Frosted-branch angiitis

FROSTED-BRANCH angiitis is a rare form of retinal vasculitis characterized by white perivascular sheathing of retinal blood vessels. The first case reported in 1976 involved a 6-year-old boy who had severe white sheathing of all retinal vessels presenting an appearance similar to the frosted branches of a tree. Affecting more males (52%) than females (48%), frosted-branch angiitis is mostly seen in children and young adults. It usually affects individuals 6 to 16 years old in Japan and 23 to 29 in other countries. It is typically bilateral although unilateral cases have been reported. This case involved a 42-year-old male who consulted at the University of the Philippines-Philippine General Hospital (UP-PGH) because of a 4-month history of progressive blurring of vision in the left eye. Visual acuity was 20/20 for the right eye and 20/40, improved to 20/ 25 on pinhole, for the left eye. Intraocular pressures were within normal limits for both eyes (OU). The anterior segment was normal. Indirect ophthalmoscopy for the right eye was normal. The left eye, seen through a hazy medium, showed dilated and tortuous retinal veins with perivascular sheathing peripherally. There were some intraretinal foci of inflammation with scattered hemorrhages mostly in the inferior nasal periphery, and numerous vitreous opacities. Fluorescein angiography (FA) of the left eye showed dilated veins with leakage of dye from the retinal vessels on late phase and multifocal areas of perivenular staining. There were areas of capillary nonperfusion on the inferonasal arcade with foci of hyperfluorescence. Systemic work-up for possible etiology and polymerase chain reaction of the aqueous humor yielded negative results. It is still unclear whether frosted-branch angiitis is a unique disease entity by itself or a clinical presentation resulting from several causes as reported by Kleiner. Its characteristic features are:

• Severe sheathing of retinal vessels appearing like frosted branches of a tree in one or both eyes;
• Acute visual disturbance associated with signs of anterior-chamber and vitreous inflammation;
• FA demonstrates no occlusion or stasis of sheathed vessels, but late staining and/or leakage along vessels;
• Otherwise healthy patient;
• Prompt response to corticosteroid;
• Typically no recurrence.

In 1998, Kleiner et al. classified the disease into 3 subgroups: idiopathic, those associated with hematologic malignancies like leukemia and lymphoma, and those caused by viral infection or autoimmune disease. Most cases of frosted-branch angiitis are idiopathic, as in the case of our patient. An immune-mediated mechanism is believed to be the main cause as evidenced by localized ocular vasculitis sparing other organs. This suggests that the immune response is directed to an inciting agent in the eye. The presence of positive titers for herpes simplex, varicella, rubella, cytomegalovirus, Epstein-Barr virus, and antistreptolysin O in some patients affected by frosted-branch angiitis suggested that viral or bacterial infection can be the triggering antigen. The prompt response to systemic steroids also indicates a probable immune-mediated mechanism. In frosted-branch angiitis associated with viral disease like cytomegalovirus and human immunodeficiency virus, it has been theorized that viral antigens form immune complexes and deposit in retinal vessels causing vasculitis. A direct viral invasion may also be responsible for the pathogenesis. Immune complexes are also responsible for retinal vasculitis secondary to autoimmune disease. Direct infiltration of retinal vessels by malignant cells is believed to be the cause of frosted-branch angiitis among patients with leukemia and lymphoma. Diagnosis is mainly by ophthalmoscopy and fluorescein angiography. Ophthalmoscopy shows the typical sheathing of retinal vessels mostly the veins giving the appearance of frosted-branches of a tree. Fluorescein angiogram shows normal blood flow but with late staining, leakage of dye from vessels, and optic-disc hyperfluorescence. Laboratory examinations usually do not show abnormalities and are mostly useful to rule out the possibility of associated systemic diseases. Despite the severe retinal appearance, the prognosis is usually good, with rapid recovery of visual acuity after prompt steroid treatment to suppress intraocular inflammation and prevent visual loss and long-term complications such as capillary nonperfusion, retinal neovascularization, neovascular glaucoma, macular scarring, and retinal detachment. Recovery usually starts 2 to 3 weeks after treatment is initiated. Steroid-sparing agents may be used when there is significant steroid toxicity or persistent relapse at high dose of steroids. The ones commonly used are cyclosporine and azathioprine. Our patient was started on high-dose oral prednisone at an initial dose of 1 mg/kg/day for 5 weeks and responded well with improvement in visual acuity and fundus findings after 2 weeks. Funduscopy showed decreased vitreous haziness and opacities, less dilatation and tortuosity of the veins, and decreased perivascular sheathing. Prognosis is relatively good.