Acta Ophthalmologica 2015
Incident retinal vein occlusions and estimated cerebrospinal fluid pressure. The Beijing Eye Study Jost B. Jonas,1,2 Ningli Wang,3 Ya Xing Wang,1 Qi Sheng You,1 Diya Yang,3 Xiaobin Xie3,4 and Liang Xu1 1
Beijing Ophthalmology and Visual Science Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China 2 Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany 3 Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China 4 Eye Hospital of China Academy of Chinese Medical Sciences, Beijing, China
ABSTRACT. Purpose: To examine whether the incidence of retinal vein occlusions (RVOs) is associated with estimated cerebrospinal fluid pressure (CSFP). Methods: The population-based Beijing Eye Study, which included 4439 subjects (age: 40 + years) in 2001, was repeated in 2011 with 2695 subjects participating (66.4% of the survivors). Fundus photographs were examined for the new development of RVOs, differentiated into central RVOs (CRVOs) and branch RVOs (BRVOs). CSFP was calculated as CSFP [mmHg] = 0.44 3 Body Mass Index [kg/m2] + 0.16 3 Diastolic Blood Pressure [mmHg] 0.18 3 Age[Years]. Results: Incident BRVOs were detected in 50 eyes and incident CRVOs in 8 eyes. BRVOs were located at arterio-venous crossings in 39 eyes. In multivariate analysis, a higher estimated CSFP was associated with a higher incidence of CRVOs (p = 0.004; standardized coefficient beta: 0.06; regression coefficient B: 5.35; 95% confidence interval (CI):1.73, 8.96) after adjusting for urban region (p < 0.001; beta: 0.52; B: 3.93; 95% CI: 4.29, 3.57), higher educational level (p = 0.001; beta: 0.13; B: 0.44; 95% CI: 0.28, 0.60), higher blood concentrations of triglycerides (p < 0.001; beta: 0.08; B: 0.11; 95% CI: 0.05, 0.16) and higher intraocular pressure (p < 0.001; beta: 0.16; B:0.21; 95% CI: 0.16, 0.27). As a corollary, a higher incidence of RVOs as a whole, as well as a higher incidence of CRVOs combined with a higher incidence of BRVOs originating at the optic nerve head, both were significantly associated with higher estimated CSFP (p = 0.002; odds ratio (OR): 1.15; 95% CI: 1.05, 1.25; and p = 0.037; OR: 1.17; 95% CI: 1.01, 1.35, respectively) after adjusting for older age. Conclusions: A higher estimated CSFP was associated with a higher incidence of RVOs originating at the optic nerve head (i.e. CRVOs, hemi-central RVOs and BRVOs originating at the optic nerve head), and vice versa, a higher incidence of RVOs was associated with a higher estimated CSFP. It suggested an influence of higher estimated CSFP on higher central retinal vein pressure. Key words: central retinal vein occlusion – cerebrospinal fluid pressure – glaucoma – translamina cribrosa pressure difference
Acta Ophthalmol. 2015: 93: e522–e526 ª 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
doi: 10.1111/aos.12575 Jost B. Jonas and Ningli Wang share the first authorship.
e522
Introduction Previous population-based studies have shown that among the main factors associated with prevalence and incidence of retinal vein occlusions (RVOs) are arterial hypertension and glaucomatous optic neuropathy (Wong et al. 2005; Liu et al. 2007). The association between RVOs and glaucomatous optic nerve damage has been discussed to be due to glaucomatous changes in the lamina cribrosa leading to an increased trans-lamina cribrosa outflow resistance (Jonas et al. 2003). The reason for the association between elevated arterial blood pressure and an intraocular outflow impediment (i.e. an RVO) on the venous side has remained unclear. As the blood pressure in the central retinal vein inside of the eye should be at least as high as the orbital cerebrospinal fluid pressure (CSFP), as retinal vein occlusions are characterized by a markedly elevated retinal vein pressure (Jonas & Harder 2007) and as recent clinical studies have shown that the CSFP is associated with arterial blood pressure, the hypothesis was put forward that the increased arterial blood pressure may lead via an increased CSFP to an increased pressure in the central retinal vein what may be a risk factor for the development of an RVO. We thus tested the hypothesis that an increased incidence of RVOs may be associated with a higher CSFP. We conducted a study in which, on the basis of a previously
Acta Ophthalmologica 2015
developed formula, we estimated the CSFP in eyes with RVOs and compared the values with the CSFP in eyes without RVOs (Ren et al. 2010, 2013; Berdahl et al. 2012; Xie et al. 2013). As study structure, we chose a populationbased design to avoid a referralinduced bias in the selection of study participants.
Methods The Beijing Eye Study is a populationbased prospective cohort study, which was performed in Greater Beijing, started in 2001 and was repeated in 2006 and 2011 (Wang et al. 2006; Xu et al. 2006; Jonas et al. 2009). The Medical Ethics Committee of Beijing Tongren Hospital approved the study protocol, and all participants gave informed written consent. The only eligibility criterion for the study was an age of 40 or more years in the year 2001. Of 5324 eligible individuals, 4439 individuals participated in the baseline study in 2001 (response rate: 83.4%). The mean age was 56.4 10.4 years (range: 40– 101 years). In 2006 and 2011, the study was repeated by inviting all participants from the survey of 2001. The details of participants and nonparticipants at baseline and at the 10-year follow-up examination and the examinations techniques have been described elsewhere (Zhou et al. 2013; Wang et al. 2014). Trained research technicians asked the questions from a standard questionnaire providing information on demographic variables such as age, gender, level of education, occupation, family income, known diagnosis of arterial hypertension and current treatment of arterial hypertension to the study participants. The blood pressure was measured with the participant sitting for at least 5 min. The study participants had refrained from smoking and drinking of coffee, tea or alcohol for at least 3 h. In addition, any exercise was not performed for the last 30 min prior to the blood pressure measurements. Arterial hypertension was defined as a systolic blood pressure ≥140 mm Hg and/or a diastolic blood pressure ≥90 mm Hg, and/or self-reported current treatment for arterial hypertension with antihypertensive medication. Colour fundus photographs (45°) (fundus camera CR6-45NM, Canon Inc., Ota, Tokyo, Japan) centred on the optic disc (Diabetic Retinopathy
Study standard field 1) and macula (Diabetic Retinopathy Study standard field 2) were taken in each eye. The photographs were examined for the presence of RVOs in a masked manner by a trained ophthalmologist (Zhou et al. 2013). Additionally, we examined the macular region by spectral-domain optical coherence tomography in 2011. A new or incident RVO was defined as an RVO which was detected in the survey from 2011 and which was not present at the time of the baseline examination in 2001. Retinal vein occlusions were differentiated into central retinal vein occlusions (CRVOs), which also included hemi-central RVOs, and into branch retinal vein occlusions (BRVOs). A recent CRVO (including hemi-central RVO) was defined by retinal oedema, optic disc hyperaemia or oedema, scattered superficial or deep retinal haemorrhages and venous dilation. Longstanding CRVOs were characterized by occluded and sheathed retinal veins or vascular anastomoses at the optic disc. A BRVO was defined by localized retinal oedema, superficial and deep retinal haemorrhages, intraretinal microvascular abnormalities or anastomotic vessels, and venous dilatation or venous sheathing within a sector of the retina corresponding to the obstructed vein. In eyes with BRVOs, the segment of the retina with the RVOs (superior temporal, inferior temporal, superior nasal or inferior nasal) and the location of the vessel occlusion (intrapapillary or extrapapillary) were recorded. Using the lumbar CSFP measurements obtained in a previous study, we assessed the associations between lumbar CSFP measurements, diastolic blood pressure, body mass index and age (Xu et al. 2006). All three parameters had been shown to be associated with CSFP (Berdahl et al. 2012; Ren et al. 2013; Xie et al. 2013). The indications for lumbar puncture in that study were peripheral neuropathy, intracranial hypertension, spontaneous intracranial hypotension, cavernous sinus syndrome, meningitis, multiple sclerosis, unilateral ischaemic optic neuropathy, unilateral optic neuritis, optic nerve atrophy and head injury (Xie et al. 2013). The measured CSFP was
Incident retinal vein occlusions and estimated cerebrospinal fluid pressure. The Beijing Eye Study Jost B. Jonas,1,2 Ningli Wang,3 Ya Xing Wang,1 Qi Sheng You,1 Diya Yang,3 Xiaobin Xie3,4 and Liang Xu1 1
Beijing Ophthalmology and Visual Science Key Lab, Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China 2 Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany 3 Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China 4 Eye Hospital of China Academy of Chinese Medical Sciences, Beijing, China
ABSTRACT. Purpose: To examine whether the incidence of retinal vein occlusions (RVOs) is associated with estimated cerebrospinal fluid pressure (CSFP). Methods: The population-based Beijing Eye Study, which included 4439 subjects (age: 40 + years) in 2001, was repeated in 2011 with 2695 subjects participating (66.4% of the survivors). Fundus photographs were examined for the new development of RVOs, differentiated into central RVOs (CRVOs) and branch RVOs (BRVOs). CSFP was calculated as CSFP [mmHg] = 0.44 3 Body Mass Index [kg/m2] + 0.16 3 Diastolic Blood Pressure [mmHg] 0.18 3 Age[Years]. Results: Incident BRVOs were detected in 50 eyes and incident CRVOs in 8 eyes. BRVOs were located at arterio-venous crossings in 39 eyes. In multivariate analysis, a higher estimated CSFP was associated with a higher incidence of CRVOs (p = 0.004; standardized coefficient beta: 0.06; regression coefficient B: 5.35; 95% confidence interval (CI):1.73, 8.96) after adjusting for urban region (p < 0.001; beta: 0.52; B: 3.93; 95% CI: 4.29, 3.57), higher educational level (p = 0.001; beta: 0.13; B: 0.44; 95% CI: 0.28, 0.60), higher blood concentrations of triglycerides (p < 0.001; beta: 0.08; B: 0.11; 95% CI: 0.05, 0.16) and higher intraocular pressure (p < 0.001; beta: 0.16; B:0.21; 95% CI: 0.16, 0.27). As a corollary, a higher incidence of RVOs as a whole, as well as a higher incidence of CRVOs combined with a higher incidence of BRVOs originating at the optic nerve head, both were significantly associated with higher estimated CSFP (p = 0.002; odds ratio (OR): 1.15; 95% CI: 1.05, 1.25; and p = 0.037; OR: 1.17; 95% CI: 1.01, 1.35, respectively) after adjusting for older age. Conclusions: A higher estimated CSFP was associated with a higher incidence of RVOs originating at the optic nerve head (i.e. CRVOs, hemi-central RVOs and BRVOs originating at the optic nerve head), and vice versa, a higher incidence of RVOs was associated with a higher estimated CSFP. It suggested an influence of higher estimated CSFP on higher central retinal vein pressure. Key words: central retinal vein occlusion – cerebrospinal fluid pressure – glaucoma – translamina cribrosa pressure difference
Acta Ophthalmol. 2015: 93: e522–e526 ª 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
doi: 10.1111/aos.12575 Jost B. Jonas and Ningli Wang share the first authorship.
e522
Introduction Previous population-based studies have shown that among the main factors associated with prevalence and incidence of retinal vein occlusions (RVOs) are arterial hypertension and glaucomatous optic neuropathy (Wong et al. 2005; Liu et al. 2007). The association between RVOs and glaucomatous optic nerve damage has been discussed to be due to glaucomatous changes in the lamina cribrosa leading to an increased trans-lamina cribrosa outflow resistance (Jonas et al. 2003). The reason for the association between elevated arterial blood pressure and an intraocular outflow impediment (i.e. an RVO) on the venous side has remained unclear. As the blood pressure in the central retinal vein inside of the eye should be at least as high as the orbital cerebrospinal fluid pressure (CSFP), as retinal vein occlusions are characterized by a markedly elevated retinal vein pressure (Jonas & Harder 2007) and as recent clinical studies have shown that the CSFP is associated with arterial blood pressure, the hypothesis was put forward that the increased arterial blood pressure may lead via an increased CSFP to an increased pressure in the central retinal vein what may be a risk factor for the development of an RVO. We thus tested the hypothesis that an increased incidence of RVOs may be associated with a higher CSFP. We conducted a study in which, on the basis of a previously
Acta Ophthalmologica 2015
developed formula, we estimated the CSFP in eyes with RVOs and compared the values with the CSFP in eyes without RVOs (Ren et al. 2010, 2013; Berdahl et al. 2012; Xie et al. 2013). As study structure, we chose a populationbased design to avoid a referralinduced bias in the selection of study participants.
Methods The Beijing Eye Study is a populationbased prospective cohort study, which was performed in Greater Beijing, started in 2001 and was repeated in 2006 and 2011 (Wang et al. 2006; Xu et al. 2006; Jonas et al. 2009). The Medical Ethics Committee of Beijing Tongren Hospital approved the study protocol, and all participants gave informed written consent. The only eligibility criterion for the study was an age of 40 or more years in the year 2001. Of 5324 eligible individuals, 4439 individuals participated in the baseline study in 2001 (response rate: 83.4%). The mean age was 56.4 10.4 years (range: 40– 101 years). In 2006 and 2011, the study was repeated by inviting all participants from the survey of 2001. The details of participants and nonparticipants at baseline and at the 10-year follow-up examination and the examinations techniques have been described elsewhere (Zhou et al. 2013; Wang et al. 2014). Trained research technicians asked the questions from a standard questionnaire providing information on demographic variables such as age, gender, level of education, occupation, family income, known diagnosis of arterial hypertension and current treatment of arterial hypertension to the study participants. The blood pressure was measured with the participant sitting for at least 5 min. The study participants had refrained from smoking and drinking of coffee, tea or alcohol for at least 3 h. In addition, any exercise was not performed for the last 30 min prior to the blood pressure measurements. Arterial hypertension was defined as a systolic blood pressure ≥140 mm Hg and/or a diastolic blood pressure ≥90 mm Hg, and/or self-reported current treatment for arterial hypertension with antihypertensive medication. Colour fundus photographs (45°) (fundus camera CR6-45NM, Canon Inc., Ota, Tokyo, Japan) centred on the optic disc (Diabetic Retinopathy
Study standard field 1) and macula (Diabetic Retinopathy Study standard field 2) were taken in each eye. The photographs were examined for the presence of RVOs in a masked manner by a trained ophthalmologist (Zhou et al. 2013). Additionally, we examined the macular region by spectral-domain optical coherence tomography in 2011. A new or incident RVO was defined as an RVO which was detected in the survey from 2011 and which was not present at the time of the baseline examination in 2001. Retinal vein occlusions were differentiated into central retinal vein occlusions (CRVOs), which also included hemi-central RVOs, and into branch retinal vein occlusions (BRVOs). A recent CRVO (including hemi-central RVO) was defined by retinal oedema, optic disc hyperaemia or oedema, scattered superficial or deep retinal haemorrhages and venous dilation. Longstanding CRVOs were characterized by occluded and sheathed retinal veins or vascular anastomoses at the optic disc. A BRVO was defined by localized retinal oedema, superficial and deep retinal haemorrhages, intraretinal microvascular abnormalities or anastomotic vessels, and venous dilatation or venous sheathing within a sector of the retina corresponding to the obstructed vein. In eyes with BRVOs, the segment of the retina with the RVOs (superior temporal, inferior temporal, superior nasal or inferior nasal) and the location of the vessel occlusion (intrapapillary or extrapapillary) were recorded. Using the lumbar CSFP measurements obtained in a previous study, we assessed the associations between lumbar CSFP measurements, diastolic blood pressure, body mass index and age (Xu et al. 2006). All three parameters had been shown to be associated with CSFP (Berdahl et al. 2012; Ren et al. 2013; Xie et al. 2013). The indications for lumbar puncture in that study were peripheral neuropathy, intracranial hypertension, spontaneous intracranial hypotension, cavernous sinus syndrome, meningitis, multiple sclerosis, unilateral ischaemic optic neuropathy, unilateral optic neuritis, optic nerve atrophy and head injury (Xie et al. 2013). The measured CSFP was
