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Guidelines for the management of open‐angle glaucoma

2024; Wiley; Volume: 102; Issue: 2 Linguagem: Inglês

10.1111/aos.16599

1755-3768

Gauti Jóhannesson, Ulf Stille, Amelie Botling Taube, Markus Karlsson, Lada Kalaboukhova, Anders Bergström, Dorothea Peters, Christina Lindén,

Retinal Diseases and Treatments

These guidelines provide a brief guide on how primary open-angle glaucoma, exfoliation glaucoma and pigment glaucoma can be diagnosed, treated and monitored. The aim is to nationally spread knowledge-based high-quality care, to stimulate the use of scientifically evaluated and effective measures, to even out differences in care and to provide support in setting priorities. Angle-closure glaucoma is not dealt with in this publication but is mentioned where relevant. The National Working Group Glaucoma has made an inventory of applicable current international, Nordic and Swedish guidelines, care programmes and guidelines for glaucoma. Through the regional representatives, we have reviewed a majority of regional and local documents. Answers to specific questions have been sought in PubMed and via Cochrane reports. In compiling these guidelines, we have primarily based our work on the European glaucoma guidelines (European Glaucoma Society, 2021) (which are evidence-graded according to the AGREE system regarding so-called key questions 2020). For evidence grading (A–D), the Finnish guidelines from 2014 were also used (Tuulonen et al., 2014). Furthermore, the current document is based on the previous Swedish guidelines, Guidelines for Glaucoma Care from 2010 (Heijl et al., 2012). On the issues where there is insufficient scientific evidence, the group has discussed its way to a consensus on best clinical practice. The goal of all glaucoma treatment is to preserve the patient's visual function, well-being and related quality of life with a long-term sustainable use of resources. Treatment costs in the form of discomfort and side effects, as well as economic costs for the individual patient and society, should be taken into account. Quality of life is strongly linked to visual function and is affected differently depending on life situation. In general, patients with mild glaucoma damage have good visual function and a largely preserved quality of life, while quality of life is severely affected if both eyes have advanced vision loss that, e.g., affects driving. Glaucoma treatment must be individualized and adapted to the patient, situation and available resources. The increasing availability of randomized controlled clinical trials (RCTs) makes it possible to base clinical recommendations to a greater extent on scientific evidence. There are a number of RCTs that clearly show that intraocular pressure lowering treatment of glaucoma is effective. Glaucoma damage can be slowed down and, in the best case, stopped if patients are properly diagnosed, treated and followed up. The degree of visual field damage and how it develops over time determines the individual treatment strategy (Figure 1). The goal is to maintain good quality of life without advanced loss of visual function throughout life. Glaucoma is a progressive disease that causes typical damage to the optic nerve head, the retinal nerve fibre layer and the visual field. Intraocular pressure is not included in the definition. In primary open-angle glaucoma, the chamber angles should be open and specific causes of glaucoma should not be identifiable. Subjects with primary open-angle glaucoma may have high (high tension glaucoma) or normal (normal tension glaucoma) intraocular pressure. In exfoliation glaucoma, there are also protein precipitates and exfoliations. This type of glaucoma is also known as pseudoexfoliation glaucoma (PEX glaucoma) or capsular glaucoma. The exfoliation material is most easily visible on the front surface of the lens. In the Nordic countries, we often include exfoliation glaucoma in the group of primary glaucomas, while in other parts of the world, it is considered a secondary glaucoma. Pigmentary glaucoma is a secondary glaucoma characterized by the Krukenberg spindle (pigment on the corneal endothelium), slits in the mid-periphery of the iris (transillumination defects) and a smooth, dark pigmented trabecular meshwork in the chamber angle. It is a rare form of glaucoma that typically affects younger people (20–50 years), often myopic and more common in men (5:1). Glaucoma is one of the most common age-related eye diseases and among the leading causes of blindness in the world. In a Swedish study, 42% of patients with open-angle glaucoma became blind in one eye and 16% in both eyes during their lifetime. The disease is uncommon before the age of 40 and increases with age. It is estimated that the global prevalence of open-angle glaucoma is 3.5% in the 40–80-year-old group and 0.5% for angle-closure glaucoma. In 2014, the number of subjects with glaucoma was estimated to reach 76 million by 2020 and is expected to increase to 112 million by 2040. In the context of glaucoma, the terms exfoliation, pseudo-exfoliation (PEX) and exfoliation syndrome are often used interchangeably. A Swedish study published in 2008 showed that about 25% of all visits to Swedish ophthalmic care providers were glaucoma-related. The number of patients in Sweden with diagnosed glaucoma is not known but has previously been estimated at around 100 000. However, this figure is very uncertain. Based on prescriptions in Sweden in 2008 and 2017, the number of unique individuals treated with intraocular pressure-lowering drops was found to be 144 000 and 172 000, respectively, an increase of almost 20% in 9 years. This increase is expected to continue. In addition to patients with diagnosed glaucoma and treated ocular hypertension, many patients with risk factors for developing glaucoma are also checked at Swedish eye clinics, such as untreated ocular hypertension, exfoliations, pigment syndrome and more. This means that significantly more patients than the 172 000 are covered by the guidelines and undergo examination at Swedish eye clinics. Life expectancy in Sweden has increased significantly in recent decades and with it the proportion of older people in the population. According to Statistics Sweden's population projection for 2019, the number of inhabitants over the age of 80 will increase by over 50% between 2019 and 2030. Several studies predict a similar percentage increase in the number of patients monitored and/or treated in glaucoma care by 2040. In order to maintain a decent level of glaucoma care, significant resources must therefore be added. Open-angle glaucoma usually does not cause symptoms until at late stages. The elevated eye pressure is usually painless. The loss of visual field usually affects the paracentral visual field first and is difficult to detect for the patient. In connection with pigment release in people with pigmentary glaucoma, acute pressure increase may occur. At the same time, corneal oedema can cause blurred vision and halo phenomena. Traditionally, the upper limit of normal intraocular pressure has been considered to be ≤21 mm Hg. It is based on several population studies where the average pressure in the adult population is about 16 mm Hg and has a standard deviation of about 2.5 mm Hg. However, this pressure level does not say anything about what eye pressure is harmful at the individual level, since some people suffer injuries at significantly lower levels, and some can tolerate higher levels. Thus, from a functional point of view, all pressure levels that do not give rise to glaucoma damage are 'normal' in the individual. There are a number of factors that increase the risk of developing and/or worsening glaucoma. Knowledge of risk factors is of great importance in order to identify persons who may require (more frequent) monitoring or (more vigorous) treatment, at least until the individual rate of progression is known. Several risk factors in the same person further increase the risk. Individual Eyes General diseases Do not correct intraocular pressure with CCT algorithms. Rule of thumb: thin CCT < 500 μm, thick CCT > 600 μm. Individual Eyes It is unclear whether cardiovascular diseases also affect the risk of glaucoma progression. The following examination and patient history data should be included in the primary assessment of patients with manifest as well as suspected glaucoma, or with risk factors for developing glaucoma. These parameters then form the basis for decisions on how any continued follow-up and treatment should be designed. OCT abnormalities alone are not sufficient to make a diagnosis of glaucoma. The above initial examination package is extensive, but of value in order to be able to perform an adequate assessment and decide on further checks and treatment. Patients with suspected or manifest glaucoma are checked regularly over a long period of time and a proper investigation helps to avoid both over- and under-diagnosis. All examinations do not necessarily have to be carried out at the same time. Rather, it may be valuable to divide these, for example into a visit to the doctor and one to a nurse, optician or optometrist. The time interval between these initial assessments is determined by the level of eye pressure and other risk factors. To get a good idea of the untreated pressure before starting treatment, at least two, but preferably three, separate pressure measurements are recommended. These are often done at different times of the day. At very high-pressure levels, treatment can be started at the first visit, but even in these cases, it should be preceded by at least two separate pressure measurements, preferably performed by different examiners and with different Goldmann tonometers. Follow each patient using the same pressure measurement method – GAT is standard. Intraocular pressure should be checked on at least 2 separate occasions (preferably at different times during the day) before any pressure-lowering treatment is initiated and further follow-up is planned. Glaucoma causes damage to the visual field, primarily within the central 20°. The standard measurement method for the diagnosis and follow-up of glaucoma is Standard Automated Perimetry (SAP). SAP is a computerized static visual field examination (perimetry) based on the principles of Goldmann perimetry, with white stimuli on a white background. Static (stimuli in predetermined test locations) threshold measuring perimetry is more sensitive and detects glaucomatous visual field damage earlier compared to manual kinetic (with moving stimuli) perimetry (Goldmann perimetry), which should therefore not be used. In addition, computerized perimetry is less subjective, the results are numerical, and there are software programmes that assist in the assessment of the results. The most common perimeter in Sweden is the Humphrey perimeter, but Octopus and other perimeters are also used. If there is only a low suspicion of glaucoma, for example when checking patients with a positive history of glaucoma, screening tests, suprathreshold tests that use bright stimuli that are well above the threshold level, should be used. These are easier to perform for patients with no prior experience with computer perimetry and generate fewer false positives. In the Humphrey perimeter, suprathreshold tests with the C-40 pattern and the 2-zone strategy are primarily chosen as screening tests. Another method called Frequency Doubling Technology (FDT) has a couple of screening programmes. C20-1 has the best combination of sensitivity and specificity and is therefore more suitable for screening. In case of greater suspicion of glaucoma, threshold programmes are used. These quantify the field of view. It is desirable to use the same program and the same test point pattern in the diagnosis and follow-up of glaucoma patients. Suitable applications include, for example, the Humphrey perimeter's SITA Standard, SITA Fast or SITA Faster or the Octopus perimeter's Normal Strategy or Dynamic Strategy. There are various indices that summarize the results of the visual field examination. The Humphrey perimeter calculates mean deviation (MD), which is the average deviation in dB from the age-adjusted normal field of view, and the visual field index (VFI), which is expressed as a percentage of a normal field of view. VFI is most often used nowadays. It is significantly less sensitive to cataract development than MD and weights central parts of the visual field higher. The mean defect (also abbreviated MD) calculated in the Octopus perimeter is similar to mean deviation, but note that the signs are different in the two instruments. Damage has a negative designation in the Humphrey perimeter (e.g. −5 dB) and positive in the Octopus perimeter (e.g. +5 dB). Also note that the results from the Humphrey and Octopus perimeters are not directly comparable as the basis of the decibel scale differs between the instruments, 10 dB in Humphrey corresponds to 6 dB in Octopus. In the Humphrey perimeter, VFI can be plotted over time and a coefficient describing the average rate of deterioration per year is calculated to illustrate the Rate of Progression (RoP). Other perimeters have similar indexes (for example, MD slope in the Octopus) that can be used to calculate the rate of progression. In the Humphrey perimeter, the SITA Faster program is the first choice for the vast majority of glaucoma patients when choosing a testing strategy. Thorough instructions and information are needed for everyone undergoing visual field examinations, especially if SITA Faster is being used for the first time. Please note that SITA Faster uses stimuli that are very close to the presumed threshold for detection and are thus more difficult to perceive compared to SITA Fast and SITA Standard. SITA Fast may therefore be a more suitable option for patients who have difficulty completing SITA Faster. In the case of severely reduced visual acuity, such as in macular degeneration, it is sometimes necessary to use another fixation light, called a large diamond (in Octopus called a ring). In the case of advanced visual field damage, it may be useful to focus more on the central part of the remaining visual field (e.g. visual field programme 10–2 in the Humphrey perimeter). There are no follow-up programmes for these test strategies. Optical Coherence Tomography (OCT) is a non-invasive method whose technique is based on the analysis of light reflected from the retina. In this way, the different layers of the retina can be visualized. In glaucoma diagnostics, it is primarily the retinal nerve fibre layer and the ganglion cell layer that are of interest. The OCT examination is easy to perform and is used frequently but cannot replace clinical assessment and/or visual field examination. Digital imaging and automatic image analysis with OCT can be helpful in diagnosing glaucoma provided that the examination is of good quality. However, the risk of artefacts that could lead to misinterpretation of the OCT results is significant. The results of the investigation should be reviewed for any sources of error before assessment. Repeated OCT examinations may show false positive progression, which means that the benefit of OCT in assessing glaucoma progression is limited. Also, the so-called floor effect, which can occur already in patients with moderate visual field damage, complicates progression assessment with OCT. In the case of optic discs that are difficult to assess, for example in cases of severe myopia or pronounced peripapillary atrophy, analysis of the ganglion cell layer in the macula may be preferable to measurements of the peripapillary nerve fibre layer. A clinical examination of the optic disc is necessary for the diagnosis and follow-up of glaucoma. When diagnosing, it is advisable to take a good-quality optic disc photograph for future comparison. Optic disc size must be taken into account in particular when assessing the cupping. Both small and large discs can be difficult to assess from a glaucoma point of view. Measuring the vertical optic disc diameter through a lens in the slit lamp can provide guidance in assessing disc size. For example, if a 60 D Volk lens is used, 2.2 mm is a large one. Another simple method is to compare the disc diameter (DD) with the disc-fovea distance (DM), measured from the centre of the disc to the fovea. The mean DM/DD ratio is 2.5. With a ratio < 2.0, the disc is large. The ISNT rule can be used to assess whether the thickness of the nerve fibres follows the normal distribution of nerve fibre bundles. Usually, the widest rim is found inferiorly, followed by superiorly, nasally and temporally in descending order. Elevated intraocular pressure without damage to the visual field, optic disc or nerve fibre layer is referred to as ocular hypertension (OH). This is usually defined as intraocular pressure > 21 mm Hg. A confirmed diagnosis of glaucoma requires an eye disease with characteristic progressive optic nerve damage with a corresponding visual field defect. Establishing the diagnosis is often easy but can sometimes be very difficult. Corresponding optic nerve and visual field damage, often in combination with elevated intraocular pressure, is a classic combination. For a completely reliable diagnosis, one should also require progression of the damage. In everyday clinical practice, one rarely waits for this. If strict glaucoma criteria are used in diagnosis, it is also not necessary. Abnormal optic disc appearance, other eye diseases, sensitivity of methods, lack of patient compliance, etc. are other factors that often complicate and/or affect making a diagnosis. The perimetric rate of progression at the group level varies, depending on the type of glaucoma, among other things. For example, exfoliation glaucoma usually has a more aggressive course compared to normal tension glaucoma. Even without treatment, visual field deterioration is often slow in subjects with normal tension glaucoma. Pigmentary glaucoma differs from others in that it often involves higher and more fluctuating intraocular pressure levels in the initial stages. Therefore, correct diagnosis is crucial for planning the continued care. If there is uncertainty as to whether glaucoma is present, one can wait and follow the development in most patients, with the possible exception of young patients or patients with very high intraocular pressures. If the intraocular pressure is normal or only slightly elevated, there is even more reason to postpone treatment. With typical glaucomatous optic nerve injury with corresponding visual field defect, no further investigation with radiology is usually needed, even if the intraocular pressure is normal. However, it is not uncommon for neurological conditions that cause optic nerve or chiasmal compression to be misdiagnosed as glaucoma. Thus, visual field defects without typical glaucomatous optic nerve damage should prompt radiological investigation. There can be several reasons for the discrepancy between visual field and optic disc appearance. The following may be helpful: The goal of all treatment for glaucoma is to preserve the patient's visual function, well-being and quality of life with a long-term sustainable use of resources. The most important factor to consider when choosing a treatment strategy is to evaluate the patient's risk of developing visual impairment and vision-related quality of life reduction during their remaining lifetime. Factors that increase the risk are long life expectancy, major damage at diagnosis and disease in both eyes. Thus, younger persons with mild bilateral visual field impairment have significantly higher risks of developing quality-of-life-affecting visual impairment during the remainder of their life compared to older persons with moderate visual field damage in one eye. In addition, the rate at which the disease worsens (RoP) varies from person to person. It is therefore important to individualize treatment. When choosing therapy, other factors should also be taken into account such as side effects, quality of life, compliance and cost. All available treatments, whether pharmacological or laser and surgery, are aimed at lowering intraocular pressure, either by reducing the production of aqueous humour or by increasing the outflow via the trabecular meshwork or the uveoscleral pathway. A target pressure should be set. Target pressure is the upper pressure limit for each eye that is currently accepted and at which the rate of deterioration is deemed acceptable and consistent with a satisfactory quality of life of the patient. The principle is that the greater the damage, the longer the life expectancy and the lower the untreated eye pressure, the lower the target pressure. More damage and high eye pressures require adequate target pressure to be achieved without delay. The presence of exfoliation syndrome warrants extra vigilance. Target pressure is continuously evaluated and adjusted depending on the development of the visual field damage. If the rate of deterioration (RoP) is too high, the target pressure is lowered. In the case of slow visual field progression but not achieved target pressure, the target pressure may be adjusted upwards, especially if the treatment is not well tolerated. Start with monotherapy (or with laser trabeculoplasty). Prostaglandin analogues have a good pressure-lowering effect, are generally well tolerated and should be used as first-line drugs. Beta-blockers have an almost equally good pressure-lowering effect but more systemic side effects and are also a possible first choice. Identify a rapid rate of progression early on and consider surgery in these cases. Many patients undergo surgery too late. A schematic overview of the step-wise increase of treatment is shown in Figure 2. There are six different classes of intraocular pressure-lowering agents, see Table 3 below. It also shows which substances belong to each group, mechanism of action, approximate pressure reduction and some significant and/or common side effects. In the event of a change in pharmacological treatment, intraocular pressure is usually checked within 1 month. In high-risk patients or patients with very high intraocular pressures, the interval may need to be shortened. For advice on the practical approach to initiating and changing treatment, please refer to the section on general treatment principles above. Uveoscleleral outflow ↑ Dosed × 1 Aqueous humour production Dosed × 1–2 Paraesthesia, fatigue, nausea, loss of appetite is common. Electrolyte imbalances, kidney stones, aplastic anaemia NB! Cave sickle cell anaemia! Aqueous production↓ Dosed × 3 (0.5%). For more info and for 1% see Swedish Medical Product Agency Aqueous humour production ↓ (+ uveoscleral outflow ↑?) Dosed × 2 Trabecular outflow ↑ Dosed × 3 Local: miosis, myopia (accommodation paralysis). Systemic: headaches Trabecular outflow ↑ and episcleral venous pressure ↓ (+ aqueous humour production↓?) Dosed × 1 Netarsudil + latanoprost 0.005% As above + uveoscleral outflow ↑ Dosed ×1 In the late 70s, when laser treatment of the chamber angle, laser trabeculoplasty (LTP), was introduced, argon lasers were used and the treatment was therefore referred to as ALT. Although other lasers came into use, the name was kept or the treatment was simply called LTP. Nowadays, a Q-switched, frequency-doubled YAG laser is most often used and selective laser trabeculoplasty (SLT) is performed. It is a gentler treatment that has fewer side effects, is easier to use and has increased repeatability. Both treatments have comparable efficacy and lower intraocular pressure approximately as much as an eye drop. At higher eye pressures, a greater effect is achieved. The effect wears off over time. At low-pressure levels ( 21 mm Hg, the risk of developing glaucoma damage with slightly elevated pressure is small. Therefore, if other risk factors are missing, a higher pressure level is often chosen as the limit for follow-up in eye care. Intraocular pressure should be checked on at least 2 separate occasions (preferably at different times during the day) before any pressure-lowering treatment is initiated and further follow-up is planned. Intraocular pressure-lowering therapy reduces the risk of developing glaucoma in patients with ocular hypertension. Patients with suspected glaucoma (suspected optic disc configuration and/or unclear visual field defects) are initially followed at intervals of 6–12 months. Extend the interval or consider terminating patient follow-up if pressure, optic nerve appearance and visual field remain unchanged after a few years of follow-up. 5–6 visual fields during the first 2 years do NOT apply to patients with newly discovered ocular hypertension! Once the rate of progression is determined after 5–6 visual field tests, further follow-up should be adjusted according to this and the patient's individual risk profile. Re-assessment after the first two years: High rate of progression → more frequent checks. Low rate of progression → less frequent follow-up visits. After identification of rapid progression when additional pressure-lowering treatment such as surgery has been necessary, a new evaluation of the rate of progression should be made (2–3 visual field tests per year) to ensure that the new lower target pressure has had a sufficient effect. In the case of a positive family history of glaucoma, checking intraocular pressure only is insufficient! The presence of several risk factors necessitates shorter intervals between check-up visits. As a diagnosis of glaucoma is often associated with great anxiety and sometimes also entails significant limitations in the patient's life situation, accurate information about the nature, treatment and prognosis of the disease is of the utmost importance. At the time of diagnosis, sufficient time should be set aside for this. Particular attention should be paid to the importance of good adherence to treatment and regular check-ups, as well as information on patient associations and appropriate information material. A quick follow-up visit or telephone contact can be of value in answering further questions and ensuring that the patient understands the meaning of their illness. The establishment of glaucoma schools can promote the above through further information and by creating affinity and exchange of experience among newly diagnosed patients and individuals with practical experience of living with a diagnosis of glaucoma. It is important that the patient is involved in decisions concerning their disease and that there is continuity in the follow-up of the disease. In the case of glaucoma-related visual impairment, rehabilitation can be crucial for a patient to maintain quality of life. It should be taken into account that loss of visual field can cause extensive functional impairment and referral to visual rehabilitation should be offered, even if central visual acuity is maintained. Many factors affect a person's ability to access and cope with glaucoma treatment. An open approach in patient contact where healthcare professionals do not hesitate to raise difficult issues is very important. Recalculate the intraocular pressure based on the CCT. There is a lack of validated correction algorithms. Base glaucoma diagnosis and progression assessment solely on OCT measurements. Abnormal OCT results are statistical deviations from a reference material and cannot be equated with clinical diagnosis. Use C/D ratio for glaucoma diagnosis and progression assessment. Normal cupping varies depending on optic disc size. Replace gonioscopy with different imaging methods. Imaging methods are not accurate enough. Replace clinical assessments with AI (artificial intelligence). Technology can support but not replace clinical assessment. Use stress tests to diagnose narrow chamber angles. A negative test does not rule out the risk of acute narrow-angle attacks. Treat blind, symptom-free eyes with high intraocular pressure. In the absence of visual function, treatment is only warranted in the case of pain. Use carbonic anhydrase inhibitors and hyperosmotic drugs in sickle cell disease. These drugs can induce a hemolytic crisis in this disease. Use 21 mm Hg as target pressure in advanced glaucoma. The intraocular pressure needs to be lowered significantly. A reasonable quality follow-up of glaucoma care in Sweden requires a national quality register. These are available for several groups of eye diseases, including cataracts, macular degeneration and corneal diseases, but not yet for glaucoma. The surveys/cross-sectional studies on glaucoma that have been conducted so far in the country, have required large and irregular efforts and are not considered to lead to a sustainable flow of data. For this, a quality register is crucial. A register can provide information on whether the proportion of severely visually impaired people varies across the country, but also on differences in incidence/prevalence, diagnostic criteria, treatment criteria and waiting times. Even if only a few parameters (e.g. only for a fraction of patients) such as social security number, diagnosis, visual acuity, intraocular pressure, VFI and any waiting time are registered annually, it would provide clear help to ensure patients' equal treatment and follow-up throughout the country.