|Year : 2015 | Volume
| Issue : 2 | Page : 61-66
Correlation between optical coherence tomography parameters and retinal sensitivity in idiopathic intracranial hypertension
Dalia H Khalil1, Dalia M Labib2
1 Department of Ophthalmology, Kasr Elaini Hospital, Cairo University, Cairo, Egypt
2 Department of Neurology, Kasr Elaini Hospital, Cairo University, Cairo, Egypt
|Date of Submission||07-Dec-2014|
|Date of Acceptance||29-Apr-2015|
|Date of Web Publication||23-Jul-2015|
Dalia H Khalil
8 Mohei El Din Street, Dokki, Cairo 12311
Source of Support: None, Conflict of Interest: None
The aim of this study was to report the findings of optical coherence tomography measurement of retinal nerve fiber layer (RNFL) thickness and ganglion cell complex (GCC) in idiopathic intracranial hypertension (IIH) patients and to assess whether the RNFL and GCC correlate with retinal sensitivity determined by automated perimetry in the form of mean deviation (MD) and pattern standard deviation.
Patients and methods
A prospective observational study was carried out for 30 patients with confirmed IIH (age ≥18 years), BMI below 25, intracranial pressure (ICP) of at least 20 cmH 2 O, and normal neurological examination (except for papilloedema and horizontal diplopia). All patients received a complete neurological examination and most recent lumbar puncture opening pressure (latest ICP) was recorded. Complete ophthalmic evaluation including best-corrected visual acuity, perimetry, RNFL, and GCC thickness within 24 h of performing lumber puncture.
In IIH patients the initial RNFL thickness was significantly higher, whereas GCC was significantly lower than controls (P = 0.045 and 0.004, respectively). The value of ICP measured was found to be positively correlated with the stage of papilloedema (r = 0.494, P = 0.000). The final recordings showed a significant decrease in GCC and RNFL values (P = 0.000 and 0.002, respectively), and improvement in MD (P = 0.003). Regression analysis showed that for every 10 μm increase in mean RNFL thickness, there was worsening in MD of 0.56 dB, whereas for every 10 μm decrease in mean GCC thickness, there was worsening in MD of 0.9 dB at the last follow-up.
GCC and RNFL thickness abnormalities assessed by optical coherence tomography in IIH patients were quantitatively correlated with visual field sensitivity losses and can be definitively useful to quantify optic nerve damage.
Keywords: Ganglion cell complex, idiopathic intracranial hypertension, optical coherence tomography, perimetry, retinal nerve fiber layer
|How to cite this article:|
Khalil DH, Labib DM. Correlation between optical coherence tomography parameters and retinal sensitivity in idiopathic intracranial hypertension. J Egypt Ophthalmol Soc 2015;108:61-6
|How to cite this URL:|
Khalil DH, Labib DM. Correlation between optical coherence tomography parameters and retinal sensitivity in idiopathic intracranial hypertension. J Egypt Ophthalmol Soc [serial online] 2015 [cited 2023 Jan 31];108:61-6. Available from: http://www.jeos.eg.net/text.asp?2015/108/2/61/161392
| Introduction|| |
Idiopathic intracranial hypertension (IIH), also known as pseudotumor cerebri, is a clinical syndrome of unknown etiology characterized by increased intracranial pressure (ICP), which typically affects young, obese women of child-bearing age with no obvious underlying brain pathological condition or any evidence of venous thrombosis . Clinical symptoms include headache, visual disturbances, pulsating tinnitus, photophobia, eye pain, diplopia, and nausea. Papilloedema with subsequent visual field loss is the most feared clinical consequence, which mainly determines the therapy and outcome of the syndrome .
However, although detection of papilloedema by the ophthalmologist is a powerful tool in primary diagnosis, it remains a limited method in producing quantitative data to evaluate longitudinal optic disc changes in patients with IIH ,.
Optical coherence tomography (OCT), a noninvasive imaging technique that obtains retinal images closely resembling histological preparations, is useful for evaluating the peripapillary nerve fiber layer. OCT can detect and quantify diffuse thickening of the retinal nerve fiber layer (RNFL) in eyes with optic disc edema associated with several neuropathies such as optic neuritis, multiple sclerosis, neuromyelitis optica, spinocerebellar ataxia, and Parkinson's disease . The goals of this study were to report the findings of OCT evaluation in adults with papilloedema associated with IIH at onset and after 6-month follow-up and to assess whether the RNFL and ganglion cell complex (GCC) thickness measured by OCT correlates quantitatively with the severity of visual dysfunction determined by automated perimetry.
| Patients and methods|| |
A prospective observational study was carried out for of 30 patients with confirmed IIH according to the International Headache Society classification criteria B  and healthy control participants. This classification is hierarchical, and you must decide how detailed you want to make your diagnosis. This can range from the first-digit level to the fifth. First, one gets a rough idea about which group the patient belongs to. Is it, for example, (a) migraine or (b) tension-type headache or (c) trigeminal autonomic cephalalgias? Then one obtains information allowing a more detailed diagnosis. The desired detail depends on the purpose. In general practice, only the first-digit or second-digit diagnoses are usually applied, whereas in specialist practice and headache centers a diagnosis at the fourth-digit or fifth-digit level is appropriate .
The study patients were recruited from the Neurology Department of Kasr Eleiny Hospital of Cairo University from October 2013 to April 2014.
Age 18 years and above, BMI below 25, CSF opening pressure (ICP) of at least 20 cmH 2 O, normal CSF composition, normal MRI and MR venography, and normal neurological examination except for papilloedema and horizontal diplopia .
BMI of at least 25, the presence of an ocular disease other than papilloedema, the presence of systemic diseases that precluded adequate follow-up and examination, and best-corrected visual acuity (BCVA) of at least 1.0 log MARs.
All patients received neurological examination and the following data were registered: current IIH symptoms (i.e. headache, visual obscurations, tinnitus, dizziness, and nausea) and lumbar puncture opening pressure (latest ICP). Lumbar puncture was performed in all patients using a standard 18- or 20-G spinal needle and a manometer positioned at a 90° angle to the spine. The opening pressure was measured, whereas the participant was placed in lateral decubitus position and as relaxed as possible. After the subarachnoid space was punctured, cerebrospinal fluid opening pressure was determined by means of a column manometer. All lumbar punctures were performed by the same neurologist (the second author)
Within 24 h of performing lumber puncture, one eye of each patient who met the study criteria underwent ophthalmic evaluation including BCVA log MARS, biomicroscopy of the anterior and posterior segments, ocular tonometry, and automated perimetry (Swedish Interactive Threshold Algorithm standard 24-2 strategy, Humphrey Visual Field Analyzer; Carl Zeiss Meditec, Dublin, California, USA). A SITA standard strategy, program 24-2, was used to decrease the duration of the exam. The outcome measures evaluated were mean deviation [(MD), dB] and pattern of visual field loss [pattern standard deviation (PSD), dB].
OCT was performed using the RTVue spectral-domain OCT (Optovue Inc., Fremont, California, USA). It is based on the new-generation Fourier-domain optical coherence technology. Two different protocols were used: the first was the macular map protocol [12 radial line scans (1024 A-scans per line) in a three-dimensional 6 × 6 mm area (2.0 s)], which allows fast macular scan for GCC measurement. The second was the peripapillary RNFL NHM4 protocol [12 radial scans (452 A-scans per line) over 3.45-mm diameter centered on the optic disc]. It has the advantage of eye tracking and signal noise reduction. All scans were performed by a single investigator with ambient lighting and without pupil dilation to ensure patient comfort. Magnification of images 400-800% with contrast enhancement allowed for proper and accurate layer delineation.
A 90-D lens biomicroscopic assessment of the grade of papilloedema done by the first author was based on the modified Frisén scale [Table 1] .
Thirty age-matched and sex-matched control participants were recruited from staff and family members of patients. Symptoms of increased ICP as well as a diagnosis of IIH were ruled out clinically and by fundus examination in the control group. The same examinations of the patient group applied to the control group with BCVA at least 0.18 (log MARs) added to the inclusion criteria.
The research followed the tenets of the Declaration of Helsinki. All participants provided a written informed consent after explanation of the nature and possible consequences of the study. The research was approved by the Research Ethical Committee of Faculty of Medicine of Cairo University.
Data were statistically described in terms of mean ± SD, median and range, or frequencies (number of cases), and percentages when appropriate. Comparison between cases and control groups was done using Student t-test for independent samples. Within-group comparison between early and late values was done using the paired t-test. Correlation between various variables was done using Pearson moment correlation equation for linear relation in normally distributed variables and Spearman rank correlation equation for either non-normal variables or those with nonlinear relation. P-values less than 0.05 were considered statistically significant. All statistical calculations were performed using SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, Illinois, USA) version 15 for Microsoft Windows.
| Results|| |
The study enrolled 30 eyes from 30 Egyptian IIH patients: 29 female and one male patient (one eye from each patient was included) with 30 age-matched and sex-matched healthy controls. As we evaluated age-matched and sex-matched healthy participants, no differences were observed in these descriptive characteristics between IIH patients and the control group. Their demographic data and clinical parameters are presented in [Table 2].
|Table 2: Demographic and clinical variables of idiopathic intracranial hypertension patients in the first visit and healthy controls|
Click here to view
As shown in [Table 2], we detected statistically significant differences in IIH cases collectively in the first visit when compared with controls regarding MD, PSD, and RNFL; on the other hand there was insignificant lower GCC thickness than that of healthy controls.
The value of ICP measured was found to be significantly positively correlated (using Spearman's ñ correlation coefficient) with the stage of papilloedema (r = 0.494, P = 0.000). Other variables including BCVA, MD, and PSD did not show this correlation. It is worth noting that the mean CSF opening pressure was not correlated either with the mean initial average RNFL thickness (P = 0.210) or with the mean initial average GCC (P = 0.337). The grade of papilloedema ranged from I to IV with median of grade II among the studied IIH patients.
Although the initial average RNFL thickness was collectively significantly higher than that of healthy controls, it was higher than normal databases in 40% of cases, within normal in 32% of cases, and below normal in 28% of cases. Concerning the initial average GCC thickness, it was within normal databases in 65% of cases and below it in 35% of cases.
When analyzing the previous data we found that 85% of patients with decreased RNFL thickness showed also decreased GCC thickness, whereas 13% of patients with elevated RNFL thickness had associated decreased GCC thickness.
After 6 months of recording the initial data, another recording was taken including BCVA, RNFL, GCC, MD, and PSD, and we compared these data with the previous ones.
The most significant decrease was in GCC value (P = 0.000), followed by RNFL (P = 0.002), and papilloedema (P = 0.023). There was significant improvement in MD (P = 0.003). Other variables including PSD and visual acuity showed insignificant change after 6 months' follow-up. [Table 3] highlights the comparison between early and late visits regarding visual parameters in IIH patients.
|Table 3: Comparison between early and late visual parameters in idiopathic intracranial hypertension patients|
Click here to view
[Table 4] illustrates the correlation between baseline OCT parameters and final perimetry by the end of 6 months of follow-up of the IIH cases. We found significant nonlinear correlation between initial peripapillary RNFL with final MD (r = −0.368, P = 0.004) [Figure 1] and PSD (r = 0.359, P = 0.005).
|Figure 1: Correlation between initial peripapillary retinal nerve fiber layer (RNFL) with final mean deviati on (MD).|
Click here to view
|Table 4: Correlation between baseline optical coherence tomography parameters and final perimetry of idiopathic intracranial hypertension patients|
Click here to view
As regards initial GCC, it showed significant linear correlation with final MD (r = 0.710, P = 0.000) [Figure 2] as well as final PSD (r = −0.450, P = 0.000) in IIH cases.
|Figure 2: Correlation between initial ganglion cell complex (GCC) with final mean deviation (MD).|
Click here to view
Regression analysis showed that for every 10 μm of mean RNFL thickness increase at baseline, there was a 0.56 dB worsening in MD; on the other hand, for every 10 μm of mean GCC thickness decrease at baseline, there was a 0.9 dB worsening in MD at the last follow-up.
| Discussion|| |
Several studies have shown that quantitative perimetry and optic nerve examination are more sensitive than visual acuity ,. The presence of papilloedema is the hallmark of suspected disease, and its severity determines the overall treatment strategy. Papilloedema can be monitored using qualitative and quantitative methods. In the present study, we evaluated the correlations between OCT parameters (including RNFL and GCC thickness) and the perimetric indices MD and PSD in patients with IIH over 6 months of follow-up. This is one of the few reports to evaluate such a relationship in adults using OCT.
In the present study, we found that in the eyes of IIH cases there was a statistically significant higher baseline average RNFL thickness as well as PSD compared with controls. As regards GCC thickness and MD, both showed significantly lower baseline values when compared with controls.
In accordance with our findings, in 2007 El-Dairi and colleagues reported a thicker average RNFL in eyes of children with pseudotumor cerebri compared with controls. The mean average RNFL thickness reported by El-Dairi et al.  (125.7 ± 29.6 μm) was lower than that in the present study (130.16 ± 46.4 μm) probably because of milder baseline optic disc edema (the median optic nerve clinical grade reported by them was 1.0 vs. 2.0 in the present study).
In 2009, Rebolleda and Mun˜oz-Negrete carried out a case-control study in patients with early papilloedema associated with IIH. Their results also agreed with ours concerning the RNFL thickness, they found that the mean average RNFL in the eyes with papilloedema was significantly greater than that of control subjects (P = 0.000) .
Our results agrees with the case-control study conducted by Skau and colleagues in 2013 for 20 newly diagnosed, 21 long-term IIH patients, and 20 healthy controls. Investigations included measurement of peripapillary RNFL thickness and total retinal thickness, automated visual field testing, and measurement of CSF opening pressure. They also found that PSD was significantly increased (P = 0.0005) and MD was significantly decreased (P = 0.0005) in IIH patients as compared with healthy controls .
When analyzing our data we found that 85% of patients with decreased RNFL thickness showed also decreased GCC thickness, whereas 13% of patients with elevated RNFL thickness had associated decreased GCC thickness. This may be explained by early retrograde optic nerve damage. These data go with that reported by Marzoli and colleagues in their prospective observational study carried out on 38 consecutive IIH patients in 2013. Their percentages were similar to ours as regards association of changes in RNFL and GCC. They found that increased RNFL thickness was associated with reduced mean GCC thickness in 10% of cases, whereas decreased RNFL thickness was associated with decreased mean GCC thickness in 83% of IIH patients .
After 6 months of recording every patient's data, another recording was taken including visual acuity, RNFL, GCC, MD, and PSD, and we compared these data with the previous ones. The most significant decrease was in GCC value followed by RNFL; on the other hand, there was significant improvement in the mean MD. Rebolleda and Mun˜oz-Negrete observed similar findings concerning RNFL thickness, MD, and PSD in their study. There was a significant decrease in the RNFL thickness (P = 0.000), whereas the mean MD and the mean PSD showed significant improvement (P = 0.000 and 0.005, respectively) .
By the end of the follow-up period, we found that the mean average baseline RNFL was inversely correlated with the final MD and directly correlated with the final PSD of IIH patients. These data go with those of Rebolleda and Mun˜oz-Negrete who observed similar correlations concerning RNFL thickness and retinal sensitivity after a 1-year follow-up in their study . Heidary and Rizzo  also suggested the presence of a correlation between RNFL thickness and visual function.
In this study regression analysis showed that for every 10 μm of mean RNFL thickness increase at baseline, there was a 0.56 dB worsening in MD, versus a 0.6 dB worsening in the Rebolleda and Mun˜oz-Negrete study .
In contrast, we found that, for every 10 μm of mean GCC thickness decrease at baseline, there was a 0.9 dB worsening in MD at the last follow-up. These data plus the highly significant correlation of the mean average GCC with the final MD and PSD indicate that the GCC thickness is a sensitive indicator for early retrograde optic nerve damage.
We agree with Skau et al.  that underestimation of RNFL thickness in cases with severe papilloedema is suspected, so a GCC thickness study may present a more reliable parameter compared with RNFL alone.
An important drawback in our study is the short follow-up period which should be extended to repeat OCT until a plateau can be firmly established to differentiate RNFL attrition versus improvement in RNFL swelling. Of furthermore importance, other SD-OCT devices (e.g. Cirrus OCT) separate RNFL from ganglion cell layer plus the inner plexiform layer; thus providing RNFL thickness and GCL+IPL thickness parameters may help in more reliable estimate of early retrograde optic nerve atrophy.
| Conclusion|| |
Our study suggests that SD-OCT imaging must be included as a noninvasive quantitative method of monitoring retinal layer thickening in IIH, as it may enhance the diagnosis of subtle disc swelling and the treatment effects, even in cases without visual loss.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology 2002; 59
Ball AK, Clarke CE. Idiopathic intracranial hypertension. Lancet Neurol 2006; 5
Friedman DI. Pseudotumor cerebri. Neurol Clin 2004; 22
Wolf A, Hutcheson KA. Advances in evaluation and management of pediatric idiopathic intracranial hypertension. Curr Opin Ophthalmol 2008; 19
Petzold A, de Boer JF, Schippling S, Vermersch P, Kardon R, Green A, et al
. Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol 2010; 9
Headache Classification Subcommittee of the International Headache Society (IHS). The International Classification of Headache Disorders
. 3rd ed. Cephalalgia: 2013. 33
Scott CJ, Kardon RH, Lee AG, Frisén L, Wall M. Diagnosis and grading of papilledema in patients with raised intracranial pressure using optical coherence tomography vs clinical expert assessment using a clinical staging scale. Arch Ophthalmol 2010; 128
Heckmann JG, Faschingbauer F, Lang C, Reulbach U, Dütsch M, Mardin CY, Schwab S. Laser scanning tomography measurement of the extent of papilledema in the follow-up examination of patients with idiopathic intracranial hypertension. J Neurosurg 2007; 107
Salgarello T, Falsini B, Tedesco S, Galan ME, Colotto A, Scullica L. Correlation of optic nerve head tomography with visual field sensitivity in papilledema. Invest Ophthalmol Vis Sci 2001; 42
El-Dairi MA, Holgado S, O′Donnell T, Buckley EG, Asrani S, Freedman SF. Optical coherence tomography as a tool for monitoring pediatric pseudotumor cerebri. J AAPOS 2007; 11
Rebolleda G, Mun˜oz-Negrete FJ. Follow-up of mild papilledema in idiopathic intracranial hypertension with optical coherence tomography. Invest Ophthalmol Vis Sci 2009; 50:5197-5200.
Skau M, Yri H, Sander B, Gerds TA, Milea D, Jensen R. Diagnostic value of optical coherence tomography for intracranial pressure in idiopathic intracranial hypertension. Graefes Arch Clin Exp Ophthalmol 2013; 251
Marzoli SB, Ciasca P, Curone M, Cammarata G, Melzi L, Criscuoli A, et al
. Quantitative analysis of optic nerve damage in idiopathic intracranial hypertension (IIH) at diagnosis. Neurol Sci 2013; 34
Heidary G, Rizzo JF III. Use of optical coherence tomography to evaluate papilledema and pseudopapilledema. Semin Ophthalmol 2010; 25
Skau M, Milea D, Sander B, Wegener M, Jensen R. OCT for optic disc evaluation in idiopathic intracranial hypertension. Graefes Arch Clin Exp Ophthalmol 2011; 249
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]