Retinal Hemangioblastomas Research Articles

First, do no harm: surgical management of von Hippel Lindau syndrome

Von Hippel Lindau (VHL) syndrome is an inherited condition that is associated with retinal and central nervous system haemangioblastomas, as well as renal and pancreatic cysts (Varshney et al., 2017). The renal cysts have a significant likelihood of neoplastic change, and act as a pre-malignant pathological finding prior to the development of clear cell renal carcinoma.

Congenital Retinal Vascular Anomalies- 2 (Coloboma, Retinal Cavernous Hemangioma, Arterio-Venous Malformation, Retinal Capillary Hemangioblastoma, Von Hippel-Lindau Syndrome)

Retinal vascular anomalies are a heterogeneous group consisting of congenital and acquired lesions. The visual prognosis varies in a wide range from asymptomatic to advanced vision loss according to the location of the lesion. Diagnosis is made by fundus examination, fluorescein angiography, and optical coherence tomography. It may be associated with systemic diseases and may require detailed systemic examination. This review includes coloboma, retinal cavernous hemangioma, arterio-venous malformation, and retinal capillary hemangioblastoma. The important clinical and diagnostic features, systemic relationships, and current treatment strategies of these anomalies are emphasized in the light of current literature.

Retinal Hemangioblastoma Revealing Von Hippel-Lindau Disease: Case Report

Von Hippel–Lindau disease (VHL), also known as Von Hippel–Lindau syndrome, is a rare genetic disorder with multisystem involvement. It is characterised by the development of multiple vascularised tumours, particularly cerebellar, retinal and/or visceral. The disease can occur at any age and usually starts with retinal hemangioblastomas We report the case of A 17 years old patient with VHL family history who presented with progressive unilateral decrease of visual acuity evolving for 6 months. The fundus examination showed a retinal examination with significant edema. The fluorescein angiography confirmed the diagnosis. The Brain MRI and the abdominal CT scan were normal. The patient had to undergo photocoagulation of the retinal lesions Management of patients with VHL disease often requires a multidisciplinary approach. The role of the ophthalmologist is important in the management of this condition since the ocular involvement may be indicative of the disease.

MP41-17 GENOTYPE-PHENOTYPE CORRELATIONS AND CLINICAL OUTCOMES OF VON HIPPEL-LINDAU DISEASE PATIENTS WITH LARGE DELETIONS

You have accessJournal of UrologyCME1 Apr 2023MP41-17 GENOTYPE-PHENOTYPE CORRELATIONS AND CLINICAL OUTCOMES OF VON HIPPEL-LINDAU DISEASE PATIENTS WITH LARGE DELETIONS Kenan Zhang and Kan Gong Kenan ZhangKenan Zhang More articles by this author and Kan GongKan Gong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Approximately 20-40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate genotype-phenotype correlations and clinical outcomes in VHL patients with LDs. METHODS: We included 119 VHL patients from 50 unrelated families in whom LDs were detected using traditional and next-generation sequencing methods in this retrospective study. Other germline mutations were confirmed by Sanger sequencing. Genotype-phenotype correlations and survival were analyzed in different groups using Kaplan-Meier and Cox regression. We also evaluated the therapeutic responses to tyrosine kinase inhibitors (TKIs) therapy. RESULTS: The overall penetrance of patients whose age was <60 was 95.2%. Two VHL patients with LDs also carried CHEK2 and FLCN germline mutations. An earlier age of onset of retinal hemangioblastoma was observed in the next generation. The patients with exon 2 deletion of VHL had an earlier onset age of renal cell carcinoma and pancreatic lesions. The risk of renal cell carcinoma was lower in VHL patients with LDs and a BRK1 deletion. The earlier onset age group received a poorer prognosis. Four of 8 (50%) patients showed a partial response to TKIs therapy. CONCLUSIONS: The number of generations and the status of exon 2 could affect onset age of VHL-related manifestation. Onset age was an independent risk factor for overall survival. TKIs therapy was effective for VHL patients with LDs. Our findings would further support clinical surveillance and decision-making processes. Source of Funding: This work was supported by the National High Level Hospital Clinical Research Funding (High Quality Clinical Research Project of Peking University First Hospital, 2022CR75), National Natural Science Foundation of China (No. 82141103; 82172617; 82172665; 81872081), the Scientific Research Seed Fund of Peking University First Hospital (2021SF01), Capital's Funds for Health Improvement and Research (2022-2-4074), and Sino-Russian Mathematics Center. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e562 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kenan Zhang More articles by this author Kan Gong More articles by this author Expand All Advertisement PDF downloadLoading ...

Non-Interventional Management of Advanced Pancreatic Neuroendocrine Neoplasms in Patients with von Hippel-Lindau Disease.

Von Hippel-Lindau (VHL) is a rare autosomal dominant hereditary cancer predisposition syndrome. Patients with VHL have a high risk for developing retinal and central nervous system hemangioblastoma, pheochromocytoma, renal cell carcinoma, and pancreatic neuroendocrine neoplasms (PNEN). About a fifth of patients with VHL will develop PNEN, and only a tenth of them will develop metastatic or unresectable (advanced) PNEN requiring medical intervention. In this review, we performed a literature search for studies, written in English, on the medical interventions for VHL-related localized and advanced PNENs and their clinical outcomes. We detail the various medical interventions for this rare group of patients, including their mode of action and potential efficacy and toxicity. Finally, based on the current literature, we delineate a possible management algorithm for patients with VHL and advanced PNEN. We can conclude that data on the efficacy of various vascular endothelial growth factor (VEGF) receptor inhibitors, and on the efficacy of belzutifan, a novel hypoxia-inducible factor 2 inhibitor, for the management of advanced PNEN in VHL, are scarce. Hence, deduction from the management of sporadic PNEN is required, and is implemented in the proposed management algorithm provided within this review.

Novel Manifestation of Retinal Hemangioblastomas Detected by OCT Angiography in von Hippel-Lindau Disease

To elucidate the clinical characteristics of atypical retinal vascular proliferation in patients with von Hippel-Lindau (VHL) disease using OCT angiography (OCTA). Prospective, observational study. Fifty-seven consecutive patients with a diagnosis of VHL disease who visited Kyoto University Hospital between January 2019 and March2022. Retinal hemangioblastomas (RHs) were assessed using multimodal imaging including OCTA. Retinal hemangioblastomas were classified into 2 phenotypes: nodular and flat. Nodular RHs were defined as typical RHs that were globular, well-circumscribed tumors, often accompanied with dilated feeder arterioles and draining venules. Flat RHs lacked a protruded red or colored mass, had variable and indistinct borders, and were not accompanied with feeder and draining vessels. The prevalence, distribution, and description of atypical flat RHs. Among 57 consecutive patients with VHL disease, 37 patients (64.9%) showed RHs in at least 1 eye. Bilateral RHs were seen in 23 patients (62.2%). Among 58 eyes of 37 patients with RHs, typical nodular RHs were detected in 54 eyes. Nodular RHs were seen mainly in the peripheral retina and occasionally in the peripapillary region, and they showed exudative changes in some cases. Flat RHs were detected in 7 eyes (12.1%). Four eyes showed only flat RHs, and 3 eyes showed both types in the same eye. Most flat RHs appeared as retinal hemorrhages or faint flat abnormal retinal vessels in the inner retina on the fundus examination, often within the macula area or peripapillary. In all eyes with flat RHs, OCTA showed abundant blood flow in the lesions. OCT revealed that flat RHs were seen mainly between the retinal nerve fiber layer and the ganglion cell layer, and occasionally within the inner nuclear layer. During a mean follow-up period of 20.4 ± 15.0 months, no flat RHs accompanied exudative change, tractional retinal detachment, or progression in size. Patients with VHL disease can demonstrate 2 distinct types of RHs: the classic nodular type and an atypical flat type. OCT angiography can be useful in improving the detection of atypical flat RHs, which can be difficult to detect clinically. Proprietary or commercial disclosure may be found after the references.

RARE CASE PRESENTAETION: VON HIPPLE LINDAU SYNDROME

Introduction: Von Hippel-Lindau syndrome (VHL) is autosomal dominant hereditary syndrome due to germline mutations of the tumor suppressor gene VHL, located on short arm of chromosome 3. 80% have a positive family history and about 20% of cases are de novo. Various multiple benign and malignant tumors occur affecting multiple organ system, central nervous system, kidneys, adrenals, pancreas, and reproductive system. Common manifestations include including retinal hemangioblastomas (HBs), central nervous system (CNS) HBs, endolymphatic sac tumors, pancreatic neuroendocrine tumors, pancreatic cystadenomas, pancreatic cysts, clear cell renal cell carcinomas, renal cysts, pheochromocytomas, paragangliomas, and epididymal and broad ligament cystadenomas. Confirmation of diagnosis is done by genetic testing in clinically and radiologically suspicious patient. A male patient of Case Report: age 30 years presented with cerebellar symptoms 2 year ago and MRI is done MRI reveal cerebellar and spinal hemangioblastoma. Patient is operated for cerebellar hemagioblastoma and histologically confirmed. On follow up study b/l renal cell carcinoma, pancreatic cyst and neuroendocrine tumor is found. VHL is a disease Conclusion: with no cure. Regular follow-up with necessary to follow the previous lesions and detect any newly developed VHL-associate tumors.

Photocoagulation for retinal hemangioblastoma in Von Hippel-Lindau disease

Introduction. Von Hippel?Lindau disease is a hereditary, autosomal dominant, tumor syndrome with a predisposition to developing various benign and malignant tumors. Retinal hemangioblastoma is often the presenting manifestation. We report a case of Von-Hippel?Lindau disease in a 13-year-old girl with bilateral eye involvement. Case outline. The patient was referred to the Eye Clinic, University Clinical Center of Serbia, with a diagnosis of Coats disease. Clinical examination revealed that best corrected visual acuity was 20/20 on her right eye, while her left eye showed counting fingers at 20 cm distance. Dilated fundoscopy of the right eye revealed multiple tortuous feeding vessels leading to orange-reddish, sharply demarcated multiple lesions on the far periphery of the upper retina, corresponding to retinal hemangioblastoma. the left eye showed edematous optic nerve head, tortuous retinal vessels, exudates, and retinal detachment including macula. Considering that the patient had multiple bilateral retinal hemangioblastomas and that her father had pathohistologically proven brain hemangioblastoma and numerous visceral tumors, Von Hippel?Lindau disease was assumed. Focal argon laser photocoagulation was performed in the region of all visible vascular tumors and feeding vessels in the right eye. The patient?s visual acuity remained unchanged five months after the disease detection. Conclusion. The importance of education about dominant inheritance pattern of Von Hippel?Lindau disease cannot be overemphasized. Role of an ophthalmologist is critical in early diagnosis of both retinal hemangioblastoma and Von Hippel?Lindau disease.

Von Hipple Lindau disease – management of two cases with mini review

Von Hipple Lindau syndrome (VHL) is genetically determined benign tumors of various organs with some tendency to malignant transformation. Two young male and female patients of 25 years and 18 years presented with bilateral retinal and central nervous system hemangioblastoma. One patient underwent panretinal photocoagulation and resection of cerebellar tumor and other received transpupillary thermotherapy (TTT). Proper genetic counseling and screening of the patients and close relatives were done. Though VHL is not curable, timely and proper treatment can save life and sight. The Ophthalmologist can play a role in reducing morbidity and mortality of patients and their family members by screening and proper referral.

Hamartomas of the Retina and Optic Disc.

Hamartomas are local malformation of cells that demonstrate abnormal proliferation in the area where they are normally present. Retinal and optic disc hamartomas include astrocytic hamartoma, congenital hypertrophy of the retinal pigment epithelium (CHRPE), simple congenital hamartoma of the retinal pigment epithelium (CSHRPE), combined hamartoma of the retina and retinal pigment epithelium (CHRRPE), retinal hemangioblastoma (retinal capillary hemangioma), and retinal cavernous hemangioma. Retinal and optic disc hamartomas can be observed sporadically as well as with systemic associations. Astrocytic hamartoma usually appears as a flat, transparent yellowish lesion. CHRPE is a round, pigmented, and flat lesion. CSHRPE usually presents as a dark black macular tumor. CHRRPE consists of vascular, glial, and pigment epithelial components, which can demonstrate peripapillary, macular, and peripheral localization. Retinal hemangioblastoma is a vascular tumor, red-pink in color with tortuous and dilated afferent and efferent vessels, typically located in the peripheral retina or optic disc. Retinal cavernous hemangioma is characterized by the formation of thin-walled saccular angiomatous structures in the retina or optic nerve head resembling concord grapes. Ultrasonography, fundus autofluorescence, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography methods are used in the diagnosis of retinal and optic disc hamartomas. Some retinal and optic disc hamartomas do not require treatment. However, complications including vitreous hemorrhage, macular exudation, retinal detachment, macular hole, epiretinal membrane, and choroidal neovascularization require treatment.

TWO CASES OF VON HIPPEL-LINDAU SYNDROME-ASSOCIATED RETINAL HEMANGIOBLASTOMA TREATED WITH BELZUTIFAN.

To describe two cases of retinal hemangioblastoma regression following treatment with belzutifan in patients with von Hippel-Lindau syndrome. Clinical information was extracted from the charts and tumor imaging of two patients with von Hippel-Lindau-associated retinal hemangioblastoma. In Case 1, a 40-year-old man was treated with belzutifan for spine hemangioblastomas after diagnosis of a 2.0 × 2.0 × 1.3 mm left-eye retinal hemangioblastoma temporal to the macula associated with intraretinal edema, subretinal fluid, and mild retinal traction. In Case 2, a 66-year-old woman presented with a right eye 2.0 × 1.5 × 1.3 mm juxtapapillary lesion with subretinal fluid, intraretinal fluid, and nasal traction, and a 4.0 × 3.5 × 1.1 mm inferior midperiphery lesion with subretinal fluid, intraretinal fluid, and active exudation. She was treated for 2.5 years with belzutifan for renal cell carcinoma on the National Institutes of Health trial. The patient in case 1 demonstrated a 10% reduction in largest tumor diameter and 8% reduction in thickness, along with improving subretinal fluid, intraretinal edema, and retinal traction, after 4 weeks of treatment. After 2.5 years of treatment, the patient in Case 2 demonstrated similar margins of her now fibrotic-appearing juxtapapillary lesion with a 45% reduction in thickness, along with resolved subretinal fluid and greatly improved intraretinal fluid and traction. The inferior lesion demonstrated 12.5% reduction in largest diameter, 36% reduction in thickness, and was without active subretinal fluid or exudation. Neither patient demonstrated new lesions while on treatment. Belzutifan is a promising treatment for retinal hemangioblastoma with the potential for both rapid and sustained tumor regression.

Von Hipple-Lindau disease complicated with central retinal vein occlusion: a case report

BackgroundCentral Retinal Vein Occlusion (CRVO) is a rare complication of von Hipple-Lindau (VHL) disease. This report presents the first case of VHL disease complicated with CRVO caused by VHL c.208G > A mutation.Case presentationA 20 s man whose left eye visual acuity gradually declined for half a year. The visual acuity of the left eye is counting fingers. Fundus examination revealed that retinal hemangioblastoma was also found in addition to typical CRVO signs such as tortuous expansion of retinal veins and flame-shaped hemorrhage of the retina. Liver tumor, cerebral infarction and erythrocytosis were found during systemic examination, and the diagnosis of polycythemia was confirmed by bone marrow smear. Furthermore, both family history and genetic analysis indicated that the patient had VHL disease caused by VHL c.208G > A. In this patient, a large number of bone marrow erythrocytes proliferated due to VHL disease, which led to the increase of blood viscosity and erythrocyte vascular adhesion, resulting in the obstruction of central retinal vein blood flow, and finally CRVO. For CRVO and its pathogenic factor polycythemia, patient received laser retinal photocoagulation and phlebotomies. After a 1-year follow-up, the vision in the left eye improved to 0.2 logMAR.ConclusionsThis is a rare case of polycythemia complicated by CRVO in patient with VHL disease. It reminds us that the systemic disease factors should be fully considered in the diagnosis of young patients with CRVO, and that treatment requires a coordinated effort of physicians.

NIMG-110. FIRST CLINICAL EXPERIENCE WITH BELZUTIFAN IN VON HIPPEL-LINDAU DISEASE-ASSOCIATED CNS HEMANGIOBLASTOMA

Abstract The authors present two cases of von Hippel-Lindau (VHL) disease-associated hemangioblastomas in the central nervous system (CNS) treated with the newly-approved HIF-2α inhibitor, belzutifan. The first case is that of a 31-year-old female with confirmed pathogenic germline VHL mutation who presented with multiple hemangioblastomas diagnosed at 25 years of age. The patient was first managed surgically with resection of three posterior fossa hemangioblastomas but re-presented five years later with headaches and paresthesias of the fingers. She was found to have interval progression of an intramedullary cervical lesion that was monitored radiographically, as well as a new cerebellar lesion. A cerebellar lesion was resected, but the cervical hemangioblastoma was not. Four months after surgery, the patient was started on belzutifan, which she tolerated without issue, and a brisk reduction in peri-lesional edema was observed in the cervical spine and remaining intracranial foci after 2 months of treatment. The second patient is a 30-year-old male with familial VHL disease, initially diagnosed after the discovery of a retinal hemangioblastoma at age 10. He was found to have multiple cerebellar hemangioblastomas, treated with resection at age 24 and then with stereotactic radiosurgery (SRS) at age 25, complicated by radiation necrosis. Imaging surveillance revealed disease progression at age 29 for which he was started on belzutifan. Follow-up imaging after three one month cycles revealed a reduction in perilesional edema and reduced lesion mass effect. Both patients tolerated belzutifan well, with only anemia and fatigue. We highlight in this report our initial experience and early imaging findings associated with belzutifan used for VHL disease-associated CNS hemangioblastomas.

Clinical and Genetic Characteristics of Retinal Capillary Hemangioblastoma in Korean Patients.

We investigated the clinical features of Korean patients with retinal capillary hemangioblastoma (RCH) and genetic variants of the von Hippel-Lindau (VHL) gene. A retrospective analysis was performed on patients with RCH from 2003 to 2021 at Seoul National University Bundang Hospital. Sporadic and hereditary RCH associated with VHL disease were classified based on the specific tumors and family history. Clinical features, including the location and number of RCH and bilateral involvement, were investigated. Multiplex ligation-dependent probe amplification and direct sequencing targeting the VHL gene were performed for six RCH cases associated with VHL disease. A total of 18 patients (23 eyes) were enrolled in this study. The mean age at diagnosis was 37 ± 15 years. Twelve patients had hereditary RCH associated with VHL disease, and six patients had sporadic RCH. All five patients with bilateral RCH were clinically diagnosed with VHL disease, and 13 patients had unilateral RCH. Juxtapapillary RCH was only observed in patients with VHL. The most common complication of RCH was the epiretinal membrane, followed by the subretinal fluid. Pathogenic variants were identified in four patients. All three patients with type 1 VHL had the well-known missense mutation p.Glu70Lys, and one patient with type 2 VHL had the nonsense mutation p.Trp88Ter. In Korean patients with RCH, bilateral involvement and juxtapapillary RCH are highly likely to be associated with VHL disease. Because RCH may be the first clinical manifestation in patients with VHL, active genetic testing of the VHL gene and systemic evaluation are required.

Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on abdominal manifestations.

Von Hippel-Lindau (VHL) disease is a monogenic autosomal dominant disorder with germline mutations of the VHL anti-oncogene on the short arm of chromosome 3 (3p25-26). It affects 1:36,000-50,000 individuals, with a penetrance greater than 90% at 65 years of age. Although of variable onset and presentation, with pleiotropism even among members of the same family who share a specific mutation, VHL disease usually manifests initially in young adults. It predisposes to the development of benign and malignant tumors of the central nervous system (CNS) and visceral organs. The clinical diagnosis of VHL disease can be made in the following circumstances: a) in patients with a family history of the disease and at least one of the tumors characteristic of it (e.g., retinal or CNS hemangioblastomas, clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, and endolymphatic sac tumors); b) in patients with two or more CNS hemangioblastomas; c) or in patients with a retinal or CNS hemangioblastoma plus at least one visceral tumor characteristic of the disease, excluding renal and epididymal cysts. Imaging plays an important role in the diagnosis and follow-up of patients with VHL disease. This pictorial essay presents characteristic images of abdominal manifestations of VHL disease-related tumors that all radiologists should be aware of.

DIAGNOSING VON HIPPEL LINDAU DISEASE BY RETINAL CAPILLARY HAEMANGIOBLASTOMAS

Introduction: Von Hippel-Lindau (VHL) syndrome is a disease characterized by the formation of tumors or cysts in many different parts of the body caused by germline. The prevalence of this autosomal dominant condition is very rare. Understanding of clinical manifestasion and diagnostic criteria is needed.&#x0D; Case Report: Female, 22-year-old was reffered from orthopaedic department suffered from blurred and misalignment of the left eye since 3 months ago . Based on indirect funduscopy examination, we found disc swelling with exudative retinal detachment on her left eye and orange-reddish retinal mass concluded as Retinal Capillary Hemangioblastoma (RCH) with tortuosity and dilatation of blood vessel on her right eye. The MRI showed multiple masses in cervical to lumbar vertebrae and multiple cyst on pancreatic gland.&#x0D; Discussion: This patient had 1 ocular RCH, multiple spinal tumor and multiple pancreatic cysts with no confirmed family history, therefore almost fulfilling the diagnostic criteria of VHL. To further confirm the diagnosis, it was necessary to find other common comorbids of VHL such as gene testing of VHL heterozygous germline mutation. Interdisciplinary approach consists of not only diagnostic and treatment plans from one speciality department, but also the ones from other related divisions and departments.&#x0D; Conclusion: Screening and interdiciplinary approach in managing Von Hippel-Lindau syndrome are required to be performed promptly.

Genotype–phenotype correlations and clinical outcomes of patients with von Hippel-Lindau disease with large deletions

BackgroundApproximately 20%–40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate...

A meta-analysis of different von Hippel Lindau mutations: are they related to retinal capillary hemangioblastoma?

Retinal capillary hemangioblastomas (RCH) is a benign tumor that represents the initial manifestation in roughly half of Von Hippel Lindau (VHL) patients. They may also occur sporadically without systemic involvement. A first meta-analysis study was investigated to estimate the prevalence of Retinal capillary hemangioblastoma (RCH) in Von Hippel Lindau (VHL) syndrome, and its relation to type and location of mutations in VHL gene. The electronic databases of PubMed, Scopus, Embase, and Google Scholar were utilized to find eligible papers published up to May 2020. Lastly, after the different prevalence of RCH in Europe compared to other continents was noted, we decided to consider European and non-European patients separately. The Random effect model was used to evaluate the relation between developing RCH and types of mutations. The overall prevalence of RCH among VHL patients is about 47%. The prevalence of RCH was significantly higher in Europe in comparison with non-Europeans (p value < 0.001). Overall, the differences between the prevalence of RCH among different mutation types were not statistically significant. However, in Europe, the prevalence of RCH was significantly higher in patients with truncation mutation (p value = 0.007). In Europe, the RCH in VHL patients who had a mutation in exon 2 was significantly lower in comparison with exon 1 (p value = 0.001); but in non-Europeans, the prevalence of RCH in VHL patients that involved exon 2 was significantly higher in comparison with VHL patients with a mutation in exon1 (p value = 0.012). The highest risk of developing RCH was reported among Europeans. Overall, this study showed that the prevalence of RCH in VHL syndrome is not related to type or location of mutations and difference of RCH prevalence is probably depends on other genetic or environmental factor that should be considered in subsequent studies.

Systemic Treatment Reduces Von-Hippel-Lindau–Associated Retinal Capillary Hemangioblastoma

A 24-year-old man with Von-Hippel-Lindau syndrome and central nervous system (CNS) hemangioblastomas was found to have multiple leaking retinal capillary hemangioblastomas in the superotemporal periphery of the left eye (Fig A). Systemic treatment was initiated with Belzutifan, a hypoxia-inducible factor-2α inhibitor. There was marked improvement in the engorgement and tortuosity of the feeding arterioles and draining veins, and a reduction in the number and size of the retinal capillary and CNS hemangioblastomas after 6 months of treatment (Fig B) (Magnified version of Fig A-B is available online at www.aaojournal.org).

Hyper-reflective retinal foci as possible in vivo imaging biomarker of microglia activation in von Hippel-Lindau disease.

Purposevon Hippel-Lindau (VHL) disease is caused by a mutation of the VHL gene and characterized by the development of retinal hemangioblastomas (RH). Current pathophysiologic mechanisms of RH development and progression are still insufficient to predict RH behavior. VHL gene is involved in the cellular response to hypoxia and in many intracellular signaling pathways expressed both in angiogenesis and inflammation. Optical coherence tomography (OCT) allows to identify hyper-reflective retinal foci (HRF) known as aggregates of activated microglial cells as possible in vivo biomarker of local inflammation. The aim of the present study was to investigate the presence of HRF in patients with genetically confirmed VHL disease.MethodsIn this cross-sectional study, patients with VHL underwent complete ophthalmological examination and OCT with HRA + OCT Spectralis. HRF were manually identified and calculated in inner (IR), outer (OR) and full retina. Age-matched healthy subjects were enrolled as controls.Results113 eyes of 63 VHL patients and 56 eyes of 28 healthy subjects were evaluated. HRF number was significantly higher in VHL than in controls in IR (28.06 ± 7.50 vs 25.25 ± 6.64, p = 0.042). No difference was observed in OR and in full retina (OR: 7.73 ± 2.59 vs 7.95 ± 2.51, p = 0.599; full retina: 35.79 ± 8.77 vs 33.20 ± 7.47, p = 0.093).ConclusionThe increase of HRF, which mirror retinal microglial activation, characterizes VHL eyes. The role of activated microglia in the retina of VHL eyes needs to be better investigated, mainly considering local VHL disease manifestations.