A clinical and molecular genetic analysis of solitary ocular angioma

doi:10.1016/S0161-6420(99)90127-6

Ophthalmology

Volume 106, Issue 3, 1 March 1999, Pages 623-629

Presented in part as a poster at the Association for Research in Vision and Ophthalmology annual meeting, Fort Lauderdale, Florida, May 1997.

https://doi.org/10.1016/S0161-6420(99)90127-6 Get rights and content

Abstract

Objectives

To determine whether ocular angioma can occur in the absence of von Hippel Lindau (VHL) syndrome, to define the clinical characteristics of sporadic (non-VHL) angioma, and to estimate a prevalence for sporadic ocular angioma.

Design and participants

A cross-sectional study of a cohort of patients with apparent sporadic ocular angiomatosis recruited from throughout the United Kingdom.

Intervention

Clinical details and a family history were obtained for the patients in the cohort. Systematic ocular examination and further systemic screening were performed on the patients and relatives when possible. Leukocyte DNA was examined for VHL germline mutations.

Main outcome measures

Patients with solitary and typical VHL-like ocular angioma, without clinical and family histories for VHL, were selected as possible sporadic (non-VHL) ocular angioma cases. An estimate of the population prevalence of sporadic (non-VHL) ocular angioma was made from patients presenting in the East Anglian region of the United Kingdom over a 25-year period.

Results

From 32 patients referred, 17 had typical solitary ocular angioma and no evidence of other VHL complications in themselves or in family members. All 17 patients were negative for germline VHL mutations. The mean age of presentation was 30.9 years (median, 27.5; range, 3–52); 11 of 17 eyes suffered visual loss and 4 of 17 tumors occurred on the optic disc. The estimated prevalence of non-VHL ocular angioma was 9.0 × 10⁻⁶, 95% confidence interval (CI) = 3.3 − 19 × 10⁻⁶ (1 in 110,000 persons, 95% CI = 1 in 53,000–300,000).

Conclusions

Sporadic ocular angioma can occur in the absence of VHL disease but appears less prevalently than VHL itself. The age of presentation, degree of visual morbidity, complications, morphology, and anatomic location of tumors are similar to those seen in VHL disease.

Section snippets

Ascertainment of cases

Patients with a solitary ocular angioma were ascertained by contacting all ophthalmic and clinical genetics departments in the United Kingdom. Full informed consent was given by each individual after an explanation of the intended research and the nature of the interview and examination. The research had been approved by the ethics committees at Addenbrooke’s Hospital, Cambridge, and at Moorfields Eye Hospital, London.

Patient interview and examination

Full documentation of each patient’s family history and medical history was

Patient details

Thirty-two individuals (13 male, 19 female) were referred for possible inclusion, but after assessment and investigation, 15 were excluded because (1) the clinical appearance of the ocular lesion or lesions was not typical of VHL ocular angioma, but instead resembled retinal telangiectasia or pseudoangioma2, 3, 21, 22 (n = 14); and (2) there were numerous ocular VHL-like angiomas suggesting underlying VHL disease (n = 1). There remained 17 patients (5 males 12 females, P = 0.14) with solitary

Discussion

The ocular lesions originally characterized by Eugene von Hippel26 have been known to be associated with the other manifestations of VHL since Arvid Lindau’s work in the 1920s.27, 28 The clinical manifestations of these ocular lesions are distinct and have been described in detail elsewhere.1, 4, 24 They can be distinguished clinically from other lesions, such as those that occur in Coats disease and similar retinopathies, arterial macroaneurysms, and from the diverse group of vascular lesions

Acknowledgements

The authors thank the many ophthalmologists and clinical geneticists throughout the United Kingdom who made this study possible and who referred patients and allowed access to their facilities for examination purposes. The cases in this study include those referred by Mr. T. A. G. Bell, Mr. L. Benjamin, Mr. J. Bolger, Mr. S. J. Charles, Mr. P. M. Jacobs, Miss J. E. Milson, Mr. J. D. Scott, Mr. G. Woodruff, and Professor I. Young. The authors also thank the patients and their families who gave

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Cited by (49)

Retinal angioma of Von hippel-lindau disease: A case report
2022, Annals of Medicine and Surgery
Citation Excerpt :
The first descriptions of this vascular retinal tumour by Eugen von Hippel were made between 1867 and 1939 [2]. The description was more detailed on the vascular nature of the disease, and since then the term retinal angiomatosis was adopted [3–5]. The genetic nature of the disease was first described by Collins [6,7].
Von Hippel–Lindau disease (VHL), also known as Von Hippel–Lindau syndrome, is a rare genetic disorder with multisystem involvement. It is characterised by the development of multiple vascularised tumours, particularly cerebellar, retinal and/or visceral. The disease can occur at any age and usually starts with retinal hemangioblastomas.
We report the case of a 45-year-old female patient with no particular pathological history, who. consulted the ophthalmology department for a change of optical correction.
The funds examination showed an uncomplicated bilateral hemangioma with no other associated signs. Fluorescein angiography confirmed the diagnosis by showing in the left eye a multiple retinal hemangioma visible in the mid-periphery facing the branches of the superior temporal arches. The brain MRI showed a multifocal hemangioblastoma in the posterior cerebral fossa. A renal ultrasound returned normal. The patient had undergone photocoagulation of the retinal lesions to avoid any complications.
The German ophthalmologist Eugen von Hippel first described angiomas in the eye. The term Von Hippel–Lindau disease was first used in 1936; however, its use became common only in the 1970s.
Tumours called hemangioblastomas are characteristic of von Hippel-Lindau syndrome. These growths are made of newly formed blood vessels and occurs in the periphery of the retina. Spontaneous progression occurs leading to visual impairment as a result of maculopathy or exudative retinal detachment.
Early recognition and treatment of specific manifestations of VHL can substantially decrease complications and improve quality of life.
Conventional treatment of the retinal hemangioblastomas is laser photocoagulation or cryotherapy depending on the location and size of the lesions. It must be based on the patient's visual symptoms and tumor progression.
Management of patients with VHL disease often requires a multidisciplinary approach. The role of the ophthalmologist is important in the management of this condition since the ocular involvement may be indicative of the disease.
Intravitreal bevacizumab for retinal capillary hemangioblastoma: A case series and literature review
2014, Canadian Journal of Ophthalmology
To evaluate the long-term outcomes of intravitreal bevacizumab for peripheral and juxtapapillary retinal capillary hemangioblastoma (RCH).
We conducted a retrospective noncomparative interventional case series.
There were 4 patients (5 eyes) presenting with RCH.
Five eyes with RCH presented with exudative changes and visual loss. Three eyes of 2 patients with peripheral RCH were treated with cryotherapy and 2 intravitreal injections of bevacizumab (0.5 mg). Two eyes with juxtapapillary RCH were treated with 3 intravitreal injections of bevacizumab. The main outcome measures were changes in best-corrected visual acuity (BCVA), lesion size, exudation, and retinal thickness.
In peripheral RCH, improvement of BCVA from counting fingers to 20/400 was obtained in 1 eye. One patient with bilateral RCH maintained a vision of 20/20 in 1 eye with complete anatomic regression of the 3 small peripheral RCH lesions. The fellow eye with fibrotic bands from the RCH to the optic nerve head developed a tractional retinal detachment after the first injection and was treated with pars plana vitrectomy. In patients with juxtapapillary RCH, bevacizumab injections resulted in an improvement of BCVA from 20/80 to 20/20 in 1 eye, whereas the second eye did not show an improvement of BCVA despite a regression of the tumour.
Intravitreal anti–vascular endothelial growth factor agents, alone or in combination with other treatment modalities, may improve visual acuity. Further trials evaluating the dose, the number of injections, and the route of administration will be important in advancing antiangiogenic therapies for RCH.
Évaluation des résultats à long terme du bevacizumab par voie vitréenne pour l'hémangiome capillaire rétinien (HCR), périphérique et juxtapapillaire.
Examen rétrospectif non comparatif d'une série de cas d'intervention chez 4 patients (5 yeux) présentant un HRC.
Cinq yeux atteints de HCR présentaient des changements exsudatifs et des pertes visuelles. Trois yeux de deux patients atteints de HRC ont été traités par cryothérapie et 2 injections intravitréennes de bevacizumab (0,5mg). Deux yeux atteints de HCRJ ont été traités par 3 injections intravitréennes de bevacizumab. Les principales mesures obtenues indiquaient des changements de la meilleure acuité visuelle corrigée (MAVC), la taille de la lésion, l'exsudation et l'épaisseur de la rétine.
Chez les HCR périphériques, l'amélioration de la MAVC du compte des doigts à raison de 20/400 avait été obtenue dans un œil. Un patient ayant un HRC bilatéral a maintenu une vision de 20/20 dans un œil avec entière régression anatomique de 3 petits HRC périphériques. L'œil contralatéral, ayant des bandes fibreuses en provenance du HRC jusqu'au nerf optique (%), avait développé un détachement tractionnel de la rétine après la première injection et a été traité par une vitrectomie par la pars plana. Chez les patients ayant un HCRJ les injections de bevacizumab ont obtenu une amélioration de la MAVC de 20/80 à 20/20 dans un œil, alors que le second œil n'a pas manifesté d'amélioration de la MAVC malgré une régression de la tumeur.
L'anti-VEGF intravitréen seul ou en combinaison avec d'autres modes de traitement peut améliorer l'acuité visuelle. D'autres essais d'évaluation de la dose, le nombre d'injections et le cheminement de l'administration seront importants pour faire progresser les thérapies anti-angiogéniques pour le HRC.
VHL Disease
2010, Best Practice and Research: Clinical Endocrinology and Metabolism
Citation Excerpt :
Neurological deficit is usually not reversible after surgery and the outcome depends on the preoperative status of the patient. Retinal capillary angiomas are the typical ocular lesions of VHL disease.15 They occur commonly in individuals affected by VHL and less frequently as a sporadic tumour.
von Hippel-Lindau disease (VHL) disease increases susceptibility to several malignancies, including renal cell carcinoma, haemangioblastomas of the central nervous system or retina and phaeochromocytomas. The VHL tumour suppressor gene, responsible for the disease, encodes for a major regulator of the hypoxic response by targeting the transcription factor hypoxia inducible factor (HIF) for degradation. In this review, we present a synopsis of clinical features of the disease and emphasise unique aspects of VHL syndrome in the paediatric population. Genotype–phenotype associations based on the risk of phaeochromocytoma have pointed to the existence of additional, HIF-independent functions of VHL that remain underexplored. We also examine the progress on these pleiotropic roles of VHL, which contribute to explain clinical features of VHL disease. These advances have important translational implications and are likely to offer a new host of therapeutic options to individuals affected by the disease in the future.
Solitary juxtapapillary capillary retinal angioma and von Hippel-Lindau disease
2007, Canadian Journal of Ophthalmology
Background: The aim of this study was to evaluate patients with solitary juxtapapillary capillary retinal angioma for the presence of von Hippel—Lindau disease (VHL).
Methods: A retrospective case series of 11 patients, each presenting with a solitary juxtapapillary capillary retinal angioma, was examined. Patients were evaluated for type of angioma, presence of other VHL lesions, and mutations of the VHL gene.
Results: Juxtapapillary angioma was exophytic in 7 patients and endophytic in 4 patients. VHL could be diagnosed in 7 patients (64%). Four patients were affected by VHL-related lesions as distinct from ocular angioma. A mutation of the VHL gene could be detected in 6 patients; in 1 of these patients, this mutation of the VHL gene was the only evidence of VHL.There was no difference in the age at manifestation or the type of juxtapapillary angioma in VHL patients compared with non-VHL patients.
Interpretation: A solitary juxtapapillary angioma may indicate the presence ofVHL in a majority of patients, irrespective of the growth pattern of the tumour. Molecular genetic diagnostics is the most effective method of detecting VHL. Because of the high risk of the presence of other VHL lesions,thorough screening for VHL is mandatory for patients presenting with a solitary juxtapapillary angioma.
Contexte: Cette étude avait pour objet d’évaluer la présence du syndrome von Hippel—Lindau (VHL) chez des patients atteints d’un angiome capillaire juxtapapillaire solitaire de la rétine.
Méthodes: On a examiné en rétrospective une série de cas chez 11 patients qui s’étaient présentés avec un angiome capillaire juxtapapillaire de la rétine. On a évalué les patients quant au type d’angiome, à la présence d’autres lésions VHL et aux mutations du gène du VHL.
Résultats: L’angiome juxtapapillaire était exophytique chez 7 patients et endophytique chez les 4 autres. On a pu diagnostiquer le VHL chez 7 patients (64%). Quatre patients étaient affectés par les lésions liées au VHL contrairement à l’angiome oculaire. Une mutation du gène du VHL a pu être dépistée chez 6 patients; chez un de ces derniers, la mutation en question était le seul signe du VHL. Il n’y avait pas de différence d’âge au moment de la manifestation ni quant au type d’angiome juxtapapillaire chez les patients atteints du VHL comparativement aux autres patients.
Interprétation: Un angiome juxtapapillaire solitaire peut indiquer la présence du VHL chez une majorité de patients, quelles que soient les caractéristiques de croissance de la tumeur. Le diagnostic génétique moléculaire est la méthode la plus efficace de dépistage du VHL. À cause du risque élevé de présence des autres lésions VHL, il faut absolument procéder au dépistage méticuleux du VHL chez les patients qui se présentent avec un angiome juxtapapillaire solitaire.
Neuro-oculocutaneous syndromes (phakomatoses)
2007, Clinical Ophthalmic Oncology with CD-ROM
Neuro-Oculocutaneous Syndromes (Phakomatoses)
2007, Clinical Ophthalmic Oncology

View all citing articles on Scopus

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View full text

A clinical and molecular genetic analysis of solitary ocular angioma☆

Abstract

Objectives

Design and participants

Intervention

Main outcome measures

Results

Conclusions

Section snippets

Ascertainment of cases

Patient interview and examination

Patient details

Discussion

Acknowledgements

Ophthalmology

Ophthalmology

Am J Ophthalmol

Am J Hum Genet

Von Hippel-Lindau diseasethe recognition and treatment of early angiomatosis retinae and the use of cryosurgery as an adjunct to therapy

Trans Am Ophthalmol Soc

Discussion

Ophthalmology

Comment onOphthalmology

Clinical features and molecular genetics of Von Hippel-Lindau disease

Ophthalmic Genet

von Hippel-Lindau disease affecting 43 members of a single kindred

Medicine (Baltimore)

Von Hippel-Lindau diseaseclinical and pathological manifestations in nine families with 50 affected members

Arch Intern Med

Clinical features and natural history of von Hippel-Lindau disease

QJ Med

Cerebellar haemangioblastoma and von Hippel-Lindau disease

Brain

Ophthalmological screening for von Hippel-Lindau disease

Eye

Identification of the von Hippel-Lindau disease tumor suppressor gene

Science

Identification of intragenic mutations in the von Hippel-Lindau disease tumour suppressor gene and correlation with disease phenotype

Hum Mol Genet

Germline mutations in the von Hippel-Lindau disease tumor suppressor genecorrelations with phenotype

Hum Mutat

Mutation and cancerstatistical study of retinoblastoma

Proc Natl Acad Sci U S A

Somatic inactivation of the VHL gene in Von Hippel-Lindau disease tumors

Am J Hum Genet

Somatic mutations of the von Hippel-Lindau disease tumour suppressor gene in non-familial clear cell renal carcinoma

Hum Mol Genet