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Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial. A multicentre, randomised controlled trial: design and methodology

Abstract

Purpose The Laser in Glaucoma and Ocular Hypertension (LiGHT) Trial aims to establish whether initial treatment with selective laser trabeculoplasty (SLT) is superior to initial treatment with topical medication for primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Design The LiGHT Trial is a prospective, unmasked, multicentre, pragmatic, randomised controlled trial. 718 previously untreated patients with POAG or OHT were recruited at six collaborating centres in the UK between 2012 and 2014. The trial comprises two treatment arms: initial SLT followed by conventional medical therapy as required, and medical therapy without laser therapy. Randomisation was provided online by a web-based randomisation service. Participants will be monitored for 3 years, according to routine clinical practice. The target intraocular pressure (IOP) was set at baseline according to an algorithm, based on disease severity and lifetime risk of loss of vision at recruitment, and subsequently adjusted on the basis of IOP control, optic disc and visual field. The primary outcome measure is health-related quality of life (HRQL) (EQ-5D five-level). Secondary outcomes are treatment pathway cost and cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, Glaucoma Quality of Life, objective measures of pathway effectiveness, visual function and safety profiles and concordance. A single main analysis will be performed at the end of the trial on an intention-to-treat basis. Conclusions The LiGHT Trial is a multicentre, pragmatic, randomised clinical trial that will provide valuable data on the relative HRQL, clinical effectiveness and cost-effectiveness of SLT and topical IOP-lowering medication. Trial registration number ISRCTN32038223, Pre-results.
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GazzardG, etal. Br J Ophthalmol 2017;0:1–6. doi:10.1136/bjophthalmol-2017-310877
ABSTRACT
Purpose The Laser in Glaucoma and Ocular
Hypertension (LiGHT) Trial aims to establish whether
initial treatment with selective laser trabeculoplasty (SLT)
is superior to initial treatment with topical medication
for primary open-angle glaucoma (POAG) or ocular
hypertension (OHT).
Design The LiGHT Trial is a prospective, unmasked,
multicentre, pragmatic, randomised controlled trial. 718
previously untreated patients with POAG or OHT were
recruited at six collaborating centres in the UK between
2012 and 2014. The trial comprises two treatment arms:
initial SLT followed by conventional medical therapy as
required, and medical therapy without laser therapy.
Randomisation was provided online by a web-based
randomisation service. Participants will be monitored
for 3 years, according to routine clinical practice. The
target intraocular pressure (IOP) was set at baseline
according to an algorithm, based on disease severity
and lifetime risk of loss of vision at recruitment, and
subsequently adjusted on the basis of IOP control, optic
disc and visual field. The primary outcome measure is
health-related quality of life (HRQL) (EQ-5D five-level).
Secondary outcomes are treatment pathway cost and
cost-effectiveness, Glaucoma Utility Index, Glaucoma
Symptom Scale, Glaucoma Quality of Life, objective
measures of pathway effectiveness, visual function and
safety profiles and concordance. A single main analysis
will be performed at the end of the trial on an intention-
to-treat basis.
Conclusions The LiGHT Trial is a multicentre, pragmatic,
randomised clinical trial that will provide valuable data
on the relative HRQL, clinical effectiveness and cost-
effectiveness of SLT and topical IOP-lowering medication.
Trial registration number ISRCTN32038223, Pre-
results.
INTRODUCTION
Primary open-angle glaucoma (POAG) is an irre-
versible optic neuropathy affecting up to 4% of
white and 15% of black populations by the age of
80,1 and a leading cause of blind registrations, falls
and loss of independence,2 significantly affecting
quality of life (QoL).3 Intraocular pressure (IOP)
is the only modifiable risk factor, the reduction of
which is proven to slow down the progression of the
disease.4 Although the effectiveness of hypotensive
drops is irrefutable, they come with a number of
potential aesthetic, sight-threatening and serious
systemic side effects,5 6 and may have a negative
impact on the success of subsequent surgical inter-
vention.7 Medical management of POAG and
ocular hypertension (OHT) requires regular moni-
toring, as well as multiple hospital visits.
Selective laser trabeculoplasty (SLT) involves a
painless outpatient application of laser to the trabec-
ular meshwork. Economic modelling has predicted
that using SLT as a first-line treatment compared
with topical medication will significantly reduce
healthcare costs,8 although this has been refuted
by others.9 Research recommendations by National
Institute for Health and Care Excellence (NICE)
and Cochrane have identified the need for robust
randomised clinical trials (RCT) investigating the
efficacy and cost-effectiveness of SLT as a first-line
treatment.10 11
This paper describes the design of the Laser in
Glaucoma and Ocular Hypertension (LiGHT)
Trial, which compares health-related quality of life
(HRQL), cost-effectiveness and clinical outcomes
of patients who start treatment with topical
IOP-lowering medication (‘Medicine-1st’ pathway)
with that of patients who are first treated with SLT
(‘Laser-1st’ pathway).
METHODS
Study design
LiGHT is a multicentre RCT unmasked to treatment
allocation. The study adheres to the tenets of the
Declaration of Helsinki and is registered at www.
controlled- trials. com (trial registration number:
ISRCTN32038223). Ethical approval was granted
by the City Road and Hampstead Research and
Ethics Committee. The trial is monitored by a Trial
Management Group, a Trial Steering Committee
and a Data and Safety Monitoring Committee.
Eligible patients are randomised on a 1:1 ratio
to receive either medical therapy or SLT as first-
line treatment for POAG or OHT. All measure-
ments influencing treatment escalation decisions,
that is, IOP, Heidelberg retina tomography (HRT)
and visual field (VF), are made by masked observers
(optometrists and/or technicians). Patients are
monitored for 3 years. Monitoring intervals and
treatment escalation decisions are guided by
Clinical science
Laser in Glaucoma and Ocular Hypertension (LiGHT)
Trial. A multicentre, randomised controlled trial:
design andmethodology
Gus Gazzard,1,2 Evgenia Konstantakopoulou,1,2,3 David Garway-Heath,1,2
Keith Barton,1 Richard Wormald,1,2 Stephen Morris,4 Rachael Hunter,5 Gary Rubin,2
Marta Buszewicz,6 Gareth Ambler,7 Catey Bunce,1,8,9 on behalf of the LiGHT Trial Study
Group
To cite: GazzardG,
KonstantakopoulouE,
Garway-HeathD, etal.
Br J Ophthalmol Published
Online First: [please include
Day Month Year].
doi:10.1136/
bjophthalmol-2017-310877
Additional material is
published online only. To view
please visit the journal online
(http:// dx. doi. org/ 10. 1136/
bjophthalmol- 2017- 310877).
For numbered affiliations see
end of article.
Correspondence to
GusGazzard, NIHR Biomedical
Research Centreat Moorfields,
Eye Hospital NHS Foundation
Trust and UCL Institute of
Ophthalmology, 162 City
Road, EC1V 2PD, London, UK;
gusgazzard@ gmail. com
Received 13 June 2017
Revised 30 July 2017
Accepted 5 August 2017
BJO Online First, published on September 13, 2017 as 10.1136/bjophthalmol-2017-310877
Copyright Article author (or their employer) 2017. Produced by BMJ Publishing Group Ltd under licence.
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2GazzardG, etal. Br J Ophthalmol 2017;0:1–6. doi:10.1136/bjophthalmol-2017-310877
Clinical science
clinical decision support software (DSS) implementing a defined
protocol based on published evidence-based guidelines, while
also attempting to capture the complexities of clinical practice.
Although this is not used in usual National Health Service prac-
tice, it was designed to mirror normal UK clinical practice and,
where it diverged from the treating clinician’s normal clinical
practice, deviations were permitted with explanatory reasons
given. Inclusion and exclusion criteria are shown in table 1.
Recruitment
Consecutive eligible patients were identified at six participating
centres from October 2012 until October 2014 (online supple-
mentary appendix 1). Patients who decided to participate were
given a baseline assessment on a different day and those who
declined were asked for a reason for their refusal.
Baseline assessment
At the baseline assessment, participants underwent visual acuity
testing (ETDRS logMAR), slit lamp examination, automated VF
testing (Humphrey field analyser (HFA) Mark II SITA standard
24–2), HRT optic disc imaging, IOP measurement, gonioscopy,
central corneal thickness (CCT) measurement, and assessment of
the optic discs, maculae and fundi. The schedule of examina-
tions is given in online supplementary appendix 2. The patients
also filled in the following questionnaires: EQ-5D five-level
(EQ-5D-5L),12 Glaucoma Utility Index (GUI),13 Glaucoma
Symptom Scale (GSS),14 Glaucoma Quality of Life-15 (GQL-15;
a visual function, rather than QoL, measure)14 and a modified
version of the ‘Client Service Receipt Inventory’ (CSRI) ques-
tionnaire to collect health-related cost data.15
Standardisation of disease stratification and individual
patient treatment IOP targets using a web-based real-time
decision support algorithm
The NICE-recommended thresholds were used for defining
disease (POAG or OHT) for entry into the study, as well as initi-
ating treatment.11 A real-time, web-based, clinical DSS, based
on the analysis of HRT, VF and IOP measurements, avoids bias
from unmasked clinicians. A disease category and stage were
defined, using preset objective severity criteria from the Cana-
dian Target IOP Workshop16 with additional central VF loss
criteria according to Mills et al.17 Severity stratification (mild,
moderate or severe) then determined the follow-up intervals
and an eye-specific ‘Treatment Target IOP’. Target IOP was
objectively defined based on both percentage reduction from
untreated IOP and an absolute value, and then adjusted during
the study according to the presence or absence of disease progres-
sion (figure 1). The lowest permitted target was 8 mm Hg for
POAG and 18 mm Hg for OHT.i Not all permutations of clinical
behaviour could be captured within the DSS, therefore deviation
by the treating consultant from DSS advice was permitted; the
reason was recorded for comparison between treatment arms,
for example, if poor concordance contributed to a failure to
meet Target IOP rather than drug effectiveness.
Randomisation and allocation of participants to treatment
groups
Randomisation was undertaken online using a web-based rando-
misation service, achieving full allocation concealment (www.
sealedenvelope. co. uk). Stratified randomisation with random
block sizes was used to randomise in a 1:1 ratio at the level of
the patient, with the stratification factors of diagnosis and treat-
ment centre. Patients with one or both eyes eligible were treated
identically.
Trial arm 1:Laser-1st pathway
Standardisation of SLT delivery was achieved by protocol-de-
fined settings and clinical endpoint of fine bubble formation
at the trabecular meshwork at least 50% of the time (online
supplementary appendix 3). One SLT retreatment was allowed,
provided there was an initial response to the treatment. After
two SLT treatments the next escalation was medical treatment.
Significant complications of laser treatment (eg, severe uveitis,
IOP spike greater than 15 mm Hg) or other new medical condi-
tions prevented repetition of SLT.
Trial arm 2: Medicine-1st pathway
Patients on the Medicine-1st pathway or patients who remained
uncontrolled on Laser-1st pathway were started on single drugs
at initiation and with each treatment switch or escalation. Drug
i
Although CCT has an effect on IOP measurement and risk of progres-
sion, the true magnitude of this interaction is unknown because of
complex non-linear interactions between CCT, ‘true’ IOP and corneal
material properties; CCT is, therefore, not used in the algorithm for
setting Target IOP. Myopia and family history are also not included in
this algorithm, as data on the effect size of these risk factors on progres-
sion rates are weak.
Table 1 Inclusion and exclusion criteria to the LiGHT Trial
Inclusion criteria Exclusion criteria
Newly diagnosed and untreated POAG or
OHT*with a decision to treat† made by a
consultant ophthalmologist‡
Advanced POAG§
18 years or older Visual acuity worse than 6/36 in a study
eye¶
Able to provide informed consent Secondary glaucoma**
Able to understand English Angle closure
Congenital/early childhood glaucoma
Previous treatment for POAG/OHT
Contraindication to SLT
Inability to use topical medical therapy
Visually significant cataract
Active treatment for another ophthalmic
condition in either eye
History of retinal ischaemia, macular
oedema or diabetic retinopathy
Age-related macular degeneration with
neovascularisation or geographic atrophy
Previous intraocular surgery††
Pregnancy or intention to become
pregnant
Medically unfit for completion of the trial
Involvement in another interventional
research study
*In one or both eyes (including pseudoexfoliation glaucoma).
†Under theNational Institute for Health and Care Excellence guidelines.11
‡Fellowship-trained glaucoma subspecialist consultant ophthalmologist.
§Visualfield loss mean deviation worse than −12 dB in the better or −15 dB in the
worse eye.
¶Uniocular patients were eligible.
**Pigment dispersion syndrome, trauma.
††Except uncomplicated phacoemulsification at least 1 year before entering the
trial.
LiGHT,Laser in Glaucoma andOcular Hypertension; OHT, ocular hypertension;
POAG, primary open-angle glaucoma; SLT, selective laser trabeculoplasty.
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classes for first-line, second-line or third-line treatment were
defined as per NICE11 and the European Glaucoma Society
(EGS) guidance18 (first line: prostaglandin analogues; second
line: beta blockers; third or fourth line: topical carbonic anhy-
drase inhibitors or alpha-agonists). Fixed combination drops
were allowed. Systemic carbonic anhydrase inhibitors were
only permitted as a temporary measure while awaiting surgery
and did not influence treatment escalation. Maximum medical
therapy (MMT) is defined as the most intensive combination
of drops an individual can reasonably, reliably and safely use
and varied between patients. MMT is defined as a maximum of
three drugs and five dosages per day for triggering the offer of
surgery, although MMT may be less for certain patients; more
agents could be used for patients who decline trabeculectomy.
Criteria for failure to meet and to reassess Target IOP are shown
in online supplementary appendix 4 .
Treatment escalation
To minimise bias for escalating treatment, standardised criteria
were used according to a protocol following the international
guidelines by the EGS, American Academy of Ophthalmology
Preferred Practice Pattern and the South East Asia Glaucoma
Interest Group. Treatment was escalated under the following
circumstances:
1. ‘Strong Evidence’ of progression irrespective of IOP
Figure 1 Process for Target IOP setting. *Disease stratification according to Mills et al.17 IOP, intraocular pressure; GON,glaucoma optic neuropathy;
OHT, ocular hypertension; POAG, primary open-angle glaucoma; VF, visual field.
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2. IOP above Target by more than 4 mm Hg at a single visit
3. IOP above Target by less than 4 mm Hg and ‘Less Strong
Evidence’ for progression; if the IOP is above Target by less
than 4 mm Hg with no evidence for progression, then the
‘Treatment Target IOP’ is re-evaluated.
The process for escalating treatment is shown in figure 2.
Defining disease progression by HRT and VF
A minimum of two reliable baseline VF measurements (based on
reliability indices and clinician judgement) and three follow-up
VF were required. ‘Possible VF Progression’ was defined as dete-
rioration of ≥3 locations on the HFA glaucoma progression
analysis (GPA) with probability of <0.05 on three consecutive
occasions. ‘Possible VF Progression’ was defined as deterioration
of ≥3 locations on the HFA GPA with probablility of <0.05
on two consecutive tests. Any treatment escalation triggered by
worsening VF loss required senior clinician verification.
Progression of optic disc damage was defined as a statistically
significant rate of neuroretinal rim loss exceeding 1% of baseline
rim area/year on a minimum of five repeat HRT images.
Progression of glaucoma was defined as ‘Strong evidence’=GPA
‘Likely progression’ and/or HRT rim area >1% per year
(p<0.001); ‘Less strong evidence’=GPA ‘Possible progression’
and/or HRT rim area >1% per year (p<0.01).
Follow-up procedure and timing
Follow-up intervals were initially set at entry to the study
according to NICE guidance11 and subsequently adjusted on
the basis of IOP control, glaucoma progression or adverse reac-
tions. The routine schedule of appointments and assessments for
patients is shown in online supplementary appendices 2 and 5,
respectively.
Adverse events
Adverse events were reported according to standard operating
procedures to achieve standardisation across sites and between
treatment allocation, with an annual safety report to the Research
and Ethics Committee.
Outcome measures
The primary outcome measure is HRQL using EQ-5D-5L
utility scores at 3 years, calculated using the EQ-5D-5L
descriptive system and value set for England (Office of Health
Economics).19 Quality-adjusted life years (QALYs) will also be
calculated over the 36-month period using the baseline and
six-monthly follow-up questionnaires, and calculating the area
under the curve. There is a risk that the EQ-5D-5L might prove
insensitive to QoL in glaucoma; if this is the case, then a differ-
ence in cost or treatment intensity outcome will also be of value.
The following are the secondary outcomes:
Treatment pathway healthcare resource use, cost and cost-ef-
fectiveness. Healthcare resource use will be ascertained from
the record of treatment episodes and additional healthcare
contacts from a modified CSRI.15 The cost components will
include the cost of SLT, number of visits, number and type of
medications and glaucoma surgeries and clinical tests.
Glaucoma-specific treatment-related QoL will be measured
using the GUI, from which QALYs can also be derived.
Patient-reported disease and treatment-related symptoms
using the GSS.
Patient-reported visual function using the GQL-15.
Objective measurements of pathway effectiveness for
IOP-lowering and visual function preservation (eg, treatment
intensity and time taken to achieve Target IOP, the number
of Target IOP revisions, proportion of patients achieving
Target after each year of treatment, number of patients with
confirmed disease deterioration and rates of ocular surgery).
Objective safety measures for each pathway.
Concordance was assessed by two questions shown to
predict the probability of non-concordance.20
Sample size calculation
A difference in EQ-5D-5L utility scores of 0.05 has been
considered to be clinically meaningful in an Medical Research
Council (MRC)-funded trial of glaucoma surgery,21 less than the
difference between mild (0.84±0.17) and moderate (0.68±0.26)
VF loss.22 A study with 305 participants in each group would
Figure 2 Process for escalating treatment in POAG. *On two consecutive visits. **As per protocol. ^Until progression confirmed/refuted. VF
progression required three follow-up VF assessments. Maximal IOP,IOP above which surgery was offered even without progression or 35 mmHg for
OHT (see text). IOP, intraocular pressure; MMT, maximum medical therapy; POAG,primary open-angle glaucoma;VF, visual field.
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Clinical science
have 90% power to detect, at 5% significance level, a difference
in means of 0.05, assuming a common SD of 0.19 and using a
two-sided test. Allowing for 15% loss to follow-up at 36 months,
the total number required for the study is 718 (359 in each
group). The sample size was calculated using Stata V.12.
Statistical analysis plan
The statistical analysis has been published elsewhere.23 The anal-
ysis will be based on all participants as randomised, irrespec-
tive of subsequent concordance with allocated treatment. The
primary outcome will be compared between treatment arms
using regression methods that adjust for baseline EQ-5D-5L
score, IOP and disease laterality. Statistical significance will be at
5%. Mixed models will be used to investigate how primary and
secondary outcomes change over time.
DISCUSSION
LiGHT is a multicentre RCT, unmasked to treatment allocation,
designed to compare HRQL, clinical effectiveness and cost-effec-
tiveness, and clinical safety of SLT versus topical IOP-lowering
medication in treatment-naïve patients with newly diagnosed
POAG or OHT. This study addresses well one of the James Lind
Alliance glaucoma research priorities.24
In the LiGHT Trial, concern about possible confounding
effects of placebo treatment and altered compliance from sham
laser require patients to be aware of their treatment allocation.
Patients’ knowledge of prior medical treatment and/or initial
treatment with laser may influence subsequent medication-taking
behaviour and compliance. Although the patients and clinicians
are unmasked to the treatment arm, all clinical measures (IOP,
VF, HRT) are made by masked observers. Moreover, treatment
decisions are masked by the use of a computerised evidence-
based DSS. The potential for bias arising from lack of masking
patients to treatment allocation will be investigated by compar-
ison of EQ-5D and GUI in patients who use eye-drops after laser
alone with those patients who never received laser and with the
prior period when laser alone was sufficient.
Very few controlled trials have compared medical with laser
treatment in patients with POAG or OHT. The LiGHT Trial
compares the two treatment pathways in previously untreated
patients, unlike previously conducted trials.25 26 The non-ran-
domised trial by Katz et al26 is the only trial to have set a person-
alised IOP Target. The Target IOP for LiGHT is eye-specific,
objectively defined and adjusted by the DSS to avoid bias from
unmasked clinicians.
The LiGHT Trial will provide valuable data on the HRQL,
clinical effectiveness and cost-effectiveness of SLT and topical
IOP-lowering medication, with the potential to define the choice
of first-line treatment.
Author affiliations
1NIHR Biomedical Research Centre at Moorfields , Eye Hospital NHS Foundation
Trust, London, UK
2Institute of Ophthalmology, University College, London, UK
3Centre for Public Health Research, School of Health Sciences, City University,
London, UK
4Department of Applied Health Research, Institute of Epidemiology and Health Care,
University College London, London, UK
5Priment Clinical Trials Unit, University College London, Royal Free Medical School,
London, UK
6Research Department of Primary Care and Population Health, University College
Medical School, London, UK
7Department of Statistical Science, Faculty of Mathematics and Physical Sciences,
University College London, London, UK
8International Centre for Eye Health (ICEH), Clinical Research Department, London
School of Hygiene & Tropical Medicine, London, UK
9Department of Primary Care and Public Health, King’s College London, London, UK
Acknowledgements We are grateful to Emily Dowse, Karine Girard-Claudon,
Seetal Savania-Dholakia, Gurveen Panesar, Ayse Barnes, Dominic Carrington,
Emerson Tingco, Charles Amoa Kanom Bibi.
Collaborators The LiGHT Trial Study Group: Rupert Bourne, David Broadway,
Amanda Davis, Anurag Garg, Yuzhen Jiang, Sheng Lim, Joanna Liput, Timothy
Manners, Neil Nathwani, Nicholas Strouthidis, Victoria Vickerstaff, Sarah Wilson,
Haogang Zhu.
Contributors GG led the initial conception and design of the trial and writing
the protocol, acquired funding and ethics approval, is the chief investigator of the
trial, and was a major contributor in writing the manuscript. DG-H was a major
contributor to the design of the trial and the trial protocol, and was involved in the
drafting of the manuscript and critical revision of the study design. EK wrote the
manuscript together with GG and is involved in the acquisition of the data. KB was
involved in the drafting of the protocol and critical revision of the study design.
RW was involved in the drafting of the manuscript and critical revision of the study
design and protocol. SM and RH contributed to the design of the outcome measures
and the data to be collected, and was involved in the drafting of the manuscript.
GR was involved in the drafting of the manuscript and critical revision of the study
design. MB contributed in overlooking the conduct of the trial and was involved
in the drafting of the manuscript. GA contributed in the design of the outcome
measures and the data to be collected, and was involved in the drafting of the
manuscript. CB contributed in the design of the outcome measures and the data to
be collected, and was involved in the drafting of the manuscript. All authors read
and approved the final manuscript.
Funding The trial was funded by the National Institute of Health Research
Health Technology Assessment Panel (Project reference number 09/104/40) and
was sponsored by Moorfields Eye Hospital NHS Foundation Trust. The sponsor or
funding organisation had no role in the design or conduct of this research. This
report presents independent research commissioned by the NIHR; the views and
opinions expressed by authors in this publication are those of the authors and do
not necessarily reflect those of the NHS, the NIHR, MRC, CCF, NETSCC, the HTA
programme or the Department of Health.
Competing interests GG, DG-H, KB, RW, SM, RH, GR, MB, GA and CB have
received a grant from the National Institute for Health Research for the submitted
work. DG-H and RW have received financial support through the Biomedical
Research Centre at Moorfields Eye Hospital and UCL Institute of Ophthalmology. GG
received a research grant from Lumenis prior to the submitted work. GG, DG-H and
KB have conflicts of interest outside the submitted work.
Ethics approval The City Road and Hampstead Research and Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement There are no additional data at the moment.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the
article) 2017. All rights reserved. No commercial use is permitted unless otherwise
expressly granted.
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22 Aspinall PA, Johnson ZK, Azuara-Blanco A, et al. Evaluation of quality of life and
priorities of patients with glaucoma. Invest Ophthalmol Vis Sci 2008;49:1907–15.
23 Vickerstaff V, Ambler G, Bunce C, et al. Statistical analysis plan for the Laser-1st
versus Drops-1st for Glaucoma and Ocular Hypertension Trial (LiGHT): a multi-centre
randomised controlled trial. Trials 2015;16:517.
24 The james lind alliance. Priorities for glaucoma research. 2015 http://www.
lindalliance. org/ top- tens. asp.
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controlled trial: design and methodology
(LiGHT) Trial. A multicentre, randomised
Laser in Glaucoma and Ocular Hypertension
Marta Buszewicz, Gareth Ambler and Catey Bunce
Barton, Richard Wormald, Stephen Morris, Rachael Hunter, Gary Rubin,
Gus Gazzard, Evgenia Konstantakopoulou, David Garway-Heath, Keith
published online September 13, 2017Br J Ophthalmol
7
http://bjo.bmj.com/content/early/2017/09/13/bjophthalmol-2017-31087
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... Each eye was stratified at baseline and after 3 years; monitoring and treatment during the 3-year trial period were done according to the LiGHT trial protocol. 12 To validate the GLAUC-STRAT tool, clinical outcomes after at least 3 years of treatment were utilised. Specific markers of disease management and progression, aligned with the tool's aims, were used. ...
... OHT, angle closure, secondary glaucoma). However, the stability of the risk presented in this study (nearly 3/4 of Green and Amber eyes) is a result of a careful, algorithm-based follow-up, 12 whilst despite this monitoring regime approximately 25% of the Green and Amber eyes still deteriorated based on GLAUC-STRAT. The timing and frequency of follow-up may affect the outcome of treatment and is directly linked to GLAUC-STRAT's aim to prioritise care. ...
Article
Background/aims: The aim of this study was to validate the Glaucoma Risk Stratification Tool (GLAUC-STRAT-fast) currently recommended by the Royal College of Ophthalmologists for the risk stratification of patients with glaucoma in the UK National Health Service Hospital Eye Service. Methods: GLAUC-STRAT fast was applied to the LiGHT trial participants by risk-stratifying the worse eye of each patient at baseline and after 3 years of treatment. Metrics of disease severity or treatment intensity used for the validation were: increased number of monitoring visits or treatment escalations; needing a trabeculectomy; a reduction of >2 dB in visual field mean deviation (VF MD) during the monitoring period; identification of rapid VF loss on total (TD) and/or pattern deviation (PD). The proportion of eyes within each baseline stratum for each of the above markers was compared against the other strata, using a χ2 test for proportions. Results: There was an association between the baseline stratification and the number of treatment escalations needed to maintain the eye-specific target intraocular pressure (p=0.001), the number of visits needed throughout the 3-year follow-up period (p=0.001), the need for trabeculectomy (p<0.001) and absolute loss of MD over the course of the monitoring period (p<0.001). The rate of VF progression was not associated with baseline risk stratification for TD or PD progression (p≥0.007, with Bonferroni correction). Conclusion: The GLAUC-STRAT fast tool is a useful tool for risk stratifying eyes with ocular hypertension or open angle glaucoma. Further research is needed to confirm and validate its applicability to more advanced glaucomas and generalisability to clinical use. Trial registration number: The LiGHT trial is registered at controlled-trials.com (ISRCTN32038223).
... Although this study reported only self-limiting adverse effects of lasers, there are some uncommon and severe complications, such as transient corneal thinning, endothelial decompensation, foveal burn, and corneal haze, as reported in the literature [11,56,86]. Significant complications, such as severe uveitis, IOP spikes that are more than 15 mmHg, etc., are contraindications for SLT repetition [87]. In this section, prevailing complications are described and case reports of sporadic serious complications are listed. ...
Article
Full-text available
Presently, there is no efficacious treatment for glaucomatous optic neuropathy; the current treatment is focused on lowering intraocular pressure (IOP). Studies have demonstrated the safety and efficacy of selective laser trabeculoplasty (SLT) in reducing the IOP in eyes with open-angle (OAG) glaucoma or ocular hypertension (OH). Moreover, the European Glaucoma Society has instated SLT as the first-line or adjunctive treatment in OAG or OH, reiterating its clinical significance. In this review, we outline the old and the new roles of SLT, with an emphasis on clinical practice, and look further into its renewed appeal and future developments.
... Evgenia Konstantakopoulou , 1 Gus Gazzard 2,3 In 2019, the Laser in Glaucoma and Ocular Hypertension (LiGHT) randomised controlled trial reported that initial treatment with selective laser trabeculoplasty (SLT) is more cost effective than initial treatment with pressurelowering eye drops, leading to a reduced number of glaucoma surgeries and very low rates of adverse events while providing drop-free intraocular pressure (IOP) control to 78% of treated eyes after 3 years. 1 2 As a result, the European Glaucoma Society, 3 the American Academy of Ophthalmology 4 and the UK National Institute for Health and Care Excellence 5 now recommend the use of SLT as initial treatment for open-angle glaucoma (OAG) and ocular hypertension (OHT). ...
Article
Full-text available
In 2019, the Laser in Glaucoma and Ocular Hypertension (LiGHT) randomised controlled trial reported that initial treatment with selective laser trabeculoplasty (SLT) is more cost effective than initial treatment with pressure-lowering eye drops, leading to a reduced number of glaucoma surgeries and very low rates of adverse events while providing drop-free intraocular pressure (IOP) control to 78% of treated eyes after 3 years.1 2 As a result, the European Glaucoma Society,3 the American Academy of Ophthalmology4 and the UK National Institute for Health and Care Excellence5 now recommend the use of SLT as initial treatment for open-angle glaucoma (OAG) and ocular hypertension (OHT).
... In some studies with longer followup, although PAS was mentioned as not being present, it was not clear when gonioscopy to look for PAS was performed [15][16][17], while others did not mention about PAS at all [18,19]. In the recent multicenter, Laser in Glaucoma and Ocular Hypertension (LiGHT) randomized controlled trial, where compulsory gonioscopy was only required at the final 36-month visit [20,21], it was reported that no PAS was noted in the 611 subjects who completed the final visit (both Laser-1st or Medicine-1st arms) [22]. Notably, very few subjects enrolled in the LiGHT trial were East Asians; the majority being whites (70%), followed by blacks (20%), South Asians (7%), and others (including Chinese, 3%) [23]. ...
Article
Full-text available
Purpose Peripheral anterior synechiae (PAS) have been reported as a complication after argon laser trabeculoplasty, but rarely reported after selective laser trabeculoplasty (SLT). This study aims to determine the incidence and predictors of this potential complication in phakic eyes of Chinese patients. Methods A retrospective review of consecutive Chinese phakic patients who underwent SLT for primary open-angle glaucoma or ocular hypertension from 2011 to 2015 was analyzed for post-operative outcomes, including the development of PAS. Results There was a total of 292 patients (509 eyes) that were of Chinese ethnicity and eligible in our analysis. The 4-year incidence of PAS was 13.57% for the 221 eyes with documented gonioscopy after SLT, and the time, since first SLT, to PAS diagnosis was 5.62 years (2052 ± 75.2 days). After accounting for the inter-eye correlation by the mixed effect Cox regression model (AUC = 0.885), the predictors of earlier PAS diagnosis were baseline intraocular pressure (≥ 18 versus < 18) (HR = 4.6, p = 0.031), baseline use of bimatoprost (HR = 14.97, p = 0.006), and pre-existing hypertension (HR = 11.78, p = 0.016). There was no significant association of earlier PAS diagnosis with age (p = 0.434), baseline number of medications used (p = 0.693), and baseline use of brinzolamide (p = 0.326). Conclusion PAS development after SLT appears to be more common in Chinese patients, with a presumed 4-year incidence of 13.6%, based on retrospective review of eyes with subsequent documented gonioscopy findings. Trial registration: Hong Kong University Clinical Trials Registry (HKUCTR-2350).
... Selective laser trabeculoplasty (SLT) is often employed as first line treatment for lowering IOP in OAG, however, few studies have quantified an improvement in quality of life scores despite the assumed benefit of IOP lowering without the use of daily eye drops. [96][97][98] To address this, Ang et al. 99 conducted an international, randomized controlled trial of 167 treatment naïve patients with mild to moderate OAG or pseudoexfoliation glaucoma who were randomized to be treated with SLT or a topical prostaglandin analog. Quality of life was quantified using the Glaucoma Outcomes Assessment Tool (GOAT) as the primary outcome and ocular surface disease was assessed as a secondary outcome. ...
Article
Purpose: To review the most recent studies in the literature regarding the ocular surface in glaucoma patients and treatment options aimed to reduce ocular surface disease in this populationMethods: We performed a literature search in the electronic databases of PubMed CENT RAL, Google Scholar, EMBASE the Register of Controlled Trials, and Ovid MEDLINE using the following terms: "ocular surface", "dry eye", "glaucoma", "selective laser trabeculoplasty", "glaucoma surgery", "preservatives", "preservative free", "ocular surface disease index", "tear break up time", "MMP-9" and "conjunctival hyperemia".Results: Over the last several years, several studies have demonstrated the changes to the ocular surface in the setting of glaucoma, the best tests for markers of dry eye, and how management can be altered to help address ocular surface disease routinely or in preparation for glaucoma surgery.Conclusion: Ocular surface disease in the glaucoma patient population is widely recognized. It should be addressed to maximize patient compliance and quality of life.
Article
Full-text available
Purpose The LiGHT trial has shown selective laser trabeculoplasty (SLT) to be clinically and cost-effective as a primary treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT) at 3 years. This paper reports health-related quality of life (HRQL) and clinical effectiveness of initial treatment with SLT compared to intra-ocular pressure (IOP) lowering eye drops, after 6 years of treatment. Design Prospective multicentre randomized controlled trial. Participants Treatment-naïve eyes with OAG or OHT, initially treated with SLT or IOP-lowering drops. Methods Patients were randomly allocated to initial SLT or eye drops. Eye specific target IOP and monitoring intervals were based on international guidelines. After the initial 3 years of the trial, patients in the SLT arm were permitted a 3rd SLT if necessary; patients in the drops arm were allowed SLT as a treatment switch or escalation. Analysis was by intention to treat. This study is registered at controlled-trials.com (ISRCTN32038223). Main outcome measures The primary outcome was HRQL at 6 years; secondary outcomes were clinical effectiveness and safety. Results Of the 692 patients completing 3 years in the LiGHT trial, 633 (91.5%) entered the extension and 524 patients completed 6 years in the trial (82.8% of those entering the extension phase, 73% of those initially randomised). At 6 years, there were no significant differences in HRQL for EQ-5D, GUI and GQL-15 (all p>0.05). The SLT arm had better GSS scores than the drops arm (83.6 (SD 18.1) vs 81.3 (SD 17.3), respectively). 69.8% of eyes in the SLT arm remained at or below target IOP without the need for medical or surgical treatment. More eyes in the drops arm exhibited disease progression (26.8% vs 19.6%, respectively, p=0.006). Trabeculectomy was required in 32 eyes in the drops arm compared to 13 eyes in the SLT arm (p<0.001); there were more cataract surgeries in the drops arm (95 compared to 57 eyes, p=0.03). There were no serious laser-related adverse events. Conclusions SLT is a safe treatment for OAG and OHT, providing better long-term disease control than initial drop therapy, with reduced need for incisional glaucoma and cataract surgery over 6 years.
Book
Full-text available
Primary open-angle glaucoma (POAG) is a multi-factorial progressive optic neuropathy characterized by retinal ganglion cell degeneration and progressive visual field loss which, if le􀀹 untreated, may lead to blindness. Increased intraocular pressure (IOP) is considered to be the main risk factor for developing POAG, and its reduction has been shown to correlate with a decrease in glaucoma incidence and progression. Considering that fewer than 10% of the subjects with ocular hypertension (OHT) will develop morphological and/or functional glaucomatous damage within 5 years if not treated, glaucoma causes and molecular changes leading to ocular tissue damage in glaucoma are still largely unknown. The contemporary treatment of POAG is mainly oriented towards reducing IOP; the importance of the IOP reduction in other types of glaucoma, such as the “normal pressure glaucoma”, is still discussed. The IOP value is maintained by balancing the amount of fluid contained within the anterior and posterior chambers of the eye; our comprehension of the mechanisms underlying the secretion and active and passive outflow of the aqueous humor is extremely important for improving the treatment of glaucoma. Innovative pharmacological approaches, and laser and surgical procedures aiming to reduce IOP, have been developed in recent years. This book provides a compendium of topics regarding IOP, aqueous humor dynamics, tonometry, and medical and surgical techniques developed to reduce the IOP in subjects with ocular hypertension or glaucoma. This is a reprint of articles from the Special Issue published online in Journal of Clinical Medicine (ISSN 2077-0383) (available at: www.mdpi.com/journal/jcm/specialissues/Ocular Hypertension).
Article
Background: Open-angle glaucoma (OAG) is an important cause of blindness worldwide. Laser trabeculoplasty, a treatment modality, still does not have a clear position in the treatment sequence. Objectives: To assess the effects of laser trabeculoplasty for treating OAG and ocular hypertension (OHT) when compared to medication, glaucoma surgery or no intervention. We also wished to compare the effectiveness of different laser trabeculoplasty technologies for treating OAG and OHT. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2021, Issue 10); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; LILACS, ClinicalTrials.gov and the WHO ICTRP. The date of the search was 28 October 2021. We also contacted researchers in the field. Selection criteria: We included randomised controlled trials (RCTs) comparing laser trabeculoplasty with no intervention, with medical treatment, or with surgery in people with OAG or OHT. We also included trials comparing different types of laser trabeculoplasty technologies. Data collection and analysis: We used standard methods expected by Cochrane. Two authors screened search results and extracted data independently. We considered the following outcomes at 24 months: failure to control intraocular pressure (IOP), failure to stabilise visual field progression, failure to stabilise optic neuropathy progression, adverse effects, quality of life, and costs. We graded the 'certainty' of the evidence using GRADE. Main results: We included 40 studies (5613 eyes of 4028 people) in this review. The majority of the studies were conducted in Europe and in the USA. Most of the studies were at risk of performance and/or detection bias as they were unmasked. None of the studies were judged as having low risk of bias for all domains. We did not identify any studies of laser trabeculoplasty alone versus no intervention. Laser trabeculoplasty versus medication Fourteen studies compared laser trabeculoplasty with medication in either people with primary OAG (7 studies) or primary or secondary OAG (7 studies); five of the 14 studies also included participants with OHT. Six studies used argon laser trabeculoplasty and eight studies used selective laser trabeculoplasty. There was considerable clinical and methodological diversity in these studies leading to statistical heterogeneity in results for the primary outcome "failure to control IOP" at 24 months. Risk ratios (RRs) ranged from 0.43 in favour of laser trabeculoplasty to 1.87 in favour of medication (5 studies, I2 = 89%). Studies of argon laser compared with medication were more likely to show a beneficial effect compared with studies of selective laser (test for interaction P = 0.0001) but the argon laser studies were older and the medication comparator group in those studies may have been less effective. We considered this to be low-certainty evidence because the trials were at risk of bias (they were not masked) and there was unexplained heterogeneity. There was evidence from two studies (624 eyes) that argon laser treatment was associated with less failure to stabilise visual field progression compared with medication (7% versus 11%, RR 0.70, 95% CI 0.42 to 1.16) at 24 months and one further large recent study of selective laser also reported a reduced risk of failure at 48 months (17% versus 26%) RR 0.65, 95% CI 0.52 to 0.81, 1178 eyes). We judged this outcome as moderate-certainty evidence, downgrading for risk of bias. There was only very low-certainty evidence on optic neuropathy progression. Adverse effects were more commonly seen in the laser trabeculoplasty group including peripheral anterior synechiae (PAS) associated with argon laser (32% versus 26%, RR 11.74, 95% CI 5.94 to 23.22; 624 eyes; 2 RCTs; low-certainty evidence); 5% of participants treated with laser in three studies of selective laser group had early IOP spikes (moderate-certainty evidence). One UK-based study provided moderate-certainty evidence that laser trabeculoplasty was more cost-effective. Laser trabeculoplasty versus trabeculectomy Three studies compared laser trabeculoplasty with trabeculectomy. All three studies enrolled participants with OAG (primary or secondary) and used argon laser. People receiving laser trabeculoplasty may have a higher risk of uncontrolled IOP at 24 months compared with people receiving trabeculectomy (16% versus 8%, RR 2.12, 95% CI 1.44 to 3.11; 901 eyes; 2 RCTs). We judged this to be low-certainty evidence because of risk of bias (trials were not masked) and there was inconsistency between the two trials (I2 = 68%). There was limited evidence on visual field progression suggesting a higher risk of failure with laser trabeculoplasty. There was no information on optic neuropathy progression, quality of life or costs. PAS formation and IOP spikes were not reported but in one study trabeculectomy was associated with an increased risk of cataract (RR 1.78, 95% CI 1.46 to 2.16) (very low-certainty evidence). Authors' conclusions: Laser trabeculoplasty may work better than topical medication in slowing down the progression of open-angle glaucoma (rate of visual field loss) and may be similar to modern eye drops in controlling eye pressure at a lower cost. It is not associated with serious unwanted effects, particularly for the newer types of trabeculoplasty, such as selective laser trabeculoplasty.
Article
Glaucoma is the leading cause of irreversible blindness and the aim of all glaucoma treatments is to lower intraocular pressure (IOP), the only modifiable risk factor. This article summarises the identification and management of open‐angle and closed‐angle glaucoma, including medical, laser and surgical treatment options.
Article
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Background The LiGHT trial (Laser-1st versus Drops-1st for Glaucoma and Ocular Hypertension Trial) is a multicentre randomised controlled trial of two treatment pathways for patients who are newly diagnosed with open-angle glaucoma (OAG) and ocular hypertension (OHT). The main hypothesis for the trial is that lowering intraocular pressure (IOP) with selective laser trabeculoplasty (SLT) as the primary treatment (‘Laser-1st’) leads to a better health-related quality of life than for those started on IOP-lowering drops as their primary treatment (‘Medicine-1st’) and that this is associated with reduced costs and improved tolerability of treatment. This paper describes the statistical analysis plan for the study. Methods/Design The LiGHT trial is an unmasked, multi-centre randomised controlled trial. A total of 718 patients (359 per arm) are being randomised to two groups: medicine-first or laser-first treatment. Outcomes are recorded at baseline and at 6-month intervals up to 36 months. The primary outcome measure is health-related quality of life (HRQL) at 36 months measured using the EQ-5D-5L. The main secondary outcome is the Glaucoma Utility Index. We plan to analyse the patient outcome data according to the group to which the patient was originally assigned. Methods of statistical analysis are described, including the handling of missing data, the covariates used in the adjusted analyses and the planned sensitivity analyses. Trial registration The trial was registered with the ISRCTN register on 23/07/2012, number ISRCTN32038223.
Article
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Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. Pfizer, UK National Institute for Health Research Biomedical Research Centre. Copyright © 2014 Garway-Heath et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.
Article
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Background: Glaucoma is the leading cause of irreversible blindness. Although primary open-angle glaucoma is more common, primary angle-closure glaucoma (PACG) is more likely to result in irreversible blindness. By 2020, 5·3 million people worldwide will be blind because of PACG. The current standard care for PACG is a stepped approach of a combination of laser iridotomy surgery (to open the drainage angle) and medical treatment (to reduce intraocular pressure). If these treatments fail, glaucoma surgery (eg, trabeculectomy) is indicated. It has been proposed that, because the lens of the eye plays a major role in the mechanisms leading to PACG, early clear lens extraction will improve glaucoma control by opening the drainage angle. This procedure might reduce the need for drugs and glaucoma surgery, maintain good visual acuity, and improve quality of life compared with standard care.EAGLE aims to evaluate whether early lens extraction improves patient-reported, clinical outcomes, and cost-effectiveness, compared with standard care. Methods/design: EAGLE is a multicentre pragmatic randomized trial. All people presenting to the recruitment centres in the UK and east Asia with newly diagnosed PACG and who are at least 50 years old are eligible.The primary outcomes are EQ-5D, intraocular pressure, and incremental cost per quality adjusted life year (QALY) gained. Other outcomes are: vision and glaucoma-specific patient-reported outcomes, visual acuity, visual field, angle closure, number of medications, additional surgery (e.g., trabeculectomy), costs to the health services and patients, and adverse events.A single main analysis will be done at the end of the trial, after three years of follow-up. The analysis will be based on all participants as randomized (intention to treat). 400 participants (200 in each group) will be recruited, to have 90% power at 5% significance level to detect a difference in EQ-5D score between the two groups of 0·05, and a mean difference in intraocular pressure of 1·75 mm Hg. The study will have 80% power to detect a difference of 15% in the glaucoma surgery rate. Trial registration: ISRCTN44464607.
Article
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To compare outcomes of selective laser trabeculoplasty (SLT) with drug therapy for glaucoma patients in a prospective randomized clinical trial. Sixty-nine patients (127 eyes) with open-angle glaucoma or ocular hypertension were randomized to SLT or medical therapy. Target intraocular pressure (IOP) was determined using the Collaborative Initial Glaucoma Treatment Study formula. Patients were treated with SLT (100 applications 360 degrees) or medical therapy (prostaglandin analog). Six visits over 1 year followed initial treatment. If target IOP range was not attained with SLT, additional SLT was the next step, or in the medical arm additional medications were added. Primary outcome: IOP; secondary: number of steps. Sixty-nine patients were treated. Data collection terminated with 54 patients reaching 9 to 12-months follow-up. Twenty-nine patients were in the SLT group, 25 patients in the medical group. Baseline mean IOP for all eyes was 24.5 mm Hg in the SLT group, 24.7 mm Hg in the medical group. Mean IOP (both eyes) at last follow-up was 18.2 mm Hg (6.3 mm Hg reduction) in the SLT arm, 17.7 mm Hg (7.0 mm Hg reduction) in the medical arm. By last follow-up, 11% of eyes received additional SLT, 27% required additional medication. There was not a statistically significant difference between the SLT and medication groups. IOP reduction was similar in both arms after 9 to 12-months follow-up. More treatment steps were necessary to maintain target IOP in the medication group, although there was not a statistically significant difference between groups. These results support the option of SLT as a safe and effective initial therapy in open-angle glaucoma or ocular hypertension.
Article
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This article introduces the new 5-level EQ-5D (EQ-5D-5L) health status measure. EQ-5D currently measures health using three levels of severity in five dimensions. A EuroQol Group task force was established to find ways of improving the instrument's sensitivity and reducing ceiling effects by increasing the number of severity levels. The study was performed in the United Kingdom and Spain. Severity labels for 5 levels in each dimension were identified using response scaling. Focus groups were used to investigate the face and content validity of the new versions, including hypothetical health states generated from those versions. Selecting labels at approximately the 25th, 50th, and 75th centiles produced two alternative 5-level versions. Focus group work showed a slight preference for the wording 'slight-moderate-severe' problems, with anchors of 'no problems' and 'unable to do' in the EQ-5D functional dimensions. Similar wording was used in the Pain/Discomfort and Anxiety/Depression dimensions. Hypothetical health states were well understood though participants stressed the need for the internal coherence of health states. A 5-level version of the EQ-5D has been developed by the EuroQol Group. Further testing is required to determine whether the new version improves sensitivity and reduces ceiling effects.
Article
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To evaluate the incidence, severity, and factors related to drug-induced keratoepitheliopathy in eyes using antiglaucoma eye drops. In a cross-sectional study, 749 eyes from 427 patients who had used one or more antiglaucoma eye drops were examined at Niigata University Medical and Dental Hospital or related facilities. The incidence and severity of superficial punctate keratitis (SPK), patient gender and age, type of glaucoma, and type of eye drops were recorded. SPK was graded according to the AD (A, area; D, density) classification. The severity score (SS) was calculated from A x D. SPK was observed in 382 (51.0%) of 749 eyes that had received any type of antiglaucoma eye drops. While 254 eyes (33.9%) were classified as A1D1 (SS 1), 34 eyes (4.6%) had severe SPK with SS 4 or more. The number of eye drops and the total dosing frequency per day were significantly greater in SPK-positive eyes than in eyes without SPK. The number of eye drops was proportional to the frequency and severity of SPK. Among eyes that were treated with three or more eye drops, SPK was more severe and more frequent in older patients (>/=71 years). In addition, a considerable difference was detected for each type of glaucoma. Drug-induced keratoepitheliopathy is often observed in eyes that have received recent antiglaucoma eye drops. The number of eye drops, the total dose frequency per day, patient age, and type of glaucoma may affect this condition. We have to consider not only the effects on intraocular pressure but also the incidence and severity of drug-induced keratoepitheliopathy as a frequent side effect of glaucoma medications.
Article
Purpose: Adjunctive Laser trabeculoplasty (LT) is an alternative to topical medications for open-angle glaucoma (OAG). The purpose was to: (1) identify predictors of LT versus glaucoma medication treatment; and (2) estimate the resource utilization and short-term costs associated with LT versus medication management. Design: Retrospective administrative claims analysis. Methods: Medical and pharmacy claims data between 2007-2012 were analyzed to identify prostaglandin analog monotherapy OAG patients with an index-date LT claim or second medication class claim. Patients were followed for 12-months pre-index and 24 months post-index. Predictive LT attributes included age, sex, employment status, medication adherence, comorbidity status, and geographic region. Short-term costs included glaucoma-specific and comprehensive healthcare encounters. Cohort comparisons were analyzed using chi-square and Student's t tests, logistic regression (predictive), and generalized linear models (cost). Results: The study included 4,743 LT and 16,484 medication patients. Baseline demographics were similar but significant differences were identified for comorbidities, adherence, and geography. Younger age (odds ratio [OR]: 1.21; P<.001), low adherence (OR: 1.18; P=.001), high comorbidities (OR: 1.12; P=.006), and region (OR: 1.50; P<.001) significantly predicted LT receipt. Within LT patients, 60% did not have a pharmacy claim 45 days post-index; by 2 years, this reduced to 20%. LT attributed significantly higher medical ($2,684 vs $1,980; P<.0001), lower pharmacy ($807 vs $1,467; P<.0001), and greater overall costs ($3,441 vs $3,408; P=.325). Conclusions: Poor adherence, younger age, and more comorbidities were predictors of receiving LT. Despite the potential for LT to address adherence, most patients had a medication claim within 2 years. Overall, LT does not provide glaucoma-specific cost savings.
Article
Objective To develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale (GSS). Design Cross-sectional study of symptoms, functional impairment, and vision-targeted health-related quality of life among persons with glaucoma. Patients A sample of 147 persons with glaucoma among a broad range of treatment categories from 4 tertiary care glaucoma centers and 44 persons without eye disease enrolled from the same 4 centers. Main Outcome Measures Participants completed a modified version of the Ocular Hypertension Treatment Study 10-item symptom checklist. Participants also completed 2 vision-specific measures, the National Eye Institute Visual Function Questionnaire and the VF-14. Participants underwent a clinical evaluation, including ocular and medical history, dilated ophthalmic examination, and Humphrey 24-2 automated visual field testing. Results The GSS has 2 underlying domains that demonstrate sufficient internal consistency reliability for between-group comparisons. The GSS discriminates well between persons with and without glaucoma. Additionally, tests of association with clinical markers of glaucoma severity support the clinical validity of the measure and tests of association with established vision-targeted measures provide evidence of construct validity. Conclusion The simplicity, brevity, and psychometric properties of the GSS support its use in clinical practice and research to quantify symptoms in patients with glaucoma and to assist in investigations concerning the effect of glaucoma and treatments.
Article
Objective: To develop and validate a predictive model to estimate the probability of being nonadherent to topical glaucoma medications. Design: Prospective cohort study. Participants: Patients being treated with once-daily prostaglandin eye drops. Methods: A predictive model for nonadherence was developed from the Travatan Dosing Aid (TDA) study (n = 196) using stepwise logistic regression. The performance of the TDA-derived model was assessed using a separate cohort of subjects from the Automated Dosing Reminder Study (ADRS; n = 407). The assessment was based on regression coefficients, discrimination, and calibration. We also developed a scoring system from the TDA-derived model to simplify the estimation of risk for clinical use. Main outcome measures: Usage of drops was monitored electronically for 3 months in both studies. Adherence was calculated as the percentage of days on which a dose was taken within 4 hours of the average dosing time for that patient. Nonadherence was defined as taking ≤ 75% prescribed doses within a window starting 2 weeks after the baseline visit until 2 weeks before the follow-up visit. Results: Six factors, including younger age, black race, worse general health status, shorter duration of glaucoma medication therapy, lower self-reported adherence, and admitting to not following doctors' orders, were associated with being nonadherent and were included in the predictive model. The coefficients for the TDA-derived and the ADRS-derived predictive models were similar. The risk scoring system developed from the TDA study had good discrimination (area under the receiver operating characteristic curve of 0.80) and calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.102) when applied to the ADRS population. Conclusions: The TDA-derived predictive model for nonadherence performed well in an independent population. A risk scoring system was developed using demographic data and patient responses to 4 questions to provide an estimate of the probability of being nonadherent.