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Original Investigation |

Topical Dorzolamide-Timolol With Intravitreous Anti–Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration

Jayanth Sridhar, MD1; Jason Hsu, MD1; Abtin Shahlaee, MD1; Sunir J. Garg, MD1; Marc J. Spirn, MD1; Mitchell S. Fineman, MD1; James Vander, MD1
[+] Author Affiliations
1Retina Service, Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University, Philadelphia, Pennsylvania
JAMA Ophthalmol. 2016;134(4):437-443. doi:10.1001/jamaophthalmol.2016.0045.
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Importance  There is a subset of eyes with neovascular age-related macular degeneration (AMD) that have persistent exudation despite fixed-interval intravitreous anti–vascular endothelial growth factor (VEGF) injections.

Objective  To evaluate the effect of topical dorzolamide hydrochloride–timolol maleate on anatomic and functional outcomes in eyes with neovascular AMD and incomplete response to anti-VEGF therapy.

Design, Setting, and Participants  An exploratory, prospective single-arm interventional study at a tertiary referral academic private practice. Patients with neovascular AMD and persistent macular edema despite fixed-interval intravitreous anti-VEGF therapy were enrolled. Baseline spectral-domain optical coherence tomography and clinical data, including visual acuity and intraocular pressure, were obtained at enrollment and from one visit before enrollment. The study was performed at the Retina Service of Wills Eye Hospital and the offices of Mid Atlantic Retina from February 1, 2015, through September 30, 2015. Patients were followed up for at least 2 visits after enrollment. Central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded at each visit.

Interventions  Enrolled eyes received a regimen of topical dorzolamide-timolol twice daily and continued to receive the same intravitreous anti-VEGF therapy at the same interval as received before enrollment for the duration of the study.

Main Outcomes and Measures  Change in central subfield thickness was the primary outcome measure. Changes in maximum subretinal fluid height, maximum pigment epithelial detachment height, and visual acuity were the secondary outcome measures.

Results  Ten patients (10 eyes) completed the study. The mean age of the patients was 78.2 years (age range, 65-91 years), and 6 were male. Eight eyes received intravitreous aflibercept, and 2 eyes received intravitreous ranibizumab. All study eyes had been receiving long-term anti-VEGF therapy with the same medication before study enrollment for a mean of 21.9 injections. The mean central subfield thickness decreased from 419.7 μm at enrollment to 334.1 μm at the final visit (P = .01). The mean maximum subretinal fluid height decreased from 126.6 μm at enrollment to 49.5 μm at the final visit (P = .02). The mean maximum pigment epithelial detachment height decreased from 277.4 μm at enrollment to 239.9 μm at the final visit (P = .12). The mean logMAR visual acuity were 0.54 at enrollment and 0.48 at the final visit (P = .60).

Conclusions and Relevance  These data suggest that topical dorzolamide-timolol may reduce central subfield thickness and subretinal fluid in eyes with persistent exudation despite consistent, fixed-interval intravitreous anti-VEGF treatment for neovascular AMD.

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Figure 1.
An 81-Year-Old Man With Neovascular Age-Related Macular Degeneration

A, The patient had persistent subretinal fluid despite monthly intravitreous aflibercept and started receiving topical dorzolamide hydrochloride–timolol maleate. B-D, On monthly follow-up, subretinal fluid decreased (B and C) until ultimately resolving (D). The spectral-domain optical coherence tomography image through the foveal center is shown in the right panel. The corresponding infrared fundus image is shown in the left panel, with the bold horizontal arrow referencing the area segmented. The same area was segmented for each visit.

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Place holder to copy figure label and caption
Figure 2.
A 70-Year-Old Man With Neovascular Age-Related Macular Degeneration

A, The patient had persistent macular edema despite monthly intravitreous aflibercept and started receiving topical dorzolamide hydrochloride–timolol maleate. B-D, On monthly follow-up, macular edema decreased (B and C) until ultimately resolving (D). The spectral-domain optical coherence tomography image through the foveal center is shown in the right panel. The corresponding infrared fundus image is shown in the left panel, with the bold horizontal arrow referencing the area segmented. The same area was segmented for each visit.

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