Ординатура / Офтальмология / Английские материалы / Mechanisms of the Glaucomas_Shields, Tombran-Tink, Barnstable_2008

subjects with intraocular pressure ≤16 mm Hg, between 17 and 21 mm Hg, and higher than 21 mm Hg were 9.7, 26.1, and 50.7%, respectively. Among the persons with asymmetrical intraocular pressure, POAG patients accounted for 35.4%, and normal persons accounted for 18.2%. In the population over 40 years old, the asymmetry of intraocular pressure was a very important risk factor no matter what the intraocular pressure level was. At the same time, this research group evaluated the relationship between POAG and myopia in this population and found the prevalence rates of POAG in the persons with and without myopia were 3.31 and 1.43%, respectively (34). The prevalence rates of POAG in patients with mild myopia and moderate and serious myopia were 2.46 and 4.49%, respectively. The average intraocular pressure of myopic patient was 0.53 mm Hg higher than that of normal individuals, indicating that myopia was an important risk factor for POAG. The higher the degree of myopia, the higher the prevalence rate of POAG.

Other Risk Factors

Wang (35) reported that ages, family history, hypertension, intraocular pressure, cardiovascular diseases, smoking, and the TIGR gene mutation (T353I) were all risk factors for POAG. Intraocular pressure was considered the principal risk factor for POAG in Chinese population while drinking was considered as a protection factor for POAG. The investigation by Huang (36) showed that the level of various types of interleukins and cytokines in the sera of POAG and normal tension glaucoma (NTG) patients were different from those in normal individuals.

SECONDARY GLAUCOMA

Diagnostic Criteria for Secondary Glaucoma

Secondary glaucoma is a group of ocular diseases characterized by increased intraocular pressure with or without optic nerve head damage or visual field impairment resulting from the ocular or systemic diseases. As it often coexists with the primary diseases, its clinical treatment is different from that of primary glaucoma. Confirmed diagnosis can be obtained if the definition of secondary glaucoma is met.

Incidence Rate of Secondary Glaucoma

There have been no investigations of the incidence of secondary glaucoma in China at present.

Prevalence Rate of Secondary Glaucoma

The prevalence rates in all of the epidemiological investigations on secondary glaucoma are the relative prevalence rates calculated based on the medical records in the local medical institutions. Song (21) reported that the secondary glaucoma cases accounted for 12.74% of the total number of glaucoma in-patients during 1978–1981 and 14.12% during 2001–2002. There was no statistically significant difference in the constituent ratio of secondary glaucoma between males and females. Lin (20) showed that the secondary glaucoma cases accounted for 14.17% of the total number of glaucoma patients admitted to Zhongshan Eye Center in Guangdong Province.

Li (22) reported that the secondary glaucoma patients accounted for 13.29% of all the glaucoma in-patients in Tongren Hospital in Beijing. Gao (37) conducted an analysis on the glaucoma patients admitted to the Second Clinical Hospital of China Medical University in Liaoning Province and found that secondary glaucoma accounted for 16.14%. The primary ocular diseases of secondary glaucoma in adult Chinese population were ocular injury, inflammation (uveitis and keratitis), corneal or scleral perforation, and cataract (38,39). In children, the leading causes for the secondary glaucoma were ocular injury (40.35%) and intraocular tumor (38.60%) (40). There are no published reports on glaucoma caused by exfoliation syndrome in Chinese population.

Risk Factors of Secondary Glaucoma

Secondary glaucoma occurs mainly in young and middle-aged people probably because these are the principal work force in China society (38,39). In children, secondary glaucoma mainly occurs in the age of 4–11 years old probably because these children are very active but vulnerable (40). The sex difference of secondary glaucoma is mainly characterized as the difference in the primary diseases (38,39). The ocular injury mainly occurs in the males probably for occupational reasons. The second cause, inflammatory diseases occur mainly in females probably because of the high susceptibility to immunological diseases. In children, secondary glaucoma also mainly occurs in boys.

CONGENITAL GLAUCOMA

Criteria for the Diagnosis of Congenital Glaucoma

Congenital glaucoma is a group of ocular diseases caused by the obstruction of aqueous humor outflow because of abnormalities of embryonic development and congenital abnormalities of the structure of anterior chamber angle (41). There are three types of congenital glaucoma in China: infantile, juvenile, and developmental glaucoma with associated anomalies. Primary infantile glaucoma usually occurs before the first 3 years after birth and becomes the most common type in Chinese children.

Incidence Rate of Congenital Glaucoma

There is no related report in China at present.

Prevalence Rate of Congenital Glaucoma

In China, congenital glaucoma, with the prevalence rate of 0.002–0.0038%, is the sixth most common congenital blinding disease (42). Previous studies (20–22,37) showed that congenital glaucoma accounted for about 5% of glaucoma in-patients in different health services.

Risk Factors of Congenital Glaucoma

Both eyes are affected in 65–80% of the congenital glaucoma patients. The proportion of males and females is 2.8:1 in China (43).

Most of the cases of primary infantile glaucoma are sporadic. Ten to twenty percent of the cases have family history and appear to be inherited in an autosomal recessive manner. The proportion of heterozygotes in the population is estimated to be 2.3–2.8%. Some parents of patients have a consanguineous marriage history (8.1%) in remote areas of China (44). The coincidence rate of congenital glaucoma in monozygotic twins (92.3%) was higher than that of dizygotic twins (12.5%), and the heritability index of congenital glaucoma of twins is 91.2% in China (45).

SUMMARY

Epidemiological investigation can be used to determine the distribution of glaucoma in different populations in different regions. The pathogenesis and related risk factors provide important data for the prevention and treatment of glaucoma. It is very important for the establishment and implementation of blindness prevention and treatment plans by the Chinese government and health agencies. The trend of development of glaucoma in the last few years has also been determined by epidemiological investigation in China. The number of myopia patients significantly increases in adolescents. This may cause the ocular anatomical changes in young people and decrease the danger in angle closure. This means that the proportion of primary angle-closure and open-angle glaucoma may be changed in current China. The improvement of medical health service also increases the confirmed diagnosis rate of glaucoma, and birth control policy significantly changes the population structure in China and leads to the epidemiological change of glaucoma.

At present, there is no multi-center correlation research in China. The prevalence rates of glaucoma in many regions have not been determined yet. There is no consensus on when to perform intervention treatment, and there are different opinions on the classification system of PACG. We believe that with the development of epidemiological study on glaucoma, these problems will be resolved in the near future, and this will provide tangible evidence for the prevention and treatment of glaucoma.

REFERENCES

1.NL Wang. Epidemiology of glaucoma. In: WB Zhou, ed, Clinical Glaucoma, 2nd Edn. 2000. Beijing: People’s Medical Publishing House, 11–17.

2.Z Hu, HL Zhao, FT Xu, et al. An epidemiological survey of glaucoma in Shunyi County in Beijing. Chin J Ophthalmol. 1989;25:115–119.

3.XW Liang, FZ Li, WX Qiu, et al. An epidemiological survey of blindness and low vision in Meixian County. Chin J Ophthalmol. 2001;37(1):12–15.

4.AY Liu, SL Sun, HZ Sun, et al. An epidemiological survey of eye disease and blindness in Rongcheng city. J Clin Ophthalmol. 2002;10(2):134–136.

5.BC Ren, Y He, L Chen, et al. Epidemiology of glaucoma in a rural population in Shanxi Province. Int J Ophthalmol. 2005;5(5):1037–1042.

6.JL Zhao, RF Sui, LJ JIA, et al. Prevalence of glaucoma and normal intraocular pressure among adults aged 50 years or above in Shunyi county of Beijing. Chin J Ophthalmol. 2002;38(6):335–339.

7.ZX Wang, LG Zhang. The epidemiological survey of ophthalmic inpatients of tri-ranks hospitals in Qingdao. Qingdao Med J. 2001;33(5):359–360.

8.PJ Foster, GJ Johnson. Glaucoma in China: how big is the problem? Br J Ophthalmol. 2001;85(11):1277–1282.

9.Brubaker RF. Delayed functional loss in glaucoma L II Edward Jackson Memorial Lecture. Am J Ophthalmol. 1996;121(5):473.

10.HR Taylor, JE Keeffe. World blindness: a 21st century perspective. Br J Ophthalmol. 2001;85:261–266.

11.NL Wang. Problems and resolving strategies in the prevention and treatment of glaucoma at present. Chin J Ophthalmol. 2002; 38(12):705–707.

12.PT Chew, T Aung. Primary angle-closure glaucoma in Asia. J Glaucoma. 2001;10(5): S7–S8.

13.DS Friedman. Who needs an iridotomy? Br J Ophthalmol. 2001;85(9):1019–1021.

14.L Xu, L Zhang, CR Xia, et al. The prevalence and its effective factors of primary angleclosure glaucoma in defined populations of rural and urban in Beijing. Chin J Ophthalmol. 2005;41(1):8–14.

15.JS Lai, DT Liu, CC Tham, et al. Epidemiology of acute primary angle-closure glaucoma in the Hong Kong Chinese population: a prospective study. Hong Kong Med J. 2001;7(2): 118–123.

16.SK Seah, PJ Foster, PT Chew, et al. Incidence of acute primary angle-closure glaucoma in Singapore. An island-wide survey. Arch Ophthalmol. 1997;115(11):1436–1440.

17.JL Zhao, TS Hu, Z Hu, et al. An epidemiological survey of primary angle-closure glaucoma in Tibet. Chin J Ophthalmol. 1990;26(2):47–50.

18.ZF Gao. An epidemiologic study of glaucoma in Tongcheng county, Anhui province. Chin J Ophthalmol. 1995;31(2):149–151.

19.Q Yu, JJ Xu, SP Zhu, et al. An epidemiological survey of primary angle-closure glaucoma in Doumen county Guangdong. Chin J Ophthalmol. 1995;31(2):118–121.

20.MK Lin, J Ge, HY Chen, et al. The analysis in proportion of hospitalized patients with glaucoma. Chin J Pract Ophthalmol. 2003;21(12):937–939.

21.S Song, XM Chen. Epidemiology of hospitalized patients with Glaucoma: the constitutive proportions and their dynamic characteristics. Chin J Pract Ophthalmol. 2003;21(12): 932–936.

22.WM Li, ZP Jiang. Statistical analysis of hospitalized patients with Glaucoma during 2002–2005. Chin Med Rec. 2006;7(2):38.

23.TC Ye, WS Mao, DP Lu, et al. Comparison of simple methods to screen predisposing eye of primary angle-closure glaucoma. Chin J Ophthalmol. 1995;31(5):341–344.

24.Q Yu, JJ Xu, SP Zhu, et al. The survey of anterior chamber angle in a population of middle and old age. Chin J Ophthalmol. 1998;34(3):224–226.

25.TC Ye, Q Yu, SX Peng, et al. Six year follow up of suspects of primary angle closure glaucoma. Chin J Ophthalmol. 1998;34(3):167–169.

26.KQ Xu, XM Chem, CM Zhu. Analysis of psychosocial factors in patients with primary angle-closure glaucoma. Res Adv Ophthalmol. 1999;19(2):119–121.

27.P Chen, XG He. Mental status and personality characteristics of patients suffering from acute or chronic glaucoma. Chin J Clin Rehabil. 2005;9(24):58–60.

28.GL Tang, YS XU, CX An, C Zhang. Psychological analysis of the patients with Primary glaucoma. Res Adv Ophthalmol. 2006;26(4):279–282.

29.YJ Dong, J Cao, QC Yan, JS Zhang. Investigation of Psychology, personality and behavior in patients with acute angle-closure glaucoma in ShenYang city. Chin J Ophthalmol. 2006;24(6):596–598.

30.YZ Zheng, SH Wang, W Sun, et al. The case-control study of risk factors in primary angle-closure glaucoma. Chin J Ophthalmol. 1995;16(1):8–10.

31.L Xu, JH Chen, JJ Li, et al. The prevalence and its screening methods of primary open angle glaucoma in defined population-based study of rural and urban in Beijing. Chin J Ophthalmol. 2004;40(11):726–732.

32.MK Lin, J Ge. The changes of proportion in hospitalized patients with glaucoma. Eye Sci. 1997;(13)2:96–99.

33.JJ Li, L Xu, RX Zhang, et al. The relationship between intraocular pressure asymmetry and POAG: the eye epidemiological investigation on urban and rural defined-populations in Beijing. Ophthalmol China. 2003;12(5):280–282.

34.JJ Li, L Xu, RX Zhang, et al. Investigation on the relationship between primary open-angle glaucoma and myopia. Ophthalmol China. 2004;13(3):168–171.

35.N Wang, ZP Peng, BJ Fan, et al. Case control study on the risk factors of primary open angle glaucoma in China. Chin J Epidemiol. 2002;23(4):293–296.

36.P Huang, C Zhang. IL-4, IL-6 and IL-12 levels in patients with open-angle glaucoma. Res Adv Ophthalmol. 2005;25(1):41–42.

37.DW Gao, QZ Nie, L Pan, et al. Surevy on 539 Hospitalized Glaucoma Patients and Analysis on its Blindness Incidence. Chin Public Health. 2002;18(11):1348–1349.

38.XH Sun, WY Guo, FR Meng. Pathogenesis exploration and research for prevention and cure of secondary glaucoma. Chin J Pract Ophthalmol. 1996;14(8):469–471.

39.XL Zhang, WY Guo. Pathogenesis exploration of secondary glaucoma. J Clin Ophthalmol. 2002;10(1):63.

40.YM Zhao. Clinical analysis of secondary glaucoma in children. Acta Acad Med. 1998;18(6): 495–496.

41.VP De luise. Congenital Glaucoma. Surv Ophthalmol. 1983;28:1–19.

42.WS Mao. An epidemiological survey of eye disease and blindness. Chin J Ophthalmol. 1982;18:170–172.

43.ZH Li. Congenital Glaucoma. Chin J Ophthalmol. 1983;8(5):276–279.

44.S Merin, and D Morin. Heredity of Congenital Glaucoma. Br J Ophthalmol. 1972;56: 414–417.

45.WQ Wang, LX Kong. Congenital glaucoma in twins. Chin J Ophthalmol. 1994;30:107.

Genetic factors seem to play the main role in the differences of glaucoma prevalence between various populations. In 1993, the first genetic locus, GLCIA, contributing to POAG (17) was described. Since that time, a considerable number of genes involved in the pathogenesis of glaucoma have been identified. Apart from genes directly connected with glaucoma, there are genetically conditioned differences in the structure of the lamina cribrosa and the vascularization of ocular nerve head (ONH), influencing the anatomy of the eye and the anterior chamber angle and thus the prevalence of glaucoma.

The number of undiagnosed individuals with glaucoma is still considerable. Even in countries with high medical standard, about 50% of individuals with glaucoma are not aware of their disease (12,18,19) partly because of the lack of adequate detection programs and partly because of the low level of social education.

Early detection and treatment of glaucoma is really important because available medical treatments do not allow the reversal of preexisting optic nerve damage and the effectiveness of therapeutic intervention is not always satisfying. Medical treatment success can only be achieved by stopping the progression or delaying further damage to the ONH. Therefore, treatment effectiveness in preventing the disability of glaucoma depends on the optic nerve condition at the time of diagnosis. Adequate screening program should enable the diagnose of a substantial number of subjects with early glaucomatous damage.

SCREENING FOR GLAUCOMA

Screening tests for glaucoma are based on the assumption that early diagnosis, and treatment in asymptomatic phase allows better results.

The time between the appearance of morphological changes of the ONH and irreversibly functional changes influencing patient’s standard of life is a potential “therapeutic window.” Even with the limited effectiveness of available medical treatments, this window gives the possibility of limiting the socioeconomic consequences of glaucoma. Therefore, the sooner it is possible to stop or delay the degeneration process of retina cells, the better the chances of improving visual acuity and standard of living of the patient.

The preclinical phase when the glaucoma patient does not suffer from any symptoms is particularly long, thus, the conditions at this stage for diagnosis and medical intervention before irreversible damage of the optical nerve are highly favorable.

The World Health Organization suggests several criteria that must be met so that screening tests are justified in terms of ethical and practical values (20). These criteria include the type of disease, possible treatment, and availability of appropriate diagnostic methods for the disease.

Disease

Glaucoma is a disease that leads to worsening of visual function and finally to irreversible blindness.

The epidemiological studies indicate that the probability of irreversible blindness caused by POAG after diagnosis and treatment is 5% within 12 years; however, with the observation time extended to 20 years, the risk of irreversible blindness at least for

one eye increases to 27% and for both eyes to 9% (2,21). The standard of living for glaucoma patients declines much earlier (22,23). Patients with relatively little changes in visual field and good visual acuity report a strong lack of self-confidence while moving around, probably caused by peripheral visual field limitation as well as reduced ability to estimate the distance and the decrease in retina sensitivity in terms of contrast (22). The patients also tend to suffer from injuries and accidents (24).

The prevalence of PACG and POAG changes dramatically in different ethnic groups. PACG is more frequent among Asian populations compared to Europeans or Africans. The highest level of prevalence of PACG, 5%, was reported among Inuits and in the population over 40 years of age in the north-west of Greenland (5,6). The epidemiological data, obtained mainly from hospital reports from the southern part of the Asian continent, show a range of prevalence of PACG from 1.4 (3) to 3% (4).

In Africa and among Afro Americans, POAG is the predominant phenotype. The prevalence is much higher than among Europeans. So far, the highest level of prevalence of POAG was reported among the black Caribbean population of Saint Lucia, 8.8% (13), and Barbados, 7.1% (15), and a little lower among the black population of Baltimore, 4.7% (14).

In Caucasian populatins, the predominant type of glaucoma is POAG. The studies for Australian population over 40 years of age show (10) the mean prevalence of POAG within the range of 0.93–3%. The prevalence of this disease increases significantly with age being 19% among the oldest groups (12). Therefore, the increase in number of individuals at risk for developing glaucoma correlates with increasing life expectancy. Taking into consideration the prevalence, the decreased quality of the patients lives and burden to family members, socioeconomic burden to the community, and the natural course of the disease, one can claim that glaucoma fulfills the criteria needed for screening procedures.

Treatment

The results of random, multi-centered clinical studies conducted in recent years showed that lowering the intraocular pressure (IOP) is an effective method to stop or at least delay the progression of glaucoma (25–28). This can be achieved by pharmacological, laser, or surgical treatment. Furthermore, the treatment efficacy in recent years tends to improve because of the introduction of new IOP-lowering agents, laser technology (selective laser trabeculoplasty), and better surgical procedures. Therefore, it can be assumed that unfavorable social effects of glaucoma can be decreased by the methods currently available and with early diagnosis.

Potential Screening Techniques

While assessing the usefulness of the diagnostic tests for glaucoma screening detection, it is necessary to take into account the costs, time, the lack of side effects as well as sensitivity and specificity values. Particularly important is the value of specificity in case of low-prevalence disease such as glaucoma, because it influences significantly positive predictive value (PPV). This parameter predicts how many people with the positive result of the test are actually ill. With a large number of “falsepositive” results, that is with low specificity, PPV is low. The effectiveness of using

this one method of screening decreases, and many people with positive results for the screening tests after additional expensive and time-consuming tests will not be diagnosed with glaucoma.

Therefore, for studies on diseases of low-prevalence level such as glaucoma, the usefulness of screening tests even with high sensitivity and specificity does not allow the high PPV to account for the costs of these tests. Considering the prevalence of glaucoma of 2% in given populations and with the sensitivity and specificity values of screening test of 96 and 93%, respectively, the PPV is approximately 12%. This would mean that 88% of the patients suspected of having glaucoma after screening test would require unnecessary, expensive, and time-consuming tests. This approach, useful in particular cases, is not economical, for the whole health system and especially in countries with limited financial resources.

Intraocular pressure measurement

IOP measurement can be carried out by means of various methods. However, independent of the accuracy of the measurement, IOP level has poor prognostic value in the diagnosis of glaucoma due to the fact that it is very difficult to define a cut-off IOP value that would connect the high values of sensitivity and specificity in a satisfying way.

The test results show that around 90% of subjects who have IOP values above 21 mmHg will probably never develop glaucoma damage, whereas one-third to one-half of those with glaucoma have IOP in the average range (29).

Stereoscopic evaluation of the ocular nerve head

Stereoscopic assessment of the ONH and retinal nerve fiber layer (RNFL) as the screening test for glaucoma detection is based on the assumption that during glaucoma progression morphological changes precede the functional ones. The problem with the implementation of this method is related to its subjectivity and lack of the well-defined diagnostic criteria of glaucomatous damage of ONH until the advanced stage occurs (30). There currently exists no generally accepted quantitative staging system of the amount of damage. However, as taking high-quality digital pictures of the disc and sending them to a “central reading center” to be interpreted by an experienced specialist is technically possible and easy to do, the implementation of this method as a screening test is advisable and possible to perform.

Scanning laser polarimetry

Scanning laser polarimetry is based on the assumption that the RNFL has birefringent properties that change the state of polarization of a laser beam. This change defined also as retardation of the light is proportional to the amount of tissue present. Unfortunately, RNFL is not the only structure in the eye that possesses birefringent properties, therefore, the polarimeter is equipped with an anterior segment compensating device, which is used to neutralize the polarization effects of the cornea and lens. In the newer version of this instrument, the originally fixed corneal compensator was replaced by a variable one. The sensitivity and specificity vary depending on the value selected as a cut off. In the early studies, a specificity of 77–92% and sensitivity between 64 and 74% was reported (31–33).

Since the high sensitivity of the glaucoma screening test is crucial, one should first of all take into account the correlation between these two parameters. At the specificity of 96%, the best parameter from the instrument with fixed corneal compensator had a sensitivity of only 32% (34), and for newer instruments with variable corneal compensator, the specificity of 97% had a sensitivity of 61% (35).

Visual field tests

Some visual field tests can also be used as screening tests. Standard achromatic perimetry (SAP) is still the golden standard in glaucoma diagnosis. However, the changes in visual field diagnosed by means of this technology occur only in cases of damage greater than approximately 40% of nerve fiber axons (36). Besides, the devices used for this type of testing are practically non-portable and require ambitious lighting that may create certain drawbacks in widespread screening tests.

Frequency doubling technology (FDT) by stimulating the subset of ganglion cells (My) of the magnocellular pathway can potentially detect earlier functional damage than SAP.

In several recent studies, it has been shown that sensitivity and specificity of this technique ranged from 78 to 99% and from 40% to 72%, respectively (37). Together with short examination time it makes this device an interesting screening tool for glaucoma.

The reduced sensitivity of testing for the fellow eye, reported by certain investigators (38–40), can potentially cause problems while using FDT in the screening.

Optical coherence tomography

Optical coherence tomography uses low coherence interferometry to obtain highresolution images of the retina and ONH and assesses the peripapillary RNFL thickness. Several studies have shown sensitivity and specificity of this technology in differentiation between normal and glaucomatous eyes from 67 to 79% and from 71 to 96%, respectively (41,42). At a fixed specificity of 95%, the best parameter from the older version of this instrument had a sensitivity of 68% (34) and from the newer instrument 71% (35).

Confocal scanning laser ophthalmoscopy

The confocal scanning laser ophthalmoscopy employs confocal scanning principles to provide topographic parameters of ONH and peripapillary retina. Mikelberg et al. (43) and Iester et al. (44) reported that using discrimination function, the sensitivity and specificity was estimated at a range from 74 and 88% to 87 and 84%, respectively. Zangwill et al. (34) reported lower sensitivity and specificity values of 42 and 90%, respectively, for this parameter. When the specificity is relaxed to 85%, the sensitivity increases to 56%. With the newer version of this instrument (HRT II), the sensitivities of 59% (34) at the specificities of 95% (35) can be achieved.

THE WROCLAW EPIDEMIOLOGICAL STUDY

Introduction

The aim of this study was to determine the prevalence of glaucoma in a population of Wroclaw inhabitants aged 40–79 years, to determine the number of undiagnosed