| Retinal
angiomatosis. Ocular manifestation of von Hippel-Lindau disease.Ophthalmologe.
2007 Feb;104(2):107-13.
Von
Hippel-Lindau disease (VHL disease) is a rare multisystem disorder
of autosomal dominant inheritance with high penetrance. Inactivation
of the VHL-protein leads to an increased expression of hypoxia
induced growth factors. Predilection sites for tumor growth are the
retina, the central nervous system and various visceral organs.
Retinal capillary hemangioblastoma is one of the earliest
manifestations of VHL disease. The lifetime risk of permanent visual
loss defined as a visual acuity of 0.5 or less is about 35% in gene
carriers. It increases to 60% if there is already retinal capillary
hemangioblastoma. If VHL disease is suspected, a careful
ophthalmological examination should be included in the clinical
screening program. Having confirmed the diagnosis, regular
ophthalmoscopic monitoring is essential in order to detect
developing tumors at an early stage. Therapeutic options for small
to medium sized peripheral tumors are laser or cryocoagulation;
larger- hemangioblastomas can be treated by brachytherapy using
ruthenium plaques, while asymptomatic juxtapapillary tumors can be
observed at regular intervals.
Capillary
hemangioma of the retina in cases of von Hippel-Lindau syndrome. New
therapeutic directions.Ophthalmologe.
2007 Feb;104(2):114-8.
Thermal
photocoagulation of small peripheral angiomas is the treatment of
choice for capillary hemangiomas in patients with von Hippel-Lindau
disease. Larger peripheral angiomas are better treated with beta-ray
brachytherapy resulting in improved results in terms of local tumor
control and the side effects of treatment. Photodynamic treatment is
an alternative option in the management of capillary hemangiomas of
the retina. Further improvement of the treatment results of
photodynamic therapy may be achieved by combination with
intravitreal drugs. External beam radiation using either
stereotactic techniques or proton radiation must be considered as
experimental. The treatment of juxtapapillary angiomas is still a
therapeutic dilemma. Vitreoretinal surgery should be confined to
advanced stages with tractional detachment or when no other
treatment option is available to salvage the eye.
Retinal capillary
hemangiomas and von Hippel-Lindau disease.Semin
Ophthalmol. 2006 Jul-Sep;21(3):143-50.
von
Hippel-Lindau disease is a multisystem familial cancer syndrome that
commonly manifests in the eye as retinal capillary hemangiomas. As
the earliest manifestation of the disease, these benign hamartomas
can lead to secondary visual loss. Their typical clinical
characteristics can lead to accurate diagnosis and appropriate
treatment with either laser photocoagulation or cryotherapy
enhancing one's probability of preserving vision before becoming
symptomatic. Accurate diagnosis can also lead to surveillance of the
various other organ systems involved in the disease such as the CNS,
kidneys, adrenal glands and pancreas. This will also enable the
clinician to provide genetic counseling for patients regarding the
lifelong manifestations of this disease.
Spontaneous
regression of retinal angiomatous lesions in v. Hippel-Lindau
disease (VHL).Eur
J Med Res. 2005 Dec 7;10(12):532-4.
BACKGROUND:
Very little documentation of spontaneous regression of an
angiomatous retinal lesion in v. Hippel-Lindau disease (VHL) exists.
It is commonly believed that a spontaneous change of hemangiomas
into fibrotic lesions occurred. PATIENTS/METHODS: Follow-up
examinations of four patients with VHL in the Freiburg VHL study
were carried out. RESULTS: A 16-year-old girl revealed a vascular
lesion at the border of the optic disc. Control examination nine
years later revealed complete spontaneous regression of the retinal
vascular changes. A slight retinal vascular change at the superior
border in her right eye was found in a 36-year-old woman. A control
examination 20 years later revealed regression of the lesion. A
41-year-old woman showed in the retinal periphery a small fibrotic
white hemangioma with a pigmented feeder vessel as sign of
spontaneous tumor regression. A 12-year-old boy had a retinal
microaneurysm inferior to the optic disc that disappeared several
years later. CONCLUSION: Documentations of spontaneous regression of
minor angiomatous retinal lesions in VHL exist. Such vascular
changes are rare. Every retinal lesion should be controlled by
follow-up examination and documentation. In case of retinal lesion
growth, treatment is necessary.
Retinal
capillary hemangiomas: clinical manifestations and visual prognosis.Chang
Gung Med J. 2002 Oct;25(10):672-82.
BACKGROUND:
To describe the clinical features, visual outcomes, and therapeutic
complications of patients with retinal capillary hemangiomas.
METHODS: A retrospective, non-comparative, observational case study
of patients diagnosed with retinal capillary hemangiomas was
conducted. Twelve patients (13 eyes) at Chang Gung Memorial Hospital
of Kaohsiung from July 1987 to June 2001 were reviewed. Pre- and
post-treatment visual acuity and ocular complications are described.
RESULTS: One patient had bilateral and another had unilateral
juxtapapillary hemangiomas. All of the other 10 patients were
diagnosed with peripheral retinal capillary hemangiomas. More
patients had retinal capillary hemangiomas located in the temporal
peripheral retina and all had endophytic growth patterns. No patient
met the diagnostic criteria of von Hippel-Lindau disease. Visual
acuity levels of peripheral retinal hemangiomas without exudative
retinal detachment often remained the same after focal laser
treatment. Two patients received vitreoretinal surgery. Patients
with juxtapapillary hemangiomas had variable visual outcomes and
visual field defects during follow-up. CONCLUSION: Early diagnosis
of capillary hemangiomas in the retinal periphery and treatment by
focal laser produced good visual outcomes. If untreated, the tumors
may eventually be complicated with exudative retinal detachment and
have a worse visual prognosis even with vitreoretinal surgery.
Retinal
hemangioblastoma in von Hippel-Lindau disease: a clinical and
molecular study.Invest
Ophthalmol Vis Sci. 2002
Sep;43(9):3067-74.
PURPOSE: To
assess the natural history of retinal manifestations in von
Hippel-Lindau (VHL) disease and to study the genotype-phenotype
correlation. METHODS: Data concerning 103 patients with VHL retinal
manifestations and 108 patients without VHL retinal manifestations
were extracted from the French VHL database. A retrospective study
was performed by questionnaire. Patients were classified into three
visual morbidity groups. Molecular analysis of the VHL gene was
performed in 196 patients. RESULTS: The mean age of ocular
manifestations detection was 24.8 years. In half of the cases, the
ocular manifestations revealed the disease. Half of the cases had
bilateral involvement. Visual morbidity was significantly associated
with the retinal hemangioblastoma count but not with other ocular or
general characteristics. One third of the patients were classified
in the worst visual morbidity group at the end of follow-up.
Mutations were detected in 81% of patients with retinal
hemangioblastomas and in 71% of patients without retinal
involvement. Using a Poisson model and a marginal approach, the
number of hemangioblastomas, age-adjusted, was 2.1 times higher in
patients who had a substitution than in patients with a truncation
(95% CI, 1.05-4.44; P < 0.05). CONCLUSIONS: Visual loss remains one
of the major complications of VHL disease, confirming the importance
of early ophthalmologic screening. Visual morbidity was not related
to the type of extraocular manifestation but appeared to be related
to the type of germline mutation. However, only further genetic and
clinical studies in a larger series of patients will clearly
determine the genotype-phenotype relationship.
Retinal
angiomatosis and von Hippel-Lindau disease.Graefes
Arch Clin Exp Ophthalmol. 2000
Nov;238(11):916-21.
BACKGROUND:
To evaluate the significance of angioma number (single or multiple)
for the presence of von Hippel-Lindau (VHL) disease in patients
presenting with capillary retinal angioma. METHODS: Forty-one
nonrelated patients presenting with capillary retinal angioma were
evaluated. An ophthalmic workup, screening for other organ lesions,
and molecular genetic screening for a mutation of the VHL gene was
performed. The diagnosis of VHL was made on the basis of the
personal and family history, the presence of other VHL-associated
organ lesions, or the presence of a mutation of the VHL gene.
RESULTS: Thirteen patients (32%) presented with a single angioma and
28 patients (68%) presented with multiple angiomas. In 81% of all
patients, VHL could be diagnosed. Diagnosis of VHL could be readily
made by the personal or family history in 51% of all patients. In
another 27% of all patients, VHL disease was evidenced by screening
for other VHL-associated lesions. In two patients (3%) VHL could be
diagnosed by molecular genetics only. All patients with multiple
retinal angiomas had VHL disease and, in 38% of patients with a
single angioma, VHL was present. Reasons for a missing family
history in patients with VHL disease were the presence of a de novo
mutation (15% of VHL patients) or clinical anticipation of VHL
disease (18% of VHL patients). CONCLUSION: The presence of multiple
retinal angiomas strongly suggests VHL disease, which, however, can
be obscured by presence of a de novo mutation or by clinical
anticipation of VHL disease in affected families. A single retinal
angioma may be sporadic as well as the presenting sign of VHL.
Diagnosis and screening for this multitumor syndrome is
substantially supported by molecular genetics.
Hemangioblastomas of the retina: impact of von Hippel-Lindau
disease.
Invest Ophthalmol Vis Sci.
2000 Jun;41(7):1909-15
PURPOSE: To
assess the prevalence of von Hippel-Lindau (VHL) disease and
prognosis of vision in patients with retinal hemangioblastomas (HBs).
METHODS: Thirty-six consecutive patients with retinal HBs were
treated at Helsinki University Hospital between 1974 and 1998.
Detailed neurologic, ophthalmologic, and radiologic examinations;
pedigree; mutation analyses; and collection of all relevant
clinical, imaging, operative, and autopsy data were performed to
identify VHL. RESULTS: The median follow-up time was 10 years. No
patient was lost to follow-up. There were three patient groups: 1)
11 patients with clinically definite VHL; 2) 10 patients with
clinically suspected VHL with more than one retinal HB (5/10) or
visceral cysts (5/10), but with no family history, no detected
germ-line mutations, and no VHL-related neoplasms; and 3) 15
patients without VHL with a single retinal HB but no other data
suggestive of VHL. In the 11 patients with definite VHL, retinal HBs
were detected at a median age of 27 years versus 40 years in the 15
non-VHL patients, and 21 of the 22 eyes were affected. Two VHL
patients were totally blind at the end of follow-up compared with
one legally blind patient with suspected VHL, but none of the non-VHL
patients was blind. The clinical appearance of HBs did not differ
among the patient groups. CONCLUSIONS: The prevalence of VHL among
patients with retinal HBs was 30% to 58% (11-21 of 36). Visual
prognosis was more favorable in non-VHL than VHL patients. All
patients with retinal HB should undergo thorough VHL exclusion.
Clinical
characteristics of ocular angiomatosis in von Hippel-Lindau disease
and correlation with germline mutation.
Arch
Ophthalmol. 1999 Mar;117(3):371-8.
OBJECTIVES:
To examine the epidemiologic and clinical characteristics of the
ocular manifestations of von Hippel-Lindau (VHL) disease and to
detect phenotype-genotype relationships of disease severity. DESIGN:
A cross-sectional clinical and molecular genetic study. PATIENTS AND
METHODS: One hundred eighty-three affected VHL gene carriers from 81
unrelated pedigrees were interviewed and examined; clinical data
were also obtained from 12 living and 39 deceased affected
relatives. DNA extracted from venous blood was used to identify
mutations in the VHL gene. RESULTS: The prevalence of ocular
angiomatosis (hemangioblastomas) in von Hippel-Lindau disease was
67.8% (124/183), and the mean number of angiomas in gene carriers
was 1.85 (range, 0-15). Neither prevalence nor angioma count
increased with age. Severe vision loss in 1 or both eyes was
associated with presentation at a young age. The cumulative
probability of incurring vision loss by age 50 years was 35% in all
gene carriers, 55% in those with angiomatosis, and significantly
worse in those coming to us with symptoms. Angiomas were nonrandomly
distributed in the fundus, occurring rarely at the posterior pole
(1% of retinal tumors) and commonly on the optic disc (8% of eyes)
and supratemporal retina. Complications of ocular angiomatosis
included disc and retinal neovascularization; secondary angioma
formation; retinal detachment, exudation, and membrane; and retinal
and vitreous hemorrhage. Germ-line VHL mutations were detected in
161 of 183 patients and 69 (85%) of 81 pedigrees and included
deletions (n= 16), missense (mutations causing amino acid
substitutions; n = 24), nonsense (premature stop codons; n = 15),
frameshift (n = 13), and splice-site (n = 1) mutations. There was no
association between the type or position of mutation and the
severity of ocular angiomatosis. CONCLUSIONS: A systematic clinical
description of a large cohort of VHL gene carriers further defines
the ocular phenotype. There is no general influence of germline
mutation on severity of ocular disease in VHL. CLINICAL RELEVANCE:
The ophthalmic and molecular genetic description of patients with
VHL disease.
Retinal vascular
hamartoma in von Hippel-Lindau disease.Arch
Ophthalmol. 1995 Sep;113(9):1163-7.
OBJECTIVE:
To diagnose von Hippel-Lindau disease at an early stage in the
presence of atypical retinal lesions. DESIGN: Case series. METHODS:
In an 11-year interdisciplinary clinical follow-up study of von
Hippel-Lindau disease, 52 patients with retinal angiomas were
investigated. RESULTS: Besides retinal angiomas, in five patients
with von Hippel-Lindau disease or in the close relatives of such
patients, unusual retinal vascular hamartomas other than retinal
angiomas were detected. Retinal hamartomas are characterized by
small, moss fiber-like, relatively flat vascular lesions with smooth
and occasionally irregular margins and without enlarged afferent and
efferent vessels. They are located within the superficial retina,
usually adjacent to a retinal vein. In addition to typical
peripheral retinal angiomas, a 28-year-old man with a
pheochromocytoma had a treelike hamartoma. In another family, a
brother and sister both had circumscribed red hamartomas with
irregular outlines close to the retinal vessels. On fluorescein
angiography, the early arterial filling of the hamartomas in two of
these patients was striking. CONCLUSION: It is prudent to be aware
of these unusual vascular retinal changes in von Hippel-Lindau
disease. They may occur in isolation without additional retinal
angiomas (as in four of our patients) but may suggest the presence
of von Hippel-Lindau disease.
Retinal
capillary hemangioma.
J Am Optom Assoc. 1991
Oct;62(10):776-9
Capillary
hemangiomas of the retina, which commonly occur as part of von
Hippel's disease, are classically composed of a retinal capillary
tumor, a large feeder arteriole, and a draining venule. The
fundamental pathology is a hamartomatous lesion. In this paper, the
case of an early, incipient lesion will be presented. Since
approximately 25 percent of patients with angiomatosis retinae
develop the life-threatening von Hippel-Lindau disease, the eye care
practitioner needs to be aware of this condition. Also included in
the discussion are the treatment options available for these retinal
abnormalities.
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