Spotlight Case: A Hereditary Anomaly
A 48-year-old male was referred for evaluation of retinal vascular changes in his left eye. The patient had no visual complaints and denied any ocular or medical history. His family history consisted of unspecified cancer in his father and maternal grandmother, and a review of systems was positive for frequent epistaxis.
Visual acuity (VA) measured 20/20 in both eyes, there was no relative afferent pupillary defect, and intraocular pressure (IOP) was 18 in both eyes. Anterior segment exam was significant for mild vascular tortuosity of conjunctival vessels and mild cataracts in both eyes.
Dilated fundus exam revealed clear vitreous, sharp and pink optic nerves, mild macular RPE mottling, and normal periphery in both eyes. The vasculature was normal in the right eye (Figure 1), but a telangiectatic, branching vascular anomaly concentrated along the papillomacular bundle was found in the left eye (Figure 2).
Fundus photography and a fluorescein angiogram (FA) were obtained. FA was normal in the right eye but revealed arterial filling of a peripapillary vascular malformation in the left eye without leakage (Figures 3 and 4).
Upon further questioning, the patient acknowledged a family history of hemorrhagic telangiectasias.
The differential diagnosis includes peripapillary choroidal neovascular membrane (degenerative, inflammatory/infectious, idiopathic causes), neovascularization of the disc (proliferative diabetic retinopathy, retinal vein occlusion, arterial insufficiency), prepapillary vascular loop, or Bergmeister's papilla. The lack of leakage on FA ruled out a choroidal neovascular membrane and neovascularization of the disc. Furthermore, the extensive branching vascular network would be uncharacteristic of prepapillary vascular loops and a Bergmeister's papilla.
This patient was diagnosed with a retinal vasculature anomaly from hereditary hemorrhagic telangiectasia (HHT, or Osler-Weber-Rendu disease).
HHT is a rare autosomal dominant disorder characterized by abnormal mucocutaneous telangiectasias and arteriovenous malformations (AVMs), which have a tendency to bleed. These vascular abnormalities most commonly occur in the:
- Oral cavity
- Central nervous system
- Abdominal viscera
The reported annual incidence is 1 to 2 cases per 100,000 population, with an overall prevalence of approximately 1 to 2 cases per 10,000 population. It occurs with equal frequency in men and women and is most common among whites.
Due to the rare nature of HHT, most literature sources involve retrospective case series which report ocular involvement in 45% to 65% of patients. The most common ophthalmic finding is conjunctival telangiectasias with hematic epiphora (32% to 65%). "Mulberry-like" iris vascular malformations at the pupillary margin have been associated with spontaneous hyphema.
Vascular abnormalities of the posterior segment have been identified in up to 37% of reported case series. The first description was published by Francois in 1938, and subsequent literature have described a variety of retinal findings including[5-7]:
- Vessel tortuosity/dilation
- Fusiform aneurysms
- Perivascular hemorrhage/exudates
- Artery occlusions
- Ectatic optic nerve vessels
Vascular abnormalities may present diffusely throughout the retina or may be located in the macula, leading to vision loss.[3,8]
Choroidal changes have also been noted with choriocapillaris atrophy or choroidal telangiectasias, in the form of prominent choroidal vessels with associated serous retinal pigment epithelial detachments.[4,9] Nonsimultaneous choroidal hemorrhages have been reported intraoperatively during a vitrectomy for 1 eye and after an uncomplicated cataract surgery in the other eye.
Symptomatic macular telangiectasias have been treated with photodynamic therapy (PDT), and cryotherapy and photocoagulation have been used for recurrent vitreous hemorrhage and neovascularization.[6,8] Although anti-VEGF therapy would likely help manage complications from abnormal vasculature changes, no use of anti-VEGF agents has been reported in literature.
HHT affects many parts of the body including:
- Oral cavity
- Central nervous system
- Abdominal viscera
Patients commonly present with recurrent epistaxis episodes and skin telangiectasia. More serious ailments include dyspnea on exertion, GI bleeding, and strokes from hemorrhage or arteriovenous shunting through abnormal vessels.
Symptom onset is often delayed until the fourth decade of life, with about 90% of patients manifesting by age 40. The prognosis varies, and life expectancy can approach that of the normal population with appropriate screening and aggressive medical/surgical management of bleeding.
HHT is a clinical diagnosis based on the presence of recurrent epistaxis, mucocutaneous telangiectasias, visceral AVMs, and history of first-degree relatives with HHT (Curacao criteria). Genetic testing can confirm the presence of:
- Mutations within endoglin
- Activin receptor-like kinase type I
- SMAD4 genes
Because of AVMs and associated sequelae, evaluation by a primary care physician should include:
- Thorough physical exam
- Complete blood count
- Coagulation profile to exclude concurrent coagulopathy
- Urinalysis to screen for hematuria
- Hemoccult test
- Liver function tests
Further work-up may include:
- CT scan and MRI techniques to screen for cerebral, pulmonary, or abdominal visceral AVMs
- Cardiac echocardiography for intracardiac shunts
- Upper/lower endoscopy for GI bleeding
- HHT is a rare autosomal dominant disorder characterized by mucocutaneous telangiectasias and arteriovenous malformations throughout the body, which have a tendency to bleed.
- Conjunctival telangiectasias is the most common ocular manifestation, but vascular malformations of the posterior segment have been reported in up to 37% of reported case series.
- While these vascular changes often do not affect vision, the treatment of symptomatic telangiectatic vessels and neovascularization has not been well described yet.
- Complications of HHT are potentially serious and can not only lead to vision loss but can also lead to heavy bleeding, organ dysfunction, stroke, and even death.
1. Begbie ME, Wallace GM, Shovlin CL. Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century. Postgrad Med J. 2003;79(927):18-24. doi:10.1136/pmj.79.927.18.
2. Green WR. Ophthalmic pathology: an atlas and textbook. 4th ed. WB Saunders, Philadelphia, 1996; 1128.
3. Cota NR, Peckar CO. Spontaneous hyphema in hereditary hemorrhagic telangiectasia. Br J Ophthalmol. 1998;82(9):1093. doi:10.1136/bjo.82.9.1090d.
4. Rinaldi M, Buscarini E, Danesino C, et al. Ocular manifestations in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): a case-series [published online December 21, 2010]. Ophthalmic Genet. 2011;32(1):12-17. doi:10.3109/13816810.2010.535891.
5. Davis DG, Smith JL. Retinal involvement in hereditary hemorrhagic telangiectasia. Arch Ophthalmol. 1971;85(5):618–623. doi:10.1001/archopht.1971.00990050620018.
6. Francois J. L'amgiomatose hemorragique familiale et ses complication oculaires. Arch Ophthalmol. 1938;2:425-432.
7. Uğurlu N, Emre S, Akcay EK, Sengun A. Hereditary hemorrhagic telangiectasia with multiple fusiform retinal aneurysms. J Ocul Biol Dis Infor. 2013;5(2):48-50. doi:10.1007/s12177-013-9100-y.
8. Mennel S, Hoerle S, Meyer CH. Photodynamic therapy in symptomatic parafoveal telangiectasia secondary to Osler-Rendu-Weber disease. Acta Ophthalmol Scand. 2006;84(2):273-275. doi:10.1111/j.1600-0420.2005.00519.x.
9. Tsai DC, Wang AG, Lee AF, et al. Choroidal telangiectasia in a patient with hereditary hemorrhagic telangiectasia. Eye. 2002;16(1):92-94. doi:10.1038/sj.eye.6700023.
10. Mahmoud TH, Deramo VA, Kim T, Fekrat S. Intraoperative choroidal hemorrhage in the Osler-Rendu-Weber syndrome. Am J Ophthalmol. 2002;133(2):282-284. doi:10.1016/S0002-9394(01)01298-3.
Dr. Ho - None
Dr. Liu - None
Dr. Rothman - None