ORIGINAL PAPER

Clinical Profile of Uveitis-Related Ocular Hypertension

Deepankur Mahajan • Reetika Sharma •

Sat Pal Garg • Pradeep Venkatesh •

Ramanjit Sihota • Tanuj Dada

Received: 2 August 2014 / Accepted: 3 October 2014

� Springer Science+Business Media Dordrecht 2014

Abstract The purpose of this article is to study the

clinical and demographic profile of uveitis-related

ocular hypertension (OHT) and evaluate risk factors

predisposing to development of OHT in uveitis. Two

hundred patients (200 eyes) with uveitis were evaluated

for type of uveitis and the presence of OHT

[IOP [ 21 mmHg]. All patients underwent a complete

ophthalmic examination and appropriate systemic eval-

uation. Patients with OHT were started on appropriate

antiglaucoma medication and were followed up for

minimum of 6 months. Forty-two eyes (21 %) were

found to have OHT. Anterior uveitis alone was seen in

22 (52.4 %), granulomatous uveitis was seen in 8

(19.1 %) eyes, while 13 eyes (30.9 %) had active

uveitis. On multiple logistic regression, age greater than

60 years (p = 0.025), peripheral anterior synechiae

(PAS) [ 180� (p = 0.029), and steroid use (p \ 0.001)

were found to have significant association with OHT.

Mean IOP at baseline was 24.6 ± 10.1 mmHg which

decreased to 17.3 ± 4.5 mmHg at 6 months

(p \ 0.001). At 6 months, 30 eyes were medically

controlled (71.4 %), 5 eyes underwent trabeculectomy

with MMC (11.9 %), and in 7 eyes, antiglaucoma

medication could be discontinued. One-fifth of eyes

with uveitis had OHT. Risk factors for IOP elevation

included increased age, PAS [ 180�, and corticosteroid

use.

Keywords Uveitis � Ocular hypertension �Glaucoma � Secondary glaucoma

Introduction

Elevated intraocular pressure (IOP) is a recognized

complication of uveitis [1, 2]. Terminology such as

‘‘secondary glaucoma’’ (SG), ‘‘uveitic glaucoma’’

(UG), or ‘‘ocular hypertension’’ (OHT) has been used

to refer to elevated IOP in uveitic cases, in a roughly

interchangeable fashion. However, strictly speaking, it

might be incorrect to use the terminology of ‘‘glau-

coma’’ in the absence of disk or field changes

suggestive of glaucoma. Various studies have reported

prevalence ranging from 5.2 [3] to 41.8 % [4] which

vary with disease patterns or case definition of OHT/

SG related to uveitis used. Certain risk factors are

known to have a higher tendency to develop elevated

IOP. These include elderly patients [4, 5], anterior

uveitis [6, 7], granulomatous uveitis [6, 8], active

uveitis [6–8], chronic uveitis [4, 6, 9, 10], prolonged

disease duration [4, 9], and steroid use [4, 7, 9, 11].

Although several retrospective reports have

described the prevalence of and various risk factors

for elevated IOP in patients with uveitis, prospective

D. Mahajan � R. Sharma � S. P. Garg � P. Venkatesh �R. Sihota � T. Dada (&)

Dr. Rajendra Prasad Centre for Ophthalmic Sciences,

All India Institute of Medical Sciences, Room No. S1,

1st Floor, New Delhi 110029, India

e-mail: tanujdada@gmail.com

123

Int Ophthalmol

DOI 10.1007/s10792-014-0008-8

studies looking at the anterior chamber angle are

lacking.

Materials and Methods

The study was performed at uvea clinic of tertiary eye

care centre. Two hundred non-consecutive patients of

uveitis were included in the study after written and

informed consent was obtained. The study conformed

to the tenets of Declaration of Helsinki. Patients with

postoperative uveitis, post-traumatic uveitis, lens

induced uveitis, masquerade syndromes, significant

corneal pathology, and pre-existing primary glaucoma

were excluded.

Detailed history was recorded, especially the

details of medication, both systemic and topical, that

patient had received in the past or were currently on,

for uveitis or elevated IOP. Complete ophthalmic

examination including slit-lamp biomicroscopy, goni-

oscopy, dilated fundus examination, and IOP mea-

surements with Goldmann Applanation tonometer

were carried out. All patients underwent systemic

investigations as per clinical suspicion of etiology on a

case to case basis.

Cases were classified as anterior, intermediate,

posterior uveitis, and panuveitis [12, 13]. Cases were

further classified as granulomatous or non-granulom-

atous, as active or healed and as acute, recurrent or

chronic, with specific etiological diagnoses when

possible [13]. Uveitis-related OHT was defined as a

documented IOP greater than 21 mmHg on at least

two occasions. Patients with OHT were evaluated for

glaucomatous neuropathy with stereoscopic evalua-

tion of the optic nerve head with a 90D lens and visual

field defects on Humphrey Visual Field (HVF 30-2

SITA Standard protocol). Patients with evidence of

glaucomatous neuropathy on either of the two inves-

tigations were labeled as having SG related to uveitis.

The diagnosis of steroid-induced (SI) OHT was made

based on an IOP rise in parallel with administration of

steroids and a decrease in the IOP with discontinuation

of steroids. All the clinical details were recorded on a

preset case proforma.

Patients with OHT or SG were followed up for

a minimum of 6 months. For OHT (i.e., IOP[21 mmHg), treatment with appropriate ocular hypoten-

sive agents (topical, systemic, or both) was initiated. If

IOP was not controlled medically, patients underwent

trabeculectomy with Mitomycin C (MMC). Target IOP

was kept at 18 mmHg or below during follow-up in eyes

with OHT. For patients with SG, treatment was titrated to

a target pressure based on existing optic nerve damage or

visual field defect on perimetry. The response to therapy

was evaluated in terms of IOP control, visual acuity, and

number of medications.

Statistical Analysis

Only one eye from each patient was enrolled for

analysis. In case both the eyes of patient satisfied the

inclusion criteria, right eye was included in the study.

Statistical tests including Fisher’s exact, Chi square,

t test, Wilcoxon rank-sum test, and Mann–Whitney U

were used to test the level of significance (p value) of

relationship between patient and disease variables

with SG. Unadjusted and adjusted odds ratio (OR) was

calculated using logistic regression and multiple

Table 1 Type of uveitis associated with ocular hypertension

Type of uveitis Frequency

in uveitis

patients (%)

Frequency

in patients

with ocular

hypertension

(%)

p-value

(p \ 0.05

considered

significant)

Anatomical type of uveitis 0.613

Anterior 105 (52.5) 22 (52.4)

Intermediate 36 (18.0) 10 (23.8)

Posterior 31 (15.5) 6 (14.3)

Panuveitis 28 (14.0) 4 (9.5)

Activity of disease 0.001

Healed 90 (45.0) 29 (69.1)

Active 110 (55.0) 13 (30.9)

Character of uveitis 0.237

Granulomatous 27 (13.5) 8 (19.1)

Non-

granulomatous

173 (86.5) 34 (80.9)

Chronology in anterior uveitis 0.016

Acute 50 (47.7656) 5 (22.7)

Recurrent 37 (35.2) 12 (54.6)

Chronic 18 (17.2) 5 (22.7)

Angle of anterior chamber 0.001

Open 140 (70.0) 20 (47.6)

Partly closed

(PAS \ 180�)

36 (18.0) 11 (26.2)

Closed

(PAS [ 180�)

24 (12.0) 11 (26.2)

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logistic regression analysis, respectively. Repeated

measure two-way ANOVA (Analysis of variance) and

Friedman test were used to calculate the level of

significance of change in variables like IOP and best

corrected visual acuity (BCVA) over the follow-up

duration. A p value of \0.05 was considered as

statistically significant. Stata SE 9 software was used.

Results

Clinical and Demographic Profile of Examined

Patients

The mean age of the study population was

31.6 ± 12.2 years (Range 9–75 years). Of 200

patients of uveitis, 123 were males (61.5 %) and

bilateral involvement was seen in 92 cases (46 %).

The distribution of uveitis type is as shown in Table 1.

Uveitic OHT was seen in 42 study eyes yielding a

prevalence of 21 %. The mean age for patients with

OHT was 35.1 ± 13.6 years (Range 18–75 years)

with 29 males (69.1 %). Anterior uveitis was seen in

22 (52.4 %) patients followed by intermediate, pos-

terior, and panuveitis in 10 (23.8 %), 6 (14.3 %), and 4

(9.5 %), respectively. Granulomatous uveitis was seen

in 8 (19.1 %) eyes and 13 (30.9 %) had active uveitis

at the time of examination. Gonioscopy revealed that

20 eyes (47.6 %) had anatomically open angle, while

11 (27.2 %) had peripheral anterior synechiae (PAS)

of greater than 180� (Table 1). SI OHT was diagnosed

in 9 out of 42 eyes with OHT (21.4 %). SG was

diagnosed in 12 cases (28.6 %).

Etiological diagnosis of uveitis was established in

76 (38 %) out of 200 cases in study population of

uveitic patients, while in patients of uveitic OHT,

etiology was established in 12 out of 42 patients

(28.6 %). The prevalence data for the same is shown in

Table 2.

Risk Factors for Uveitic Glaucoma

There was a significant difference between the means

of age of uveitic patients with and without OHT

(p = 0.0331, t-test). Sex of patient (p = 0.258, Chi

square) did not show any significant association with

OHT.

Anatomical distribution of uveitis (p = 0.613, Chi

square) and pattern of uveitis, that is, granulomatous

or non-granulomatous (p = 0.241, Chi square), did

not reveal any statistically significant association with

raised IOP. OR of developing OHT in healed uveitis

was determined to be 3.55 (95 % CI 1.71–7.35)

compared to active uveitis. Among the patients of

anterior uveitis, the course of disease, determined as

acute, recurrent, or chronic, was found to be associated

with raised IOP (p = 0.016, Chi square). The odds of

developing OHT in recurrent and chronic uveitis was

determined to be 4.90 (95 % CI 1.54–15.59) and 3.61

(95 % CI 0.91–14.42), respectively, when compared

to acute uveitis. However, mean number of recur-

rences in the former and total disease duration in the

latter revealed no association with raised IOP. Overall,

mean total duration of disease was higher in eyes with

OHT (36.5 ± 60.4 months) as compared to others

(20.5 ± 48.6 months), but this was not significant

statistically (p = 0.235, Wilcoxon rank-sum test).

Analysis of gonioscopic findings revealed statisti-

cally significant association between the presence of

PAS and OHT (p \ 0.001, Chi square). The OR of

developing OHT was 5.08 (95 % CI 2.00–12.89) with

PAS greater than 180� and 2.64 (95 % CI 1.13–6.19)

with PAS less than 180� when compared to open angle

seen on gonioscopy.

Table 2 Ocular hypertension in uveitis patients (Etiology

specific)

Disease entity No. of

cases

No. of

patients

with ocular

hypertension

Prevalence

(%)

Presumed ocular

tuberculosis

11 1 9.1

Herpetic

iridocyclitis

9 3 33.3

Serpiginous

choroiditis

8 2 25

Toxoplasma

retinochoroiditis

5 1 20

Posner schlossman

syndrome

3 3 100

Fuchs heterochromic

iridocyclitis

3 1 33.3

Seronegative

rheumatoid

arthritis

1 1 100

Other etiologies 36 0 0

Idiopathic 124 30 24.19

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The presence of OHT was significantly more

common in patients with history of steroid use (topical

or periocular or systemic or any combination of these)

(p \ 0.001, Chi square) with OR of 4.04 (95 % CI

1.92–8.5) (Table 3). This significant difference was

valid individually for the use of topical (p = 0.050),

systemic (p = 0.004), and periocular (p \ 0.001)

steroids with OR of developing glaucoma being

1.98, 2.90, and 4.625, respectively, for the three

modes of use of steroid.

Using multiple logistic regression analysis, age

greater than 60 years (p = 0.025), closed angles (PAS

greater than 180�) on gonioscopy (p = 0.029), and

steroid use (p \ 0.001) were found to have significant

association with OHT related to uveitis (Table 3).

Follow-up of Patients With OHT

Eyes with uveitic OHT were followed up on average

for 7.4 ± 2.3 months (range 6–13 months). Overall,

there was reduction in mean IOP level from

24.6 ± 10.1 mmHg at baseline examination to

17.3 ± 4.5 mmHg at 6-month follow-up (p \ 0.001

repeated measure ANOVA).

Median BCVA in patients with ocular hypertension

ranged from 6/12 to 6/60 on Snellen visual chart, while

those without OHT ranged from 6/6 to 6/12

(p = 0.003 on Mann–Whitney) at baseline. It revealed

significant improvement in patients with ocular hyper-

tension over follow-up duration of 6 months

(p \ 0.001 with Friedman test) so as to be placed in

the group with Snellen acuity ranging from 6/6 to 6/12.

At baseline, 23 patients (54.8 %) were already on

ocular hypotensive medication, and 2 patients had

history of undergoing surgery (trabeculectomy with

MMC). At 6-month follow-up, 30 eyes (71.4 %) were

on medical treatment. None of the eyes required

systemic medication at the end of 6 months. IOP

recorded in eyes on medical management decreased

from 24.3 ± 8.6 mmHg to 17.3 ± 3.6 mmHg at

6-month follow-up (p \ 0.001 repeated measure

ANOVA). Overall, 5 eyes (11.9 %) had undergone

trabeculectomy with MMC at a follow-up duration of

6 months. IOP in these eyes decreased from

33.4 ± 10.9 mmHg (on topical and systemic ocular

hypotensive medication) to 12.2 ± 2.6 mmHg at

6-month follow-up (p = 0.05 repeated measure

ANOVA). None of these eyes were on any ocular

hypotensive medication after surgery. Remaining 7

eyes (16.7 %) did not require any ocular hypotensive

medication at 6 months of follow-up (Table 4).

Discussion

Glaucoma represents a severe and potentially sight

threatening complication of uveitis. Uveitis is a fairly

common cause of SG [14]. An important difference

with patients having primary glaucoma is that in

secondary uveitic glaucoma, the damaging mecha-

nism is nearly always raised IOP, and hence treatment

is guided toward controlling IOP alongwith inflam-

mation in these cases [2]. However, raised IOP

associated with uveitis is a challenging condition to

manage, often with poor visual outcome [6].

The present study was conducted in a tertiary eye care

centre in India and 200 patients of uveitis patients were

Table 4 Antiglaucoma treatment profile of uveitis-related

ocular hypertension patients

Intervention Number of

patients

at baseline (%)

Number of patients

at 6-m follow-up

(%)

Medical 23 (54.8 %) 30 (71.4 %)

One topical drug 7 8

Two topical drugs 5 16

Three topical drugs 2 6

Systemic drugs 9 0

Surgical 2 (4.8 %) 5 (11.9 %)

No Treatment 17 (40.4 %) 7 (16.7 %)

Table 3 Risk factors for developing ocular hypertension in

uveitis

Logistic Regression [Odds Ratio]

Closed Angle (PAS [ 180�) [5.08]

Recurrent Uveitis [4.90]

Steroid Use [4.04]

Healed Uveitis [3.55]

Partly Closed Angle (PAS \ 180�) [2.64]

Age

Multiple Logistic Regression

Age [ 60 yrs

Closed angle (PAS [ 180�)

Steroid Use

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included. OHT was defined as documented IOP of

greater than 21 mmHg on at least two occasions. Out of

200 eyes of 200 patients evaluated in the study, OHT

was diagnosed in 42 eyes (21 %). Many studies have

reported similar prevalence of raised IOP in uveitis.

Merayo-Lloves et al. in their study found the prevalence

of uveitic patients with IOP greater than 21 mmHg to be

17 % [6]. Takahashi et al. reported SG in 293 eyes

(18.3 %) of 217 patients (19.6 %) in a retrospective

study of 1,099 patients (1,604 eyes) from Japan [7].

Panek et al. found 23 patients (31 eyes) out of 100

patients (161 eyes) to have SG by criteria of IOP alone

yielding prevalence of 23 % (19.3 % of eyes) [10].

Mean age in patients who developed OHT related to

uveitis was found to be higher when compared to

uveitic patients who did not have raised IOP. This was

also confirmed on multivariate analysis. Similar results

have been cited by Herbert et al. [4] and Barton et al.

[5]. The effects of age probably represent an imbalance

between trabecular meshwork function and the inflam-

matory load reflecting on declining trabecular mesh-

work function with increasing age, where even a

nominal inflammatory attack will unmask compro-

mised trabecular meshwork function [15].

Similar to previous studies, anterior uveitis was the

predominant clinical type associated with OHT which

might be expected as anterior uveitis is the most

common type of uveitis seen [6, 16]. The possible

inflammatory load and trabeculitis associated with this

type of uveitis is more making it the predominant type

associated with OHT. The present study did not find

any significant association between raised IOP and

anatomical distribution of uveitis, which too has been

reported in few previous studies. [4, 9, 11] It may be

that the propensity to increased use of steroids with

intermediate and posterior uveitis will act to mask any

significant association of raised IOP with anatomical

location of inflammation per se.

Granulomatous uveitis is usually said to be asso-

ciated with greater propensity of posterior and PAS

formation and hence greater risk of elevated IOP [6, 8]

in these cases, but we did not find the same. This was

probably due to lower prevalence of granulomatous

uveitis cases noted in this study (eight cases) and

hence, larger numbers will probably be needed to

establish or discard a significant relationship. Neri

et al. in their study found posterior synechiae to be

seen more frequently in patients with SG but we could

not find any such association [9].

Presence of healed uveitis was noted as another

risk factor for raised IOP in uveitis. Previous studies,

however, have noted raised IOP to be in phase with

intraocular inflammation, [7, 8] but few have

suggested for this factor to be interpreted with

caution in view of marginally significant association

[4]. The association of healed uveitis with raised IOP

probably reflects cumulative effect of restoration of

secretory function of the ciliary body, the longer

duration of the disease process, and the effects of

corticosteroids given as therapy. Failure to establish

an association on multivariate analysis reflects on the

same hypothesis.

In patients with anterior uveitis, recurrent and

chronic patterns of uveitis were found to be associated

with raised IOP. Overall, patients with OHT had

longer mean duration of disease process. Previous

studies have reported chronic and recurrent course of

uveitis as to be predominantly associated with SG [4,

6, 9, 10]. Increasing prevalence of glaucoma with

recurrent pattern of uveitis, chronicity, and longer

duration reflects the cumulative detrimental effect of

inflammation and probably the consequence of

chronic corticosteroid therapy on an initially normal

trabecular meshwork [15].

Although angles were open in most cases of OHT,

presence of PAS on gonioscopy were found to be risk

factors for SG in uveitis. Open angles have been

reported in majority of eyes with SG in past [6, 7]. To

the best of our knowledge, no previous study reports

the association of the extent of PAS seen on gonios-

copy to raised IOP in uveitis. Presence of PAS on

gonioscopy may be predisposing to OHT due to

obstruction of outflow pathway especially when

grossly open angle is already compromised by the

effects of trabecular inflammation, scarring, pigment

deposition, steroid response, and so on. Noting the

location of PAS is also important pre-operatively to

decide the site for glaucoma filtration surgery.

Again, there was significant association seen

between steroid use and raised IOP which was

maintained on multivariate analysis. Previous studies

support association between raised IOP and steroid use

however; usually lower prevalence has been reported

[4, 7, 9–11]. It is generally accepted that the steroid

dose should be tapered as soon as possible, according

to clinical criteria, to avoid serious side effects. It is

postulated that a treatment of more than 6 months

represent an additional risk to develop glaucoma [9].

Int Ophthalmol

123

At the end of 6 months of follow-up, there was

significant reduction in mean IOP. Nearly 90 %

patients were controlled on either without ocular

hypotensive agents or with topical agents alone,

without requirement of systemic antiglaucoma medi-

cation. Only 5 out of 42 patients (11.9 %) with OHT

had undergone trabeculectomy with MMC. Takahashi

et al. reported the use of surgical therapy in 12.7 % of

patients with uveitic glaucoma with IOP controlled in

89.5 % eyes at a mean follow-up duration of

71.6 ± 47.1 months [7] which is similar to our study.

In a retrospective review by Neri et al., 11.1 % patients

of chronic uveitis and 7.6 % patients with acute uveitis

developed SG and 7 patients (12.5 %) of the former

group required trabeculectomy, while none of the

patients in the latter group required any surgery [9].

In conclusion, OHT is a commonly encountered

problem in patients with uveitis, seen in nearly one out

of every five patients. Risk factors for OHT in uveitis

include increasing age, healed uveitis, recurrent uveitis,

presence of PAS on gonioscopy, and steroid use.

Anterior chamber anatomy using gonioscopy needs to

be studied as PAS is an indicator to higher chance of

developing OHT. Steroid use by any route also remains

a significant risk factor for IOP elevation in uveitis, and

hence treatment needs to be monitored. Patients with

these risk factors should be monitored closely and raised

IOP should be treated promptly. Medical management is

able to control IOP in nearly 90 % of patients, hence a

good evaluation and follow-up is needed.

Conflict of Interest None.

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