Capillary Hemangioblastoma Research Articles

SUCCESSFUL TREATMENT OF VON HIPPEL-LINDAU DISEASE-ASSOCIATED RETINAL CAPILLARY HEMANGIOBLASTOMA WITH BELZUTIFAN IN A PEDIATRIC PATIENT.

The authors describe a case of a retinal capillary hemangioblastoma (RCH) in a pediatric patient with von Hippel-Lindau (VHL) syndrome that was successfully treated with systemic belzutifan. The clinical course was documented with serial fundus examinations and multimodal imaging, including Optos widefield fundus photography and optical coherence tomography. A literature review was conducted to look for similar cases and/or discussion. A left RCH was noted on a standard VHL surveillance retinal examination of a then 15-year-old male patient with VHL syndrome. Over the course of 17 months, this RCH was treated with focal laser therapy, photodynamic therapy, cryotherapy, bevacizumab injection, and endolaser ablation. Complications of these treatments included subretinal fluid and vitreomacular traction necessitating laser retinopexy, scleral buckle, and pars plana vitrectomy with membrane stripping. After a 6-month interval from the last local therapy (endolaser treatment), there was minimal regression of the lesion, and many concerning features persisted. At 22 months from presentation, the patient started belzutifan 120 mg PO daily with subsequent regression in size and less perfusion to the hemangioblastoma within 4 months. The patient is tolerating the systemic belzutifan with only the expected normocytic anemia and has not required transfusion therapy after 12 months of treatment. von Hippel-Lindau disease is a rare and serious condition associated with multiple types of benign and malignant tumors. Belzutifan is tolerated in the adolescent population and can provide a systemic treatment alternative for VHL-associated RCH.

Significant Improvement in Retinal Capillary Hemangioblastoma With Belzutifan.

Significant Improvement in Retinal Capillary Hemangioblastoma With Belzutifan.

Role of optical coherence tomography angiography in retinal tumors: A narrative review.

Intraocular tumors constitute a small subset of cases in ophthalmologic practice. Proper diagnosis of intraocular tumors is crucial because some pose threat to vision and life, while others may indicate underlying systemic disorders. Intraocular tumors comprise benign and malignant lesions affecting the retina, choroid, optic disc, iris, and ciliary body. Retinal tumors can be classified as vascular, neural, glial, and retinal pigment epithelial tumors. Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality employed in diagnosis and management of retinal and choroidal vascular diseases, and has enhanced our knowledge in better understanding of the vascular physiology and pathology. Multiple case reports and small series evaluating the role of OCTA in retinal tumors are published in literature. OCTA helps in better understanding of the vascularity of intraocular tumors. In addition to this, OCTA has its role in clinical practice. It helps in identification of small retinal capillary hemangioblastoma (RCH), assessment of treatment response, and identification of tumor recurrence in RCH. It aids in identification of retinal astrocytic hamartoma missed on clinical examination and differentiating retinal astrocytic hamartoma and presumed solitary circumscribed retinal astrocytic proliferation. It helps in assessment of risk of tumor recurrence in retinoblastoma. It helps in differentiating tumors of retinal pigment epithelium (RPE) origin from pigmented tumors of the choroid. It also helps in detection of choroidal neovascular membrane in combined hamartoma of the retina and RPE.

Indocyanine green-enhanced transpupillary thermotherapy for juxtapapillary retinal capillary hemangioblastoma.

To study the clinical presentation and treatment outcomes of indocyanine green-enhanced transpupillary thermotherapy (ICG-TTT) for treatment-naïve juxtapapillary retinal capillary hemangioblastoma (JRCH). A prospective interventional case series. The technique involved ICG dye infusion 45 seconds prior to application of TTT. The main study outcomes were local tumor control, resolution of subretinal fluid (SRF), and improvement in best-corrected visual acuity (BCVA). Eight eyes of seven patients (5 males and 2 females) were included. The mean age was 26 years (range: 5-56 years). Systemic evaluation revealed von-Hippel Lindau (VHL) disease in five patients. The most common location was the temporal aspect of the optic disc (5 eyes). The mean basal diameter was 2.9 mm (range: 1-8 mm), and tumor thickness was 1.4 mm (range: 1-4 mm). All eight eyes were treated with multiple sessions of ICG-TTT (mean: 3 sessions). Six eyes received adjuvant intravitreal injection of dexamethasone implant (4 eyes) and/or bevacizumab (4 eyes). Post treatment, six eyes (75%) had tumor regression with reduction of SRF. One eye had a partial response with persisting SRF, and one eye showed poor response to TTT for which external beam radiotherapy was performed. At the last follow-up (median: 11 months; range: 6-29 months), the BCVA remained stable in seven eyes and improved in one eye (hand motion to 20/40). Multiple ICG-TTT sessions can be considered as an alternative treatment option for JRCH with effective local tumor control and SRF resolution.

Retinal phakomatosis and Von Hippel-Lindau peripheral capillary hemangioblastoma: proposal for staged surgery.

Retinal capillary hemangioblastoma (RCH) is present in about half of the carriers of the VHL (von Hippel-Lindau) gene mutation and can lead to the evolution of blindness. Herewith is a proposal for surgical intraretinal feeder vessel ligature to induce ischemia the phakoma and to resolve the exudative secondary retinal detachment, with satisfying results at the 6 months follow-up end point. The patient underwent a chandelier-assisted 23 G pars plana vitrectomy with valved trocars. A bimanual transretinal ligature of the hemangioblastoma's feeder vessel was performed, followed by localized endolaser to ablate the surrounding retina and capillaries, and a Polydimethylsiloxane 1000 (PDMS 1000) final tamponade. After 3 months, exchange PDMS/air/balanced salt solution (BSS), phacoemulsification, and in-the-bag intraocular lens (IOL) implantation were performed. At sixth month, fundus fluorescein angiography (FFA) showed a significant reduction of blood flow in the phakoma. Final best-corrected visual acuity (BCVA) was 6/6 (9 lines gain obtained compared to the baseline time). This surgical technique seems to be effective and promising for the treatment of VHL retinal capillary hemangioblastomas and their related retinal complications.

Surgical and visual outcomes after vitreoretinal surgery for complex retinal capillary hemangioblastoma.

We evaluated the anatomical and functional outcomes after vitreoretinal surgery for complex retinal capillary hemangioblastoma (RCH). This was a retrospective case series of 15 patients (16 eyes) with tractional or combined retinal detachment (RD) managed with pars plana vitrectomy and tumor endoresection (ER) with/without feeder vessel ligation. The mean age at the time of surgery was 30 years (range, 14-46 years). The most common tumor locations were inferotemporal (six eyes) and temporal (six eyes) quadrants. Indications for surgery included exudative RD with fibrovascular proliferation (eight eyes), combined RD (five eyes), vitreous hemorrhage (four eyes), and rhegmatogenous RD (two eyes). Tumor destruction was performed with laser and/or cryotherapy in nine eyes (57%) and ER in seven eyes (43%). Feeder vessel was ligated and cauterized in 10 (63%) and six eyes (37%), respectively. Anatomical success after initial surgery was 50% (eight eyes), which improved to 88% (14 eyes) after they underwent a repeat procedure for recurrent RD (eight eyes). At the last visit, visual acuity improved in seven eyes (44%), was stable in four eyes (25%), and worsened in five eyes (31%) with a mean follow-up of 29 months (6-79 months). Comparison between the ER group and the laser/cryotherapy group revealed no significant difference in final retinal reattachment rate (89% vs. 86%, P > 0.05), with better visual outcomes in laser/cryotherapy group (57% vs. 78%, P < 0.05). Pars plana vitrectomy with/without tumor endoresection can be a safe and effective treatment option for complex RCHs, achieving good tumor control and anatomical success with limited functional success.

Pre-Induction Scalp Block in a Patient of von HippelLindau Disease: Promising Use in High-Risk Neurosurgical Procedures

Multiple modalities have been tried for post-craniotomy pain relief, but controversy exists as to the optimal approach. Pre-induction scalp block is a promising technique in high-risk neurosurgical procedures, which reduces the haemodynamic response to skull pin insertion and craniotomy incision, and affords post-operative analgesia. von hippel-lindau (VHL) disease is a rare autosomal dominant disorder with multi-system involvement and various visceral manifestations, the most common of these-being cerebellar hemangioblastoma. Other anomalies include pancreatic-renal cysts, erythrocytosis, hypernephroma, pheochromocytoma and retinal capillary hemangioblastoma. Central nervous system (CNS) hemangioblastomas are often an early manifestation of the disease, and are typically seen in the second decade of life. The majority of hemangioblastomas occur in the cerebellum followed by the spinal cord and brain stem. They are benign vascular tumours but can cause neurological symptoms secondary to pressure or haemorrhage. We hereby present a case of previously diagnosed VHL with recurrent cerebellar hemangioblastoma scheduled for neurosurgical tumour excision and the beneficial use of a pre-induction scalp block to compliment anaesthesia for the patient.

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.

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.

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.

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).

Immediate Post Laser Blanching of a Retinal Capillary Hemangioblastoma

Immediate Post Laser Blanching of a Retinal Capillary Hemangioblastoma

Transvitreal Feeder Vessel Ligation and En Bloc Resection of a Retinal Capillary Hemangioblastoma

This video illustrates a healthy 24-year-old female with a one-year history of vision loss in her right eye due to a total tractional-rhegmatogenous retinal detachment associated with a large retinal capillary hemangioblastoma (RCH). Because the lesion and its overlying fibrotic membranes mechanically impeded retinal reattachment, decision was made to perform pars plana vitrectomy (PPV) with tumor resection. While diathermy of the feeder vessels can be done in this scenario, we opted instead for suture ligation to optimize intraoperative hemostasis.

Anaesthetic Management of a Patient with Von-Hippel-Lindau Syndrome: A Conglomeration of Perplexities

Von-Hippel-Lindau (VHL) syndrome is an autosomal dominant disease with multisystem involvement. Tumours associated with VHL include, hemangioblastomas of the spine and brain, retinal capillary hemangioblastomas, renal cell carcinoma, pheochromocytoma, and neuroendocrine tumours of pancreas. We present a case of a 54 year old female second-degree uterovaginal prolapse scheduled for laparoscopic assisted vaginal hysterectomy. She was diagnosed with adult polycystic kidney disease, pheochromocytoma, parathyroid adenoma, vertebral hemangioma and multiple renal and hepatic cysts. Though genetic testing was not feasible, the co-existing systemic manifestations in this patient were strongly suggestive of Von Hippel Lindau syndrome. Owing to the multi-morbidities, central neuraxial block was deemed appropriate as opposed to general anaesthesia. In concert with the surgeons, it was decided to change the surgical plan to vaginal hysterectomy and avoid adrenaline infiltration at the surgical site, as it is known to precipitate arrythmias. We placed an intra-arterial catheter for continuous blood pressure monitoring before administration of the subarachnoid block and co-loaded the patient with fluids to avoid any drastic hypotension. The patient remained hemodynamically stable throughout the procedure, which could be attributed to extensive pre-operative work-up multi-disciplinary pre-operative optimization and synergistic management with surgical team. Providing anaesthesia to patients with multisystem involvement such as Von Hippel Lindau syndrome can be very challenging. Meticulous pre-anaesthetic evaluation and pre-operative optimization are often crucial. A multidisciplinary approach is often employed to achieve the best possible pre-operative functional status of these patients. Well-coordinated team with flexibility in management tailored to the patient helps achieve the best possible outcomes. Disclaimer: Informed consent was obtained from the patient prior to publication Main Points • Von-Hippel-Lindau (VHL) syndrome is an autosomal dominant disease with multisystem involvement; associated tumours include hemangioblastomas of the CNS, retinal capillary hemangioblastomas, renal cell carcinoma, pheochromocytoma, endolymphatic sac tumours of the middle ear, serous cystadenomas and neuroendocrine tumours of pancreas. • Providing anaesthesia to patients with multisystem involvement such as Von Hippel Lindau syndrome can be very challenging. Meticulous pre-anaesthetic evaluation and pre-operative optimization are often crucial. • A detailed anaesthetic plan, tailored to each patient, has to be formulated in elective cases, after an extensive work-up of the associated tumours. • Extensive pre-operative work-up, a multi-disciplinary approach towards pre-operative optimization and synergistic management with surgical team remains vital in minimizing peri-operative complications. • Anaesthetic implications are often at the nexus of surgical outcomes, hence, proper communication with the surgical team and arrival at a joint plan is crucial.

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 hemangioblastomas (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.

Acute Mastoiditis and Cerebellar Capillary Hemangioblastoma Demonstrated by FDG PET/CT Images

Acute Mastoiditis and Cerebellar Capillary Hemangioblastoma Demonstrated by FDG PET/CT Images

Multimodal Imaging in the Diagnosis of Exophytic Juxtapapillary Retinal Capillary Hemangioblastoma

Exophytic juxtapapillary retinal capillary hemangioblastoma (JRCH) can be difficult to diagnose. We explore the value of multimodal imaging to aid in the diagnosis. Retrospective case series. Medical records and multimodal imaging studies were reviewed on all patients diagnosed with RCH at Bascom Palmer Eye Institute, Miami, Florida, between January 2013 and December 2019. Patients with exophytic lesions within 2mm of the disc were included. One patient from the Baylor College of Medicine, Houston, Texas was included. Patient demographics, referring diagnosis, history of von Hippel-Lindau syndrome, initial and last visual acuity, and treatments were recorded. Fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, optical coherence tomography (OCT), OCT angiography, and B-scan images were reviewed. Twelve patients were identified with exophytic JRCH. The mean age was 54 years (range 38-73 years). Five patients had von Hippel-Lindau syndrome. The most common referral diagnoses were choroidal neovascularization and neuroretinitis. Imaging features included nodular outer retinal thickening with shadowing and intra-/subretinal fluid on OCT, hypoautofluorescence on fundus autofluorescence, middle to outer retinal hypervascularity on OCT angiography, early hyperfluorescence with late leakage on fluorescein angiography, and lack of choroidal vascular lesion on indocyanine green angiography. Treatments included photodynamic therapy (6 patients), intravitreal anti-vascular endothelial growth factor therapy (6 patients), argon laser photocoagulation (2 patients), intravitreal or sub-Tenon's triamcinolone (3 patients), and observation (4 patients). A key to the accurate diagnosis of exophytic JRCH is its intraretinal location, typically involving the outer retinal layers, which results in a clinical appearance that is distinct from the more common and easily recognizable endophytic RCH. Multimodal imaging can aid in ruling out choroidal neovascularization and disc edema by demonstrating an absence of involvement of those structures.

Thermography in clinical ophthalmic oncology.

The aim of this study was to present our own experience with the use of thermography as a complementary method for the initial diagnosis and differentiation of intraocular tumors, as well as for the evaluation of the efficacy of treatment of intraocular melanomas. The study group comprised 37 patients with intraocular tumors, including 9 with uveal melanoma, 8 with uveal melanoma after I125 brachytherapy, 12 with a focal metastasis to the uvea, and 8 with retinal capillary hemangioblastoma. A FLIR T640 camera was used to capture images in the central point of the cornea, eye area, and orbital cavity area. Eyes with uveal melanoma had higher temperature compared with the fellow normal eye of the patient in the range of all measured parameters in the regions of interest. In the group of patients with melanoma after unsuccessful brachytherapy, higher temperature was observed at the central point of the cornea. In patients with tumor regression, all measured parameters were lower in the affected eye. We observed lower tempe-ratures in the range of all tested parameters and areas in eyes with choroidal metastases. Eyes with diagnosed intraocular hemangioblastoma were characterized by higher parameters for the regions of interest versus eyes without this pathology. A thermographic examination of the eye can be used as an additional first-line diagnostic tool for the differentiation of intraocular tumors. Thermography can be a helpful tool in monitoring the treatment outcome in patients with intraocular melanoma.

Comparison of Current Optical Coherence Tomography Angiography Methods in Imaging Retinal Hemangioblastomas.

PurposeTo compare spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) for imaging retinal capillary hemangioblastomas (RCHs) in von Hippel-Lindau disease (VHLD).MethodsProspective single-center cross-sectional study. Tumor size (TS) of perfused RCHs was assessed clinically in relation to the optic disc size. For both technologies, SD-OCTA and SS-OCTA, corresponding images with a scan size of 3 × 3 mm2 and 6 × 6 mm2, respectively, were overlaid according to the set of marker positions to determine the TS.ResultsFrom 200 patients with VHLD, 48 patients showed 84 RCHs. SD-OCTA images of 39 RCHs (46.4%) and SS-OCTA images of 48 RCHs (57.2%) were suitable for analysis. The average in OCTA-measured TS of 1.60 ± 2.58 mm2 (range, 0.01–10.43) was congruent to the clinically assessed TS in 81.3% of cases (r = 0.86, P < 0.0001). TS measured in SD-OCTA compared to SS-OCTA showed similar values and a high correlation (all P < 0.0001). Nevertheless, despite the similarities, a slight trend in SS-OCTA was observed whereby with increasing TS, an elevated TS was detected compared to SD-OCTA (3 × 3-mm2 scans: mean difference of 0.03 ± 0.04 mm2, 6 × 6-mm2 scans: 0.08 ± 0.19 mm2). However, within the same imaging technology method, TS values almost did not differ (SD-OCTA: mean difference of 0.01 ± 0.02 mm2, SS-OCTA: 0.001 ± 0.01 mm2).ConclusionsOCTA may serve as an additional tool for diagnosis and monitoring of RCHs. Nevertheless, due to the differences between the technologies, the values cannot be used interchangeably.Translational RelevanceSD-OCTA and SS-OCTA are suitable to detect and monitor RCHs and provide a more detailed assessment about the TS than this is clinically possible.