Pathophysiology and management of glaucoma associated with phakomatoses

Abstract

The phakomatoses, encephalotrigeminal angiomatosis (ETA; Sturge-Weber Syndrome), neurofibromatosis type 1 (NF1 or von Recklinghausen disease), Von Hippel-Lindau (VHL) disease, tuberous sclerosis (TSC), oculodermal melanocytosis (ODM), and phakomatosis pigmentovascularis are a group of neurocutaneous disorders that have characteristic systemic and ocular manifestations. Through many different mechanisms, they may cause glaucomatous damage of the optic nerve and subsequent vision loss varying from mild to severe. Glaucoma commonly affects patients with ETA (43-72%), orbito-facial NF1 (23-50%), and ODM (10%). Rarely, it may present as neovascular glaucoma in VHL and TSC. In ETA, glaucoma typically occurs ipsilateral to the port-wine stain, which is caused by a mutation in the GNAQ gene. Specifically, mechanical malformation of the anterior chamber angle and elevated episcleral venous pressure has been implicated as causes of glaucoma in ETA. In NF1, which is caused by a mutation in the NF1 tumor suppressor gene, glaucoma commonly occurs ipsilateral to lid plexiform neurofibromas. Histological studies of eyes with NF1 have revealed direct anterior chamber infiltration by neurofibromas, secondary angle closure, fibrovascularization, and developmental angle abnormalities as mechanisms of glaucoma. Lastly, phakomatosis pigmentovascularis is a rare combination of ODM and port-wine stain. Affected patients are at very high risk of developing glaucoma. Despite the many different mechanisms of glaucomatous damage, management follows similar principles as that for congenital glaucoma and primary open angle glaucoma. First-line therapy is topical intraocular pressure-lowering eye drops. Surgical management, including goniotomy, trabeculotomy, trabeculectomy, and tube shunt placement may be required for more severe cases.

Progressive ectropion uveae and secondary angle-closure glaucoma in type 1 neurofibromatosis

“… 2 Ipsilateral congenital glaucoma is present in 23–50% of NF-1 patients with eyelid plexiform neurofibromas. 2 , 3 , 6 Various mechanisms for IOP elevation have been implicated including infiltration of the anterior chamber angle by neurofibroma cells, PAS formation in association with ectropion uveae, and other angle abnormalities such as the presence of an anterior and flat iris insertion, abundant iris processes, or increased pigmentation of the angle. 3 , 6 , 8 , 9…”

Ocular Findings in Neurofibromatosis

“…Glaucoma has been found to occur in about 1 in 300 NF-1 patients [5]. Patients with orbito-facial involvement have been linked to higher rates of glaucoma at 23-50% [6][7][8]. It was also found that patients with eyelid plexiform neurofibromas have ipsilateral globe enlargement up to 36 mm axial length [6].…”

“…The most commonly described mechanism is the presence of neurofibromas in the angle causing aqueous outflow obstruction [6]. Other suggested processes include secondary angle closure due to the anterior displacement of the peripheral iris by an abnormally thickened ciliary body or developmental anomalies in the angle [7].…”

Intraocular Tumors and Glaucoma

“…Nörofibromatoziste glokom hastaları pleksiform nörofibromlar ve ektropiyon üvea ile sık birliktelik gösterdiği için bu bulguların ortaya konması glokom açısından sıkı takip gerektirir. 26 Glokom eşlik eden hastaların prognozu genellikle kötüdür ve sıklıkla cerrahi tedavi gerektirir. Morales ve ark.nın, 13 hastalık NF ve glokom serisinde, tüm hastalara cerrahi gerekmiştir.…”

“…27 Von Hippel Lindau (VHL) ve tuberoskleroza ise nadiren NVG hastalarının eşlik ettiği literatürde bildirilmiştir. 26 İntraoküler tümörlerde, tümöre bağlı vitreus hemorajisi, tedavi veya biyopsi örnekleri alınırken ortaya çıkan hemorajiler nedeni ile hemorajik glokom sık olarak görülebilmektedir. Glokom ilk haftalarda ortaya çıkarsa hemolitik karakterde iken, eğer hemorajiden aylar sonra ortaya çıkarsa hayalet hücreler nedeni ile olduğu düşünülmelidir.…”