Ocular Findings Associated With Rhodopsin Gene Codon 267 and Codon 190 Mutations in Dominant Retinitis Pigmentosa Gerald A. Fishman, MD; Kimberlie Vandenburgh; Edwin M. Stone, MD, PhD; Leonardo D. Gilbert, COT; Kenneth R. Alexander, PhD; Val C. Sheffield, MD, PhD \s=b\ Two members of a family with autosomal dominant retinitis pigmentosa were found to have a cytosine-to-thymine mutation in the second nucleotide of codon 267 in the rhodopsin gene that resulted in a proline-to-leucine change. Two members of another family with autosomal dominant retinitis pigmentosa showed a guanine-to-thymine mutation in the first nucleotide of codon 190 in the rhodopsin gene that resulted in an aspartate-to-tyrosine change. Three members from a third family with autosomal dominant retinitis pigmentosa were also found to have a mutation in codon 190; however, this guanine-toadenine mutation in the first nucleotide of codon 190 resulted in an aspartate-toasparagine change. The relatively less severe functional retinal impairment in our patients with a transmembrane codon 267 rhodopsin gene mutation is generally comparable with that observed in a previously described codon 58 transmembrane mutation. The two families with different intradiscal codon 190 mutations showed a considerable difference in severity of their disease.
(Arch Ophthalmol. 1992;110:1582-1588)
number of distinct mutations in the rhodopsin gene have now been found in different families with autoso¬ mal dominant retinitis pigmentosa (RP).116 Mutations within the intradiscal, transmembrane, and cytoplasmic portions of rhodopsin have been L*-
identified. We present herein the ocular fea¬ tures of three separate rhodopsin gene mutations in three different families: a mutation in codon 267, resulting in a proline-to-leucine change17; a mutation in codon 190, resulting in an aspartate-
Accepted for publication July 15, 1992. From the Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago (Drs Fishman and Alexander and Mr Gilbert); and the Departments of Ophthalmology (Ms Vandenburgh and Dr Stone) and Pediatrics (Dr Sheffield), University of Iowa, Iowa City. Reprint requests to Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W Taylor St, Chicago, IL 60612 (Dr Fishman).
to-tyrosine change; and a mutation in codon 190, resulting in an aspartate-toasparagine change.13 Although two of these mutations (proline to leucine and aspartate to asparagine) have been pre¬ viously identified, their ocular findings have not, to our knowledge, been re¬ ported. Both the clinical and genetic ¡features of the aspartate-to-tyrosine change are described here for the first
time. The two patients with a proline-toleucine change in codon 267 (Pro-267Leu) (family I) had an altered amino acid sequence in a transmembrane por¬ tion of rhodopsin. They showed clinical and electrophysiologic similarities to some patients with a codon 58 rhodopsin gene mutation, which also alters the amino acid sequence in a transmem¬ brane portion of rhodopsin. Both of these transmembrane mutations are characterized by relatively less severe overall functional impairment than is traditionally noted in patients with RP. Two patients (family II) with a muta¬ tion in codon 190 (aspartate to tyrosine) had more extensive functional impair¬ ment, particularly as determined by electrophysiologic testing, than other patients with mutations in the intradiscal portions of rhodopsin, such as those reported for changes in codons 17, 23, 106, and 182.11,16,18 A third family (family III) with a different mutation in codon 190 (aspartate to asparagine) showed a distinct regional predilection for pig¬ mentary retinal changes and less severe functional impairment similar to that reported for other mutations that have affected the intradiscal portion of the
rhodopsin molecule.11,16,18
PATIENTS AND METHODS The three pedigrees described herein identified by screening probands from families with previously described subtypes of autosomal dominant RP19 for the presence of rhodopsin gene mutations. When muta¬ tions were identified in probands, additional family members were tested. All patients were questioned about their subjective complaints of poor night vision, restricted peripheral vision, and decreased were
central visual acuity. Best corrected distance visual acuities were determined with the use of a Snellen visual acuity projection chart. Slit-lamp examination of the anterior seg¬ ment, lens, and vitreous was also performed. A dilated fundus examination was performed with an indirect ophthalmoscope to record the distribution of any pigment clumping or hypopigmentation in the retina, which was subsequently documented by color fundus
photography.
A kinetic visual field examination with a Goldmann perimeter and the II-4-e, V-4-e, and II-2-e test targets documented any pe¬ ripheral visual field impairment. Darkadapted thresholds were psychophysically determined with the use of either a Goldmann-Weekers dark adaptometer or a Tübinger perimeter in accordance with pre¬ viously described procedures.20,21 Ganzfeld
electroretinographic (ERG) recordings were obtained with the use of one of two previ¬ ously described procedures.2224 Report of Cases I.—Patient II-l.—The proband Family (Fig 1), a 30-year-old white woman of Welsh
and Swedish ancestry, was first seen at age 20 years with complaints of poor night vision and photoaversion. She did not report de¬ creased central visual acuity. She had had poor night vision since she was 10 years old. On her most recent visit, she complained of a gradual worsening of her night vision dur¬ ing the preceding 5 years and of her periph¬ eral vision during the previous 3 years. Her overall health was good and she was not tak¬ ing any medication. Visual acuity was correctable to 20/20+1 OD with a refraction of -1.50 +2.50 X75, and to 20/20+2 OS with a refraction of -1.00 + 1.75 X110. Slit-lamp examination findings in the cor¬ nea, anterior chamber, iris, and lens were normal in both eyes. The vitreous showed a small number of cells and posterior vitreous detachment in both eyes. Applanation pres¬ sures were 14 mm Hg in the right eye and 16 mm Hg in the left eye. A fundus examina¬ tion revealed nonspecific pigment mottling within both foveae, and epiretinal mem¬ branes were seen in both maculae. The ret¬ inal arterioles were mildly attenuated, while the optic discs appeared normal on gross ex¬ amination. Regions of hypopigmentation were apparent within the midperipheral re¬ gion of the retina, which extended posteri¬ orly to the vascular arcades. These changes were also readily apparent nasal to the optic
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/28/2015
12/17/81 b
2/18/91
Normal
Tb
b
Photopic White
100µ |_ 20
ms
30-min
Scotopic White
l4 Blue Flicker 10 cps
Fig 1.—Pedigree of family I showing affected (solid symbols) and unaffected (open sym¬ bols) family members. Asterisk indicates pa¬ tient examined by one of us (G.A.F.); arrow, proband (patient 11-1). approximately 3 disc di¬ ameters temporal to the foveal margin. A sparse amount of bone spicule-like pigment clumping was seen primarily in the inferior and inferonasal portions of the retina. The changes were similar in both eyes. Visual field testing revealed bilateral par¬ tial ring scotomas to a II-4-e test target in both eyes. The most recent findings were moderately worse than those obtained 7 years previously. Psychophysical testing with a Tübinger perimeter showed that rods were mediating thresholds in the far periph¬ eral portions of the retina while cones medi¬ ated thresholds to both long- and middlewavelength stimuli within approximately
l8
Red Flicker 30 cps
discs and extended
the central 30°. Threshold elevations were somewhat more noticeable in the inferior than in the the superior portion of the retina, although major regional differences were not apparent. The pattern of elevation was con¬ sistent with the Massof and Finkelstein25 type 2 autosomal dominant RP. An ERG showed a reduction in cone single-flash b-wave amplitude to 40% below the lower normal limit for her age group with a prolonged implicit time. With use of a 30-Hz (cycles per second) flicker stimulus, the cone response was reduced 36% below the lower normal limit with a prolonged im¬ plicit time. Isolated rod b-wave function to a single-flash blue stimulus was reduced 60% from our lower normal limit with a prolonged implicit time. A blue-flicker stimulus at 10 Hz, also isolating rod responses, showed a 56% reduction below the normal range with a prolonged implicit time. A comparison of ERG amplitudes during a 10-year period showed essentially no change (Fig 2). Patient 1-1.—A 61-year-old white man, the father of patient II-l (Fig 1), first noted some difficulty adjusting to dark environ¬ ments in the second decade of life, but he continued to drive at night. He did not com¬ plain of peripheral visual field impairment. He had a 14-year history of diabetes mellitus that had been controlled with oral hypogly¬ cémie agents. He reported only mild subjec¬ tive change in both night vision and periph¬ eral vision during the previous 10 years. On his most recent visit, visual acuity was correctable to 20/20-2 OD with a refraction of -1.00 +1.25 X110 and to 20/20-1 OS with a refraction of -1.25 +1.75 X120. Slit-lamp examination of the cornea, anterior chamber,
I 20µ
a
rWVVWV 5µ
VWvW
Fig 2.—Electroretinogram from the right eye of patient III-1 showing a reduction in cone and, a greater extent, rod a- and b-wave amplitudes with prolonged b-wave implicit times. A comparison of electroretinogram amplitudes over a 10-year period shows no change.
to
12/17/81 b
3/8/91
Photopic White
b 100
µ
|_ 20
ms
30-min
_b Scotopic White 30-min
Scotopic Blue
l4 Blue Flicker
a
10 cps
I
20
µ
Na/vVWV
l„ Red Flicker
5µ
30 cps
v\AA/vv
Fig 3.—Electroretinograms from the right eye of patient 11-1 over a 10-year period. Note sub¬ normal cone and more markedly reduced rod amplitudes with prolonged implicit times. The re¬ sponses are essentially unchanged over this decade. and iris yielded normal findings. The lens in both eyes showed mild posterior subcapsular opacity and nuclear yellowing, and the vit¬ reous showed trace cells in both eyes. Ap¬ planation pressures were 12 mm Hg in the right eye and 13 mm Hg in the left eye. The fundus examination revealed hypo¬ pigmentation along the vascular arcades that extended 1.5 disc diameters temporal to the foveal margin. Similar changes were noted nasal to the optic discs, where bone spiculelike pigment clumping was also seen. The retinal vessels were mildly to moderately attenuated. Both optic nerves showed a moderate amount of pallor. The macula of the right eye showed minimal background dia-
betic
retinopathy, including
dot hemor¬ and hard exudates. The left macula showed a linear-shaped nerve fiber layer hemorrhage and a few intraretinal dot hem¬ orrhages. The foveae of both eyes appeared normal. Angioid streaks were noted in the parapapillary regions of both eyes. The patient's visual field findings on his most recent visit showed a primarily superotemporal partial ring scotoma in both eyes that broke through to the periphery in the superotemporal quadrant, similar to findings noted 8 years previously. Psychophysical testing with a Tübinger perimeter showed that thresholds in the far periph¬ ery were rod-mediated but elevated for
rhages
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/28/2015
both long- and middle-wavelength test stimuli. Within the central 20°, the thresh¬ old profile for the long-wavelength test stimulus was similar to that of patient II-l, his daughter, while thresholds for the middle-wavelength test stimulus were rodmediated, but elevated, at a few locations within this region. There was a tendency for thresholds to be moderately more ele¬ vated in the inferior and nasal portions of the retina than in the superior and tempo¬ ral quadrants. The pattern of elevation was consistent with the Massof and Finkelstein25 type 2 autosomal dominant RP. The patient showed a prolonged re¬ covery of rod threshold at 30° superior to the foveola after a 5-minute bleach with a Goldmann-Weekers dark adaptometer. Thresholds remained elevated 1.3 log units above baseline dark-adapted thresholds even aftei 1 hour 40 minutes of dark ad¬ aptation. Control subjects returned to their prebleach baseline dark-adapted thresholds by 39 minutes under similar test conditions. An ERG on the patient's most recent visit showed a reduction in cone single-flash b-wave amplitude to 40% below the lower normal limit, while a 30-Hz flicker stimulus showed a cone am¬ plitude reduction to 60% below the lower normal limit for his age. Both stimuli showed a prolonged b-wave implicit time. Isolated rod function to a single-flash blue stimulus was nondetectable. A blue-flicker stimulus at 10 Hz, also isolating rod re¬ sponses, showed a 79% reduction in ampli¬ tude below the lower normal range with a prolonged b-wave implicit time. The re¬ cordings were essentially unchanged from those obtained approximately 10 years
Fig 4.—Pedigree of family II showing affected (solid symbols) and unaffected (open symbols) members. Asterisk indicates patient examined by one of us (G.A.F.); arrow, proband (patient III-1).
6/18/90
Normal
Photopic White
30-Hz White
Scotopic
previously (Fig 3).
Family II.—Patient III-l.—A 24-year-old woman (Fig 4) initially noted poor night vision in her early teens that had gradually worsened. She did not complain of difficulty with her peripheral or central vi¬ sion. A review of the patient's family history white
disclosed that her mother had RP. Visual acuity was correctable to 20/20-2 OD with a refraction of -1.25 +1.50 xlOO and to 20/20-1 OS with a refraction of -1.00 + 1.50 X80. A motility examination revealed mild alternating exotropia. Slit-lamp exami¬ nation findings in the cornea, anterior cham¬ ber, and lens were normal. The vitreous con¬ tained a small number of cells in each eye. Applanation pressures were 14 mm Hg in both eyes. The fundus examination disclosed hypo¬ pigmentation that was most apparent ante¬ rior to the vascular arcades and temporal to the macula. A sparse amount of bone spiculelike pigment clumping was noted predomi¬ nantly in the inferior and nasal quadrants. The foveae were normal on gross examina¬ tion, except for epiretinal membranes. The optic discs showed mild waxy-appearing pal¬ lor and peripapillary atrophy. The retinal vessels were attenuated. Visual field testing with a Goldmann pe¬ rimeter showed mild to moderate restriction in the superior hemisphere of both eyes to the II-4-e and V-4-e test targets and gener¬ alized restriction to the II-2-e target. Psychophysical testing with a Tübinger
50-min White
Q.
E
(Arch Ophthalmol. 1992;110:1582-1588)
number of distinct mutations in the rhodopsin gene have now been found in different families with autoso¬ mal dominant retinitis pigmentosa (RP).116 Mutations within the intradiscal, transmembrane, and cytoplasmic portions of rhodopsin have been L*-
identified. We present herein the ocular fea¬ tures of three separate rhodopsin gene mutations in three different families: a mutation in codon 267, resulting in a proline-to-leucine change17; a mutation in codon 190, resulting in an aspartate-
Accepted for publication July 15, 1992. From the Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago (Drs Fishman and Alexander and Mr Gilbert); and the Departments of Ophthalmology (Ms Vandenburgh and Dr Stone) and Pediatrics (Dr Sheffield), University of Iowa, Iowa City. Reprint requests to Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W Taylor St, Chicago, IL 60612 (Dr Fishman).
to-tyrosine change; and a mutation in codon 190, resulting in an aspartate-toasparagine change.13 Although two of these mutations (proline to leucine and aspartate to asparagine) have been pre¬ viously identified, their ocular findings have not, to our knowledge, been re¬ ported. Both the clinical and genetic ¡features of the aspartate-to-tyrosine change are described here for the first
time. The two patients with a proline-toleucine change in codon 267 (Pro-267Leu) (family I) had an altered amino acid sequence in a transmembrane por¬ tion of rhodopsin. They showed clinical and electrophysiologic similarities to some patients with a codon 58 rhodopsin gene mutation, which also alters the amino acid sequence in a transmem¬ brane portion of rhodopsin. Both of these transmembrane mutations are characterized by relatively less severe overall functional impairment than is traditionally noted in patients with RP. Two patients (family II) with a muta¬ tion in codon 190 (aspartate to tyrosine) had more extensive functional impair¬ ment, particularly as determined by electrophysiologic testing, than other patients with mutations in the intradiscal portions of rhodopsin, such as those reported for changes in codons 17, 23, 106, and 182.11,16,18 A third family (family III) with a different mutation in codon 190 (aspartate to asparagine) showed a distinct regional predilection for pig¬ mentary retinal changes and less severe functional impairment similar to that reported for other mutations that have affected the intradiscal portion of the
rhodopsin molecule.11,16,18
PATIENTS AND METHODS The three pedigrees described herein identified by screening probands from families with previously described subtypes of autosomal dominant RP19 for the presence of rhodopsin gene mutations. When muta¬ tions were identified in probands, additional family members were tested. All patients were questioned about their subjective complaints of poor night vision, restricted peripheral vision, and decreased were
central visual acuity. Best corrected distance visual acuities were determined with the use of a Snellen visual acuity projection chart. Slit-lamp examination of the anterior seg¬ ment, lens, and vitreous was also performed. A dilated fundus examination was performed with an indirect ophthalmoscope to record the distribution of any pigment clumping or hypopigmentation in the retina, which was subsequently documented by color fundus
photography.
A kinetic visual field examination with a Goldmann perimeter and the II-4-e, V-4-e, and II-2-e test targets documented any pe¬ ripheral visual field impairment. Darkadapted thresholds were psychophysically determined with the use of either a Goldmann-Weekers dark adaptometer or a Tübinger perimeter in accordance with pre¬ viously described procedures.20,21 Ganzfeld
electroretinographic (ERG) recordings were obtained with the use of one of two previ¬ ously described procedures.2224 Report of Cases I.—Patient II-l.—The proband Family (Fig 1), a 30-year-old white woman of Welsh
and Swedish ancestry, was first seen at age 20 years with complaints of poor night vision and photoaversion. She did not report de¬ creased central visual acuity. She had had poor night vision since she was 10 years old. On her most recent visit, she complained of a gradual worsening of her night vision dur¬ ing the preceding 5 years and of her periph¬ eral vision during the previous 3 years. Her overall health was good and she was not tak¬ ing any medication. Visual acuity was correctable to 20/20+1 OD with a refraction of -1.50 +2.50 X75, and to 20/20+2 OS with a refraction of -1.00 + 1.75 X110. Slit-lamp examination findings in the cor¬ nea, anterior chamber, iris, and lens were normal in both eyes. The vitreous showed a small number of cells and posterior vitreous detachment in both eyes. Applanation pres¬ sures were 14 mm Hg in the right eye and 16 mm Hg in the left eye. A fundus examina¬ tion revealed nonspecific pigment mottling within both foveae, and epiretinal mem¬ branes were seen in both maculae. The ret¬ inal arterioles were mildly attenuated, while the optic discs appeared normal on gross ex¬ amination. Regions of hypopigmentation were apparent within the midperipheral re¬ gion of the retina, which extended posteri¬ orly to the vascular arcades. These changes were also readily apparent nasal to the optic
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/28/2015
12/17/81 b
2/18/91
Normal
Tb
b
Photopic White
100µ |_ 20
ms
30-min
Scotopic White
l4 Blue Flicker 10 cps
Fig 1.—Pedigree of family I showing affected (solid symbols) and unaffected (open sym¬ bols) family members. Asterisk indicates pa¬ tient examined by one of us (G.A.F.); arrow, proband (patient 11-1). approximately 3 disc di¬ ameters temporal to the foveal margin. A sparse amount of bone spicule-like pigment clumping was seen primarily in the inferior and inferonasal portions of the retina. The changes were similar in both eyes. Visual field testing revealed bilateral par¬ tial ring scotomas to a II-4-e test target in both eyes. The most recent findings were moderately worse than those obtained 7 years previously. Psychophysical testing with a Tübinger perimeter showed that rods were mediating thresholds in the far periph¬ eral portions of the retina while cones medi¬ ated thresholds to both long- and middlewavelength stimuli within approximately
l8
Red Flicker 30 cps
discs and extended
the central 30°. Threshold elevations were somewhat more noticeable in the inferior than in the the superior portion of the retina, although major regional differences were not apparent. The pattern of elevation was con¬ sistent with the Massof and Finkelstein25 type 2 autosomal dominant RP. An ERG showed a reduction in cone single-flash b-wave amplitude to 40% below the lower normal limit for her age group with a prolonged implicit time. With use of a 30-Hz (cycles per second) flicker stimulus, the cone response was reduced 36% below the lower normal limit with a prolonged im¬ plicit time. Isolated rod b-wave function to a single-flash blue stimulus was reduced 60% from our lower normal limit with a prolonged implicit time. A blue-flicker stimulus at 10 Hz, also isolating rod responses, showed a 56% reduction below the normal range with a prolonged implicit time. A comparison of ERG amplitudes during a 10-year period showed essentially no change (Fig 2). Patient 1-1.—A 61-year-old white man, the father of patient II-l (Fig 1), first noted some difficulty adjusting to dark environ¬ ments in the second decade of life, but he continued to drive at night. He did not com¬ plain of peripheral visual field impairment. He had a 14-year history of diabetes mellitus that had been controlled with oral hypogly¬ cémie agents. He reported only mild subjec¬ tive change in both night vision and periph¬ eral vision during the previous 10 years. On his most recent visit, visual acuity was correctable to 20/20-2 OD with a refraction of -1.00 +1.25 X110 and to 20/20-1 OS with a refraction of -1.25 +1.75 X120. Slit-lamp examination of the cornea, anterior chamber,
I 20µ
a
rWVVWV 5µ
VWvW
Fig 2.—Electroretinogram from the right eye of patient III-1 showing a reduction in cone and, a greater extent, rod a- and b-wave amplitudes with prolonged b-wave implicit times. A comparison of electroretinogram amplitudes over a 10-year period shows no change.
to
12/17/81 b
3/8/91
Photopic White
b 100
µ
|_ 20
ms
30-min
_b Scotopic White 30-min
Scotopic Blue
l4 Blue Flicker
a
10 cps
I
20
µ
Na/vVWV
l„ Red Flicker
5µ
30 cps
v\AA/vv
Fig 3.—Electroretinograms from the right eye of patient 11-1 over a 10-year period. Note sub¬ normal cone and more markedly reduced rod amplitudes with prolonged implicit times. The re¬ sponses are essentially unchanged over this decade. and iris yielded normal findings. The lens in both eyes showed mild posterior subcapsular opacity and nuclear yellowing, and the vit¬ reous showed trace cells in both eyes. Ap¬ planation pressures were 12 mm Hg in the right eye and 13 mm Hg in the left eye. The fundus examination revealed hypo¬ pigmentation along the vascular arcades that extended 1.5 disc diameters temporal to the foveal margin. Similar changes were noted nasal to the optic discs, where bone spiculelike pigment clumping was also seen. The retinal vessels were mildly to moderately attenuated. Both optic nerves showed a moderate amount of pallor. The macula of the right eye showed minimal background dia-
betic
retinopathy, including
dot hemor¬ and hard exudates. The left macula showed a linear-shaped nerve fiber layer hemorrhage and a few intraretinal dot hem¬ orrhages. The foveae of both eyes appeared normal. Angioid streaks were noted in the parapapillary regions of both eyes. The patient's visual field findings on his most recent visit showed a primarily superotemporal partial ring scotoma in both eyes that broke through to the periphery in the superotemporal quadrant, similar to findings noted 8 years previously. Psychophysical testing with a Tübinger perimeter showed that thresholds in the far periph¬ ery were rod-mediated but elevated for
rhages
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 05/28/2015
both long- and middle-wavelength test stimuli. Within the central 20°, the thresh¬ old profile for the long-wavelength test stimulus was similar to that of patient II-l, his daughter, while thresholds for the middle-wavelength test stimulus were rodmediated, but elevated, at a few locations within this region. There was a tendency for thresholds to be moderately more ele¬ vated in the inferior and nasal portions of the retina than in the superior and tempo¬ ral quadrants. The pattern of elevation was consistent with the Massof and Finkelstein25 type 2 autosomal dominant RP. The patient showed a prolonged re¬ covery of rod threshold at 30° superior to the foveola after a 5-minute bleach with a Goldmann-Weekers dark adaptometer. Thresholds remained elevated 1.3 log units above baseline dark-adapted thresholds even aftei 1 hour 40 minutes of dark ad¬ aptation. Control subjects returned to their prebleach baseline dark-adapted thresholds by 39 minutes under similar test conditions. An ERG on the patient's most recent visit showed a reduction in cone single-flash b-wave amplitude to 40% below the lower normal limit, while a 30-Hz flicker stimulus showed a cone am¬ plitude reduction to 60% below the lower normal limit for his age. Both stimuli showed a prolonged b-wave implicit time. Isolated rod function to a single-flash blue stimulus was nondetectable. A blue-flicker stimulus at 10 Hz, also isolating rod re¬ sponses, showed a 79% reduction in ampli¬ tude below the lower normal range with a prolonged b-wave implicit time. The re¬ cordings were essentially unchanged from those obtained approximately 10 years
Fig 4.—Pedigree of family II showing affected (solid symbols) and unaffected (open symbols) members. Asterisk indicates patient examined by one of us (G.A.F.); arrow, proband (patient III-1).
6/18/90
Normal
Photopic White
30-Hz White
Scotopic
previously (Fig 3).
Family II.—Patient III-l.—A 24-year-old woman (Fig 4) initially noted poor night vision in her early teens that had gradually worsened. She did not complain of difficulty with her peripheral or central vi¬ sion. A review of the patient's family history white
disclosed that her mother had RP. Visual acuity was correctable to 20/20-2 OD with a refraction of -1.25 +1.50 xlOO and to 20/20-1 OS with a refraction of -1.00 + 1.50 X80. A motility examination revealed mild alternating exotropia. Slit-lamp exami¬ nation findings in the cornea, anterior cham¬ ber, and lens were normal. The vitreous con¬ tained a small number of cells in each eye. Applanation pressures were 14 mm Hg in both eyes. The fundus examination disclosed hypo¬ pigmentation that was most apparent ante¬ rior to the vascular arcades and temporal to the macula. A sparse amount of bone spiculelike pigment clumping was noted predomi¬ nantly in the inferior and nasal quadrants. The foveae were normal on gross examina¬ tion, except for epiretinal membranes. The optic discs showed mild waxy-appearing pal¬ lor and peripapillary atrophy. The retinal vessels were attenuated. Visual field testing with a Goldmann pe¬ rimeter showed mild to moderate restriction in the superior hemisphere of both eyes to the II-4-e and V-4-e test targets and gener¬ alized restriction to the II-2-e target. Psychophysical testing with a Tübinger
50-min White
Q.
E
