Journal of Neuro-Ophthalmology, September 2005, Volume 25, Issue 3

Camputed Tomography Demonstrates Short Axial Globe Length in Cases with Idiopathic Intracranial Hypertension

BACKGROUND: Cases with idiopathic intracranial hypertension (IIH) have been anecdotally found to demonstrate relatively short axial lengths on ultrasound A-scans. This finding has not been rigorously documented. We therefore systematically investigated globe shape in these cases using computed tomography. METHODS: Computed tomographic 0.625-mm sections of 10 cases with IIH and 10 control subjects were reformatted on a workstation. Globe lengths and widths were measured from axial reformats. Globe lengths and heights were measured from oblique sagittal reformats. Two masked observers took all the measurements. RESULTS: The mean axial lengths of the globes of cases with IIH were significantly shorter than those of controls (t test for independent samples, P<0.001). Both observers also found globe height to be significantly greater than globe length in oblique sagittal sections of cases with IIH compared with control subjects (Mann-Whitney U tests, P<0.01). The difference between length and width in axial sections was not different between cases with IIH and control subjects. Using a critical cutoff of 0.6-mm difference between globe height and length in oblique sagittal sections returned a sensitivity of 0.75 and a specificity of 0.75 for IIH detection from both right and left eyes. CONCLUSIONS: There are significant differences in globe shape and axial length between cases with IIH and control subjects. The differences in globe shape manifest significantly only in oblique sagittal sections. This imaging sign could be a useful marker for subclinical IIH.

ORIGINAL CONTRIBUTION Computed Tomography Demonstrates Short Axial Globe Length in Cases with Idiopathic Intracranial Hypertension Stephen A. Madill, FRCOphth, and Stephen E. J. Connor, MRCP, FRCR Background: Cases with idiopathic intracranial hyperten­sion ( IIH) have been anecdotally found to demonstrate relatively short axial lengths on ultrasound A- scans. This finding has not been rigorously documented. We therefore systematically investigated globe shape in these cases using computed tomography. Methods: Computed tomographic 0.625- mm sections of 10 cases with IIH and 10 control subjects were reformatted on a workstation. Globe lengths and widths were measured from axial reformats. Globe lengths and heights were mea­sured from oblique sagittal reformats. Two masked ob­servers took all the measurements. Results: The mean axial lengths of the globes of cases with IIH were significantly shorter than those of controls ( ttest for independent samples, P < 0.001). Both observers also found globe height to be significantly greater than globe length in oblique sagittal sections of cases with IIH compared with control subjects ( Mann- Whitney U tests, P < 0.01). The difference between length and width in axial sections was not different between cases with IIH and control subjects. Using a critical cutoff of 0.6- mm difference between globe height and length in oblique sagittal sections returned a sensitivity of 0.75 and a specificity of 0.75 for IIH detection from both right and left eyes. Conclusions: There are significant differences in globe shape and axial length between cases with IIH and control subjects. The differences in globe shape manifest signifi­cantly only in oblique sagittal sections. This imaging sign could be a useful marker for subclinical IIH. ( J Neuro- Ophthalmol 2005; 25: 180- 184) Eye Department ( SAM) and the Department of Neuroradiology ( SEJC), King's College Hospital, London, U. K. Address correspondence to Stephen A. Madill, FRCOphth, Eye Department, King's College Hospital, Denmark Hill, London, SE5 9RS, U. K.; E- mail: samadill@ hotmail. com diopathic intracranial hypertension ( IIH) is defined clinically by the modified Dandy criteria ( 1). These include symptoms and non- localizing signs of increased intracranial pressure such as papilledema and sixth nerve palsies without additional localizing signs. Because the original criteria were developed in 1985, they have recently been updated ( 2) to include advances in neuroimaging. Findings associated with IIH on magnetic resonance imag­ing ( MRI) include the empty sella, enlargement of the optic nerves in the transverse plane ( 3), and, more specifically, enlargement of the perioptic subarachnoid spaces ( 4), flat­tening of the posterior sclera ( 5), increased vertical tortu­osity of the optic nerve ( 5), enhancement of the pre laminar optic nerve ( 5), and visualization of the elevated optic discs ( 6). Some imaging abnormalities are more sensitive for IIH than others, but their value is multiplied when considered in combination ( 5). Brodsky ( 5) reported 90% sensitivity and 100% specificity for IIH detection using a constellation of MRI signs. Posterior scleral flattening is known to be associated with IIH but has not been quantified. We have also noted anecdotally that cases with IIH tend to demonstrate shorter axial lengths on ultrasound A- scans. This finding is associ­ated with choroidal folds ( 7) but has not been described as a general finding in cases with IIH, although a hyperopic shift had previously been suggested to explain enlargement of the blind spot around the papilledematous disc ( 8). We therefore decided to investigate globe shape in cases with IIH using high- resolution computed tomography ( CT) with a view to defining useful diagnostic criteria. METHODS Case Selection The CT scans of ten cases with IIH and ten control subjects were studied. The cases with IIH were consecutive cases seen in the neuroradiology department of King's College Hospital between April 2003 and January 2005 who had CT scans available on the workstation. The mean age for the cases with IIH was 34 years ( standard deviation [ SD] = 14.1 years) and for control subjects it was 49 years 180 J Neuro- Ophthalmol, Vol. 25, No. 3, 2005 Idiopathic Intracranial Hypertension J Neuro- Ophthalmol, Vol. 25, No. 3, 2005 ( SD = 13.4 years). There were two men and eight women in the IIH group, and five men and five women in the control group. All cases with IIH met the updated Dandy criteria. Cerebrospinal fluid opening pressures ranged from 26.5 cm H20 to 40 cm H20. All ten cases with IIH had marked papilledema at the time of CT scanning according to the subjective grading in the clinical record. Three of the cases with IIH were hyperopic and seven were emmetropic. Crite­ria for the selection of control subjects were normal optic nerve heads and no clinical evidence of raised intracranial pressure. Brain CT was normal. The control subjects' diagnoses are listed in Table 1. Image Analysis CT scans consisting of 0.625- mm axial sections were reformatted on a workstation to create double- oblique sag­ittal and axial sections through the globes of each case along the respective antero- posterior axis. This section was defined as a line that intersected the internal corneal surface at 90°, passed through the geometric center of the lens, and pro­duced back to the posterior pole of the globe ( or more strictly the internal surface of the posterior sclera). This line roughly corresponds to the optical axis of the eye ( 9). The antero­posterior axes were defined in this way for both axial and oblique sagittal sections. To increase accuracy of measure­ment, the reformats were then magnified fourfold. Globe length and width were measured for oblique axial reformats, and globe length and height were measured for oblique sagit­tal reformats using the software calipers on the workstation. Measurements were made in millimeters to one decimal place. The method for measuring globe length, width, and height is demonstrated in Figure 1. For both oblique axial and oblique sagittal reformats, globe length was measured along the antero- posterior axis. This meant that the measurement would avoid the presumptive optic nerve head, which could artifacrually shorten globe lengths if markedly papilledematous. Globe width for axial sections was defined as a line bisecting the antero- posterior axis at right angles and running from nasal to temporal internal TABLE 1. Clinical diagnoses of control patients Diagnoses Number Previous maxillary sinus surgery 1 Anterior communicating artery aneurysm without subarachnoid or parenchymal hemorrhage 2 Previously treated aneurysm 1 Abnormal cervical vertebral marrow 1 Small hemorrhagic brain infarct 1 Small ischemic brain infarct 1 Normal brain imaging 3 scleral surfaces. Globe height for oblique sagittal sections was defined as a line bisecting the antero- posterior axis at right angles and running from superior to inferior internal scleral surfaces. Two masked observers ( SM, SC) in­dependently performed all the measurements. Statistical Analysis Axial lengths for cases with IIH and control subjects were compared using two- tailed t tests for independent samples. As a measure of globe shape, globe height was subtracted from globe length to give the difference between the two measurements for oblique sagittal reconstructions. Globe width was subtracted from globe length to give the difference between the two measurements for axial recon­structions. A negative difference indicated that globe length was the lesser value. Scatterplots for the combined differ­ences of both observers demonstrated that the results from cases with IIH were not normally distributed. The differ­ences for IIH and control groups were therefore compared using non- parametric Mann- Whitney U tests. The critical cutoff for the differences was determined from the scatterplots. Inter- observer agreement was assessed by converting the results into categorical data using the critical cutoff. We applied the critical cutoff to both eyes but the cases need only demonstrate the cutoff in one. The numbers of IIH suspects thus generated from both ob­servers' measurements were then cross- tabulated using the kappa statistic for inter- observer agreement ( 10). RESULTS There was no significant difference between axial lengths measured in the oblique sagittal and axial sections. We therefore compared axial lengths between cases with IIH and control subjects in oblique sagittal sections only. Combining the results of both observers, for cases with IIH, the mean axial lengths were 21.0 mm for left and right eyes ( 95% confidence interval [ CI], 20.5- 21.6 mm). For the control subjects, the mean axial length was 22.7 mm for right eyes ( 95% CI, 22.1- 23.3 mm) and 22.6 mm for left eyes ( 95% CI, 22.0- 23.3). This returned a significant difference between cases with IIH and control subjects with regard to axial length of P < 0.001 ( two- tailed t test for independent samples) for both right and OSs. Table 2 documents the differences between globe length and height in oblique sagittal reformats and between globe length and width in axial reformats. The difference between sagittal and axial reformats for cases with IIH and control subjects is illustrated in Figure 2. Both observers found a significant difference between globe length and height in oblique sagittal sections comparing cases with IIH and control subjects ( P < 0.01). Thirty- seven of forty obser­vations from the globes of cases with IIH showed height 181 J Neuro- Ophthalmol, Vol. 25, No. 3, 2005 Madill and Connor FIG. 1. Antero- posterior axes ( broken lines), width, and height ( solid lines) for axial ( A) and oblique sagittal ( B) reconstructions. greater than length. Comparing the differences between length and width in axial sections, there was no significant difference between cases with IIH and control subjects. Figure 3 demonstrates the scatterplots for the results of both observers considering length minus height differ­ences in oblique sagittal sections for cases with IIH and control subjects. Considering the scatterplot, a critical cutoff of- 0.6- mm difference returns a sensitivity for IIH detection of 0.75 and a specificity of 0.75 using either left or right eyes. The number of IIH suspects generated from the measurements of observer 1 using - 0.6 mm as the critical cutoff in either eye was 13 ( nine cases with IIH and four control subjects) and from observer 2 was 11 ( eight cases with 8 IIH and three control subjects). This returned a kappa of 0.79 representing " substantial" inter- observer agreement ( assuming " substantial" agreement corresponds to a kappa of 0.61 to 0.80) ( 10). DISCUSSION We found significantly shorter axial lengths in cases with IIH compared with control subjects. As an indication of globe shape, we also found globe height to be signif­icantly greater than length in oblique sagittal reformats of cases with IIH compared with control subjects, but no significant difference between width and length in axial reformats. The control subjects'results support the assump­tion that non- pathologic globes are roughly spherical in both axial and oblique sagittal sections. The enlarged retrobulbar optic nerve most probably exerts antero- posterior compression on the globe evidenced by the posterior scleral flattening associated with IIH ( 5) and the difference in axial lengths that we have noted. The tendency for a globe to expand more vertically than horizon­tally may therefore be a feature of antero- posterior globe compression of whatever cause. Alternatively, the increase TABLE 2. Length minus height differences in oblique sagittal sections and length minus width differences in axial sections for five IIH patients and five control subjects Mean difference between globe length and height in oblique sagittal sections ( 95% confidence interval) Mean difference between globe length and width in axial sections ( 95% confidence interval) Observer 1 Controls IIH patients P = Observer 2 Controls IIH patients P = (" (" (" (" Right eye + 0.2 mm - 0.7 mm, + 0.1 mm) - 1.6 mm - 2.2 mm, - 0.9 mm) 0.005 + 0.3 mm - 0.5 mm, + 1.1 mm) - 1.2 mm - 1.9 mm, - 0.4 mm) 0.009 (" (" (" (" Left eye + 0.1 mm - 0.7 mm, + 1.0 mm) - 1.5 mm - 2.2 mm, - 0.9 mm) 0.005 + 0.3 mm - 0.5 mm, + 1.0 mm) - 1.1 mm - 1.8 mm, - 0.5 mm) 0.005 (" (" (" (" Right eye 0 mm - 0.7 mm, + 0.6 mm) 0 mm - 0.4 mm, + 0.5 mm) 0.912 - 0.7 mm - 1.5 mm, + 0.1 mm) - 0.5 mm - 0.7 mm, - 0.2 mm) 0.739 (" (" (" (" Left eye - 0.1 mm - 0.8 mm, + 0.7 mm) 0 mm - 0.5 mm, + 0.3 mm) 0.684 - 0.4 mm - 1.2 mm, + 0.4 mm) - 0.7 mm - 1.1 mm, - 0.2 mm) 0.393 182 © 2005 Lippincott Williams & Wilkins Idiopathic Intracranial Hypertension J Neuro- Ophthalmol, Vol. 25, No. 3, 2005 FIG. 2. Reformats for a single con­trol subject ( left) and a single case with idiopathic intracranial hyper­tension ( IIH) ( right). Oblique sagittal reformats are on top and oblique axial reformats are on the bottom. This example demonstrates the typical finding, namely that the dif­ference in globe shape between control subjects and cases with IIH is more marked in the oblique sagittal reformats. in height may be specific to papilledema and involve a process other than simple compression. Congestion at the posterior pole could lead to a localized swelling posteriorly and to an increase in apparent height. The concept of localized swelling could be pertinent to our results because we measured the internal dimensions of the globes. Studies on eyeball trauma provide some insight into the response of an eye to antero- posterior compression. It has been suggested that expansion of a globe's transverse diameter after a sudden anterior impact may cause trau­matic retinal breaks as a result of the sclera's expanding dis­proportionately to the vitreous ( 11). If the globe tended to preferentially expand in the vertical plane, post- traumatic retinal breaks should be more common in the vertical plane, but they are not, as Weidenthal ( 11) demonstrated. How­ever, blunt trauma that compresses the globe at its anterior pole differs from compression secondary to an enlarged optic nerve, which acts at the posterior pole. We can hypothesize that the most significant difference between the two situations would be the tension of the recti muscles. Anterior compression would weaken rectus tension, whereas posterior compression would increase it. Horizon­tal recti have a greater resting tone in primary position and greater potential force than do the vertical recti ( 12) when the globe is directed 40° into the field of action of the re­spective muscles. We could therefore suggest that the stron­ger horizontal recti could act as a band around the horizontal equator of the globe, leading to preferential expansion verti­cally when the globe is compressed from behind. Choroidal folds are undulations of Bruch's membrane and the inner choroidal layer of the eye ( 13), and have a characteristic appearance of horizontal striations across the posterior pole ( 14). A consequent shortening of the globe axially induces a hyperopic change in refractive error. Etiologies include orbital tumors, thyroid eye disease, posterior scleritis, and ocular hypotony Folds can also be associated with papilledema ( 15). Jacobson ( 7) reported three cases diagnosed with idiopathic choroidal folds that had subclinical IIH. In one case, the symptoms and signs of IIH ( including disc swelling) did not develop until years after the folds were noted. In light of this finding, cases with idiopathic folds are advised to undergo imaging and a lumbar puncture ( 7). Dailey et al ( 16) had earlier described the CT appearance of the globes of seven cases with idiopathic choroidal folds. In 10 of 11 eyes with folds, flattening of the posterior pole was present, similar to that more recently associated with IIH. Dailey et a/( 16) note that changes in globe shape to be " most evident on parasagittal reformations" ( no formal measurements were published). In five of the seven cases, the optic nerve was noted as widened on the more affected side with four nerves demonstrating a distended perioptic subarachnoid space. We believe that this article agrees with our findings but has incorrectly attributed the changes in globe shape to idiopathic choroidal folds. Because we have reviewed only cases with papil­ledema, we are unable to comment on whether the globes would show a similar shape in cases with disc swelling of other etiologies such as inflammatory or infiltrative optic 183 J Neuro- Ophthalmol, Vol. 25, No. 3, 2005 Madill and Connor Right eyes 01 E c c " oO E0) c c < o o +• » + 5 £ O • s w 0 cfl 92 " 5 ce be lique c - a < D 0 1_ ffe 2- 1- 0- - 1- - 2- - 3- - 4 J 1 • • • • • $ • • i t • • IIH patients • Controls Left eyes °> E o c c ^ ro o 1 i: o • 3 w c | i* o o o £" 8 1 0) O I OH - 1 H • 4 A A * • IIH patients A Controls - 3J u FIG. 3. Scatterplots for the combined results of length minus height in oblique sagittal sections for cases with idiopathic intracranial hypertension ( IIH) and control subjects from both observers. The difference between the two groups can be attributed mostly to shortened axial length in the cases with IIH. neuropathies. Because all papilledema gradings were similar at the time of scanning and because we have not followed up the cases longitudinally with repeat scans, we cannot com­ment on an association between papilledema grade and the degree of globe distortion. Although the case with IIH with the lowest cerebrospinal fluid opening pressure had the smallest amount of globe distortion, this trend was not continued across the rest of the cases with IIH. We can suggest that the results are not an artifact of refractive error ( three of the ten cases with IIH were hyperopic) because, although myopia can increase the length of a globe, hyperopia is not known to increase its height ( 17). Our retrospective series suggests that shorter axial lengths and globes with height greater than length or width are significantly associated with a diagnosis of IIH. 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