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The right eye of a patient with essential thrombocytosis and age-related macular degeneration. Photograph by C.L.
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The major complications of Philadelphia-negative (Ph-Negative) myeloproliferative neoplasms (MPNs) are thrombosis, haemorrhage and leukemic transformation. As systemic and haematological diseases, MPNs have the potential to affect many tissues and organs. Some complications lead to the diagnosis of MPNs, but other signs and symptoms are often misdi...
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Citations
... The majority of patients with MPNs share a mutation in JAK2 that affects haematopoetic signal-transduction pathways (95-98% of patients with PCV and 50-60% of those with ET/PMF), resulting in haematologic disruption that increases thrombotic risk across all organ systems, including the central nervous system and the eye. 3 Vision loss due to MPN is uncommon but may occur in the setting of cerebral venous sinus thrombosis (CVST) secondary to severe papilloedema. Less than 1% of patients with known MPN develop CVST, and fewer still present with visionthreatening papilloedema as a consequence. ...
... Ocular complications are common among patients with MPNs. The prevalence of ocular and neuro-ophthalmologic complications in the MPNs has been estimated to be between 7.5% and 25% in both treated and untreated patients [65]. Microvascular disturbances and hyperviscosity (in polycythemia vera) can promote retinal microvascular occlusions. ...
The most common causes of morbidity and mortality in the myeloproliferative neoplasms (MPNs), with the exception of myelofibrosis, are venous and arterial thrombosis, as well as more recently discovered cardiovascular disease (CVD). Clonal hematopoiesis of indeterminate potential (CHIP) is the subclinical finding in an individual of somatic mutations that are also found in clinically overt MPNs and other myeloid malignancies. The prevalence of “silent” CHIP increases with age. CHIP can transform into a clinically overt MPN at an estimated rate of 0.5 to 1% per year. It is likely, therefore, but not proven, that many, if not all, MPN patients had antecedent CHIP, possibly for many years. Moreover, both individuals with asymptomatic CHIP, as well as clinically diagnosed patients with MPN, can develop thrombotic complications. An unexpected and remarkable discovery during the last few years is that even CHIP (as well as MPNs) are significant, independent risk factors for CVD. This review discusses up-to-date information on the types of thrombotic and cardiovascular complications that are found in CHIP and MPN patients. A systemic inflammatory state (that is often subclinical) is most likely to be a major mediator of adverse reciprocal bone marrow–cardiovascular interplay that may fuel the development of progression of MPNs, including its thrombotic and vascular complications, as well as the worsening of cardiovascular disease, possibly in a “vicious cycle”. Translating this to clinical practice for hematologists and oncologists who treat MPN patients, attention should now be paid to ensuring that cardiovascular risk factors are controlled and minimized, either by the patient’s cardiologist or primary care physician or by the hematologist/oncologist herself or himself. This review is intended to cover the clinical aspects of thrombosis and cardiovascular complications in the MPN, accompanied by pathobiological comments.
... [4][5][6][7][8] Microvascular disturbances can also lead to inadequate cerebral perfusion, resulting in neuro-ophthalmological symptoms such as monocular blindness, transient blindness, and visual disturbances resembling transient ischemic attacks or migraine-like episodes. [9][10][11][12] Treatment goals in PV primarily revolve around reducing vascular risks, typically achieved through cytoreductive therapy and acetylsalicylic acid (ASA) administration. [2] PV and altered choroidal and retinal blood flow, with studies examining parameters such as subfoveal choroidal thickness (SFCT), ocular pulse amplitude, and retrobulbar hemodynamics using Doppler ultrasonography. ...
Purpose
This study aims to assess the impact of polycythemia vera (PV) on retinal and optic nerve head (ONH) vessel density (VD) parameters, macular ganglion cell complex (mGCC) thickness, and retinal nerve fiber layer (RNFL) thickness compared to healthy controls.
Methods
Forty eyes of 20 patients with PV and 40 eyes of 20 age-gender-matched healthy controls underwent comprehensive ophthalmologic assessments and optic coherence tomography angiography (OCTA). RNFL and macular GCC measurements were obtained simultaneously with vascular parameters by AngioVue OCTA using the single-scan protocol. Peripapillary VD was examined across eight sectors, whereas parameters including RNFL, GCC, and macular VD were analyzed in four quadrants.
Results
Patients with PV exhibited significant reductions in the average RNFL thickness ( P = 0.014) and RNFL thickness in superior ( P < 0.001) and inferior ( P = 0.003) quadrants compared to controls. Additionally, mGCC thickness in all quadrants significantly reduced in the PV group ( P < 0.001). ONH VD parameters, including whole-image VD ( P < 0.001) and peripapillary VD ( P < 0.001), were significantly reduced in patients with PV. Similarly, macular VD parameters were significantly lower in the PV group ( P < 0.001).
Conclusion
This study highlights substantial vascular and structural alterations in the retina and ONH of patients with PV compared to healthy controls. These changes likely stem from microvascular dysfunction associated with PV. These findings suggest further research to understand the underlying mechanisms and develop targeted therapeutic strategies for managing ocular complications in patients with PV.
... Increased hyperviscosity in patients with PV is associated with thromboembolic complications. [13][14][15] The effects of elevated plasma viscosity are more significant at low flow rates than at high flow rates and are therefore more pronounced in the venous system than in the arteries. Hence, retinal venous tortuosity and dilatation are the earliest signs of elevated plasma viscosity. ...
Purpose
To evaluate retinal and choroidal microvascular structures using optical coherence tomography angiography (OCTA) in patients with anemia and polycythemia vera (PV).
Methods
In this prospective study, 142 patients (142 eyes) were enrolled and divided into 3 groups: the anemia (n = 56), PV (n = 46), and healthy groups (n = 40, controls). For each patient, 6- × 6-mm macular angiography images were taken using an OCTA system (optovue, Inc., Fremont). For each eye analyzed, the software automatically measured vessel density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP; superior, nasal, temporal, and inferior quadrants), choriocapillaris (CC), and foveal avascular zone (FAZ).
Results
The OCTA analysis revealed that the VD of the DCP was significantly decreased in the superior and inferior hemispheres of the whole area, multiple quadrants of the perifovea, and CC with a 1-mm² flow area in the anemia group compared with the PV group (p < 0.017), but the VD of the SCP did not show any significant difference in any quadrant between the two groups (p > 0.017). When compared with the healthy group, the anemia and PV groups showed a significant difference in multiple quadrants of the parafovea and temporal quadrant of the perifovea in the VD of the SCP and CC with a 2-mm² flow area (p < 0.017). The FAZ and non-flow area did not manifest any significant difference between the groups (p > 0.017). The hemoglobin concentrations in the anemia, PV, and healthy groups were 8.11 ± 1.33, 17.5 ± 1.2, and 15.6 ± 0.73 g/dL, respectively, indicating statistically significant differences between the groups (p < 0.001).
Conclusion
In this study, quantitative OCTA analysis revealed a higher tendency for retinal and choroidal microvascular morphological changes in patients with anemia and PV. The outcomes of the current investigation can provide new insights into the retinal and choroidal pathophysiologies found in patients with hemoglobin abnormalities.
... Наиболее часто описываемые глазные проявления при ХМПН представляют собой вторичные изменения органа зрения, связанные с гематологическими аномалиями, такими как тромбоцитоз, эритроцитоз и лейкоцитоз [13]. Эти преобразования в составе крови вызывают нарушения микрососудистого кровообращения, связанные с агрегацией и спонтанной активацией лейкоцитов и тромбоцитов. ...
The course of chronic myeloproliferative neoplasms (CMPN), a group of systemic hematological diseases, can be accompanied by various complications and changes in tissues and organs of the whole organism. The eye is the only organ where damage of nerve fibers and blood vessels can be directly observed and examined, and ocular symptoms can be the initial, manifest of systemic pathology, the toxic effects of modern targeted therapy, or the first manifestation of a relapse of the disease after treatment. The most frequently described manifestations are caused by hematological anomalies that cause microvascular disorders. Such changes today remain insufficiently studied in terms of the using new research methods and contemporary targeted therapy. In addition, ocular symptoms may precede more serious extraocular complications. Combined ophthalmological and hematological examination of patients with CMPN can become a preventive approach for early diagnosis and timely treatment.
... The classical BCR-ABL-negative myeloproliferative neoplasms (MPN) of acquired clonal hematopoietic stem cell disorders include polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF). In general, the signal-transduction pathways responsible for haematopoiesis are affected in these MPN [1,2]. PV is a condition in which over-proliferation of erythroid progenitors cause elevated red blood cell (RBC) mass and is usually accompanied by higher white blood cell (WBC) count, as well as an excessive number of platelets and bone marrow hypercellularity [3]. ...
Classical BCR-ABL-negative myeloproliferative neoplasms (MPN) include polycythaemia vera, essential thrombocythaemia, and primary myelofibrosis. Unlike monogenic disorders, a more complicated series of genetic mutations are believed to be responsible for MPN with various degrees of thromboembolic and bleeding complications. Thrombosis is one of the early manifestations in patients with MPN. To date, the driver genes responsible for MPN include JAK2, CALR, MPL, TET2, ASXL1, and MTHFR. Affords have been done to elucidate these mutations and the incidence of thromboembolic events. Several lines of evidence indicate that mutations in JAK2, MPL, TET2 and ASXL1 gene and polymorphisms in several clotting factors (GPIa, GPIIa, and GPIIIa) are associated with the occurrence and prevalence of thrombosis in MPN patients. Some polymorphisms within XRCC1, FBG, F2, F5, F7, F12, MMP9, HPA5, MTHFR, SDF-1, FAS, FASL, TERT, ACE, and TLR4 genes may also play a role in MPN manifestation. This review aims to provide an insightful overview on the genetic perspective of thrombotic complications in patients with MPN.
... Patients with MPNs have a huge symptom and associated disease burden/ comorbidity burden, and some of these are presented in this figure. For ocular manifestations in these patients please see review byLiisborg et al. (2020).Created with BioRender. ...
Dansk Resumé (Danish summary)
Aldersrelateret makuladegeneration (AMD) er den hyppigste årsag til uopretteligt synstab og blindhed i højindkomstlande. Det er en progredierende nethindesygdom som gradvist fører til ødelæggelse af de celler som er ansvarlige for vores centralsyn. De tidlige stadier er ofte asymptomatiske, imens senstadie AMD, som opdeles i to former, neovaskulær AMD (nAMD) og geografisk atrofi (GA), begge udviser gradvist synstab, dog generelt med forskellig hastighed. Tidlig AMD er karakteriseret ved tilstedeværelsen af druser og pigmentforandringer i nethinden mens nAMD og GA udviser henholdsvis karnydannelse i og atrofi af nethinden. Ætiologien er multifaktoriel og udover alder omfatter patogenesen miljø‐ og genetiske risikofaktorer. Forskning har specielt fokuseret på lokale forandringer i øjet hvor man har fundet at inflammation spiller en betydelig rolle for udviklingen af sygdommen, men flere studier tyder også på at systemiske forandringer og specielt systemisk inflammation spiller en væsentlig rolle i patogenesen.
De Philadelphia‐negative myeloproliferative neoplasier (MPNs) er en gruppe af hæmatologiske kræftsygdomme med en erhvervet genetisk defekt i den tidlige pluripotente stamcelle som medfører en overproduktion af en eller flere af blodets modne celler. Sygdommene er fundet at udvikle sig i et biologisk kontinuum fra tidligt cancerstadie, essentiel trombocytose (ET) over polycytæmi vera (PV) og endelig til det sene myelofibrose stadie (PMF). Symptomer hos disse patienter skyldes især den ændrede sammensætning af blodet, hyperviskositet, kompromitteret mikrocirkulation og nedsat vævsgennemblødning. Den øgede morbiditet og mortalitet beror i høj grad på tromboembolier, blødninger og leukemisk transformation. En række mutationer som driver MPN sygdommene er identificeret, bl.a. JAK2V617F ‐mutationen som medfører en deregulering JAK/STAT signalvejen, der bl.a. har betydning for cellers vækst og overlevelse. Et tidligere stort registerstudie har vist at patienter med MPNs har en øget risiko for neovaskulær AMD og et pilotstudie har vist øget forekomst af intermediær AMD. Dette ønsker vi at undersøge nærmere i et større studie i dette Ph.d.‐ projekt. Flere studier har også vist at kronisk inflammation spiller en vigtig rolle for både initiering og udvikling af den maligne celleklon hos MPNs og herfra er en “Human Inflammationsmodel” blevet udviklet. Siden er MPN sygdommene blevet anvendt som “model sygdomme” for en tilsvarende inflammationsmodel for udvikling af Alzheimers sygdom. I dette Ph.d.‐projekt vil vi tilsvarende forsøge at undersøge systemisk inflammation i forhold til forekomst af druser. Det vil vi gøre ved at sammenligne systemiske immunologiske markører som tidligere er undersøgt hos patienter med AMD og sammenligne med MPN. Specielt er vi interesseret i systemiske immunologiske forskelle på patienter med MPN og druser (MPNd) og MPN med normale nethinder (MPNn).
Denne afhandling består af to overordnede studier. I Studie I, undersøgte vi forekomsten af retinale forandringer associeret med AMD hos 200 patienter med MPN (artikel I). Studie II, omhandlede immunologiske ligheder ved AMD og MPN, og var opdelt i yderligere tre delstudier hvor vi undersøgte hhv. systemiske markører for inflammation, aldring og angiogenese (artikel II, III og IV). Vi undersøgte markørerne i fire typer af patienter: nAMD, intermediær AMD (iAMD), MPNd og MPNn. Undersøgelsen af forskelle mellem MPNd og MPNn, vil gøre det muligt at identificere forandringer i immunsystemet som kunne være relevante for AMD‐patogenesen. Vi vil endvidere sammenholde resultaterne for patienter med MPN med patienter som har iAMD og nAMD.
I studie I (Artikel I) fandt vi at patienter med MPN har en signifikant højere prævalens af store druser og AMD tidligere i livet sammenlignet med estimater fra tre store befolkningsundersøgelser. Vi fandt også at forekomst af druser var associeret med højere neutrofil‐lymfocyt ratio, hvilket indikerer et højere niveau af kronisk inflammation i patienterne med druser sammenlignet med dem uden druser.
I studie II (Artikel II, III og IV) fandt vi flere immunologiske forskelle mellem patienter med MPNd og MPNn. Da vi undersøgte markører for inflammation, fandt vi en højere grad af systemisk inflammation i MPNd end MPNn. Dette blev vist ved en højere inflammationsscore (udregnet på baggrund af niveauer af pro‐inflammatoriske markører), en højere neutrofil‐lymfocyt ratio, samt indikationer på et dereguleret komplementsystem. Ved undersøgelse af aldringsmarkører fandt vi tegn på accelereret immunaldring hos MPNd i forhold til MPNn, hvilket kommer til udtryk ved en større procentdel af “effector memory T celler”. Endelig fandt vi en væsentlig lavere ekspression af CXCR3 på T celler og monocytter hos patienter med nAMD sammenlignet med iAMD, MPNd og MPNn. Dette er i overensstemmelse med tidligere studier hvor CXCR3 ekspression er fundet lavere end hos raske kontroller. Derudover fandt vi en faldende CXCR3 ekspression på monocytter over det biologiske MPN‐kontinuum. Disse studier indikerer en involvering af CXCR3 i både nAMD og PMF, begge sygdomsstadier som er karakteriseret ved angiogenese og fibrose.
Ud fra resultaterne af denne afhandling kan vi konkludere at forekomsten af druser og AMD hos MPN er øget i forhold til baggrundsbefolkningen. Endvidere viser vores resultater at systemisk inflammation muligvis spiller en væsentlig større rolle i udviklingen af AMD end tidligere antaget. Vi foreslår derfor en AMD‐model (Figur 18) hvor inflammation kan initiere og accelerere den normale aldersafhængige akkumulation af affaldsstoffer i nethinden, som senere udvikler sig til druser, medførende øget lokal inflammation og med tiden tidlig og intermediær AMD. Dette resulterer i den øgede risiko for udvikling til de invaliderende senstadier af AMD.
English summary
Age‐related macular degeneration (AMD) is the most common cause of irreversible vision loss and blindness in high‐income countries. It is a progressive retinal disease leading to damage of the cells responsible for central vision. The early stages of the disease are often asymptomatic, while late‐stage AMD, which is divided into two entities, neovascular AMD and geographic atrophy (GA), both show vision loss, though generally with different progression rates. Drusen and pigmentary abnormalities in the retina characterise early AMD, while nAMD and GA show angiogenesis in and atrophy of the retina, respectively. The aetiology is multifactorial and, in addition to ageing, which is the most significant risk factor for developing AMD, environmental‐ and genetic risk factors are implicated in the pathogenesis. Research has focused on local changes in the eye where inflammation has been found to play an essential role, but studies also point to systemic alterations and especially systemic inflammation to be involved in the pathogenesis.
The Philadelphia‐negative myeloproliferative neoplasms (MPN) are a group of haematological cancers with an acquired genetic defect of the pluripotent haematopoietic stem cell, characterised by excess haematopoiesis of the myeloid cell lineage. The diseases have been found to evolve in a biological continuum from early cancer state, essential thrombocythemia, over polycythaemia vera (PV), to the advanced myelofibrosis stage (PMF). The symptoms in these patients are often a result of the changes in the blood composition, hyperviscosity, microvascular disturbances, and reduced tissue perfusion. The major causes of morbidity and mortality are thromboembolic‐ and haemorrhagic events, and leukemic transformation. A group of mutations that drive the MPNs has been identified, e.g., the JAK2V617F mutation, which results in deregulation of the JAK/STAT signal transduction pathway important, for instance, in cell differentiation and survival. A previous large register study has shown that patients with MPNs have an increased risk of neovascular AMD, and a pilot study has shown an increased prevalence of intermediate AMD. We wish to study this further in a larger scale study. Several studies have also shown that systemic inflammation plays an essential role in both the initiation and progression of the malignant cell clone in MPNs. From this knowledge, a “Human inflammation model” has been developed. Since then, the MPNs has been used as model diseases for a similar inflammation model for the development of Alzheimer's disease. In this PhD project, we would like to investigate systemic inflammation in relation to drusen presence. We will do this by comparing systemic immunological markers previously investigated in patients with AMD and compare with MPN. We are primarily interested in systemic immunological differences between patients with MPN and drusen (MPNd) and MPN with normal retinas (MPNn).
This thesis consists of two main studies. Study I investigated the prevalence of retinal changes associated with AMD and the prevalence of different AMD stages in 200 patients with MPN (paper I). Study II examined immunological similarities between AMD and MPNs. This study was divided into three substudies exploring systemic markers of inflammation, ageing and angiogenesis, respectively. This was done in four types of patients: nAMD, intermediate AMD (iAMD), MPNd and MPNn. Investigating, differences between MPNd and MPNn, will make it possible to identify changes in the immune system, relevant for AMD pathogenesis. Additionally, we will compare patients with MPNs with patients with iAMD and nAMD.
In study I (Paper I), we found that patients with MPNs have a significantly higher prevalence of large drusen and consequently AMD from an earlier age compared to the estimates from three large population‐based studies. We also found that drusen prevalence was associated with a higher neutrophil‐to‐lymphocyte ratio indicating a higher level of chronic low‐grade inflammation in patients with drusen compared to those without drusen.
In study II (papers II, III and IV), we found immunological differences between patients with MPNd and MPNn. When we investigated markers of inflammation, we found a higher level of systemic inflammation in MPNd than MPNn. This was indicated by a higher inflammation score (based on levels of pro‐inflammatory markers), a higher neutrophil‐to‐lymphocyte ratio, and indications of a deregulated complement system. When examining markers of ageing, we found signs of accelerated immune ageing in MPNd compared to MPNn, shown by more senescent effector memory T cells.
Finally, when exploring a marker of angiogenesis, we found a lower CXCR3 expression on monocytes and T cells in nAMD compared to iAMD, MPNd and MPNn, in line with previous studies of nAMD compared to healthy controls. Further, we found decreasing CXCR3 expression over the MPN biological continuum. These studies indicate CXCR3 involvement in both nAMD and PMF, two disease stages characterised by angiogenesis and fibrosis.
From the results of this PhD project, we can conclude that the prevalence of drusen and AMD is increased in patients with MPN compared to the general population. Further, our results show that systemic inflammation may play a far more essential role in AMD pathogenesis than previously anticipated. We, therefore, propose an AMD model (Figure 18) where inflammation can initiate and accelerate the normal age‐dependent accumulation of debris in the retina, which later evolve into drusen, resulting in increased local inflammation, and over time early‐ and intermediate AMD. This results in the increased risk of developing the late debilitating stages of AMD.
... It is diagnosed by the 95-98% of presence of a JAK2V617F mutation, as well as an increase in haemoglobin/haematocrit above the threshold level defined by the 2016 World Health Organization revised criteria (>16.5 g/dL/49% for males and >16 g/dL/48% for females). [1][2][3] This condition, also known as primary polycythaemia, is characterized by an erythrocytosis of unknown origin in the bone marrow. 4,5 Given the systemic and haematological nature of PV, many tissues and organs are likely to be affected. ...
... Patients are predisposed to thrombotic and haemorrhagic events, as well as leukemic transformation, which are the leading causes of morbidity and mortality. 3,[5][6][7][8] Other symptoms, including ophthalmic, which are more often incorrectly identified as being caused by other ocular disorders, vary greatly and are frequently induced by haematological issues. These ophthalmic symptoms range from monocular vision loss due to retinal ischemia and papilledema, to combined retinal vein occlusion and anterior ischemic optic neuropathy. ...
Objective: To assess polycythaemia vera (PV)-related retinal microvascular morphological changes using optical coherence tomography angiography (OCTA).
Material and Methods: In this cross-sectional case-control study, 30 PV patients (Group 1) and 30 healthy individuals (Group 2) underwent a comprehensive ophthalmological examination, followed by OCTA acquisition in Angio Retina mode (6x6 mm). Macular superficial and deep vascular plexus vessel densities (VDs) in foveal, parafoveal, and perifoveal, as well as foveal avascular zone (FAZ) area, FAZ perimeter, and foveal VD in 300-µm wide region around FAZ (FD-300) were automatically analysed using AngioVue Analytics software. Sequential measurements were compared for statistical significance.
Results: Mean ages were 46.97±3.20 and 47.42±2.55 years in Groups 1 and 2, respectively (p=0.350). Group 1 had significantly increased superficial foveal VD than Group 2 (p=0.032). Besides, Group 1 had non-significantly increased VDs than Group 2 in the following areas: superficial whole (p=0.468), superficial parafoveal (p=0.692), deep foveal (p=0.752), deep perifoveal (p=0.369), FAZ perimeter (p=0.209), and FD-300 (p=0.914). The FAZ area decreased non-significantly in Group 1 compared to Group 2 (p=0.529).
Conclusion: PV appears to be associated with considerable retinal microvascular morphological changes, indicating a potential hyperviscosity impact on retinal VDs that would necessitate careful consideration during PV patient evaluation.
Keywords: Hyperviscosity syndrome; optical coherence tomography angiography; retinal microvasculature; polycythaemia vera; vessel density
... Ocular symptoms and signs in polycythemia usually occur mainly as a result of hyperviscosity from elevated hematocrit levels [10]. It has been reported that during episodes of retinal migraine and amaurosis fugax, fundus fluorescein angiography performed during that time can show delayed filling of the central retinal vessels [11]. ...
There are many causes of amaurosis fugax, including polycythemia. Polycythemia is associated with elevated hematocrit levels and hyperviscosity, which can lead to ocular manifestations. We report a polycythemia patient with amaurosis fugax, who had resolution of ocular symptoms following venesection. A 29-year-old gentleman presented with a six-month history of episodic bilateral transient loss of vision (amaurosis fugax), followed by slow recovery back to normal after 15-20 minutes. The symptoms worsened with fatigue. He also had an unsteady gait for the preceding one year. Ocular examination was unremarkable. His visual acuity was 20/20 OU. Neurological examination revealed gait ataxia and dysdiadochokinesia. Computed tomography (CT) angiogram showed an old cerebellar infarct. Blood investigations showed persistent elevated hemoglobin and hematocrit with positive JAK-2 V617F mutation. Infective and connective tissue workups were all negative. A diagnosis of polycythemia was made by the haematology team. In addition to oral aspirin given by the neurology team, he underwent venesection with improvement in ocular symptoms following each episode of venesection. The frequency of amaurosis fugax reduced from 2-3 episodes a week to once a month, then resolved completely after five venesections. Systemically, his cerebellar symptoms also resolved and there were no neurological deficits. Polycythemia is a rare disease that can cause amaurosis fugax and thrombotic events in young patients. Better knowledge and accurate diagnosis are important, as early treatment may improve the symptoms and long-term morbidity.
... Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) characterized by an abnormally elevated production of blood cells by the bone marrow [1,2]. Due to the resulting hyperviscosity, patients with PV are at high risk of developing thrombotic complications [1][2][3][4]. Ocular involvements include retinal artery occlusion, retinal vein occlusion, peripheral non-perfusion, retinal hemorrhages and visual field defects corresponding to cerebral nonperfusion [5][6][7][8]. These vascular occlusions usually lead to irreversible changes in the ocular blood flow [8][9][10]. ...
... Mutations in the tyrosine kinase gene Janus Kinase 2 (JAK2) are the leading cause of PV. Since the elevated red blood cell mass leads to an increased hemoglobin concentration, hematocrit value and blood viscosity, patients with PV are at high risk of developing thrombosis [1][2][3][4]. ...
Background
Polycythemia vera (PV) is a myeloproliferative neoplasm with increased hemoglobin, hematocrit, platelet count and leukocytosis, resulting in increased blood viscosity. PV which is initially presenting with ocular symptoms is rare, but irreversible retinal vessel occlusions leading to the diagnosis of PV have been described in literature.
Case presentation
We describe a patient with PV, initially presenting with attacks of monocular temporary loss of vision due to intermittent retinal artery occlusions of different retinal arteries. The patient was immediately treated with phlebotomy and the impaired arterial retinal perfusion could be restored without permanent retinal ischemia. We were able to document these transient arterial occlusions with fundus photography as well as fluorescein angiography. To the best of our knowledge, a case like this has never been documented before.
Conclusion
This report is pertinent, in order to raise awareness among clinicians for polycythemia vera, as it can in fact be used as a differential diagnosis for patients with retinal artery occlusion. We would like to stress that early therapy might reverse the vessel complications.
