Resolution of right sixth-nerve palsy with zoledronic acid therapy. A, Attempted far right gaze before treatment, demonstrating poor abduction of the right eye. B, Far right gaze 7 months after the first zoledronic acid infusion, with improved right eye abduction.
Computed tomographic scan shows massive thickening of the skull base bones, with a cotton-wool bone appearance.
Pane A. Paget Disease Manifesting With Compressive Sixth-Nerve Palsy That Resolved With Intravenous Zoledronic Acid Therapy. Arch Ophthalmol. 2007;125(10):1440-1441. doi:10.1001/archopht.125.10.1440
Copyright 2007 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2007
Paget disease is a common condition characterized by increased bone turnover and abnormal bone deposition in the skull and vertebral column.1 This article describes a previously undiagnosed case of Paget disease in which the manifesting clinical symptom was gradually progressive diplopia from sixth-nerve compression due to skull base hyperostosis. The sixth-nerve palsy, which was severe at the initial examination, slowly resolved after the patient was treated with intravenous zoledronic acid. To my knowledge, Paget disease has not previously been reported to manifest initially with diplopia, nor has diplopia due to this condition been reported to improve with medical therapy.
A 74-year-old man was referred with a 4-month history of gradually worsening horizontal diplopia, worse on looking to the right. He also had gradually worsening right hemifacial pain and paresthesia.
On examination, visual acuity was 6/7.5 OU. There was a 40–prism diopter (PD) right esotropia for distance in primary position, with the right eye abducting to the midline but not beyond in attempted far right gaze (Figure 1A). Other ocular ductions were normal. There was right corneal anesthesia as well as reduced cutaneous sensation to light touch on the right forehead and cheek, with normal lower facial sensation. There were no other cranial neuropathies.
The patient underwent magnetic resonance imaging of the brain, which revealed extensive skull base thickening. A subsequent computed tomographic scan demonstrated extensive diffuse demineralization of the skull base extending into the skull vault, a loss of cortical medullary differentiation, a cotton-wool bone appearance, and an overgrowth of bone at the petrous apex in the region of the Dorello canal bilaterally (Figure 2). Blood tests revealed an alkaline phosphatase level of 616 U/L (reference range, 30-115 U/L; to convert units per liter to microkatals per liter, multiply by 0.0167), and Paget disease was diagnosed.
Treatment was commenced with an intravenous infusion of 4 mg of zoledronic acid. Six weeks after the treatment, the patient began to notice a gradual improvement in the diplopia. Three months after the infusion, the right eye was able to abduct beyond the midline. A second infusion was given 6 months after the first. At last follow-up, 7 months after commencement of treatment, the patient can achieve binocular single vision with a slight right head turn; there is an 8-PD right esotropia in primary position and markedly improved right eye abduction (Figure 1B). The previously severe right hemifacial pain and paresthesia have completely resolved. Right corneal sensation has returned, although it is still subjectively reduced; there are no signs of neurotrophic keratopathy.
The gradual onset and slow progression of the sixth-nerve palsy suggest that progressive compression of the sixth nerve by skull base hyperostosis was the cause of the patient's diplopia. Patients with known Paget disease have previously been described to have developed diplopia due to cranial nerve compression2; however, to my knowledge, the disease has not previously been reported to initially manifest with diplopia.
Bisphosphonates achieve a rapid reduction in bone turnover in Paget disease by inhibiting osteoclast resorption.3 Zoledronic acid is a potent new bisphosphonate. Intravenous infusion of this drug has recently been demonstrated to provide a greater and more rapid effect on bone metabolism than oral agents.4 The gradual improvement in the severity of the sixth-nerve palsy in this case presumably was due to slow reduction in the extent of bony compression of the nerve at the petrous apex.
Although diplopia due to Paget disease is rare, the condition should be considered in the differential diagnosis of slowly progressive diplopia in elderly patients. The use of new bisphosphonate agents may be an effective treatment for diplopia caused by this disease.
Correspondence: Dr Pane, Queensland Eye Institute, 41 Annerley Rd, South Brisbane, Queensland 4101, Australia (firstname.lastname@example.org).
Financial Disclosure: None reported.