Corneal Topography in Parents of Patients With Keratoconus
Computer-Assisted
Victor
\s=b\
Gonzalez, MD, Peter J. McDonnell,
MD
Recently developed computer-as-
sisted devices allow detection of early topographic abnormalities of the cornea, including mild or abortive forms of keratoconus. To address the possibility that keratoconus is an inherited condition, we examined both parents of 12 randomly selected patients with keratoconus whom we were following up. Of the 12 sets of parents, at least one parent in each of seven sets had abnormal corneal characteristics. Using previously determined quantitative criteria (eg, central corneal steepening, greater steepening inferiorly than superiorly, and asymmetry between the two eyes) to distinguish normal from keratoconic corneas we found evidence of keratoconus in at least one of the 14 parents. The remaining five patients had parents with normal corneal characteristics. These data support the hypothesis that keratoconus is sometimes an inherited condition, exhibiting, at least in some families, autosomal dominant inheritance with incomplete penetrance.
(Arch Ophthalmol. 1992;110:1412-1414) T7"eratoconus is -"-*-
a
noninflammatory
corneal ectasia characterized by progressive thinning of the corneal stroma with resultant irregular myopic astigmatism and corneal scarring. It is commonly bilateral, and its progression varies. Reported estimates of the inci¬
dence of keratoconus vary significantly, ranging from 50 to 230 per 100 000 per¬ sons.1 The large discrepancy in these estimates is likely a result of the differ¬ ing criteria used for the diagnosis. Con¬ ventional keratometric instruments can miss early cases of keratoconus,2 an im¬ portant consideration, since most of the larger series reported used irregular mires on keratometry as an important criterion in establishing the diagnosis of keratoconus.
Accepted
for publication January 24, 1992. From the Department of Ophthalmology, University of Southern California School of Medicine, and the Doheny Eye Institute, Los Angeles, Calif. The authors have no proprietary interest in the companies or products mentioned in this article. Reprint requests to Doheny Eye Institute, 1450 San Pablo St, Los Angeles, CA 90033 (Dr McDonnell).
The role of heredity in this condition is unclear. Friedrich Von Ammon is credited with the first report (in 1830) of a familial occurrence of keratoconus, and studies of twins3 have verified the etiologic role of heredity in some cases of keratoconus. Some studies have re¬ ported a female preponderance of cases,4 while other studies have not confirmed a male-female difference in rates of occurrence.5 Other reports im¬ plicate sex-linked,5 autosomal reces¬ sive,6 and sporadic3 mechanisms of transmission. The largest of these stud¬ ies demonstrate an autosomal dominant mode of transmission, with a frequency of inheritance of about 8%.7 These dif¬ ferent conclusions as to inheritance and frequency of occurrence may be the re¬ sult of failure to recognize early or mild keratoconus in some family members. Maguire and Bourne2 demonstrated that early cases of keratoconus can be identified with the use of a computerassisted topographic analysis system
(Corneal Modeling System [CMS], Computed Anatomy Ine, New York,
NY). Rabinowitz and McDonnell8 found that certain quantitative parameters, when applied to the data obtained from the CMS, could distinguish normal from keratoconic corneas and could be used to identify early or subclinical cases of keratoconus. Using this technique, they identified evidence of autosomal domi¬ nant transmission of keratoconus in the families of the five selected patients with keratoconus.9 To determine whether this observation remained valid in larger numbers of unselected families, we examined both parents of 12 patients with keratoconus (the pa¬ tients' conditions were being followed up by us), reasoning that one parent of each patient should have abnormal cor¬ neal characteristics if the condition is inherited in an autosomal dominant fashion and exhibits complete penetrance.
SUBJECTS AND METHODS We examined 24 parents of 12 unselected
patients with keratoconus. Parental recruit¬ ment began by mailing letters to 50 patients
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/15/2015
with keratoconus. Patients were asked if their parents resided in Southern California and would be willing to travel to our institute for examination. To prevent recruitment bias, we did not inquire as to whether the parents had histories of keratoconus or other ocular abnormalities or whether corrective lenses were required for good vision. Letters were followed up with phone calls. Because contact lens use has been demonstrated to cause both transient and permanent topo¬ graphic changes in the cornea,10 we excluded any parent who had a history of contact lens use or who had a history of ocular surgery. We identified 12 patients for whom both parents were available for examination. All eyes were examined using the CMS, which uses 32 illuminated rings that span the cornea from limbus to limbus. The data obtained using the photokeratoscope were digitized and curves describing them were generated. This information was then trans¬ lated into a color-coded topographic map. The CMS has been demonstrated to provide measurements of curvature of calibrated steel balls that are as accurate as those ob¬ tained with a keratometer. Its SD for human corneas is about ±0.25 diopters.11 In addition to qualitative analysis of topo¬ graphic patterns, we used quantitative mea¬ surements, as described by Rabinowitz and McDonnell," to identify subclinical cases of keratoconus. Four photographs were taken of each eye using the CMS. The best one of the four was used in the study. Photographs with artifact from dry spots, movement, or inappropriate fixation were excluded from the study. We measured the following three parameters: (1) central corneal power (ob¬ tained when the cursor is placed at the cen¬ ter of the central ring); (2) the difference in central corneal dioptric power between both eyes of the same individual; and (3) the amount of steepening of the inferior cornea compared with that of the superior cornea, expressed as the I-S (inferior-superior) value (ie, the difference between the average inferior corneal dioptric power and the aver¬ age superior corneal dioptric power). To cal¬ culate the I-S value, we measured the diop¬ tric power at five points along the inferior cornea, 3 mm from the center of the cornea, at 30° intervals (210°, 240°, 270°, 300°, and 330°); and at five points along the superior cornea, also 3 mm from the center of the cor¬ nea (30°, 60°, 90°, 120°, and 150°). The read¬ ings were averaged, and the values for the superior cornea were subtracted from the values for the inferior cornea and expressed as the I-S value. Therefore, a positive I-S
Eyes vs Eyes With
Table 1.—Characteristics of Normal
Normal Corneas
Keratoconic Corneas
_(N=15)
(N=25) Central corneal power, D Mean (range) SD
RESULTS
Keratoconus*
52.13(43.10-60.20)
43.67(41.60-46.6)
5.95
1.44
Computer-Assisted
Victor
\s=b\
Gonzalez, MD, Peter J. McDonnell,
MD
Recently developed computer-as-
sisted devices allow detection of early topographic abnormalities of the cornea, including mild or abortive forms of keratoconus. To address the possibility that keratoconus is an inherited condition, we examined both parents of 12 randomly selected patients with keratoconus whom we were following up. Of the 12 sets of parents, at least one parent in each of seven sets had abnormal corneal characteristics. Using previously determined quantitative criteria (eg, central corneal steepening, greater steepening inferiorly than superiorly, and asymmetry between the two eyes) to distinguish normal from keratoconic corneas we found evidence of keratoconus in at least one of the 14 parents. The remaining five patients had parents with normal corneal characteristics. These data support the hypothesis that keratoconus is sometimes an inherited condition, exhibiting, at least in some families, autosomal dominant inheritance with incomplete penetrance.
(Arch Ophthalmol. 1992;110:1412-1414) T7"eratoconus is -"-*-
a
noninflammatory
corneal ectasia characterized by progressive thinning of the corneal stroma with resultant irregular myopic astigmatism and corneal scarring. It is commonly bilateral, and its progression varies. Reported estimates of the inci¬
dence of keratoconus vary significantly, ranging from 50 to 230 per 100 000 per¬ sons.1 The large discrepancy in these estimates is likely a result of the differ¬ ing criteria used for the diagnosis. Con¬ ventional keratometric instruments can miss early cases of keratoconus,2 an im¬ portant consideration, since most of the larger series reported used irregular mires on keratometry as an important criterion in establishing the diagnosis of keratoconus.
Accepted
for publication January 24, 1992. From the Department of Ophthalmology, University of Southern California School of Medicine, and the Doheny Eye Institute, Los Angeles, Calif. The authors have no proprietary interest in the companies or products mentioned in this article. Reprint requests to Doheny Eye Institute, 1450 San Pablo St, Los Angeles, CA 90033 (Dr McDonnell).
The role of heredity in this condition is unclear. Friedrich Von Ammon is credited with the first report (in 1830) of a familial occurrence of keratoconus, and studies of twins3 have verified the etiologic role of heredity in some cases of keratoconus. Some studies have re¬ ported a female preponderance of cases,4 while other studies have not confirmed a male-female difference in rates of occurrence.5 Other reports im¬ plicate sex-linked,5 autosomal reces¬ sive,6 and sporadic3 mechanisms of transmission. The largest of these stud¬ ies demonstrate an autosomal dominant mode of transmission, with a frequency of inheritance of about 8%.7 These dif¬ ferent conclusions as to inheritance and frequency of occurrence may be the re¬ sult of failure to recognize early or mild keratoconus in some family members. Maguire and Bourne2 demonstrated that early cases of keratoconus can be identified with the use of a computerassisted topographic analysis system
(Corneal Modeling System [CMS], Computed Anatomy Ine, New York,
NY). Rabinowitz and McDonnell8 found that certain quantitative parameters, when applied to the data obtained from the CMS, could distinguish normal from keratoconic corneas and could be used to identify early or subclinical cases of keratoconus. Using this technique, they identified evidence of autosomal domi¬ nant transmission of keratoconus in the families of the five selected patients with keratoconus.9 To determine whether this observation remained valid in larger numbers of unselected families, we examined both parents of 12 patients with keratoconus (the pa¬ tients' conditions were being followed up by us), reasoning that one parent of each patient should have abnormal cor¬ neal characteristics if the condition is inherited in an autosomal dominant fashion and exhibits complete penetrance.
SUBJECTS AND METHODS We examined 24 parents of 12 unselected
patients with keratoconus. Parental recruit¬ ment began by mailing letters to 50 patients
Downloaded From: http://archopht.jamanetwork.com/ by a Oakland University User on 06/15/2015
with keratoconus. Patients were asked if their parents resided in Southern California and would be willing to travel to our institute for examination. To prevent recruitment bias, we did not inquire as to whether the parents had histories of keratoconus or other ocular abnormalities or whether corrective lenses were required for good vision. Letters were followed up with phone calls. Because contact lens use has been demonstrated to cause both transient and permanent topo¬ graphic changes in the cornea,10 we excluded any parent who had a history of contact lens use or who had a history of ocular surgery. We identified 12 patients for whom both parents were available for examination. All eyes were examined using the CMS, which uses 32 illuminated rings that span the cornea from limbus to limbus. The data obtained using the photokeratoscope were digitized and curves describing them were generated. This information was then trans¬ lated into a color-coded topographic map. The CMS has been demonstrated to provide measurements of curvature of calibrated steel balls that are as accurate as those ob¬ tained with a keratometer. Its SD for human corneas is about ±0.25 diopters.11 In addition to qualitative analysis of topo¬ graphic patterns, we used quantitative mea¬ surements, as described by Rabinowitz and McDonnell," to identify subclinical cases of keratoconus. Four photographs were taken of each eye using the CMS. The best one of the four was used in the study. Photographs with artifact from dry spots, movement, or inappropriate fixation were excluded from the study. We measured the following three parameters: (1) central corneal power (ob¬ tained when the cursor is placed at the cen¬ ter of the central ring); (2) the difference in central corneal dioptric power between both eyes of the same individual; and (3) the amount of steepening of the inferior cornea compared with that of the superior cornea, expressed as the I-S (inferior-superior) value (ie, the difference between the average inferior corneal dioptric power and the aver¬ age superior corneal dioptric power). To cal¬ culate the I-S value, we measured the diop¬ tric power at five points along the inferior cornea, 3 mm from the center of the cornea, at 30° intervals (210°, 240°, 270°, 300°, and 330°); and at five points along the superior cornea, also 3 mm from the center of the cor¬ nea (30°, 60°, 90°, 120°, and 150°). The read¬ ings were averaged, and the values for the superior cornea were subtracted from the values for the inferior cornea and expressed as the I-S value. Therefore, a positive I-S
Eyes vs Eyes With
Table 1.—Characteristics of Normal
Normal Corneas
Keratoconic Corneas
_(N=15)
(N=25) Central corneal power, D Mean (range) SD
RESULTS
Keratoconus*
52.13(43.10-60.20)
43.67(41.60-46.6)
5.95
1.44
