The Genetic Study of Primary Angle-Closure Glaucoma
The Genetic Study of Primary Angle-Closure Glaucoma
The purpose of this study is to evaluate the possible candidate gene of Primary Angle-Closure
 Glaucoma.
Glaucoma has long been recognised as a leading cause of blindness, and that the scale of the
 problem will only increase with future population growth and increasing life expectancy (1).

 The epidemiological information available in 1993 in the World Health Organization's (WHO)
 global data bank on blindness was reviewed by Thylefors and Négrel (1). They developed a
 simple model estimating the number of glaucoma blind people in each World Bank region.
 Primary open angle glaucoma (POAG) was judged to be responsible for three million blind,
 primary angle closure glaucoma (PACG) for two million, and for congenital glaucoma the figure
 was 200 000, giving a total of 5.2 million blind. This represents 15% of global blindness.
 The number of people affected by glaucoma was estimated to be about 20 million.

 In 1996, Quigley used 111 published reports of glaucoma prevalence to construct a statistical
 model of the number of people affected by glaucoma worldwide (2). Data were included only if
 the study design, methods, and reported results met certain specific criteria. The countries
 of the world were arranged in seven groups according to similarities in ethnicity and
 presumed characteristics of glaucoma. For each region, the available age specific prevalence
 of OAG and ACG were applied to population projections for the year 2000. It was estimated
 that 66.8 million people were affected by OAG and ACG, with nearly equal numbers of people
 affected by each disease. Few prevalence studies described secondary glaucoma separately, but
 an estimate of six million for secondary glaucoma was reached, making a total, without
 childhood glaucoma, of around 73 million affected. Of these, 6.7 million were thought to be
 blind (2).

 There was reliable epidemiologic evidence to suggest that PACG is more common among Eskimos
 (3) and Chinese (4). As POAG was common in the western countries, there was a large
 population at risk in Asia (5). PACG among Asians was more frequently chronic and has few
 symptoms (6). Therefore, persons might not be motivated by symptoms to present to medical
 attention until significant visual damage has occurred in this region. A population-based
 study of screening techniques for PACG was performed in the township of Jin Shan in rural
 Taiwan (7). This joint US-Taiwanese project, published in 1996, identified a target
 population of 5441 people aged 40 years and older, of whom 562 were examined. A gonioscopic
 examination was carried out on all subjects. PACG was diagnosed in people with a "narrow"
 angle and either an IOP >18 mm Hg, an increase in IOP 8 mm Hg on dark prone provocation test,
 or a previous "acute" episode of angle closure with an iridectomy. The diagnosis did not
 depend on the presence of a visual field defect or structural optic neuropathy. There were 17
 people diagnosed as suffering PACG (3.0%). Only 35% of cases gave a history of symptoms
 characteristic of "acute" angle closure. Two of these 17 people (12%) were blind in both eyes
 (7). As aforementioned, Taiwan has a high prevalence of PACG, which usually leads to
 blindness ultimately. There are many reported studies on genes of POAG and normal-tension
 glaucoma from Asia, including Japan (14,21,29), China (25), and Korea (24). However, studies
 about genetics of PACG were lacking. Hence, in this study, we use the model of genomewide
 microsatellite genotyping with method of linkage disequilibrium to study the possible
 candidate gene of PACG. Then, we will further sequence the cDNA forPAX6 to find out the
 possible mutation in the family with well-defined pedigree.
Inclusion Criteria:

 -  An occludable angle was defined as one in which less than 90° circumference of the
 pigmented trabecular meshwork was visible. Persons in whom primary angle-closure was
 suspected (PACS) had an occludable angle and no other abnormality. Primary angle
 closure (PAC) was diagnosed in persons with a normal visual field and optic disc but
 having an occludable angle and evidence of angle dysfunction. Dysfunctional features
 included elevated IOP (>19 mm Hg) or a positive darkroom-prone provocation test,
 peripheral anterior synechiae, pigment smearing in superior drainage angle, sequelae
 of acute angle closure (iris whorling or glaukomflecken), or a clear history of
 symptomatic angle closure with evidence of a peripheral iridectomy. An IOP of 19 mm Hg
 was chosen by taking the mean +2 SDs from other data on Sino-Mongoloid people.

 Primary angle-closure glaucoma was diagnosed in subjects with an occludable drainage angle
 and glaucomatous optic neuropathy with compatible visual morbidity. Optic neuropathy was
 defined as a CDR of 0.7 or more, or asymmetry of 0.2 or more. In early to moderate cases
 (CDR of 0.7 or 0.8 or asymmetry of 0.2), a reproducible visual field defect was required to
 confirm the diagnosis. In advanced cases (CDR >=0.9 or CDR asymmetry >0.3), perimetric
 evidence of visual loss was not an absolute requirement. Primary angle-closure glaucoma was
 diagnosed if the disc was not visible, but iris stromal atrophy and whorling were seen in
 conjunction with a visual acuity less than 20/400.

 Exclusion Criteria:

 -  Individuals are excluded if there is known ocular disease or insult that could
 predispose to myopia, such as retinopathy of prematurity or early-age media
 opacification, or if they had a known genetic disease associated with myopia, such as
 Stickler or Marfan syndrome.