Retinal Glial Cells in Von Hippel–Lindau Disease: A Novel Approach in the Pathophysiology of Retinal Hemangioblastoma

Background: Von Hippel–Lindau (VHL) disease is a neoplastic syndrome caused by a mutation of the VHL tumor suppressor gene. Retinal hemangioblastoma (RH) is a vascularized tumor and represents the most common ocular manifestation of this disease. At the retinal level, VHL protein is able to regulate tumor growth, angiogenic factors, and neuroinflammation, probably stimulating retinal glial cells. The aim of the present study was to analyze in vivo the optical coherence tomography (OCT) biomarkers of retinal macroglia and microglia in a cohort of VHL patients. Methods: The mean thicknesses of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), and peripapillary retinal nerve fiber layer (pRNFL) were measured with OCT as biomarkers of retinal macroglia. OCT images were also analyzed to detect and quantify hyperreflective retinal foci (HRF), a biomarker of retinal activated microglia. Results: 61 eyes of 61 VHL patients (22 eyes (36.07%) with peripheral RH and 39 eyes (63.93%) without RH) and 28 eyes of 28 controls were evaluated. pRNFL was thinner in VHL patients (p < 0.05) and in VHL without RH (p < 0.01) compared to controls, and thicker in VHL patients with RH than in those without RH (p < 0.05). The thickness of mRNFL (p < 0.0001) and GCL (p < 0.05) was reduced in VHL patients and in VHL without RH compared to controls, whereas mRNFL (p < 0.0001) and GCL (p < 0.05) were increased in VHL patients with RH compared to those without RH. HRF were significantly higher in number in VHL patients and in VHL without RH, than in controls, and significantly lower (p < 0.05) in the eyes of VHL patients with RH, than in those without RH. Conclusions: The OCT analysis, which detects and allows to quantify the biomarkers of retinal microglia (HRF) and macroglia (pRNFL, mRNFL and GCL), showed a different behavior of these two retinal glial cells populations in VHL patients, related to the presence or absence of peripheral RH. These data allow to hypothesize a novel pathophysiologic pathway of retinal hemangioblastoma in VHL disease.

Optical Coherence Tomography Angiography of Early Stage 1a Retinal Hemangioblastoma in Von-Hippel-Lindau

Von-Hippel-Lindau (VHL) syndrome is characterized by focal vasoproliferative tumors of retinal capillaries called retinal capillary hemangio-blastomas (RCH). These tumors are initially small and can be easily missed if not looked for carefully. As they grow, these tumors are more demanding to treat and hence the importance of detecting them early and treating them. Herein, we describe and review the optical coherence tomography angiography (OCTA) of the early-stage lesion, which suggested the involvement of superficial and a deeper retinal capillary plexus. In addition, to helping us detect these lesions earlier, OCTA may also help to understand the in vivo changes occurring at an earlier phase.

Clinical and Laboratory Characteristics of a Large Iranian Kindred Afflicted with Von Hippel Lindau Disease

Introduction: Von Hippel Lindau (VHL) disease is a hereditary disorder characterized by the development of benign or malignant tumors in the brain, spinal cord, eyes, adrenal medulla, kidney, pancreas, and many other organs. Advances in molecular diagnosis have led to the identification of the affected members of families at earlier stages. We present the clinical, laboratory, and genetic characteristics of five generations of large Iranian kindred with VHL. Case Presentation: The proband, a 52-year-old Iranian man, was recognized with VHL. All family members underwent clinical, laboratory, imaging, and genetic evaluation. Medical files and histopathology reports of patients who had been operated on before were also reviewed. Diagnosis of the disease was based on clinical findings, positive family history of VHL, and development of a central nervous system or retinal hemangioblastoma or pheochromocytoma. Based on diagnostic criteria, our initial evaluations revealed that 10 members of the family had already been affected by the disease. Among them, nine had pheochromocytoma, and one had retinal hemangioblastoma. There was no case of kidney tumors among the kindred. Conclusions: Study results show the high penetrance of the disease and focus on the large burden imposed by the disease on the health and quality of life of patients afflicted with the disease, emphasizing the importance of surveillance from early childhood for detection and management of the disease as early as possible.

Retinal Hemangioblastoma with Extraocular Extension: Report of Three Cases

Retinal hemangioblastoma (RH) is the earliest and most common clinical manifestation in Von Hippel-Lindau (VHL) disease. RH can also present in isolation without any evidence of VHL. Clinical course of RH can be stationary or progress to exudation and chronic retinal detachment requiring surgical intervention. We report 3 cases of aggressive RH with extraocular extension in young males causing painful blind eye requiring enucleation. Two of our cases were bilateral involvement and had systemic manifestations of VHL. The third patient had unilateral involvement with no systemic evidence of VHL. This manifestation of RH is rarely reported. Two of our patients with VHL had early manifestations of RH and had undergone multiple cryotherapy sessions as well as retinal detachment surgery for exudative retinal detachment. This differential should be considered in vascular lesion arising from intraocular structures especially in diagnosed patients of VHL. The cases also highlight the aggressive behaviour and long-term progression of RH in some patients despite early treatment.

Photodynamic Therapy in Ocular Oncology

Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis.