ARCH OPHTHALMOL / VOL 118, APR 2000 481 WW W . ARCHOPHTHALMOL . COM Downloaded from www.archophthalmol.com on August 17, 2011 G CLINICAL SCIENCES Rate of Visual Field Loss in Progressive Glaucoma Marga T. E. Rasker, MD; Aad van den Enden, MSc; Douwe Bakker; Philip F. J. Hoyng, MD, PhD Objective: To investigate the rate of visual field (VF) loss in progressive glaucoma. Setting: Outpatient department, nonreferral base. Methods: A cohort of 34 patients with normal- pressure glaucoma (NPG), 68 patients with primary open- angle glaucoma (POAG), and 125 patients with ocular hypertension (OHT) were followed up for an average of 9 years. Visual fields were obtained annually with auto- mated perimetry. The rate of VF loss as a percentage per year was calculated. Results: Twenty-three eyes with NPG, 31 with POAG, and 10 with OHT showed progression of VF loss. The mean (±SD) rates of VF deterioration were 3.7% ± 3.3% per year in NPG, 2.5% ± 1.8% in POAG, and 2.3% ± 1.3% in OHT converting to POAG, and did not differ significantly. No difference in the rate of VF loss was found between eyes with and without optic disc hemorrhages (2.7% ± 2.9% and 3.1% ± 2.1%, respectively). The rate of VF loss was not related to the initial VF status. The rate of VF loss be- tween the superior and inferior hemifields was correlated in patients with NPG (r s = 0.67, P = .04). Comparison of visual field loss with linear regression analysis showed significant slopes in only 37.5% of eyes with progression, which had a progression rate of 4.2% ± 3.0%. Conclusions: The rate of VF loss did not differ be- tween patients with NPG and POAG. The rate of dete- rioration was related neither to initial VF status nor to the presence of disc hemorrhages. Linear regression is applicable only in a portion of the patients who have pro- gression of VF loss. Arch Ophthalmol. 2000;118:481- 488 LAUCOMA IS a widespread chronic optic neuropa- thy characterized by ex- cavation of the optic nerve head and typical vi- sual field (VF) defects; in approximately 1-4 initial VF status on the rate of progres- sion. Therefore, a possible relationship be- tween the defect volume at the moment the diagnosis was established and the rate of VF loss with time is of interest. Fur- thermore, it was observed that the pres- 60% to 70% of cases it is accompanied by ence of DHs increased the hazard rate for From the Netherlands Ophthalmic Research Institute (Drs Rasker and Hoyng and Mr van den Enden), St Lucas Hospital (Dr Hoyng ),
Rate of Visual Field Loss in Progressive GlaucomaMarga T. E. Rasker, MD; Aad van den Enden, MSc; Douwe Bakker; Philip F. J. Hoyng, MD, PhD
Objective: To investigate the rate of visual field (VF)loss in progressive glaucoma.
Setting: Outpatient department, nonreferral base.
Methods: A cohort of 34 patients with normal- pressure glaucoma (NPG), 68 patients with primary open- angle glaucoma (POAG), and 125 patients with ocular hypertension (OHT) were followed up for an average of9 years. Visual fields were obtained annually with auto- mated perimetry. The rate of VF loss as a percentage per year was calculated.
Results: Twenty-three eyes with NPG, 31 with POAG, and 10 with OHT showed progression of VF loss. The mean (±SD) rates of VF deterioration were 3.7% ± 3.3% per year in NPG, 2.5% ± 1.8% in POAG, and 2.3% ± 1.3% in OHT converting to POAG, and did not differ significantly. No
difference in the rate of VF loss was found between eyes with and without optic disc hemorrhages (2.7% ± 2.9% and 3.1% ± 2.1%, respectively). The rate of VF loss was not related to the initial VF status. The rate of VF loss be- tween the superior and inferior hemifields was correlated in patients with NPG (rs = 0.67, P = .04). Comparison of visual field loss with linear regression analysis showed significant slopes in only 37.5% of eyes with progression, which had a progression rate of 4.2% ± 3.0%.
Conclusions: The rate of VF loss did not differ be- tween patients with NPG and POAG. The rate of dete- rioration was related neither to initial VF status nor to the presence of disc hemorrhages. Linear regression is applicable only in a portion of the patients who have pro- gression of VF loss.
Arch Ophthalmol. 2000;118:481-488
LAUCOMA IS a widespread chronic optic neuropa- thy characterized by ex- cavation of the optic nerve head and typical vi-
sual field (VF) defects; in approximately1-4
initial VF status on the rate of progres- sion. Therefore, a possible relationship be- tween the defect volume at the moment the diagnosis was established and the rate of VF loss with time is of interest. Fur- thermore, it was observed that the pres-
60% to 70% of cases it is accompanied by
ence of DHs increased the hazard rate for
From the Netherlands Ophthalmic Research Institute (Drs Rasker and Hoyng and Mr van den Enden), St Lucas Hospital (Dr Hoyng ), and Glaucoma
Department, Academic Medical Center(Drs Rasker and Hoyng andMr Bakker), Amsterdam, the Netherlands.
elevated intraocular pressure (IOP). De- spite presumed effective IOP-lowering therapy and after a considerable period of IOP at estimated target, deterioration of VFs is known to occur.5 In previous work6 it was observed that patients with normal- pressure glaucoma (NPG) and without disc hemorrhages (DHs) showed deterioration in 3.6% of cases per year. This rate was not different from the proportion of 3.9% of cases per year observed in patients with pri- mary open-angle glaucoma (POAG) with- out DHs in that study.
Not only the proportion of patients with progression, but the rate of the glau- comatous process, ie, the rate of decay of VFs during long-term follow-up, is of in- terest. An investigation of the rate of de-
terioration may answer the question of whether this rate is similar in patients with NPG and POAG. Contradictory findings have been reported7-9 on the influence of
VF progression with factors of 5 and 4 in patients with NPG and POAG, respec- tively.6 The question may arise whether VFs of eyes with DHs deteriorate faster than those of eyes without DHs.
To assess the rate of VF loss, quanti- tative VF analysis must be performed. Vari- ous methods for quantification of VF de- fects have been reported.10-14 A few studies analyzed the rate of progression by means of VF loss found at different ages15,16 retro- spectively, while others used linear regres- sion analysis of consecutive VF tests.7-9,17
The purpose of this study was to in- vestigate the rate of VF loss per year in pa- tients with NPG, POAG, and ocular hy- pertension (OHT) who were prospectively followed up during a mean period of 9 years. The influence of the defect volume at the start of the study and the presence of DHs on the rate of VF loss were also as- sessed. Finally, the rate of VF loss as cal-
At the outpatient clinic of the St Lucas Hospital in Am- sterdam, the Netherlands, 227 patients with glaucoma were enrolled in a long-term study.4,6 The cohort con- sisted of 34 patients with NPG, 68 patients with POAG, and 125 patients with OHT. All patients had newly de- tected disease and were followed up for at least 3 years. Informed consent was obtained from all patients partici- pating in the study.
At the start of the study, visual acuity, refraction, an- terior segment evaluation, and gonioscopy were per- formed, as were funduscopy and binocular examination of the optic disc. The IOP was assessed with an applanation tonometer (Goldmann; Haag-Streit AG, Liebefeld, Switzerland). At the start of the study, in all patients, 4 IOP measurements during daytime were assessed in the ab- sence of medication. Visual field examination was per- formed with computerized perimetry (Peritest; Roden- stock, Munich, Germany). Furthermore, color stereoslides of the optic nerve heads were made.
Every 3 months the patients revisited the outpatient clinic for visual acuity, anterior segment biomicroscopy, IOP measurement, and optic disc examination. In addition, ev- ery year the VFs were screened, diurnal IOP curves were per- formed, and stereoslides of the optic nerve head were made.
Patients were regarded as having NPG or POAG if they had an arcuate scotoma within the central 30° or a nasal step at at least 2 examinations, a glaucomatous optic disc, an open angle, and 4 measurements of IOP during day- time without medication and during the entire study of 22 mm Hg or lower for patients with NPG and exceeding
22 mm Hg without medication for patients with POAG. The optic nerve head was considered abnormal if the vertical cup-disc ratio was 0.7 or greater, if notching of the neural retinal rim area was present, or if bayoneting of retinal vessels entering the optic disc or baring of the circumlin- ear vessels occurred. Subjects with OHT had an average of4 IOP measurements during daytime that exceeded 22 mm Hg, or 1 IOP measurement greater than or equal to25 mm Hg without medication, had open angles, and were without VF defects. Patients with OHT who developed VF defects during the study were referred to as having OHT and were not included in the POAG group.
Patients with NPG received therapy if the IOP ex- ceeded 18 mm Hg, the VF worsened, or glaucomatous change of the optic nerve head occurred. Patients with POAG were treated when diagnosed, and patients with OHT re- ceived therapy when their IOP exceeded 26 mm Hg, if they showed an increasing cup-disc ratio, or when their condi- tion converted to POAG. The presence of a DH was not an indication for starting or changing therapy.
The perimeter used for VF testing screens 206 tar- gets, of which 151 are located within the central 25° of the VF. The VF tests were suprathreshold gradient adapted.18,19
A VF defect was considered significant when a sensitivity reduction of at least 10 dB at a cluster of 3 or more loca- tions occurred as an arcuate scotoma within the central 30° area or as a nasal step. This may seem a crude measure, but it should be noted that the Peritest screens more than twice the number of targets obtained with the Humphrey (Carl Zeiss, Jena, Germany) or Octopus (Interzeag, Zurich, Swit- zerland) perimeter test. The defects found had to be re- producible. A patient’s condition was considered to be pro- gressive when a reproducible change of at least 10 dB at 3
culated from the first to the last field was compared with linear regression of all VF data.
RESULTS
Of 227 patients included in this study, 18 patients with NPG (23 eyes), 27 with POAG (31 eyes), and 8 with OHT (10 eyes) showed deterioration of VF during follow-up. Approximately all patients had newly detected disease and were not taking glaucoma medication at the start of the study. The mean ages, mean initial VF defects in deci- bels (approximates mean deviation) and as a percentage of maximum defect (−1 dB is comparable with 4% loss of total VF), and the mean follow-up period of patients with and without VF deterioration are listed in Table 1. The mean age of patients with OHT without progres- sion (62.2 ± 10.7 years) was significantly lower (P,.04) than that of patients with OHT with progressing VF de- fects (69.5 ± 9.1 years) and that of patients with NPG and POAG, whether they had VF progression or not. The fol- low-up period of approximately 9 years did not differ be- tween the patient groups. There was no difference in mean
initial VF defect between patients with NPG and POAG, being 28.9% ± 26.4% and 23.6% ± 29.2%, respectively. The period between consecutive VF tests was 1.2 ± 0.2 years.
No difference was observed in the percentage of mean defect between the superior and inferior hemifields of eyes
with progression in patients with NPG (34.0% ± 35.3% and 23.9% ± 24.7%, respectively), POAG (24.7% ± 31.8% and 22.6% ± 30.8%, respectively), and OHT (1.6% ± 2.9% and 0.5% ± 1.8%, respectively).
The period from the start of the study until the oc- currence of reproducible VF deterioration was 4.8 ± 2.3 years in patients with NPG, 3.6 ± 2.4 years in patients with POAG, and 7.1 ± 3.4 years in patients with OHT.
Table 2 gives the mean rates of VF loss per year for the whole VF; the rates were 3.7% ± 3.3% in 23 eyes of 18 patients with NPG, 2.5% ± 1.8% in 31 eyes of 27 patients with POAG, and 2.3% ± 1.3% in 10 eyes of 8 pa- tients with OHT. The rates were not different between the glaucoma groups but were significantly different from the rates for the stable eyes. Table 3 indicates that the rate of VF loss between superior and inferior hemifields did not differ within and between the glaucoma groups. The mean rate of VF loss of all eyes with progression was 2.93% per year, which approximates −0.73 dB per year.
The rate of VF loss may have been influenced by a possible learning effect or intertest fluctuation. There- fore, the rate of deterioration was also calculated from the second to the last VF. The rates of VF loss obtained from the second to the last whole VF were 3.3% ± 2.7%,2.9% ± 3.2%, and 2.8% ± 3.2% per year, respectively, for patients with NPG, POAG, and OHT and did not differ from the rates as calculated from the first to the last VFs.
No. of Patients Age, Mean ± SD, y dB %Follow-up, y
or more locations in a cluster or contiguous to an existing defect could be observed. If a VF indicated deterioration, it was repeated after a delay of approximately 4 months. The VFs were evaluated and rated as stable or progressing by 2 independent observers (D.B. and P.F.J.H.) in a masked fashion. Visual field changes not induced by glaucoma were screened for by evaluating changes in visual acuity and the effect of progression of cataracts 2 weeks before the VF de- termination. Defects of the VF induced by spectacles, eye- lid, and a general loss of sensitivity owing to cataract were corrected for. The evening before the VF examination, patients receiving miotics interrupted this therapy.
Within the VFs of the eyes with progression, the follow- ing areas were discerned: in the superior hemifield, the supe- rior central area (within 25° eccentricity) and the superior pe- ripheral area (outside 25° eccentricity), with 70 and 26 targets, respectively; and in the inferior hemifield, the inferior central area (within 25° eccentricity) and the inferior peripheral area (outside 25° eccentricity), with 68 and 29 targets, respectively.
As maximum sensitivity loss per stimulus point was reached at a loss of 24 dB, the maximum sensitivity losses per area were 1680 dB (superior central area), 624 dB (superior peripheral area), 1632 dB (inferior central area), and 696 dB(inferior peripheral area), respectively.12 The blind spot (13 stimulus points) was not taken into account. The VF defects were quantified as a percentage of the maximum sensitivity loss of that area. The formula used for each area was as follows:
n
oxi
Da = i = 1 3 100%n z −24 dB
i = 1
where Da indicates mean VF defect of an area as a percentage of the maximum defect of that area; x, sensitivity loss (in deci- bels) of a stimulus point i; and n, number of stimulus points in an area.
The differences in density and total number of stimu- lus points of the separate areas are equated by this formula. From the Da values of the 4 separate areas, the mean defect as a percentage of the superior hemifield, the inferior hemi- field, and the total VF can be calculated. The rate of VF loss as a percentage per year was obtained by dividing the differ- ence between the first and the last mean VF defect (percent- age) by the years of follow-up. This was done for the total fields and for the superior and inferior hemifields.
To determine the effect of intertest fluctuations and a possible learning effect, the rate of VF deterioration per year was obtained not only from the first to the last but also from the second to the last VF. In addition, on all VFs, linear regression analysis was performed and the results ob- tained were compared with our method of evaluation of the fields with the Wilcoxon matched pairs test and Spear- man rank order correlation.
Target pressure for patients with POAG was 20 mm Hg or less with a reduction in IOP of at least 20%. For patients with NPG, if treated, target pressure was 16 mm Hg, with at least a 20% reduction in IOP. For patients with OHT, if treated, target pressure was 22 mm Hg or less with a reduc- tion in IOP of at least 20%.
Correlations between the rate of VF loss of superior and inferior hemifields were analyzed with the Wilcoxon matched pairs test and the Spearman rank order correla- tion. Further statistical analysis was performed with the un- paired t test and the Mann-Whitney test. Unless indicated otherwise, data are expressed as mean ± SD.
Table 1. Mean Age, Mean Initial Visual Field Status, and Mean Follow-up of 34 Patients With NPG, 68 With POAG, and 125 With OHT*
Visual Field Defect, Mean ± SD
*NPG indicates normal-pressure glaucoma; POAG, primary open-angle glaucoma; and OHT, ocular hypertension.†Unpaired t test; P,.04.
Linear regression analysis was performed on all VFs. The regression was considered significant if P,.05. The re- sults with regression analysis were compared with the re- sults of calculated VF loss from the first to the last field of each eye. These rates did not differ within the patient groups with and without a significant regression coefficient (Table 4) (Wilcoxon matched
pairs test and Spearman rank order correlation). However, the pooled data of eyes with NPG, POAG, and OHT that showed progression and had significant linear regression showed a progression rate
of 4.2% ± 3.0% VF loss per year vs 3.4% ± 2.5% per year as calculated from the first to the last VF, the difference be- ing significant (P,.03). The pooled data of eyes with pro- gression that had a nonsignificant linear regression showed deterioration, with 2.8% ± 2.5% as calculated from the first to the last VF and 2.4% ± 2.6% with linear regression, and did not differ.
Table 5 gives the progression rate (percentage per year) of nonprogressing eyes in patient groups with ei- ther significant or nonsignificant regression coeffi-
Table 2. Rate of VF Loss as Calculated From the First to theLast VF Between Eyes With and Without VF Deterioration*
cients. Of interest is the progression rate of 0.65% per year of 12 eyes with OHT with a significant regression coefficient, which may indicate that these eyes are likely to convert to POAG.
ConditionVF LossPresent
No. ofPatients
VF Loss,Mean ± SD, %/y The progression rate in 24 (38%) of the 64 eyes
with progression in which the rate of progression was signifi-
Table 3. Rate of VF Loss in Superior and Inferior Hemifields of Eyes With Progression of Patients With NPG,POAG, and OHT*
VF Loss, Mean ± SD, %/y
cant with linear regression is plotted against the progres- sion rate obtained from the first to the last VF in indi- vidual eyes in Figure 1. Analysis with Spearman rank order correlation show a high correlation between the 2 rates (r = 0.86, P,.001). Also, in 40 eyes with progres- sion (62%) without a significant linear regression, the 2 rates were highly correlated (r = 0.82 P,.001) (Figure 2).
In 40 eyes without progression, the regression coef- ficient was not significant. This was because of a Schub-type course of the glaucomatous process (12 eyes), too small a number of VFs to perform linear regression analysis (16 eyes), and too much intertest fluctuation (12 eyes) (Table 6).
Table 7 shows that, among the patients with NPG, deterioration in 7 eyes was located only in superior hemi- fields, in 6 eyes in inferior hemifields, and in 10 eyes (8 patients) (43%) in both hemifields. In all cases in which
NPG(23 Eyes)
POAG(31 Eyes)
OHT(10 Eyes) both hemifields deteriorated, this occurred at a similar
point in time. In the 11 of 31 eyes with POAG that hadSuperior hemifield 3.4 ± 3.9 2.3 ± 2.0 2.3 ± 1.5Inferior hemifield 4.0 ± 4.0 2.8 ± 3.2 2.2 ± 2.1
progression, deterioration occurred in superior hemi- fields only and in 8 eyes in inferior hemifields only. Twelve eyes (39%) of 11 patients had simultaneous deteriora- tion in the superior and inferior hemifields. In patients
Table 4. Rate of VF Loss as Calculated From the First to the Last VF and by Regression Analysis in Deteriorating EyesHaving Significant and Nonsignificant Regression Coefficients*
Regression Coefficient
Rate of VF Loss, Mean ± SD, %/y
Spearman RankOrder Correlation
(Linear Regression Analysis) First to Last VF Linear Regression Analysis r PNPG (23 eyes) Significant (n = 8) 4.72 ± 3.77 5.24 ± 3.71 0.97 ,.001
Table 5. Rate of VF Loss as Calculated From the First to the Last VF and by Regression Analysis in Nondeteriorating EyesHaving Significant and Nonsignificant Regression Coefficients*
Regression Coefficient(Linear Regression
Rate of VF Loss, Mean ± SD, %/y
Spearman RankOrder Correlation
Analysis)† First to Last VF Linear Regression Analysis r P
*VF indicates visual field; NPG, normal-pressure glaucoma; POAG, primary open-angle glaucoma; OHT, ocular hypertension; and ellipses, too small a number to perform a valid regression.
†Eyes not accounted for in this column are those that were stable (9 in the NPG group, 52 in the POAG group, and 61 in the OHT group).
11
Rate
of V
F Pr
ogre
ssio
n F
rom
Firs
t to
Last
VF,
%
Rate
of V
F Pr
ogre
ssio
n F
rom
Firs
t to
Last
VF,
%
VF L
oss
in S
uper
ior H
emifi
eld,
%
/ y
Table 6. Eyes With VF Loss With a Nonsignificant10 Regression Coefficient*9
8 Reason for Nonsignificant7 Regression Coefficient, No.6
*VF indicates visual field; NPG, normal-pressure glaucoma; POAG, primary open-angle glaucoma; OHT, ocular hypertension; and n, number of
Rate of VF Progression With Linear Regression, %
Figure 1. Scattergram of 24 deteriorating eyes in which the rate of progression was significant with linear regression and is plotted against the progression rate obtained from the first to the last visual field (VF). Spearman rank order correlation, r = 0.86, P,.001.
eyes with VF deterioration.
Table 7. Deterioration of One or Both Hemifields of EyesWith Progression of Patients With NPG, POAG, and OHT*
14
No. ofOne Hemifield, No.
Both Hemifields, No.
With an12 Eyes Superior Inferior Concurrently Interval
0 2 4 6 8 10 12Rate of VF Progression With Linear Regression, %
10Figure 2. Scattergram of 40 deteriorating eyes with a nonsignificant linearregression. Abscissa shows the rate of visual field (VF) progression with linear regression; ordinate, the rate of VF loss as calculated from the first to the last VF (r = 0.82, P,.001).
5
with OHT, 3 of 10 eyes deteriorated only in superior hemi- fields, 1 eye in the inferior hemifield only, and 6 eyes(60%) (in 4 patients) had deterioration in both hemi- 0
fields, of which 4 eyes showed concurrent deterioration 0 5
10 15
of the superior and inferior hemifields. The other 2 eyes had a latency period between deterioration of the supe- rior and inferior hemifields of 3 and 9 years.
Ten eyes with NPG that had progression showed de- terioration in both hemifields. The rate of deterioration was correlated between superior and inferior hemifields (Spearman rank order correlation, rs = 0.67; P = .04; Figure 3). In eyes with deterioration in both hemi- fields in patients with POAG, the rate of VF loss did not correlate between superior and inferior hemifields (rs = −0.01, P..99; Figure 4). The proportion of eyes deteriorating in single or in both hemifields was equally divided in eyes with and without DHs of patients with NPG as well as those with POAG.
We investigated whether the rate of VF loss was re- lated to the initial VF status. Figure 5 shows the rate of VF loss in 46 superior and 41 inferior hemifields dete-
riorating at a rate of more than 0.5% per year. In these hemifields, no correlation was observed between VF loss at baseline and the rate of loss per year (Spearman rank
11VF Loss in Inferior Hemifield, %/ y
Figure 3. Rate of visual field (VF) loss of superior (ordinate) and inferior (abscissa) hemifields of 10 eyes of 8 patients with normal-pressure glaucoma progressing in both hemifields (rs = 0.67, P = .04).
order correlation, rs = 0.03). Furthermore, Figure 5 shows the rate of VF loss compared between eyes with smaller and larger initial defects in hemifields. The median ini- tial defect of hemifields was 5.4%. Forty-three hemi- fields had smaller and 44 had larger defects than 5.4%. The rate of VF loss was 3.8% ± 2.6% per year in eyes with progressive hemifields with initial VF defects smaller than5.4% and 3.7% ± 3.1% per year in eyes with a median de- fect larger than 5.4%, and these rates did not differ.
In 27 eyes with progressing VF loss of patients with NPG, POAG, or OHT with DHs, deterioration occurred at a rate of 2.7% ± 2.9% per year, which was not differ- ent from the rate of VF loss of eyes of patients without DHs who had no progression, which was 3.1% ± 2.1% per year.
15
Det
erio
ratio
n, %
/ y
VF L
oss
in S
uper
ior H
emifi
eld,
%
/ y
Table 8. Rate of VF Loss in Patients With and Without DHs*
Figure 4. Rate of visual field (VF) loss of superior (ordinate) and inferior (abscissa) hemifields of 12 eyes of 11 patients with primary open-angle glaucoma progressing in both hemifields (rs = −0.01, P..99).
15
10
5
0
with NPG, POAG, and OHT. The rate of VF loss was simi-lar for deteriorating eyes of all 3 patient groups, being approximately 3% per year, or a sensitivity loss of −0.7 dB of mean deviation per year. Hence, patients with NPG experience VF deterioration at a rate similar to that of patients with POAG.
Several reports have dealt with the rate of VF loss.7-10,15-17 However, a comparison of results may be hampered by differences in perimeters, methods of quantifying VFs, follow-up periods, and the fact that some studies are cross-sectional. The method used for obtaining a single index for the VF defect as a percent- age resembles the mean deviation of Flammer et al11
and Greve and Bakker’s defect volume.12 Although, dur- ing follow-up, episodes of progression may be followed by stabilization,8 we calculated the rate of VF loss as a percentage per year from the first and last VFs to have an impression of the progression rate during the whole
0 10 20 30 40 50 60 70 80 90Initial Defect, %
100 period the patient was followed up. It should be taken into consideration that the rate of deterioration given in
Figure 5. Scattergram showing initial visual field defect (abscissa) and rateof deterioration of hemifields (ordinate) of 87 progressive hemifields in patients with normal-pressure glaucoma, primary open-angle glaucoma, and ocular hypertension (hemifields with a rate of deterioration of 0.5% or more per year only).
Superior and inferior hemifields deteriorated at a simi- lar rate in patients with and without DHs (Table 8).
During the study, in addition to medical treatment, laser trabeculoplasty was performed in 6 eyes of pa- tients with NPG, 32 eyes of patients with POAG, and 19 eyes of patients with OHT. Argon laser trabeculoplasty was performed in patients with OHT when, despite maxi- mal conservative treatment, the IOP exceeded 26 mm Hg in the absence of a pathologic excavated optic nerve head, or exceeded 22 mm Hg in the presence of a suspect ex- cavated optic nerve head (vertical cup-disc ratio, .0.7), or in the case of OHT converting to POAG. Trabeculec- tomy was performed in 6 eyes of patients with NPG, 31 eyes of patients with POAG, and 6 eyes of patients with OHT converting to POAG (3 eyes) or IOPs greater than30 mm Hg despite maximum therapy and a vertical cup- disc ratio greater than 0.8. It should be noted that, throughout the study, patients with OHT converting to POAG were included in the OHT group.
COMMENT
In this prospective study, the rate of VF loss per year dur- ing a mean period of 9 years was evaluated in patients
15this study may be underestimated, since in eyes with progression the glaucomatous process may have been slowed down or stabilized by additional medical treat- ment or surgical procedures.
In a cross-sectional study, Jay and Murdoch15 esti- mated the interval between early field loss and end- stage glaucoma in patients with optimum treatment to be 38 years. In our prospective long-term follow-up study, only patients with glaucoma whose VF was deteriorat- ing had an average rate of VF loss of about 30% of total VF per decade. This indicates that eyes with early glau- coma and under glaucoma treatment that show progres- sion may reach end-stage glaucoma in about 33 years.
It should be noted that, in our study, only approxi- mately one third of patients with NPG and POAG had progression.6
The estimation of progression was based on clus- ters of deteriorating points, the deterioration being con- firmed by an additional VF examination approximately4 months later. Visual field loss was expressed as a per- centage of total VF loss. Our mean progression rate of3% per year (−0.7 dB/year mean deviation) in eyes with progression in all 3 glaucoma groups together is in agree- ment with those reported in other studies,7,9,20 ranging between −0.96 and −1.39 dB of loss per year of mean de- viation. These data were obtained from long-term pro- spective studies and assessed with linear regression.
Processing of all our VF data with linear regression revealed that only 37.5% of all eyes with progression had
significant progression. It has been stated that linear re- gression is a simple method to estimate trends in longi- tudinal data such as progressive slopes of mean devia- tions of VFs.7 The use of linear regression is dependent on intertest variability, number of VFs available, and of the decay of the glaucomatous process.7 The assump- tion has to be made that the glaucomatous VF loss is gradual and linear. However, in several studies, the pro- gression in glaucoma has been reported to be epi- sodic.21,22 In our study, in 62.5% of the eyes with pro- gression, VF loss was not significant with linear regression. This was due partly to the episodic nature of the glau- comatous process, partly to the large intertest fluctua- tion, and partly to too small a number of VF tests (,7).
These observations question the use of linear re- gression as the ultimate test to analyze whether signifi- cant VF loss exists. Moreover, it is debatable whether data from psychophysical tests such as VF examinations in the pathologic glaucomatous process fit in a statistical analysis with linear regression. On the other hand, Spear- man rank order correlation tests between the progres- sion rates as calculated by our method and as obtained by linear regression analysis show a high correlation, re- gardless of whether the regression slopes were signifi- cant. From this we conclude that regression analysis of the global VF index mean deviation is a useful statistical tool, but it should not be decisive regardless of whether a patient with glaucoma has progression. In addition, lin- ear regression analysis of data from nonprogressive OHT showed 12 eyes with a significant linear regression co- efficient and a progression rate of 0.7% ± 0.5% per year. Especially in this group of patients with long-term follow- up, linear regression may be useful to detect early trends indicating imminent VF loss.
It was observed earlier8 that the rate at which indi- vidual patients experience deterioration is variable. Also, in this study, a large range of velocities of VF loss within all 3 glaucoma groups was observed. The question arises whether this might be caused by differences in initial VF status. The large SDs of the mean initial VF defects re- flect the diversity of glaucomatous damage of patients vis- iting an ophthalmologist for the first time. Mikelberg and associates8 stated that a greater rate of further VF loss oc- curred when more advanced VF loss existed at the time the diagnosis was established. In contrast, O’Brien and associates9 found a greater rate of VF loss at earlier stages of the disease. In our study, we observed that the rate of VF loss was not related to the initial VF defect, which is in accordance with the observation of Smith and associ- ates.7 Therefore, in our opinion, it is not possible to pre- dict from the initial VF status which patients will have deterioration in time6,7,20 or the rate at which deteriora- tion will occur in individual patients.
Since DHs are known to increase the hazard rate for VF deterioration in glaucoma,6 it would make sense to presume that VF losses in patients with DHs might progress at a faster rate. However, the rates of VF loss per year were 2.7% ± 2.9% and 3.1% ± 2.1% in patients
with and without DHs, respectively, and were not dif- ferent. This supports earlier observations6,23-26 that DHs are not likely to be the cause of VF deterioration but rather are a sign of the ongoing glaucomatous process.
Heijl and Bengtsson27 reported a substantial influ- ence of learning in patients who underwent repeated au- tomated VF examinations, while this was not observed by Werner et al28 and Smith et al.7 Learning effects are not likely to have influenced the results of our study, as there was no difference between the defect changes per year calculated from the first to the last and from the sec- ond to the last VFs. This might be because the 1-year in- tervals between subsequent VF tests are too long to in- duce a significant learning effect, in contrast to the 1-week intervals used by Heijl and Bengtsson.27
In earlier studies,21,22,29 it was reported that one or both hemifields are at risk for deterioration during a certain period. We observed that 56% of eyes with pro- gression in patients with NPG and 61% of eyes with progression in patients with POAG had VF loss in one hemifield only during the entire follow-up period. In eyes with deterioration in both hemifields, a different pat- tern of deterioration rate was present between patients with NPG and POAG. Although in both groups deterio- ration of superior and inferior hemifields occurred con- currently, there was no correlation of rate of VF loss between both hemifields in patients with POAG. In con- trast, in eyes of patients with NPG in which both hemi- fields had progression, the velocities of VF loss in the hemifields were correlated (rs = 0.67; P = .04). In con- clusion, despite individual differences, the eyes with NPG that show progression do not deteriorate faster than those with POAG or OHT converting to POAG. Although eyes with DHs are more at risk for progression than eyes with- out DHs,6 the rate of the decay of VF also did not differ between eyes with and without DHs. No correlation was observed between initial VF status and rate of VF dete- rioration. These results indicate a final common path- way in glaucoma whether patients suffer from POAG, NPG, or OHT and whether they do or do not have DHs.
Accepted for publication December 10, 1999.This study was supported by grant 28-2326 from the
Praeventiefonds, The Hague, the Netherlands.Presented in part at the Association for Research in
Vi- sion and Ophthalmology Annual Meeting, Fort Lauder- dale, Fla, May 9, 1999 (ARVO abstract 368).
Reprints: Philip F. J. Hoyng, MD, PhD, The Nether- lands Ophthalmic Research Institute, PO Box 12141, 1100AC Amsterdam ZO, the Netherlands (e-mail: [email protected]).
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