Efficacy of topical brinzolamide in children with retinal dystrophies

Abstract

Background: Inherited retinal dystrophies are a leading cause of irreversible blindness in children in the United States. Topical carbonic anhydrase inhibitors have improved central vision and cystoid macular edema in patients with retinal dystrophies, but few studies have assessed their efficacy in children. Materials and Methods: A retrospective chart review was performed with Institutional Review Board approval to identify pediatric patients with inherited retinal dystrophies who received topical brinzolamide at a single university center between 2008 and 2015. Serial visual acuity and central macular thicknesses were compared to assess the efficacy of brinzolamide. Results: Seven subjects were identified who met the inclusion criteria. Four had juvenile X-linked retinoschisis, two had retinitis pigmentosa, and one had Leber congenital amaurosis. All were prescribed brinzolamide thrice daily; however, one patient was completely non-compliant. Four of the six treated patients exhibited a mild decrease in central macular thickness in both eyes during the study with all six treated patients having significantly improved vision at the first endpoint, 33.2 ± 8.2 months after treatment initiation. For treated patients, average visual acuity (LogMAR) ± standard error of the mean improved from 0.5 ± 0.04 pre-treatment to 0.3 ± 0.1 at the second endpoint, 50.2 ± 7.3 months after treatment initiation. Conclusions: Mild anatomic improvement of macular cysts was seen in pediatric patients using brinzolamide. Visual acuity improvement occurred even without significant reduction in macular cysts. Further studies are needed to determine whether the beneficial effects of carbonic anhydrase inhibitors are sustained in children with inherited retinal degenerations.

Keywords: Brinzolamide/carbonic anhydrase inhibitors; Leber congenital amaurosis (LCA); Retinitis pigmentosa (RP); X-linked juvenile retinoschisis (XLRS); inherited retinal dystrophy.

Figure 1:. Optical coherence tomography (OCT) and best corrected visual acuity (BCVA) in the right eye (OD) and the left eye (OS) for three patients with varying medication compliances at baseline and the two study enpoints.

Patient 7’s OCT are shown in the upper panels; he was the only patient who did not use topical brinzolamide in this study. However, he did receive systemic carbonic anhydrase inhibitor therapy prior to the second endpoint. Patient 1 had intermediate compliance with topical drops, and his OCTs are shown in the middle panels. Patient 6 had the best compliance with the treatment regimen, and his OCTs are shown in the bottom panels. The central macular thicknesses in microns are shown along the bottom edge of each OCT image, and the BCVA is listed in the upper right corner of each image.

Figure 2:. Best corrected visual acuity of all treated patients at baseline (pre-treatment) and the first and second study endpoints.

The visual acuities for the right eyes (A), left eyes (B) and both eyes averaged (C) for each treated patient are recorded in LogMAR at baseline (black), the first endpoint (blue), and the second endpoint (green). Patients 1, 2, 3 and 6 had XLRS. Patient 4 had LCA, and patient 5 had X-linked RP. D. The individual LogMAR visual acuities per eye for all treated patients at baseline (black), the first endpoint (blue), and the second endpoint (green) are shown as individual points. The black horizontal bars represent the average of all treated eyes at that time point; error bars represent standard error of the mean. A LogMAR acuity of 0.0 indicated 20/20 vision whereas a LogMAR acuity of 1.0 indicated 20/200 on the Snellen chart. Significance was defined as **p<0.01 compared to baseline. Patient 7 was not treated, and, thus, was not included.

Figure 3:. Best corrected visual acuity of all treated patients at baseline (pre-treatment) and the first and second study endpoints.

The visual acuities for the patients with X-linked retinoschisis (A) and the patients with LCA or X-linked RP (B) are shown over the three study time points. Each line represents a single treated patient. Patients 1, 2, 3 and 6 had XLRS. Patient 4 had LCA, and patient 5 had X-linked RP. The individual LogMAR visual acuities averaged for both eyes are shown as individual points. A LogMAR acuity of 0.0 indicated 20/20 vision whereas a LogMAR acuity of 1.0 indicated 20/200 on the Snellen chart. Patient 7 was not treated, and, thus, was not included.

Figure 4.. Comparison of optical coherence tomography (OCT), best corrected visual acuity (BCVA), and intraocular pressure (IOP) in a single patient with X-linked retinoschisis and excellent drop compliance.

Serial OCT images from different clinic visits are shown for the right and left eyes with documentation of the BCVA, central macular thickness, and IOP (if recorded) for each eye. Brinzolamide was prescribed as thrice daily dosing in the right eye then the left eye in July 2012. Brinzolamide was discontinued in December 2014, approximately 2.5 years after starting the topical therapy. The patient subsequently developed acute angle closure and recurrence of cystoid macular edema in the left eye (red text). Upon restarting brinzolamide, the macular edema improved in both eyes, the IOP normalized, and the vision returned to baseline.