 7.265

Range 0.486–43.451 4.591–31.538

2 yrs

Mean 6 SD 17.641 6 14.789 15.789 6 8.405

Range 0.567–51.544 5.420–36.410


1 yr

Mean 6 SD 135.3 6 29.3 133.5 6 24.4 —

Range 66–188 105–203

2 yrs

Mean 6 SD 161.5 6 40.3 166.7 6 52.5 —

Range 56–256 115–356

Eyes with change in area of CNVM

for 2 yrs (no. [%])

,80% 1 (4.3) 0 (0.0)

80%–120% 1 (4.3) 2 (10.5)

.120% 21 (91.3) 17 (89.5)


Baseline

Mean 0.114 (20/175.4) 0.105 (20/190.5)

Range 0.04–0.2 0.05–0.2

LogMAR 0.943 6 0.166 0.976 6 0.186 —

1 yr

Mean 0.079 (20/253.2) 0.060 (20/333.3)

Range 0.01–0.4 0.02–0.1

LogMAR 1.101 6 0.300 1.223 6 0.243 —

2 yrs

Mean 0.070 (20/285.7) 0.041 (20/487.8)

Range 0.01–0.3 0.01–0.08

LogMAR 1.154 6 0.376 1.388 6 0.289 .0304



1 yr 10.158 6 0.256 10.247 6 0.230 —

2 yrs 10.272 6 0.308 10.412 6 0.269 —



,20.2 1 (4.3) 1 (5.0)

20.2–10.2 9 (39.1) 2 (10.0)

.10.2 13 (56.5) 17 (85.0)


resolution.



TABLE 7. Comparison of Changes in Area of CNVM and Best-corrected Visual AcuityAmong Classic, Mixed, and Occult Groups


Classic Type


Age (yrs)

Mean 6 SD 73.190 6 6.071 72.095 6 4.979 —

Range 64–89 64–81

Area of CNVM (mm2)*

Baseline

Mean 6 SD 7.393 6 6.635 6.606 6 5.097 —

Range 0.213–25.641 0.213–16.325

1 yr

Mean 6 SD 10.450 6 8.703 9.609 6 7.173 —

Range 0.501–31.538 0.501–23.859

2 yrs

Mean 6 SD 13.012 6 10.173 12.526 6 8.889 —

Range 0.586–36.410 0.568–27.156


1 yr

Mean 6 SD 163.1 6 46.0 164.7 6 45.2 —

Range 78–311 105–311

2 yrs

Mean 6 SD 220.4 6 91.4 229.0 6 91.3 —

Range 75–412 118–412

Eyes with change in area of

CNVM for 2 yrs (no. [%])

,80% 4 (14.3) 0 (0.0)

80%–120% 3 (10.7) 1 (4.4)

120% 21 (75.0) 21 (95.5)


Baseline

Mean 0.187 (20/107.0) 0.200 (20/100.0)

Range 0.04–0.5 0.04–0.5

LogMAR 0.728 6 0.372 0.699 6 0.348 —

1 yr

Mean 0.078 (20/256.4) 0.071 (20/281.7)

Range 0.02–0.4 0.02–0.4

LogMAR 1.107 6 0.380 1.147 6 0.379 —

2 yrs

Mean 0.046 (20/434.8) 0.040 (20/500.0)

Range 0.01–0.5 0.01–0.3

LogMAR 1.334 6 0.409 1.393 6 0.414 —



(mean 6 SD)

1 yr 10.379 6 0.305 10.447 6 0.305 —

2 yrs 10.606 6 0.385 10.693 6 0.395 —



,20.2 2 (7.1) 0 (0.0)

20.2–10.2 9 (32.1) 1 (4.3)

.10.2 17 (60.7) 22 (95.7)

Mixed Type


Age (yrs)



TABLE 7. (Continued) Comparison of Changes in Area of CNVM and Best-corrected VisualAcuity Among Classic, Mixed, and Occult Groups


Mean 6 SD 72.182 6 6.416 70.727 6 5.495 —

Range 60–83 60–89

Area of CNVM (mm2)*

Baseline

Mean 6 SD 9.191 6 6.890 7.594 6 8.064 —

Range 0.477–19.877 0.421–25.641

1 yr

Mean 6 SD 10.723 6 9.363 8.880 6 9.657 —

Range 0.413–24.051 0.476–31.538

2 yrs

Mean 6 SD 13.035 6 12.101 10.695 6 11.714 —

Range 0.385–36.772 0.568–36.410

Change of area of CNVM (%)

1 yr

Mean 6 SD 124.1 6 31.9 119.6 6 10.2 —

Range 73–165 106–135

2 yrs

Mean 6 SD 144.6 6 42.9 151.1 6 34.6 —

Range 68–208 115–234



,80% 2 (18.2) 0 (0.0)

80%–120% 2 (18.2) 1 (10.0)

.120% 7 (63.6) 9 (90.0)


Baseline

Mean 0.171 (20/117.0) 0.225 (20/88.9)

Range 0.04–0.5 0.04–0.4

LogMAR 0.765 6 0.263 0.648 6 0.369 —

1 yr

Mean 0.127 (20/157.5) 0.134 (20/149.3)

Range 0.06–0.5 0.06–0.3

LogMAR 0.897 6 0.345 0.874 6 0.220 —

2 yrs

Mean 0.107 (20/186.9) 0.083 (20/241.0)

Range 0.04–0.5 0.05–0.3

LogMAR 0.971 6 0.395 1.079 6 0.235 —



(mean 6 SD)

1 yr 10.132 6 0.317 10.226 6 0.266 —

2 yrs 10.207 6 0.338 10.431 6 0.325 —



,20.2 2 (18.2) 1 (10.0)

20.2–10.2 4 (36.4) 1 (10.0)

10.2 5 (45.5) 8 (80.0)

Occult Type

No. of patients 6 7

Age (yrs)

Mean 6 SD 70.000 6 7.014 72.714 6 7.342 —

Range 60–82 60–84

Area of CNVM (mm2)*



groups. In the classic and mixed groups, no significantdifference was found in changes in area of choroidalneovascular membrane and visual acuity for 1 and 2 yearsbetween the two groups.

In the occult group, the treatment group showed a

smaller decrease in area of choroidal neovascular mem-brane for 1 and 2 years, but the difference was notsignificant. Changes in logMAR visual acuity for 1 and 2years in the treatment group (10.008 6 0.162 and10.066 6 0.205) were significantly smaller than those in

TABLE 7. (Continued) Comparison of Changes in Area of CNVM and Best-corrected VisualAcuity Among Classic, Mixed, and Occult Groups


Baseline

Mean 6 SD 4.311 6 4.569 2.342 6 1.630 —

Range 0.426–12.356 0.521–4.877

1 yr

Mean 6 SD 4.739 6 5.137 2.712 6 1.894 —

Range 0.239–13.468 0.589–5.403

2 yrs

Mean 6 SD 5.638 6 6.695 3.127 6 2.144 —

Range 0.222–17.546 0.745–6.120


1 yr

Mean 6 SD 97.5 6 25.2 115.9 6 14.0 —

Range 56–120 103–142

2 yrs

Mean 6 SD 105.8 6 35.7 135.7 6 25.5 —

Range 52–142 112–186



,80% 2 (33.3) 0 (0.0)

80%–120% 2 (33.3) 2 (28.6)

.120% 2 (33.3) 5 (71.4)


Baseline

Mean 0.240 (20/83.3) 0.314 (20/63.7)

Range 0.1–0.4 0.1–0.5

LogMAR 0.620 6 0.299 0.503 6 0.343 —

1 yr

Mean 0.231 (20/86.6) 0.153 (20/130.7)

Range 0.08–0.8 0.07–0.4

LogMAR 0.636 6 0.367 0.814 6 0.289 —

2 yrs

Mean 0.206 (20/97.1) 0.138 (20/144.9)

Range 0.08–0.8 0.07–0.5

LogMAR 0.686 6 0.358 0.857 6 0.234 —



(mean 6 SD)

1 yr 10.008 6 0.162 10.310 6 0.228 .0204

2 yrs 10.066 6 0.205 10.353 6 0.208 .0297



,20.2 2 (33.3) 0 (0.0)

20.2–10.2 3 (50.0) 2 (28.6)

.10.2 1 (16.7) 5 (71.4)


resolution.



the control group (10.310 6 0.228 and 10.353 6 0.208)(P 5 .0204; P 5 .0297).

DISCUSSION

THE NATURAL COURSE OF THE VISUAL ACUITY IN PA-

tients with age-related macular degeneration is poor. Inour control group of patients without any treatment, meanvisual acuity decreased from 0.224 (20/89.3) to 0.061(20/327.9) after 2-year follow-up. These findings in ouruntreated patients are almost identical to those reported inthe control patients in foveal Macular PhotocoagulationStudy.2–4

Although strenuous efforts were made to follow uppatients, the overall complete follow-up rate was 84.1%.Six patients in the treatment group and 10 patients in thecontrol group were lost to follow-up. The lost patients didnot change the statistical results in this study.

Serous retinal detachment has an effect on visualfunctions, in addition to type and area of choroidalneovascular membrane.41–43 In this study, we performedthree-dimensional analysis on retinal elevation by meansof a confocal scanning laser tomograph. At baseline, therewas no significant difference in their area, volume, andmaximal height between the treatment and control groups.

In previous studies, a variety of total dose and fraction-ation schedules have been used.15–32 A few studies haveused relatively large fraction sizes, and these nonstandardfraction schedules make it difficult to evaluate the biologiceffectiveness of the dose. Chakraverthy and associates15,16

reported that there was no significant difference betweenthe treatment results in patients treated with 10 Gy and 15Gy. Sasai26 showed that the dose of 20 Gy in 10 fractionswas more effective in treating neovascular membranesthan the dose of 10 Gy in five fractions. The neovascularmembranes in the eyes treated with the higher doseseemed to shrink faster than those in the eyes treated withthe lower dose.26 Bergink and associates17,18 reported thata radiation dose of 8 Gy in one fraction was not effectiveand the larger doses were useful in the treatment ofchoroidal neovascular membrane. These escalationstudies showed that the higher dose resulted in betteroutcome. In this study, we used the dose of 20 Gy in 10fractions to treat choroidal neovascular membrane tominimize the adverse effect of the radiotherapy. How-ever, a further study is needed to determine a total doseand fractionation schedule.

Results in this study were better than those in many ofthe previously reported articles on radiation therapy forsubfoveal choroidal neovascular membrane. These findingsmay result from the use of a relatively high dose forsubfoveal choroidal neovascular membrane, and a rela-tively large percentage of cases with small choroidalneovascular membrane and good visual acuity.

Hart and associates16 reported a relationship between

the initial lesion size and visual outcome after radiother-apy. They subdivided their treated patients on the basis ofthe baseline entry criteria of visual acuity and lesion size.The initial lesion size and visual acuity showed no signif-icant correlation with visual outcome, which was evalu-ated by means of a 6-line decrease in visual acuity as aserious visual event.

In this study, radiotherapy induced different effects onpatients with small choroidal neovascular membranescompared to those with large choroidal neovascular mem-branes. In the small choroidal neovascular membranegroup, the treatment group showed a significantly smallerincrease in area of choroidal neovascular membrane and asmaller decrease in visual acuity, whereas there was nosignificant difference between the two groups in patientswith large choroidal neovascular membranes. Treatedpatients with good baseline visual acuity also showed asignificantly smaller increase in area of choroidal neovas-cular membrane and a smaller decrease in visual acuitythan untreated patients. In patients with poor visual acuityat baseline, radiotherapy induced no significant effect.Therefore, favorable factors for radiotherapy for subfo-veal choroidal neovascular membrane were the smallerarea of choroidal neovascular membrane and the bettervisual acuity.

Stalmans and associates27 reported that, after radiother-apy, patients with occult choroidal neovascular membraneshowed a slowly progressive growth of choroidal neovas-cular membrane, whereas patients with classic choroidalneovascular membrane showed fast growth of the mem-brane and continuous increase in size. In this study, thetype of choroidal neovascular membrane also showed asignificant correlation with changes in visual acuity andarea of choroidal neovascular membrane. In patients withclassic- and mixed-type choroidal neovascular membrane,radiotherapy induced no effect on changes in area ofchoroidal neovascular membrane and visual acuity. Inpatients with occult-type choroidal neovascular mem-brane, treated patients showed a significant smaller de-crease in visual acuity. The increase in area of choroidalneovascular membrane in treated patients was smaller, butthe difference was statistically significant. The limitednumber of cases in this study may result in no significantdifference.

In summary, we presented a randomized study of long-term results of radiotherapy for choroidal neovascularmembrane associated with age-related macular degenera-tion. Radiotherapy showed a beneficial treatment effectand safety in eyes with choroidal neovascular membranecompared to untreated eyes. Favorable factors for radio-therapy for choroidal neovascular membrane were thesmaller area of choroidal neovascular membrane, occultchoroidal neovascular membrane, and the better visualacuity. However, further investigation on more cases andfollow-up longer than 2 years are needed.


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