The manifestations and complications of RCH are usually visually significant even in optimally treated eyes. More than 25% of affected patients have vision less than 20/40 and about 20% have vision less than 20/100 [68]. Visual outcome is largely dependent on the size, location, and number of RCHs and the presence of associated findings such as exudative or tractional retinal detachment. The probability of visual loss is age dependent and the lifetime cumulative probability of permanent visual loss is 60%, with most of the risk (43%) in the first 30 years of life [64, 68]. Asymptomatic lesions have better visual outcome than symptomatic tumors. The cumulative probability of permanent visual loss by the age of 40 years was 35% in asymptomatic cases and 82% in symptomatic cases.

Systemic manifestations of VHL disease include CNS hemangioma (49–57%), renal cyst, renal cell carcinoma (24–47%), pheochromocytoma (19%), pancreatic cysts, islet cell tumors (15%), and epididymal cystadenoma (16%) [64]. Recently, bilateral endolymphatic sac tumors and adnexal papillary cystadenoma of probable mesonephric origin (APMO) were added to the list [64, 84]. Very few VHL patients develop all of the systemic findings and about 50% of patients manifest only one feature [73, 77]. There is great intrafamilial and interfamilial variability in expression [73]. The mean age at diagnosis of CNS hemangioma, renal cell carcinoma, and pheochromocytoma are 30 years, 44 years, and 30 years, respectively. With aging, the cumulative probability of manifesting cerebellar hemangioma and renal cell carcinoma increases from 44 and 50% at 30 years of age to 84 and 69% at 60 years of age, respectively [77].

7.3.9  Signs and Symptoms

7.3.9.1  Ocular Manifestations

Retinal Capillary Hemangioma

RCHtypicallypresentsasasolitarytumor.Approximately one-third of patients have multiple lesions and up to half the patients have bilateral involvement [81, 85, 86]. On ophthalmoscopy, RCH appears as an orange–red, circumscribed, round retinal lesion (Fig. 7.5). Intraretinal and subretinal exudation is often present in the vicinity of the lesion. Occasionally, exudation in the macula is

Fig. 7.5  Fundus photograph showing a typical retinal capillary hemangioma. Note circumscribed round orange–red retinal lesion with prominent retinal feeder vessels, subretinal fluid, and retinal exudation. Reproduced with permisson from: Singh et al. [229]

evident. Retinal or vitreous hemorrhages occur in less than 3% of cases [68].

The majority of RCH is located in the peripheral retina, with the superotemporal (39%) and inferotemporal quadrants (27%) most commonly affected [68, 87]. Peripherally located lesions are supplied by a pair of dilated and tortuous vessels emerging from the optic disk. In lesions smaller than 1.5 mm, feeder vessels may not be prominent and may be difficult to detect ophthalmoscopically. In 11–15% of VHL cases, RCHs occur in the juxtapapillary region [80, 88]. These tumors are usually located along the temporal quadrant of the optic disk [68, 88–91]. They vary in appearance based on their endophytic, exophytic, or sessile growth pattern. Endophytic juxtapapillary lesions appear as orange red protrusion from the anterior surface of the optic disk and adjacent retina. Exophytic tumors surrounding the disk can simulate chronic disk edema. Sessile variants are often subtle and can be very difficult to diagnose [92]. Juxtapapillary RCH should be considered in the presence of juxtapapillary retinal exudation or exudative retinal detachment.

Rare cases of retinal vascular hamartomas other than RCH have been observed in patients with VHL [93]. These tumors are relatively flat, located in the superficial retina, and without dilated feeder vessels. These tumors likely represent variations of RCH although their true nature and significance remain unclear. Retinal “twin vessels,” defined as a pair of retinal arteriole and venules separated by less than the diameter of one venule, have been described as a manifestation of VHL disease [83]. The twin vessels look like normal retinal vessels except for their course.