Retinal Vascular Changes of Incontinentia Pigmenti Robert C. Watzke, MD; Thomas S. Stevens, MD; Robert G. Of 19 patients with incontinentia seven had a bizarre retinal that consisted of a zone of abnormal arteriovenous connections and preretinal fibrotic tissue at the temporal
pigmenti, anomaly
equator, with no perfusion peripheral to it. In one patient, the vascular changes progressed and required photocoagulation. This retinal lesion may represent an early stage of the pseudoglioma that so commonly is reported with this skin disease. Incontinentia pigmenti should be considered in the differential diagnosis of retinal vascular disease in girls and women of any age.
(Arch Ophthalmol 94:743-746, 1976)
Incontinentia
pigmenti is a rare skin disease in infant girls that is char¬ acterized by recurrent vesiculobullous
dermatitis that resolves spontaneous¬ ly and leaves irregularly pigmented atrophie scars on the trunk and lower extremities. In addition to the skin Accepted
for publication April 15, 1975. From the departments of ophthalmology, University of Iowa College of Medicine, Iowa City (Dr Watzke), and the University of Wisconsin Medical School, Madison (Dr Stevens). Dr Carney is in private practice in Decatur, Ill. Presented at the spring meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla, April 25-29, 1974. Reprint requests to C. S. O'Brien Library, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242
(Dr Watzke).
Carney, Jr,
MD
lesions, associated mesodermal and
ectodermal anomalies occur. The con¬ dition is probably autosomal domi¬ nant, but is lethal for boys, so most observed cases will be found in girls. The general signs and symptoms consist of the neonatal development of inflammatory vesicles and verrucae scattered over the body, mainly on the trunk and lower extremities. These resolve and leave irregularly pigmented scars in the form of whorls, lines, and patches of pigment. With time, these become depigmented and often are barely recognizable. There is usually a partial alopecia, with delayed dentition and malformed teeth. A few patients have neurologic
deficits, such as mental retardation, seizures, and spastic paralysis. Bone
abnormalities occur infrequently. Ocular abnormalities occur in about 35% of patients. The most common is strabismus (18.2%), and the next most common is pseudoglioma that consists of a retrolental mass (15.4%).· Patho¬ logically, this has been found to consist of a total retinal detachment with retinal rosettes and fibrous tissue, characteristic of a retinal dysplasia. Other ocular lesions consist of optic atrophy, cataract, strabismus, blue sclerae, and nystagmus. Conjunctival and retinal pigmentation also have been reported recently.-
SUBJECTS AND METHODS Our first patient was referred to us because of macular vascular anomalies. We also examined the eyes of 19 additional patients with incontinentia pigmenti. All of the patients were in the healed or quiescent phase of the disease. They had been examined previously and reported as having either normal eyes or the usual ocular changes that are well known to occur in incontinentia pigmenti. There was no history of prematurity or oxygen adminis¬ tration. Results of hemoglobin electrophoresis performed in one patient (patient
Fig 1.—Temporal fundus periphery of 8year-old girl with incontinentia pigmenti.
Arteries and veins appear normal until equator, where they arborize and form irregular kinked arteriovenous shunts with aneurysmal dilations and masses of dense white preretinal tissue. From this zone to ora, retina is avascular; brown, wavy line lies midway in zone.
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Fig 2.—Higher magnification of area in temporal equator showing sclerotic ghost vessels and clumps, dots and white preretinal tissue.
Retinal Vascular Patient/ Age, yr 1/8
Eye OS
2/12f
OD
3/42t
OD
4/14
OS
masses
Fig 3.—Irregular kinked vessels with abnormal connections and enlargements.
of
in Patients With Incontinentia
Changes
Pigmenti
Ocular
Fundus
Other Ocular
Symptoms
Changes* Temporal RVD,
Signs
None Decreased vi¬ sual acuity Decreased vi¬ sual acuity Decreased visual acuity, vitreous
None
macular RVD Temporal RVD
Optic atrophy OD
Temporal RVD,
Optic atrophy OD
macular RVD
Temporal RVD,
macular RVD
Optic atrophy OS, exotropia OS
hemorrhage
5/2 6/2 7/4 *
t
OD OS OD
None Blind OD, Blind OD,
Temporal OS none OS
none
RVD
Temporal RVD
Temporal
RVD
None
Pseudoglioma OD Pseudoglioma OS
RVD indicates retinal vascular disease. Patients 3 and 2 are mother and daughter.
1) disclosed
a
migration compatible
with
group A hemoglobin. A bizarre and little known retinal vascular abnormality was found to occur in 7 of the 19 patients (Table). The patients had no symptoms asso¬ ciated with the retinal vascular disorder, and, with the exception of five who had either recognizable optic atrophy or pseu¬ doglioma, all had 6/6 or 6/7 vision. One patient (patient 4) had a history of vitreous hemorrhage, which cleared spontaneously.
FUNDUS FINDINGS The fundus findings may be divided into peripheral, macular and fluorescein changes.
Peripheral Fundus Changes The peripheral changes consisted of an aberrant retinal vascularization and hypoplasia. As the retinal vessels approached the temporal equator,
both venules and arterioles became tortuous, kinked, and irregular in caliber (Fig 1 to 3). They arborized at the equator and connected in the form of arteriovenous anastomoses. Aneurysmal-like dilations and branching frond-like clusters of new vessels occurred. From this equatorial zone of abnormal vascularization to the ora serrata, the peripheral temporal part of the retina was completely avascular. While some vessels carried blood, others were completely sclerotic, and consisted of white lines or ghost
Fig 4.—Posterior pole of 8-year-old girl with incontinentia pigmenti showing small intraretinal aneurysmal-like dilations of paramacular venules, intraretinal di¬ lated microvascular anomalies, and white dots and clumps of preretinal tissue clus¬ tered about macula. fibrous tissue was quite dense and opaque. A more subtle peripheral change consisted of a difference in color or texture of the very peripheral avas¬ allar retina (Fig 1). Midway between the equator and the ora, the retina changed from a normal reddish color to a whiter more fibrotic and less transparent membrane. The demarca¬ tion between these two zones was marked by a wavy brownish line similar to an angioid streak. This appeared deep to the retina, near the
pigment epithelium. In
area
eye. Macular
vessels. Both on the retinal surface and over it were dots, clumps, and larger masses of white tissue. Much of this tissue projected from the vessels into the vitreous. Some tissues originated from the vessels, but others occurred independently of vessels. Some of the
one
where the brownish line intersected the long posterior ciliary artery and nerve, the line continued uninter¬ rupted, which indicates that it was internal to this structure. Of seven patients with this condi¬ tion, five had unilateral changes with¬ out any abnormalities visible in the fundus of the fellow eye. Two patients had bilateral changes, each with the vascular abnormalities heretofore described in one eye and a typical pseudoglioma retinae in the opposite
Changes
patient, the macula of the same eye with peripheral involvement In
one
also the site of vascular abnormal¬ (Pig 4). These consisted of kinked, tortuous vessels usually ema¬ nating from paramacular venules. What at first appeared to be hemwas
ities
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5 —Fluorescein angiograms of same area as Fig 2. There is early perfusion of abnormal arteries and veins, with late intraretinal shunts and microvascular anomalies. Note lack of perfusion peripheral to equator.
Fig
or microaneurysms, close examination showed were terminal enlargements of these abnormal ves¬ sels. Other vascular anomalies consisted of short segments of dilated almost capillary-sized vessels that could not be seen to originate from any visible larger arterioles or venules. They resembled the intraretinal microvas¬ cular anomalies seen at some stages of diabetic retinopathy. In the macular area, there were also a few fibrotic round opacities that appeared on the surface of the retina and resembled the fibrotic paravascular and preretinal changes seen in the periphery. Central vision was unaffected by these macular changes.
orrhages
Fluorescein
one year, only one patient (patient 1) has shown progres¬
six months to
sion of the vascular lesions. This patient was an alert and intelligent 8-
year-old girl (Table). During 21 months, the equatorial vascular ano-
leakage
from
progressively enlarged in one quadrant (Fig 6, top left and right). There was a fusiform growth of the mass to a sinusoid-like lesion approxi¬ mately one third of the disc diameter. Bordering this, there was an increase malíes
Fig 6—During 21-month interval, vascular anomalies enlarged with development of cavity filled with blood (arrow) (top left and right). Photocoagulation was performed (bottom left), and six months later, lesion is scarred and quiescent (bottom right).
sinusoid
Angiographie Changes
Fluorescein angiography was per¬ formed in two patients who were old enough to be cooperative (Fig 5). The abnormal vessels and terminal dilated segments filled with fluorescein early and leaked fluorescein through their walls into the vitreous. Both the abnormal shunts and interconnections and kinked, tortuous, terminal vessels in the macula and in the periphery showed this late leakage. There was no perfusion of the sclerotic ghost vessels or the white preretinal fibrotic tissue, and there was no perfusion of fluorescein into the avascular periph¬ eral zone of the temporal part of the retina. CLINICAL COURSE For a follow-up period ranging from
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of fibrotic tissue. No changes in the macular lesions have occurred. Because of this enlargement, this patient received photocoagulation with the light coagulator (Zeiss) under general anesthesia (Fig 6, bottom left). The fusiform hemorrhagic mass was eliminated and there has been no enlargement of the lesion during the past 6 months (Fig 6, bottom right). COMMENT
To our knowledge, three reports of retinal vascular anomalies associated with incontinentia pigmenti exist in the world literature. The report by Lieb and Guerry lists vessel changes in the posterior pole that consisted mainly of dilated tortuous arteries and veins with an exudative chorioretinitis-like response.·1 There are two very recent reports of single patients with peripheral vascu¬ lar changes that consisted of ectatic veins and pathologic anastomoses.1 :' In both of these cases, the retina was avascular at the periphery of temporal area.
It may be that pseudoglioma may be the end stage of this asymptomatic retinal vascular abnormality. So far, only one of our patients has shown evidence of progression to a point where treatment by photocoagulation seemed advisable. Photocoagulation was attempted in one eye of Best and Rentsch's patient and was not re¬ ported as having arrested the progres¬ sive changes.1 None of our patients have progressed to the point of a pseudoglioma, but, on prolonged fol¬ low up, this may well occur. The value of photocoagulation is unknown, but we certainly intend to use it in the presence of abnormal vessels that leak fluorescein and appear to cause exudative and fibrotic reaction in the surrounding retina and vitreous. Of the seven patients with this condition, one is 42 years old with typical vascular changes but with no history of loss of vision since child¬ hood. One patient was 12 years old and another was 14 years old, and neither has had any history of progressive visual loss or signs of progression
during a six-month period of observa¬ tion. The one patient who has shown progressive change is 8 years old. Therefore, a uniformly pessimistic prognosis is probably not warranted. What can explain this association
between this rare skin disease and aberrant retinal vascularization? The old pathological concept of incontinentia pigmenti was that the disease was an inflammatory re¬ sponse to pigment released from incontinent pigment cells. This is no longer tenable. The disease is now classified as genodermatosis, ie, a dermatologie disease caused by an inherited gene or chromosomal aber¬ ration." Recently, evidence has appeared that certain dermatologie conditions may stem from an epidermal cellular response to abnormal or altered melanin in the underlying dermis.7 Silverstein, in a recent experimental study, was able to produce extensive retinal dysplasia and rosette forma¬ tion following trauma to the pigment epithelium in the developing eye of the fetal lamb.s The concept of a retinal dysplasia caused by abnormal or altered melanin in the underlying pigment epithelium could explain an otherwise puzzling series of anomalies of two seemingly unrelated organ
systems. These retinal vascular changes also have a striking similarity to the vascular lesions of early retrolental fibroplasia. Both have abnormal arteriovenous connections and intraret¬ inal microvascular anomalies at the temporal equator. This zone of vascu¬ lar anomalies formed even a pseudodemarcation line in a few patients. Preretinal fibrotic tissue is present in both conditions, and both show no retinal perfusion peripheral to the
equator.
The two conditions are dissimilar, however, in the unilaterality and posterior pole changes of inconti¬ nentia pigmenti. Although there is a superficial resemblance to the retinal vascular changes of sickle cell hemoglobinopathy, the incontinentia pigmenti eyes do not show the multiple stages of
occlusion, hemorrhage, and prolifera¬
tion that are seen in active sickle cell disease. This report adds yet another sys¬ temic condition to the numerous syndromes associated with retinal vascular disease. It demonstrates that the developing retinal vasculature has a limited and patterned response to many different stimuli, if applied at the appropriate time in its develop¬ ment.
All patients with a history of incon¬ tinentia pigmenti should have a complete fundus examination that includes indirect ophthalmoscopy and contact lens examination. The skin lesions fade with age, and, unless specifically examined by an expert, the dermatologie diagnosis is difficult to make in the adult. Because of this, it is likely that this skin condition is not as rare as the dearth of reports indicates. Incontinentia pigmenti certainly should be considered in the differen¬ tial diagnosis of retinal vascular disease in a female patient. In such patients, follow-up examinations are mandatory, and photocoagulation therapy may prove beneficial. This study was supported by grant rr-59 from the General Clinical Research Centers Program, Division of Research Resources, National Insti¬
tutes of Health.
Robert Keller, MD, referred patient 1. Robert allowed us to examine the 19 other
Carney, MD, patients.
References 1. Carney RG: Incontinentia pigmenti: A world statistical analysis. Arch Dermatol to be
published. 2. McCrary JA, Smith JL: Conjunctival and retinal incontinentia pigmenti. Arch Ophthalmol
79:417-422, 1968. 3. Lieb WA, Guerry D: Fundus changes in
incontinentia pigmenti. Am J Ophthalmol 45:265\x=req-\
271, 1958.
4. Best W, Rentsch F: \l=U"\berdas pseudoglom bei der incontinentia pigmenti. Klin Monatsbl
Augenheilkd 165:19-32, 1974. 5. Krey H, Laux U: Netzh\l=a"\utgessver\l=a"\nderungen bei Incontinentia pigmenti (Bloch-Sulzberger Syndrome). Klin Monatsbl Augenheilkd 164:138-142, 1974. 6.
Montgomery
H:
Dermatopathology.
New
York, Harper & Row Publishers, 1967, vol 1, p 104. 7.
Roenigk HH, Deadhar SS, Krebs JA, et al: Immunological studies in halo nevus, vitiligo, alopecia areata, and malignant melanoma. Arch Dermatol to be published. 8. Silverstein AM: Retinal dysplasia induced by experimental intrauterine trauma. Am J Ophthalmol 77:51-58, 1974.
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pigmenti, anomaly
equator, with no perfusion peripheral to it. In one patient, the vascular changes progressed and required photocoagulation. This retinal lesion may represent an early stage of the pseudoglioma that so commonly is reported with this skin disease. Incontinentia pigmenti should be considered in the differential diagnosis of retinal vascular disease in girls and women of any age.
(Arch Ophthalmol 94:743-746, 1976)
Incontinentia
pigmenti is a rare skin disease in infant girls that is char¬ acterized by recurrent vesiculobullous
dermatitis that resolves spontaneous¬ ly and leaves irregularly pigmented atrophie scars on the trunk and lower extremities. In addition to the skin Accepted
for publication April 15, 1975. From the departments of ophthalmology, University of Iowa College of Medicine, Iowa City (Dr Watzke), and the University of Wisconsin Medical School, Madison (Dr Stevens). Dr Carney is in private practice in Decatur, Ill. Presented at the spring meeting of the Association for Research in Vision and Ophthalmology, Sarasota, Fla, April 25-29, 1974. Reprint requests to C. S. O'Brien Library, Department of Ophthalmology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242
(Dr Watzke).
Carney, Jr,
MD
lesions, associated mesodermal and
ectodermal anomalies occur. The con¬ dition is probably autosomal domi¬ nant, but is lethal for boys, so most observed cases will be found in girls. The general signs and symptoms consist of the neonatal development of inflammatory vesicles and verrucae scattered over the body, mainly on the trunk and lower extremities. These resolve and leave irregularly pigmented scars in the form of whorls, lines, and patches of pigment. With time, these become depigmented and often are barely recognizable. There is usually a partial alopecia, with delayed dentition and malformed teeth. A few patients have neurologic
deficits, such as mental retardation, seizures, and spastic paralysis. Bone
abnormalities occur infrequently. Ocular abnormalities occur in about 35% of patients. The most common is strabismus (18.2%), and the next most common is pseudoglioma that consists of a retrolental mass (15.4%).· Patho¬ logically, this has been found to consist of a total retinal detachment with retinal rosettes and fibrous tissue, characteristic of a retinal dysplasia. Other ocular lesions consist of optic atrophy, cataract, strabismus, blue sclerae, and nystagmus. Conjunctival and retinal pigmentation also have been reported recently.-
SUBJECTS AND METHODS Our first patient was referred to us because of macular vascular anomalies. We also examined the eyes of 19 additional patients with incontinentia pigmenti. All of the patients were in the healed or quiescent phase of the disease. They had been examined previously and reported as having either normal eyes or the usual ocular changes that are well known to occur in incontinentia pigmenti. There was no history of prematurity or oxygen adminis¬ tration. Results of hemoglobin electrophoresis performed in one patient (patient
Fig 1.—Temporal fundus periphery of 8year-old girl with incontinentia pigmenti.
Arteries and veins appear normal until equator, where they arborize and form irregular kinked arteriovenous shunts with aneurysmal dilations and masses of dense white preretinal tissue. From this zone to ora, retina is avascular; brown, wavy line lies midway in zone.
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/05/2015
Fig 2.—Higher magnification of area in temporal equator showing sclerotic ghost vessels and clumps, dots and white preretinal tissue.
Retinal Vascular Patient/ Age, yr 1/8
Eye OS
2/12f
OD
3/42t
OD
4/14
OS
masses
Fig 3.—Irregular kinked vessels with abnormal connections and enlargements.
of
in Patients With Incontinentia
Changes
Pigmenti
Ocular
Fundus
Other Ocular
Symptoms
Changes* Temporal RVD,
Signs
None Decreased vi¬ sual acuity Decreased vi¬ sual acuity Decreased visual acuity, vitreous
None
macular RVD Temporal RVD
Optic atrophy OD
Temporal RVD,
Optic atrophy OD
macular RVD
Temporal RVD,
macular RVD
Optic atrophy OS, exotropia OS
hemorrhage
5/2 6/2 7/4 *
t
OD OS OD
None Blind OD, Blind OD,
Temporal OS none OS
none
RVD
Temporal RVD
Temporal
RVD
None
Pseudoglioma OD Pseudoglioma OS
RVD indicates retinal vascular disease. Patients 3 and 2 are mother and daughter.
1) disclosed
a
migration compatible
with
group A hemoglobin. A bizarre and little known retinal vascular abnormality was found to occur in 7 of the 19 patients (Table). The patients had no symptoms asso¬ ciated with the retinal vascular disorder, and, with the exception of five who had either recognizable optic atrophy or pseu¬ doglioma, all had 6/6 or 6/7 vision. One patient (patient 4) had a history of vitreous hemorrhage, which cleared spontaneously.
FUNDUS FINDINGS The fundus findings may be divided into peripheral, macular and fluorescein changes.
Peripheral Fundus Changes The peripheral changes consisted of an aberrant retinal vascularization and hypoplasia. As the retinal vessels approached the temporal equator,
both venules and arterioles became tortuous, kinked, and irregular in caliber (Fig 1 to 3). They arborized at the equator and connected in the form of arteriovenous anastomoses. Aneurysmal-like dilations and branching frond-like clusters of new vessels occurred. From this equatorial zone of abnormal vascularization to the ora serrata, the peripheral temporal part of the retina was completely avascular. While some vessels carried blood, others were completely sclerotic, and consisted of white lines or ghost
Fig 4.—Posterior pole of 8-year-old girl with incontinentia pigmenti showing small intraretinal aneurysmal-like dilations of paramacular venules, intraretinal di¬ lated microvascular anomalies, and white dots and clumps of preretinal tissue clus¬ tered about macula. fibrous tissue was quite dense and opaque. A more subtle peripheral change consisted of a difference in color or texture of the very peripheral avas¬ allar retina (Fig 1). Midway between the equator and the ora, the retina changed from a normal reddish color to a whiter more fibrotic and less transparent membrane. The demarca¬ tion between these two zones was marked by a wavy brownish line similar to an angioid streak. This appeared deep to the retina, near the
pigment epithelium. In
area
eye. Macular
vessels. Both on the retinal surface and over it were dots, clumps, and larger masses of white tissue. Much of this tissue projected from the vessels into the vitreous. Some tissues originated from the vessels, but others occurred independently of vessels. Some of the
one
where the brownish line intersected the long posterior ciliary artery and nerve, the line continued uninter¬ rupted, which indicates that it was internal to this structure. Of seven patients with this condi¬ tion, five had unilateral changes with¬ out any abnormalities visible in the fundus of the fellow eye. Two patients had bilateral changes, each with the vascular abnormalities heretofore described in one eye and a typical pseudoglioma retinae in the opposite
Changes
patient, the macula of the same eye with peripheral involvement In
one
also the site of vascular abnormal¬ (Pig 4). These consisted of kinked, tortuous vessels usually ema¬ nating from paramacular venules. What at first appeared to be hemwas
ities
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/05/2015
5 —Fluorescein angiograms of same area as Fig 2. There is early perfusion of abnormal arteries and veins, with late intraretinal shunts and microvascular anomalies. Note lack of perfusion peripheral to equator.
Fig
or microaneurysms, close examination showed were terminal enlargements of these abnormal ves¬ sels. Other vascular anomalies consisted of short segments of dilated almost capillary-sized vessels that could not be seen to originate from any visible larger arterioles or venules. They resembled the intraretinal microvas¬ cular anomalies seen at some stages of diabetic retinopathy. In the macular area, there were also a few fibrotic round opacities that appeared on the surface of the retina and resembled the fibrotic paravascular and preretinal changes seen in the periphery. Central vision was unaffected by these macular changes.
orrhages
Fluorescein
one year, only one patient (patient 1) has shown progres¬
six months to
sion of the vascular lesions. This patient was an alert and intelligent 8-
year-old girl (Table). During 21 months, the equatorial vascular ano-
leakage
from
progressively enlarged in one quadrant (Fig 6, top left and right). There was a fusiform growth of the mass to a sinusoid-like lesion approxi¬ mately one third of the disc diameter. Bordering this, there was an increase malíes
Fig 6—During 21-month interval, vascular anomalies enlarged with development of cavity filled with blood (arrow) (top left and right). Photocoagulation was performed (bottom left), and six months later, lesion is scarred and quiescent (bottom right).
sinusoid
Angiographie Changes
Fluorescein angiography was per¬ formed in two patients who were old enough to be cooperative (Fig 5). The abnormal vessels and terminal dilated segments filled with fluorescein early and leaked fluorescein through their walls into the vitreous. Both the abnormal shunts and interconnections and kinked, tortuous, terminal vessels in the macula and in the periphery showed this late leakage. There was no perfusion of the sclerotic ghost vessels or the white preretinal fibrotic tissue, and there was no perfusion of fluorescein into the avascular periph¬ eral zone of the temporal part of the retina. CLINICAL COURSE For a follow-up period ranging from
Downloaded From: http://archopht.jamanetwork.com/ by a University of Arizona Health Sciences Library User on 06/05/2015
of fibrotic tissue. No changes in the macular lesions have occurred. Because of this enlargement, this patient received photocoagulation with the light coagulator (Zeiss) under general anesthesia (Fig 6, bottom left). The fusiform hemorrhagic mass was eliminated and there has been no enlargement of the lesion during the past 6 months (Fig 6, bottom right). COMMENT
To our knowledge, three reports of retinal vascular anomalies associated with incontinentia pigmenti exist in the world literature. The report by Lieb and Guerry lists vessel changes in the posterior pole that consisted mainly of dilated tortuous arteries and veins with an exudative chorioretinitis-like response.·1 There are two very recent reports of single patients with peripheral vascu¬ lar changes that consisted of ectatic veins and pathologic anastomoses.1 :' In both of these cases, the retina was avascular at the periphery of temporal area.
It may be that pseudoglioma may be the end stage of this asymptomatic retinal vascular abnormality. So far, only one of our patients has shown evidence of progression to a point where treatment by photocoagulation seemed advisable. Photocoagulation was attempted in one eye of Best and Rentsch's patient and was not re¬ ported as having arrested the progres¬ sive changes.1 None of our patients have progressed to the point of a pseudoglioma, but, on prolonged fol¬ low up, this may well occur. The value of photocoagulation is unknown, but we certainly intend to use it in the presence of abnormal vessels that leak fluorescein and appear to cause exudative and fibrotic reaction in the surrounding retina and vitreous. Of the seven patients with this condition, one is 42 years old with typical vascular changes but with no history of loss of vision since child¬ hood. One patient was 12 years old and another was 14 years old, and neither has had any history of progressive visual loss or signs of progression
during a six-month period of observa¬ tion. The one patient who has shown progressive change is 8 years old. Therefore, a uniformly pessimistic prognosis is probably not warranted. What can explain this association
between this rare skin disease and aberrant retinal vascularization? The old pathological concept of incontinentia pigmenti was that the disease was an inflammatory re¬ sponse to pigment released from incontinent pigment cells. This is no longer tenable. The disease is now classified as genodermatosis, ie, a dermatologie disease caused by an inherited gene or chromosomal aber¬ ration." Recently, evidence has appeared that certain dermatologie conditions may stem from an epidermal cellular response to abnormal or altered melanin in the underlying dermis.7 Silverstein, in a recent experimental study, was able to produce extensive retinal dysplasia and rosette forma¬ tion following trauma to the pigment epithelium in the developing eye of the fetal lamb.s The concept of a retinal dysplasia caused by abnormal or altered melanin in the underlying pigment epithelium could explain an otherwise puzzling series of anomalies of two seemingly unrelated organ
systems. These retinal vascular changes also have a striking similarity to the vascular lesions of early retrolental fibroplasia. Both have abnormal arteriovenous connections and intraret¬ inal microvascular anomalies at the temporal equator. This zone of vascu¬ lar anomalies formed even a pseudodemarcation line in a few patients. Preretinal fibrotic tissue is present in both conditions, and both show no retinal perfusion peripheral to the
equator.
The two conditions are dissimilar, however, in the unilaterality and posterior pole changes of inconti¬ nentia pigmenti. Although there is a superficial resemblance to the retinal vascular changes of sickle cell hemoglobinopathy, the incontinentia pigmenti eyes do not show the multiple stages of
occlusion, hemorrhage, and prolifera¬
tion that are seen in active sickle cell disease. This report adds yet another sys¬ temic condition to the numerous syndromes associated with retinal vascular disease. It demonstrates that the developing retinal vasculature has a limited and patterned response to many different stimuli, if applied at the appropriate time in its develop¬ ment.
All patients with a history of incon¬ tinentia pigmenti should have a complete fundus examination that includes indirect ophthalmoscopy and contact lens examination. The skin lesions fade with age, and, unless specifically examined by an expert, the dermatologie diagnosis is difficult to make in the adult. Because of this, it is likely that this skin condition is not as rare as the dearth of reports indicates. Incontinentia pigmenti certainly should be considered in the differen¬ tial diagnosis of retinal vascular disease in a female patient. In such patients, follow-up examinations are mandatory, and photocoagulation therapy may prove beneficial. This study was supported by grant rr-59 from the General Clinical Research Centers Program, Division of Research Resources, National Insti¬
tutes of Health.
Robert Keller, MD, referred patient 1. Robert allowed us to examine the 19 other
Carney, MD, patients.
References 1. Carney RG: Incontinentia pigmenti: A world statistical analysis. Arch Dermatol to be
published. 2. McCrary JA, Smith JL: Conjunctival and retinal incontinentia pigmenti. Arch Ophthalmol
79:417-422, 1968. 3. Lieb WA, Guerry D: Fundus changes in
incontinentia pigmenti. Am J Ophthalmol 45:265\x=req-\
271, 1958.
4. Best W, Rentsch F: \l=U"\berdas pseudoglom bei der incontinentia pigmenti. Klin Monatsbl
Augenheilkd 165:19-32, 1974. 5. Krey H, Laux U: Netzh\l=a"\utgessver\l=a"\nderungen bei Incontinentia pigmenti (Bloch-Sulzberger Syndrome). Klin Monatsbl Augenheilkd 164:138-142, 1974. 6.
Montgomery
H:
Dermatopathology.
New
York, Harper & Row Publishers, 1967, vol 1, p 104. 7.
Roenigk HH, Deadhar SS, Krebs JA, et al: Immunological studies in halo nevus, vitiligo, alopecia areata, and malignant melanoma. Arch Dermatol to be published. 8. Silverstein AM: Retinal dysplasia induced by experimental intrauterine trauma. Am J Ophthalmol 77:51-58, 1974.
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