We performed a detail analysis of children with systemic autoimmune diseases who had undergone treatment with oral steroids for more than 6 months. We found that ocular hypertension and cataracts are the most common ocular complications and the patients with ocular hypertension had a higher percentage of cataracts than the patients with normal IOP. We also found that the pRNFL was thicker in patients with SIOH than the HC group.
In this study, 59.5% of the patients got IOP hypertension. Previous studies have reported that children are considered to be particularly susceptible to developing SIOH [11] [12]. Kwok et al. found that ocular hypertension occurs more frequently, more severely and more rapidly in children than in adults using topical dexamethasone [13]. Systemic steroids can also be considered to cause significant, but asymptomatic, ocular hypertension in paediatric patients [14] [15]. Grossman [16] reported on 1133 children treated with a systemic steroid and found that 37% of the patients developed elevated IOP. Because of oral steroids and topical steroids elevate IOP in different ways, Savleen Kaur reported that the elevation of IOP was lower and was controlled with fewer doses of drugs in patients receiving oral steroids in comparison to patients using topical steroids [17]. A majority of studies have reported that IOP increases 3–6 weeks after the beginning of topical steroid use, and some IOP hypertension can be found as early as the first or second week[2] [18] [19] [20]. Prasad found that increased IOP occurred in 61% of patients in the first month and in 87.9% of patients in the first 6 months of systemic steroid treatment [21].
In our study, the earliest response happened during the first week, and most of the patients got ocular hypertension during the first year. in half of the patients with ocular hypertension, elevated IOP appeared within the first 6 months. The number of new patients with ocular hypertension decreased gradually with the extension of the duration of steroid use and the number of anti-glaucoma medications decreased. Chen reported that the IOP can return to baseline once the use of corticosteroids is terminated [22]. We consider that, as the steroid dose is decreased, the IOP can gradually return to normal and fewer number of patients will have IOP hypertension. The pathophysiology of IOP hypertension is such that the steroids act on the glucocorticoid receptors on the trabecular meshwork, induce decreased cellularity of the trabecular meshwork and increase extracellular matrix deposition; this blocks the outflow of aqueous humour and increases IOP [23].
There were 32.4% of the patients got PSC. Kaye [24] and Hayasaka [25] reported that 30% and 33.3% of the patients in their study got PSC after long-term oral prednisone therapy. The prevalence of cataracts was similar to that reports. Some studies have claimed that the incidence of PSC was influenced by the medication dose and the duration of the cataracts; a higher total steroid dose and a longer time could induce a higher incidence of cataracts [25][26]. In our study, the earliest onset time of cataracts was 6 months after steroid treatment and most of the cataracts happened over the course of 1 to 1.5 years. It demonstrates that the occurrence of cataracts is dependent on the duration of the steroid therapy; thus, the longer the treatment time, the greater the possibility of developing cataracts. Loredo et al. reported that two patients got cataracts within the first year of steroid treatment [27]. Bachmann found that two children with nephrotic syndrome (NS) developed PSC after 7 and 8 months of steroid treatment [28]. The mechanism of SI-PSC is unknown, and there is no effective treatment except for removal of the cataracts if vision is significantly decreased [6] [29]. In our study, none of the patients’ vision was affected by cataracts, and Urban et al. reported that visual impairment was rare in the PSC induced by corticosteroid use [30]. However, If cataract seriously affects the patient's vision, surgery is the best choice.
In our study, the incidence of cataracts was higher in the patients with IOP hypertension than in the patients with normal IOP (45.5% vs 13.3%, p = 0.07). Moreover, all but one of the patients with cataracts got IOP hypertension during the follow-up period. Is there a relationship between steroid-induced IOP hypertension and cataracts? The association between SIOH and SI-PSC has not been reported. A study on 336 patients found that 19 had cataracts caused by long-term oral corticosteroid therapy and 1 had glaucoma attributed to systemic steroid therapy [31]. The patient with glaucoma also had cataracts. The pathogenesis of glucocorticoid-induced cataract is complex. While many theories have been put forward [33], the formation process of PSC cannot be fully explained. TGF-β had been proven to be related to the develop of posterior capsule transition [32]. Fini et al. stated that excessive TGF-β signalling could lead to ocular hypertension in mouse models [33]. TGF-β signalling for PSC and ocular hypertension is a subject for further research.
One patient in our study got glaucoma after using a low-dose oral steroid for 3 years. This demonstrates that, although most of the patients had normal ocular hypertension after their steroid dose is decreased, some patients can still get glaucoma. Thus, IOP should be monitored if a patient is still using steroids.
We found that the pRNFL was thicker in the group of patients with IOP hypertension than in the HC group. This is an interesting finding. We speculate that the observed increase in pRNFL thickness in our patients may reflect an early transient change caused by IOP hypertension. To the best of our knowledge, no previous study has reported a similar result. Aksoy et al. found that there were no statistically significant differences between the ocular hypertension group and the control group [34]. A longer observation time and more subjects are needed to study this further.
This study had several limitations. First, there may have been a bias in choosing the patients because most of our patients were from the Department of Rheumatology and Immunology. Second, we could not obtain visual field data for all the patients because visual field acuity results for children are less reliable due to poor patient cooperation and because the follow-up time was not long enough. Third, the sample size is small. Fourth, the follow-up time is too short.
In conclusion, ocular hypertension and cataracts are the most common complications in children that have long-term oral steroid use. The highest incidence of ocular hypertension occurs in the first 6 months of steroid use and the highest incidence of cataracts occurs after the first year. Regular IOP and slit-lamp examinations should be done in children with long-term steroid use. The incidence of cataract is higher in patients with IOP hypertension than in patients with normal IOP.