Exfoliation syndrome (XFS) is an age-related generalized disorder characterized by the production and deposition of a fibrillar extracellular material in ocular tissues and various visceral organs.1 It was first described by Lindberg2 in a Finnish population in 1917. Exfoliation syndrome has been etiologically associated with glaucoma [exfoliative glaucoma (XFG)], cataract, lens subluxation, and severe complications at the time of cataract extraction, such as zonular dialysis, capsular rupture, and vitreous loss.3 The diagnosis of XFS is confirmed by the presence of whitish gray deposits of exfoliation material (XFM) at the papillary border or on the anterior lens capsule, exhibiting 3 distinct zones (central disk, clear intermediate zone, and peripheral granular zone) in its complete presentation.3,4
Exfoliation syndrome is predominantly seen over those aged 50 years, and the prevalence increases steadily with age. Although it occurs throughout the world, there is wide geographic and ethnic variation among populations.3 It is especially common in Scandinavian countries, but even here, different prevalences are found in different countries. Åström et al5 reported that XFS affected every fourth individual reaching the age of 66 years in northern Sweden. The prevalence rates in other ethnic populations were as follows: Greenland Eskimos (0%), Minnesotans (0.3%), Estonians (25.5%), black South Africans (6.0%–7.7%), Upper Egyptians (4.1%), South Indians (3.8%–6.0%), and Japanese (3.4%).6–13 In contrast, XFS has been generally considered to be rare in Chinese people. A hospital-based study in Hong Kong revealed a prevalence rate of 0.4% in patients with cataract aged 60 years or older.14 Another study further reported that the age and sex standardized rate was 0.7% in Chinese Singaporean adults over those aged 60 years.15 Recently, in the Beijing Eye Study 2011, we reported the prevalence of definite XFS was 2.38%, suspect XFS was 3.4%, and overall XFS was 5.82% in a North Chinese population aged 50 years or older.16
Beijing Tongren Eye Center is a tertiary eye care center in the north of China, which serves a large number of patients from all over the country, especially the northern region. The present study in the hospital setting was undertaken to determine the frequency and clinical features of XFS and XFG in Northern China.
MATERIALS AND METHODS
The study was approved by the ethics committee for human research of Beijing Tongren Hospital, Capital Medical University. The medical charts of consecutive inpatients who presented for cataract or glaucoma surgery at the Beijing Tongren Eye Center between January 2002 and November 2009 were reviewed in this retrospective study. All patients with XFS or XFG were identified in the database using diagnosis codes.
Exfoliation syndrome was diagnosed clinically if the patient had XFM on the pupillary margin or anterior lens capsule. Exfoliative glaucoma was defined by the presence of XFS and the following features: (1) glaucomatous changes in the optic disk, described as vertical cup-to-disk ratio greater than or equal to 0.7, a cup-to-disk ratio asymmetry greater than 0.2, or notching of the disk rim; (2) characteristic glaucomatous visual field loss; and (3) intraocular pressure (IOP) greater than or equal to 22 mm Hg in either eye. A characteristic glaucomatous visual field loss was considered to be present when no systemic or ocular disorder was found to account for the visual field defects except for the glaucoma.
Patients who had a history of uveitis, trauma, pigment dispersion syndrome, or iridocorneal endothelial syndrome, or any other causes for secondary glaucoma, were excluded.
The statistical analysis was performed using SPSS for Windows (version 16.0, SPSS Inc, Chicago, Ill). Quantitative data are presented as mean (SD).
A total of 73,976 patient charts were available in our database. Forty-five patients (75 eyes) were diagnosed with XFS or XFG and were enrolled in the study, including 27 males and 18 females. Exfoliation syndrome/XFG accounted for 0.55% (45/8205) of hospitalized patients with cataract aged 60 years or older. The mean (SD) age was 75.9 (6.8) years (range, 67–85 years). All subjects except 2 were Han Chinese.
The ocular characteristics of XFS/XFG are summarized in Table 1. Presence of XFM on the pupillary margin (66.7%) and anterior lens surface (65.3%) were the most common features. Loss of pupillary ruff (13.3%) was uncommon. Increased pigmentation (49.3%) and flecks of XFM (9.3%) were seen on the trabecular meshwork, and 25 eyes (33.3%) had narrow angles. Of the 45 subjects, 36 (80%) had glaucoma. The mean (SD) IOP at initial diagnosis was 19.97 (6.6) mm Hg (range, 8–49 mm Hg). Exfoliative glaucoma accounted for 4.3% (36/838) of hospitalized patients with open-angle glaucoma. For those with bilateral XFS/XFG (66.7%, 30/45), 7 patients had bilateral XFS, 15 patients had bilateral XFG, and 8 patients had XFS in 1 eye but XFG in another eye.
Twenty-two patients (44.4%) had hypertension, and 7 (15.6%) had ischemic heart diseases. Other recorded systemic diseases included diabetes mellitus (3 patients), cerebrovascular diseases (2 patients), and osteoarthritis (2 patients).
In our hospital-based study from Northern China, the frequency rate of XFS/XFG among hospitalized individuals with cataract aged 60 years or older is 0.55% (45/8205) with male predominance. Exfoliative glaucoma accounted for 4.3% (36/838) of hospitalized patients with open-angle glaucoma. Most of the subjects were Han Chinese and age between 70 and 80 years in our study. Exfoliation syndrome/XFG presented more frequently bilaterally than unilaterally.
In another population-based, cross-sectional study with those aged 50 years or older in Northern China,16 we reported the prevalence of XFS was 5.8%, which was higher than in 2 previous studies of Chinese: a hospital-based study from Hong Kong with a prevalence of 0.4%14 and the population-based Singaporean Tanjong Pagar Study with a prevalence of 0.2%.15 The differences in the reported prevalence of XFS may be due to differences in the study populations, detection technique, and definition of XFS. The prevalence of XFS both with and without glaucoma varies considerably due to racial, ethnic, and geographic variations. It comprises greater than or equal to 50% of the open-angle glaucoma in some countries, including Norway, Ireland, Greece, and Saudi Arabia.3 Recent reports indicate that it comprises 25% of open-angle glaucoma in South African Zulus.7 In the United States, it is much more common in white than in persons of African ancestry, comprising about 12% of glaucoma populations.3
Thus far, genetic and environmental factors have been implicated in the etiology of XFS/XFG. Our previous genetic study indicated that lysyl oxidase-like 1 (LOXL1) is a susceptibility gene of XFS/XFG in the Chinese population, and the association is mainly attributed to SNP rs1048661.17 More recent studies in the United States found that northern-tier residence was associated with an increased hazard of XFS and that ambient temperature and sun exposure may be important environmental triggers.18,19 However, in comparison with previous studies on Chinese in the southern-tier regions such as Hong Kong and Singapore, there is no significant difference on prevalence of XFS/XFG in the northern-tier of China, considered by the regional differences in climate, geography, and physical traits.
In Caucasians, a hallmark of XFS is pigment loss from the iris sphincter region and its deposition on anterior chamber structures.3 In our study, deposits of XFM on the pupillary margin and anterior lens capsule were the most common clinical findings. Increased trabecular meshwork pigmentation was prominent, but loss of pupillary ruff was scarce. Ye et al20 described loss of pigment at the pupillary ruff and dense pigmentation on the trabec ular meshwork as the early signs of 11 patients with XFS in southern China. The reason leading to the discrepancy with our study is uncertain.
As the leading identifiable cause of open-angle glaucoma worldwide, XFG progresses more rapidly with poorer prognosis than primary open-angle glaucoma. Exfoliative glaucoma is typically related to higher mean IOP, greater diurnal variations, more serious optic neuropathy, and progressive visual field loss.21 Blockage of the meshwork by XFM or iris pigment and trabecular cell dysfunction result in IOP elevation and progressive glaucoma. Patients with XFS are also predisposed to develop angle-closure glaucoma.22 Our finding that approximately 30% of eyes with XFS had narrow angles may reflect the predisposing characteristics of XFS, including zonular weakness and associated forward lens movement, iris stiffness and rigidity, and smaller pupil. We also found that most patients had bilateral involvement, which is consistent with previous evidence suggesting that XFS basically affects both eyes.23
Exfoliation material has been identified in several extraocular organs such as the skin, heart, liver, blood vessels, and meninges, suggesting that XFS is a systemic disease.24,25 Evidence has demonstrated its association with systemic vascular abnormalities, ranging from peripheral vascular occlusions, coronary artery disease, and stroke to neurodegenerative disorders such as Alzheimer’s disease, and hearing loss.24–27 An age-matched case-control study implied that XFS is associated with and may be a risk factor for peripheral vascular disease.27 Consistently, our data found that hypertension and ischemic heart disease are the 2 most frequent systemic diseases. Hypertension and ischemic heart diseases are common for old people, and the systemic diseases of those not having XFS/XFG were not analyzed as control. So, it is hard to indicate the 2 systemic diseases are related to XFS. Further study is required to clarify the underlying mechanism.
It should be noted that we did not attempt to address the prevalence of XFS/XFG in the Chinese population through this retrospective chart review. The data obtained from the current hospital-based retrospective study are less precise than from population-based surveys, and varied examination techniques among physicians may exacerbate this bias. In addition, the manifestations of XFS in the very early stages of disease may be missed on examination. We speculate that the true prevalence rate may be underestimated. However, most of the medical charts contained enough information for us to sum up the characteristics of XFS/XFG in north Chinese.
In conclusion, our hospital-based study demonstrates an uncommon prevalence of XFS/XFG among northern Chinese. Presence of XFM on the pupillary margin and anterior lens capsule and increased trabecular meshwork pigmentation are common clinical features.
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