Intraocular Pressure in the Eyes of Patients With Carotid-Cavernous Fistulas: Profile, Intereye Asymmetry, and Treatment Outcomes.

PRECIS: Secondary ocular hypertension (OHT) is common in carotid-cavernous fistulas (CCFs). Management of elevated intraocular pressure (IOP) is possible with a multidisciplinary approach. The ipsilateral normal eyes may have higher IOP than the contralateral eyes. PURPOSE: To study the IOP profile of the eyes of patients with a CCF, treatment outcomes for elevated IOP, and intereye IOP asymmetry in the eyes with normal IOP. METHODS: This was a retrospective case series. A total of 64 eyes of 60 patients with digital subtraction angiography-proven CCF diagnosed from the year 2000 to 2016 were included. The demographics, clinical features, management, and outcomes were recorded. The primary outcome included understanding of the cause of elevated IOP. The secondary outcomes included comparison of the IOP between contralateral eyes and ipsilateral normal eyes (IOP <21 mm Hg) and management outcomes for elevated IOP. RESULTS: The mean age of the patients was 45.6±18.2 years. In the study population, 70% of the patients were males. Indirect CCF was present in 55% of the eyes. It was found that 64.06% (n=41) of the eyes had elevated IOP, glaucoma, or were glaucoma suspects. Among all the eyes, 40.62% (n=26) of the eyes had secondary OHT due to elevated episcleral venous pressure, whereas 7.81% (n=5) of the eyes had secondary open-angle glaucoma. The mean IOP was higher in the ipsilateral eyes than in the other eyes (22.95±7.1vs. 15.11±2.99 mm Hg; P<0.001). The mean IOP in the ipsilateral normal eyes was higher than that in the contralateral eyes, with a mean difference of 2.92±2.29 mm Hg (confidence interval of the mean difference: 1.90-3.94 mm Hg; P<0.0001). IOP reduction (<21 mm Hg) was achieved in 70.7% of the patients following CCF management with intermittent carotid massage, endovascular treatment, IOP-lowering medications, or a combination among these. CONCLUSIONS: Secondary OHT due to elevated episcleral venous pressure was more common than secondary open-angle glaucoma. Ipsilateral normal eyes had higher IOP than contralateral eyes. IOP-lowering agents and management of CCF resulted in IOP control in most patients.

Effects of deferasirox dose and decreasing serum ferritin concentrations on kidney function in paediatric patients: an analysis of clinical laboratory data from pooled clinical studies.

BACKGROUND: Serious and fatal deferasirox-induced kidney injury has been reported in paediatric patients. This study aimed to investigate the effects of deferasirox dose and serum ferritin concentrations on kidney function and the effect of impaired kidney function on dose-normalised deferasirox minimum plasma concentration (Cmin). METHODS: We did a case-control analysis using pooled data from ten clinical studies. We identified transfusion-dependent patients with thalassaemia, aged 2-15 years, who were receiving deferasirox and had available baseline and follow-up serum creatinine and ferritin measurements. Cases of acute kidney injury (AKI) were defined according to an estimated glomerular filtration rate (eGFR) threshold of 90 mL/min per 1·73 m2 or less (if baseline eGFR was ≥100 mL/min per 1·73 m2), an eGFR of 60 mL/min per 1·73 m2 or less (if baseline eGFR was <100 mL/min per 1·73 m2), or an eGFR decrease from baseline of at least 25%. Cases were matched to control visits (eGFR ≥120 mL/min per 1·73 m2) on age, sex, study site, and time since drug initiation. We calculated rate ratios for AKI using conditional logistic regression, and evaluated the effect of eGFR changes on Cmin. FINDINGS: Among 1213 deferasirox-treated paediatric patients, 162 cases of AKI and 621 matched control visits were identified. Patients with AKI had a mean 50·2% (SD 15·5) decrease in eGFR from baseline, compared with a 6·9% (29·8) decrease in controls. A significantly increased risk for AKI (rate ratio 1·26, 95% CI 1·08-1·48, p=0·00418) was observed per 5 mg/kg per day increase in deferasirox dispersible tablet dose (equivalent to a 3·5 mg/kg per day dose of film-coated tablets or granules), above the typical starting dose (20 mg/kg per day). An increased risk (1·25, 1·01-1·56, p=0·0400) for AKI was also observed per 250 µg/L decrease in serum ferritin, starting from 1250 µg/L. High-dose deferasirox (dispersible tablet dose >30 mg/kg per day) resulted in an increased risk (4·47, 1·25-15·95, p=0·0209) for AKI when serum ferritin was less than 1000 µg/L. Decreases in eGFR were associated with increased Cmin. INTERPRETATION: Deferasirox can cause AKI in a dose-dependent manner. The increased AKI risk with high-dose deferasirox and lower serum ferritin concentration is consistent with overchelation as a causative factor. Small decreases in eGFR correlate with increased deferasirox Cmin, especially in younger patients. Physicians should closely monitor renal function and serum ferritin, use the lowest effective dose to maintain acceptable body iron burden, and interrupt deferasirox treatment when AKI or volume depletion are suspected. FUNDING: None.