Q1. What are the recommended tests at first assessment?

The following tests are recommended at first assessment:

• Visual acuity and refractive error (strength of recommendation: strong)

• Slit lamp examination (strength of recommendation: strong)

• Gonioscopy (strength of recommendation: strong)

• Tonometry (strength of recommendation: strong)

• Central corneal thickness (CCT) (strength of recommendation: weak) - Use of CCT-adjusted intraocular pressure (IOP) values is not recommended.

• Visual field (VF) testing (strength of recommendation: strong)

• Clinical assessment of the optic nerve head (ONH), retinal nerve fiber layer (RNFL) and macula. Binocular examination under pupil dilatation is preferable (except in angle closure). Optic disc and RNFL photography can be used (strength of recommendation: strong)

• Optical coherence tomography (OCT) of disc/RNFL/macula can be useful but the diagnosis of glaucoma cannot be made on the basis of OCT alone. (strength of recommendation: weak)

Level of evidence: The direct evidence addressing this specific question is ‘very low’ for all recommendations.

Q2. Alternative tonometers other than Goldmann applanation tonometry (GAT): are they recommended in clinical practice?

Recommendation: Consensus could not be reached about which alternative tonometers other than GAT can be used in clinical practice.

Level of evidence: very low

Strength of recommendation: weak

Comment: Many forms of tonometry have been licensed for clinical use through comparison with GAT which is considered the current reference standard.

In general, all measurements with tonometers which applanate the cornea are influenced by corneal biomechanics (both geometry, e.g. thickness and curvature, and material properties, e.g. stiffness and viscoelasticity). The effect is greater with tonometers which applanate the cornea more quickly (such as air-puff and rebound tonometers).

In recent times, new tonometers have been introduced which intend to make IOP measurements less influenced by corneal parameters. The impact of tonometer inaccuracy and/or imprecision on clinical outcomes has not been established.

There is sizeable inter- and intra-observer variability observed for all tonometers, including GAT.

The accuracy and precision of a tonometer should influence the choice for use in clinic. For a given patient, the same tonometer should be used for follow-up.

Q3. Is it recommended to set a target IOP?

Recommendation: A target IOP should be set as a treatment goal at diagnosis. Target IOP should be updated at each monitoring visit on the basis of changes in glaucoma or other ocular or systemic diseases.

Level of evidence: low

Strength of recommendation: strong

Comment: Therapy in glaucoma management aims to lower IOP to slow the rate of VF deterioration sufficient to maintain the patient’s QoL.

Target IOP is the upper limit of IOP judged to be compatible with this treatment goal. We recommend the use of target IOP. It should be re-evaluated regularly and modified accordingly when progression of the disease is identified or when ocular or systemic comorbidities develop. If the target IOP has not been reached, but the glaucoma is stable, then the target may be revised upwards. There is no single target IOP level that is appropriate for every patient, so the target IOP needs to be estimated separately for each eye of every patient, and adapted to changing patient status.

Q4. Central corneal thickness (CCT): is it recommended to use CCT to risk profile patients? (see also Q1 and Q2)

Recommendation: CCT may be useful for baseline risk profiling.

Level of evidence: low

Strength of recommendation: weak

Comment: CCT is one parameter which influences the accuracy of most tonometers. In eyes with thin corneas IOP tends to be underestimated. Thinner CCT is associated with a higher risk of conversion of ocular hypertension (OHT) to glaucoma and a higher risk of glaucoma progression in multiple variable models. However there is no strong evidence that CCT is an independent risk factor. IOP correction algorithms based on CCT are not validated and should be avoided.

Q5. Anterior chamber angle evaluation with imaging tests: are they recommended to diagnose people with angle closure?

Recommendation: Anterior chamber angle imaging cannot replace gonioscopy. Gonioscopy should be performed in every patient being evaluated for glaucoma.

Level of evidence: low

Strength of recommendation: strong

Comment: Anterior chamber angle imaging devices can be useful to identify the iris configuration of a narrow angle, to assess the influence of the lens, for triage or in eyes where the angle cannot be visualised by gonioscopy. However anterior chamber angle imaging should not replace gonioscopy since features as peripheral anterior synechia, pigment and other secondary causes of trabecular dysfunction may be missed.

Q6. Optical coherence tomography (OCT): what is the role of OCT for diagnosis of glaucoma? Answered in Q1 (see also flow chart (FC) III).

Q7. What are the recommended tests for monitoring?

Visual acuity (strength of recommendation: strong)

VF testing (strength of recommendation: strong) - Same instrument and strategy are recommended for follow-up tests

• Use software-based progression analyses

• VF remains the most important test to monitor progression

Clinical examination of the optic disc and RNFL (strength of recommendation: strong).

Tonometry (strength of recommendation: strong)

OCT disc/RNFL/macula imaging (strength of recommendation: weak))

• OCT disc/RNFL/macula scan using the same instrument with the software- based analysis can be useful

• OCT progression analysis cannot replace VF progression analysis

• At present OCT progression analysis is not age-corrected (there is an aging- related decline)

• Apparent OCT progression and VF progression are not always correlated

Repeated gonioscopy in some circumstances (strength of recommendation: weak)

Level of evidence: The direct evidence addressing this specidic question is ‘very low’ for all recommendations.

Q8. What is the role of OCT for monitoring glaucoma? Answered in Q7

Q9. Alternative models of care: virtual clinics / asynchronous decision making: are they acceptable?

Recommendation: virtualclinics / asynchronous decision making can be an efficient way of delivering glaucoma care.

Level of evidence: very low

Strength of recommendation: weak

Comment: Models of care with virtual clinics / asynchronous decision making are potentially valuable when improvements in access to care is needed. Proper governance and safety measures must be in place. Patients acceptability and preferences should be confirmed.

Q10. Medical treatment: what is the most effective and what is the first- choice medication for open angle glaucoma?

Recommendation: Prostaglandinanalogues (PGAs) are the most effective medication and they are usually recommended as first choice treatment for open angle glaucoma.

Level of evidence: High for IOP reduction but very low for other outcomes.

Strength of recommendation: strong

Comment: Factors like possible adverse effects, co-morbidities, systemic therapy, adherence, patient preferences, life expectancy, cost and availability should be considered in selecting a drug for a given patient.

Q11. What interventions can improve adherence to medical treatment?

Recommendation: simplified regime, education, effective communication (e.g., ask open questions), alarms/messages.

Level of evidence: very low

Strength of recommendation: weak

Q12. Is selective laser trabeculoplasty (SLT) recommended as initial treatment?

Recommendation: SLT can be offered as a first choice treatment for open angle glaucoma.

Level of evidence: moderate (only one high quality trial, LiGHT see I.7.3.3)

Strength of recommendation: strong

Comment: One high quality trial showed that SLT is at least as effective as eye drops and SLT should be considered as an option for initial treatment in patients with mild or moderate open angle glaucoma or OHT (LiGHT trial, see I.7.3.3). There is no evidence regarding effectiveness of SLT in patients with severe glaucoma and pigmentary glaucoma (PG). SLT and argon laser trabeculoplasty (ALT) probably have similar efficacy. Factors like co-morbidities, systemic therapy, adherence, ability to administer drops, patient preference, cost and availability should be considered when offering laser trabeculoplasty as a first choice treatment.

Q13. What is the recommended surgical treatment for open angle glaucoma?

Recommendation: Trabeculectomy augmented with antifibrotic agents is recommended as an initial surgical treatment for open angle glaucoma.

Level of evidence: low

Strength of recommendation: strong

Comment: Trabeculectomy with antifibrotic agents is the standard glaucoma surgical procedure. Depending on patient circumstances such as target pressure, safety profile and patient preferences, other options can be considered, e.g., drainage devices (glaucoma shunts) in people with high risk of trabeculectomy failure, or less invasive filtering surgery, or bleb-less surgery such as canaloplasty, or minimally invasive glaucoma surgery in people with early disease may be considered. Factors like cost, availability and surgeon’s preference should also be considered when selecting a type of surgery.

Combined glaucoma surgery with phacoemulsification may be considered in some patients with coexisting glaucoma and cataract.

Q14. What is the recommended intervention for primary angle closure disease?

With the exclusion of eyes with cataract, following an acute attack of angle closure (AAC) or nanophthalmos.

Interventions depend on the spectrum of disease and presence of cataract.

Laser and surgical treatment is typically combined with medical treatment.

• Primary angle closure suspect (PACS):

  • Comment: Not all patients with PACS need laser peripheral iridotomy (LPI). Evidence from China suggests that there is a low risk of disease progression without LPI (ZAP trial, see I.7.2.1). No studies in white European eyes.

  • Recommendation: LPI in high risk individuals, e.g., high hyperopia, patients requiring repeated pupil dilatation for retinal disease or with difficult access to healthcare facilities.

  • Level of evidence: low

  • Strength of recommendation: “weak”

• Primary angle closure (PAC) and primary angle closure glaucoma (PACG), for people under 50 years of age:

  • Recommendation: LPI

  • Level of evidence: low

  • Strength of recommendation: “strong”

• PAC and PACG, for people over 50 years of age:

  • Comment: Lens extraction is associated with better clinical and QoL outcomes

  • (EAGLE trial, see I.7.4.1), but risk considerations need to be individualised.

  • Recommendation: lens extraction or LPI

  • Level of evidence: moderate (one good quality trial, EAGLE)

  • Strength of recommendation: strong

Q15. Medical treatment: what is the most effective and the first choice medication for PACG (after interventions for widening the anterior chamber angle have been done)?

Recommendation: Prostaglandin analogues are the most effective medication.

Level of evidence: low

Strength of recommendation: strong

Comment: Trials in East Asia may not be generalisable to European populations. Factors like possible adverse effects, co-morbidities, systemic therapy, adherence, patient preferences, life expectancy, cost and availability should be considered in selecting a drug for a given patient.

In some exceptional cases long-term treatment with miotics may be recommended (e.g, plateau iris syndrome after LPI and with recurrent attacks of angle closure and when lens extraction cannot be done).

Q16. Glaucoma surgery for PACG (after interventions for widening the anterior chamber angle have been done)?

Interventions depend on the lens status and glaucoma severity.

• Pseudophakic with PACG:

  • Recommendation: filtration surgery (trabeculectomy)

  • Level of evidence: very low

  • Strength of recommendation: strong

• Phakic with PACG:

  • Recommendation: phacoemulsification a lone or combined phacoemulsification + glaucoma surgery

  • Level of evidence: very low

  • Strength of recommendation: strong

Comment: In patients with severe glaucoma phaco-trabeculectomy may be advisable.

FC I – Suggested questions for your glaucoma patient

• At baseline

  • History/risk factors

    Specifically enquire about

    • All medications

      Family history (general/ophthalmological/blindness)

      Corticosteroid therapy (topical/systemic)

      Ocular trauma or inflammation Refractive surgery

      Cardiovascular or respiratory diseases/other chronic or severe diseases Vascular disorders

      Drug allergies

  • Do you have any questions or anything that you would like to discuss?

• Direct questions at follow-up

  • How are you?

    How do you think your eyes are doing?

    Do you think your condition is better, stable or worse? Do you have difficulty with your daily tasks? Do you understand your diagnosis?

    Are you having any problems with your drops? Are you worried about your sight?

    Have you been using your eye drops as prescribed?

    Do you administer the drops by yourself or by a relative? If by yourself, please show me how you do it

    Do you have any questions or anything that you would like to discuss?

I.5.1 Anxiety associated with glaucoma

Diagnosis - especially when unexpected - is an obvious moment of anxiety for patients, and one which can be mitigated by the provision of timely support or more information. Empathy is particularly important when providing a diagnosis - put yourself in the patient’s shoes, try to understand what they are thinking and feeling and give them plenty of opportunity to ask questions and express their fears.

Anxiety does not dissipate once the shock of diagnosis has passed: concerns about future deterioration in sight, about ability to hold a driving license, about difficulties with healthcare provision, and about age-related difficulty in managing treatment are all common. The perception of disease is likely influenced by family history and how family members have been affected by glaucoma.

I.5.2 The information gap

A lack of information can in itself be a source of anxiety and uncertainty. Not understanding clinical systems, being unable to formulate pertinent questions and feeling undervalued in clinical consultations are all common experiences for patients, and exacerbate the information gap. In contrast, the presence of information can enable engagement in self-care and can support changes in lifestyle which result in a more effective management of glaucoma.

Key information gaps include:

• Nature of glaucoma sight loss

  Even long-term patients may struggle to understand the nature of glaucoma sight loss. Helping people to understand the specifics of their own field loss can also help them develop techniques to avoid trips and falls. People may assume that surgery or laser will improve vision, so volunteering the correct information is often helpful.

• Glaucoma and driving

  This is one of the major sources of stress and anxiety for patients, yet there is confusion amongst professionals about local driving regulations and when a patient may need to notify the authorities, and patients continue to receive incorrect or inconsistent advice. This anxiety is understandable given the potential impact of losing a driving licence.

• Eye drops

  Patients’ ability to manage their condition varies depending on their personal circumstances. Drops change, personal circumstances change, attitudes to treatment evolve. Continue checking in with your patients, encourage discussion and frame questions to avoid judgement or censure. E.g., “Do you have any concerns or difficulties with your eye drops?”.

  For the patient, it often seems that every clinician thinks drops is someone else’s job. Every clinic should have a health care professional who takes pro- active responsibility for drop education. Patients need ongoing information about adherence – not just when their drop regime changes or when there are supply issues or side effects. Patients need to be encouraged to speak up when they have problems with drops, and need to know where they can go for help.

• Surgery and laser

  The route to making a treatment decision is complex, and many patients need considerable support, advice and time. Take the time to explain to patients the possible outcomes and risks of their condition and treatment, in a manner suitable to each individual. Trabeculectomy or another glaucoma surgery is a routine procedure for a surgeon, but for the patient, the prospect of someone taking a knife to their eye is terrifying, and they’re likely to forget how you delivered the news to them. Providing accurate timely written information for people to take away can mean patients are reassured and empowered to go ahead with treatment, and where an informed patient declines surgery, they are in a better position to understand the risk they are taking and the potential impact.

• Asking questions is difficult

  Patients often find it hard to ask for information from healthcare professionals. Some find the clinical setting is not conducive to engagement, others describe doctors who do not want to engage with them, and many ration their time with their healthcare provider because they feel guilty about using doctors’ time.

  For others, the difficulty lies in not knowing how to frame questions about their glaucoma. It might be that a lack of knowledge makes it hard for them to shape or construct meaningful questions, they may lack confidence, or it might be difficulties with memory or hearing that inhibits people.

  Clinicians should help by inviting questions at every single appointment, encouraging patients to bring written questions with them, or to bring a friend or relative along for support.

• Glaucoma support groups

  These are excellent vehicles for information dissemination and valuable peer support opportunities.

In summary, remember that patients’ information needs are complex – and equally complex for those newly diagnosed as those diagnosed decades ago. Even patients who initially appear well-informed often lack key information or skills to manage their condition. Offer them information about their condition and treatment and encourage them to ask questions. And provide a means for them to get back in touch with the clinic if required.

Functional loss over time guides Individualised treatment

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Figure I.4.1 Evaluation of functional loss/time for individualised treatment
IOP = IOP level causing damage
L = difference of visual function between the age-matched normal and the function at the time of diagnosis
RoP = angle representing physiological loss and disease progression
T = time interval between birth and the time of diagnosis

I.6.1 Burden of glaucoma

Glaucoma is among the leading causes of blindness worldwide.¹⁴ The estimated global prevalence of open angle glaucoma (OAG) is 3.5% in 40-80-year olds and of angle closure glaucoma (ACG) 0.50%.^15,16 The number of people with glaucoma was estimated to be 76 million in 2020 and expected to increase to 112 million by 2040. The prevalence of glaucoma is influenced by race: OAG is more prevalent in black populations, while ACG is more prevalent in East Asian populations.

I.6.2 Natural history of glaucoma and blindness

While OAG is far more common than ACG, blindness is more likely to happen in ACG than in OAG (estimated 25% and 10% over the patient lifetime, respectively).^14,15 Due to the established benefit of IOP-lowering treatment in glaucoma, there have been very few opportunities to study the course of untreated glaucoma over time. Valuable data on the natural course of OAG have also been provided by the Early Manifest Glaucoma Trial (EMGT, see I.7.1.4), the United Kingdom Glaucoma Treatment Study (UKGTS, see I.7.1.5) and the Collaborative Normal-Tension Glaucoma Study (see I.7.1.1). In the untreated arm of the EMGT, the overall natural rate of progression in the VF was 1.08 dB/year. Participants with different disease phenotypes exhibited different rates of progression (1.31 dB/year in high tension glaucoma, 0.36 dB/year in normal tension glaucoma and 3.13 dB/year in pseudoexfoliative glaucoma (PXFG).¹³

I.6.3 Risk factors for glaucoma

Older age, elevated IOP, non-White ethnicity (particularly Black), family history of glaucoma, pseudoexfoliation, disc haemorrhage and myopia (see also II.2.2) have been reported as major risk factors for the development of OAG.^15,17,18 Highest prevalence of PACG appears in East-Asian and Chinese race.¹⁵

I.6.4 Under-and overdiagnosis of glaucoma

Several population-based studies have reported that at least 50% of glaucoma cases remain undiagnosed in Europe.^8,18,19 Glaucoma associated with normal range of IOP is more likely to be underdiagnosed. Higher rates of undiagnosed glaucoma have been reported in Asia and Africa.

Conversely, there are very limited data on the overdiagnosis and overtreatment of OAG, which is also expected to occur in clinical practice. The Thessaloniki Eye Study recently reported that the overdiagnosis of OAG is actually substantial in an elderly, white European population.²⁰

References, with an emphasis on European studies:

• 1. Dielemans I, Vingerling JR, Wolfs RC, Hofman A, Grobbee DE, de Jong PT.The prevalence of primary open angle glaucoma in a population-based study in The Netherlands. The Rotterdam Study. Ophthalmology 1994;101:1851-55

• 2. Topouzis F, Wilson MR, Harris A, Anastasopoulos E, Yu F, Mavroudis L, Pappas T, Koskosas A, Coleman AL. Prevalence of open angle glaucoma in Greece: the Thessaloniki Eye Study. Am J Ophthalmol 2007;144:511-19.

• 3. Astrom S, Stenlund H, Linden C. Incidence and prevalence of pseudoexfoliations and open angle glaucoma in northern Sweden: II. Results after 21 years of follow-up. Acta Ophthalmol 2007;85:832-37.

• 4. Höhn R, Kottler U, Peto T, Blettner M, Münzel T, Blankenberg S, Lackner KJ, Beutel M, Wild PS, Pfeiffer N. The ophthalmic branch of the Gutenberg Health Study: study design, cohort profile and self-reported diseases. PLoS One 2015 16;10(3):e0120476.

• 5. Saarela V, Karvonen E, Stoor K, et al. The Northern Finland Birth Cohort Eye Study: Design and baseline characteristics. BMC Ophthalmol 2013;13:51. Published 2013 Oct 8.

• 6. Chan MPY, Broadway DC, Khawaja AP, et al. Glaucoma and intraocular pressure in EPIC- Norfolk Eye Study: cross sectional study. BMJ 2017;358:j3889. Published 2017 Sep 13.

• 7. Karvonen E, Stoor K, Luodonpaa K, et al. Prevalence of glaucoma in the Northern Finland Birth Cohort Eye Study. Acta Ophthalmol 2019;97:200-207.

• 8. McCann P, Hogg R, Wright DM, et al. Glaucoma in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA): cohort profile, prevalence, awareness and associations. Br J Ophthalmol 2020 Feb 7;bjophthalmol-2019-315330.

• 9. Bengtsson BO. Incidence of manifest glaucoma. Br J Ophthalmol 1989;73:483-87.

• 10. De Voogd S, Ikram MK, Wolfs RC, Jansonius NM, Hofman A, de Jong PT. Incidence of open angle glaucoma in a general elderly population: the Rotterdam Study. Ophthalmology 2005;112:1487-93.

• 11. Czudowska MA, Ramdas WD, Wolfs RC, Hofman A, De Jong PT, Vingerling JR, Jansonius NM. Incidence of glaucomatous visual field loss: a ten-year follow-up from the Rotterdam Study. Ophthalmology 2010;117:1705-12.

• 12. Springelkamp H, Wolfs RC, Ramdas WD, Hofman A, Vingerling JR, Klaver CC, Jansonius NM. Incidence of glaucomatous visual field loss after two decades of follow-up: the Rotterdam Study. Eur J Epidemiol 2017;32:691-99.

• 13. Heijl A, Bengtsson B, Hyman L, Leske MC. Natural history of open angle glaucoma. Ophthalmology 2009;116:2271-76.

• 14. Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP. Global data on visual impairment in the year 2002. Bull World Health Organ 2004;82:844-51.

• 15. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology 2014;121:2081-90.

• 16. Day AC, Baio G, Gazzard G, et al. The prevalence of primary angle closure glaucoma in European derived populations: a systematic review. Br J Ophthalmol 2012;96:1162-67

• 17. Topouzis F, Harris A, Wilson MR, Koskosas A, Founti P, Yu F, Anastasopoulos E, Pappas T, Coleman AL. Increased likelihood of glaucoma at the same screening intraocular pressure in subjects with pseudoexfoliation: the Thessaloniki Eye Study. Am J Ophthalmol 2009;148:606-613.

• 18. Burr JM, Mowatt G, Hernandez E, et al. The clinical and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation. Health Technol Assess 2007;11(41):iii-190.

• 19. Topouzis F, Coleman AL, Harris A, Koskosas A, Founti P, Gong G, Yu F, Anastasopoulos E, Pappas T, Wilson MR. Factors associated with undiagnosed open angle glaucoma: the Thessaloniki Eye Study. Am J Ophthalmol 2008;145:327-35.

• 20. Founti P, Coleman AL, Wilson MR, Yu F, Anastasopoulos E, Harris A, Pappas T, Koskosas A, Kilintzis V, Salonikiou A, Raptou A, Topouzis F. Overdiagnosis of open angle glaucoma in the general population: the Thessaloniki Eye Study. Acta Ophthalmol 2018;96:e859-e864.

I.7.1 Treatment vs no treatment trials in open angle

I.7.2 Treatment vs. no treatment trials on angle closure

I.7.3 Studies comparing treatments in open angle

I.7.4 Studies comparing treatments in angle closure

I.8.1 Case detection and screening for glaucoma

There are no systematic reviews or studies that provide evidence for direct or indirect links between glaucoma screening and VF loss, visual impairment, optic nerve damage, IOP, or patient-reported outcomes. Also economic simulation models of cost effectiveness of screening reported inconclusive results with large uncertainties. There is no evidence that interventions (e.g., training) improve opportunistic case finding.

I.8.2 Clinical and cost effectiveness of diagnostic tests used for screening, detection and monitoring for glaucoma

Although there are numerous comparative diagnostic studies, there is no evidence which test, or combination of tests improve patient outcomes, at a sustainable cost. There is a high degree of variability in the design and suboptimal quality of studies of diagnostic accuracy of technologies for glaucoma. Moreover, cost varies with different national or regional health-systems.

I.8.3 Effectiveness of treatment of glaucoma and ocular hypertension in preventing visual disability

There is high-level evidence that treatment decreases IOP and reduces the risk of conversion to and deterioration of glaucoma compared to no treatment.

Based on the economic simulation models in the US, UK, Holland, and China, treating glaucoma is likely to be cost-effective compared to ‘no treatment’. There is uncertainty about the cost-effectiveness of treating OHT.^1,7-9

Comment:

The published simulation models are based on characteristics of participants enrolled in RCTs which may not include all important predictors in the general population and every-day practice. In addition, RCTs may give an optimistic impression of outcomes compared to ‘real life’ with poorer compliance and adherence to care both in patients and clinicians in implementing the guidelines and care protocols. As the data of glaucoma inducing visual disability are limited, the blindness rates in the modelling studies use different estimates. Similarly, the data on utility values and influence of glaucoma severity in health status are limited. Retrospective observational data is incomplete and selective. Reliable and ‘realistic’ data (preferably from large randomised trials or prospective cohorts of ‘usual patients’) is not available so far.

I.8.4 Follow-up practices and models of care

There is no solid evidence of the optimum monitoring schemes, (e.g. frequency and timing of visits, technologies to be used for detecting progression) for patients with manifest glaucoma or OHT. Some modeling and retrospective studies suggest that more treatment may allow less frequent monitoring visits in OHT and stable glaucoma. It has been proposed that more frequent visits in the first two years from the first diagnosis may be cost-effective.

II.1.1.1.1 Goldmann applanation tonometry (GAT)

The most frequently used instrument, and the current reference standard, is the GAT, mounted at the slit lamp. The method involves illumination of the biprism tonometer head with a blue light (obtained using a cobalt filter). The prism is used to flatten the anesthetised cornea which has fluorescein in the tear film. The scaled knob on the side of the instrument is then turned until the inner border of the two hemi-circles of fluorescent tear meniscus, visualised through each prism, just touch (Fig. II.1.1).

There are potential problems of using GAT in that contact with the tear film and the cornea may raise concerns regarding transmissible disease. Chemical disinfection or the use of disposable tonometer heads is recommended. The tonometer calibration should be verified regularly according to the manufacturer instructions.

Errors with GAT can be due to incorrect technique (Fig. II.1.2) and to the biological variability of the cornea and eye. Valsalva’s manoeuvre, breath-holding, squeezing the lids or the examiner touching the lids or a tight tie can all falsely increase the IOP reading. The Perkins tonometer is a portable version of GAT. All precautions to sterilize the GAT prism should be taken.

Technique of Goldmann Applanation Tonometry.

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Figure II.1.1 When there is contact between the tonometer prism (right) and the cornea, the stained tear meniscus can be observer through the prism.

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Figure II.1.2 The correct technique is shown in (A): the prism is correctly aligned to the centre of the cornea and the applied pressure is then adjusted until the inner part of the semicircles touch each other. When the reading is taken before the semicircles are aligned as in (A), the applanation pressure will not correspond correctly to the IOP shown on the dial (B). Incorrect alignment can combine with the wrong amount of fluorescein, adding error on error (C).

II.1.1.1.2 Alternative tonometers (in alphabetical order) (see also I.3, question 2)

A complete list of all available technologies is beyond the scope of the guidelines.

Dynamic contour tonometry (DCT, or Pascal)

This slit-lamp mounted instrument contains a sensor tip with concave surface contour and a miniaturised pressure sensor. The result and a quality score measure are provided digitally. This technique may be less influenced by CCT than GAT. The DCT additionally measures the ocular pulse amplitude which is the difference between the mean systolic and the mean diastolic IOP.

Non-contact tonometry (NCT)

The NCT or air-puff tonometry uses a rapid air pulse to flatten the cornea, thus working on the same basic principle as the Goldmann tonometer. The advantages include speed, no need for topical anaesthesia and no direct contact with the eye. There are several models available in the market. Some patients find the air-puff uncomfortable. The average of several readings per eye is recommended.

Ocular Response Analyser (ORA) and 7CR

The ORA utilises air-puff technology to record two applanation measurements, one while the cornea is moving inward, and the other as the cornea returns towards its normal shape. The average of these two IOP values provides a Goldmann- correlated IOP measurement. The difference between these two IOP readings is called corneal hysteresis, a result of viscous damping in the corneal tissue. The two applanation measurements provide a basis for two additional new parameters: corneal-compensated IOP (IOPcc) and corneal resistance factor. The corneal-compensated IOP is a measurement that is less affected by the corneal properties. The average of several good quality readings per eye is recommended.

Corvis ST tonometer

The Corvis ST is an air-puff tonometer combined with a high-speed Scheimpflug camera which records the corneal deformation during the air-puff. Outputs include an uncorrected IOP, a corneal biomechanically-corrected IOP and CCT.

Rebound tonometry

The rebound tonometer (iCare), is portable and easy to use. Although it is a contact tonometer topical anaesthetic drops are not required and the tonometer has a disposable tip to minimise the risk of cross-infection. The device processes the rebound movement of a rod probe resulting from its interaction with the eye; rebound increases (shorter duration of impact) as the IOP increases.

Six measurements are taken and their average is displayed. The rebound tonometer can be particularly useful in children. The iCare Home device is a variation that has been designed for self tonometry.

Tono-Pen

The Tono-Pen is a hand-held portable tonometer that determines IOP by making contact with the cornea (central contact is recommended) through a probe tip, causing applanation/indentation of a small area. Topical anaesthetic eye drops are used. After four valid readings are obtained, the averaged measurement is given together with the standard error.

Both the iCare and Tono-Pen are useful for patients with corneal disease and surface irregularity as the area of contact is small.

II.1.1.1.3 Self-tonometry

Self-tonometry (e.g., with iCare Home) can be useful in some circumstances. However, it cannot replace clinic-based IOP measures.

II.1.2.1.1 Reference landmarks

Schwalbe’s line: this collagen condensation of the Descemet’s membrane between the trabecular meshwork (TM) and the corneal endothelium appears as a thin translucent line. Schwalbe’s line may be prominent and anteriorly displaced (posterior embryotoxon), or there may be heavy pigmentation over it. A pigmented Schwalbe’s line may be misinterpreted as the TM, particularly when the iris is convex and the angle is narrow. The corneal wedge method is helpful to distinguish between the structures by reliably identifying Schwalbe’s line.

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Figure II.1.3 The ‘corneal wedge’, is a goniscopy technique that helps the examiner identify the Schwalbe’s line in patients where the anterior border of the TM is difficult to see, either because of a lack of pigment or because of excessive pigment. By aiming a thin bright slit at the peripheral cornea, the point where the anterior and posterior reflections of the optical section of the cornea meet identifies the Schwalbe’s line.

Trabecular Meshwork (TM): this extends posteriorly from Schwalbe’s line to the scleral spur. Close to Schwalbe’s line is the non-functional TM, blending into the posterior, functional and often pigmented TM. Most difficulties concerning examination of the TM relate to the determination of whether observed features are normal or pathological (particularly pigmentation), blood vessels and iris processes. Indentation (‘dynamic’) gonioscopy is helpful to detect TM in angle closure.

Schlemm’s canal: it is located anterior to the scleral spur and it is not visible, though it may be seen if it contains blood. Blood reflux from episcleral veins may occur in cases of carotid-cavernous fistulae, Sturge Weber syndrome, venous compression, ocular hypotony, sickle cell disease or due to suction from the goniolens during gonioscopy.

Scleral spur: is of white appearance and located between the pigmented TM and the ciliary body.

Ciliary band and iris root: the iris insertion is usually located at the anterior face of the ciliary body, though the site is variable. The ciliary band may be wide, as in myopia, aphakia or following trauma, or narrow or not seen as in hyperopia, angle closure, and anterior insertion of the iris.

Pigmentation: pigment is found predominantly in the posterior TM. It is seen in adults, rarely before puberty and the extent can be highly variable. The most common conditions associated with dense pigmentation are: PXF, pigment dispersion syndrome (PDS), previous trauma, previous laser treatment of the iris, uveitis and after angle closure episodes.

II.1.2.1.2 Other anatomical features

Blood vessels: these are often found in normal iridocorneal angles in subjects with blue/light irides. They characteristically have a radial or circumferential orientation, have few anastomoses and do not run across the scleral spur. Pathological vessels e.g., neovascularisation, are usually thinner, have a disordered orientation and run across the scleral spur. Abnormal vessels are also seen in Fuchs’ heterochromic iridocyclitis and chronic anterior uveitis.

Iris processes: are present in one third of normal eyes, more evident in younger subjects. When numerous and prominent they may represent a form of Axenfeld-Rieger syndrome/ anomaly. They are distinguished from goniosynechiae which are thicker and wider and may go beyond the scleral spur.

II.1.2.2.1 Gonioscopy technique without indentation

Patient should be instructed to look straight ahead. With indirect Goldmann-type lenses it is helpful to start by viewing the inferior angle, which often appears wider and more pigmented than the superior angle. Then to continue rotating the mirror. The anterior surface of the lens should be kept perpendicular to the observation axis so that the appearance of the angle structure is not changed as the examination proceeds. The four quadrants are examined by a combination of slit-lamp movements and prism rotation.

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Figure II.1.5 The “double hump” is a sign observed in plateau iris.

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Figure II.1.6 Dynamic indentation gonioscopy. When no angle structure is directly visible before indentation, angle closure may be present, and it can be synechial or appositional (1). If during indentation the iris moves peripherally backwards and the angle recess widens (2), the picture in (1) is to be interpreted as appositional closure and a suspicion of relative pupillary block is raised (2). When during indentation the angle widens but iris strands remain attached to the angle outer wall (3), the picture in (1) is to be interpreted as synechial closure. A large and/or anteriorly displaced lens causes the iris to move only slightly and evenly backwards during indentation (4) making the lens a likely component of angle closure.

II.1.2.2.2 ‘Dynamic’ gonioscopy by indentation or compression

It is recommended to use a small diameter lens for indentation (e.g.: 4-mirror). When gentle pressure is applied by the lens on the centre of the cornea, the aqueous humour (AH) and iris are pushed back. In appositional angle closure, the angle can be re-opened. If there is adhesion between the iris and the meshwork, as with goniosynechiae, that portion of angle remains closed (Fig. II.1.6 (3)).

When pupillary block is the prevalent mechanism the iris becomes peripherally concave during indentation. In plateau configuration this iris concavity will not be extended by indentation to the extreme periphery, which is a sign of anteriorly placed ciliary processes called double hump sign (Fig II.1.5). When the crystalline lens has a particularly prominent role in angle closure, indentation causes the iris to move only slightly backwards, retaining a convex profile (Fig. II.1.6 (4)).

II.1.2.3.1 Slit lamp-grading of peripheral AC depth - The Van Herick method

The Van Herick grading (Fig. II.1.8) is an indirect estimation of angle width, but it is not a substitute for gonioscopy. This technique is based on the use of corneal thickness as a unit measure of the depth of the anterior chamber at the furthest periphery, preferably on the temporal side.

Grade 0 represents iridocorneal contact, i.e., angle closure.

A space between iris and corneal endothelium of less than 1/4 corneal thickness, is equivalent to a Shaffer grade I and is interpreted as a high risk of anatomical angle closure. When the space is between 1/4 and 1/2 corneal thickness the grade is II, with very low risk of angle closure. A grade III is not occludable, with an irido/endothe- lial distance more than 1/2 corneal thickness. Alternatively, the peripheral anterior chamber depth may be expressed as a percentage of the peripheral corneal width.

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Figure II.1.7 The Spaeth Grading System of gonioscopy finding.

II.1.3.1.1 Neuroretinal rim

In a healthy eye, the shape of the rim is influenced by size, shape and tilting of the ONH. The disc is usually slightly vertically oval, often more so in black subjects who may also have larger discs. In medium-size discs, the neuroretinal rim is typically at least as wide at the 12 and 6 o’clock positions as elsewhere and usually widest in the infero-temporal sector, followed by the supero-temporal, nasal and then temporal sectors (see Fig. II.1.9). This pattern, described as ISN’T distribution, is less obvious in larger discs, in which the rim is distributed more evenly and in a smaller discs where cupping may not be evident. Larger and a smaller discs are harder to interpret: e.g., in small discs the changes associated with glaucoma may not result in cupping, but ‘saucerization’ of the disc surface instead. In large optic discs the normal rim width is relatively narrow and can potentially be misinterpreted as glaucomatous.

The exit of the optic nerve from the eye may be oblique, giving rise to a tilted disc. Tilted discs are more common in myopic eyes, and show a wider, gently sloping rim in one disc sector in the direction of the tilt and a narrower, more sharply-defined rim in the opposite sector. Discs in highly myopic eyes are even harder to interpret.

Glaucoma is characterised by progressive narrowing of the neuroretinal rim. The pattern of rim loss varies and may take the form of diffuse narrowing, localised notching, or both in combination (Fig. II.1.10). Narrowing of the rim, while occurring in all disc sectors, is generally more common and greatest at the inferior and superior poles.

II.1.3.1.2 Retinal nerve fibre layer

The RNFL appearance can be best assessed in the central 60° at the posterior pole with a blue filter photograph. Clinically at the slit lamp, the RNFL is best evaluated with a red-free light and low magnification and/or with a short, narrow beam of bright white light at high magnification around the circumference of the optic disc within about two disc diameters of the disc margin. The RNFL surface is best seen if the focus is adjusted just anterior to the main retinal vessels.

The fibre bundles are seen as radial silver striations around the disc, Slit-like, groove- like, or spindle-shaped apparent defects, narrower than the retinal vessels, may be seen in the normal fundus. The RNFL may become less visible with age, and is more difficult to see in less pigmented fundi.

Local (wedge and slit) defects are seen as dark bands, wider than retinal vessels which will extend to the disc margin. These local defects are more easily seen than generalised thin- ning of the RNFL, which manifests as a loss of brightness and density of striations. When the RNFL is thinned, the blood vessel walls appear sharp against a matt and mottled back- ground. The initial abnormality in glaucoma may be either diffuse thinning or localised defects.

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Figure II.1.9 The ISNT rule.

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Figure II.1.10 Progression of glaucomatous damage at the optic disc:
Early localized loss (A1), advancing to localized plus diffuse rim loss (A2).
Early localized rim loss, polar notches (B1); more advanced polar notches (B2). Diffuse or concentric rim loss, early (C1); advanced (C2).
Diffuse rim loss (D1), followed by localized rim loss (notch) (D2).

II.1.3.1.3 Optic disc haemorrhages

A large proportion of glaucoma patients have optic disc haemorrhages at one time or another (Fig. II.1.11). They are very often overlooked at clinical examinations, and are easier to find in photographs. The clinical examination should include actively looking for disc haemorrhages. Many studies have shown that optic disc haemorrhages are associated with a higher risk for glaucomatous progression.

II.1.3.1.4 Vessels at the optic disc

Narrowing of the neuroretinal tissue will change the position of the vessels at the optic disc with bending, bayoneting or baring of circumlinear vessels. Those positional changes are particularly important to observe when looking for progression, and can be detected with sequential photographs.

II.1.3.1.5 Parapapillary atrophy

Parapapillary atrophy can be differentiated into an alpha zone, which is present in most eyes, and into a beta zone, which is present in some normal eyes and in a high percentage of eyes with glaucoma. Beta parapapillary atrophy is common in myopic and older eyes.

In clinical practice, a large beta zone can be regarded as a clue, and not as a definite sign of glaucoma (Fig. II.1.12).

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Figure II.1.11 Optic disc haemorrhage.

II.1.3.1.6 Optic disc size (vertical disc diameter)

The optic disc size greatly varies in the population. The width of the rim and the size of the cup vary with the overall size of the disc. The mean vertical disc diameter is approximately 1.9 mm.

The vertical diameter of the optic disc can be measured at the slit lamp using a hand- held high power convex lens. The slit beam should be coaxial with the observation axis; a narrow beam is used to measure the vertical disc diameter using the inner margin of the white Elschnig’s ring as the reference. A correction factor needs to be used depending on the magnification of the handheld lens (Fig. II.1.13).

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Figure II.1.12 ONH with parapapillary atrophy. The alpha zone is located peripheral to beta zone, and is characterized by irregular hypo- and hyperpigmentation. The beta zone of atrophy is adjacent to the optic disc edge, external to Elschnig’s ring (a white circular band that separates the intra- from the peri-papillary area of the optic disc), with visible sclera and large choroidal vessels.

II.1.3.1.7 Rim width and cup to disc ratio (CDR) (see “Things to avoid - choosing wisely” I.4)

A large CDR has been used as a sign of glaucoma damage. However, the CDR depends mainly on the disc size, and a large CDR in normal large discs may be erro- neously considered glaucomatous and a small CDR in glaucomatous small discs may be erroneously considered as normal (Fig. II.1.13). The use of CDR to classify patients is not recommended and the attention should be focused on the neuroretinal rim.

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Figure II.1.13 Optic disc size assessed at the slit lamp with handheld high power convex lens.

II.1.3.2.1 Quantitative imaging (also see I.3)

Quantitative imaging of the ONH, retinal nerve fibre layer and inner macular layers have been used widely to assist glaucoma diagnosis and to detect glaucomatous progression during follow-up. They should not and cannot replace clinical examination and VF testing. See details about OCT testing and interpretation at the EGS book “Glaucoma Imaging” (2017): https://www.eugs.org/eng/books.asp

Optical coherence tomography

OCT is based on interferometry and is a commonly used test. Current instruments are spectral domain and swept-source OCT systems. Their technical, software and reference database characteristics vary; therefore values measured with different OCT systems are not interchangeable. Three main parameter groups are measured and analysed for classification and detection of progression: ONH, peripapillary retinal nerve fibre layer and macular inner retinal layers.

Interpretation of apparent progression in OCT has to be done with caution due to the possible variability of the measurements and possible non-glaucoma related changes. In cases of advanced loss, progression analysis may be beyond the dynamic range of the instrument.

OCT angiography is a rapidly evolving technology the role of which is not yet defined in glaucoma management.

Confocal Scanning laser

The HRT (Heidelberg Engineering, Heidelberg, Germany) is used to profile and meas- ure the three-dimensional anatomy of the ONH and surrounding tissues. It can also help detect progressive changes in ONH surface topography but apparent changes need to be interpreted in the clinical context.

II.1.3.2.2 OCT for glaucoma diagnosis (also see I.3)

OCT imaging instruments typically provide three potential outcomes: ‘within normal limits’, ‘borderline’ and ‘outside normal limits’. No imaging device provides a clinical diagnosis but just a statistical result, based on comparison of the measured parameters with the corresponding reference database of healthy eyes. Therefore an interpretation of the result in the context of all clinical data is mandatory. For instance, imaging artefacts and software errors are quite common and more frequent in eyes that are highly myopic or have tilted nerves. The clinician should assess the quality of the image and segmentation analysis and judge whether the reference database is relevant for the particular patient.

The various imaging technologies have their own advantages and limitations, and their classification shows only partial agreement with clinical exam in diagnosing glaucoma. Agreement between classification with quantitative imaging and VF testing is only moderate. Diagnosis of glaucoma based only on OCT exam should be avoided.

An OCT test “outside normal limits” may be a false positive and can be ignored especially if the clinical examination and VF test are normal and if there are no risk factors for glaucoma.

II.1.3.2.3 Detection of progression with OCT (also see I.3)

Most commercial imaging devices have software for quantifying glaucomatous pro- gression, including the rate of progression. These results may serve as additional tools for the assessment of glaucomatous progression but need careful interpretation in conjunction with other tests and patients circumstances. High quality baselines images are important. The user should assess the test series for the quality of images and software analysis before including the software output in the assessment of the patient. Agreement between structural progression and functional deterioration, over the relatively short duration of reported studies, is only partial or poor because of the measurement variability of both structural and functional tests. Most commercially available software does not compensate for aging, therefore statistically significant slopes do not necessarily mean true glaucomatous progression. Results acquired with different instruments are not interchangeable.

II.1.4.1.1 Automated threshold perimetry

The term, standard automated perimetry (SAP), refers to static computerised threshold perimetry performed using standard Goldmann white stimuli on a white background, and is the recommended standard in glaucoma management.

Testing algorithms and programs

Various perimeters attempt to estimate perimetric threshold sensitivity using different testing algorithms and patterns. Commonly used threshold algorithms in the Humphrey perimeter are Swedish interactive threshold algorithm (SITA) Standard, SITA Fast and SITA Faster. In the Octopus perimeter the Dynamic Strategy is often recommended. The Octopus TOP algorithm (tendency-oriented perimetry) is also often used. TOP is a fast strategy, as it exposes only one stimulus at each test point location, interpolating thresholds between several points.

In glaucoma patients and suspects, perimetry is usually performed using a Goldmann size III stimulus in the central 24° or 30° field, where the great majority of retinal ganglion cells are located. The VF outside 30° is seldom tested. In recent years it has sometimes been recommended to perform additional testing focussing on the central 10° of the field, in order to detect more central field loss. EGS does not recommend decreasing the frequency of standard 24° or 30° testing by replacing these tests with 10° tests. Such additional testing may be helpful in patients where structure/function findings do not agree, e.g., in eyes with normal central 24° or 30° VFs but pathological or suspect optic nerve or RNFL findings. Central field loss is very common in glaucoma and such loss even at very central points, often referred to as ‘threat to fixation’ is clinically worrysome since central VF defects can be symptomatic and compromise the ability to drive.

To the extent possible, it is advantageous to follow patients using a consistent test pattern and strategy, in order to facilitate detection and quantification of progression. In eyes with advanced VF loss, it may become necessary to switch to a larger stimulus size, e.g. to a Goldmann size V stimulus rather than size III, or to a test point pattern which focuses more closely on the remaining area of functioning vision. In most perimeters one may use test point patterns covering only the central 10° of the field in eyes which have only ‘tunnel’ fields left.

II.1.4.1.2 Non-conventional perimetry

Some modalities of computerised perimetry use testing stimuli that differ from those used in SAP. Examples include SWAP, frequency doubling technology (FDT), and flicker perimetry. These techniques were developed with the hope that they would be able to recognise glaucomatous field loss earlier than conventional SAP, but lacking such evidence they are not often used today in glaucoma management.

II.1.4.1.3 Patient instructions

The role of the perimetric technician is of greatest importance in patients who are new to automated perimetric testing. Perimetrically inexperienced patients will produce more reliable test results if the operator simply explains what to expect and how to respond to stimuli. It must be pointed out to perimetric novices that most stimuli will be very dim and that even subjects with normal VFs will see only half of the stimuli. A demonstration lasting just a few seconds, in which the novice sees what the stimuli look like, where they will appear and how they change brightness will help the patient understand the test, and will reduce patient anxiety, thus making patients more willing to return for future perimetric testing. Most experienced patients require only minimal re-instruction. However, even with experienced patients, the operator should remain in the vicinity of the perimeter in order to hear and respond to any patient queries. A quiet, dimly lit environment should be ensured. All perimetric technicians should have taken enough threshold perimetry tests themselves to understand first-hand what it is like to take a test.

II.1.4.2.1 Test data elements commonly seen in perimetry reports

• – The numerical threshold map provides the ‘raw’ estimated threshold values at each test point location.

• – The grey scale maps provide a graphical representation of the numerical threshold map, while the colour-coded maps provide a graphical representation of the deviations from age-corrected normal values.

• – The numerical total deviation map shows point-wise differences between the age- corrected normal threshold sensitivity at each test point location and the patient’s measured threshold value.

• – The numerical pattern deviation map and the corrected deviation map show the same values but after correction for any diffuse loss of sensitivity. Thus, both types of deviation maps highlight localised field loss.

• – Probability maps provide the statistical significance of the numerical deviations, compared to age corrected normative data.

II.1.4.2.2 Reliability indices

These indices are meant to estimate the reliability of test results, and were developed in the early days of automated perimetry. Over time it has become clear that these indices are themselves not very reliable. Thus, high frequencies of false negative (FN) responses have been shown to be of relatively little value in the evaluation of glaucomatous VFs, since abnormal fields often have high FN values even in patients who are very attentive and responsive. High rates of fixation losses (FL) assessed using the blind spot technique may indicate poor fixation, but if the blind spot position is erroneously located, a high FL rate will be indicated even if fixation is perfect. It is probably better to rely on the automatic eye/ gaze tracker of the perimeter or the judgement of the perimetrist. High frequencies of false positive (FP) answers, may be a sign of poor reliability, but many tests with relatively high FP rates have been found to provide useful information. Most patients will deliver very useful perimetry test results if properly instructed, and one should avoid discarding fields a priori only because one or more reliability parameters has been flagged by the instrument’s software.

II.1.4.2.3 Visual field indices

VF indices are numbers summarising perimetric test results. MD (mean deviation in the ­Humphrey or mean defect in the Octopus) represents the average difference between age-corrected normal sensitivity and measured threshold sensitivity values at all test point locations. The visual field index (VFI - Humphrey) is similar to the MD but more heavily centre-weighted. VFI results are expressed in percent rather than in decibels and are more resistant to cataract effects, compared to MD. The Humphrey PSD and the Octopus loss variance (LV) index are designed to detect localised loss. In general, global indices are not primarily meant for and should not be used alone for diagnosis.

II.1.4.2.4 Interpretation methods and aids

A first-time normal exam can be accepted if reliable, but a first-time apparently abnormal exam should be repeated and confirmed if not consistent with other clinical findings i.e., with the appearance of the optic nerve and RNFL (see FC III).

Analysis of single field test results, based on clustered points

Clusters of test point locations with significantly reduced sensitivity are more reliable indicators of early glaucomatous field loss than are an equal number of significantly depressed points that are randomly scattered about the VF. One rule which is often used to classify a test result as outside normal limits requires a minimum of three clustered points having significantly depressed sensitivity, of which at least one should have a significance of p<1%.

The Bebié curve

The Bebié curve, which also is known as the cumulative defect curve of the Octopus perimeter is a summary graph of localised and diffuse sensitivity loss. In entirely diffuse loss the overall curve shows reduced sensitivity compared to normal. This is typically associated with media opacities and not with glaucoma. In focal loss, the right part of the curve is depressed as compared to the normal reference curve. Focal loss is much more consistent with a diagnosis of glaucoma than is diffuse loss.

The Glaucoma Hemifield Test (GHT)

The Glaucoma Hemifield Test of the Humphrey perimeter has been developed specifically for glaucoma diagnosis and classifies results as ‘within normal limits’, ’outside normal limits’ or ‘borderline’. Other GHT classifications are ‘general depression of sensitivity’, – typically found in eyes with media opacities but no manifest glaucoma – and ‘abnormally high sensitivity’ which indicates that the patient has pressed the response button also when not perceiving stimuli.

II.1.4.2.5 Confirmation of classification

Field defects which appear clearly glaucomatous and which are consistent with other clinical findings usually do not need confirmation to support a diagnosis. VFs with subtle defects may require confirmatory tests.

II1.4.2.6 Detecting and quantifying glaucomatous visual field deterioration

It is important to detect and also to quantify VF deterioration in patients under care for glaucoma (see FC IV).

There are two main approaches to computer-assisted VF progression analyses:

• Event analyses

  Progression event analyses seek to detect whether or not a statistically significant VF change has occurred. Indices or test points/clusters are flagged if they have deteriorated more than the expected test-retest variation. Event based analyses have been used in all the large randomised controlled glaucoma trials, e.g. EMGT, AGIS, CIGTS and UKGTS. In clinical practice, event analysis is less important than trend analyses. Event analyses usually require confirmation testing.

• Trend analyses

  Regression analysis to determine the VF rate of progression is widely accepted and used in the management of eyes having glaucomatous field loss. The perimetric rate of progression is the velocity of worsening of the VF, and is usually quantified using linear regression analysis over time of the global indices MD or VFI. Rate of progression is expressed in dB/year or in %/year. Plotting the MD or VFI value of an eye over time can show if the observed rate of progression is likely to lead to loss of QoL during the patient’s expected life-time. PSD and LV should not be used for trend analysis, because in early disease they increase as the field worsens, but then peak and start decreasing again as VF damage becomes moderate to advanced.

II.1.4.2.7 Number and frequency of tests

Determining the rate of progression of an individual eye requires a significant time span, typically at least two years, and enough field tests. It has been proposed that newly diagnosed glaucoma patients should be tested with SAP three times per year during the first two years after diagnosis. The other proposal is to cluster tests. In this way rate of progression can be determined early, and rapidly progressing eyes can be revealed with great certainty. Most often, the frequency of testing can then be reduced and tailored to the observed progression rate, and stage of disease. Patients with OHT do not need frequent VF testing.

II.2.1.1 Primary congenital glaucoma: from birth to the first years of life

• – Neonatal or newborn onset (0-1 month)

• – Infantile onset (>1 until 24 months)

• – Late onset or late recognised (>2 years), also see II.2.1.2

• – Spontaneously non-progressing cases with normal IOP but typical signs of PCG may be classified as self-healed PCG

Epidemiology:

Congenital glaucoma occurs in about 1 in 12-18,000 births among white Europeans. Incidence can be 5 to 10 times higher if consanguinity of parents is present. Severe visual disability is common. PCG is more common in males (65%), and is bilateral in 70% of patients. Isolated trabeculodysgenesis is the most common form of primary congenital glaucoma.

Aetiology and mechanism:

Angle dysgenesis is caused by incomplete development of the TM before and/or after birth. There is a strong monogenetic influence. Heredity shows recessive inheritance with variable penetrance in most cases or is sporadic. Specific chromosomal abnormalities have been identified at chromosomes 1p36 and 2q212. Genetic testing is recommended to rule out other congenital abnormalities that may have impact on family planning.

Decreased aqueous outflow causes significant elevation of IOP.

Features:

• – Photophobia, tearing, blepharospasm, and eye rubbing are typical early signs

• – Not always symptomatic

• – Crying, unhappy child during first weeks or year of life may raise suspicion

• – Larger corneal diameter (>10.5 mm at birth and >12 mm in the first year of life)

• – Increased axial length (>20 mm at birth or >22 mm after 1 year)

• – Corneal epithelial (sometimes stromal) oedema

• – Ruptures of Descemet’s membrane (Haab’s striae)

• – IOP best measured in the awaked child (hand-held tonometers)

• – Under general anesthesia the level of IOP is often artificially lowered by sedation and anesthetic medications

• – Diagnostic value of IOP values alone is insufficient

• – Disc cupping typically occurs only after some months

• – Gonioscopic signs: anterior insertion of the iris, forming a scalloped line with persistent uveal tissue and poorly differentiated structures and/or trabeculodysgenesis often described as Barkan‘s “membrane”

• – The older the age of onset, the fewer the signs and symptoms

Treatment:

Management of these cases is particularly challenging.

Initial surgery is indicated in nearly all cases with primary congenital glaucoma. Medical treatment is usually neither effective nor practicable in long term. Medications, including oral CAIs can be used while decision is made on a surgical approach and in case of failed surgery while awaiting for further options.

Primary surgery: early goniotomy, trabeculotomy, filtration surgery; long-tube drainage devices may be indicated if these are unsuccessful. Repeat surgery is relatively frequent.

Systematic review:

• – Ghate D, Wang X. Surgical interventions for primary congenital glaucoma. Cochrane Database Syst Rev. 2015;1:CD008213.

II.2.1.2 Late-onset childhood open angle glaucoma with onset from more than two years of age to puberty

Aetiology and pathophysiology: as in PCG (see II.2.1.1), except:

• – No ocular enlargement

• – No congenital ocular anomalies or syndromes

• – Asymptomatic until field loss advanced

Features:

• – Open angle

• – Elevated IOP

• – Optic nerve and VF damage depending on disease stage

Treatment:

Cases with later manifestation usually do not have enlargement of the globe and may have a more favourable outcome with surgery.

II.2.1.3 Secondary childhood glaucoma

A variety of pathogenetic mechanisms are possible. A complete list and extensive discussion are outside the scope of the guidelines.

Genetic testing should be strongly recommended due to the large overlap of phenotypes.

Treatment of secondary childhood glaucoma

See Treatment for PCG (II.2.1.1)

Management to be adapted to the primary anomaly, the mechanism of IOP elevation and the QoL of the patient. These cases require highly specialised care.

II.2.2.1 Primary open angle glaucoma (POAG)

Definition: POAG is a chronic, progressive, potentially blinding, irreversible eye disease causing optic nerve rim and RNFL loss with related VF defects. Angle appearance is normal, and major risk factors include the level of IOP and older age. Visual disability is usually prevented by early diagnosis and treatment.

Aetiology and mechanism:

The aetiology remains unclear. Multiple genetic factors and the influence of co-morbidities are likely to play a role. The current concept of how damage is elicited includes deformation of the lamina cribrosa caused by IOP levels that are not tolerated by the individual eye. This is thought to result in axonal damage with consequent apoptotic death of the retinal ganglion cells. Vascular factors also probably play a role.

Any increase in IOP is caused by elevated outflow resistance in the TM outflow pathways. A substantial proportion of patients develop POAG at IOPs within the normal range.

POAG has been arbitrarily subdivided into ’high pressure’ and ’normal-pressure’ disease, even though they represent a spectrum of optic neuropathies. It is presumed that risk factors other than IOP have a relatively greater importance if there is glaucoma at the lower pressure levels. The treatment principles are the same, but there may be some differences in clinical features. Glaucoma with lower IOP levels may be more common in women with vascular dysregulation (eg migraine, Raynaud). Disc haemorrhages and paracentral scotomas may be more common. (See FC V)

Epidemiology

Glaucoma is one of the leading causes of irreversible blindness both in Europe and worldwide. POAG is unusual under the age of 40 yrs. Its prevalence increases with age.

Risk factors for the onset of POAG:

• – Older age

• – Higher IOP

• – Race/Ethnicity: The prevalence of glaucoma is highest in people of black race (see glaucoma epidemiology, I.6)

• – Family history of glaucoma: the risk of having OAG is higher for individuals with a first-degree relative with confirmed OAG

• – Moderate to high myopia

• – Low diastolic blood pressure

• – Thinner CCT: thinner CCT is not independent prognostic factor for the onset of OAG in univariate analyses

Data from the literature on diabetes, systemic high blood pressure, migraine, Raynaud syndrome and obstructive sleep apnoea are inconsistent

Risk factors for progression of POAG

Early Manifest Glaucoma Trial (EMGT), Advanced Glaucoma Intervention Study (AGIS), Collaborative Initial Glaucoma Treatment Study (CIGTS), Collaborative Normal Tension Glaucoma Study (CNTGS) have identified the following risk factors for progression (for details on studies see I.7):

• – Older age

• – Higher IOP

• – Presence of disc haemorrhages

• – Thinner CCT: thinner CCT is not independent prognostic factor for progression of OAG in univariate analyses

Treatment:

See part I and chapter II.2

Choice of primary therapeutic modality needs to be made on an individual patient basis.

FC V – Assessment and follow-up Intervals

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II.2.2.1.1 Primary late-onset juvenile glaucoma

Aetiology and mechanism: Decreased aqueous outflow

Features:

Onset: beyond infancy, usually after puberty or early adulthood. Heredity: if familiar frequently dominant trait. Genes associated with primary juvenile glaucoma have been identified as MYOC.

• – Elevated IOP without treatment

• – ONH and RNFL: Diffuse damage typical, but any type of glaucomatous damage

• – Visual field: glaucomatous defects

• – Gonioscopy: wide open anterior chamber angle, often poorly differentiated

• – No congenital or developmental anomalies

Treatment (See FC VI):

• a) Medical therapy: any effective and well tolerated topical regimen

• b) Surgery: early surgery often required (filtering procedure or goniotomy/ trabeculotomy; consider antimetabolites)

• c) Laser trabeculoplasty: not recommended

FC VI – Treatment options

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II.2.3.1 Secondary open angle glaucomas caused by ocular disease

II.2.3.2 Secondary open angle glaucoma due to ocular trauma

Ocular trauma leads to glaucoma by several different mechanisms. The secondary traumatic glaucomas can be caused by both open angle and angle closure mechanisms. In order to identify and treat the causes of IOP elevation; careful evaluation of the ocular damage must be performed.

Aetiology / Pathogenic mechanism:

Blunt non-penetrating or penetrating trauma to the eye can damage intraocular structures.

Any trauma can lead to reduced trabecular outflow due to traumatic changes of the TM. Scarring and inflammation of the TM, obstruction by red blood cells and debris, angle recession, lens-induced glaucoma.

Features:

• – Elevated IOP may occur a very long time after the trauma

• – Clinical features depend on the aetiology of the trauma

Treatment:

• – Anti-inflammatory medication

• – Topical and systemic IOP lowering medication

• – Long-term IOP lowering and follow up in the presence of permanent anterior segment damage

• – Glaucoma surgery

II.2.3.3 Iatrogenic secondary open angle glaucomas

II.2.3.4 Secondary open angle glaucoma caused by extraocular disease

II.2.4.1 Primary angle closure (PAC)

Staging of primary angle closure

• – Primary angle closure suspect (PACS)

  • Two or more quadrants of iridotrabecular contact (lTC), normal IOP, no peripheral anterior synechiae (PAS), no evidence of glaucomatous optic neuropathy.

• – Primary angle closure (PAC)

  • ICT resulting in PAS and/or raised IOP. No evidence of glaucomatous optic neuropathy.

• – Primary angle closure glaucoma (PACG)

  • ITC causing glaucomatous optic neuropathy.

    PAS and raised IOP may be absent at the time of initial examination.

Gonioscopy remains the gold standard for confirming ITC and diagnosing angle closure. Angle closure is defined by the presence of appositional or synechial lTC in at least 180 degrees.

Most patients with angle closure are asymptomatic. Although symptoms of pain, redness, blurring of vision or haloes may help identify people with sub-acute episodes of elevation of IOP due to angle closure, the sensitivity and specificity of symptoms for identifying angle closure are very poor.

Angle closure may impair aqueous outflow through simple obstruction of the TM, or by causing irreversible degeneration and damage of the TM. The absence of identifiable causes defines PAC.

Risk factors:

Risk factors for PAC disease include older age, family history, female sex, hypermetropia, and race, being more common in South and East Asians e.g. Chinese. Other factors associated with PAC include a thick peripheral iris, a more anterior iris insertion, and more prominent and anterior lens vault. PXF may also be associated with PAC, probably due to loose zonules. In most cases, the predisposition to pupillary block and angle closure is due to a small anterior segment and to the age-related increased lens volume (see II.2.3).

The prevalence of PACG is approximately 0.4% in white Europeans. Three-quarters of cases occur in female subjects.

II.2.4.1.1 Primary angle closure suspect (PACS) or ’occludable’ angle

Aetiology and mechanism:

Features: See II.2.4.1

Treatment:

LPI is recommended for PACS in high risk eyes such as those very high hyperopia, family history, or patients requiring pupil dilatation due to retinal disease (see Evidence). If the angle remains appositionally closed after LPI for PACS further interventions are not necessary.

FC VII – Management of chronic angle closure

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II.2.4.1.4 Status post-acute angle closure attack

Aetiology and mechanism:

Previous episode of acute angle closure attack

Features:

• – Patchy iris atrophy Iris torsion/spiralling

• – posterior synechiae

• – Pupil either poorly reactive or non-reactive

• – “Glaukomflecken” (epithelial and anterior cortical lens opacities)

• – PAS

• – Even without synechia, the TM can be damaged with reduced outflow

• – Endothelial cell count can be decreased

• – Zonules are often weak

• – The disc may become pale but flat, suggesting an anterior ischaemic optic neuropathy, or it can show the typical glaucomatous optic disc cupping

Therapy:

Management according to angle, lens, IOP and disc/visual field. In case of cataract surgery a non-dilatable pupil, low endothelial cell count and loose zonules are of concern.

FC VIII – Management of acute primary angle closure attack

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II.2.5.1 Secondary angle closure with pupillary block

Aetiology and mechanism:

Pupillary block pushes the iris forward to occlude the angle. In iritis or iridocyclitis, the development of posterior synechiae may lead to seclusion of the pupil and absolute pupillary block with consequent forward bowing of the iris or ’iris bombé’. Acute secondary angle closure glaucoma may result.

The following is a limited list of other aetiologies for relative or absolute pupillary block:

• – Enlarged, swollen lens (cataract, traumatic cataract)

• – Anterior lens dislocation (trauma, zonular laxity; Weill-Marchesani’s syndrome, Marfans’s syndrome etc.)

• – Protruding vitreous face or intravitreal silicone oil in aphakia

• – Microspherophakia

• – Miotic-induced pupillary block (also the lens moves forward)

• – IOL-induced pupillary block; anterior chamber IOL, phakic intraocular lens, anteriorly dislocated posterior chamber IOL.

Features:

• – IOP > 21 mmHg

• – Appositional or synechial angle closure on gonioscopy.”

Treatment:

• – Several steps may be considered, according to the clinical picture of causative mechanisms

• – Topical and systemic IOP lowering medication (not sufficient on its own)

• – Nd:YAG LPI

• – Peripheral surgical iridectomy

• – Lens extraction, vitrectomy

• – Discontinuing miotics in miotic-induced pupillary block

• – Pupillary dilatation

• – Nd:YAG laser synechiolysis of posterior synechiae

II.2.5.2 Secondary angle closure with anterior ’pulling’ mechanism synechial closure without pupillary block

Aetiology and mechanism:

The TM is obstructed by iris tissue or a membrane. The iris and/or a membrane are progressively pulled forward to occlude the angle.

Features:

• – IOP > 21 mmHg

• – Appositional or synechial angle closure

• – Disc features compatible with glaucoma may be present

II.2.5.3 Secondary angle closure with posterior ‘pushing’ mechanism without pupillary block

II.3.3.1 Setting the target IOP

There is little evidence to support any particular algorithm to set the target IOP.

In newly diagnosed patients, the target IOP is initially determined according to stage of disease and the baseline IOP. The treatment goal is typically estimated as a specific pressure level or a percentage reduction. For instance, in early glaucoma, an IOP of 18 to 20 mmHg with a reduction of at least 20% may be sufficient. In moderate glaucoma, an IOP of 15 to 17 mmHg with a reduction of at least 30% may be required. Lower target IOP, e.g., 10 to 12 mmHg may be needed in more advanced disease. (See FC X).

Factors to consider when setting the target IOP include:

• – Stage of glaucoma

  The greater the pre-existing glaucoma damage, the lower the target IOP should be

• – Age and life expectancy

  Whilst younger age implies greater life expectancy and, therefore, a lower Target IOP, older age is a risk factor for more rapid progression

• – Untreated IOP

  The lower the untreated IOP levels, the lower the Target IOP should be

• – Goldmann IOP is underestimated if the cornea is thin

• – Additional risk factors, e.g., PXF (see II.2.3.1.1)

• – Rate of progression during follow-up

  The faster the rate of progression, the lower the Target IOP should be

• – Other factors to consider: adverse consequences of intervention, patient preference, family history, status of the other eye

FC IX – Considerations on target IOP

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Greater initial VF loss is the most important predictor of blindness from glaucoma. In a newly-diagnosed patient, the RoP is unknown and Target IOP is based on risk factors for progression (see II.2.2.1). After sufficient follow-up and with sufficient VF tests to reliably determine the progression status, usually 2-3 years, the importance of the risk factors for decision-making decreases and importance of the measured rate of progression increases; the RoP should be used to adjust the target IOP, taking into account IOP levels over the observation period, life expectancy, and current levels of visual function damage (See FC X).

FC X – Setting the target IOP

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Figure II.3.2 Diagrammatic evaluation of target IOP. The target IOP is frequently situated whitin the shaded area. The percentage IOP reduction targeted (i.e. 20%, 30%, 40%) depends mainly on VF damage at diagnosis and on rate of progression. (see also FC X).

II.3.3.2 Achieving and re-evaluating the target IOP

The principles of adjusting therapy to achieve treatment targets are shown in FCs XI to XIV.

If the VF is worsening at a rate that may threaten QoL during the patient’s expected lifetime, then the Target IOP should be lowered futher and treatment changed.

In consultation with the patient the risks and benefits of the additional intervention should be weighed. (See FC XI)

If there are sufficient VFs to judge the rate of progression, and this rate is sufficiently slow not to impact on the patient’s QoL, then the Target IOP may be revised upward if the Target IOP has not been met or if the patient is on excessive therapy or is experiencing side effects.

If there are insufficient VFs to judge the rate of progression and the Target IOP has not been met, then additional therapy should be considered, as above.

FC XI – Adjustment of target IOP

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II.3.4.1 Start with monotherapy

To minimize side effects, the least amount of medication required to achieve the desired therapeutic response should be given. It is recommended to initiate the treatment with monotherapy (See FC XII, XIII and XIV), except in cases with very high IOP and severe disease. Treatment is considered “effective” when the IOP reduction on treatment is comparable to the published range for that drug in a similar population. The highest reduction of IOP is obtained with PGAs, followed by non-selective β-blockers, Rho kinase inhibitors, alpha-adrenergic agonists, selective β-blockers and at last topical carbonic anhydrase inhibitors. IOP-lowering treatment efficacy depends on untreated IOP, with larger reductions in patients with higher untreated IOP levels. Uniocular drug trial may be useful to evaluate the efficacy of therapy.

FC XII – Considerations on first choice medical treatment

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Systematic review:

• – Li T, Lindsley K, Rouse B, et al. Comparative Effectiveness of First-Line Medications for Primary Open Angle Glaucoma: A Systematic Review and Network Meta-analysis. Ophthalmology. 2016;123(1):129-140.

FC XIII – Medical management – choosing therapy

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II.3.4.2 Switch to another monotherapy

If the initial therapy is not effective or the drug is not tolerated, one should switch to another monotherapy (in the same or another class) rather than adding a second drug. Laser trabeculoplasty is an option (See FC XIV).

FC XIV – Therapeutical algorithm in glaucoma topical therapy

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II.3.4.3 Add second drug / combination therapy

If monotherapy is well tolerated and effective, but has not lowered IOP to the target pressure, an additional drug of a different class should be considered. (see Tables 3.1 to 3.6). Multiple topical treatments may reduce adherence and increase exposure to preservatives. Therefore, fixed combination therapy, when available, is preferable to two separate instillations of agents.

Most fixed combinations available in Europe contain a β-blocker. β-blockers may improve local tolerability of the other agent but can be associated with systemic side effects and need to be used cautiously in patients with relevant contraindications. The most frequently used combination is a PGA with a β-blocker. Other combinations include CAI with α-2 agonist and PGA with Rho kinase inhibitor.

Fixed combinations usually have clinical equivalence to unfixed combinations. Combination therapy is not recommended as first choice treatment. However, in selected cases, such as advanced glaucoma and/or very high IOP, the target pressure is unlikely to be achieved by a single agent and combination therapy may be advisable.

Occasionally, in case of uncertainty about the efficacy, consider temporarily stopping IOP lowering medication to re-evaluate untreated IOP.

If a patient is insufficiently controlled with two agents then a third agent, laser or incisional surgery may be considered. (see FC XIV)

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Figure II.3.3 The pre - post IOP graph. Circles in red here represent an increase of IOP from baseline. Green diamonds represent a decrease of IOP from baseline. The yellow triagle is on the ‘no effect line’.

The Following pages outline the most frequently used anti-glaucoma medications, and emphasize their mode of action, dosage and side effects. A complete list of all possible medications is beyond the scope of the Guidelines.

Antiglaucoma drugs have been available since 1875. The following diagram shows the chronology of the introduction of topical IOP-lowering medications (Fig. 3.3).

The text should be considered as a general guide, and cannot be all-inclusive. Only latanoprost has been tested in a trial on children.

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Figure II.3.4 IOP lowering molecules and year of first clinical use. FC: fixed combination.

II.3.5.1 Prostaglandin analogues (PGAs)

PGAs have become the first-choice therapy largely on the basis of their efficacy, once- daily dosing and safety profile.

The primary mechanism of action of PGAs is to increase uveoscleral outflow. Reduction of IOP starts approximately 2-4 h after the first administration, with the peak effect within approximately 8-12 h PGAs may reduce short-term IOP variability compared to other classes of drugs.

Differences in efficacy within the class are not clinically significant. When combined with most of the other IOP-lowering drugs, PGAs provide additive IOP lowering, but two different PGAs should not be combined. Conjunctival hyperaemia, generally mild, is a common finding with difference in frequency and level among PGAs. Hyperaemia may decrease over time. Other PGA side effects are reported in Table 3.1.

Latanoprost is the only IOP-lowering agent studied in children and was shown to have a good safety profile.

Details on the mode of action, IOP lowering effect, contraindications and side effects of other first line drugs (β-blockers, carbonic anhydrase inhibitors, alpha-2 selective adrenergic agonists, Rho kinase inhibitors) and second line drugs are listed in Tables 3.2-3.7.

II.3.5.2 Local toxicity of topical treatment: the role of preservatives

Preserved topical glaucoma medications may cause and/or exacerbate pre-existing ocular surface disease (OSD), such as dry eye and Meibomian gland dysfunction, which has a high prevalence in adults. Benzalkonium chloride (BAC) is the most common preservative in glaucoma medications. Symptoms of OSD often diminish if BAC- preserved drops are substituted with non-preserved drops. A possible unwanted effect of long-term BAC use is a reduction in the success rate of filtering surgery.

Therapeutic options to reduce OSD include preservative-free or BAC-free medication, decreasing the number of eye drops (i.e. by using fixed combinations), treating the ocular surface with unpreserved tear substitutes and performing earlier laser or surgery. Regarding OSD, several factors have to be considered: e.g. the active compound, the specific preservative and other excipients, the ability of the patient to use single-dose preparations and the patient’s ocular surface.

The European Medicines Agency (EMA) has suggested that the use of preservatives should be avoided in patients who do not tolerate eye drops with preservatives and in those on long-term treatment, or to use concentration at the minimum level consistent with satisfactory antimicrobial function in each individual preparation, with a specific indication to avoid mercury containing preparations.

Not all patients are sensitive to preservatives and not all the local side effects observed with topical IOP-lowering medications are induced by preservatives.

Particular attention should be paid to glaucoma patients with pre-existing OSD or to those developing dry eye or ocular irritation over time. This can be done by assessment of the redness of the eyelid margin, positive corneal and conjunctival fluorescein staining or reduced tear break-up time.

II.3.5.3 Generic IOP-lowering topical medications

By definition a generic drug is identical to a brand name drug in dosage, strength, route of administration, performance characteristics and intended use. For the purposes of drug approval, the interchangeability of a generic drug and the corresponding brand-name drug is based on the criterion of ‘essential similarity’. With systemic drugs, bioequivalence studies are performed using blood samples to determine whether the plasma concentration within certain limits equals the branded drug. Clinical studies are usually not required for generic approval in ophthalmology, and a ±10% difference between the concentration of the active compound between the generic and the branded products is considered acceptable by the EMA. Whereas the active compound is assumed to be equal, the excipients can vary considerably. This is an important issue because different adjuvants may alter the viscosity, osmolarity and pH of the eye drops and therefore have an impact on tolerability and corneal penetration. Many drugs are now off-patent and generic alternatives abound. The extent to which these generics are similar in efficacy and tolerability to the branded alternative is not well studied, but there are differences concerning the drop size, the body of the bottle and the bottle tips. Closer monitoring of patients may be required after switching.

Systematic reviews:

• – Hedengran A, Steensberg AT, Virgili G, et al. Efficacy and safety evaluation of benzalkonium chloride preserved eye-drops compared with alternatively preserved and preservative-free eye-drops in the treatment of glaucoma: a systematic review and meta- analysis. Br J Ophthalmol 2020.

• – Steensberg AT, Müllertz OO, Virgili G, et al. Evaluation of Generic versus Original Prostaglandin Analogues in the Treatment of Glaucoma: A Systematic Review and Meta-Analysis. Ophthalmology Glaucoma 2020;3:51–59.

II.3.10.1 Terminology

The commonly used term ‘compliance’ has been increasingly replaced in recent times by the term ‘adherence’. Both are defined as the ‘cooperation of the patient with the recommendations given by the doctor’.

The former is more passive while the latter implies the active part of the patient. ‘Persistence’ is defined as the length of time during which the patient is taking the medication as prescribed.

II.3.10.2 Factors associated with non-adherence

The following factors encountered as common obstacles to glaucoma medication adherence have been described:

• – Medication (for example costs of the drugs, side effects, complicated dosing regimen)

• – Individual

  • Situational / environmental (for example a major event in the patients life, unsteady life-style with many travels)

  • Forgetfulness, comorbidity, poor understanding of the disease Gender (men are more likely to be non-adherent)

  • Stage of the disease (patients with a less advanced disease tend to be less adherent)

• – Clinician (for example lacking communication with the doctor)

II.3.10.3 Identifying non-adherence

Clinicians are unable to detect non-adherence, unless volunteered by patients.

Non-adherence is best identified by asking how and who administers the eye drops, taking an empathetic approach and asking open-ended questions, e.g., have you forgotten to use your eye drops during the last week? If yes, how many times?. Sometimes asking the patient to demonstrate their drop instillation technique is useful.

II.3.10.4 Improving adherence

Adherence may be improved by simplifying the drop regime, patient education, improving communication and setting alarms/messages.

Systematic review:

• – Waterman H, Evans JR, Gray TA, et al. Interventions for improving adherence to ocular hypotensive therapy. Cochrane Database Syst Rev 2013:CD006132.

II.3.11.1 Laser peripheral iridotomy (LPI)

Indications:

Angle closure disase (high risk PACs, PAC, PACG)

Treatment of AAC with suspected pupillary block or plateau iris mechanism (See FC VII and VIII).

Preoperative preparation:

Instil topical pilocarpine. If the cornea is edematous, use topical glycerin 10% if available. Systemic acetazolamide, IV mannitol or oral hyperosmotic agents (See FC XI) may be needed to clear the cornea in cases of AAC. For prevention of IOP spikes use topical alpha 2 agonist 1 hour prior to the procedure and immediately afterwards.

Procedure:

After instillation of topical anesthetic an iridotomy contact lens with contact lens fluid is placed onto the cornea. The lens keeps the eyelids open, stabilises the eye, provides additional magnification, focuses the laser beam and acts as a heat sink.

Iridotomy site is usually chosen in the superior quadrants of the iris well covered by the upper eyelid (to reduce visual symptoms), in a thin looking area or a crypt in the iris periphery. Whole thickness perforation of the iris is assumed when pigment, mixed with aqueous, flows from the posterior into the anterior chamber. Once a full thickness hole has been made, it should be enlarged horizontally to achieve an adequate size (200 microns). Iridotomy size should be sufficient for patency in spite of iris oedema, pigment epithelial proliferation and pupil dilatation. Transillumination through the peripheral iridotomy is not a reliable indicator of success.

Laser parameters for Nd:YAG LPI

In case of thick dark irides, to reduce total Nd:YAG energy, pretreatment with argon laser in 2 stages may be considered. In the first stage a low power argon of 90-250 mW, duration 0.05 sec, spot size 50 μm is applied, followed by the high power argon of 700 mW, duration 0.1 sec, spot size 50 μm to create a punched-out crater appearance. LPI is completed with Nd:YAG laser.

Complications:

• – Intraoperative complications

  • Bleeding from the iridotomy site can usually be stopped by gentle pressure applied to the eye with the contact lens.

• – Postoperative

  • Visual disturbances, e.g. glare, blurring, ghost images, halo, crescent are less likely to occur when the peripheral iridotomy is completely covered by the eyelid.

Transient IOP elevation a few hours after the procedure is the most frequent early complication.

Postoperative inflammation is transient and mild, rarely resulting in posterior synechiae. Rare complications include cystoid macular oedema and aqueous misdirection.

Postoperative management:

Check the patency of the peripheral iridotomy immediately after treatment.

Check the IOP after 1-3 hours and treat accordingly.

Topical anti-inflammatory drops during the first week.

Check the angle with gonioscopy.

II.3.11.2 Laser trabeculoplasty

Indications:

Lowering of IOP in POAG, PXFG and PDG, high risk OHT:

• – As initial treatment (See FC VI)

• – As an add-on or replacement treatment (e.g. for reasons of efficacy, tolerability and adherence) (See FC XIV)

Contraindications:

• – Angle closure

• – Neovascular glaucoma

• – Uveitic glaucoma

• – Post-traumatic glaucoma with angle recession

• – Angle dysgenesis

Preoperative preparation:

Use topical anesthesia. For prevention of IOP spikes, medications to lower the IOP are recommended. Options include topical alpha-2 agonist, pilocarpine or acetazolamide prior to or immediately after the procedure.

Systematic review:

• – Zhang L, Weizer JS, Musch DC. Perioperative medications for preventing temporarily increased IOP after laser trabeculoplasty. Cochrane Database Syst Rev 2017;2:CD010746.

Procedure:

Most frequently used lasers are:

• – Q-switched, short pulsed, frequency–doubled Nd:YAG (532 nm) laser – SLT

• – Argon continuous-wave laser (green or blue/green) - ALT.

Lenses:

Goldmann type gonioscopy lens, Ritch trabeculoplasty lens©, CGA©, Meridian©, Latina© (SLT), Magnaview©.

Identify angle landmarks and place the laser spots at the pigmented TM over 360° (in eyes with highly pigmented TM, 180° initial treatment may be preferred).

Laser parameters for laser trabeculoplasty

Complications:

• – Transient elevation of IOP

• – Inflammation (mild)

• – PAS (after ALT)

• – Corneal endothelial damage

Post-operative management:

Consider checking IOP within 24hours or after 1 hour in high risk patients (e.g. with advanced glaucomatous damage). Topical corticosteroids or non-steroidal anti- inflammatory medication may be prescribed for 4-7 days, but often is not needed. Efficacy of the treatment may be evaluated 4-8 weeks later.

Effectiveness of laser trabeculoplasty:

ALT and SLT have the same efficacy.

Laser trabeculoplasty is initially effective in 80 to 85% of treated eyes with a mean IOP reduction of 20 to 25% (of 6 to 9 mmHg). The effect wears off over time, for both ALT and SLT.

Repeat treatment:

If the first complete treatment is effective but the target pressure is not reached or if the effect wears off after a period of control, a retreatment may be effective. Evidence for further retreatments is lacking.

Predictors of efficacy:

Higher baseline IOP is associated with greater IOP reduction after SLT and ALT.

ALT is less successful in eyes with no pigmentation of TM. SLT seems to be independent

II.3.11.3 Thermal laser peripheral iridoplasty (TLPI)

Indication:

It may be helpful in plateau iris syndrome with remaining angle closure despite a patent peripheral iridotomy and elevated IOP, although the efficacy in reducing IOP is limited. (See FC VIII)

Lasers:

Different types of continuous wave lasers can be used for photocoagulation.

Preoperative preparation:

Instillation of pilocarpine. For prevention of IOP spikes use topical alpha 2 agonist prior to the procedure and immediately afterwards.

Lens:

Contact TLPI lenses.

Laser parameters for laser iridoplasty

Complications:

• – Mild iritis

• – Corneal endothelial burns

• – Transient elevation of IOP

• – Post-operative synechiae of the pupil

• – Permanent pupil dilatation

• – Peripheral iris atrophy

Post-operative management:

• – Anti-inflammatory medication instilled for the first week.

• – Prevention of IOP spike

• – Gonioscopy

II.3.13.1 General principles

Indications for different techniques of incisional surgery depend on:

• – the type of glaucoma

• – the target IOP

• – the previous history (e.g. surgery, medications, degree of VF loss)

• – the risk profile (e.g. single eye, occupation, refractive status)

• – the preferences and experience of the surgeon

• – the patient preference, expectation and postoperative compliance

Surgery should be considered whenever medical or laser treatment is unlikely to maintain sight in the glaucomatous eye. It should not be left as a last resort (see II.3.1).

The ophthalmologist must assess the risks and benefits of early surgery in each individual case.

The primary goal of surgery is to reduce the IOP, ideally achieving a target IOP without additional medication. Additional medications can be used if a target IOP is not reached by surgery alone. Success rates of a surgical method in terms of IOP lowering can be best evaluated in the absence of additional IOP-lowering medical treatment. Also, it is useful to count the percentage of “successes” below a defined IOP level as in Fig. II.3.3. It is important to consider not just IOP but complication rates and functional outcomes. Filtration surgery is a generic term used for procedures where the IOP-lowering effect is obtained by creating a way for the aquous to drain in the episcleral/subconjunctival space. PCG is usually treated with surgery, likely trabeculotomy or goniotomy, or filtration surgery with antifibrotic agents (see II.2.1).

Complicated glaucoma cases such as those that have failed previous surgery, many secondary glaucomas, and congenital glaucomas, require specialist treatment. In addition to trabeculectomy, other forms of therapy may be necessary.

For repeated surgery, cyclodestructive procedures and long-tube implants are more commonly used (See FC VI).

II.3.13.2 Techniques

Glaucoma surgery is successfully practiced in many ways. A detailed description of surgical techniques is not within the scope of this text.

II.3.13.3 Methods of preventing filtering bleb scarring