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Show The Clinical Validity of the Spontaneous Retinal Venous Pulsation Sui Hsien Wong, MRCP, Richard Patrick White, MD, FRCP Background: The validity of the clinical dictum "the pres-ence of spontaneous retinal venous pulsation (SVP) excludes raised intracranial pressure" has not been previ-ously tested. We set out to determine the specificity and positive predictive value (PPV) of the presence of SVP to indicate normal intracranial pressure (ICP) in a routine clin-ical setting. Methods: We prospectively recruited patients undergoing lumbar puncture (LP), and 2 clinicians were blinded to the indications for LP and cerebrospinal fluid opening pressure (OP). Interobserver reliability was assessed. Results: There were 106 patients in our cohort with a median age of 44 years (range, 18-79 years) and median body mass index of 27.5 kg/m2 (range, 18-48 kg/m2). SVP was present in 94 of 106 patients (88.7%). Thirteen of 106 (12.3%) patients had high OP ($30 cmH2O), and SVP was present in 11 of 13 patients (86%) with high OP. The sen-sitivity (95% confidence interval) of the presence of SVP to exclude raised ICP was 0.89 (0.88-0.92), specificity of 0.15 (0.05-0.37), PPV of 0.88 (0.87-0.9), and negative predictive value of 0.17 (0.05-0.4). Interobserver agree-ment was moderate for SVP (kappa = 0.42). Conclusions: Although the sensitivity and PPV of the presence of SVP to exclude raised ICP is high, it is not absolute. SVP can be seen in some patients with high ICP. Relying on the presence of SVP to exclude raised ICP may give a false sense of reassurance. Journal of Neuro-Ophthalmology 2013;33:17-20 doi: 10.1097/WNO.0b013e3182622207 © 2012 by North American Neuro-Ophthalmology Society Spontaneous retinal venous pulsation (SVP) is subtle, rhythmic, narrowing, and dilation of a retinal vein, synchronous with the cardiac cycle. SVP is usually observed at the point where the vessels penetrate the optic disk and is seen in up to 90% of the normal population (1). Jacks and Miller (2) published a review of the proposed mechanism and presented compelling evidence that SVP is a result of fluctuations of the pressure gradient between the intraocular and the retrolaminar cerebrospinal fluid (CSF) pressure. The difference in pulse pressure between the intraocular space and the CSF results in changes in retinal vein diam-eter (seen as venous pulsation) as it crosses the lamina cribrosa. A rise in intracranial pressure (ICP) would affect this fluctuation of pressure gradient, resulting in the loss of the SVP. A well-known clinical dictum states that "the presence of SVP excludes raised intracranial pressure" (3,4). However, the clinical validity of this dictum has not been tested. Our anecdotal experience of observing SVP immediately before lumbar puncture (LP) in some patients with high ICPs suggests that this dictum is not absolute. The aim of our study was to determine whether the presence of SVP is a valid test to exclude raised ICP. METHODS In a prospective manner, from November 2009 to August 2010, we recruited an unselected population of adult patients scheduled for LP as part of their neurological evaluation. Patients were excluded if they were known to have glaucoma, optic neuritis or if they were receiving topical treatment for ocular disease. By examining a portion of our patient cohort, 2 observers were selected to assess interobserver reliability. The observers were blinded to the indications for LP and the CSF opening pressure (OP). The OP was measured in the left lateral decubitus position. Patients were examined before LP with direct ophthalmo-scope through undilated pupils in the sitting or upright position. SVP was noted to be either present or absent in each eye. If SVP was present, the degree of change in diameter was graded on a scale described by Hedges et al (5): Grade 1, up to 33% change in vessel diameter; Grade 2, 33%-66% change in diameter; and Grade 3, more than Department of Neurology (SHW, RPW), The Walton Center NHS Foundation Trust, Liverpool, United Kingdom. The authors report no funding or conflicts of interest. Address correspondence to Sui Hsien Wong, MRCP, Neurology Office 2, Department of Neurology, The Walton Center, Lower Lane, Liverpool L9 7LJ, United Kingdom; E-mail: suiwong@doctors.org.uk Wong and White: J Neuro-Ophthalmol 2013; 33: 17-20 17 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. 66% change in diameter. SVP was considered to be present in a patient if SVP is seen in one or both eyes. Results were analyzed using SPSS version 16.0. For the purposes of data analysis, an OP of ,30 cmH2O was considered normal and $30 cmH2O was considered elevated. This study received local ethics committee approval. RESULTS A total of 106 patients were included of which 76 were women. The median age was 44 years (range, 18-79 years) and the body mass index was 27.5 kg/m2 (range, 18-48 kg/m2). All patients were examined by Observer 1 (S.H.W.), and a random subset of 33 patients were examined both by Observer 1 and Observer 2 (R.W.). The median time interval from LP to ophthalmoscopy was 1 hour 45 minutes (range, 15 minutes to 6.5 hours). Indications for LP were for the investigation of headache (43 patients), possible central nervous system (CNS) inflammation (30 patients), peripheral nervous system symptoms (15 patients), and other CNS symptoms (18 patients). Table 1 shows the observation of SVP per patient. SVP was considered present if it was observed in at least 1 eye. Results of each SVP observed are summarized in Tables 2 and 3. Ninety-three of 106 patients had CSF OP ,30 cmH2O and 83 (89%) of them had SVP. Thirteen of 106 patients (12%) had OP $ 30 cmH2O of whom 11 had SVP. In a group of 33 patients who were examined by Observer 2, 5 of 33 patients (15%) hadOP $ 30 cmH2O and 4 patients (80%) of whom had SVP. Sensitivity (95% confidence interval), that is, how likely the presence of SVP was indicative of normal ICP, was 0.89 (0.82-0.92). Positive predictive value (PPV), that is, the proportion of patients with SVP who have normal ICP, was 0.88 (0.87-0.9). Specificity, that is, how likely is the absence of SVP indicative of increased ICP, was 0.15 (0.05-0.37). Negative predictive value, that is, the proportion of patients with absent SVP who have high ICP, was 0.17 (0.05-0.4). Table 4 compares the statistical test results of both observers, showing similar results between both observers. The interobserver reliability between Observer 1 and Observer 2 was moderate (kappa = 0.42). Twenty patients being evaluated for idiopathic intracranial hypertension had mild papilledema. All patients were exam-ined by Observer 1; 16 patients had bilateral papilledema and 4 unilateral papilledema. SVP was observed in 12 of 20 patients of whom 5 of 7 patients had an OP $30 cmH2O (mean 36.1 cmH2O) and 6 of 12 patients with OP 26-30 cmH2O. Observer 2 examined a subset of 7 patients with mild papilledema seen by Observer 1 and found SVP in 3 patients (mean OP 30.5 cmH2O). There was good interob-server agreement for papilledema (kappa, 0.79). DISCUSSION Our study was designed to test the clinical dictum that "the presence of SVP excludes raised ICP." Patients were exam-ined in a routine manner using a direct ophthalmoscope, with undilated pupils and in the sitting or upright position. From the studies showing a direct relationship between ICP and SVP (1,6-8), SVP is reported to disappear with a CSF pressure above 20 cmH2O. However, the position in which patients were examined may be relevant. In these studies, many patients were examined in the recumbent position. Yet, ICP is higher in the recumbent than in the sitting position (9), and this factor may affect the presence of SVP. By examining the patient in the supine position, the SVP may disappear at a lower CSF OP (as measured on LP) because of the relative increase in ICP. Conversely, the CSF pressure in the brain is lower in the sitting position, possibly increasing the likelihood of observing SVP in this position. Thus, detection of SVP in the supine versus the sitting position may not be comparable. We chose 30 cmH2O as a cutoff for purposes of calcu-lating sensitivity and PPV, so as to be unequivocal with respect to raised ICP. The upper limit of the 95% TABLE 1. Results of Observer 1 and Observer 2 Observer 1 Observer 2 OP , 30 cmH2O OP $ 30 cmH2O OP , 30 cmH2O OP $ 30 cmH2O SVP present 83 11 21 4 SVP absent 10 2 7 1 All 33 patients examined by Observer 2 were also examined by Observer 1. SVP, spontaneous retinal venous pulsation; OP, opening pressure. TABLE 2. Observer 1's examination of 210 eyes SVP Absent SVP Grade 1 SVP Grade 2 SVP Grade 3 OP , 30 cmH2O 35 116 26 7 OP $ 30 cmH2O 10 14 2 0 106 patients, missing data from 2 eyes of different patients due to the lack of a clear fundus view. TABLE 3. Observer 2's examination of 66 eyes (33 patients) SVP Absent SVP Grade 1 SVP Grade 2 SVP Grade 3 OP , 30 cmH2O 9 42 4 1 OP $ 30 cmH2O 2 7 1 0 OP, opening pressure; SVP, spontaneous retinal venous pulsation. 18 Wong and White: J Neuro-Ophthalmol 2013; 33: 17-20 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. confidence interval for a normal CSF OP in the left lateral position is 25 cmH2O (10). Repeating the statistical anal-ysis using 25 cmH2O as the upper limit for normal ICP resulted in a sensitivity of 0.94 (0.89-0.97) and PPV of 0.78 (0.74-0.81). Sensitivity and PPV are useful statistical values to test the validity of the "presence of SVP" to exclude raised ICP because both these statistical values describe the "presence of SVP." Although the results for sensitivity and PPV are high, they are not 100%. Patients with high ICPs may have SVP. This is contrary to the previous reports (1,6-8), where no SVP was seen with increased ICP (1,6-8), implying a 100% sensitivity. In our study, the proportion of patients with normal ICPwas more than those with high ICP. In statistical terms, this would affect the PPV (i.e., patients with SVP and normal ICP/all patients with SVP observed) but not the sensitivity (i.e., patients with SVP and normal ICP/all patients with normal ICP). In our group of patients with high ICPs, the proportion observed to have SVP were 11 of 13 patients (85%) and 4 of 5 patients (80%) by Observers 1 and 2, respectively. Similarly, a recent retrospective cross-sectional analysis of patients with IIH with and without papilledema (IIHWOP) reported SVP in 12 of 16 patients (75%) with IIHWOP and mean CSF pressures of 31 cmH2O (range, 26-42 cmH2O) (11). Our results demonstrated a low specificity and negative predictive value to this test, that is, the absence of SVP is not a helpful clinical sign. This is in keeping with the previous observations that SVP may be absent in up to 40% of patients with normal ICP (8). The absence of SVP should not be relied upon to indicate high ICP. One potential confounding factor is that ICP fluctuates throughout the day (9). We believe that the time interval from ophthalmoscopy to LP in our study was close enough to avoid this confounding factor. We observed SVP in 12 of 20 patients with mild papilledema. This could reflect the borderline raised ICP and/or resolving papilledema because these patients were under treatment for IIH. Most of these patients had OPs ranging from 26 to 30 cmH2O. The numbers in this sub-group with mild papilledema and SVP are too small for us to draw a firm conclusion. Although the clinical observations were similar between Observers 1 and 2 (i.e., sensitivity, PPV values, and kappa test), this study also demonstrates that interobserver variability does occur. It is possible that this variability may be reduced with pupillary dilation. Although some of this variability may be reduced with improved funduscopy following pupillary dilation, our goal was to reflect our usual practice in an outpatient setting. A number of factors might be evaluated in future studies to further investigate the relativity of SVP and ICP. Recording the intraocular pressure and a description of anatomic variations of retinal veins may influence the visibility of SVP (2). Correlation of the ICP with SVP grad-ing and examination in both the supine and sitting position would add important information. Use of newer technolo-gies such as video (12) and time-lapse photography (13) might affect both detection and grading of SVP. Finally, a larger number of observers would improve the statistical strength and assessment of interobserver reliability. In conclusion, the presence of SVP as a clinical sign to exclude raised ICP should be used with caution. We have shown that although the sensitivity and PPV of this clinical sign is high, it is not absolute, and patients with increased ICP could be missed if this clinical sign was solely relied upon. ACKNOWLEDGMENTS The authors thank Dr Gordon T. Plant for helpful discussions and comments on the first draft of the manu-script; Dr Antonio Eleuteri for statistical advice on power of study; Dr Brian Faragher for helpful discussions on di-agnostic statistics; Mrs Ann Bailey, Sister Anne-Marie Antoine Payet, and nursing staff on Jefferson Day Unit, Consultant Neuroradiologists, and Neurology Senior House Officers who performed the lumbar punctures; Consultant Neurologists at The Walton Centre who allowed recruitment of their patients. The results of this study were presented at the United Kingdom Neuro-Ophthalmology Special Interest Group annual meeting, March 18, 2011, in Birmingham, United Kingdom; the Association of British Neurologists annual meeting, April 5 2011, in Havana, Cuba; and the American Academy of Neurology annual meeting, April 13, 2011, in Honolulu, Hawaii. REFERENCES 1. Levin B. The clinical significance of spontaneous pulsations of the retinal vein. Arch Neurol. 1978;35:37-40. TABLE 4. A comparison of the results from Observer 1 and Observer 2: sensitivity, specificity, and positive and negative predictive values of "presence of SVP" as a test to exclude raised intracranial pressure Results Observer 1 (95% Confidence Interval) Observer 2 (95% Confidence Interval) Sensitivity 0.89 (0.88-0.92) 0.75 (0.72-0.82) Specificity 0.15 (0.05-0.37) 0.2 (0.04-0.58) PPV 0.88 (0.87-0.91) 0.84 (0.81-0.92) NPV 0.17 (0.05-0.37) 0.13 (0.02-0.36) Sensitivity refers to how likely is the presence of SVP to indicate normal intracranial pressure. Specificity refers to how likely is the absence of SVP to indicate high intracranial pressure. PPV is the proportion of patients with SVP who have normal intracranial pres-sure. NPV is the proportion of patients with absent SVP who have high intracranial pressure. NPV, negative predictive value; PPV, positive predictive value; SVP, spontaneous retinal venous pulsation. Wong and White: J Neuro-Ophthalmol 2013; 33: 17-20 19 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. 2. Jacks A, Miller N. Spontaneous retinal venous pulsation: aetiology and significance. J Neurol Neurosurg Psychiatry. 2003;74:7-9. 3. Ropper A, Brown R. Adams and Victor's Principles of Neurology. New York, NY: McGraw Hill, 2005:212. 4. Walsh T. Spontaneous Venous Pulse. Neuro-ophthalmology: Clinical Signs and Symptoms. Philadephia, PA: Lea & Febiger, 1992:25. 5. Hedges TJ, Baron E, Hedges TI, Sinclair S. The retinal venous pulsation. Ophthalmology. 1994;101:542-547. 6. Kahn E, Cherry G. The clinical importance of spontaneous retinal venous pulsation. Univ Mich Med Bull. 1950;16: 305-308. 7. Walsh T, Garden J, Gallagher B. Relationship of retinal venous pulse to intracranial pressure. In: Smith JL, ed. Neuro-ophthalmology, 4th edition. St Louis, MO: CV Mosby, 1968;288-292. 8. LoZito J. 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Presented at: Annual Meeting of American Academy of Neurology, April 13, 2011. [poster P04.273]. 20 Wong and White: J Neuro-Ophthalmol 2013; 33: 17-20 Original Contribution Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. |