ArticlePDF Available

Is poor life expectancy a predictive factor in the progression of primary open angle glaucoma?

Authors:

Abstract and Figures

To investigate the disease progression and final visual outcome of glaucoma patients with poor life expectancy, compared to matched patients with a longer life expectancy. Visual fields at diagnosis and at the last ophthalmic appointment before death were analysed for glaucoma patients referred between 1991 and 1995, and deceased before the end of 2001. These patients were matched to the patients living beyond 2001. Functional vision was also assessed, and classified as better than the NHS partial sighted criteria. A total of 61 deceased patients were identified, resulting in 40 matched pairs. In all, 6.5% of the patients with poor life expectancy progressed from functional vision to beyond partial sighted criteria, and none of the matched patients progressed to this extent. At final assessment an association between poor life expectancy and progression beyond functional vision was found existing (P = 0.02), with a lesser association at diagnosis (P = 0.06). Visual field scores of the matched pairs who had test results available for both initial and final assessment (n = 23 pairs) showed no statistically significant difference between the two groups at diagnosis (P = 0.52); However, a significant difference at final the assessment did exist (P = 0.042). No difference between the initial (off medication) intraocular pressures (IOPs) was found (P = 0.82). At the final assessment a significant difference existed (P = 0.025), with the surviving group having a higher final mean pressure (15.9 mmHg, SD 2.8, vs 18.3 mmHg, SD 4.9). Patients with poor life expectancy progressed more than the matched surviving patients, when measured from an initially similar position, despite better IOP control.
Content may be subject to copyright.
Is poor life
expectancy
a predictive factor
in the progression
of primary open
angle glaucoma?
CL Tattersall, SA Vernon and A Negi
Abstract
Aim To investigate the disease progression
and final visual outcome of glaucoma patients
with poor life expectancy, compared to
matched patients with a longer life expectancy.
Method Visual fields at diagnosis and at the
last ophthalmic appointment before death
were analysed for glaucoma patients referred
between 1991 and 1995, and deceased before
the end of 2001. These patients were matched
to the patients living beyond 2001. Functional
vision was also assessed, and classified as
better than the NHS partial sighted criteria.
Results A total of 61 deceased patients were
identified, resulting in 40 matched pairs. In all,
6.5% of the patients with poor life expectancy
progressed from functional vision to beyond
partial sighted criteria, and none of the
matched patients progressed to this extent. At
final assessment an association between poor
life expectancy and progression beyond
functional vision was found existing (P ¼ 0.02),
with a lesser association at diagnosis (P ¼ 0.06).
Visual field scores of the matched pairs who
had test results available for both initial and
final assessment (n ¼ 23 pairs) showed no
statistically significant difference between the
two groups at diagnosis (P ¼ 0.52); However, a
significant difference at final the assessment
did exist (P ¼ 0.042). No difference between
the initial (off medication) intraocular
pressures (IOPs) was found (P ¼ 0.82). At the
final assessment a significant difference
existed (P ¼ 0.025), with the surviving group
having a higher final mean pressure
(15.9 mmHg, SD 2.8, vs 18.3 mmHg, SD 4.9).
Conclusion Patients with poor life
expectancy progressed more than the matched
surviving patients, when measured from an
initially similar position, despite better IOP
control.
Eye (2005) 19, 387–391. doi:10.1038/sj.eye.6701514
Published online 13 August 2004
Keywords: glaucoma; disease progression; life
expectancy; visual field; functional vision
Introduction
Chronic glaucoma is a progressive disease. It
has been suggested that in untreated glaucoma,
blindness will occur in an average of 14.4 years
with intraocular pressures (IOPs) between 21
and 25 mmHg, and 6.5 years for pressures
between 25 and 30 mmHg.
1
Even on treatment,
an estimated 9% of the patients will become
bilaterally blind after 20 years of treatment.
2
Some studies have considered glaucoma and its
relationship to shortened survival,
3–7
Others
have considered the effects of systemic disease
on glaucomatous progression.
8,9
These studies,
however, do not consider poor life expectancy
as a factor in glaucomatous progression.
Patients with poor life expectancy tend to be
excluded from many studies, due to protocol
criteria or social/travel problems. To our
knowledge, this group of patients has not been
studied in any detail regarding their final visual
outcome or progression of the disease while
under hospital care. With functional vision for
life being the ultimate aim for all glaucoma
patients under hospital care, this patient group
needs to be considered. This study is a case–
control study, matching patients to others with a
longer life expectancy.
Method
Newly diagnosed patients, referred to a
glaucoma clinic from the community between
January 1991 and December 1995, in a large
Received: 10 December
2003
Accepted: 9 April 2004
Published online: 13 August
2004
Department of
Ophthalmology
Queens Medical Centre
Nottingham, UK
Correspondence:
CL Tattersall
Eye out-patient department
Department of
Ophthalmology
Queens Medical Centre
Nottingham NG7 2UH, UK
Tel: þ 44 115 9249924
ex 35651/43200
Fax: þ 44 1159709749
E-mail: stephen.vernon@
mail.qmcuh-tr.trent.nhs.uk
Eye (2005) 19, 387–391
& 2005 Nature Publishing Group All rights reserved 0950-222X/05 $30.00
www.nature.com/eye
CLINICAL STUDY
teaching hospital were reviewed as to their life status at
the end of 2001. Deceased patients were identified by
using the hospital’s computerised ‘Patient
Administration System’. For patients whose status was
unclear (no hospital visit within 1 year, but not identified
as deceased), true status was determined by direct
contact with their general practitioner. Patients known to
be deceased were then matched for year of diagnosis and
age at diagnosis (74 years) to patients alive at the end of
2001. The live patients were also required to have
survived at least a year longer than the deceased
matched patient. Deceased patients (poor life
expectancy) will be known as group 1, with their matches
being group 2. Comparisons were then made regarding
the initial and final visual status, where the ‘final’ visual
status of group 2 patients were considered as the nearest
visual field test within a year of group 1 patients’ last
appointment.
Visual fields and assessment of functional vision
formed the basis of the study. Visual fields were only
used if they were dated within a year of diagnosis, or
within a year of group 1 patient’s final ophthalmic
appointment. Owing to the variety of visual fields used,
(Friedmann, Goldmann, Humphrey 24-2, Humphrey 76
point) all were analysed using the staging system as
described by Aulhorn et al
10
(Table 1).
The visual fields were scored independently by two
observers, a research nurse (CT), and a senior trainee
ophthalmologist (AN), who was masked to the life status
of the patients. All scores for visual fields were in
agreement (Kappa score: 1).
The criteria for functional vision in this study was
based on the NHS guidelines for partial sight
registration. Vision considered as being incompatible
with daily functioning was therefore based on a visual
acuity of 6/24 or less, with moderate contraction of their
visual field, or a visual acuity of 6/18 or better with a
gross visual field defect in the patient’s better eye. In
assessing the initial and final visual field scores, only the
patient’s better eye was used; this is because functional
vision requires only one eye, and the emphasis of care for
an individual patient may be to keep functional vision in
one eye, while keeping the other comfortable. Using a
random eye, or a mean score would therefore wrongly
bias the results. The initial best eye was therefore not
necessarily the best eye at the final assessment. The
majority of statistical analysis, including visual field
analysis, was conducted using the Wilcoxon signed rank
test for matched pairs. The w
2
test was also employed
when considering functional vision.
Results
In all, 123 patients were identified as deceased. Of these
78 were diagnosed with a classification of glaucoma or
ocular hypertension, with one patient having rubeotic
glaucoma in one eye and CSG in the other (Table 2).
Rubeotic and angle closure glaucoma patients were
excluded from the study, due to the lack of data for
analysis, and the variation in the underlying cause.
Ocular hypertensive patients were also excluded.
Pseudoexfoliative glaucoma was considered within the
analysis. No patient with pigmentary glaucoma were
identified. Matching was made without the knowledge of
visual or glaucomatous status. Owing to the study
criteria of matching patients by age and year of
diagnosis, only 40 of the remaining 61 patients could be
matched to surviving patients, and made up the study
cohort. The mean age of the deceased patients at
diagnosis was 74.7 years (95% confidence interval 72.7–
76.7). For surviving patients, it was 74.3 years (95%
confidence interval 72.4–76.2). The age range of deceased
and surviving patients at diagnosis is shown in Figure 1.
Deceased patients spent an average of 4.2 years under
hospital care (95% confidence interval 3.5–4.9).
IOP
IOP was assessed at presentation in order to identify any
disparity between the group 1 and 2’s level of glaucoma
off treatment. The mean initial IOP of group 1 was
25.5 mmHg (SD 9), with group 2’s being 24.9 mmHg
(SD 6.6). The matched mean initial IOPs were compared
using the Wilcoxon signed rank test. No statistically
Table 1 Aulhorn visual field staging system
Stage 1 Exclusively relative defects
Stage 2 Spot-like or arcuate absolute defects, still without
connection to blind spot
Stage 3 Arcuate absolute defects connected to blind spot, with or
without a nasal break through into the periphery
Stage 4 Extensive ring-or half-ring-shaped defects, keeping
central island of sensitivity
Stage 5 Central island collapsed, and only the peripheral
temporal visual field is kept
Table 2 Classification of glaucoma in deceased cohort
n (Patients) n (Eyes)
Chronic simple (CSG) 48 93
Normal tension (NTG) 10 20
Pseudoexfoliative 3 6
Rubeotic 2 2
Acute angle closure 2 2
Ocular hypertension 13 26
Total 79 151
Life expectancy in chronic glaucoma
CL Tattersall et al
388
Eye
significant difference was found (P ¼ 0.8). There was,
however, a significant difference at final assessment
(P ¼ 0.025), where group 1’s mean pressure was
15.9 mmHg (SD 2.8), and group 2’s was 18.3 mmHg
(SD 4.9). All IOPs were recorded in the morning.
Progression-functional vision
No patient from group 2 progressed from functional
vision at diagnosis to fulfilling the partially sighted
criteria at the final assessment. However, 6.5% (n ¼ 2) of
group 1 patients, with functional vision at diagnosis
progressed beyond functional vision. The w
2
test was
applied to the 40 matched pairs, in order to identify any
association between life expectancy and functional
vision. This was conducted at diagnosis (P ¼ 0.06), and
final assessment (P ¼ 0.02). A greater association
therefore, existed at the final assessment.
Progression-visual fields
Using the Wilcoxon signed rank test, the matched visual
field scores of patient’s better eyes were examined at
diagnosis, and at the final assessment, in order to identify
any difference between the progression of the disease in
the two groups. Only matched pairs, where both the
patients could be assessed at initial and final assessments
were used, this resulted in 23 matched pairs. The mean
initial visual field scores of groups 1 and 2, respectively
was 1.13 (SD 1.1) and 1.13 (SD 0.5) with a significance
using the Wilcoxon signed rank test of P ¼ 0.52. At the
final assessment the mean scores were 1.4 (SD 0.9) and
0.9 (SD 0.6) with a significance of P ¼ 0.042. In order to
ensure that a valid comparison of matched patients was
used, the time lapse between first and last visual field
tests was assessed. The median time for groups 1 and 2
respectively was 47 months and 43 months. The
Wilcoxon signed rank test, showed no significant
difference between the two groups (P ¼ 0.2).Visual field
scores for deceased patients who were not matched but
had available visual fields, were compared to the scores
of the deceased matched patients. This was carried out to
ensure that no bias was present in the analysis of the
matched progression. Comparison was made at initial
assessment (mean 1, SD 0.93) P ¼ 0.2, and at final
assessment (mean 1.3, SD 0.95) P ¼ 0.49. There was
therefore no significant difference between these groups.
The Wilcoxon signed rank test was used to identify any
significant difference between the reliability indices of
the matched pairs’ final visual fields; this was conducted
to ensure that the comparisons were valid. When
considering fixation losses (P ¼ 0.32), false-positive errors
(P ¼ 0.22), and false-negative errors (P ¼ 0.84), Of the 23
pairs, seven could not be quantitatively assessed for
reliability, due to the use of Friedmann visual fields;
however, none of the deceased group was classed as
‘poor by the operating technician. There was therefore
no significant difference between the reliability indices of
the two groups.
Possible variables
A number of variables may have had an influence on the
results of the progression analysis. Data on these
variables were therefore assessed, which included
surgery (Table 3), medication (Table 4), and gender
(Table 5).
Discussion
Of the studies that have examined glaucoma and its
relationship to shortened survival,
3–7
the majority
showed some association.
3,5–7
One study
5
showed the
lowest survival rate to be among males using
acetazolamide. In our study, of the 23 pairs of patients
who could be considered for visual field progression, the
male/female mix in each group was identical (Table 5).
In examining the use of medication at the final
assessment, no patient in groups 1 or 2 was using
acetazolamide, and both the groups were using a mean
of 1.25 topical medications each day. The finding of
increased usage of topical beta blockers in the survivors
Figure 1 Age range of patients at diagnosis.
Table 3 Ophthalmic surgery in matched pairs
Cataract
surgery
Glaucoma
surgery
General
anaesthetic
Local
anaesthetic
Deceased
(group 1)
912312
Surviving
(group 2)
59112
Wilcoxon test
(P)
0.3 0.58 0.37 1
Life expectancy in chronic glaucoma
CL Tattersall et al
389
Eye
is interesting (36 vs 54%, P ¼ 0.048). No morbidity from
the use of such agents was reported in the ‘ocular
hypertensive treatment study’,
11
but these drugs do have
recognised systemic effects, particularly in the elderly.
12
A possible reason for the increased use of beta blockers in
the surviving group (group 2) could have resulted from
the reluctance by ophthalmologists to prescribe such
agents for patients in group 1, possibly due to medical
conditions, such as asthma, which were not recorded in
the medical notes. These unrecorded medical conditions
could have contributed to the shortened survival, or
indeed to the progression of the disease, as vascular and
respiratory factors have been linked to glaucoma.
8,13–16
This reluctance to prescribe beta blockers could explain
an increased use of pilocarpine in those who did not
survive. A possible consequence of the increased use of
pilocarpine could have resulted in the worsening of the
visual field scores seen in group 1, due to the adverse
effect of the drug on the patients’ visual fields,
17–19
or the
poorer intraocular lowering effect of pilocarpine than
beta blockers.
20,21
No other classification of eye
medication was significant in its use between groups
(Table 4). The w
2
-test was used in order to investigate the
hypothesis that the use of pilocarpine is associated with
the visual field progression in group 1. There was,
however, no such association in our study (P ¼ 0.6).
Repeating this study, using a baseline in the mid- to late
1990s after the introduction of new topical medications,
such as prostaglandin analogues, and the subsequent
reduction in the use of pilocarpine, would therefore be of
interest. Some studies have considered shortened
survival among other ophthalmic conditions. In
researching patients with cataracts, it has been shown
that cataracts can be linked to the shortened
survival.
4,22,23
One study
24
showed a link between
cataract surgery and shortened survival in middle-aged
patients. It is unclear, however, whether this was due to
the cataract or the surgery. In our study, there was no
significant difference between the rate of cataract surgery
(including phacotrabeculectomy) P ¼ 0.3, glaucoma
surgery (including phacotrabeculectomy) P ¼ 0.6, or type
of anaesthetic (P ¼ 0.37 for general anaesthesia) between
the groups (Table 3).
Matched IOPs only show a difference at the final
assessment (initial P ¼ 0.8, final P ¼ 0.025), with group 1
having lower pressures. Lowering of pressures in these
patients is therefore attainable, but with a higher rate of
progression also in this group, it could be suggested that
factors other than the pressure are greatly influencing the
outcome, within this group.
The statistical tests used show a greater progression of
glaucoma in patients with a poor life expectancy, but a
similar presenting stage. These results may be explained
by considering glaucomatous progression as being on a
progressive downward slope. Patients with a poor life
expectancy (group 1), may be on a steeper gradient
throughout the course of their disease, than the surviving
matched patients (group 2). These slopes may therefore
be diverging throughout time (Figure 2). Assessments at
point (A) will give an insignificant difference, whereas at
point (B) a significant difference is evident. Data for this
study were taken retrospectively from the medical notes,
and is therefore limited to information, which was
deemed necessary to record at the time of attendance.
The numbers used in this study are small, with the
possibility of results being biased by very few patients in
group 1 having unstable glaucoma. With the cohort being
the maximum that the protocol would allow, much larger
multicentred, case–control studies are required, with in-
depth analysis of the patients’ medical condition,
Table 4 Ophthalmic medication in matched pairs
Latanoprost Beta-blocker Miotic Alphagan CAI’s Total
Deceased (group 1) 9 17 11 2 10 49
Surviving (group 2) 11 27 3 0 8 49
Wilcoxon test(P) 0.66 0.048 0.058 1 0.67
Table 5 Gender in matched pairs
Female Male Total
Deceased (group 1) 10 13 23
Surviving (group 2) 10 13 23
Figure 2 Model of glaucomatous progression.
Life expectancy in chronic glaucoma
CL Tattersall et al
390
Eye
systemic medications, cause of death, medication
compliance, social history, and ethnic origin. Further
research into the systemic conditions and their impact on
glaucomatous progression is needed. A possibility could
involve the circulatory system of the patients condition,
as it is not only the largest cause of death in the UK,
25
but
has also been proven to have a role in glaucoma.
8,13,14
Such studies will be made easier to perform with the use
of electronic data management systems, such as
Eyetrack
26
in which health-care professionals are
prompted to record data on general health. If larger
studies were to confirm our results, the impact may well
be to shift practice towards a more holistic, systemic
focus of glaucoma management.
27
With functional vision for life being the ultimate aim in
ophthalmology, it would be useful to assess the patients’
quality of life, possibly by a social assessment, or direct
questioning, rather than making a decision based on
previously considered disease progression and mortality.
This case–control study has shown a link between the
worsening of glaucoma and reduced survival. It is
unclear, however, whether glaucomatous progression is a
cause of, a result of, or a marker for reduced life
expectancy.
References
1 Jay J, Murdoch J. The rate of visual field loss in untreated
primary open angle glaucoma. Br J Ophthalmol 1993; 77:
176–178.
2 Hattenhauer M, Johnson D, Ing H, Herman D, Hodge D,
Butterfield L et al. The probability of blindness from open-
angle glaucoma. Ophthalmology 1998; 105: 2099–2104.
3 Hiller R, Podgor M, Sperduto R, Wilson P, Chew E,
D’Agostino R. High intraocular pressure and survival: the
Framingham studies. Am J Ophthalmol 1999; 128: 440–445.
4 Klein R, Klein B, Moss S. Age related eye disease and
survivalFthe Beaver Dam Eye Study. Arch Ophthalmol 1995;
113: 333–339.
5 Egge K, Zahl P. Survival of glaucoma patients. Acta
Ophthalmol Scand 1983; 77: 397–401.
6 Thorburn W, Lindblom B. Survival time among patients
with glaucomatous visual field defects. Acta Ophthalmol
1983; 61: 728–731.
7 Bengtsson B. Survival of elderly ophthalmic out-patients.
Acta Ophthalmol 1984; 62: 725–730.
8 Graham S, Drance S. Nocturnal hypotension: role in
glaucomatous progression. Surv Ophthalmol 1999; 43:
S10–S16.
9 Bonomi L, Marchini G, Marraffa M, Bernardi P, Morbio R,
Varotto A. Vascular risk factors for primary open angle
glaucoma. The Egna–Neumarkt Study. Ophthalmology 1999;
107: 1287–1293.
10 Aulhorn E, Karmeyer H. Frequency distribution in early
glaucomatous visual field defects. Doc Ophthalmol Proc
Series 1977; 1: 75–83.
11 Kass M, Heuer D, Higginbotham E, Johnson C, Keltner J,
Miller J et al. The ocular hypertension treatment study. Arch
Ophthalmol 2002; 120: 701–713.
12 Diggory P, Heyworth G, Chau G, Mckenzie S, Sharma A,
Luke I. Improved lung function tests on changing from
topical timolol: non-selective beta-blockade impairs lung
function tests in elderly patients. Eye 1993; 7: 661–663.
13 Flammer J, Orgul S, Costa V, Orzalesi N, Krieglstein G,
Serra L et al. The impact of ocular blood flow in glaucoma.
Prog Retinal Eye Res 2002; 21: 359–393.
14 Flammer J, Haefliger I, Orgul S, Resink T. Vascular
dysregulation: a principle risk factor for glaucomatous
damage? J Glaucoma 1999; 8: 212–219.
15 Mojon D, Hess C, Goldblum D, Bochnke M, Koerner F,
Gugger M et al. Normal tension glaucoma is associated
with sleep apnea syndrome. Ophthalmologica 2002; 216:
180–184.
16 Marcus D, Costarides A, Gokhale P, Papastergiou G,
Miller J, Johnson P et al. Sleep disorders: a risk factor
for normal tension glaucoma? J Glaucoma 2001; 10:
177–183.
17 Edgar D, Crabb D, Rudnicka A, Lawrenson J, Gutterige N,
O’Brien C et al. Effects of dipivefrin and pilocarpine on
pupil diameter, automated perimetry and LogMAR acuity.
Graefes Arch Clin Exp Ophthalmol 1999; 237: 117–124.
18 Webster A, Luff A, Canning C, Elkington A. The effect of
pilocarpine on the glaucomatous visual field. Br J
Ophthalmology 1993; 77: 721–725.
19 Vogel R, Crick R, Mills K, Reynolds P, Sass W,
Clineschmidt C et al. Effect of timolol versus pilocarpine on
visual field progression in patients with primary open angle
glaucoma. Ophthalmology 1992; 99: 1505–1511.
20 Zadok D, Geyer O, Zadok J, Lazar M, Krakowski D, Nemet
P. Combined timolol and pilocarpine vs pilocarpine alone
and timolol alone in the treatment of glaucoma. Am J
Ophthalmology 1994; 117: 728–731.
21 Nyman K. Intraocular pressure reduction with topically
administered pilocarpine, timolol and betaxolol in
normal tension glaucoma. Acta Ophthalmol 1993; 71:
686–690.
22 Wang J, Mitchell P, Simpson J, Cumming R, Smith W. Visual
impairment, age-related cataract, and mortality. Arch
Ophthalmol 2001; 119: 1186–1190.
23 West S, Munoz B, Istre J, Rubin G, Friedman M, Fried L
et al. Mixed lens opacities and subsequent mortality. Arch
Ophthalmol 2000; 118: 393–397.
24 McKibbin M, Mohammed M, James T, Atkinson P. Short-
term mortality among middle-aged cataract surgery
patients. Eye 2001; 15: 209–212.
25 National Statistics. Mortality statisticsFgeneral. The
Stationary Office: London, 1999.
26 Vernon SA. Electronic patient management systems in
glaucoma. Glaucoma World 2002; 25: 11–15.
27 Vernon SA. The concept of ‘Quality-of-Life-based Target
Pressures’ in chronic glaucoma. Int Glaucoma Rev 2003;
5(2): 221.
Life expectancy in chronic glaucoma
CL Tattersall et al
391
Eye
Article
Authored by three prominent specialists in the field, this text provides comprehensive coverage of diagnostic and treatment modalities for optimal glaucoma management. Revised throughout, this new edition presents the latest guidance in clinical examination, randomized trials, medical treatment, laser therapy, and surgical procedures. Hundreds of illustrations-with many classic black and white figures from the previous editions supplemented with new color images-depict the features of glaucomas and step-by-step procedures for their management, while expanded use of highlighted boxes, lists, and summary tables make the material easy to access. Evidence-based and updated information on all aspects of the glaucomas-including physiology, genetics, interventional trials, and new surgical techniques-offer a well-rounded foundation of knowledge for making the most informed diagnoses and choosing the most effective course of treatment. Combines the cumulative experience of three prominent glaucoma specialists-addressing a full range of clinical needs for practitioners of all levels-for a uniquely written coherent perspective. Includes extensive references to current and historically important sources to provide comprehensive interpretation of the latest medical literature. Synthesizes a classical approach to the glaucomas-based on seven earlier editions spanning over 40 years-with the most up-to-date evidence-based and epidemiologically-derived classifications and outcomes. Coherently correlates with authoritative consensus documents on key areas of glaucoma, drawn up by the world-wide specialists of the World Glaucoma Association, and reprinted in the text. Revamps traditional teachings on the angle closure glaucomas, in concert with the newest international literature and technologies, to keep you up to date on the latest advances. Illustrates detailed surgical interventions applicable to the complete spectrum of clinical settings-from the developing world through contemporary operating rooms. Examines the newest and most promising developments in pharmacology, laser and surgical advances for glaucoma management, to enable you to choose the most effective patient approach. Illustrates invaluable but little-known instruments for clinical and research diagnoses, including optic nerve cupping scales, bleb assessment instruments, and more.
Article
Full-text available
The aim of this study was to investigate the causes of mortality in individuals with open-angle glaucoma (OAG). All-cause mortality data from the Registry of Births, Deaths and Marriages for the Australian state of Tasmania, for all people who were at least 40 years of age at the time of death, were classified using International Classification of Diseases-10 guidelines. This information was cross-referenced to identify participants in the Glaucoma Inheritance Study in Tasmania (GIST) who had died. Contingency tables were used for crude analysis and then models were constructed, adjusting for age at death as well as gender. Between 1996 and 2005, a total of 33 879 deaths were recorded. Data were unavailable for 4868 (14.4%) people. The mean age at death for the study sample was 78.4+/-11.5 (range 41-109) years. Of those cases known to have OAG by their participation in GIST (n=2409), full mortality data were available for 741 (92.0%). Following adjustment for the age at death and male gender, the odds ratio for death due to ischaemic heart disease in people with OAG compared to the general population not known to have OAG was significant (OR=1.30, 95% CI: 1.08-1.56; P=0.006). Crude analysis revealed that there were significantly fewer people with OAG who died due to metastatic cancer (P<0.001); however, this did not remain significant following adjustment for age and gender. The pathoaetiological relationship between OAG and ischaemic heart disease is unclear and requires further investigation. Increased awareness of the association between cardiovascular disease and OAG is warranted.
Article
To determine the mortality within ten years of diagnosis of chronic open angle glaucoma and the visual field progression amongst survivors of a group of patients who were followed for 10 years. Of the 436 patients seen in a glaucoma case-finding clinic between July 1994 and December 1995 a diagnosis of chronic open angle glaucoma was made in 65. Ten years after diagnosis the outcome of the 57 patients who were treated at the Oxford Eye Hospital was determined. The causes of death were obtained from the general practitioner records and from the official death certificates. The probability of death was analysed using a Kaplan-Meier survival curve. The visual field of each eye of survivors was graded using a nine-stage severity scale. The visual outcome was analysed at the 10-year follow up visit. Seventeen patients (29.8%) died during the 10-year period, including nine from cardiovascular disease. The mean (SD) age at presentation of those that died was 76.4 years (9.7) compared with 69.5 years (10.9) for survivors (p = 0.029). Using a nine-stage grading system, 42 eyes (52.5%) did not deteriorate, 30 eyes (37.5%) deteriorated by one stage, seven eyes (8.75%) two stages and one eye (1.25%) three stages over the 10-year period. The average time to first deterioration by one stage was 8.51 years (CI 7.92 to 9.10). The mean (SD) intraocular pressure was 25.6 mmHg (5.8 mmHg) on presentation and 15.7 mmHg (3.0 mmHg) at the end of 10 years. Approximately two thirds of patients will still be under care 10 years after presentation. In older, white patients with glaucoma the overall goal of preventing visual handicap is achievable for most patients 10 years after diagnosis.
Article
Full-text available
To assess whether open angle glaucoma (OAG) screening meets the UK National Screening Committee criteria, to compare screening strategies with case finding, to estimate test parameters, to model estimates of cost and cost-effectiveness, and to identify areas for future research. Major electronic databases were searched up to December 2005. Screening strategies were developed by wide consultation. Markov submodels were developed to represent screening strategies. Parameter estimates were determined by systematic reviews of epidemiology, economic evaluations of screening, and effectiveness (test accuracy, screening and treatment). Tailored highly sensitive electronic searches were undertaken. Most potential screening tests reviewed had an estimated specificity of 85% or higher. No test was clearly most accurate, with only a few, heterogeneous studies for each test. No randomised controlled trials (RCTs) of screening were identified. Based on two treatment RCTs, early treatment reduces the risk of progression. Extrapolating from this, and assuming accelerated progression with advancing disease severity, without treatment the mean time to blindness in at least one eye was approximately 23 years, compared to 35 years with treatment. Prevalence would have to be about 3-4% in 40 year olds with a screening interval of 10 years to approach cost-effectiveness. It is predicted that screening might be cost-effective in a 50-year-old cohort at a prevalence of 4% with a 10-year screening interval. General population screening at any age, thus, appears not to be cost-effective. Selective screening of groups with higher prevalence (family history, black ethnicity) might be worthwhile, although this would only cover 6% of the population. Extension to include other at-risk cohorts (e.g. myopia and diabetes) would include 37% of the general population, but the prevalence is then too low for screening to be considered cost-effective. Screening using a test with initial automated classification followed by assessment by a specialised optometrist, for test positives, was more cost-effective than initial specialised optometric assessment. The cost-effectiveness of the screening programme was highly sensitive to the perspective on costs (NHS or societal). In the base-case model, the NHS costs of visual impairment were estimated as 669 pounds. If annual societal costs were 8800 pounds, then screening might be considered cost-effective for a 40-year-old cohort with 1% OAG prevalence assuming a willingness to pay of 30,000 pounds per quality-adjusted life-year. Of lesser importance were changes to estimates of attendance for sight tests, incidence of OAG, rate of progression and utility values for each stage of OAG severity. Cost-effectiveness was not particularly sensitive to the accuracy of screening tests within the ranges observed. However, a highly specific test is required to reduce large numbers of false-positive referrals. The findings that population screening is unlikely to be cost-effective are based on an economic model whose parameter estimates have considerable uncertainty. In particular, if rate of progression and/or costs of visual impairment are higher than estimated then screening could be cost-effective. While population screening is not cost-effective, the targeted screening of high-risk groups may be. Procedures for identifying those at risk, for quality assuring the programme, as well as adequate service provision for those screened positive would all be needed. Glaucoma detection can be improved by increasing attendance for eye examination, and improving the performance of current testing by either refining practice or adding in a technology-based first assessment, the latter being the more cost-effective option. This has implications for any future organisational changes in community eye-care services. Further research should aim to develop and provide quality data to populate the economic model, by conducting a feasibility study of interventions to improve detection, by obtaining further data on costs of blindness, risk of progression and health outcomes, and by conducting an RCT of interventions to improve the uptake of glaucoma testing.
Article
Full-text available
To compare the safety and efficacy of earlier vs later treatment in preventing primary open-angle glaucoma (POAG) in individuals with ocular hypertension. One thousand six hundred thirty-six individuals with intraocular pressure (IOP) from 24 to 32 mm Hg in 1 eye and 21 to 32 mm Hg in the fellow eye were randomized to observation or to topical ocular hypotensive medication. Median time of treatment in the medication group was 13.0 years. After a median of 7.5 years without treatment, the observation group received medication for a median of 5.5 years. To determine if there is a penalty for delaying treatment, we compared the cumulative proportions of participants who developed POAG at a median follow-up of 13 years in the original observation group and in the original medication group. Cumulative proportion of participants who developed POAG. The cumulative proportion of participants in the original observation group who developed POAG at 13 years was 0.22 (95% confidence interval [CI], 0.19-0.25), vs 0.16 (95% CI, 0.13-0.19) in the original medication group (P = .009). Among participants at the highest third of baseline risk of developing POAG, the cumulative proportion who developed POAG was 0.40 (95% CI, 0.33-0.46) in the original observation group and 0.28 (95% CI, 0.22-0.34) in the original medication group. There was little evidence of increased adverse events associated with medication. Absolute reduction was greatest among participants at the highest baseline risk of developing POAG. Individuals at high risk of developing POAG may benefit from more frequent examinations and early preventive treatment. clinicaltrials.gov Identifier: NCT00000125.
Article
Objective To explore associations between visual impairment, cataract, and mortality in older persons after adjusting for other factors associated with mortality.Methods A population cohort of 3654 persons aged 49 years or older (82.4% of eligible residents in the Blue Mountains region, west of Sydney, Australia), were examined at the Blue Mountains Eye Study baseline period (1992-1994) and followed up 5 years later (1997-1999). Australian National Death Index data were used to confirm persons who had died since baseline. Associations between mortality and presence of visual impairment and cataract at baseline were assessed using the Cox proportional hazards regression model, controlling for age, sex, demographic and socioeconomic status, medical history, and health risk behaviors.Results By June 30, 1999, 604 participants (16.5%) had died. The age- and sex-standardized 7-year cumulative mortality rate was 26% among persons with any visual impairment and 16% in persons without visual impairment. After adjusting for factors found significantly associated with mortality, including age, male sex, low self-rated health, low socioeconomic status, systemic medical conditions, and negative health risk behaviors, the presence at baseline of any visual impairment was independently associated with increased mortality risk (risk ratio [RR], 1.7; 95% confidence interval, 1.2-2.3). The presence of age-related cataract, either nuclear (RR, 1.5), cortical (RR, 1.3), or posterior subcapsular cataract (RR, 1.5), was also significantly associated with increased mortality risk. These associations remained statistically significant when visual impairment and each type of cataract were included simultaneously in the multivariate Cox model.Conclusion Visual impairment and age-related cataract may be independent risk factors for increased mortality in older persons.
Article
Background Primary open-angle glaucoma (POAG) is one of the leading causes of blindness in the United States and worldwide. Three to 6 million people in the United States are at increased risk for developing POAG because of elevated intraocular pressure (IOP), or ocular hypertension. There is no consensus on the efficacy of medical treatment in delaying or preventing the onset of POAG in individuals with elevated IOP. Therefore, we designed a randomized clinical trial, the Ocular Hypertension Treatment Study.Objective To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of POAG.Methods A total of 1636 participants with no evidence of glaucomatous damage, aged 40 to 80 years, and with an IOP between 24 mm Hg and 32 mm Hg in one eye and between 21 mm Hg and 32 mm Hg in the other eye were randomized to either observation or treatment with commercially available topical ocular hypotensive medication. The goal in the medication group was to reduce the IOP by 20% or more and to reach an IOP of 24 mm Hg or less.Main Outcome Measures The primary outcome was the development of reproducible visual field abnormality or reproducible optic disc deterioration attributed to POAG. Abnormalities were determined by masked certified readers at the reading centers, and attribution to POAG was decided by the masked Endpoint Committee.Results During the course of the study, the mean ± SD reduction in IOP in the medication group was 22.5% ± 9.9%. The IOP declined by 4.0%± 11.6% in the observation group. At 60 months, the cumulative probability of developing POAG was 4.4% in the medication group and 9.5% in the observation group (hazard ratio, 0.40; 95% confidence interval, 0.27-0.59; P<.0001). There was little evidence of increased systemic or ocular risk associated with ocular hypotensive medication.Conclusions Topical ocular hypotensive medication was effective in delaying or preventing the onset of POAG in individuals with elevated IOP. Although this does not imply that all patients with borderline or elevated IOP should receive medication, clinicians should consider initiating treatment for individuals with ocular hypertension who are at moderate or high risk for developing POAG.
Article
Objective: To investigate the relationship of cataract, age-related maculopathy, glaucoma, and visual impairment to survival in the population-based Beaver Dam Eye Study. Design: In this population-based study, visual acuity was measured with use of standardized protocols. At baseline, stereoscopic color fundus photographs and color slit-lamp and retroillumination photographs were graded in a masked fashion to determine the presence of age-related maculopathy and cataract, respectively. Deaths were ascertained by contacting family members, daily review of obituaries, and use of vital status records. Participants: Subjects aged 43 through 84 years who lived in Beaver Dam, Wis, were identified and examined between 1988 and 1990. Results: From the time of the baseline examination until a median of 4 years later, 9.5% (467/4926) of the population had died. After correcting for age and sex, poorer survival was associated with more severe nuclear sclerosis (5-year survival of 88.9% for the most severe compared with 94.1% for the least severe stage) and visual impairment (5-year survival of 87.5% for impaired compared with 91.8% for unimpaired vision). However, after controlling for systemic factors, only more severe nuclear sclerosis in people without diabetes was significantly associated with poorer survival (hazard ratio per level of severity, 1.19; 95% confidence interval, 1.00 to 1.40). Conclusions: These data suggest that after controlling for age and sex, nuclear sclerotic cataract severity, cataract surgery, and visual impairment are risk indicators for poorer survival. Cortical cataract, posterior subcapsular cataract, glaucoma, and age-related maculopathy were unrelated to poorer survival.
Article
The role of systemic blood pressure in glaucomatous damage remains undefined, with systemic hypertension and hypotension being implicated in different studies. We have previously reported that the physiologic nocturnal blood pressure “dip” may be exaggerated in some glaucoma patients with progressive field loss. A 24-hour ambulatory blood pressure recording was originally performed on 84 patients with glaucoma. The mean result across all our glaucoma patients were within the ranges reported in the literature for normal subjects. The normal-tension glaucoma and primary open-angle glaucoma groups did not differ significantly in blood pressure variables. Nocturnal blood pressure variables were lower in the patients with progressive field defects compared to those with stable visual fields. To determine long-term outcomes in these patients, we reevaluated the visual fields of the original 84 patients studied. In 70 patients with long-term visual field data (mean, 5.1 years), those who had shown greater nocturnal blood pressure dips were more likely to have shown field progression at some stage, despite good intraocular pressure control. Patients who had field progression showed significantly lower nocturnal blood pressure variables, with the dips of the systolic, diastolic, and mean arterial pressure significantly larger (systolic dip, P = 0.01). They also had a greater history of disk hemorrhages. A review of other 24-hour blood pressure studies in the literature shows that most are in agreement with these findings. The nocturnal reduction in blood pressure may, therefore, be an additional risk factor in glaucoma patients.
Article
Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long-term effect of two ocular hypotensive agents on preservation of visual field. In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32. Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily. Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine.
The optimization of visual field screening programs for glaucoma requires precise knowledge of where glaucoma defects occur and whether any relation exists between the size of defects and the associated retinal disease. The visual field results from 109 eyes of patients with early glaucomatous damage were investigated with a Friedmann Mark II Visual Field Analyser. The frequency distribution of scotomas as a function of location demonstrated that the tested field could be divided into four zones, one where scotomas occur frequently, one where scotomas occur a reasonable number of times, one where scotomas occur rarely, and one which corresponds to the blind spot (BS) region. The distribution of scotoma size in the first three zones was found to be about the same. Differences among the distributions of defects measured in this study and those of previous studies are attributed to different examination techniques.
Article
Elderly ophthalmic out-patients that had visited an eye-clinic were searched in a population register 7 years later. Observed numbers of survivors were compared with those expected according to appropriate life tables. Most observed numbers of survivors came close to the expected ones. Patients, aged more than 80 years when visiting the eye-clinic, had, however, a consistently increased survival rate. Glaucoma patients, less than 80 years old, had a slightly (not significantly) lower survival rate than expected.
Article
During our studies on glaucoma we have made an important and surprising observation. We think it is urgent to report that we have found the survival time of glaucoma patients seems to be substantially shortened. To the best of our knowledge this has not been previously reported.