Problems with UK Glaucoma (POAG) Treatment

Problems with UK Glaucoma (POAG) Treatment CHAPTER 1: INTRODUCTION Glaucomas are a group of diseases which have the potential of causing damage to the eye and are distinguished from other eye related diseases by the fact that they can cause an increase in intraocular pressure inside which in turn causes damage to the optic nerve and to the retina. Primary Open Angle glaucoma (POAG) is the second commonest cause of registerable blindness and partial sight registrations in the UK (Bougard et al 2000). It is particularly dangerous because of its progressive nature and ability to go unnoticed for years thereby preventing treatment of the disease until, in some cases it can be too late to rescue the vision completely. Therefore the only way to detect the disease before it becomes a serious problem is with a thorough screening program. Optometrists usually are the first in line to examine a patients ocular health and refer patients onto the hospital based on several risk factors. The prevalence of POAG increases with age. This was shown in the Framingham Eye Study which estimated prevalence to be 1.2% between 50 and 64 years, 2.3% from 65 to 74 years and 3.5% in 75 years and over (Leibowitz et al, 1980). Another study has shown that POAG is positively related to the levels of intraocular pressure. The Baltimore Eye Survey concluded that the prevalence of the disease was 1.18% in patients with IOPs less than 22mmHg and 10.32% above this IOP level (Tielsch, 1991). Hereditary links have also been associated with POAG especially African-Americans who are at higher risk of developing the condition than Caucasians and, if there is a family history of glaucoma, the risk is up to six times higher than for the general population. Also, patients who are highly myopic, have diabetes mellitus or cardiovascular problems are at high risk of developing glaucoma and so these are the individuals who need to be monitored and checked regularly. Thus, in the first instance it may seem appropriate to test all individuals who present as being at a (low) threshold risk of developing the disease at regular intervals for disease progression; however the numbers of patients who are referred for suspect chronic open angle glaucoma and then found to have no glaucoma is around 40%. These false positive referrals are thought to cause unnecessary anxiety to the patient, alongside adding to the volume of paperwork that is needed to be completed by the practitioner and also thought to be a waste of local hospital resources (Parkins, 2006). Hence, these matters alongside the increasing requirements for patient centered care and reducing the costs occurred by the NHS have led to the development of certain criteria which enables optometrists to refine their own referrals for glaucoma prior to deciding whether or not a patient should be referred. This can be made easier by carrying out simple procedures or following specific protocols, for e xample, repeating suspicious IOP measurements preferably at a different time of day by using a contact method (Perkins or Goldmann) and repeating visual field tests on a separate occasion. (Parkins, 2006). More importantly, further schemes have been introduced where referrals are directed to specially trained optometrists who then decide on whether to refer the patient to the hospital eye service (HES) or return the patient for management under primary care. This appears to have ultimately increased the role played by optometrists in diagnosing and referring patients thought to be suffering from POAG, increasing their abilities to reach and treat individuals within the community more effectively. This in turn reduces the number of cases of POAG observed within the population as individuals are able to gain access to primary or more conventional methods of health care, i.e. hospitals. By reviewing the literature which has been published regarding the treatment and management of patients with POAG by optometrists, this paper aims to look at the way new schemes and interventions will affect the treatment and management of the disease within the UK. In addition, the ability of optometrists to prescribe certain drugs and the potential benefits will be discussed. CHAPTER 2: GLAUCOMA IN THE UK. (EPIDEMIOLOGY) This chapter will focus on the distribution, occurrence and control of the disease within the UK population. Glaucoma, as described above is one of the most frequent causes of blindness, predominantly in the industrialized world and therefore accounts for a high proportion of blindness observed within the UK. (Coyle and Drummond, 1995) The disease accounts for 14% of blind registrations in the UK and many cases around the country present at an advanced symptomatic stage (Aclimandos Galloway, 1988). With the potential to cause blindness in both eyes glaucoma has a dramatic effect on the individuals who are suffering from it but it also has a severe economic burden upon the nation, including direct and indirect costs. Within the UK alone these were estimated to be  £132 million in 1990. (Zhang et al, 2001) The most frequently prescribed drug for treatment of glaucoma is timolol which is a non-selective beta-adrenergic receptor blocker. The drug is used to treat open-angle glaucoma due to its ability to reduce the aqueous humour production by blocking the beta receptors on the ciliary epithelium. However, beta-adrenergic receptors blockers are thought to have serious side effects on patients who are suffering from cardiovascular or pulmonary disorders. For this reason an additional drug, 2-4 Pilocarpine, which is a cholinergic agonist may be used. This acts on a specific type of muscarinic receptor (M3) found on the iris sphincter muscle which causes contraction of the muscle and therefore miosis. This widens the trabecular meshwork through increased pressure on the scleral spur which aids the aqueous humor to leave the eye and reduce intraocular pressure. However this drug also has its limitations which are primarily associated with the requirement for it to be administrated four times per day and its ability to cause miosis, myopia and occasionally in some patients, retinal detachment and progressive closure of the anterior chamber angle. Thus, new drugs which will be more effective and safer methods of treating open-angle glaucoma are required. There have been many agents suggested for use for the treatment of the disease, however they often fail on several counts, including their failure to control intraocular pressure. (Schwab et al, 2003) This problem is observed within the three non-beta blocker drugs: latanoprost (a prostaglandin F2à ¡ analogue), dorzolamide (a topical carbonic anhydrase inhibitor), and brimonidine (a Selective à ¡2 agonist). However, out of these three drugs, Latanoprost seems to be the most highly promising because of its comparable or, in some cases, better efficacy when compared with timolol. (Zhang et al, 2001) Risk factors, which are associated with the development of the disease, include individuals who are members of a family pedigree, which have suffered from glaucoma in the past. (OMIM, 2006) It is thought that a family history of the disease increases ones likelihood of developing the disease by 6%. This is suggestive of a genetic link or predisposing factor which may be associated with the development of the disease. Diabetes and being of African descent are also factors which are thought to increase the likelihood of developing the disease, and individuals with either of these factors, are three times more likely to develop the disease than the average individual. Asian populations have a dramatically higher risk of developing glaucoma than Caucasians, increasing their chances of disease development by a staggering twenty to forty percent. Men are also three times more likely to develop open-angle glaucoma than women due to the presence of wider anterior chambers in the eye. (Paron and Craig, 1976) Evidence is becoming increasingly available to suggest that the levels of ocular blood flow are involved within the pathogenesis of glaucoma. Fluctuations in blood flow are more harmful in those with glaucomatous optic neuropathy than those who experience a steady reduction in the blood flow to their eye through the optic nerve head. This also correlates with the damage observed to the optic nerve head and to the deterioration in the visual field acuity. (National Institute of Health, web Reference) There are also a number of studies which suggest that there is a correlation between glaucoma and systemic hypertension. This is linked with the fluctuations in blood flow mentioned above, as varying blood pressure can affect blood flow. There is however, no evidence that vitamin deficiencies play any role in the development of glaucoma. A survey carried out (Rhee et al, 2002) revealed that it is highly unlikely that vitamin supplements provide a useful treatment method for any individual suffering from the disease. CHAPTER 3: SCREENING FOR GLAUCOOMA IN THE UK. As we are now aware of the epidemiology of glaucoma within the population in the UK, it is clear that screening of individuals, particularly of those individuals at high risk of disease development is required. Many factors influence whether or not screening is considered a necessary precaution by ophthalmologists. However, it is perhaps first, most useful to provide an overview of what screening is and why it is a procedure invested in for treatment of open angle glaucoma. 3.1 Definition of screening Screening may be defined as the examination of a group of usually asymptomatic individuals to allow the early diagnosis or detection of those individuals with a high probability of having a given disease, (Collegeboard, 2008) and it is often carried out on individuals who are considered to theoretically have a high chance of inheriting or suffering from the disease, due to either genetic or environmental factors or even a combination of these issues. It is thought that screening is useful when it enables the diagnosis of a disease earlier than it would usually have been detected giving the ability to improve the patients outcome. However, there are several ethical issues surrounding screening processes as some individuals are of the opinion that it is only right to screen for some diseases when an individual is at an age to consent to such a procedure. This raises issues surrounding the onset of screening procedures, and whether siblings and offspring of individuals with a family history of open angle glaucoma should be screened for the disease because of certain opinions that suggest the patient themselves should decide whether or not to be screened. This is debatable because of the implications on the individuals life and the worry which is associated with the knowledge of perhaps developing such a disease which could eventually lead to blindness. However, due to the fact that the screening procedure gives the potential for treatment of the disease symptoms, it is likely that many ethical issues which surround some screening processes are not relevant to the screening of individuals at high risk of open angle glaucoma, particularly due to the fact that the genetic risk is minimal in comparison to the environmental risk factors and thus, genetic screening of parents and their offspring is not yet (and is unlikely to become) an issue. 3.2 Tests for glaucoma There are several tests that are used to identify those patients with glaucoma, however, there is no single test that can determine whether a patient has the disease or not. To start with a thorough eye examination is a prerequisite prior to undergoing the specific tests for glaucoma. Following this examination, the management of glaucoma involves serial tests which are carried out at regular intervals over several years allowing the practitioner to determine whether the pressure in the eye has become stable and hence further damage will be avoided. Good record keeping is vital as it is only possible to determine whether the pressure has worsened by using previous values and measurements as a comparison. The ‘Gold Standard tests for glaucoma are determination of eye pressure with an application tonometer, assessment of optic nerve head and visual field screening. In optometric practice these tests are carried out once every year under NHS regulation, however, a patient under hospital management will usually be seen at least 3 or 4 times to monitor their intraocular pressure. The established ‘Gold Standard for intraocular pressure measurement is the Goldman applanation tonometer. To carry out this procedure, the Goldman head is mounted on a slit lamp and a drop of anesthetic a dye (fluorescein) is placed in the eye. Then a gonioprism is placed in contact with the cornea through which practitioner is able to see green rings and make adjustments to arrive at the end point where the half rings overlap. The eye pressure reading (in mmHg) is recorded at this position. There are several other means of recording intraocular pressure using different types of tonometers, which include the air puff tonometer, Perkins tonometer, Pneumotonometer and Schiotz tonometer. In addition, there are tonometers, which allow the estimation of eye pressure at home. One such example is the ‘proview eye pressure monitor (Bausch and Lomb, 2001). The visual field is usually the first to be affected in glaucoma and by the time the central vision is affected, the disease is already far advanced with almost all of the vision in the periphery permanently lost (Parks, 2006). Perimetric threshold-measuring techniques are sensitive to the early progression of such glaucomatous field loss and full threshold screening programs are seen as the ‘Gold Standard. However, threshold tests can be lengthy and can induce fatigue within a patient causing them to lose fixation and overall lead to unreliable results. This lead to the development of SITA testing which reduced the testing time while maintaining the same quality of results as full threshold testing (Bengtsson, et al 1998). The computers, which are used to compute the visual field, are those such as the Humphrey or the Octopus perimeters. These machines use a light point that is presented in a predetermined fashion (location sequence) in a lighted bowl and the patient is asked to press a button when they see the light point. The patients responses are analyzed statistically and compared with a database of ‘normal responses. From this information, any deviations from normal are marked on a printout as black squares which represent visual field-defect areas. à ¢Ã¢â€š ¬Ã‚ ¨ Optic nerve head assessment is mandatory in all eye examinations performed and the ‘Gold Standard method is the use of a Volk lens with the patient dilated. The preliminary signs of the disease occur at the optic nerve head where nerve fibre loss is apparent. However, it only until the loss of fibres exceeds a certain threshold that visual field impairment is noticed. Evidence from histological studies and glaucoma modelling has shown that up to 40% of optic fibres can be damaged before a loss of visual function takes place (Quigley, et al 1982). Diffused thinning and localised notching of the neuroretinal rim (NRR) indicate early signs of the disease. The cup is affected due to the loss of fibres and it widens and deepens as a result. Also, the optic disc of a glaucomatous patient will not follow Jonas ISNT rule where the NRR is thickest at the inferotemporal sector, then at superotemporal, followed by nasal and temporal. Clinical examination using a Volk lens is, however, affected by inter-observer variability amongst optometrists. Another useful technique is stereoscopic optic nerve photography which is a cost-effective method for the detection of glaucoma and its progression. With the benefit of 3-dimensional and permanent data, practitioners can study the optic nerve features (disc cupping, vessel baring) over time (Tielsch et al, 1988). Under hospital management, comparison of these photos which have been taken over the course of the year is a highly effective method of following glaucoma progression. CHAPTER 4:HOW SUCCESSFUL ARE OPTOMETRISTS AT SCREENING FOR GLAUCOMA? A number of studies and clinical trials have been carries out on the effects of treatment on newly discovered primary open-angle glaucoma patients, and it has been noted on several occasions that immediate treatment leads to a slower rate of disease progression. (Bullimore, 2002) As one must first identify that a patient has the disease before the individual can be treated, this ultimately implies that effective screening procedures would be beneficial in the treatment of glaucoma. However, one question which this leads to is: how successful are optometrists at screening for glaucoma and are all patients who should be screened, being checked for disease progression or any clinical symptoms. 4.1 The Baltimore eye Survey The Baltimore eye survey (Tielsch, 1991) was carried out to evaluate the efficacy of population level screening procedures and evaluate the performance of the screening methods used to test for glaucoma. The research team noted that â€Å"†¦screening for glaucoma has a long history and is a well-established activity† (Tielsch, 1991). However, they also were aware that most screening organizations used tonometry as the screening technique even though it is known to have several limitations associated with its use. The efficacy of the other known screening processes were thought, by the research team, to have not received deep enough investigations into their effectiveness, and this was considered to be a reason why these methods were not being utilized in the screening processes. In research studies which had been carried out prior to this study, only small research groups had been used or the studies had proved to being biased towards individuals who have a family history of the disease and therefore highly likely to developing glaucoma themselves. (Leibowitz et al, 1980) Hence the studies were thought to provide false information about the usefulness of the analyzed screening methods. The Baltimore Eye survey looked at a total of 5,308 individuals who were forty years of age or older, including both black and white individuals and analyzed the success of screening each individual for glaucoma using â€Å"†¦tomometry, visual fields, stereoscopic fundus photography and a detailed medical and ophthalmic history.† (Tielsch et al, 1991) The survey was not limited to looking at individuals who were known to be at a high risk of developing glaucoma as this would influence the analysis of the success of certain screening methods. After the examination was complete, a diagnosis of glaucoma was made for any participant found to have indicative symptoms. Out of the 5,308 individuals participating in the study, 196 were diagnosed with glaucoma. (Tielsch et al, 1991) The research team then evaluated tonometry, cup to disc ratio, and narrowest neuroretinal rim width for their ability to correctly classify subjects into diseased or non-diseased states. There was no defined cutoff values at which these variables provided a reasonable balance of sensitivity and specificity, (separately or in combination) as this made the test more robust and thus allowed the screening method to only gain positive results if it was able to identify an individual who did indeed have glaucoma. The statistical analytical methods used to analyze the data obtained from the study included making logistic regression models of the results, which were then fit to the data. These models included demographic and other risk factors, to ensure that the analysis of the data was as accurate as possible. Sensitivities and specificities were then calculated for varying cutoff levels on the distribution of predicted probabilities. The research team came to the conclusion that there was no cut off for reasonable sensitivity and specificity and that the effectiveness of current techniques for glaucoma screening was limited. (Tielsch et al, 1991) The research said that although â€Å"at first glance, glaucoma fits the model of a disease for which screening could make a significant impact on the burden of disability in the population†¦unfortunately, objective assessments of the most commonly used technique for screening†¦demonstrate its ineffectiveness.† (Tielsch et al, 1991) The study identified that tonometry was a poor technique when it came to correctly classifying subjects as diseased or non-diseased. It also mentioned that despite intraocular pressure remaining as one of the strongest known risk factors for open angle glaucoma; measurements of this were not used as a criterion for referral in order to maximize the sensitivity of the screening examination. Tielsch et al (1991) identified only Only 215 subjects out of 1770 who were referred for further tests simply because of their intraocular pressure measurements and only four of these individuals actually had definite or probable glaucoma. This was a detection rate of 1.86 percent which is very low. Thus, the use of the intraocular pressure as a guide added little additional sensitivity beyond what was contributed by the other referral criteria. Other methods of screening for the development of glaucoma were also considered to be ineffective and cumbersome. Despite this study being carried out forty years after the initiation of screening programmes for glaucoma, the program still appeared to require extra work in order to develop a more successful screening programme. 4.2 Frequency-doubling technology study In contrast to the study carried out by Tielsh et al (1991) a study was carried out by Yamada et al (1999) with the aim to assess glaucoma screening using frequency-doubling technology (FDT) and Damato campimetry. The research group carried out a two day public glaucoma screening programme which was implicated at two different institutions. Each participant underwent the following visual field tests: Damato campimetry, FDT perimetry in screeningmode and Humphrey perimetry(24-2 FASTPAC). A full ophthalmologic examination, for each eye was also carried out. The data collected from this study was then divided into four categories, including normal, ocular hypertensive, glaucoma suspect and definite glaucoma. The sensitivity and specificity level of each test was then estimated with â€Å"receiver operating characteristic curves† (Yamada et al, 1999). The results of the eye examinations revealed that out of the 240 individuals who underwent testing, 151 were identified as being no rmal, 28 were classified as ocular hypertensive, 35 were described as having suspect glaucoma and 26 were classified as being definite glaucoma individuals when using the FDT perimetry screening mode. Out of the one hundred and seventy five subjects who underwent Damato campimetry, the numbers for the same groups were 118, 19, 19 and 19 respectively. The specificities for each test were 92-93% for the FDF perimetry and 53-90% for the Damato campimetry tests respectively, hence leading to the conclusion that FDT perimetry was superior to Damato campimetry in the screening for glaucoma within the study. (Yamada et al, 1999) However, these methods for screening are rarer than the usual tonometer and visual field analysis methods described within this paper. Despite the fact that they appear to be useful and effective methods for glaucoma screening in this case, the tests are rarely used in conventional practice and therefore the results of this study should be regarded with caution. 4.3 Burton Hospital screening study The aim of this study was to investigate the â€Å"referral practices to the outpatient clinic of a consultant ophthalmologist† and also to identify the current screening routines of optometrists and general practitioners in regards to glaucoma and diabetic retinopathy diagnosis. (Harrison, et al 1988) A total of 1437 patients were referred to Burton District Hospital, from 1 November 1986 to 31 December 1987, to be viewed by a consultant ophthalmologist. The patients were grouped into urgent, semi-urgent or non-urgent depending on their referral letters. Only 1113 patients were ultimately reviewed as the remaining 324 could not be seen by the end of the study. (Harrison, et al 1988) Selected biographical data was recorded from the case notes such as age, sex and more importantly the source of referral. Any symptoms as well as the reasons for referral were looked for in the referral letters. A classification system was used for the reason for referral; this was based on symptoms and bodily location. Furthermore, there was an analysis on the referral data for the procedures used by the referring source, in this case assessment of visual acuity, visual fields, binocular vision and the optic nerve head. Also, intraocular pressure readings as well as any fluorescein checks for corneal staining. (Harrison, et al 1988) The results showed that optometrists were responsible for 39% of the referrals (439 patients) in comparison to the 49% (546 patients) of general practitioners. The most important reason for referral was visual field loss which account for 31% (345) of cases, followed by suspected glaucoma which accounted for 13% (145). The reasons for referral were also different when comparing the two referrers. GPs referred 107 (84%) patients due to eyelid disorders and 66 (77%) patients with conditions on the outer adnexa. On the other hand optometrists were responsible for referring 118 (81%) of the patients on suspicion of glaucoma. (Harrison, et al 1988) In total there were 70 referrals for possible asymptomatic glaucoma and another 77 for symptomatic disease. In 33 cases glaucoma was confirmed (20 asymptomatic) and borderline glaucoma was found in 73 cases (48 asymptomatic). â€Å"The diagnosis was confirmed in 96 (80%) of the referrals from ophthalmic opticians but in only 10 (37%) cases referred by general practitioners.† (Harrison, et al 1988) This showed that optometrists were far more accurate in referring suspect glaucoma patients, i.e. a greater number of true positives. Using information from the referral letters, the diagnostic procedures undertaken by both referral sources was explored. Optometrists relied on intraocular pressure readings in 52 of the 96 referrals (54%). The rest of the patients were referred because of suspicious cup-disc ratios, visual field loss or other clinical aspects. However, GPs would refer mainly on the grounds of symptoms that are present. Also, the ophthalmologist did not confirm suspect glaucoma in 24 patients from the optometrists referrals and 17 from the referrals by GPs. The main conclusions from the report show that optometrist were far more likely to refer retinal or optic disc disorders. There was insufficient evidence to show that GPs screened for glaucoma â€Å"whereas ophthalmic opticians screened for glaucoma with considerable skill.† (Harrison, et al 1988). Several factors contribute to these differences between the referral abilities of both professional groups. Patients will normally visit an optometrist when they are experiencing visual loss because they are usually under the impression that they require new glasses. However, when patients have external symptoms they normally go to their GP. Due to the equipment available to optometrists they are also more likely to pick up on pathologies within the eye especially those affecting the retina and optic nerve head, hence â€Å"maintaining a high degree of vigilance for asymptomatic conditions such as glaucoma.† (Harrison, et al 1988) The suggested diagnostic accuracy, however, u ndermined the actual accuracy of the opticians examination. Any difference was due to the importance given to the findings of the ophthalmologist. The quality of referrals to the hospital is vital for maintaining an effective service, especially in Britain where many outpatients departments are overstretched. Improvement in the accuracy of referrals eventually leads to less false positive referrals, therefore enhancing the value of true positive referrals. One of the protruding reasons for false positive referrals in this study was suspected glaucoma but with â€Å"greater utilisation or development of community based screening programmes† the false positive referral rate could be reduced. Harrison, et al (1988) states that currently the closest approach to a screening programme is offered by optometrists. Harrison et al (1988) is also of the opinion that by establishing a planned screening service where ophthalmologists and optometrists work in conjunction on the basis of a fixed referral criteria, the progression of the disease in patients will reduce and so will the burden on HES. There is evidence from the data within the study to show that such glaucoma screening programme would have an influence. The 41 false positive glaucoma referrals would have been prevented and so would most of the 73 referrals for borderline glaucoma. A potential 100 outpatient appointments could have been saved with a community based screening strategy and this in turn would free up follow-up appointments. The study does show the benefit of current screening procedures and how optometrists are successful at accurately referring suspect glaucoma patients. Harrison, et al (1998) highlights that this is an invaluable skill which would prove more beneficial if used within a community based screening scheme. 4.4 England and Wales survey The objective of this survey was to investigate â€Å"the efficiency of referral for suspected glaucoma to general practitioners and consultants by optometrists.† (Tuck Crick, 1991) This survey involved 241 optometrists who represented areas clustered in England and Wales. Majority were enrolled through an interview procedure, but some responded to an advert in optometric publications. The scheme ran from November 1988 to February 1989 and each time a referral took place the optometrist would fill out a questionnaire on the individual patient. In total the respondents completed 275600 sight tests, which accounted for â€Å"about five per cent of the national total†. The actual number of referrals was 1505 for those suspected of glaucoma. For people over the age of 40 an estimated 0.9% referral rate was found. The end result of the referral was established for 1228 individuals. There were 125 patients were not examined at all and the remaining 1103 were examined by a consultant ophthalmologist. (Tuck Crick, 1991) An analysis was done on 704 cases to assess the accuracy of the referrals. Glaucoma was confirmed in 40.19% (283) of patients and 31.53% (222) of patients were further monitored. The data showed that in nearly all the confirmed patients the disease was at a chronic stage. Optometrists were further questioned to specify the key reasons for referral in each of the cases. There were 171 patients referred due to intraocular pressure in at least one eye being greater than 30mmHg. From these, 112 (65%) were positively diagnosed with glaucoma and only 20 were discharged as false positives. It was noted, however, that accuracy of referral in patients with lower IOPs (20-25mmHg) was much less. Only 7 individuals out of the 87 with lower IOPs were found to have glaucoma. Amongst them 50 patients who were released with no glaucoma. (Tuck Crick, 1991) When the optometrist recorded optic nerve head changes and visual field plots, the IOP referral accuracy was greater. However, when the referral was based on optic disc appearance and visual fields alone the accuracy was low. This category of referral accounted for 28 (10%) of confirmed cases. Furthermore, only 331 of the 704 patients had undergone a visual field test. This explained those cases in which visual field loss was not described as a reason for referral because the screening test had not been carried out in the first place. Even so, the analysis stressed â€Å"that field screening generally enables a case to be more precisely described and the risk of glaucoma thereby better assessed at the primary level.† (Tuck Crick, 1991) Gathering the evidence from th