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

12.Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP; Parrish II RK, Wilson MR, Gordon MO, for the Ocular Hypertension Treatment Study Group. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:701–13.

13.Ehlers N, Kruse-Hensen F. Central corneal thickness in low-tension glaucoma. Acta Ophthalmol (Copenh) 1974;52:740–6.

14.Brandt JD, Beiser JA, Kass MA, Gordon MO. Central corneal thickness in the ocular hypertension treatment study (OHTS). Ophthalmology 2001;108:1779–88.

15.Grodum¨ K, Heijl A, Bengtsson B. A comparison of glaucoma patients identified through mass screening and in routine clinical practice. Acta Ophthalmol Scand 2002;80:627–31.

16.Eysteinsson Th, Jonasson F, Sasaki H, Arnarsson A, Sverrisson Th, Sasaki K, Stefánsson E. Central corneal thickness radius of the corneal curvature and intraocular pressure in normal subjects using non-contact techniques: Reykjavik Eye Study. Acta Ophthalmol Scand 2002;80:11–15.

17.Eysteinsson Th, Jonasson F, Arnarsson A, Sasaki H, Sasaki K. Relationship between ocular dimensions and adult stature among participants in the Reykjavik Eye Study. Acta Ophthalmol Scand 2005;83:734–8.

18.Foster PJ, Buhrmann R, Quigley HA, Johnson GJ. The definition and classification of glaucoma in prevalence surveys. Br J Ophthalmol 2002;86:238–42.

19.Wang L, Damji KF, Munger R, Jonasson F. Arnarsson A. Sasaki H. Sasaki K. Increased disc size in glaucomatous eyes versus normal eyes in the Reykjavik Eye Study. Am J Ophthalmol 2003;135:226–8.

20.Jonsson O, Damji KF, Jonasson F, Arnarsson A, Eysteinsson Th, Sasaki H, Sasaki K. Epidemiology of the optic nerve grey crescent in the Reykjavik Eye Study. Br J Ophthalmol 2005;89:36–9.

21.Shields MB. Gray crescent in the optic nerve head. Am J Ophthalmol 1980;89:238–44.

22.Shields MB. Textbook of Glaucoma, 4th ed. Philadephia, PA: Lippincot Williams and Wilkins, 1997.

23.Wensor MD, McCarty CA, Stanislavsky YL, Livingston PM, Taylor HR. The prevalence of glaucoma in the Melbourne Visual Impairment Project. Ophthalmology 1998;105:733–9.

24.Tielsch JM, Sommer A, Katz J, Royall RM, Quigley H, Javitt J. Racial variations in the prevalence of primary open angle glaucoma. The Baltimore Eye Survey. JAMA 1991;266:369–74.

25.Coffey M, Reidy A, Wormald R, Xian WX, Wright L, Courtney P. Prevalence of glaucoma in the West of Ireland. Br J Ophthalmol 1993;77:17–21.

26.Bathija R, Gupta N, Zangwill L, Weinreb RN. Changing definition of glaucoma. J Glaucoma 1998;7:165–9.

27.Tuulonen A, Airaksinen PJ, Erola E, Forsman E, Friberg K, Kaila M, Klemetti A, Makela M, Oskala P, Puska P, Suoranta L, Teir H, Uusitalo H, Vainio-Jylha E, Vuori ML. The Finnish evidence-based guideline for open-angle glaucoma. Acta Ophthalmol Scand 2003;81:3–18.

28.Wong EY, Keeffe JE, Rait JL, Vu HT, Le A, McCarty C, Taylor HR. Detection of undiagnosed glaucoma by eye health professionals. Ophthalmology 2004;111:1508–14.

29.Klein BE, Klein R, Sponsel WE, Franke T, Cantor LB, Martone J, Menage MJ. Prevalence of glaucoma. The Beaver Dam Eye Study. Ophthalmology 1992;99:1499–504.

30.Bonomi L, Marchini G, Marraffa M, Bernardi P, De Franco I, Perfetti S, Varotto A, Tenna V. Prevalence of glaucoma and intraocular pressure distribution in a defined population. The Egna-Neumarkt Study. Ophthalmology 1998;105:209–15.

31.Dielemans I, Vingerling JR, Wolfs RC, Hofman A, Grobbee DE, de Jong PT. The prevalence of primary open angle glaucoma in a population based study in the Netherlands. The Rotterdam Study. Ophthalmology 1994;101:1851–55.

32.Schlötzer-Shrehardt U, Naumann GO. Perspective, ocular and systemic pseudoexfoliation syndrome. Am J Ophthalmol 2006;141:921–37.

33.Grödum K, Heijl A, Bengtson B. Risk of glaucoma in ocular hypertension with and without pseudoexfoliation. Ophthalmology 2005;112:386–90.

34.Odberg T, Jakobsen JE, Hultgren SJ, Halseide R. The impact of glaucoma on the quality of life of patients in Norway. Acta Ophthalmol Scand 2001;79:116–20.

35.Ekström C. Prevalence of pseudoexfoliation in a population 65–74 years of age. Acta Ophthalmol (Copenh) 1987;65(suppl 182):9–10.

36.Ringvold A, Blika S, Elsas T, Guldahl J, Brevik T, Hesstvedt P, Johnsen H, Hoff K, Hoisen H, Kjorsvik S, Rossvoll I. The middle Norway Eye Screening Study. Epidemiology of pseudoexfoliation syndrome. Acta Ophthalmol (Copenh) 1988;66:652–58.

37.Ringvold A. Epidemiology of pseudoexfoliation syndrome. Acta Ophthalmol Scand 1999;77:371–5.

The earliest epidemiological survey on blindness and low vision in China was conducted by Hu in 1987 and showed that blindness caused by glaucoma accounted for 8.8% of the total number of blind persons, and glaucoma was the fourth leading blindness disease (2). According to the findings in this survey by Hu in Shunyi County of Beijing, it was estimated there were 6.5 million glaucoma patients in China, and 600 thousand persons became blind due to glaucoma, and the number of suspected glaucoma patients requiring long-term follow-up examination might be 10 times of that of glaucoma patients.

In 1999, Liang used stratified random sampling principles and WHO blindness standard to perform an epidemiological study on blindness and low vision at Mei county in Guangdong province and found that glaucoma took the second place in the eye diseases leading to blindness and low vision while cataract was in first place

(3). Liu used the same way to conduct an epidemiological survey on eye diseases and blindness in Rongcheng city in Shandong Province and found the prevalence rate of blindness was 0.142% (4). Among them, cataract took the first place (38.1%), glaucoma was in the second place (14.3%), optic atrophy, keratoleukoma, and diabetic retinopathy were at the third place, and other eye diseases accounted for 19.1%. Ren used proportional random group sampling method to investigate the mobility of glaucoma in the people ≥50 years old in the countryside of Shanxi province, China, during July–October 2003, and found that the prevalence rate of glaucoma was 2.14% (5). The glaucoma patients had varying degrees of vision impairments, among which monocular low vision, binocular low vision, monocular blindness and binocular blindness accounted for 18.42, 5.26, 18.42, and 13.16%, respectively. Patients with undiagnosed glaucoma accounted for 71.05%, and among the other 28.95% of glaucoma patients with a confirmed diagnosis, only 54.55% had received treatment. Zhao (6) showed in a population-based survey in Shunyi County in Beijing that 64% of glaucoma patients [80% of them were diagnosed as primary angle-closure glaucoma (PACG)] had damaged visual function. Based on an analysis of in-patients in five hospitals in Qingdao between 1997 and 1999, the proportion of glaucoma patients (11.89%) was the second after the rates of cataract patients (43.36%) (7). In recent years, based on the prevalence rates of glaucoma in Singapore and Mongolia (corresponding to the prevalence rates of glaucoma of urban population and rural population in China), Foster (8) deduced that there are 9.4 million glaucoma patients with optic nerve impairment and over 5.2 million blind glaucoma patients in China. If the deduction is correct, the number of glaucoma patients is similar to the number of cataract patients. That means, glaucoma is one of the principal blinding diseases in China.

Glaucoma not only brings enormous agony to the patients themselves and their families, but also results in a heavy social economic burden and serious loss of human resources. There have not been any analyses of the costs of glaucoma in China. With the development of “Vision 2020” and the progress in the knowledge and treatment of glaucoma, the Chinese government and people will pay more and more attention to glaucoma. At present, clinical researchers in China have learned that there is difference in the distribution of various types of glaucoma in different populations in different regions even in China and that the types of glaucoma may change with the rapid

development of the economy. Epidemiological investigations will provide important data for the prevention and treatment of glaucoma and assist the government and health agencies to establish healthcare policy and carry out blindness prevention plans.

PRIMARY GLAUCOMA

Primary Angle-Closure Glaucoma

Diagnosis of PACG

According to the classification system of angle-closure glaucoma established in China, PACG is divided into acute and chronic primary angle-closure glaucoma. Based on the course of disease, acute angle-closure glaucoma is divided into preclinical stage, prodromal stage, acute attack stage, interval stage, chronic stage, and absolute stage. Recently, a new international classification system for the diagnosis of angle-closure glaucoma has been suggested (9–13). If there is glaucomatous optic nerve impairment and 90° of the trabecular meshwork tissues can be seen, the patient is diagnosed as PACG. If there is similar angle closure and the intraocular pressure increases or there is peripheral-anterior synechia (PAS) without glaucomatous optic nerve impairment, the patient is diagnosed as primary angle closure (PAC). The patients with narrow angle but without the evidences of glaucoma or angle impairment (i.e., there is no increase in intraocular pressure or PAS) should be diagnosed as narrow angle instead of PACG. The new classification method has been in dispute and has not been widely used in China.

The intraocular pressure and anterior angle in Chinese population were described for the diagnosis of glaucoma. Zhao found the range of normal intraocular pressure in the population with age ≥50 years old was 9.23–17.85 mm Hg and the intraocular pressure decreased with age (6). In the population with age ≥50 years old, the mean of normal intraocular pressure was lower than the expected value, suggesting that when glaucoma screening was performed in the population over 50 years old, the upper limit value of normal intraocular pressure should be lowered to 18 mm Hg. The criteria for the diagnosis used by Xu (14) in the epidemiological investigation on PACG in the population over 40 years old in Beijing were as follows: There was one of the following indications besides the closure of peripheral anterior chamber angle. (i) The initial intraocular pressure or intraocular pressure after mydriasis > 30 mm Hg (measured using non-contact tonometer); (ii) there were signs of iris ischemia (partial atrophy of iris, discoria and glaucomatous fleck) after acute attack of PACG; (iii) typical glaucomatous optic nerve impairment (based on the evaluation on optic nerve and nerve fiber layer using fundus stereoscopy); and (iv) Typical glaucomatous visual field defect. Secondary glaucoma should be excluded (such as those due to inflammatory reactions and traumas, etc.). The diagnostic criteria for anterior chamber angle closure of PACG were as follows: when gonioscope was used to observe the degree of angle closure, the posterior trabecular meshwork could not be seen in ≥3/4 of anterior chamber angle or there is partial or whole angle closure or PAS ≥1/3.

Incidence Rate of PACG

There is difference in the morbidity of angle-closure glaucoma between different races in different regions in the world. As it is not easy to estimate the specific onset time of PACG in epidemiological survey, it is very difficult to investigate the incidence rate of PACG. The available data were determined based on the results of the hospitalized glaucoma patients and the local population survey results, and there is no investigation and survey report on the incidence rate of PACG in Mainland China. In Hong Kong, Lai estimated that the incidence rate of acute PACG was 10.4/100,000 annually in the Chinese population over 30 years and 58.7/100,000 annually in the Chinese population over 50 years (15). However, a study performed in Singapore showed the incidence rate of acute PACG in the population over 30 years was 12.2/100,000 annually (16).

Prevalence Rate of PACG

Most of the epidemiological investigations on glaucoma carried out in China are the reports about the prevalence rate of PACG. These data can be divided into two types: One type is large sample investigation using proper sampling method with confirmed criteria of diagnosis based on population and the another type is using the routine medical record of local medical services to estimate the relative prevalence rate.

There are only a few epidemiological investigations on PACG based on population. The investigation conducted by Hu showed that the prevalence rate of PACG was 0.41% in natural population while 1.37% in the population over 40 years old (2). However, the investigation conducted by Zhao indicated that the prevalence rates of PACG in the natural population over 20 years old and the natural population over 40 years old were, respectively, 0.08 and 0.15% in Tibet, which were significantly lower than those in the Beijing population of the same age group (17). The investigation performed at Tongcheng County in Anhui province in the same year showed the prevalence rate of 0.31%, which was similar to that conducted in Shunyi County in Beijing (18). The epidemiological survey on PACG conducted by Yu in Doumen County in Guangdong Province in the South China showed that the prevalence rate of PACG in the population over 45 years old was 0.64% and the prevalence rate of PACG in the population over 50 years old was 0.85%, which were significantly different from the findings in the population of the same age group in Shunyi County in Beijing (the prevalence rate of PACG was 1.99% in the population over 50 years old) (19).

There may be regional difference on the prevalence of PACG in the same race. Xu (14) screened glaucoma in the rural and urban population in Beijing. His results showed that the prevalence rate of PACG in the population over 40 years old was 1.2%, and the prevalence rate of PACG in the rural area (1.6%) was higher than that in the urban area (1.1%). The proportions of monocular low vision (39.3%) and monocular blindness (28.6%) in rural area were higher than those in urban area (20.6 and 14.7%, respectively). The above research data indicate that the prevalence rates of PACG are different in different regions, specifically that the prevalence rate in north China is higher than that in south China (see Fig. 1).

Lin (20) performed a statistical analysis on the data of the glaucoma in-patients at Zhongshan Eye Center in Guangdong Province between September 1996 and June

Fig. 1. Prevalence of primary angle-closure glaucoma (PACG) by region in China.

2002 and found that PACG was most common and accounted for 54.42% of the total number of glaucoma cases. Song (21) performed a statistical analysis on the data of all the glaucoma in-patients at Huaxi Hospital in Sichuan Province during January 1978–December 1981 and January 2001–December 2002. The results indicate that the primary glaucoma patients accounted for 81.30 and 81.40% of all the glaucoma in-patients, respectively, during the two periods, and there was no statistical difference between them. The proportion of PACG during January 1978–December 1981 was 88.7% and decreased to 76.1% during January 2001 to December 2002. The analysis by Li on all the glaucoma in-patients at Tongren hospital between 2002 and 2005 showed that PACG patients accounted for 59.31% of all the glaucoma in-patients (22). As the admission criteria of different hospitals are different, the above data can only be used for reference.

Risk Factors of PACG

Demographic Indices

Age. Most of the population-based studies showed that the number of PACG significantly increased with age over 40 years old (2,6). Xu suggested that the prevalence rate of PACG increased with age, and there was an age range with sudden increase of prevalence rate (14). This age range in the countryside (60–69 years old) was 10 years younger than that in the urban area (70 years or over). Similar results were obtained in the statistical analysis on in-patients and the analytic results by Lin showed in the primary glaucoma patients, 80.97% were over 40 years old, 97.11% of PACG patients were over 40 years old, and angle-closure glaucoma accounted for 82.09% of the patients over 40 years old (20). Other research showed that 71.78% of primary glaucoma in-patients were over 40 years old, most of the PACG patients were between 50 and 70 years, 95.31% of PACG patients were over 40 years old, and the median age of PACG patients increased for 54 years old during 1978–1981 to 63 years old during 2001–2002 (21). The reasons could include the prolongation of average life, the aging of population, and the increase of the proportion of old people in the population. In addition, with the socioeconomic development and the improvement of life quality, the

rate of old people seeking medical assistance increases. Moreover, the relation between PACG and age distribution in Chinese may be related to the anatomical characteristics of the anterior segment, such as shallow anterior chamber, narrow angle of anterior chamber, and short optic axis. And in easterner, with the increase of age, the lens is thickened, the pupil becomes small, pupil block is produced, and the periphery anterior chamber gradually turns shallow.

Sex. The results from most investigations showed that the number of females was significantly more than that of males in PACG patients. The investigation by Hu in 1989 showed that the prevalence rate of PACG was 0.13% in male and 0.47% in female, a significant sex difference (2). Xu reported that the prevalence rate of PACG was 1.7% in female and 0.8% in male in North China, also a significant difference (14). However, Lin reported that in primary glaucoma in-patients, male : female = 1:1.01 in South China (14). In this study, the male/female ratio was 1:1.53 in PACG, 1:2.29 in acute PACG patients, and 1:1.18 in chronic PACG patients. The reason might be that angle-closure glaucoma was easily induced in the females in conditions when they had high mood fluctuation and vegetative nerve functional disturbances.

Race. Many studies have found that the prevalence rate of PACG is the highest in Eskimo, followed by those in Chinese, Mongolian, and Indian, and the lowest in Caucasian (1). In China, Zhao reported that the prevalence rate of the Han nationality was higher than that of Tibetan (6,17).

Ocular Factors

Anatomical factors may be involved in the incident of PACG. Ye (23) reported that, in the population over 40 years old, all individuals had angle-closure glaucoma if their axial depth of anterior chamber was ≤1.4 mm. If the axial depth of anterior chamber was ≤1.6 mm, 77.8% of all had angle-closure glaucoma. And if the axial depth of anterior chamber was ≤2.0 mm, only 10% of all had angle-closure glaucoma. Therefore, the depth of the peripheral anterior chamber ≤1/4 corneal thickness (CT) and ≤1/4 iris light band ratio (ILBR) in oblique illumination method is recommended as the criteria for the preliminary screening of PACG. Yu (24) studied the conditions of anterior chamber angle in the middle-aged and old people in Guangdong province and found that in people over 50 years, 12 (lower quadrant)-30% (upper quadrant) had anterior chamber angle ≤2 (in Shaffer system), and 11.3 (lower quadrant)-26.4% (upper quadrant) of them had serious peripheral iris bomb. The iris root attached at the scleral spur in 27.7 (lower quadrant)–42.6% (upper quadrant) of them. The incidence rate of the above three types of anterior chamber angle in females was higher than that in males, and the incidence rate of narrow angle increased with age. This provided evidence from the aspect of ocular anatomy for the higher prevalence rate of PACG in females than that in males and the increase of prevalence rate of PACG with the increase of age in China. In other research (25), the PACG suspects have been studied and had at least one of the following conditions: (i) Axial depth of anterior chamber ≤2.0 mm; (ii) The depth of peripheral anterior chamber ≤¼ CT; and (3) flashlight oblique illumination =¼ ILBR. A 6-year followup investigation on 485 PACG suspects found 4.1% of incidence rate of PACG in 6 years, and this rate was inversely proportional to the axial depth of the anterior chamber

and the depth of peripheral anterior chamber. Therefore, the depth of anterior chamber and the depth of peripheral anterior chamber may be the main risk factors for PACG.

Other risk factors

There is substantial evidence that PACG patients have special psychological characteristics, such as irascibility and temperament (26–29). Other risk factors include occupations requiring near vision and hypertension. Diabetes, myopia, smoking, drinking, and ABO blood types are unrelated to PACG (30). 25.2% of PACG patients had a family history although the genetic component has not yet been determined. Lai found that 23.6% of PACG patients had a history of upper respiratory tract infection before an acute attack of PACG (15). Seah found a positive correlation between an acute attack of PACG and the sunspot number per month (16).

Primary Open-Angle Glaucoma

Diagnosis of POAG

The criteria for the diagnosis of primary open-angle glaucoma (POAG) widely accepted in China are as follows (31):

1.Fundus photos to observe the characteristic rim of optic disc and the retinal nerve fiber layer (RNFL).

2.Repeatable characteristic visual field defect of POAG in agreement with pathological changes of glaucomatous optic nerve.

3.Increased or normal intraocular pressure.

4.No PAS in ≥3 quadrants under gonioscopy examination.

5.Secondary glaucoma must be excluded.

Incidence Rate of POAG

As POAG is a chronic ocular disease, it is difficult to determine its incidence rate. There has been no studies of this in China yet.

Prevalence Rate of POAG

The prevalence rates of POAG in Chinese population appear to have increased over time. Hu (2) recorded a 0.4% prevalence rate of POAG in Beijing in 1989. The investigation conducted by Zhao (6) at an exurban area in Beijing (Shunyi County) in 1996 showed a 0.29% prevalence rate of POAG in the population over 50 years old. Xu (31) performed a glaucoma screening in the population over 40 years old in Beijing in 2001, and the results showed the prevalence rates of POAG in the males in the exurban and urban were 1.97% and 2.07%, respectively, whereas in the females they were 1.04% and 1.42%, respectively. In the POAG-diagnosed patients, about 50% had a first measured intraocular pressure <21 mm Hg. In this study, the monocular blindness of POAG in exurban and urban were 15.40 and 10.90%, respectively. On the other hand, Lin (20) performed a statistical analysis on the data of the glaucoma in-patients at Zhongshan Eye Center in Guangdong province between September 1996 and June 2002 and found that POAG took the second place (PACG took the first place) and accounted for 21.73% of the total number of glaucomas. Song (21) reviewed all

the glaucoma in-patients at the Huaxi Hospital in Sichuan Province during January 1978–December 1981 and January 2001–December 2002 and found that POAG cases accounted for 11.3% in all primary glaucoma cases during January 1978–December 1981 and 23.9% in all primary glaucoma cases during January 2001–December 2002. The analysis by Li (22) on all the glaucoma in-patients at Tongren hospital in Beijing between 2002 and 2005 showed that POAG patients accounted for 8.11% of all the glaucoma in-patients. Further multi-center epidemiological studies are clearly required in China for verification of the increase in the prevalence of POAG.

Risk Factors of POAG

Demographic Indices

Age. In China, the POAG patients were relatively younger. Lin found that 80.97% of the primary glaucoma patients were over 40 years old (20). The investigation by Song (21) showed that in the primary glaucoma in-patients, POAG patients were between 18 and 78 years old and had a peak in the population over 40 years old. There was a positive correlation between POAG and age. The median age of POAG patients was 47.5 years old during 1978–1981 and 47 years during 2001–2002. Although 38.2% of the POAG patients were less than 40 years old during 1978–1981, 42.7% of the POAG patients were less than 40 years old during 2001–2002. Although the difference was not statistically significant, there seems to be a trend of a younger patient population.

Sex. The number of male patients with POAG may be more than that of female ones. Xu reported that the prevalence rates of POAG in the males in exurban and urban were 1.97 and 2.07%, respectively, and the prevalence rates of POAG in the female population in countryside and city were, respectively, 1.04 and 1.42% (31). One investigation showed that the number of male POAG patients was 2.55 times that of female POAG patients (32).

Race. It has been found in many studies that the prevalence rate of POAG was the highest in the blacks (even 3–4 times higher than in Caucasian), followed by that in Caucasians, and the prevalence rate was the lowest in easterners, especially Chinese and Eskimo (1). There has been no statistical analysis on the prevalence rates of POAG among the different races in China.

Ocular Factors

Asymmetrical intraocular pressure and myopia are risk factors of POAG. Xu (33,34) performed an analysis on the asymmetry of intraocular pressure in the population receiving glaucoma screening. (The asymmetry of intraocular pressure was defined as the difference of intraocular pressure 3 mm Hg.) According to the statistical results of reliable measured intraocular pressure values, the average intraocular pressure of right eye was 16.03 ± 3.25 mm Hg, and the average intraocular pressure of left eye was 16.08 ± 3.17 mm Hg. The incidence rate of asymmetrical intraocular pressure in the total population was 20.01% and increased with age, which was 18.4% in the group of 40–49 years and 26.6% in the group of over 70 years. In addition, the incidence rate of asymmetrical intraocular pressure correlated with a general increase of intraocular pressure of both eyes. The incidence rates of asymmetrical intraocular pressure in the