White Paper - QoIOP Control Concept in Glaucoma

Expert Recommendations for Glaucoma
CONFIDENTIAL – for internal and faculty distribution only 1

Expert Recommendations for Glaucoma
Management in Asia
Practical clinical guide for ophthalmologists to

implement the quality of intraocular pressure (QoIOP)
control concept in Asian patients with glaucoma
Supported by Santen Pharmaceuticals Asia Pte. Ltd.

Disclaimer
The information disclosed is based on the best available scientific data as interpreted by
an expert faculty of ophthalmologists from across Asia with a special interest in glaucoma
and a desire to implement the quality of intraocular pressure (QoIOP) control concept in
clinical practice across the region. The development of this document followed an
iterative process, with regular feedback and input from all members of the expert faculty.
This document includes a comprehensive overview of the considerations for

ophthalmologists to implement the QoIOP control concept in Asian patients with
glaucoma. Availability of assessment tools, diagnostics, and treatments may differ
between countries across Asia, as well as within regions and clinics. The
information presented is not intended to promote or recommend any indication, dosage,
or other claim not supported by licensed product information. Santen only supports the
promotion of products in a manner consistent with approved labeling. References
to specific drugs, instruments, and other products are made for illustrative purposes only
and are not intended to constitute an endorsement of such.
The information presented provides guidance for the pattern of practice, not for the care
of any individual. While all efforts have been made to provide solid clinical evidence for all
information contained within this paper, this is not always available; some information
therefore is based on the opinion and clinical experience of the expert faculty. The
information is intended to meet the general needs of most ophthalmologists
and patients, it cannot possibly meet the needs of all. Any treatment decisions should be
made on an individual patient basis after evaluation of the benefits and risks of available
therapies. Important points to consider in making decisions in clinical practice
include: (1) clinical circumstances (personal and material settings, clinical
practice guidelines, etc.); (2) appropriateness of the direct application of the information
to the patient’s symptoms and signs; (3) the availability and/or limitations in tools,
treatments, and time of the attending physician; (4) the resource constraints imposed by
the medical facility; and (5) health insurance system limitations.

Asian glaucoma expert faculty members:
Dr Seng Kheong Fang (International Specialist Eye Centre, Malaysia)
Dr Ronnie George (Sankara Nethralaya, Chennai, India)
Prof. Kessara Pathanapitoon (Faculty of Medicine, Chiang Mai University, Thailand)
Assoc. Prof. Shamira Perera (Singapore National Eye Centre, Singapore)
Prof. Chungkwon Yoo (Department of Ophthalmology, Korea University Hospital, Korea

University College of Medicine, Korea)

List of abbreviations
AGIS Advanced Glaucoma Intervention Study
APGS Asia Pacific Glaucoma Society
BAK Benzalkonium chloride
CAI Carbonic anhydrase inhibitors
CCT Central corneal thickness
CLS Contact lens sensors
EGS European Glaucoma Society
GAT Goldmann applanation tonometry
HFA Humphrey Field analyzer
LASIK Laser assisted in situ keratomileusis
LiGHT Laser in Glaucoma and Ocular Hypertension
MIGS Minimally invasive (or micro-incisional) glaucoma surgery
NTG Normal-tension glaucoma
OCT Optical coherence tomography
OH Ocular hypertension
OPP Ocular perfusion pressure
OSD Ocular surface disease
OSDI Ocular Surface Disease Index
PACG Primary angle-closure glaucoma
PAPS Prostaglandin-associated periorbitopathy syndrome
PF Preservative-free
PGA Prostaglandin analogs
POAG Primary open-angle glaucoma
QoIOP Quality of intraocular pressure
SITA Swedish Interactive Thresholding Algorithm
SLT Selective laser trabeculoplasty
UKGTS United Kingdom Glaucoma Treatment Study
VF Visual field
WDT Water drinking test

Table of contents
Disclaimer .............................................................................................................................................. 3
Asian glaucoma expert faculty members: .......................................................................................... 4
List of abbreviations ............................................................................................................................. 5
Table of contents ................................................................................................................................... 6
Abstract .................................................................................................................................................. 7
Introduction............................................................................................................................................ 8
Overview of glaucoma in Asia ............................................................................................................. 8
Challenges to effective glaucoma management in Asia ..................................................................... 8
Screening ..........................................................................................................................................8
Diagnosis and beyond ......................................................................................................................8
Guideline-recommended glaucoma therapies ...............................................................................10
Poor patient adherence to glaucoma treatment .............................................................................10
Moving away from quantity-based IOP measurements and toward QoIOP control in clinical practice
........................................................................................................................................................... 11
Methods ................................................................................................................................................ 11
Results: Considerations for ophthalmologists to implement the QoIOP control concept in Asian
patients with glaucoma....................................................................................................................... 12
IOP reduction ..................................................................................................................................... 12
Suggested target IOP (range) ........................................................................................................12
IOP reduction methods ...................................................................................................................14
Other options for lowering IOP .......................................................................................................18
IOP response rate ............................................................................................................................. 21
Why is it important to consider IOP response rate? .......................................................................21
When to conduct IOP measurements to determine response rate to medication .........................21
How to define ‘non-response’ to treatment.....................................................................................22
Long-term IOP control and VF stability ............................................................................................. 24
Why is it important to consider long-term IOP control? ..................................................................24
When to assess VF: Recommended frequency of VF evaluation .................................................24
How to achieve an adequate number of VF tests to monitor disease progression .......................26
24-hour IOP fluctuations and monitoring........................................................................................... 28
Why is it important to consider IOP fluctuations?...........................................................................28
When and how to measure IOP to determine IOP fluctuations .....................................................29
Treatment adherence and persistence in patients ............................................................................ 32
Why is it important to consider treatment adherence? ...................................................................32
How to identify and improve patient adherence .............................................................................32
Conclusion ........................................................................................................................................... 35
References ........................................................................................................................................... 36

Abstract
Glaucoma is the leading cause of irreversible blindness around the world, affecting a
disproportionately high number of patients in Asia (~60%). Providing effective glaucoma treatment
in Asia can be challenging because of numerous factors: a general lack of awareness of the
importance of glaucoma screening, an insufficient ability to correctly evaluate, diagnose and
monitor patients, restricted access to appropriate medications, and poor treatment adherence.
Currently, glaucoma management is mainly focused on the quantity-based numerical reduction of
intraocular pressure (IOP) rather than holistic, quality-based approaches to glaucoma and IOP
management. In addition to IOP reduction, key considerations should include: rate of response to
treatment, long-term control of IOP as well as visual field (VF) stability, the role and impact of 24-
hour fluctuations in IOP, and the importance of ensuring patients adhere to their prescribed
treatments. Together, these considerations constitute the quality of IOP (QoIOP) control concept.

Introduction
Overview of glaucoma in Asia
By 2040, it is estimated that ~111.8 million patients aged 40–80 years will be living with glaucoma
globally.1 This is a significant rise from the 2020 global estimate of ~76 million,1 and is largely
attributable to the increase in glaucoma cases predicted in Asia (from ~59.5 million cases in 2020
to ~80.9 million, in 2040).2
Furthermore, by 2040, South-Central Asia is expected to have the highest number of patients with
primary open-angle glaucoma (POAG; ~23.3 million) and secondary glaucoma (~4.3 million),
surpassing East Asia which is currently ranked first for these subtypes. East Asia is still expected
to have the highest number of patients with primary angle-closure glaucoma (PACG;
~9.1 million).2
Given the large and increasing number of patients currently living with glaucoma across Asia,
particularly in South-Central and East Asia, it is vital that patients are identified and managed
appropriately using quality-based approaches to reduce the burden on patients and healthcare
systems.
Challenges to effective glaucoma management in Asia
Screening
While patient education and population-based screening initiatives are key, such programs can
be difficult to implement and are largely dictated by the national health insurance system or
policies. In resource-poor countries, this can be further complicated by a lack of access to
adequate resources and acceptable screening techniques.2 Thus, it is important to focus on
improving partnerships between ophthalmologists, optometrists, and allied healthcare
professionals to increase awareness of early detection as well as better implementation of the
QoIOP control concept in clinical practice following diagnosis.
“To date, a Malaysian initiative to encourage partnerships between ophthalmologists and

optometrists has shown promising results in urban areas, while rural involvement has
been more challenging. Additionally, nurses in Thailand are being trained to evaluate
patients, and social media initiatives during World Glaucoma Week have been used to
raise awareness and educate patients on glaucoma.”
– Commentary by faculty members
Diagnosis and beyond
Another challenge faced by ophthalmologists relates to diagnosing different types of glaucoma,

which brings into question the best method for screening patients to ensure a correct diagnosis.

“It is important to consider glaucoma beyond quantity-based IOP measurements and
incorporate ancillary testing of visual field (VF) and/or gonioscopy to evaluate the optic
nerve or anterior chamber angle as part of a quality-based approach.”
Such measurements are particularly important for the diagnosis and management of normal-
tension glaucoma (NTG), as patients with this glaucoma subtype present with IOP that is within
the normal range.3
“Despite the importance of looking beyond quantity-based IOP measurements,

there is currently little emphasis on performing ancillary testing.”
Relying on quantity-based IOP measurements alone, and consequently

overemphasizing IOP reduction, may lead to other clinically relevant aspects of
glaucoma being overlooked.
Where access to VF and/or gonioscopy is limited, it may be tempting to rely on optical coherence
tomography (OCT) to support diagnosis. However, this non-standard technique often results in
false-positives (‘red disease’) that lead to misdiagnosis and unnecessary treatment.4 OCT is less
sufficient for the detection of disease progression in patients with advanced glaucoma, even with
macular or retina nerve fiber layer scans, and thus should not be used as a replacement for VF
testing.5
Further complications may arise when attempting to diagnose glaucoma in patients with other
ocular conditions. For example, high myopia (refractive error of ≥-6.00 diopters) not only
increases a patient’s risk for developing glaucoma,6 but may lead to optic nerve changes that are
indistinguishable from those seen in patients with glaucoma.4 Given the prevalence of high
myopia is increasing, particularly in patients from East Asia,6 it is important to consider its impact
on glaucoma diagnosis. Additionally, although a large cup-to-disc ratio has historically been used
to diagnose glaucoma and predict the likelihood of disease progression, there are large
differences in the size and shape of optic discs which make cup-to-disc ratio assessment
unreliable.
Follow-up assessment to determine response/VF preservation and the rate of VF progression is

important when monitoring glaucoma, to enable the provision of long-term, quality-based
assessment and informed treatment choices. While IOP measurements determined during office
hours may be considered normal or within the target IOP range, these measurements do not
reflect IOP fluctuations throughout the day, which are known to increase the risk of accelerated
disease progression.7,8 In fact, the Advanced Glaucoma Intervention Study (AGIS) reported that
for every 1 mmHg increase in IOP fluctuation, the odds of VF progression increases by ~30%.9 As

such, by relying on singular IOP measurements alone to assess treatment adequacy, a large
number of patients may receive inadequate management, leading to further visual impairment or
even blindness.10 This highlights the importance of VF assessments as part of a quality-based
approach to glaucoma management. However, the challenges of performing VF testing noted
above will need to be overcome to allow ophthalmologists to provide targeted care for patients.
Increasing awareness and placing an emphasis on the need for more frequent VF testing as part
of a quality-based approach may help secure better resources to enable sufficient VF analysis.
Guideline-recommended glaucoma therapies
While the Asia Pacific Glaucoma Society (APGS) and European Glaucoma Society (EGS)
guidelines outline ideal treatment practices in the absence of more specific local guidelines, such
guidelines may not be relevant across Asia due to lack of access to appropriate treatments in
some countries. The cost of prostaglandin analogs (PGAs) is generally not an issue across the
Asia Pacific region, but other barriers are faced such as limited market access. Additionally, the
quality of ophthalmic generics is a global issue, largely occurring because clinical studies are not
usually required for the approval of generics in ophthalmology.5
Poor patient adherence to glaucoma treatment
Patient adherence is a complex issue with multiple and varied contributing factors.11 Non-
adherence rates of up to 80% have been reported for medical treatments in general,12 and
critically, a lack of adherence has been associated with VF progression and blindness in patients
with glaucoma.12,13
Side effects of glaucoma medications can have a major impact on adherence to treatment.
Corneal and conjunctival toxicity commonly result from a reaction to preservatives, particularly
benzalkonium chloride (BAK), in glaucoma medications.14
“In the short-term, adverse effects may include hyperemia,

while evidence of ocular surface disease (OSD) may be seen in the long-term.”
Prostaglandin-associated periorbitopathy syndrome (PAPS) is also now recognized as a clinical

and cosmetic side effect of long-term treatment with topical PGA, particularly in patients over 60
years.15 The occurrence of PAPS may not only have an impact on treatment adherence,15 it can
also affect IOP measurements, potentially confounding follow-up assessment to determine
treatment response and monitor disease progression.
Poor treatment adherence has been associated with VF progression and blindness.12,13
Therefore, better communication with patients to educate them on the side effects and expected
benefits from treatment may lead to improved treatment adherence, and should form part a

quality-based approach to glaucoma management. Furthermore, initiating PF formulations for the
treatment of dry eye disease (or switching to such medications as needed) may help to mitigate
the negative effects experienced by patients.16
Moving away from quantity-based IOP measurements and toward QoIOP

control in clinical practice
A shift in mindset from ‘quantity-based IOP measurements’ to ‘quality-based IOP control’ is
needed for better management and treatment of patients with glaucoma. Given the large and
increasing number of patients currently living with glaucoma across Asia, particularly in South-
Central and East Asia,1,2 it is vital that clear and consistent, practical clinical guidelines are
available to assist ophthalmologists with the implementation the QoIOP control concept in clinical
practice.
The QoIOP concept incorporates five key areas to provide a holistic approach to glaucoma and
IOP management:
1. IOP reduction
2. IOP response rate
3. Long-term IOP control and VF stability
4. Twenty-four (24)-hour fluctuations
5. Treatment adherence and persistence in patients
This paper outlines and provides a detailed discussion of these key aspects, to provide
ophthalmologists with a better understanding of the QoIOP control concept with the hope of
facilitating wider implementation of QoIOP throughout Asia.
Methods
Three meetings were held between August 2020 and October 2022 to solicit insights and
feedback from glaucoma experts from the Asia Pacific region. The aims of these meetings were
to address the importance of the QoIOP control concept, the challenges associated with its
practical implementation, and to develop a practical clinical guide for ophthalmologists.
The aim of this paper is to provide recommendations from glaucoma experts to inform
ophthalmologists about the QoIOP control concept, to facilitate wider implementation of QoIOP
throughout Asia.

Results: Considerations for ophthalmologists to implement the QoIOP
control concept in Asian patients with glaucoma
IOP reduction
Suggested target IOP (range)
The ultimate aim when treating patients with glaucoma is to reduce IOP to slow the deterioration
of VF and maintain or improve the patient’s quality of life.5 Target IOP is defined by the APGS as
‘the pressure range estimated to slow or halt disease progression’ while the EGS guidelines
define target IOP as ‘the upper limit of IOP judged to be compatible with [the] treatment goal’.5,17
There are various methods for calculating the target IOP; however, all provide similar target
ranges according to the stage of glaucoma. As such, no specific algorithm is recommended. Initial
target ranges are outlined in Figure 1.
Figure 1: Initial target IOP ranges based on the stage of glaucoma.5,17

IOP: intraocular pressure.
“Although the guideline above outlines target IOP ranges based on numerical values,
target IOP may need to be set on a case-by-case basis. For example, when initially
prescribing treatment for patients with severe/advanced glaucoma, setting a numerical IOP
target or target range can be useful as these patients require a more significant initial
reduction in IOP. However, for patients with mild/early or moderate glaucoma, it may be
useful to set the target IOP based on a percentage reduction from baseline instead. This
can be used throughout the patient life cycle and adjusted as needed or updated to
numerical values during follow-up visits. This may help to make the goal more ‘realistic’.
An important factor to keep in mind is that it may be difficult to achieve a 20% IOP
reduction in patients whose initial baseline IOP that is very low (e.g. early teens). In this
case, numerical targets may be more appropriate.”

The stage of glaucoma (e.g. mild/early, moderate, or severe/advanced) is determined based on
the severity of mean VF defect (rather than IOP measurement), where the mean VF defect
ranges are defined as follows:5
• Mild/early glaucomatous loss: mean VF defect of ≤6 decibels

• Moderate glaucomatous loss: mean VF defect of >6 decibels and ≤12 decibels
• Severe/advanced glaucomatous loss: mean VF defect of >12 decibels
Several additional factors should be considered when setting the target IOP for individual
patients, including the patient’s life expectancy, baseline IOP, additional risk factors (e.g.
pseudoexfoliation syndrome/glaucoma), and the estimated rate of progression (a patient
expected to have a fast rate of progression will require a lower target IOP).5,17 Other factors to
consider include family history, planned interventions and any expected adverse outcomes,
patient preference, socio-economic factors, as well as the non-glaucomatous eye (if applicable).5
Furthermore, it is important to also consider the possibility of confounding factors when

performing IOP measurements. Decreased central corneal thickness (CCT) is a known
independent risk factor for glaucoma progression. In addition, in patients with thin corneas, IOP
measurements may be underestimated. Additionally, an awareness of a patient’s ocular history
may facilitate better understanding of results and a tailored treatment and monitoring approach.
For example, the laser assisted in situ keratomileusis (LASIK) procedure is known to cause
corneal thinning; patients who have previously undergone this procedure may need more
careful monitoring to compensate for their artifactually lower IOP measurements.18 It is also
important to note that average baseline CCT ranges may differ between patient populations (for
example, a mean CCT of ~505 µm [SD ~30 µm] has been observed in patients from rural India
and in Mongolians compared with a mean CCT of ~540 µm [SD ~35 µm] in patients from Europe
or in Chinese Singaporeans).17 As such, a thorough understanding of the patient’s CCT will
enhance interpretation of IOP.17
The EGS also recommends that a patients’ target IOP is re-evaluated regularly, and adjusted
where there is evidence of disease progression (per quality-based assessments) or where a
patient has developed ocular or systemic comorbidities (Figure 2).5

Figure 2: Adjustment of target IOP.
Source: European Glaucoma Society (EGS) Terminology and Guidelines for Glaucoma. 5th ed.5
IOP: intraocular pressure; NR: not reached.
IOP reduction methods
For newly diagnosed patients, both the APGS and EGS guidelines recommend initiating
treatment with monotherapy.5,17 Overall, medications within the PGA drug class have the greatest
efficacy for reducing IOP with a good safety profile, and are thus recommended for
first-line treatment. Other types of anti-glaucoma medications include β-receptor antagonists (β-
blockers; selective and non-selective), α₂-adrenergic agonists (selective), carbonic anhydrase
inhibitors (CAI), Rho kinase inhibitors, cholinergic drugs, and hyperosmotic agents (Table 1).5,17
Four PGAs (bimatoprost, latanoprost, travoprost, and tafluprost), have been shown to selectively
target the F-prostanoid receptor and exhibit similar mean IOP-lowering capabilities in patients
with POAG and NTG.19-21 If IOP control is insufficient following initial monotherapy, it is
recommended to switch patients to a different monotherapy rather than adding another
medication.5,17 There is evidence to suggest that some patients who did not respond to initial
treatment with one PGA may respond to a different PGA upon switching.21 This may therefore be

considered, in addition to switching to a drug of a different class.5 It should be noted that patients
with very high IOP and severe disease at baseline may be initiated with fixed-dose combinations
or combination therapy with medications from different drug classes.5,17
If IOP control is insufficient following monotherapy, the addition of a second medication (with a
different pharmacological action) may be considered. However, as part of a quality-based
approach to patient care, it is important to keep in mind that addition of a second medication may
reduce patient adherence to treatment as well as increase preservative exposure, increasing the
risk of adverse reactions to treatment. Fixed-dose combinations are therefore preferred.5,17
“Fixed-dose combinations of PGA-β-blockers are preferred over other combinations.”
The fixed-dose combination of tafluprost-timolol is generally well accepted for IOP control.
Evidence suggests that in patients with POAG and ocular hypertension (OH) who have ceased
PGA or β-blocker monotherapy due to insufficient IOP control or intolerance may benefit from
switching to tafluprost-timolol fixed-dose combination.22 Patients can administer the drug in the
morning or evening,22,23 and Konstas and colleagues demonstrated significantly reduced 24-hour
IOP with either morning or evening administration of tafluprost-timolol fixed-dose combination
compared with latanoprost. Evening dosing with tafluprost-timolol was associated with
significantly improve daytime and 24-hour IOP control when compared with morning dosing.23
Table 1. Dosage and efficacy of various anti-glaucoma drug classes.5,17,24-27
Daily Efficacy
Drug class Mechanism of action
dosage (IOP reduction)
PGAs Increases aqueous outflow via uveoscleral pathway 1x 25–35%
β-blockers* Decreases aqueous humor production 1x to 2x 20–25%
α₁-blockers Increases aqueous outflow via uveoscleral pathway 2x 15–20%
Decreases aqueous humor production and
α₂-agonists† 2x to 3x 18–25%
increases aqueous outflow via uveoscleral pathway
α₁β-blockers Increases aqueous outflow via uveoscleral pathway 2x 20%
CAIs
Topical 2x to 3x 20%
Decreases aqueous humor production
Systemic 2x to 4x 30–40%
Rho-kinase inhibitors Increases aqueous outflow via trabecular meshwork 1x to 2x 20%

Cholinergic drugs Increases aqueous outflow via trabecular meshwork 3x to 4x 20–25%
Stat
Hyperosmotic agents Dehydrates and reduces vitreous volume 15–30%
dose(s)
Increase aqueous outflow via trabecular meshwork

EP2 receptor agonists 1x 15–35%
and uveoscleral pathway
Nitric oxide Increase aqueous outflow via trabecular meshwork

1x 26–34%
donating-PGA and uveoscleral pathway

Proprietary fixed-dose As described for each monotherapy
combinations
β-blocker + CAI 2x 25–30%
β-blocker + PGA 1x 25–35%
β-blocker + pilocarpine 2x 25–30%
β-blocker + α₂-agonist 2x 25–35%
CAI + α₂-agonist 2x to 3x 25–35%
Rho-kinase inhibitor + 1x 30–36%
PGA
*If a patient is taking systemic β-blockers, the decrease in IOP with topical β-blockers is likely to be reduced, and the
potential for systemic side effects increased: consider other drug classes first; †α₂-Agonists are absolutely
contraindicated for patients taking MAOIs and for children <2 years.
CAI: carbonic anhydrase inhibitors; EP2: E-prostanoid subtype 2; PGA: prostaglandin analog.
Newer anti-glaucoma medications have emerged in recent years, and include non-prostaglandin,
selective E-prostanoid subtype 2 (EP2) receptor agonists, Rho kinase inhibitors, and nitric oxide
donating-PGAs. Omidenepag isopropyl is a promising PGE2 receptor agonist with similar IOP-
lowering capabilities to traditional PGAs. Furthermore, as omidenepag is a non-prostaglandin
agonist, it exerts its IOP-lowering mechanism without causing PAPS, a common side effect of
traditional PGAs.28
The MERCURY-1 and MERCURY-2 studies reported that Rho kinase inhibitors (i.e. netarsudil or
ripasudil) can reduce IOP in patients with POAG or OH.29,30 However, this class of drug appears
to be inferior compared with timolol or latanoprost monotherapies.
“The expert faculty concluded that combination of Rho kinase inhibitors

with latanoprost or timolol may lead to an additional reduction in IOP
compared with monotherapy using any of these three medications.”
It was noted that none of the trials included in the review reported data related to disease
progression (e.g. VF defects, evaluation of optic discs) or patient reported outcomes, thus, more
research is needed to confirm the role of Rho kinase inhibitors for the treatment of glaucoma.31
Latanoprostene bunod is an example of a nitric oxide donating-PGA that can lower IOP in
patients with POAG and OH.32 It provides a dual mechanism of action for IOP reduction (via
conversion of the active ingredient to latanoprost acid and nitric oxide, both of which are capable
of independently lowering IOP), and may be superior to monotherapy with latanoprost or timolol.
Furthermore, latanoprostene bunod is generally well tolerated, with a safety profile similar to that
of latanoprost.32

Safety and tolerability considerations (topical medications)
Preservatives are responsible for many of the adverse effects observed in patients administering
topical glaucoma medications, causing discomfort and poor treatment adherence. The presence
of preservatives, particularly BAK which is found in ~70% of ophthalmic medications, has been
associated with corneal and conjunctival toxicity.14 More specifically, BAK is commonly found in
glaucoma medications, with concentrations ranging from 0.004% to 0.02% per mL (Table 2).24-
26,33-43
Wolfram and colleagues have demonstrated that patients using preservative-containing
medications are more than twice as likely to report non-adherence compared with those on PF
formulations.44 Furthermore, real-world data have shown that switching to PF-fixed-dose
combinations improves patient tolerability without compromising IOP reduction.22 Given the
increased likelihood of VF progression and blindness in patients who are non-adherent to their
anti-glaucoma medications,12,13 initiating or switching to PF-fixed-dose combinations should be
considered as part of QoIOP control practice. Furthermore, given the risk of developing OSD with
the use of preservative-containing medications, PF medications should be preferentially
prescribed for pre-operative patients and those with pre-existing OSD.
Long-term and/or unilateral use of traditional PGAs is also commonly associated with
development of periocular changes and PAPS, reported in >40% of patients treated for at least
three months, and >60% of patients after six months of treatment.45,46 Furthermore, patients aged
>60 years are up to three times more likely to develop signs of PAPS.15,46 PAPS is characterized
as a constellation of adverse events occurring around the eye, including hyperpigmentation of the
iris and skin around the eye, excessive eyelash growth, deepening of the upper eyelid sulcus,
flattening of the lower eyelid bags, mild enophthalmos, orbital fat atrophy, tight orbit and eyelids,
inferior scleral show, and involution of dermatochalasis.47-49 Furthermore, PAPS is markedly more
frequent and severe in patients treated with bimatoprost compared with latanoprost and
travoprost.50
“Nonetheless, PAPS should be considered as a part of a quality-based management

approach, as it can impact on adherence to PGAs, the patient’s QoL,
and may lead to erroneous IOP measurements.”
Clear communication to inform patients of the possible side effects of treatment and that PAPS is
generally reversible upon halting treatment is vital for managing patient expectations and
improving treatment adherence, and should be incorporated as part of the QoIOP control
concept.

Table 2. Concentrations of BAK used in common glaucoma medications
Glaucoma medication Trade name BAK concentrations (% per mL)
Latanoprost Xalatan 0.02%

Latanoprostene bunod Vyzulta 0.02%
Apraclonidine Iopidine 0.01%
Brinzolamide Azopt 0.01%
Pilocarpine Isopto Carpine 0.01%
Travatan 0.015%
Travoprost
Travatan Z 0%
Netarsudil Rhopressa 0.015%
Timolol Tiopex/Timoptol 0.012%
Dorzolamide Trusopt 0.0075%
Alphagan 0.005%
Brimonidine Alphagan P 0%
Bimatoprost Lumigan 0.005%
Eybelis (Asia)
Omidenepag isopropyl 0.005%
Omlonti (US)
Ripasudil Glanatec 0.004%
Taflotan 0.001%
Tafluprost Taflotan-S (Asia) 0%
Zioptan (US) 0%
Other options for lowering IOP
Selective laser trabeculoplasty

Selective laser trabeculoplasty (SLT) is a painless laser procedure conducted in the outpatient
setting to reduce IOP by increasing the trabecular meshwork aqueous outflow.
It may be useful in a select group of patients, i.e. those who are 1) young, 2) have
high IOP, 3) have difficulty using eye drops correctly, and/or 4) have
early-to-moderate disease.”
The Laser in Glaucoma and Ocular Hypertension (LiGHT) trial examined the effects of SLT
compared with eye drops alone, as first-line treatment in patients with POAG or ocular
hypertension. The trial demonstrated that patients in the SLT group achieved their target IOP at
more study visits (93.0%) compared with patients receiving eye drops alone (91.3%), and 74.2%
did not require eye drops at 36 months post-SLT. Additionally, first-line SLT was more cost-
effective (based on UK standards) compared with the use of eye drops in the first-line.57 It should
be noted that the majority of patients in the trial were Caucasian, with Asian patients accounting
for less than 10% of patients in either treatment arm.57

“As such, results from this trial should be interpreted carefully when
considering SLT as an option for Asian patients while results from similar
ongoing studies in Asian populations are awaited.”
Nonetheless, it is important for patients to be aware that any benefit obtained from SLT will not be
permanent (although the procedure can be repeated), and follow-up appointments to monitor their
glaucoma are advised.57
“Anecdotally, second- or third-line SLT can result in an IOP reduction of ~15–20% in

approximately 60% of patients after two months, while SLT in the first-line is
successful in two thirds of patients.”
Surgery
Patients who have failed medical and/or laser treatment may require surgery to control IOP and
minimize glaucoma progression;17 however, challenges associated with availability of and
accessibility to these procedures across the Asia Pacific region may be significant barriers to use
of these techniques.
“The only minimally invasive (or micro-incisional) glaucoma surgery (MIGS)

procedure available in Thailand is Xen®, which is only partially reimbursed in a small
proportion of patients (~20%), while in India, accessibility to SLT has improved in recent
years but access is largely limited to major cities.”

Tips and tricks: IOP reduction
1. Target IOP range must be set prior to initiating treatment, based on ocular and
patient-specific factors
2. Confounding factors such as CCT must be considered when measuring IOP
3. Record the initial IOP, documenting the time and the type of IOP measurement.
Share this information with specialists upon referral
4. Monotherapy is recommended as first-line treatment, except in cases with very

high IOP and severe disease. If more than one treatment is required, consider
fixed-dose combinations. The highest reduction of IOP is obtained with PGAs
5. Alternative treatment options including SLT and surgery are available as first line
therapy in some cases and for patients who have failed treatment with topical
anti-glaucoma therapies

IOP response rate
Why is it important to consider IOP response rate?
“Response rate data should be key when selecting anti-glaucoma medication,

and it is important to consider response rates with different types of medications.
The percentage reduction in IOP compared with baseline must be considered to
determine when and if a patient has responded to treatment. As such, accurate recording
of a patient’s initial IOP measurement is critical for assessment of patient response to
treatment as part of the QoIOP concept. Baseline IOP should be provided to glaucoma
specialists upon referral; without this, it becomes difficult to assess the mean IOP
reduction and response rate of the medications in patients who have already
commenced treatment. Additional information to be documented includes the
time of IOP measurements (since IOP is known to fluctuate during the day), as well
as the type of tonometer used (i.e. air-puff tonometer or Schiotz analog tonometer
[which are less reliable but sometimes used in rural hospitals in Thailand] vs
Goldmann applanation tonometry [GAT]).”
There is evidence that patients who do not respond to a PGA may respond better when switched
to another PGA. A prospective, randomized, multicenter cross-over study by Mizuguchi et al.
showed that some patients only responded to one type of PGA administered (i.e. tafluprost vs
travoprost), where a small number of patients did not respond to either medication.21
“Additionally. switching to omidenepag isopropyl may be an option for patients who do

not respond to a PGA.”
Furthermore, the EGS guidelines note that for patients who previously had poor response to
monotherapy, combination therapy consisting of two agents with different modes of action can
improve response rates.5
When to conduct IOP measurements to determine response rate to medication
“To determine the response to treatment accurately, an appropriate

amount of time should be allowed for the medication to elicit a response. Typically, in
patients who are treated with PGAs, response to medication should be assessed after four
weeks of treatment, but it is important to keep in mind that some patients may be defined
as delayed (or late) responders to treatment.”

A Japanese study reported that 10–15% of patients exhibited a better response after an
additional four weeks of treatment.58
“Similarly, a review of 100 patients showed that for patients with early glaucoma and a
poor initial response to treatment, an additional 3–4 weeks of treatment may be required to
accurately measure treatment response rates (unpublished data, Prof. Chungkwon Yoo).
For other anti-glaucoma medications, assessment of treatment response after two weeks
of treatment should be sufficient, though high incidence of hyperemia is seen with Rho
kinase inhibitors meaning true assessment of response to treatment may occur after
three months.
Hyperemia may be driving the delayed responses seen in some patients, however this side
effect typically improves over time. As such, it may be prudent to follow patients prior to
their initial assessment of efficacy after four weeks of treatment to assess the presence of
any side effects and thus likelihood of a delayed response.”
The Monocular Trial, which demonstrated utility in assessing a patient’s response to medication
based on the response in one eye, may also be useful for estimating a patient’s likely response to
treatment.59
How to define ‘non-response’ to treatment
While the expected response rates to glaucoma medications are known (Table 1), the definition of
‘non-response’ to treatment is poorly defined and varies across studies. Mizoguchi and
colleagues,21 along with others,60,61 have used 10% as the cut-off value to define non-response.
Others define non-responders as those whose IOP was not reduced by 20% compared with
baseline,62 or based on either 15% or 20% reduction in IOP compared with baseline.63
Alternatively, an open-label study of bimatoprost in patients with POAG or OH refractory to
latanoprost defined non-responders based on an absolute reduction in IOP of <3 mmHg
compared with baseline.64
“Taking the expected variability observed with IOP measurements into consideration, the
10% threshold for non-response to monotherapy appears reasonable, with clinical
judgment to be used on a case-by-case basis. For example, for patients with severe
disease, the non-response cut-off may need to be 15% when compared with baseline. It is
important to note that these definitions related to patients receiving an initial
monotherapy. In patients receiving a secondary glaucoma medication, a less substantial
decrease in IOP can be expected.”

Tips and tricks: IOP response rate and timing of IOP measurements
1. Unless immediate IOP reduction is necessary, obtain 2 or more untreated IOP

readings at different times for the baseline IOP (especially in eyes with IOP
within normal range). It is important to document the initial untreated IOP and
inform glaucoma specialists when referring patients
2. Monocular trial is helpful to assess the medication efficacy in eyes with low-teen
untreated IOP
3. Regarding delayed responders: some eyes may show delayed responses to

PGA. Re-assess the medication efficacy in another 2–4 weeks if the initial
response seems insufficient in eyes with early glaucomatous damage
4. In patients who are poor responders, consider the following:

a. Check patient adherence to medication and/or side effects
b. Switch to another PGA or other medications such as OMDI
c. Switching to a fixed combination (PGA/BB, CAI/BB, AA/BB, CAI/AA)
5. For assessment of the medication efficacy, it is desirable to measure IOP at a

similar time of the day to minimize the effect of diurnal IOP variations

Long-term IOP control and VF stability
Why is it important to consider long-term IOP control?
Maintaining long-term IOP control reduces the risk of disease progression. The AGIS
demonstrated that for every 1 mmHg increase in IOP fluctuations, the odds of VF progression
increased by approximately 30%.9 As such, assessment of long-term IOP control, as well as the
method(s) employed to achieve it, should be a key consideration when implementing the QoIOP
control concept in clinical practice.
Several studies have highlighted the long-term IOP-lowering effects of PGAs. Of note, the LOTUS
study retrospectively examined the long-term safety and efficacy of three PGAs (tafluprost,
travoprost, and latanoprost) in Korean patients with POAG or NTG who had received one of the
three PGAs as initial monotherapy prior to study initiation. The study showed no significant
difference in VF progression between patients who received tafluprost, travoprost, or latanoprost
monotherapies, demonstrating the role of PGA monotherapy in minimizing VF progression in
patients with early-stage glaucoma.20 Additionally, the United Kingdom Glaucoma Treatment
Study (UKGTS) study which evaluated latanoprost in patients with POAG across ten sites in the
UK was the first randomized placebo-controlled trial to show that the use of IOP-lowering
medication preserved VF in this patient population.65 Two caveats to note are that the majority
(~90%) of study participants were White, and the study excluded patients with advanced
glaucoma (defined as mean VF deviation >–10 decibels in the better eye or >–16 decibels in the
worse eye).
When to assess VF: Recommended frequency of VF evaluation
Rates of VF progression are known to vary from patient to patient.66 Evaluation of VF progression
over time (in conjunction with assessments to determine long-term IOP control) is essential to
identify patients with disease progression, and allows ophthalmologists to better understand the
quality of IOP control achieved by the prescribed IOP reduction methods. It is clear that VF
testing should be carried out more than once per year, with the EGS recommending six tests
(three tests/year) in the first 2 years following diagnosis to assess VF progression.5 Chauhan and
colleagues suggest that at least three examinations are required each year to detect moderate
progression (~0.5 decibels/year) after 4.3 years, or fast progression (~2 decibels/year) after 1.7
years (at 80% power); the time taken to detect disease progression is extended if fewer
examinations are performed.10 However, a UK-based study has shown that the number of VF
tests performed in practice falls below the recommended number, largely because of a lack of
resources/impracticality, and difficulties faced by patients when undertaking the test.66
“Even for glaucoma specialists, achieving the recommended number of tests is difficult.
As such, some aim to complete 5 VF tests during the first 2 years, while others perform 2

VF tests in the first 6 months followed by another within the next 6–12 months
(depending on the stage of the glaucomatous damage).”
Of course, the frequency of VF testing should be modified based on the stage of disease. For
example, more frequent testing is required for patients who have a high risk of VF loss or those
with advanced disease in whom it is more difficult to detect progression.10,67
“It is also worth noting that in patients with pre-perimetric/early stage glaucoma, structural
changes usually precede functional VF changes. Some patients develop VF progression in
the non-linear rate. Therefore, a focus should also be placed on monitoring and evaluation
of structural changes when determining glaucoma progression in an attempt to avoid a
delay in the identification of VF changes in these patients.”
VF analysis and interpretation
Analysis of VF progression can be based on ‘events’ (i.e. analysis comparing a patient’s VF

status at a follow-up examination to baseline), or ‘trends’ (i.e. the rate of change based on a
regression analysis).5,10
Automated perimetry is most commonly It is acknowledged that resource availability

performed using the Humphrey Field
®
varies throughout the Asia Pacific region, which
Analyzer (HFA and HFA2; Zeiss, Jena, puts an added strain on the existing challenges
associated with the management of glaucoma
Germany), which operates Swedish
patients. It is acknowledged that while it may be
Interactive Thresholding Algorithm (SITA) feasible to perform optimal VF examinations in a
Standard 24-2 and SITA Fast 24-2. As the particular country or region, in others, it may not.
The discussion related to equipment/resources
name suggests, the Fast program can be
is based on best practices, which should be
performed in a shorter period of time afforded to everyone.
compared with the Standard program,
which should make VF assessment easier for patients. However, at lower VF sensitivities, the
SITA Standard method is more precise than SITA Fast,68 and therefore is the ideal method for
testing if the patient can tolerate it. A newer version (HFA3) can perform SITA Faster 24-2 and
SITA Faster 24-2c, which takes even less time than to perform. Yet ophthalmologists should use
caution if using the faster program as although it has shown a similar perimetric test results when
compared with SITA Standard 24-2 and SITA Fast 24-2, its ability to detect early disease is
limited.69 As such, SITA Faster 24-2c may have some utility in a selected patient population (e.g.
very old patients who find the VF assessment very difficult), or its use may be prioritized at follow-
up visits rather than for initial testing (though switching test methods is not recommended as

mentioned earlier).5,10 In this case, if an abnormal result is seen using the SITA faster 24-2c, a
more thorough and standard VF test such as the SITA Standard 24-2 should be performed.
The Octopus perimeter (Haag-Streit, Köniz, Switzerland) is an alternative option for VF

assessment, which provides results that are analogous to those produced using the HFA.67 For
this perimeter, the algorithms commonly used are the Dynamic Strategy, and tendency-oriented
perimetry, the latter providing a fast option for testing.5
Furthermore, the 24-2 test pattern is considered the gold standard for assessment of VF in
patients with, or suspected to have, glaucoma, while the 10-2 test pattern may be useful in
patients with advanced VF loss.5,17
“Additionally, the 10-2 test pattern may be utilized in patients with suspected central
involvement based on clinical assessment or imaging (e.g. OCT demonstrated
involvement of the macular ganglion cell layer).”
How to achieve an adequate number of VF tests to monitor disease progression
Lack of resources/testing impracticality remains a barrier to performing an adequate

number of VF tests. While it is noted that it may not be possible in all jurisdictions,
expansion of testing times and locations to allow VF testing to occur outside of scheduled
hospital visits (e.g. two weeks prior) may help to achieve an adequate number of tests. For
example, this may be facilitated through engagement and development of networks with
optometrists. However, logistics related to the safe and confidential transfer of data from
external/satellite sites must be considered.”
Crabb and colleagues also highlighted several barriers to VF testing that may discourage patients
from performing the test. Their research showed that patients dislike VF testing because they find
the test procedure too long and tiring, and find it difficult to concentrate.66 Additionally, patients
expressed concern about the communication/instructions received on how to perform the test,
what to expect from it, and how to interpret the results.66 This highlights the importance of
providing clear communication to patients, to explain what to expect from the test (with respect to
dim lighting and stimuli), even of providing a demonstration (especially for perimetric novices).5
Such measures are needed to overcome barriers for patients and help to achieve the required
number of VF tests in order to monitor disease progression, which is essential for determining the
quality of the IOP control achieved with treatment.
“One suggestion may be to have a technician present (by the patient’s side) while
performing the test, to talk the patient through what is required and answer any questions

as they arise. Furthermore, it is important to explain the VF testing process and need for
frequent tests during the patient’s first visit, so they are aware of the testing requirements
from treatment commencement. Highlighting the impact on important patient-centric
aspects, such as the impact on their ability to performance activities of daily life
is essential, and patient reported outcome measurements need to be taken
into consideration.”
Tips and tricks: Long-term IOP control and VF stability
1. Evaluation of VF progression over time (in conjunction with assessments to

determine long-term IOP control) is essential to identify patients with disease
progression
2. Achieving the recommended number of VF tests is difficult, even for glaucoma

specialists. The frequency of VF testing should be modified based on the stage
of disease
3. The structural change can occur before functional change. Some patients
develop visual field progression in the non-linear rate therefore we should
monitor both structure and function in detecting glaucoma progression
4. Use caution if using the SITA-faster program: it has shown similar perimetric
test results when compared with SITA Standard 24-2 and SITA Fast 24-2, but
its ability to detect early disease may be limited. Consider 10-2 tests in patients
with advanced VF loss and/or suspected central involvement
5. Providing a demonstration/explanation and support on how to perform the VF

test may help overcome barriers for patients and help to achieve the required
number of VF tests

24-hour IOP fluctuations and monitoring
Why is it important to consider IOP fluctuations?
Multiple studies show that large and irregular 24-hour fluctuations, which may not be accurately
detected by single office-hour IOP measurements, are associated with, and considered a risk for,
VF deterioration in glaucoma.7,8,70-72 Furthermore, IOP can fluctuate over a 24-hour period by
more than 10 mmHg in patients with glaucoma, compared with 2–6 mmHg in healthy subjects.
This has prompted the investigation
of extended-hour IOP monitoring,
particularly in patients who are at IOP terminology
high risk for disease progression or Peak IOP: highest IOP measurement in a series
those with unexplained progression
Trough IOP: lowest IOP measurement in a series
(i.e. patients with VF deterioration
IOP fluctuation: changes in IOP throughout the day
despite normal office IOP
and/or over several days
measurements).7,8,73
Types of IOP fluctuations:
As such, it is important to think
beyond singular IOP measurements - Ultra-short term: occur within minutes
as a means of assessing treatment - Short term: occur over hours to days

adequacy and consider monitoring
- Long term: occur over months or years
of 24-hour IOP fluctuations, to gain a
Extended-hour IOP: mean IOP measurement during
better understanding of the quality of
an extended period
IOP control achieved with therapy.
Office IOP: IOP measured during office hours
However, extended-hour IOP
Circadian IOP: IOP variation during a single
monitoring is time-consuming and
24-hour period
impractical for both patient and
clinician. Thus, assessment of Diurnal IOP: IOP measured during the day
fluctuations commonly relies on Nocturnal IOP: IOP measured during the night
repeated IOP measurements with
the GAT or air-puff tonometer over
an extended period of time during office hours.74
Additionally, home tonometry may be employed. When using equipment such as the iCare HOME
(Icare Finland Oy, Vantaa, Finland) patient compliance as well as the patient’s ability to correctly
use the equipment must be considered. The iCare HOME may be useful for patients who
continue to progress despite office IOP appearing to be controlled. However, it is known to be
difficult for patients to use which may lead to the reporting of incorrect IOP measurements or
underestimate of IOP compared with GAT.75

“Difficulty is commonly seen in patients who are older/frail or those who have PAPS/tight
eye lids. Additionally, access to the iCare HOME equipment may be limited in some
countries, and even if it is available, it is not affordable to majority of patients, making
extended-hour IOP monitoring increasingly difficult. Given cost is a major prohibitive
factor, implementation of rental programs whereby patients are able to lease the
equipment for a reduced cost may prove to be helpful.”
Continuous 24-hr IOP monitoring has been evaluated using the SENSIMED Triggerfish®
(SENSIMED AG, Etagnières, Switzerland) contact lens sensors (CLS), however, there are
several caveats to consider. Cost is a major prohibitive factor, with the estimated cost of the
SENSIMED Triggerfish® CLS (based on the UK’s National Institute for Health and Care
Excellence website estimates) is ~£500 per single-use contact lens.76
“Furthermore, the SENSIMED Triggerfish® CLS is not readily accessible in certain

countries (such as Thailand, Malaysia, and India) and is only available for research
purposes in others (i.e. Korea). Interpretation of results can be challenging and the ability
of patients to use the device correctly despite proper training may also pose a barrier to
clinical utilization of the device.”
When and how to measure IOP to determine IOP fluctuations
“Given the difficulties associated with extended-hour IOP monitoring, it is recommended

that it is prioritized in patients who are high risk for disease progression and/or those with
unexplained progression when implementing the QoIOP concept. Where continuous
extended-hour IOP monitoring using a device such as the SENSIMED Triggerfish® CLS is
unavailable, consider measuring IOP at different times (e.g. morning, afternoon, and
evening on different visits). An alternative monitoring time-course of IOP measurements is
to measure every 2–4 hours from 8 am to 5 pm using a GAT. Despite the potential
difficulties with the iCare HOME, its use may also still prove valuable for gaining additional
information otherwise missed during office visits.”
Air-puff tonometry may be more convenient and preferred by patients as a non-contact method of
measurement. However, IOP values determined using air-puff tonometry, particularly in patients
with an IOP of >24 mmHg, may be higher than IOP determined using a GAT.77 This suggests that
air-puff tonometry is not the most reliable method of IOP assessment, although its utility in mass
screenings of IOP may still be valid.

The Ocular Response Analyzer® (Reichert Technologies, Munich, Germany) is another non-
contact device which analyses the corneal hysteresis to calculate the corrected (cornea
compensated) IOP measurement.5 Thus, it may be useful in patients with a history of refractive
surgery. To date, the Ocular Response Analyzer® has generally been used for research purposes
only and is costly, so its use in mainstream clinical practice is yet to be seen. Furthermore, given
the success and acceptance of pacemakers and glucose-monitoring implants, implantable
intraocular devices may eventually be used for continuous and long-term IOP monitoring, and
would eliminate any confounding corneal factors present when using a CLS or traditional
tonometers.78
Ocular perfusion pressure

The ‘vascular theory’ of glaucoma indicates that if perfusion pressure decreases (spontaneously
or due to antihypertensive medications), blood flow to the optic nerve may become insufficient
and could lead to glaucomatous optic neuropathy. Ocular perfusion pressure (OPP) relates to the
difference in arterial and venous blood pressure in the eye, where venous pressure is marginally
higher than IOP under normal circumstances.79,80 As a result, the mean OPP can be calculated by
substituting venous pressure such that mean OPP is equal to the difference between the mean
arterial pressure and IOP:80
Mean OPP = 2/3 (diastolic BP + 1/3 [systolic BP – diastolic BP]) – IOP
where mean arterial pressure is equal to diastolic BP + (1/3 [systolic BP – diastolic BP]).
Although studies have demonstrated that low OPP is associated with an increased risk for
development and progression of glaucoma,81,82 the relationship between blood pressure, IOP, and
OPP is complex.79,83 It is also important to consider that measurement of OPP using the
calculation above provides an estimate only.79 As such, OPP has limited use in routine clinical
practice as it is difficult to accurately assess and can be more challenging to evaluate than 24-
hour IOP.
Water drinking test

Originally designed as a diagnostic tool for glaucoma, the water drinking test (WDT) is currently
under investigation for the prediction of IOP fluctuations and estimation of peak IOP (as solicited
during the test).84 The mechanism of IOP elevation during the WDT remains unclear, but it is
thought to provide an indirect measure of the outflow facility of the eye, where it is expected that
patients with an intact and active outflow facility would experience a rapid IOP recovery. Patients
with a compromised outflow facility are more likely to experience a sustained elevation of IOP.84
Susanna and colleagues have retrospectively assessed the WDT in a group of patients with
treated POAG, to determine the association between the magnitude and timing of IOP peaks
elicited during the WDT and glaucoma-related VF loss.85 Generally, following baseline IOP

assessment, the test involves the patient ingesting 800 mL of water within a five-minute period.
The patient's IOP is then measured approximately three additional times at 15-minute increments
and the highest IOP recorded is regarded as the peak IOP during the WDT.84,85 Patients are
required to stop ingesting liquid two hours before the test.85 However, it is currently unclear where
the WDT test fits into glaucoma management and more research in this field is needed.
Tips and tricks: 24-hour IOP fluctuations and monitoring
1. Extended hours IOP monitoring should be prioritized in patients who are high
risk for disease progression and/or those with unexplained progression
2. Where continuous extended hours IOP monitoring using a device such as the
SENSIMED Triggerfish® CLS is unavailable, consider measuring IOP at
different times and/or home monitoring
3. Consider measure IOP at different times, such as morning, afternoon and

evening on different visits
4. Despite high costs and difficulties with patient utilisation, the iCare HOME may
be valuable for gaining additional information otherwise missed during
office visits
5. Air-puff tonometry is not the most reliable method of IOP assessment, although
its utility in mass screenings of IOP may still be valid

Treatment adherence and persistence in patients
Why is it important to consider treatment adherence?
Patient adherence to treatment is a complex issue, with several contributing factors. These
include patient-related factors such as the incorrect administration of prescribed medication,
safety and tolerability issues, and other factors such as access to transport or forgetfulness;11,86
and clinician-related factors such as time constraints, making it difficult to identify patients who
are non-adherent/accurately assessing adherence and appropriately communicate with patients
about the importance of adherence, how to correctly administer medications, and the expected
side effects.5 Additionally, restrictive reimbursement policies which make patient access to certain
medications unobtainable.
How to identify and improve patient adherence
Non-adherence can be extremely difficult to identify.5 However, it remains critical to identify

patients who are non-adherent to avoid misinterpretation as poor treatment response and
subsequent prescription of additional, unnecessary therapies.87 Monitoring of refill adherence
(where the expiry of the medication and expected prescription refill is known) is an adequate
measure of treatment adherence that may be useful to assist clinicians identify non-adherent
patients.87 Gently questioning patients about their glaucoma and treatment strategy may help to
elicit self-reporting of non-adherence, for example, asking how often they collect their prescription
or if they have forgotten to use their eye drops in the last week.5,87 Additionally, asking patients to
demonstrate instillation of their eyedrops may help to identify incorrect technique,5 which should
be followed up with training if needed.
“Assessment of side effects may also help identify patients who might not be
administering the correct dose (based on limited evidence side effects).”
In general, patient adherence may be enhanced using some simple strategies, including
simplifying the treatment regimen (i.e. prescribe medications with lower toxicity and complexity
such as once-daily or single-dose PF glaucoma medications), providing adequate patient
education and improving communication, encouraging the use of reminders/alarms to avoid
missing doses.
Simplifying the treatment regimen
Barriers to adherence, such as side effects of treatment and of preservatives, may be overcome
by initiating or switching to PF formulations.16

“Using fixed-dose combinations or single-dose units when possible may help to reduce
the burden of treatment on patients, where the use of single-dose units also allows for
easier identification of non-adherence based on the unused medication.
In patients experiencing ocular side effects, it is important to consider the role of, and
adequately assess patients for, OSD. It is important to note however, that symptoms may
not necessarily match the signs when using the Ocular Surface Disease Index (OSDI)88,
and that frequent administration of the OSDI may not be feasible in clinical practice.
Overall, it is agreed that PF medications are preferred in pre-operative patients, as well as
patients with pre-existing OSD.”
For patients who develop OSD as a result of anti-glaucoma medication, treatment of the OSD
symptoms may also greatly improve patient adherence and tolerability.16
“If available, switching to a long-term drug delivery system may be useful for
improving patient adherence to treatment.”
Patient education and communication

A potential strategy to educate patients on the benefits of treatment adherence is to utilize VF
results to explain the disease to patients, including why it is important to continue using the
medication prescribed to stabilize the disease. In cases where early imaging data (e.g. from OCT)
are available, images captured over time may be used to show and explain to the patient how
their glaucoma has progressed, reinforcing the need to use their medications as prescribed.
“It is also important to educate patients about any expected side effects before
initiating treatment. For example, when prescribing treatment with PGAs, patients should
be informed about the potential for developing conjunctival hyperemia, highlighting that it
is not sight-threatening and reversible, and that most patients are able to tolerate mild
(Grade 1–2) conjunctival hyperemia.”
Given the time restraints faced by doctors, reimbursement models around the world would likely
need to change to facilitate and incentivize ophthalmologists to take the time to educate and
counsel patients. Educational pamphlets, videos, and links to online patient educational resources
to help explain the disease to patients may also be helpful. Employing nurse counselors to
connect with and educate patients is a popular and effective alternative. It should be noted
however, that the impact of educational interventions on patient adherence does vary between
studies, with some finding it to have little impact.89

Reminders/alarms
There is evidence to suggest that the use of tele-reminders may help to improve patient
adherence.86,90,91 Encouraging patients to set an alarm or reminder using their smart phone (if
available) may help improve treatment adherence.5 Utilization of adherence-specific resources
such as the Aiming for Continuous Treatment program, may also result in better treatment
adherence among patients with glaucoma. The Aiming for Continuous Treatment program
distributed in Asia in conjunction with Glaucoma society from 2022 onwards, and provides
patients with hard copy materials and/or access to a phone application designed to deliver
reminders and educate patients on the importance of adhering to, and persisting with, their
glaucoma medication.
Furthermore, asking patients to check the unused units of the medications prescribed may make
them more aware of their lack of adherence, prompting more diligent administration of their
medications.
Tips and tricks: Treatment adherence and persistence
1. Patients who are non-adherent need to be identified to avoid misinterpretation

of lack of a response as a poor treatment response
2. Treatment adherence may be improved by prescribing medications with lower

toxicity and complexity such as once-daily or single-dose preservative free
glaucoma medications
3. Improved communication with the patient and their immediate family members
(care-givers) is needed to educate patients, manage patient’s expectations,
and improve adherence
4. Patients should be encouraged to set reminders/alarms to improve treatment

adherence
5. Educational pamphlets, videos and links to online resources on the importance

of treatment, regular monitoring and follow up, and treatment adherence should
be provided to patients and immediate family members

Conclusion
A large and increasing number of patients is currently living with glaucoma across Asia,
particularly in South-Central and East Asia. It is more important than ever that glaucoma is
identified early to ensure patients can receive adequate treatment to reduce the burden of
disease. However, glaucoma detection rates remain low, due to a lack of early diagnosis
strategies. Asia has several challenges to providing effective glaucoma management, including
the approach of focusing on quantity-based IOP measurements and IOP reduction alone. This
approach, however, must change so that patients are provided with a holistic approach to
glaucoma and IOP management.
The QoIOP control concept highlights the need to evaluate key factors, including the
rate of response to treatment, the long-term control of the patient’s IOP, as well as VF
stability, the role and impact of 24-hour fluctuations, and the importance of ensuring
patients adhere to their prescribed treatments.
This paper provides ophthalmologists with a better understanding of the QoIOP control concept,
with the aim of facilitating wider implementation of QoIOP throughout Asia, to move away from
quantity-based IOP measurements and quality-based IOP control in clinical practice.

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Expert Recommendations for Glaucoma

CONFIDENTIAL – for internal and faculty distribution only 1

Practical clinical guide for ophthalmologists to

Supported by Santen Pharmaceuticals Asia Pte. Ltd.

CONFIDENTIAL – for internal and faculty distribution only 2

This document includes a comprehensive overview of the considerations for

CONFIDENTIAL – for internal and faculty distribution only 3

Dr Ronnie George (Sankara Nethralaya, Chennai, India)

Prof. Kessara Pathanapitoon (Faculty of Medicine, Chiang Mai University, Thailand)

Assoc. Prof. Shamira Perera (Singapore National Eye Centre, Singapore)

Prof. Chungkwon Yoo (Department of Ophthalmology, Korea University Hospital, Korea

CONFIDENTIAL – for internal and faculty distribution only 4

CONFIDENTIAL – for internal and faculty distribution only 5

CONFIDENTIAL – for internal and faculty distribution only 6

CONFIDENTIAL – for internal and faculty distribution only 7

Challenges to effective glaucoma management in Asia

“To date, a Malaysian initiative to encourage partnerships between ophthalmologists and

– Commentary by faculty members

Diagnosis and beyond

Another challenge faced by ophthalmologists relates to diagnosing different types of glaucoma,

CONFIDENTIAL – for internal and faculty distribution only 8

– Commentary by faculty members

“Despite the importance of looking beyond quantity-based IOP measurements,

– Commentary by faculty members

Relying on quantity-based IOP measurements alone, and consequently

Follow-up assessment to determine response/VF preservation and the rate of VF progression is

CONFIDENTIAL – for internal and faculty distribution only 9

Guideline-recommended glaucoma therapies

Poor patient adherence to glaucoma treatment

“In the short-term, adverse effects may include hyperemia,

– Commentary by faculty members

Prostaglandin-associated periorbitopathy syndrome (PAPS) is also now recognized as a clinical

CONFIDENTIAL – for internal and faculty distribution only 10

Moving away from quantity-based IOP measurements and toward QoIOP

CONFIDENTIAL – for internal and faculty distribution only 11

Suggested target IOP (range)

Figure 1: Initial target IOP ranges based on the stage of glaucoma.5,17

– Commentary by faculty members

CONFIDENTIAL – for internal and faculty distribution only 12

• Mild/early glaucomatous loss: mean VF defect of ≤6 decibels

Furthermore, it is important to also consider the possibility of confounding factors when

CONFIDENTIAL – for internal and faculty distribution only 13

IOP reduction methods

CONFIDENTIAL – for internal and faculty distribution only 14

“Fixed-dose combinations of PGA-β-blockers are preferred over other combinations.”

– Commentary by faculty members

Table 1. Dosage and efficacy of various anti-glaucoma drug classes.5,17,24-27

Rho-kinase inhibitors Increases aqueous outflow via trabecular meshwork 1x to 2x 20%

Increase aqueous outflow via trabecular meshwork

Nitric oxide Increase aqueous outflow via trabecular meshwork

CONFIDENTIAL – for internal and faculty distribution only 15

“The expert faculty concluded that combination of Rho kinase inhibitors

– Commentary by faculty members

CONFIDENTIAL – for internal and faculty distribution only 16

“Nonetheless, PAPS should be considered as a part of a quality-based management

– Commentary by faculty members

CONFIDENTIAL – for internal and faculty distribution only 17

Glaucoma medication Trade name BAK concentrations (% per mL)

Latanoprost Xalatan 0.02%