Background To investigate the outcomes of glaucoma referrals across different European countries.
Methods 250 patients newly referred to tertiary referral glaucoma specialist practices in the UK, Hungary, Slovenia, Italy and Greece were prospectively enrolled (50 consecutive patients per centre). Referral accuracy and predictive value of referral criteria for an intervention or further monitoring (positive predictive value) were analysed.
Results Same-day discharges occurred in 43% (95% CI 39% to 75%) (12/28) of optometrist-initiated referrals (UK only), 37% (95% CI 30% to 45%) (59/158) of ophthalmologist-initiated referrals (all centres) and 54% (95% CI 40% to 68%) (26/48) of self-referrals (Hungary, Italy and Greece). The percentages from all referral sources were 46% (95% CI 32% to 60%) in the UK, 56% (95% CI 44% to 70%) in Hungary, 30% (95% CI 17% to 43%) in Slovenia, 22% (95% CI 11% to 34%) in Italy and 60% (95% CI 46% to 74%) in Greece (p<0.001). Overall, the referring criterion was confirmed in 54% (95% CI 45% to 63%) (64/119) for intraocular pressure (IOP) >21 mm Hg, 56% (95% CI 43% to 69%) (33/59) for a suspicious optic disc and 61% (95% CI 45% to 77%) (22/36) for a suspicious visual field, with large between-country differences (p<0.05 for all comparisons). Of all referrals, 32% (95% CI 26% to 37%) were initiated on the basis of IOP >21 mm Hg only. By combining the IOP criterion with any other referring criterion, the positive predictive value increased from 56% (95% CI 45% to 67%) to at least 89% (95% CI 68% to 100%). In the UK, a hypothetical IOP threshold of >26 mm Hg, as a requirement for IOP-only referrals, would reduce IOP-only referrals by 44%, while not missing any definite glaucoma cases.
Conclusion The accuracy of referrals was poor in the UK and the other countries. Requiring a combination of criteria and raising the IOP threshold for IOP-only referrals are needed to cut waste in clinical care.
- Diagnostic Tests/investigation
- Intraocular Pressure
- Optic Nerve
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The insidious nature and irreversible course of glaucoma, compounded by the knowledge that at least 50% of patients with glaucoma remain undiagnosed,1 necessitate appropriate referral for early diagnosis. However, the burden of processing false-positive cases puts a great strain on hospital glaucoma services resources. This translates into increased waiting times for new and follow-up appointments, and increased costs for the hospitals, patients and taxpayers in government-funded systems. It also exposes healthy individuals to unnecessary stress and possibly even unnecessary treatment.
In the UK most glaucoma referrals are initiated by community optometrists.2 Prospective data suggest that the accuracy of glaucoma referrals in England is moderate to low.2–8 Even with agreed guidelines and referral criteria, the positive predictive value of referrals for suspected glaucoma is in the region of 40%.6 9 Following the publication of the National Institute for Health and Care Excellence (NICE) guidelines for glaucoma and ocular hypertension (OHT) in 2009,10 the number of new referrals has significantly increased, while the absolute numbers of glaucoma and glaucoma suspects have remained unchanged.8
As opposed to the UK, little is known about the outcomes of glaucoma referrals in other European countries, where the collaborative practice model for eye care between optometrists and ophthalmologists may not apply. The current study aims to address this gap in the literature by investigating the outcomes of glaucoma referrals across different European countries, including the UK (data represent only England and Wales, as referral guidelines are different in Scotland). Such data could be of interest to public health services and may help formulate better guidelines for glaucoma referrals in the future.
Materials and methods
This was a multicentre, prospective, observational, cross-sectional study. Data from 250 patients newly referred to five tertiary referral glaucoma specialist practices (50 consecutive patients per centre) were ascertained in the UK (Moorfields Eye Hospital, London), Hungary (Semmelweis University, Budapest), Slovenia (University Medical Centre Ljubljana), Italy (Azienda Ospedaliera Universitaria San Martino-IST, Genoa) and Greece (Aristotle University of Thessaloniki). All data were collected from May 2013 to March 2014 in the context of locally performed clinical audits, which did not involve disturbance of patients over and above normal clinical management. Therefore, research ethics committee approval was not required.
Patients ≥18 years old who had not previously attended the above specialist practices were eligible for enrolment (henceforth, the terms ‘centres’ and ‘glaucoma experts’ will be used for the tertiary referral glaucoma specialist practices and for the glaucoma subspecialists in these practices, respectively). These patients were either referred by a healthcare practitioner or were self-referrals, meaning that they requested a consultation in one of the above centres without having received such advice from a healthcare practitioner. Patients who had previously attended other glaucoma practices were also eligible for enrolment.
A standardised case report form (CRF) was used for data collection, which consisted of three sections: (1) patient demographics, (2) data collected by the referral source and (3) data collected at the centre (online supplementary table 1). To reflect everyday clinical practice, subjects were examined according to the standard examination protocol followed in each centre, respectively, and the diagnosis was left to the discretion of the glaucoma expert in each centre. The following mutually exclusive categories were used:
glaucoma (definitely glaucomatous optic disc and/or visual field (VF), irrespective of intraocular pressure (IOP))
glaucoma suspect (the patient does not clearly fall into any of the other diagnostic categories and further follow-up is deemed necessary to reach a diagnosis)
OHT (IOP >21 measured at the centre, and definitely non-glaucomatous optic disc and VF)
primary angle closure (PAC)/primary angle closure suspect (PACS) as defined by Foster et al 11
other ocular pathology
normal (absence of all of the above).
Supplementary file 1
The CRF specifically queried whether each referral met one or more of the criteria listed in the 2010 Joint College Guidance (JCG) on the referral of glaucoma suspects by community optometrists in the UK12:
‘a. There are optic disc signs consistent with glaucoma in either eye; b. The IOP in either eye exceeds 21 mmHg; c. A visual field defect consistent with glaucoma is detected in either eye; d. A narrow anterior drainage angle on van Herick testing consistent with a significant risk of acute angle closure within the foreseeable future; e. Conditions often associated with glaucoma (eg, pigment dispersion syndrome or pseudoexfoliation)’.
To the best of our knowledge these are the only currently available guidelines for glaucoma referrals in a European country. We also added (f) family history of glaucoma and (g) ‘other reason’ as possible referring criteria.
An outcome was defined as positive when the management plan was an intervention or active monitoring and as negative when the management plan was same-day discharge. To identify which criterion (or combination of criteria) is better at predicting a positive outcome, we defined its positive predictive value.
The comparison of quantitative variables among centres was assessed with analysis of variance; the Kruskal-Wallis test was used when data were not normally distributed. The association between qualitative variables was assessed with a χ2 test or Fisher’s exact test when the expected count was less than 5. All p values were two-tailed; p Values <0.05 were considered statistically significant. Statistical analyses were performed using IBM/SPSS Statistics V.22 software.
Outcomes of glaucoma referrals
Demographics and clinical characteristics of the 250 newly referred patients are presented in online supplementary table 2. A glaucoma diagnosis was made in 10% (95% CI 2% to 18%) of patients in the UK, 10% (95% CI 2% to 18%) in Hungary, 48% (95% CI 34% to 62%) in Slovenia, 42% (95% CI 28% to 56%) in Italy and 14% (95% CI 4% to 24%) in Greece (Fisher’s exact test, p<0.001) (table 1). A diagnosis of OHT was more common in the UK (24%; 95% CI 12% to 36%) compared with other countries (14% or less), as was a diagnosis of PAC/PACS in Hungary (20%; 95% CI 9% to 31%), compared with other countries (6% or less). The percentages of negative outcomes were 46% (95% CI 32% to 60%) in the UK, 56% (95% CI 44% to 70%) in Hungary, 30% (95% CI 17% to 43%) in Slovenia, 22% (95% CI 11% to 34%) in Italy and 60% (95% CI 46% to 74%) in Greece (Fisher’s exact test, p<0.001).
The UK was the only country with optometrist-led referrals, which represented 56% (95% CI 42% to 70%) of all patients (table 2). Ophthalmologist-led referrals were recorded in 40% (95% CI 26% to 54%) of patients in the UK, 64% (95% CI 51% to 77%) in Hungary, 94% (95% CI 87% to 100%) in Slovenia, 54% (95% CI 40% to 68%) in Italy and 64% (95% CI 51% to 77%) in Greece. Almost a third of all referred patients in Hungary, Italy and Greece were self-referrals; there were no self-referrals in the UK and Slovenia.
Negative outcomes were documented in 43% (95% CI 39% to 75%) of optometrist-initiated referrals (UK only), in 37% (95% CI 30% to 45%) of ophthalmologist-initiated referrals (all centres) and in 54% (95% CI 40% to 68%) of self-referrals (Hungary, Italy and Greece). The percentages of negative outcomes among ophthalmologist-led referrals were 50% (95% CI 28% to 72%) in the UK, 47% (95% CI 30% to 64%) in Hungary, 28% (95% CI 15% to 41%) in Slovenia, 19% (95% CI 4% to 33%) in Italy and 50% (95% CI 33% to 67%) in Greece (table 2).
Criteria for referral, accuracy and positive predictive value
Overall, IOP >21 mm Hg was by far the the most common referring criterion (48%; 95% CI 41% to 54%) (table 3). A suspicious optic disc (24%; 95% CI 18% to 29%) and a suspicious VF (14%; 95% CI 10% to 19%) were less common referring criteria. In Greece, family history of glaucoma as referring criterion was as common as high IOP (42%; 95% CI 10% to 32%). Overall, IOP >21 mm Hg as a referring criterion was confirmed in 54% (95% CI 45% to 63%) of patients, although there was large variation between the centres (table 3 and online supplementary figure 1). A suspicious optic disc was confirmed in 29% (95% CI 8% to 51%) of patients in the UK, 0% (0/2) in Hungary, 76% (95% CI 59% to 93%) in Slovenia, 83% (95% CI 54% to 100%) in Italy and 44% (95% CI 12% to 77%) in Greece (χ2, p<0.001).
Supplementary file 2
Figure 1 presents the positive predictive value of different referring criteria (detailed data in online supplementary table 3). IOP >21 mm Hg as a sole referring criterion had a positive predictive value of 56% (95% CI 45% to 67%). When high IOP was combined with a suspicious optic disc or a suspicious VF, the positive predictive value increased to 89% (95% CI 78% to 100%) and 94% (95% CI 82.0% to 100%), respectively. Family history of glaucoma had a low positive predictive value (35%; 95% CI 22% to 49%), even when it was combined with other referring criteria. Among sole referring criteria, a narrow angle on van Herick test had the highest positive predictive value (92%; 95% CI 76% to 100%).
Overall, among those who met the IOP >21 mm Hg criterion, only 49% (95% CI 40% to 58%) had Goldmann tonometer measurement by the referral source; in 17% (95% CI 10% to 24%) the method was not specified and in 10% (95% CI 5% to 16%) the IOP was not recorded (self-reported high IOP). Of all referrals, 32% were made on the basis of IOP >21 mm Hg only (IOP-only referrals): 32% (95% CI 19% to 45%) of patients in the UK, 34% (95% CI 21% to 47%) in Hungary and Slovenia, 20% (95% CI 9% to 31%) in Italy and 38% (95% CI 25% to 52%) in Greece. Among IOP-only referrals, the Goldmann tonometer was used in 44% (95% CI 33% to 55%) of patients. However, there were large variations between the centres in the method of IOP measurement (detailed data in online supplementary tables 4 and 5).
Outcomes of hypothetical IOP thresholds for glaucoma referrals
Using the UK data, we assessed the effect of hypothetical IOP thresholds, as required referring criteria, on the outcomes of IOP-only referrals (figure 2). For IOP >23, >24 and >26 mm Hg, the percentages of positive outcomes and of avoided negative outcomes increased as the threshold increased, but the percentage of positive outcomes that would have been missed remained the same at 13% (95% CI 0% to 29%). This represents two individuals, neither of whom had definite glaucoma. An IOP threshold of >26 mm Hg would reduce IOP-only referrals by 44%, while providing the highest percentage of positive outcomes (78%; 95% CI 51% to 100%) and while keeping the potentially missed positive outcomes to a minimum (detailed data in online supplementary table 6). We reanalysed data for all IOP-only referrals in the study and results were in the same direction (online supplementary table 7).
The principal findings of our study are the following: (1) 43% of optometrist-initiated referrals (UK only), 37% of ophthalmologist-initiated referrals (all centres) and 54% of self-referrals (Hungary, Italy and Greece) resulted in same-day discharges. (2) Only 10% of newly referred patients had glaucoma in the UK; results were similarly low in Hungary and Greece. (3) Of all referrals, 32% were IOP-only referrals. By combining the IOP criterion with any other JCG referring criterion, the positive predictive value increased from 56% to at least 89%. (4) Family history of glaucoma had a low positive predictive value. (5) A hypothetical IOP threshold of >26 mm Hg, as a requirement for IOP-only referrals, would reduce the latter by 44%, while not missing any definite glaucoma cases.
Our study adds to the literature, as there are no previous reports on the outcomes of glaucoma referrals across different European countries. The prospective design, the use of a standardised protocol pro forma for data collection and the fact that results reflect everyday clinical practice are additional strengths of the study. The participating centres were chosen as typical examples of tertiary referral glaucoma specialist practices to represent diverse European countries in terms of healthcare systems and resources, including primary eye healthcare and glaucoma referral pathways. In the UK optometrists are the main primary eye care providers,2 whereas in other European countries primary eye healthcare is the responsibility of general ophthalmologists. In the UK and Slovenia access to glaucoma specialist practices can only be granted via a healthcare professional. Conversely, in Hungary, Italy and Greece individuals can request appointments at a glaucoma specialist practice through the hospital booking system without a formal referral. These differences are reflected in our data and explain the considerable number of self-referrals found in the study. Possible reasons for self-referrals include a known or potential family history of glaucoma, a verbal suggestion by an optician or an ophthalmologist and high health anxiety. In all participating countries there are also general and subspecialised ophthalmologists in the private sector who can refer patients to tertiary specialist practices for second opinions or further management.
In view of the very limited data from other European countries, comparisons with the literature would be appropriate mainly for the UK setting. Among optometrist-led referrals 43% were same-day discharges, which is in agreement with previously published data.2 7 13 Only 10% of all newly referred patients actually had glaucoma, which is in agreement with other UK studies conducted after the publication of the NICE guidelines.7 8 In addition, this study presents clinically useful information on other aspects of the glaucoma referrals, which can be used by the participating countries to inform policies and to identify educational needs. By examining the UK data in relation to other European countries, this study also helps us put into perspective how much the UK actually benefits from the existing well-structured system for glaucoma referrals. For example, the accuracy of referring criteria and the outcomes of glaucoma referrals were similarly suboptimal in the UK, Hungary and Greece. It is noteworthy that in the latter two countries at least a third of all referrals were self-recruited individuals, among whom the prevalence of glaucoma is known to be low.14 15 It is also interesting that, overall, referrals initiated by general practitioners resulted more often in same-day discharges than self-referrals. The large numbers of referrals by private ophthalmologists in Slovenia and of patients with a glaucoma-related history in Italy are possible explanations for the higher percentages of positive outcomes found in these centres.
In the UK, a raised IOP was confirmed in 67% of patients, which is in agreement with a previous study of optometrist-led referrals.16 Interestingly, in Greece the Goldmann tonometer was used more often than elsewhere, and yet the confirmation rate was lower. These data suggest that discrepancies in IOP measurement cannot be explained by the method of measurement alone. Poor measurement technique,17 measurement error and IOP fluctuation are other possible explanations. A single IOP measurement >21 mm Hg is known to have low sensitivity and specificity in diagnosing glaucoma.18 Our data further suggest that IOP-only referrals have low value in predicting the need to treat or to monitor a patient. By combining the IOP criterion with any other JCG criterion,12 the predictive value increased substantially, and this is in agreement with previously published data.3 6 13 Thus, our findings support the statement that ‘IOP-only referrals represent a waste of hospital outpatient resource’.13 Interestingly, family history of glaucoma had a low positive predictive value, even when it was combined with other referring criteria. Due to the fact that population screening for glaucoma would not be cost-effective, it has been suggested that selective screening of groups with higher prevalence, such as those with family history, might be worthwhile.19 Although family history is an established risk factor for glaucoma,20 21 the self-reported information is subject to recall bias22 and cannot always be distinguished from OHT.23 Based on our data, glaucoma case finding strategies cannot rely solely on self-reported family history of glaucoma.
According to the Academy of Medical Royal Colleges, protecting resources and cutting waste in clinical care are major priorities to preserve the standards of care.24 In this context, refinement schemes for glaucoma referrals have been introduced in the UK.13 25 26 Despite their efficiency, such schemes may be difficult to implement as they require specific training, setting or infrastructure. Using the UK data we found that a hypothetical threshold of >26 mm Hg, as a requirement for IOP-only referrals, would reduce the latter by 44%, while protecting patients’ safety. When we tested this hypothesis in all IOP-only referrals in the study, results were in the same direction. In England the estimated number of new glaucoma referrals per year is 203 534.27 28 According to our findings and previously published data,7 8 13 one-third of these are expected to be IOP-only referrals. The UK National 2014–2015 tariffs for an outpatient attendance in ophthalmology is £104 and for one diagnostic procedure in glaucoma is £81.29 Thus, the estimated cost for examining IOP-only referrals in the hospital is £12 551 140 per year (assuming parsimoniously that only one diagnostic test is performed in each visit). According to our data, using the threshold of 26 mm Hg would reduce IOP-only referrals by 44%, and thus would save the National Health Service £5 491 123.75 per year.
Based on this strategy, patients with IOP below the ‘26’ threshold (and who do not fulfil other referring criteria) would remain under monitoring in the primary care setting, but could still be referred in the future if needed. Given that the ‘positive outcomes which would have been missed’ cannot be eliminated, this strategy implies that there would be a residual, though very small risk for conversion to glaucoma among those who would not be referred. According to the Ocular Hypertension Treatment Study, ‘delaying treatment for 7.5 years in low risk participants resulted in only a small absolute increase in the overall frequency of open angle glaucoma’. 30 In addition, based on the rating of more than 1000 scenarios of glaucoma suspects, there is agreement among glaucoma specialists that for most ocular hypertensives with IOP <26 mm Hg who do not have a suspicious optic disc or strong risk factors for glaucoma IOP-lowering treatment is unlikely to be appropriate.31 It is important to prioritise resources in favour of those at greater risk of visual disability.32 In a large retrospective study of 3790 UK patients attending glaucoma clinics, most patients were not at high risk of progressing to statutory blindness, whereas the vast majority of those predicted to suffer visual impairment in their lifetime had advanced VF loss at presentation.33 Although VF loss at the time of glaucoma diagnosis has become less severe in the last decade, there are still large numbers of patients with significant vision loss at presentation.34 Therefore, the main concern for glaucoma-related blindness is the late presentation of the disease, and efforts should focus on glaucoma case finding. In this context, primary eye healthcare needs to be better organised and supported. The main barriers to the detection of glaucoma in the community seem to be time constraints limiting the options for repeat testing and lack of financial remuneration to perform the additional tests required.35 Although optometrists are keen to develop their professional skills and knowledge, they need sufficient financial incentives to participate in enhanced optometric services.36
There are some limitations in our study. We included only one centre per country and only one glaucoma expert per centre. Although clinical practice in glaucoma follows published guidelines,10 37 variability in the diagnostic and management outcomes of glaucoma experts cannot be excluded.17 In addition, direct comparisons of study results between the participating countries may not be appropriate due to the wide differences in the way primary eye healthcare is organised. For the same reason, our clinical recommendations on IOP-only referrals may be applicable only to countries with substantial and skilled optometric workforce to provide community eye care, such as the UK. Another limitation is that our study was not designed to assess the levels of negative predictive values. This is an important issue to be addressed in a prospective study, which should also assess the cost-effectiveness of the above clinical recommendations. Health economics of glaucoma health service delivery are particularly complex and all proposed practices require economic evaluation.38
In summary, the outcomes of glaucoma referrals reflect a poor use of resources in the UK (England and Wales) and other European countries. About a third of all glaucoma referrals were IOP-only referrals, and these represent an immense waste of hospital outpatient resources. By combining the IOP criterion with any other referring criterion, the predictive value for a positive outcome increases substantially. Increasing the IOP threshold for IOP-only referrals would be a simple strategy to cut clinical waste, while maintaining patients’ safety. However, under no circumstances should this strategy encourage the use of IOP thresholds to identify glaucoma suspects. It is well known that IOP is only a risk factor and not a diagnostic criterion for glaucoma. Optic disc and VF assessment remain the hallmarks of clinical examination for glaucoma.37
Contributors Substantial contributions to the conception or design of the work: PF, FT, GH, BC, MI, ACV. Acquisition, analysis or interpretation of data for the work: PF, FT, GH, BC, MI, ABH, PK, AK, DK, ACV. Drafting the work: PF. Revising the work critically for important intellectual content: PF, FT, GH, BC, MI, ABH, PK, AK, DK, ACV. Final approval of the version to be published: PF, FT, GH, BC, MI, ABH, PK, AK, DK, ACV. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding All data were collected in the context of locally performed clinical audits.
Competing interests All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare no support from any organisation for the submitted work. PF is a contributor to the extant European Glaucoma Society Guidelines, and a contributor and chapter coauthor of the World Glaucoma Association consensus series published in 2016. FT reports grants and personal fees from Alcon, grants and personal fees from Novartis, grants and personal fees from Thea, personal fees from Bayer, personal fees from Allergan, grants and personal fees from Pfizer, personal fees from Santen, outside the submitted work. FT is a member and chapter editor of the extant European Glaucoma Society Guidelines Development Task Force, and a contributor and chapter editor of the extant World Glaucoma Association consensus series published in 2016. FT is also Lead of the Education Theme European Glaucoma Society (2016), Chair of Program Planning Committee of the European Glaucoma Society and Co-Chair of the Education Committee of the European Glaucoma Society (2012), Member of the International Council of Ophthalmology Residency Curriculum Panel (2012), General Secretary of the Greek Glaucoma Society Board (2013), Member of the Committee of the European Board of Ophthalmology (EBO) Glaucoma Subspecialty examination (2015), Section Leader Glaucoma Education Center of the American Academy of Ophthalmology (2016), Co-Chair in the Program Planning Committee of the Glaucoma Research Society (2016) and Associate Editor in the Journal of Glaucoma (2017). GH reports personal fees from Alcon, personal fees from Santen, non-financial support from Optovue, outside the submitted work. GH is a member of the National Liaison Committee and the Delivery of Care Committee of the European Glaucoma Society. BC reports personal fees from Alcon, Allergan and Thea, and non-financial support from Allergan, outside the submitted work. BC is a member and contributor of the extant European Glaucoma Society Guidelines. MI reports personal fees from Thea, grants from Sooft-Glaucoom and personal fees from Saten, outside the submitted work. MI is Member of the EGS Guidelines Development Task Force. ACV reports grants and personal fees from Allergan, personal fees from Alcon, personal fees from Bausch + Lomb and grants from Thea, outside the submitted work. ACV is author of the PROGRESSOR visual field software with royalties paid and is a member and chapter editor of the extant European Glaucoma Society Guidelines Development Task Force.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The full data set is available from the corresponding author at firstname.lastname@example.org. All data were collected in the context of locally performed clinical audits so consent for data sharing was not obtained, but the presented data are anonymised and risk of identification is low.
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