Glaucoma detection rate: a useful concept, to be distinguished from accuracy of referral (positive predictive value)
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Glaucoma↗
Biomedical subjects
R P Crick
Publications and source records attributed to R P Crick.
The age distribution of primary open angle glaucoma.
Prevalence data for primary open angle glaucoma (POAG), taken from eight population surveys, was smoothed by curve-fitting to derive composite estimates with respect to quinqennial age groups from 40-44 to 85-89 years. These were applied to national population figures to provide a distribution of cases with respect to age. Estimated prevalence for age 40-89 years in mainly white Caucasian people was 1.2%, rising from 0.2% for those in their 40s to 4.3% for those in their 80s. Of the total cases, 7% were less than 55 years old, 44% were aged 55-74 years, and 49% were older. 'Implied incidence' was estimated from the prevalence results, being 0.11% per year in people aged 55 to 74 years. The analysis applied to relatively narrow definitions of POAG. If 'probable' cases and also 'ocular hypertensives requiring treatment' (of relevance for glaucoma screening) were included, the prevalence would be almost twice as high. Also, a larger proportion of potential cases for a screen would be less than 55 years old, partly because the average age of incident (i.e., newly developed) cases is less than that of prevalent (i.e., all existing) cases.
Adult↗
Localization of the fourth locus (GLC1E) for adult-onset primary open-angle glaucoma to the 10p15-p14 region.
One of the major causes of blindness is primary open-angle glaucoma, which affects millions of elderly people worldwide. Genetic studies have so far mapped three loci for the adult-onset form of this condition to the 2cen-q13, 3q21-q24, and 8q23 regions. Herein, we report the localization of a fourth locus, to the 10p15-p14 region, in one large British family with a classical form of normal-tension open-angle glaucoma. Of the 42 meioses genotyped in this pedigree, 39 subjects (16 affected) inherited a haplotype compatible with their prior clinical designation, whereas the remaining 3 were classified as unknown. Although a maximum LOD score of 10.00 at a recombination fraction of straight theta=.00 was obtained with D10S1216, 21 other markers provided significant values, varying between 3.77 and 9.70. When only the affected meioses of this kindred were analyzed, LOD scores remained statistically significant, ranging from 3.16 (D10S527) to 3.57 (D10S506). Two critical recombinational events in the affected subjects positioned this new locus to a region of approximately 21 cM, flanked by D10S1729 and D10S1664. However, an additional recombination in a 59-year-old unaffected female suggests that this locus resides between D10S585 (or D10S1172) and D10S1664, within a genetic distance of 5-11 cM. However, the latter minimum region must be taken cautiously, because the incomplete penetrance has previously been documented for this group of eye conditions. A partial list of genes that positionally are considered as candidates includes NET1, PRKCT, ITIH2, IL2RA, IL15RA, IT1H2, hGATA3, the mRNA for open reading frame KIAA0019, and the gene for D123 protein.
Adult↗
Screening for glaucoma. Why is the disease underdetected?
A review of 15 population-based glaucoma prevalence surveys in Western Europe, the US, the West Indies and Japan shows that the proportion of patients with the condition who had previously gone undetected was generally at least 50%. Possible reasons for underdetection of glaucoma have been considered in relation to England and Wales, where most patients with glaucoma are initially detected during the course of sight tests in connection with providing spectacle lenses. It was found that: (i) a high proportion of the population over 40 years of age attends fairly regularly for a sight test, (ii) the standard of primary testing for glaucoma is very uneven--those examiners who test comprehensively detect about 50% more cases than average; and (iii) referral criteria, which reflect the need not to overload hospital eye clinics, inevitably exclude many patients who are in apparently low risk categories. Both the population survey data and the subsequent analysis suggest that underdetection is most pronounced in patients with glaucoma of the normal pressure type.
Glaucoma↗
The cost-effectiveness of various modes of screening for primary open angle glaucoma.
Various modes of screening for glaucoma were defined in terms of different combinations of the three main tests (ophthalmoscopy (O), tonometry (T), and perimetry (P)), together with associated referral criteria. The number of referrals and true positives generated by each mode was estimated for a model population, which was distributed with respect to age, intraocular pressure (IOP), optic disc condition, visual field defects, family history of glaucoma, and myopic status, as indicated by epidemiological studies. The costs of primary examination, and also of the secondary examination of referrals, were estimated for each mode, thus enabling the total cost per true positive to be calculated (in Pound sterling at 1995 UK prices, subsequently converted to US dollars at Pound 1.00 = $1.55.) The modes using O and T routinely, with P either routinely or selectively on all glaucoma high-risk groups, were found to provide the best balance between sensitivity (> or = 80%) and cost per true positive. The latter was around $850 when the cost of ophthalmoscopy could be shared as part of a general eye examination. The calculations assumed a 0.6% prevalence of previously undetected glaucomas in the community: with higher prevalences, costs per true positive would be lower. Screening the 40-59 years age group was found to be about as economic as for older people, when life expectancy was taken into account. It was concluded that glaucoma screening of people over age 40 years could be justifiable, provided that it is worth more than about $850 to detect a new case. Whilst based on UK values, the analysis could be applied to different primary health care settings in other countries.
Adolescent↗
Identification of a new 'TIGR' mutation in a family with juvenile-onset primary open angle glaucoma.
Positional mapping of families segregating for juvenile-onset primary open angle glaucoma (JOAG) has previously identified a locus (GLCIA) for this condition on the long arm of chromosome I. Recently, three mutations in the TIGR gene (Trabecular meshwork Inducible Gluco-corticoid Response protein) have been described in a total of ten familial, three sporadic, and one normal subject. One of the familial cases has also been indicated to be of an adult-onset type. Herein, we report the identification of a new mutation in the TIGR gene in a six generation well-documented Edinburgh family with JOAG. We have sampled and screened the living affected members of this family and identified an 'A'-to-'G' transition at amino acid 337 that has changed the glutamine (Gln) to arginine (Arg). This newly identified mutation resides 27 amino acids 5-prime from the previously reported mutation of Gly-to-Val. This mutation created a new MspI restriction site that has co-segregated perfectly with inherited affected haplotype of the pedigree and, furthermore, it has not been observed in 142 chromosomes of randomly selected subjects of the same population. This report, therefore, confirms the role of the TIGR gene in the etiology of JOAG and adds a new mutation to the three reported previously.
Chromosomes, Human, Pair 1↗
Localization of a locus (GLC1B) for adult-onset primary open angle glaucoma to the 2cen-q13 region.
Primary open angle glaucoma (GLC1) is a common ocular disorder with a characteristic degeneration of the optic nerve and visual field defects that is often associated with an elevated intraocular pressure. The severe but rare juvenile-onset type has previously been mapped to 1q21-q31, and its genetic heterogeneity has been established. Herein, we present a new locus (GLC1B) for one form of GLC1 on chromosome 2cen-q13 with a clinical presentation of low to moderate intraocular pressure, onset in late 40s, and a good response to medical treatment. Two-point and haplotype analyses of affected and unaffected meioses in six families provided maximum linkage information with D2S417, GATA112EO3, D2S113, D2S373, and D2S274 (lod scores ranging from 3.11 to 6.48) within a region of 8.5 cM that is flanked by D2S2161 and D2S2264. Analysis of affected meioses alone revealed no recombination with an additional two markers (D2S2264 and D2S135) in a region of 11.2 cM that is flanked by D2S2161 and D2S176. Analysis of unaffected meioses identified only one healthy 86-year-old male who has inherited the entire affected haplotype and, hence, is a gene carrier for this condition. Eight additional families with similar and/or different clinical presentation did not show any linkage to this region and, therefore, provided evidence for genetic heterogeneity of adult-onset primary open angle glaucoma.
Age of Onset↗
The proportion of confirmed glaucomas who have a family history of the disease.
In a large survey of glaucoma detection in practice, only 46 (10%) of 465 confirmed glaucomas had a family history of the disease. Together with other studies, this indicates that family screening would fail to detect the large majority of glaucoma cases.
Family Health↗
How can we improve the detection of glaucoma?
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Glaucoma, Open-Angle↗
Epidemiology and screening of open-angle glaucoma.
Two major prevalence surveys for chronic open-angle glaucoma have been published in the last year. These are discussed in relation to the comprehensive Baltimore Eye Survey of 2 years ago, which also studied the blindness arising from the disease and comparative figures for white and black individuals. The newer tests for identification of loss of visual function prior to visual field loss as demonstrated by conventional automated perimetry are considered. The three main screening tests for chronic open-angle glaucoma--ophthalmoscopy, tonometry, and perimetry--are evaluated in the light of case finding experience in the United Kingdom. The maximum detection of asymptomatic early chronic open-angle glaucoma in the community is likely to be best achieved by a combination of public awareness of glaucoma aided by patient-based associations and the promotion of improved glaucoma testing and case finding by the army of professionals who are already in place in most developed countries and who carry out primary eye examinations.
Electroretinography↗
Use of visual field tests in glaucoma detection by optometrists in England and Wales.
This paper is based on a survey of 241 optometrists (5% of the national total) in England and Wales, which covered many aspects of glaucoma detection. There were 45 optometrists (19%) who did not use a field screener. Of the 196 who did, 173 reported their criteria for deciding which patients to test: 17 (estimated at 8% of the original sample) used a field screener routinely in patients over 40 years; 40 (19%) selectively tested all patients with intraocular pressure > 20 mmHg, together with most others in whom any glaucoma risk factor was present, (this required a visual field test in only one in five patients aged over 40 years and may be relatively cost-effective); the remaining 116 (55%) on average tested less than one in ten of their patients with a field screener, practice which is shown to contribute little to the number of glaucomas detected. Routine field testers had the highest glaucoma detection rates, and those of the selective testers were not significantly lower.
Age Factors↗
Non-contact tonometry: optometrists' current practice in England and Wales.
A survey of 133 optometrists who used a non-contact tonometer indicates that in only a half of patients tested were more than two readings per eye taken. Most optometrists made the number of readings conditional on the intraocular pressure (IOP) shown by the initial readings. About 1% of patients aged over 40 years were called back for a second IOP test. In a follow-up questionnaire with 90 respondents, only 24 (27%) stated that they had rechecked any patient by Goldmann applanation tonometry during the previous 6 months. Of these 90 optometrists, 20 (22%) had not had their tonometer serviced within the previous 24 months. It was concluded that, whilst non-contact tonometry makes a major contribution to glaucoma detection, improvements could be made in current practice which require little extra time.
Adult↗
Screening for glaucoma: the time taken by primary examiners to conduct visual field tests in practice.
A panel of 101 primary examiners (optometrists or their ancillary staff) in England and Wales prospectively recorded the time taken to examine the central visual fields of each of 10 (or more) of their patients. The results indicate that the time depended not only on the test procedure but on how frequently the examiner conducted such a test. A basic test with semi-automated field screening equipment, applied routinely by 30 examiners on 547 patients, took an average 3.7 min per patient; (lower quartile 2.8 min). For such examiners, a standard extended test took 4.9 min. Similar times applied whether tests were conducted by an optometrist or an assistant. It was concluded that visual field screening in a normal population could reasonably be assumed to take an average 4 min per patient.
Adult↗
Relative effectiveness of different modes of glaucoma screening in optometric practice.
This study analyses records from 189 optometric practices in England and Wales on the glaucoma screening of 123,415 patients aged > 40 years during a prospective 6 month period. Its purpose is to compare the effectiveness of the various modes of screening which were used. All optometrists tested every patient by ophthalmoscopy. The 146 who, in addition, conducted tonometry on a routine basis detected a confirmed glaucoma in 0.35% of their patients, whilst the 43 who used tonometry 'on suspicion' detected a case in 0.25%, (P < 0.02). The 47 optometrists who conducted perimetry frequently (i.e. in > or = 15% of sight tests) detected a case in 0.46% of patients, whilst the other 142, who did little or no perimetry, detected a case in 0.29%, (P < 0.001). Eleven optometrists who relied mainly on ophthalmoscopy had a detection rate of only 0.12%. Optometrists with the most comprehensive modes of screening had the greatest referral accuracy. It was concluded that more widespread adoption of routine tonometry for people aged approximately greater than 40 years is necessary to reduce the present substantial number of false negatives; and that the frequent use of visual field analysis is additionally required to achieve the best results.
Adult↗
Effect of timolol versus pilocarpine on visual field progression in patients with primary open-angle glaucoma.
BACKGROUND: Relatively few studies have been conducted linking decreasing intraocular pressure (IOP) to preservation of visual field. This investigation was conducted to determine if this link could be made and to compare the long-term effect of two ocular hypotensive agents on preservation of visual field. METHODS: In an observer-masked study, 189 patients with primary open-angle glaucoma received either timolol or pilocarpine by random allocation. The dose of antiglaucoma agent was increased from 0.25% to 0.5% twice daily for timolol or from 2% to 4% four times daily for pilocarpine if the initial IOP response was inadequate. After an on-treatment baseline, visual fields were followed every 4 months for 2 years using the Octopus program 32. RESULTS: Compared with timolol, significantly more patients receiving pilocarpine discontinued use because of inadequate IOP control (P < or = 0.01). By comparing the mean visual field scores, it can be seen that the pilocarpine group had a significantly worse score at all timepoints from month 4 to month 24. The pilocarpine group also had a greater mean number of test loci with decreased sensitivity of 5 or more decibels (dB) at all timepoints. The mean within-patient regression slope for timolol was 0.01 dB/month and for pilocarpine was -0.06 dB/month (P < 0.01). The study has shown that over a 2-year period, patients treated with pilocarpine 2% or 4% four times daily experienced a significantly greater visual field deterioration than that seen in patients receiving either 0.25% or 0.5% timolol twice daily. CONCLUSION: Although these data do not support a link between lowering of IOP and visual field preservation, treatment with timolol was associated with significantly less visual field loss than treatment with pilocarpine.
Double-Blind Method↗
Doppler carotid artery studies in asymmetric glaucoma.
Doppler carotid artery studies were performed in 12 glaucoma patients with marked asymmetry in bilateral visual field loss. The resistance index and the pulsatility index of the internal carotid artery velocity waveforms were significantly greater on the same side as the eye with the greater visual field loss. The increased resistance to blood flow in the internal carotid artery on the side with advanced field loss might predispose the eye on this side to the effects of raised intraocular pressure by causing a reduction in the perfusion pressure at the optic nerve head. The role of ocular perfusion pressure in the pathogenesis of glaucoma is discussed. More extensive studies are necessary.
Carotid Arteries↗
Screening for glaucoma: age and sex of referrals and confirmed cases in England and Wales.
This paper is based on a prospective survey covering 275,600 sight tests by optometrists in England and Wales. It analyses the age and sex distribution of 1402 referrals for suspected glaucoma and 456 confirmed cases of the disease. The proportion of sight tests which led to a confirmed case increased with age, for both sexes, to a maximum at approximately 70 years, and then tended to decline. Cases of glaucoma in people aged 36-51 years accounted for about a tenth of the total, which is more than is generally recognized. Wider adoption of routine tonometry for middle aged people would help to ensure that these cases are detected at an early stage. Confirmed cases of glaucoma in which raised intraocular pressure had not been given as a reason for referral, i.e. probable low tension glaucomas, increased from 5% of patients < 51 years old to 13% of patients > 75 years old. Glaucoma was found to be much more common in men.
Adult↗
Efficiency of referral for suspected glaucoma.
OBJECTIVE: To examine the efficiency of referral for suspected glaucoma to general practitioners and consultants by optometrists. DESIGN: A prospective survey covering 5% of all sight tests performed by optometrists in England and Wales over six months, with analysis of referred patients. SETTING: 241 optometrists' practices in areas representative of England and Wales in socioeconomic terms. SUBJECTS: Of 275,600 people attending for a sight test, 1505 were referred with suspected glaucoma (0.9% of those aged over 4%). Outcomes were recorded for 1228 patients, 1103 (90%) of whom attended for examination by a consultant ophthalmologist (8% on a private basis). The analysis was confined to the 704 cases in which the information on diagnosis was received directly from a consultant or general practitioner. MAIN OUTCOME MEASURES: Diagnoses reported by consultant ophthalmologists. Waiting times before an appointment for examination by a consultant ophthalmologist. RESULTS: Glaucoma was confirmed in 283 of the 704 referred patients, and another 222 patients were considered to require further monitoring. In all, 112 (41%) of 275 confirmed cases of glaucoma were in patients with intraocular pressures greater than or equal to 30 mm Hg. At all levels of intraocular pressure the accuracy of referral was greater when the optometrist also recorded the presence of suspicious optic discs or loss of visual field, or both; but only 331 (47%) out of the 704 referred patients had been tested with a field screener. The median waiting time for an NHS clinic appointment was nine weeks. Almost a 10th of confirmed cases of glaucoma were in people in a high risk category for glaucoma who had to wait at least 14 weeks for an appointment. CONCLUSIONS: Closer cooperation, especially at the local level, among consultants, general practitioners, and optometrists is needed to improve testing and referral for suspected glaucoma. Optometrists should be encouraged to perform all the three main tests--ophthalmoscopy, tonometry, and perimetry--in patients before referral and to report precisely on reasons for referral to help prioritisation. The optometrist's referral letter to the general practitioner should always be passed on to the consultant. Similarly, the diagnosis should always be reported back to the optometrist.
Aged↗