1. Grand Rounds Conference Reema Syed, MBBS University of Louisville Department of Ophthalmology and Visual Sciences June 19, 2015

2. Subjective CC: “Droopy eyelids” for a few years HPI: 75 year old white female with chronic low vision OS complains of bilateral droopy eyelids, OS>OD, obstructing vision

3. History POH: Eyelid surgery OS 1980s PMH: Neurofibromatosis I Meds: none Allergies: none

4. Objective ODOS BCVA:20/20 -3 CF @ 2 ft Pupils: 3 to 2 mm 3 to 2 mm + rAPD + rAPD IOP:16 mmHg 14 mmHg EOM: Full OU, orthophoric in primary gaze CVF:constricted superiorly OU

5. Dermatochalasis OU, Ptosis LUL, MRD 4mm/1mm, LF 12/11 mm Objective

6. Objective Pulsatile left globe, Hertel 92 11,12 12

7. Anterior segment exam: wnl OU Dilated fundus exam: OD wnl OS optic nerve pallor

8. CT Scan Absence of left sphenoid wing, temporal lobe herniation into orbit

9. CT Scan Left orbital enlargement, defect in posterior orbital roof

10. Assessment 75 year old white female with 75 year old white female with Neurofibromatosis I Neurofibromatosis I Left sphenoid wing dysplasia Chronic low vision OS secondary to optic atrophy Dermatochalasis OU obstructing vision Ptosis left upper lid

11. Plan Plan Neuro-surgery referral for possible reconstruction of skull base defect Upper lid blepharoplasty OU, Ptosis repair to improve peripheral vision

12. NF 1/von Recklinghausen disease Autosomal dominant disorder, mutation of neurofibromin gene on chromosome 17 q11.2 Autosomal dominant disorder, mutation of neurofibromin gene on chromosome 17 q11.2 Incidence of 1 in 3,500 live birth Incidence of 1 in 3,500 live birth Women and men are affected equally Women and men are affected equally

13. NF-1 Neurofibromin - expressed in neurons, Schwann cells, oligodendrocytes, astrocytes and leukocytes Neurofibromin - expressed in neurons, Schwann cells, oligodendrocytes, astrocytes and leukocytes Disease characterized by multiple neurofibromas. Variable phenotypic expression Disease characterized by multiple neurofibromas. Variable phenotypic expression 2-4x increased risk of other tumors (leukemia, meningioma, pheochromocytoma, rhabdomyosarcoma)

14. NF1 – Cutaneous manifestations

15. NF1 – ophthalmic manifestations

16. Optic nerve glioma – fusiform dilation of the nerve. T1 images of optic gliomas appear as hypointense, whereas T2 images hyperintense

18. Diagnostic criteria

19.  Some debate in the literature about the pathogenesis of sphenoid wing dysplasia  congenital maldevelopment vs progressive sphenoid dysplasia due to the presence of adjacent tumors causing early closure of cranial sutures that in turn precipitate an abnormal development of the sphenoid bone as the skull expands during childhood Or direct bone resorption by the tumor in older patients

20. Decalcification of sphenoid bone (arrowheads) adjacent to neurofibroma infiltration of the lateral rectus muscle (arrows). Bilateral facial soft-tissue tumor infiltration, bilateral enlarged middle cranial fossae (arrowheads) and bilateral large globes (buphthalmos) independent of glaucoma

21. References BCSC orbits, eyelids and lacrimal system BCSC orbits, eyelids and lacrimal system BCSC ophthalmic pathology and intraocular tumors Orbitofacial neurofibromatosis: clinical characteristics and treatment outcome. Chaudhry IA. Eye (Lond). 2012 Apr; 26(4): 583–592. Dysplasia of the Orbit and Adjacent Bone Associated with Plexiform Neurofibroma and Ocular Disease in 42 NF-1 Patients. Friedrich RE. Anticancer Research May 2010 vol. 30 no. 51751-1764

22. Thank you