• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Evidence Table 3Any treatment vs. no treatment

Study detailsPatientsInterventionsOutcome measuresEffect sizeComments
Kass et al., 200272

Ocular Hypertension Treatment Study (OHTS)

Study design:
RCT
Single masked

Evidence level:
1+

Duration of follow-up:
Median follow-up for African American participants 72 months and 78 months for other participants.
Patient group: OHT patients

Inclusion criteria:
Age between 40–80 years, a qualifying IOP between 24 mmHg and 32 mmHg in one eye and between 21 mmHg and 32 mmHg in the other eye, gonioscopically open angles, 2 normal and reliable visual field tests per eye and normal optic discs

Exclusion criteria:
Visual acuity worse than 20/40 in either eye, previous intraocular surgery (other than uncomplicated cataract extraction with posterior chamber lens implantation), and diabetic retinopathy or other diseases capable of causing visual field loss or optic disc deterioration.

Setting: 22 clinical centres, USA

All patients
N: 1636

Group 1
N: 817
N medication withdrawn:40
M/F: 359/458
Age categories:
40 to ≤ 50 years: 291 (35.6%)
>50 to ≤ 60 years: 270 (33.0%)
>60 to ≤ 70 years: 202 (24.7%)
>70 to 80 years: 64 (6.6%)
Previous use of OHT medication: 35.0%
First-degree family history of glaucoma: 34.0%
Myopia ≥ 1-diopter spherical equivalent: 34.4%
Oral B-adrenergic antagonist: 5.4%
Oral calcium channel blocker: 12.8%
History of migraine: 10.4%
History of diabetes: 11.5%
History of hypertension: 37.5%
History of low blood pressure: 4.8%
History of cardiovascular disease: 6.8%
History of stroke:0.9%
Drop outs: 115 (28 died)

Group 2
N: 819
N medication initiated:42
M/F: 346/473
Age categories:
40 to ≤ 50 years: 287 (35.0%)
>50 to ≤ 60 years: 259 (31.6%)
>60 to ≤ 70 years: 210 (25.6%)
>70 to 80 years: 63 (7.7%)
Previous use of OHT medication: 39.3%
First-degree family history of glaucoma: 35.6%
Myopia ≥ 1-diopter spherical equivalent: 33.7%
Oral B-adrenergic antagonist: 4.6%
Oral calcium channel blocker: 14.0%
History of migraine: 11.7%
History of diabetes: 12.1%
History of hypertension: 38.1%
History of low blood pressure: 4.0%
History of cardiovascular disease: 6.5%
History of stroke: 1.6%
Drop outs: 113 (29 died)
Group 1
Topical ocular hypotensive medication. Treatment to achieve a target IOP of 24 mm Hg or less and a minimum 20% reduction in IOP from the average of the qualifying IOP and IOP at the baseline randomisation visit. Topical medication was changed and/or added until both of these goals were met or the participant was receiving maximum tolerated topical medical therapy. Medications were added and changed in one-eyed therapeutic trials.

Included all topical occular hypotensive medications commercially available in the US. Follow-up visits every six months.

Group 2
No treatment
Patients developed POAG (end points of visual field abnormality or optic disc deterioration)Group1: 36/817 (4.4%)
African American: 14/203
Other: 22/614
Group 2: 89/819 (10.9%)
African American: 26/205
Other: 63/614
Funding:
Study was supported by grants EY09341 and EY09307 from the National Eye Institute and the National Centre on Minority Health and Health Disparities, National Institutes of Health, Bethesda, Md; Merck Research Laboratories, White House Station, NJ; and by an unrestricted grant from Research to Prevent Blindness, New York, NY.

Limitations:
Patient and clinician were not blinded to randomisation during follow-up.

Additional outcomes:
Cumulative probability of developing a reproducible visual field abnormality or an optic disc deteriorations due to POAG or a variety of other caused was reported.
Estimated of the effect of treatment after adjusting.
Treatment benefit for reproducible visual field abnormality attributed to POAG and for reproducible optic disc deterioration attributed to POAG reported.

Notes:
Randomisation method was adequate and primary outcome assessment was masked. 3328 screened but 1636 entered into study (1692 not eligible for various reasons).
Cumulative probability of developing POAGHazard Ratio: 0.40 (95% CI: 0.27 to 0.59)
p value: <0.0001
Cumulative probability of developing POAG at 60 months:Group1: 4.4%
Group 2: 9.5%
Cumulative probability of developing POAGAfrican-American participants:
Hazard ratio: 0.54 (95%
CI:0.28–1.03
Other participants:
Hazard ratio: 0.34 (95%
CI:0.21–0.56
P=0.26
Change in IOPGroup 1:
Baseline: 24.9±2.6
Reduction from baseline: − 22.4%±9.9

Group 2:
Baseline: 24.9±2.7
Reduction from baseline: − 4.0%±11.6
Adverse effects:Ocular symptoms:
Group1: 57%
Group 2: 47%
P value: <0.001
Symptoms affecting skin, hair or nails:
Group1: 23%
Group 2: 18%
P value: <0.001
Difference between groups total hospitalisationsP=0.56
Difference between groups worsening of pre-existing conditionsP=0.28
Difference between groups mortality ratesP=0.70
Other adverse events (≥10%)Medication (%)Observation(%)
Tearing/watering12.613.2
Itching11.411.8
Blurry or dim vision11.411.6
Feels like object in eye10.110.6
Poor night vision12.211.8
Difficulty Sleeping17.216.8
Headache10.711.8
Loss of libido11.212.6
Numbness/tingling arms13.916.3
Heijl et al., 200259
Early Manifest Glaucoma Trial (EMGT)

Study design:
RCT
Single masked

Evidence level:
1+

Duration of follow-up:
At least 6 years.

Open label design but outcome measurement was masked
Patient group: patients with chronic open angle glaucoma

Inclusion criteria:
Men and women with newly diagnosed, previously untreated COAG (POAG, NTG or PEX) with repeatable visual field defects in at least one eye measured using Humphrey 24-2 full programme. Age between 50 and 80 years

Exclusion criteria:
  • Advanced visual field defects (MD-16dB or threat to fixation)
  • Visual acuity < 0.5
  • Mean IOP >30 mmHg
  • Lens opacities exceeding N1, C1 or P1 in Lens Opacities Classification System
  • Patients with glaucomatous visual field defects in both eyes eligible if MD = −10 dB or better in one eye and −16 dB in other eye.
Setting: 2 clinical centres (1 reading and 1 co-ordinating), Sweden

All patients
N: 255

Group 1
N: 129
Both eyes eligible:: 34 (26%)
One eye eligible: 95 (74%)
Age ± SD: 68.2 ± 4.8 (range 58–78)
M/F: 47/82
Mean Baseline IOP mmHg ± SD: 20.6 ± 4.1
Patients with IOP < 21 mmHg: 69
Mean Visual Acuity: ± SD: 0.9 ± 0.1
Mean deviation ± SD: −5.0 ± 3.7 dB
Number of optic disc abnormalities (cupping, notching, haemorrhage): 147
Myopia ≤1-diopter spherical equivalent: 19(12%)
Exfoliation Syndrome: 9 (6%)
Disease History:
Family history of glaucoma: 26 (20%) 34.4%
Cardiovascular disease: 19 (15%)
Stoke/low blood pressure: 12 (9%)
General artheriosclerosis: 4 (3%)
Peripheral vasospasms and migraine: 21 (16%)
Pulmonary disease: 3 (2%)
Diabetes: 3 (2%)
Medication use:
Antihypertensives: 31 (24%)
Corticosteroids: 0
Insulin or oestrogen: 57 (44%)
Drop outs: 24 (3 lost to follow up, 15 died, 6 received ALT but discontinued medications)

Group 2
N: 126
Both eyes eligible: 27 (21%)
One eye eligible: 99 (79%)
Age ± SD: 68.0 ± 5.0 (range 50–79)
M/F: 39/87
Mean Baseline IOP mmHg ± SD: 20.9 ± 4.1
Patients with IOP < 21 mmHg: 63
Mean Visual Acuity: ± SD: 1.0 ± 0.1
Mean deviation ± SD: −4.4 ± 3.3 dB
Number of optic disc abnormalities (cupping, notching, haemorrhage): 138
Myopia ≤1-diopter spherical equivalent: 23(15%)
Exfoliation Syndrome: 16 (10%)
Disease History:
Family history of glaucoma: 24 (19%)
34.4%
Cardiovascular disease: 14 (11%)
Stoke/low blood pressure: 5 (4%)
General artheriosclerosis: 5 (4%)
Peripheral vasospasms and migraine: 26 (21%)
Pulmonary disease: 0
Diabetes: 6 (5%)
Medication use:
Antihypertensives: 31 (25%)
Corticosteroids: 4 (3%)
Insulin or oestrogen: 55 (44%)
Drop outs: 10 (3 lost to follow up, 7 died)
Group 1
Betaxolol 5 mg/ml 2/day and argon laser trabeculoplasty (ALT) 360 degrees performed 1 week after inclusion. If eligible eye achieved 25 mmHg in 2 consecutive visits or other eye was 35 mmHg in 1 visit then latanoprost 50 μm/day.

Group 2
No treatment

Examination methods:
Patients were followed up at 3 month intervals for visual acuity, Goldmann tonometry, Humphrey 30-2 Full threshold visual field testing, ophthalmoscopy, slit lamp examination and optic disc photographs every 6 months.

*Visual field progression defined as worsening of 3 consecutive points in the Glaucoma Change Probability map, confirmed by 3 consecutive visual fields.

*Optic disc progression detected from baseline line and follow up photographs by a masked reader using flicker chronoscopy and
Glaucoma progression (visual or optic disc changed*) after follow up of 48 months
Data from Rolim et al., 2007124
Group 1: 39/129 (30%)
Group 2: 62/126 (49%)
p value: 0.002 (calculated by NCC-AC Chi-squared test)
Funding:
Study was supported by grants U10EY10260 and U10EY10261 from the National Eye Institute, Bethseda, USA and K2002- 74X-10426-10A from the Swedish Research Council, Stockholm

Limitations:

Additional outcomes:
Health-related quality of life scores

Notes:
Randomised using computer generated sequence.
Computerised visual field and optic disc photographs read by masked observers.
IOP evaluation also masked.
An Intention to Treat analysis was used.

Patients and clinicians were not masked to treatment allocation
Glaucoma progression (visual field and optic disc) after 6 years (range 51–102 monthsGroup 1: 58/129 (45%)
Group 2: 78/126 (62%)
p value: 0.07
Visual field progression alone after 6 years (range 51–102 monthsGroup 1: 57/129 (44%)
Group 2: 78/126 (62%)
p value: 0.005 (calculated by NCC-AC Chi-squared test)
Ocular side effects (reduction in visual acuity, floaters or conjunctivitis)Group 1: 21/129 (16%)
Group 2: 16/126 (13%)
p value: 0.43 (calculated by NCC-AC Chi-squared test)
Systemic side effects (asthma, bradycardia, depression)Group 1: 6/129 (4.6%)
Group 2: 1/126 (0.8%)
p value: 0.12 (calculated by NCC-AC Fishers exact test)
Collaborative Normal-Tension Glaucoma Study Group, 199824

Collaborative Normal-Tension Glaucoma Study (CNTGS)

Study design:
RCT

Evidence level:
1+

Duration of follow-up:
5 years.
Patient Group: Normal tension glaucoma

Inclusion criteria:
Unilateral or bilateral normal tension glaucoma with optic disc abnormalities and visual field defects and IOP ≤ 24 mmHg in either eye. Age 20 to 90 years. After 4 week washout patients required to have a median of 10 IOP readings of ≤ 20 mmHg and 3 good baseline visual fields.

Exclusion criteria: Setting: 24 clinical centres, international

All patients
N: 145

Group 1
N: 79
Age ± SD: 65.5 ± 9.6
M/F: 30/49
Mean IOP at randomisation mmHg ± SD: 16.1 ± 2.3
Visual Acuity: 0.89 ± 2.86
Mean deviation at randomisation ± SD: −7.54 ± 4.31 dB
Refraction: −0.66 ± 2.86
Ethnicity
Asian: 9
Black: 2
Hispanic: 2
White: 65
Drop outs: 5

Group 2
N: 61
Age ± SD: 66.3 ± 10.3
M/F: 17/44
Mean IOP at randomisation mmHg ± SD: 16.9 ± 2.1
Visual Acuity: 0.89 ± 0.15
Mean deviation at randomisation ± SD: −8.38 ± 5.26 dB
Refraction: −1.09 ± 3.3
Ethnicity
Asian: 3
Black: 5
Hispanic: 1
White: 51
Drop outs:
Group 1
Achieved 30% change in IOP using medical or surgical interventions except for beta-blockers or adrenergic agonists.

Group 2
No treatment

Examination methods:
Patients were followed up at 3 month intervals for first year and every 6 months thereafter. Tests performed for visual acuity, visual field using Humphrey and appearance of optic disc and optic disc photographs every year.

Visual field progression was defined by deepening of existing scotoma, expansion of an existing scotoma or new or expanded threat to fixation (cluster of 3 points) or fresh scotoma in previously normal part of visual field.
*Visual field progression was confirmed by 4/5 consecutive follow up visits showed progression relative to baseline.
Optic disc damage was independently assesses by masked observers using stereo photographs and agreed.
Glaucoma progression (optic disc or visual field progression*)
Data from Sycha et al., 2003146
Group 1: 22/61 (31%)
Group 2: 31/79 (39%)
p value: 0.7 (calculated by NCC-AC Chi-squared test)
Funding:
Glaucoma research
Foundation with grants from Oxnard
Foundation and Edward J Daly Foundation, San Francisco, USA

Limitations:
Allocation concealment and masking of outcome assessment was not clearly reported

Additional outcomes:

Notes:
Randomisation using block randomisation scheme occurred after selected eye had a visual field defect that threatened fixation.

Intention to treat analysis was performed

The study was carried out before the introduction of topical carbonic anhydrase inhibitors and prostaglandin analogues.
Visual Field Progression*Group 1: 11/61 (18%)
Group 2: 24/79 (30%)
p value: 0.09 (calculated by NCC-AC Chi-squared test)
Cataract FormationGroup 1: 23/61 (38%)
Group 2: 11/79 (14%)
p value: 0.011 (calculated by NCC-AC Chi-squared test)

Abbreviations: NR=not reported, M/F=male/female, NA=not applicable, N=total number of patients randomised, SD=Standard Deviation, CI95%= 95% Confidence Interval, ITT=Intention to Treat

From: Appendix D, Evidence tables

Cover of Glaucoma
Glaucoma: Diagnosis and Management of Chronic Open Angle Glaucoma and Ocular Hypertension.
NICE Clinical Guidelines, No. 85.
National Collaborating Centre for Acute Care (UK).
Copyright © 2009, National Collaborating Centre for Acute Care.

Apart from any fair dealing for the purposes of research or private study, criticism or review, as permitted under the Copyright, Designs and Patents Act, 1988, no part of this publication may be reproduced, stored or transmitted in any form or by any means, without the prior written permission of the publisher or, in the case of reprographic reproduction, in accordance with the terms of licences issued by the Copyright Licensing Agency in the UK. Enquiries concerning reproduction outside the terms stated here should be sent to the publisher at the UK address printed on this page.

The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore for general use.

The rights of National Collaborating Centre for Acute Care to be identified as Author of this work have been asserted by them in accordance with the Copyright, Designs and Patents Act, 1988.

PubMed Health. A service of the National Library of Medicine, National Institutes of Health.