“bear tracks.” If the retinal lesions are present, the diagnosis is made even before the appearance of polyps in a patient with family history. The lesions have become very useful for genetic counseling.

References

1.Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med. 2009;361:2066–78.

2. Fauci A, Kasper D, Longo D, Braunwald E, Hauser E, et al, editors. Inflammatory bowel disease. In: Harrison’s principles of internal medicine. 17th ed. New York: McGraw-Hill; 2008. pp. 1887–1899.

3.Cho JH, Weaver CT. The genetics of inflammatory bowel disease. Gastroenterology. 2007;133:1327–39.

4.Danzi JT. Extraintestinal manifestations of idiopathic inflammatory bowel disease. Arch Intern Med. 1988;148:297–302.

5. Kochhar R, Mehta SK, Nagi B, et al. Extraintestinal manifestations of idiopathic ulcerative colitis. Indian J Gastroenterol. 1991;10:88–9.

6.Hopkins DJ, Horan E, Burton IL, Clamp SE, Dombal FT, Goligher JC. Ocular disorders in a series of 332 patients

with Crohn’s disease. Br J Ophthalmol. 1974;58: 732–7.

7. Tasman W, Jaeger E, editors. Ocular manifestations of gastrointestinal diseases. In: Duane’s ophthalmology. Philadelphia: Williams & Wilkins; 2008.

8. Lyons JL, Rosenbaum JT. Uveitis associated with inflammatory bowel disease compared with uveitis associated with spondyloarthropathy. Arch Ophthalmol. 1997;115:61–4.

9. Wright R, Lumsden K, Luntz MH, et al. Abnormalities of the sacro-iliac joints and uveitis in ulcerative colitis. Q J Med. 1965;34:229–36.

10.Salmon JF, Wright JP, Murray AD. Ocular inflammation in Crohn’s disease. Ophthalmology. 1991;98:480–4.

11. Orchard TR, Chua CN, Ahmad T, et al. Uveitis and erythema nodosum in inflammatory bowel disease: clinical features and the role of HLA genes. Gastroenterology. 2002;123:714–8.

12.Knox DL, Schachat AP, Mustonen E. Primary, secondary and coincidental ocular complications of Crohn’s disease. Ophthalmology. 1984;91:163–73.

13.Ellis PP, Gentry JH. Ocular complications of ulcerative colitis. Am J Ophthalmol. 1964;58:779–85.

14.Macoul KL. Ocular changes in granulomatous ileocolitis. Arch Ophthalmol. 1970;84:95–7.

15.Banares A, Jover JA, Fernandez-Gutierrez B, et al. Patterns of uveitis as a guide in making rheumatologic

and immunologic diagnoses. Arthritis Rheum. 1997;40:358–70.

16. Ernst BB, Lowder CY, Meisler DM, et al. Posterior segment manifestations of inflammatory bowel disease. Ophthalmology. 1991;98:1272–80.

17.Tappeiner C, Dohrmann J, Spital G, Heiligenhaus A. Multifocal posterior uveitis in Crohn’s disease. Graefes Arch Clin Exp Ophthalmol. 2007;245:457–9.

18.Ugarte M, Wearne IM. Serpiginous choroidopathy: an unusual association with Crohn’s disease. Clin Exp Ophthalmol. 2002;30:437–9.

19. Rouleau J, Longmuir R, Lee AG. Optic disc edema with adjacent cilioretinal artery occlusion in a male with ulcerative colitis. Semin Ophthalmol. 2007;22:25–8.

20. Duker JS, Brown GC, Brooks L. Retinal vasculitis in Crohn’s disease. Am J Ophthalmol. 1987;102:664–8.

21. Heuer DK, Gager WE, Reeser FH. Ischemic optic neuropathy associated with Crohn’s disease. J Clin Neuro-Ophthal. 1982;2:175–81.

22. Saatci OA, Kocak N, Durak I, Ergin MH. Unilateral retinal vasculitis, branch retinal artery occlusion and subsequent retinal neovascularization in Crohn’s disease. Int Ophthalmol. 2001;24:89–92.

23.Soukiasian SH, Foster CS, Raizman MB. Treatment strategies for scleritis and uveitis associated with

inflammatory bowel disease. Am J Ophthalmol. 1994;118:601–11.

24. Towler HM, Cliffe AM, Whiting PH, et al. Low dose cyclosporin A therapy in chronic posterior uveitis. Eye. 1989;3:282–7.

25.Kilmartin DJ, Forrester JV, Dick AD. Tacrolimus (FK506) in failed cyclosporin A therapy in endogenous posterior uveitis. Ocul Immunol Inflamm. 1998;6:101–9.

26.Dobbins III WO. Whipple’s disease. Springfield: Charles C Thomas; 1987.

27.Keinath RD, Merrell DE, Vlietstra R, Dobbins III WO. Antibiotic treatment and relapse in Whipple’s disease: long term follow-up of 88 patients. Gastroenterology. 1985;88:1867–73.

28. La Scola B, Fenollar F, Fournier PE, Altwegg M, Mallet MN, Raoult D. Description of Tropheryma whipplei gen. nov., sp. nov., the Whipple’s disease bacillus. Int J Syst Evol Microbiol. 2001;51:1471–9.

29.Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F, Raoult D. Whipple’s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis. 2008;8:179–90.

30.Gerard A, Sarrot-Reynauld F, Liozon E, et al.

Neurologic presentation of Whipple disease: report of 12 cases and review of the literature. Medicine (Baltimore). 2002;81:443–57.

31. Nishimura JK, Cook Jr BE, Pach JM. Whipple disease presenting as posterior uveitis without prominent gastrointestinal symptoms. Am J Ophthalmol. 1998;126:130–2.

32. Rickman LS, Freeman WR, Green WR, et al. Brief report: uveitis caused by Tropheryma whippelii (Whipple’s bacillus). N Engl J Med. 1995;332: 363–6.

33.Avila MP, Jalkh AE, Feldman E, Trempe CL, Schepens CL. Manifestations of Whipple’s disease in the posterior segment of the eye. Arch Ophthalmol. 1984;102: 384–90.

34. Drancourt M, Raoult D, Lepidi H, et al. Culture of Tropheryma whippelii from the vitreous fluid of a patient presenting with unilateral uveitis. Ann Intern Med. 2003;139:1046–7.

35. Slater GH, Ren CJ, Siegel N, et al. Serum fat-soluble vitamin deficiency and abnormal calcium metabolism after malabsorptive bariatric surgery. J Gastrointest Surg. 2004;8:48–55.

36.Genead MA, Fishman GA, Lindeman M. Fundus white spots and acquired night blindness due to vitamin A deficiency. Doc Ophthalmol. 2009;119:229– 33. Epub 2009 Oct 7.

37. Lee WB, Hamilton SM, Harris JP, Schwab IR. Ocular complications of hypovitaminosis A after bariatric surgery. Ophthalmology. 2005;112:1031–4.

38.McBain VA, Egan CA, Pieris SJ, Supramaniam G, Webster AR, Bird AC, Holder GE. Functional observations in vitamin A deficiency: diagnosis and time course of recovery. Eye. 2007;21:367–76.

39. Morrison SA, Russell RM, Carney EA, Oaks EV. Zinc deficiency: a case of abnormal dark adaptation in cirrhotics. Am J Clin Nutr. 1978;31:276–81.

40. Ugarte M, Osborne NN. Zinc in the retina. Prog Neurobiol. 2001;64:219–49.

41. Núñez L, Cubiella J, Moreno C, Díez MS, Sánchez E, Vega M. Purtscher’s retinopathy: a rare complication

of acute non-alcoholic pancreatitis. Gastroenterol Hepatol. 2003;26:541–4.

42.Sharma AG, Kazim NA, Eliott D, Houghton O, Abrams GW. Purtscher’s retinopathy that occurred 6 months before acute pancreatitis. Am J Ophthalmol. 2006;141:205–7.

43.Burton TC. Unilateral Purtscher retinopathy. Ophthalmology. 1980;87:1096–105.

44.Behrens-Baumann W, Scheurer G, Schroer H. Pathogenesis of Purtscher’s retinopathy. An experimental study. Graefes Arch Clin Exp Ophthalmol.

1992;230:286–91.

45. Tiret A, Parc C. Fundus lesions of adenomatous polyposis. Curr Opin Ophthalmol. 1999;10:168–72.

46. Blair NP, Trempe CL. Hypertrophy of the retinal pigment epithelium associated with Gardner’s syndrome. Am J Ophthalmol. 1980;90:661–7.

47. Tiret A, Sartral-Taiel M, Tiret E, Laroche L. Diagnostic value of fundus examination in familial adenomatous polyposis. Br J Ophthalmol. 1997;81:755–8.

48.Valanzano R, Cama A, Volpe R, Curia MC, Mencucci R, Palmirotta R, et al. Congenital hypertrophy of the retinal pigment epithelium in familial adenomatous polyposis: novel criteria of assessment and correlations with constitutional adenomatous polyposis coli gene mutations. Cancer. 1996;78:2400–10.

Introduction

The oculoneurocutaneous syndromes (ONCS) are a group of disorders characterized by systemic hamartomas of the eye, brain, skin, and sometimes the viscera [1–38]. The term “phakomatoses,” previously used to designate these entities, is

J.A. Shields, M.D. ( )

Wills Eye Institute, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA

e-mail: jerryashields@gmail.com

C.L. Shields, M.D.

Wills Eye Institute, Thomas Jefferson University Hospital, 840 Walnut Street, Suite 1440, Philadelphia, PA 19107, USA

e-mail: carol.shields@shieldsoncology.com

nonspecific and is used less often in the literature. As a result, we have chosen to group these entities under the rubric oculoneurocutaneous syndromes (ONCS), which more accurately reflects their true nature. However, we realize that better terminology may be adopted in the future when the genetics of these conditions are better understood. The syndromes described herein include tuberous sclerosis complex (TSC), neurofibromatosis (NF), von Hippel-Lindau (VHL) syndrome, Sturge-Weber (SW) syndrome, Wyburn-Mason (WM) syndrome, and oculoneurocutaneous cavernous hemangiomatosis. This chapter discusses these syndromes with emphasis on their fundus manifestations, in keeping with the goals of this textbook. Although the genetics, central nervous system (CNS), dermatological,

and systemic features of these syndromes are mentioned briefly, they are discussed in more detail in recent textbooks [1–3].

Tuberous Sclerosis Complex

(Bourneville’s Syndrome)

Definition

Tuberous sclerosis complex (TSC) is characterized by retinal astrocytic hamartomas, cutaneous abnormalities, CNS astrocytomas, and internal tumors such as cardiac rhabdomyoma, renal angiomyolipoma, and other tumors [1–9]. It is best known to produce a triad of adenoma sebaceum (cutaneous angiofibromas), seizures, and mental deficiency.

Demographics

The incidence of TSC is about 1 in 10,000 [5]. Although TSC usually is diagnosed during the first few years of life, it has occasionally been recognized in patients as young as 1 month of age or as old as 50 years. This syndrome has been identified in all races, and there is no predilection for gender.

Genetics

Most evidence suggests that TSC is transmitted by an autosomal dominant mode with incomplete penetrance. In many cases, the family history is unremarkable and examination of family members is normal. Such patients are considered to be sporadic mutations. About half of the families show linkage to chromosome 9q34 and about half to chromosome 16p13 [1].

Fundus Manifestations

The retinal astrocytic hamartoma is the characteristic fundus lesion of TSC (Figs. 17.1 and 17.2) [1–3]. However, an identical lesion occasionally is found in patients who have no other clinical or genetic evidence of TSC. In either

Fig. 17.1 Tuberous sclerosis complex. Noncalcified retinal astrocytic hamartoma

Fig. 17.2 Tuberous sclerosis complex. Calcified retinal astrocytic hamartoma

case, a small noncalcified tumor can be extremely subtle and appear only as ill-defined translucent thickening of the retinal nerve fiber layer. A slightly larger tumor is more opaque and appears as a sessile white lesion at the level of the nerve fiber layer of the retina (see Fig. 17.1). The calcified variant contains characteristic dense yellow, refractile, structures that resemble fish eggs or tapioca (see Fig. 17.2). Although it is generally stable and does not usually cause serious complications, it can occasionally produce retinal traction or vitreous hemorrhage. Retinal astrocytic hamartoma generally is a small asymptomatic lesion that does not show enlargement. However,