Family History in Primary Open-Angle Glaucoma Dong H. Shin, MD;
Bernard
Becker, MD; Allan
\s=b\ A family history of glaucoma was found in 50% of patients with primary open-angle glaucoma (POAG) and 43% of patients with ocular hypertension (OH). Positive family history was twice as prevalent in those with OH and either HLA-B7 or B12 antigens than in OH with neither antigen (P < .01). Although POAG occurred equally in men and women, the prevalence of a positive family history of glaucoma on the maternal side of the family in POAG patients was six to seven times greater than on the paternal side (P < .0005). However, in patients with OH, but no glaucomatous field loss, there was no difference in prevalence of maternal and paternal family history. Even in OH with HLA-B7 or B12 antigens, there was no predominance of maternal family history. The implication that offspring were more likely to develop POAG when their mother's side of the family rather than their father's side had the disease has provided an additional potentially useful risk factor in patients with OH. In addition, it has raised interesting questions as to possible maternal cytoplasmic factors in the transmission and pathogenesis of POAG.
(Arch Ophthalmol 95:598-600, 1977)
E.
Kolker, MD
Although the role of genetic factors the pathogenesis of primary open-angle glaucoma (POAG) is generally accepted, the exact mode of II in
transmission appears to be variable.'•Some pedigrees are compatible with autosomal dominant inheritance,'"'' but others suggest recessive modes of transmission.''-7 Furthermore, many patients with POAG fail to give a family history of glaucoma,1''"" and recent evidence suggests the disease may be heterogeneous.1"" Studies of corticosteroid responses in vivo and in vitro suggest that the highly responsive state associated with POAG is inherited in autosomal recessive fashion." --" However, only a small group of high responders develop POAG. Therefore, the inheritance of POAG is best described as multifactorial.'-"1" -" The present study attempts to identify some of the factors in the transmission of POAG. PATIENTS AND METHODS One hundred
fifty patients
with POAG
(84 white and 66 black, 80 men and 70 women) and 88 patients (58 white and 30 black, 45 men and 43 women) with ocular
hypertension (intraocular
pressure > 20
Hg), hut no visual field loss, were selected randomly from the Glaucoma Center of Washington University School of mm
Accepted
for publication Sept 20, 1976. From the Glaucoma Center, Washington University School of Medicine, St Louis. Reprint requests to Glaucoma Center, Washington University School of Medicine, 660 S Euclid, St Louis, MO 63110 (Dr Becker).
Medicine. Patients with
pigmentary
dis-
persion syndrome, inflammatory disease,
and congenital defects were omitted. All of the subjects had been followed in the Glaucoma Center for 5 to 15 years,
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 05/29/2015
during which time they underwent
re-
eye examinations at regular intervals. The examinations included applana-
peated
tonography, gonioscopy> and both kinetic and static Goldmann perimetry. Testing for HLA antigens was done as previously described.-' A positive family history of glaucoma (PH + ) was defined as a reasonably clear-cut history of chronic glaucoma in any relative. Further classification divided the group with positive family history into four subdivisions—materna' side (FHM + ), paternal side (FHP + ), both maternal and paternal (FHM+ and P+)i and only siblings and offspring (FHS +
tion tonometry,
ophthalmoscopy,
and 0 + ). If individuals gave a history °' glaucoma in siblings and offspring as well as the families of parents, only the parental data were used in the subclassificationFor the statistical analysis Yates' chisquare test or paired chi-square-- was
employed.
RESULTS
prevalence of a positive family history (FH + ) of glaucoma in the total POAG population was 50% (75 of 150) and in those with ocular hyper' tension (OH) was 43% (38 of 88) (Table The
1). The FH+ was noted in 55% of white patients with POAG, 44% of blacks, 49% of men and 51% of women. These differences were not statisti-
In white patients with OH, 45% had FH+ as to 40% of blacks, 42% of men had FH + and 44% of women. The POAG patients with FH + were subdivided into four categories
cally significant.
compared
follows: maternal side (FHM + ), Paternal side (FHP + ), both maternal
COMMENT
as
and and
paternal sides (FHM+ and P + ), sibling and offspring (FHS+ and ° + ) (Table 2). Among both white and
Since HLA B7 and B12 antigens are transmitted genetically-''-' and are associated with POAG,-' it is not surprising to find that FH+ is twice as prevalent in the group with either antigen (Table 3). It merely confirms the hereditary nature of glaucoma and its relationship to HLA B7 and B12 antigens. It is most startling, however, to find that the prevalence of FHM+ is six to seven times greater than FHP+ among patients with POAG (Table 2). No such sex predominance is seen in the POAG patients themselves (Table 1). Also patients with OH demonstrate no difference in prevalence of FHM + and FHP+ (Table 2). Furthermore, OH individuals who have the B7 and B12 antigens which relate to POAG, show no increase in prevalence of FHM + These findings have clinical and theoretical implications. It is immediately apparent that the risk factor, "family history of glaucoma," which is often used in clinical judgment both for prognosis and therapy of OH, must be modified.-'-" The FHM + increases markedly the chance of development of field loss, whereas FHP+ appears to carry no additional risk over that of OH with a negative family history of glaucoma. In addition to the practical consequences, the observations made in this study raise provocative questions about the transmission of POAG. Is the glaucoma gcne(s) from the mother's side somehow more strongly expressed phenotypically than that
black,
male and female POAG paFHM+ was significantly greater than FHP + In contrast, among the OH population there was no significant différence between FHM+ and FHP+ (Table 2). Furthermore, the prevalence of FHP'twas significantly greater in the OH objects (17%) than in the POAG
tients,
.
Patients (4%) (P < .0005). In the 88 patients with OH, either
HLA B7 or B12 antigens were present
prevalence of FH + significantly greater (P < .01) in the group with either antigen (63%) than in those OH patients with »either antigen (31%) (Table 3). Howler, the prevalence of either B7 or "*2 antigens in the OH patients with 'n
33 (38%). The
Was
.
FHm +
did not differ at all from those With FHP+ or from the total OH Sfoup with FH + .
Table I.—Family History of Glaucoma in Patients With POAG and OH
^Jotal
POAG
._White POAG _Black POAG ._Men POAG _Women POAG
No. With FH+ (%) 75 (50) 46 (55) 29 (44) 39 (49)
No. 150 84 66 80 70
_Total OH_
36(51)
88
38
._White OH _Black OH ._Men OH
58 30 45
26 (45)
,_Women
43
OH
(43)
12(40) 19(42) 19(44)
Black POAG
White
Male POAG
Female
POAG
Total POAG
Total OH
+
P
FHS +
_and
+_1
(1%)
3(5%)
0+_14(17%)
10(15%)
*P < .0005 (FHM + vs FHP + ). TP< .005 (FHM + vs FHP + ).
ÍP
Bernard
Becker, MD; Allan
\s=b\ A family history of glaucoma was found in 50% of patients with primary open-angle glaucoma (POAG) and 43% of patients with ocular hypertension (OH). Positive family history was twice as prevalent in those with OH and either HLA-B7 or B12 antigens than in OH with neither antigen (P < .01). Although POAG occurred equally in men and women, the prevalence of a positive family history of glaucoma on the maternal side of the family in POAG patients was six to seven times greater than on the paternal side (P < .0005). However, in patients with OH, but no glaucomatous field loss, there was no difference in prevalence of maternal and paternal family history. Even in OH with HLA-B7 or B12 antigens, there was no predominance of maternal family history. The implication that offspring were more likely to develop POAG when their mother's side of the family rather than their father's side had the disease has provided an additional potentially useful risk factor in patients with OH. In addition, it has raised interesting questions as to possible maternal cytoplasmic factors in the transmission and pathogenesis of POAG.
(Arch Ophthalmol 95:598-600, 1977)
E.
Kolker, MD
Although the role of genetic factors the pathogenesis of primary open-angle glaucoma (POAG) is generally accepted, the exact mode of II in
transmission appears to be variable.'•Some pedigrees are compatible with autosomal dominant inheritance,'"'' but others suggest recessive modes of transmission.''-7 Furthermore, many patients with POAG fail to give a family history of glaucoma,1''"" and recent evidence suggests the disease may be heterogeneous.1"" Studies of corticosteroid responses in vivo and in vitro suggest that the highly responsive state associated with POAG is inherited in autosomal recessive fashion." --" However, only a small group of high responders develop POAG. Therefore, the inheritance of POAG is best described as multifactorial.'-"1" -" The present study attempts to identify some of the factors in the transmission of POAG. PATIENTS AND METHODS One hundred
fifty patients
with POAG
(84 white and 66 black, 80 men and 70 women) and 88 patients (58 white and 30 black, 45 men and 43 women) with ocular
hypertension (intraocular
pressure > 20
Hg), hut no visual field loss, were selected randomly from the Glaucoma Center of Washington University School of mm
Accepted
for publication Sept 20, 1976. From the Glaucoma Center, Washington University School of Medicine, St Louis. Reprint requests to Glaucoma Center, Washington University School of Medicine, 660 S Euclid, St Louis, MO 63110 (Dr Becker).
Medicine. Patients with
pigmentary
dis-
persion syndrome, inflammatory disease,
and congenital defects were omitted. All of the subjects had been followed in the Glaucoma Center for 5 to 15 years,
Downloaded From: http://archopht.jamanetwork.com/ by a New York University User on 05/29/2015
during which time they underwent
re-
eye examinations at regular intervals. The examinations included applana-
peated
tonography, gonioscopy> and both kinetic and static Goldmann perimetry. Testing for HLA antigens was done as previously described.-' A positive family history of glaucoma (PH + ) was defined as a reasonably clear-cut history of chronic glaucoma in any relative. Further classification divided the group with positive family history into four subdivisions—materna' side (FHM + ), paternal side (FHP + ), both maternal and paternal (FHM+ and P+)i and only siblings and offspring (FHS +
tion tonometry,
ophthalmoscopy,
and 0 + ). If individuals gave a history °' glaucoma in siblings and offspring as well as the families of parents, only the parental data were used in the subclassificationFor the statistical analysis Yates' chisquare test or paired chi-square-- was
employed.
RESULTS
prevalence of a positive family history (FH + ) of glaucoma in the total POAG population was 50% (75 of 150) and in those with ocular hyper' tension (OH) was 43% (38 of 88) (Table The
1). The FH+ was noted in 55% of white patients with POAG, 44% of blacks, 49% of men and 51% of women. These differences were not statisti-
In white patients with OH, 45% had FH+ as to 40% of blacks, 42% of men had FH + and 44% of women. The POAG patients with FH + were subdivided into four categories
cally significant.
compared
follows: maternal side (FHM + ), Paternal side (FHP + ), both maternal
COMMENT
as
and and
paternal sides (FHM+ and P + ), sibling and offspring (FHS+ and ° + ) (Table 2). Among both white and
Since HLA B7 and B12 antigens are transmitted genetically-''-' and are associated with POAG,-' it is not surprising to find that FH+ is twice as prevalent in the group with either antigen (Table 3). It merely confirms the hereditary nature of glaucoma and its relationship to HLA B7 and B12 antigens. It is most startling, however, to find that the prevalence of FHM+ is six to seven times greater than FHP+ among patients with POAG (Table 2). No such sex predominance is seen in the POAG patients themselves (Table 1). Also patients with OH demonstrate no difference in prevalence of FHM + and FHP+ (Table 2). Furthermore, OH individuals who have the B7 and B12 antigens which relate to POAG, show no increase in prevalence of FHM + These findings have clinical and theoretical implications. It is immediately apparent that the risk factor, "family history of glaucoma," which is often used in clinical judgment both for prognosis and therapy of OH, must be modified.-'-" The FHM + increases markedly the chance of development of field loss, whereas FHP+ appears to carry no additional risk over that of OH with a negative family history of glaucoma. In addition to the practical consequences, the observations made in this study raise provocative questions about the transmission of POAG. Is the glaucoma gcne(s) from the mother's side somehow more strongly expressed phenotypically than that
black,
male and female POAG paFHM+ was significantly greater than FHP + In contrast, among the OH population there was no significant différence between FHM+ and FHP+ (Table 2). Furthermore, the prevalence of FHP'twas significantly greater in the OH objects (17%) than in the POAG
tients,
.
Patients (4%) (P < .0005). In the 88 patients with OH, either
HLA B7 or B12 antigens were present
prevalence of FH + significantly greater (P < .01) in the group with either antigen (63%) than in those OH patients with »either antigen (31%) (Table 3). Howler, the prevalence of either B7 or "*2 antigens in the OH patients with 'n
33 (38%). The
Was
.
FHm +
did not differ at all from those With FHP+ or from the total OH Sfoup with FH + .
Table I.—Family History of Glaucoma in Patients With POAG and OH
^Jotal
POAG
._White POAG _Black POAG ._Men POAG _Women POAG
No. With FH+ (%) 75 (50) 46 (55) 29 (44) 39 (49)
No. 150 84 66 80 70
_Total OH_
36(51)
88
38
._White OH _Black OH ._Men OH
58 30 45
26 (45)
,_Women
43
OH
(43)
12(40) 19(42) 19(44)
Black POAG
White
Male POAG
Female
POAG
Total POAG
Total OH
+
P
FHS +
_and
+_1
(1%)
3(5%)
0+_14(17%)
10(15%)
*P < .0005 (FHM + vs FHP + ). TP< .005 (FHM + vs FHP + ).
ÍP
