Graves' orbitopathy: frequency of ocular hypertension and glaucoma


Graves’ orbitopathy:
frequency of ocular
hypertension and
glaucoma

FLM da Silva, M de Lourdes Veronese Rodrigues,

PMS Akaishi and AAV Cruz

Abstract

Purpose To determine the relationship

between ocular hypertension and glaucoma

in patients with Graves’ orbitopathy.

Methods A total of 107 patients with a

diagnosis of Graves’ orbitopathy, followed

at the Oculoplasty sector of the University

Hospital, Medical School of Ribeirão Preto,

were evaluated by applanation tonometry,

computed visual campimetry (Humphrey

30-2, Full Threshold) and analysis and

photographic documentation of the optic

nerve. The patients considered to have the

suspicion of glaucoma were re-evaluated

1 year later for diagnostic confirmation or

exclusion.

Results A 3.74% prevalence of ocular

hypertension (four patients) and a 2.8%

prevalence of glaucoma (three patients) was

observed. When considering only patients

older than 40 years, the prevalence of ocular

hypertension was 5.4% (four patients) and the

prevalence of glaucoma was 4.76% (three

patients).

Conclusion The present study did not reveal

a statistically significant difference in the

prevalence of ocular hypertension or glaucoma

between patients with Graves’ orbitopathy

and the general population.

Eye (2009) 23, 957–959; doi:10.1038/eye.2008.155;

published online 6 June 2008

Keywords: frequency; glaucoma; graves’

orbitopathy; intraocular hypertension

Introduction

Graves’ orbitopathy (GO) is an autoimmune

disease characterized by the presence of eyelid

retraction, proptosis and restrictive

strabismus.1,2 Most patients with GO have

autoimmune thyroid dysfunctions, especially

hyperthyroidism or Graves’ disease (GD),

which occurs in 90% of the cases.3 Although

there is a strong temporal relationship between

the onset of hyperthyroidism and orbitopathy,4

a large number of patients with GD only show

minimal signs of orbitopathy. Depending on the

sensitivity of the method of orbitopathy

detection the prevalence of eye disease in

unselected patients with GD ranges from

25 to 70%.1,5

Intraocular hypertension is a common finding

in some patients with GO. Several mechanisms

have been implicated in the raise of intraocular

pressure. Hypertrophy of the extraocular

muscles may induce a marked orbital

congestion and increase the episcleral venous

pressure.6,7 Restrictive fibrosis of the inferior

rectus muscle causes mechanical compression

in the primary position of gaze, which leads to

abnormal pressure readings in the slit lamp.

Another mechanism that may also contribute to

the increase in intraocular pressure, is the

accumulation of mucopolysaccharides in the

network of aqueous drainage, which would

reduce drainage of the aqueous humor.7

The prevalence of ocular hypertension and

glaucoma in patients with GO has been studied,

with controversial results.

The objective of the present study was to

determine the prevalence of glaucoma and ocular

hypertension in patients with a diagnosis of GO.

Materials and methods

We evaluated 107 consecutive patients with a

diagnosis of Graves’ orbitopathy seen at the

Oculoplasty sector of the University Hospital,

Medical School of Ribeirão Preto. The diagnosis

of GO was based on the criteria of Bartley and

Gorman,2 which establish the clinical diagnosis

of GO in patients who present eyelid retraction

associated with at least one of the following

signs: thyroid dysfunction, proptosis,

Received: 24 October 2007
Accepted in revised form:
15 April 2008
Published online: 6 June
2008

Department of
Ophthalmology,
Othorhinolaringology and
Head and Neck
SurgeryFMedical School of
Ribeirão Preto, University of
São Paulo, São Paulo, Brazil

Correspondence: M de
Lourdes Veronese
Rodrigues,
Department of
Ophthalmology,
Otolaringology and Head
and Neck Surgery,
Medical School of Ribeirao
Preto,
University of Sao Paulo,
Hospital das
Clı́nicasFOftalmologia,
Campus USP,
Av. Bandeirantes 3900,
Ribeirao Preto,
Sao Paulo
14048-900,
Brazil
Tel: 55 16 3602 2523;
Fax: 55 16 3602 2860.
E-mail: mdlvrodr@
fmrp.usp.br

Eye (2009) 23, 957–959
& 2009 Macmillan Publishers Limited All rights reserved 0950-222X/09 $32.00

www.nature.com/eye
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http://dx.doi.org/10.1038/eye.2008.155
mailto:mdlvrodr@fmrp.usp.br
mailto:mdlvrodr@fmrp.usp.br
http://www.nature.com/eye


strabismus or optic neuropathy, after the exclusion of

other possible causes When there is no eyelid retraction,

the diagnosis of GO can be considered if some of the

signs mentioned above are associated with thyroid

dysfunction in the absence of other causal factors.

A comprehensive ophthalmic evaluation was

performed in all patients including aplanation

tonometry, biomicroscopy of the optic nerve head with

digital photography and visual campimetry (Humphrey

campimeter, 30-2 full threshold strategy). All

examinations were performed by one examiner and the

findings were re-evaluated by three glaucoma specialists

who divided the sample in three categories: normal,

glaucoma and glaucoma suspect.

The diagnosis of glaucoma was based on the presence

of two of the following parameters: indicative signs of

glaucoma in optic nerve head, ocular hypertension and,

or visual field losses. The criteria for inclusion in ocular

hypertension group was intraocular pressure above

21 mmHg without other parameters indicative of

glaucoma.

The patients who received a diagnosis of glaucoma

suspect (borderline) continued to be followed at the

responsible outpatient sectors of the University Hospital

and were re-evaluated about 1 year later by evaluation of

GD status, refraction examination, determination of risk

factors, repeated tonometry and campimetry and a new

photographic documentation of the optic nerve. These

new tests were again evaluated by the examiners

together with the previous tests for the observation of

possible progression of the optic nerve alterations,

and/or visual field losses, characteristic of glaucoma.

Statistical analysis was performed using Fisher exact

test and, when one of the numbers was less than five, the

w2 test.
We certify that all applicable institutional and

governmental regulations concerning the ethical use of

human volunteers were followed during this research.

Results

Of the 107 patients with GO submitted to exams for the

diagnosis of glaucoma, 20 (18.7%) were males and 87

(81.3%) were females. Mean age was 41.57 years and

median age 42 years (range: 10–74 years).

Ocular hypertension in at least one eye was detected in

four patients (3.74%; Confidence interval 95: 1.03–9.30%),

all of them females. The physical comorbidities

presented are anaemia (2) and hepatitis (1).

The tests and retinographies of these patients were

evaluated by three examiners (specialists in glaucoma)

and, on the basis of the diagnosis of at least two

examiners, 84 were considered to be normal, 22

suspected and one received a diagnosis of glaucoma.

The 22 patients considered to be suspected were then

submitted to a new evaluation 1 year later to verify the

evolution of GD and to determine or exclude the

diagnosis of glaucoma. Eighteen of these 22 patients do

not present progression of the GD; GD became more

severe in one patient; and three patients were submitted

to orbital decompression surgery. The examiners

evaluated again the glaucoma tests together with the

previous ones and concluded that two of the 22 patients

re-evaluated had a diagnosis of glaucoma. Thus, of the

total number of 107 patients with GO evaluated, three

had a diagnosis of glaucoma, corresponding to 2.80%

(Confidence Interval 95: 0.58–7.98%) of the total

population. When only patients older than 40 years were

considered, the prevalence of intraocular hypertension

was 5.4% and the frequency of glaucoma was 4.76%.

Discussion

Glaucoma is the second most frequent cause of blindness

in the world. The estimate is that by 2010 there will be

60.5 million people with glaucoma, with the number

increasing to 79.6 million in 2020, and that bilateral

blindness due to glaucoma will affect 8.4 million people

by 2010 and 11.2 million by 2020.8

Several studies on the prevalence of glaucoma have

been conducted in different countries, but the frequency

of glaucoma in the general population is estimated at

1.5–2%.9 In the US, the prevalence of open angle

glaucoma in the population older than 40 years is

estimated at 1.86%.10 In a study conducted in Spain on

persons aged 40–79 years, the prevalence of primary

open angle glaucoma was found to be 2.1%.11

In Brazil there are no multicenter studies for the

determination of the prevalence of glaucoma. Two

studies were conducted in the Southeast and South

regions of the country. In the first, a prevalence of 1.48%

was observed among 8061 patients starting at 40 years of

age, increasing to 2.07% above the age of 50 years.12 In

the second, conducted on 1953 patients older than 40

years, 79 cases of glaucoma were detected (4.05%), with

73 being patients with primary open angle glaucoma and

six (0.31%) having a diagnosis of secondary glaucoma or

narrow angle glaucoma.13

In the present study, there was a 3.74% prevalence of

ocular hypertension and a 2.80% prevalence of glaucoma

in patients with GO, values similar to those observed in

the general population. Considering only the patients

older than 40 years the prevalence was found to be

higher than the other studies, except the one carried out

by Sakata et al.13

In a retrospective study of 482 patients with GO,

Kalmann and Mourits14 detected a 3.9% prevalence of

intraocular hypertension in these patients compared to a

Graves orbitopathy and glaucoma
FLM da Silva et al

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prevalence of 1.6% in the general population. A study15

carried out in Pittsburgh on 500 patients with GO

revealed a 24% prevalence of ocular hypertension

compared to 5% in the general population. In that study15

only seven patients were classified as glaucomatous and

two patients showed progressive abnormalities of the

visual field and optic disc. Ohtsuka and Nakamura

observed a 22% prevalence of ocular hypertension in

patients with GO16 and a 13% prevalence of glaucoma in

patients with GD (Table 1).17

Despite the controversial results obtained thus far,

intraocular pressure should be carefully monitored in

patients with GO. It is necessary to point out that the

number of participants of the present study is small, and

it is a limitation. However, the results indicate that the

progressive glaucomatous changes of the optic nerve and

visual fields are probably not more common among these

patients than in the general population.

Treatment of GO, particularly orbital decompression,

may have a beneficial effect on intraocular pressure.

Patients with ocular hypertension should be monitored

for changes in the optic disc and visual field. Anti-

glaucoma medical therapy may be necessary, but surgical

treatment of glaucoma is not necessary for most patients

with GO and ocular hypertension.18–20

Acknowledgements

This study was financially supported by CAPES, Brazil.

We acknowledge our collaboration with Professor Dr

Jayter Silva de Paula, Professor Dr Eduardo Melani

Rocha and Dr Daniela Felipe Crosta.

References

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3 Bartley GB, Fatourechi V, Kadrmas EF, Jacobsen SJ, Ilstrup
DM, Garrity JA et al. Chronology of Graves’
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4 Gorman CA. Temporal relationship between onset of
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5 Feldon SE. Graves’ ophthalmopathy. Is it really thyroid
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6 Dallow RL, Netland PA. Management of thyroid
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7 Higginbotham EJ. Glaucoma associated with increased
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9 Giampani J. Hereditariedade e Genética. In: Susanna Junior
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10 Friedman DS, Wolfs RC, O’Colmain BJ, Klein BE, Taylor HR,
West S et al. Prevalence of open-angle glaucoma among
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11 Anton A, Andrada MT, Mujica V, Calle MA, Portela J,
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12 Ghanem CC. Levantamento de casos de Glaucoma em
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14 Kalmann R, Mourits MP. Prevalence and management of
elevated intraocular pressure in patients with Graves’
orbitopathy. Br J Ophthalmol 1998; 82: 754–757.

15 Cockerham KP, Pal C, Jani B, Wolter A, Kennerdell JS. The
prevalence and implications of ocular hypertension and
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16 Ohtsuka K. Intraocular pressure and proptosis in 95 patients
with Graves ophthalmopathy. Am J Ophthalmol 1997; 124:
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17 Ohtsuka K, Nakamura Y. Open-angle glaucoma
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19 Danesh-Meyer HV, Savino PJ, Deramo V, Sergott RC,
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Table 1 Prevalence (%) of intraocular hypertension and
glaucoma in patients with Graves’ Orbitopathy

Intraocular
hypertension

Glaucoma
(%)

(%)

Silva et al. (present study) 3.7 2.8
Kalmann & Mouritt (1998)14

(n ¼ 482)
3.9 0.8

Cockerham et al. (1997)15 (n ¼ 500) 24 1.4
Ohtsuka & Nakamura (1997)16 and
(2000)17 a

22 13

aPatients with Graves’ disease (irrespective of orbitopathy).

Graves orbitopathy and glaucoma
FLM da Silva et al

959

Eye


	Graves' orbitopathy: frequency of ocular hypertension and glaucoma
	Introduction
	Materials and methods
	Results
	Discussion
	Acknowledgements
	References