Conclusions
This study on 113 patients from a real-life setting identifies risk factors long-term optical nerve atrophy after an increased intracerebral pressure, independent from the underlying aetiology and using OCT.
Total peripapillary retinal thickness has been used to quantify initial papilloedema because it is a more reliable value for high-grade papilloedema and because it compares favourably with the clinical staging of Frisén.6 Indeed, RNFL treatment algorithms often fails to provide a proper segmentation in high-grade papilloedema while total retinal thickness works more better.
Albrecht et al demonstrated that initial RNFL thickness is a predictor of RNFL loss over time in patients with IIH.11 The similar study by Kabatas et al prospectively followed eyes with papilloedema due to IIH. Patients with optic atrophy had the following characteristics: higher cerebrospinal fluid opening pressure, higher grade of papilloedema, thicker mean peripapillary RNFL thickness, thinner GCL layer and severe visual field loss.12 Our study confirms these findings in stasis papilloedema regardless of the underlying aetiology.
Older studies have already identified clinical risk factors for optic atrophy based on visual acuity impairment but without the use of OCT. They include the grade of papilloedema according to the Frisén classification, the presence of peripapillary haemorrhage and advanced age.7 Initial visual acuity is impaired in 5%–17% of patients in the literature.13 This clinical presentation is a major risk factor for visual pathway damage. A more recent study has also shown that the Frisen grade of papilloedema is also a risk factor for optic atrophy in the paediatric population.14
We chose to use OCT parameters as the primary outcome measure because it is an objective and reproducible criterion that reliably reflects anatomical optic loss. Regarding the functional consequences of optic atrophy, it has been demonstrated that visual acuity is generally preserved and is not the first visual function affected.15 16 It is not a reproducible and discriminative criterion reflecting the occurrence of optic atrophy. Therefore, we did not select it as the primary outcome measure. Nevertheless, it remains an important evaluation criterion since there is still a risk of decreased visual acuity, as it was the case in 5% of our patients.
Visual field testing is a much better assessment of visual function in patients with optic atrophy. Optic atrophy can lead to visual field defects characterised by diffuse and unsystematic scotomas with a decrease in mean deviation. Because this is a retrospective study, most of the visual fields conducted were Goldman visual fields rather than automated visual fields due to the routine practices of the services. Furthermore, there were missing values of mean deviation, which prevented us from choosing it as the primary outcome measure. Because of this methodological difference, it is not possible to directly compare the data from Goldman visual fields with that of automated visual fields. However, it has been shown that RNFL thickness is strongly correlated with mean deviation in optic atrophy, regardless of the underlying causes,15 confirming the relevance of analysing the final RNFL as a marker of optic atrophy occurrence. Future analyses are required to confirm the correlation between final RNFL and visual field in cases of optic atrophy due to papilloedema.
Severe optic disc oedema with elevated ICP makes the optic disc highly vulnerable to ischaemia because of compression of the vessels within. There is an increased vascular resistance due to the compression of capillaries by swollen axons and accumulation of extracellular fluid in the oedema and venous stasis.17 According to Micieli et al, the severity of papilloedema is not associated with age, race, gender or BMI in patients with IH but is significantly higher with elevated CSF opening pressure.18 In this study, there was no observed correlation between BMI and optic atrophy, which aligns with the findings in Orcutt et al.'s study, where no significant correlation was found in the idiopathic intracranial hypertension (IIH) subgroup.7 On the other hand, a retrospective study of 414 patients found a tendency to loss of vision associated with a severe BMI (greater than 40 kg/m2) with an OR=1.4 (95% CI 1.03 to 1.91, p=0.03).19
Unilateral involvement represented 3.5% of our patients. This is a rare phenomenon but described in the literature as being around 4% in papilloedema.20 One study suggests that asymmetric papilloedema stems from asymmetries in the bony optic canal that interfere with the flow of cerebrospinal fluid between the perioptic subarachnoid spaces.20
This study also found a strong association between the alteration of the initial GCL and the final optic atrophy. We used GCL volume instead of the thickness because we did not have access to thickness values at the inception of the study. Furthermore, both in our clinical practice and in the literature, we observe that GCL volume is a highly relevant metric for assessing the entire GCL layer, as it reflects a potential localised loss that could be missed if we were to rely solely on the average thickness value. Hence, we employed this data to evaluate the MGCL. This strong association between the alteration of the GCL and the final optic atrophy, which is consistent with the study by Marzoli et al, indicates that, in patients with IH, signs of optic neuropathy can be identified even in the presence of papilloedema.21 Thus, OCT, which is already useful for quantifying papilloedema, may show retinal ganglion cell damage in an early phase of the disease.22
The sex ratio in our study in favour of females is explained by a preponderance of females in IIH and cerebral venous thrombosis with the important role of sex hormones.23,24 However, male or female sex is neither a risk factor nor a protective factor for optic atrophy, which partly contradicts the Bruce et al study in which men with IIH were twice as likely as women to develop severe visual loss, but this study used visual acuity as the principal outcome.25
The size of the scleral canal usually measures about 1.5 mm in healthy patients. This cohort presents a larger size because of a higher cerebrospinal fluid pressure in the optic nerve sheath for patients with IH. It also appears to be moderately correlated with progression to optic atrophy.
OCT is a marker of treatment efficacy and disease progression in IH.26 It is a quick and easy alternative to repeated lumbar punctures for monitoring patients with IIH, and facilitates monitoring of disease progression and response to treatment. In addition, several studies have shown that the rise in ICP correlates with the hike in RNFL during the follow-up of these patients.27 28
However, this study shows some limitations. It is a retrospective study and some clinical data from the interview or clinical examination were not always specified, such as the presence of certain symptoms or peripapillary haemorrhages. Also, children were mostly excluded from the study because OCT was often impossible to perform due to lack of compliance with the examination. The prevalence of IIH was low in our cohort because the more serious aetiologies (tumours, thromboses) are overestimated in connection with the region’s reference neurosurgery department attached to our ophthalmology department. However, the aetiology of IH had no correlation with the primary outcome. Finally, non-significant relationship could be due to an underpowered assessment. For example, ICP and scleral canal size are significantly correlated with atrophy in univariate analysis but were not included in the multivariate analysis due to a large amount of missing data.
In conclusion, this study identified risk factors for optic atrophy in papilloedema. The initial grade of oedema is easily quantifiable with OCT and is an important reflection of the risk of optic suffering. The presence of an initial severe visual acuity drop, early GCL damage or peripapillary haemorrhages are also associated with progression to optic atrophy. It would then be interesting to follow up after the medical treatment those patients who show these characteristics.