Dorzolamide-timolol Drops With Injections to Treat AMD, RVO or DME.

Effect of Topical Aqueous Suppressants on Response to Intravitreal Anti-vascular Endothelial Growth Factor Injections in Age-related Macular Degeneration (AMD), Retinal Vein Occlusions (RVO) or Diabetic Macular Edema (DME).

This study seeks to evaluate the effect of topical aqueous suppression on the anatomic and functional response to intravitreal anti-vascular endothelial growth factor (VEGF) injections in non-responders with wet age-related macular degeneration.

Intravitreal anti-vascular endothelial growth factor (VEGF) agents, including bevacizumab, ranibizumab, and aflibercept, have become the gold standard treatment for neovascular age-related macular degeneration (AMD). Various treatment modalities using these agents have been proposed, including monthly, pro re nata, and treat-and-extend philosophies. Despite frequent and consistent treatment with anti-VEGF therapy, there is a subset of patients who are incomplete or non-responders and have persistent evidence of exudation on spectral-domain optical coherence tomography (SD-OCT), including subretinal fluid (SRF) and/or intraretinal edema. While clearance of intravitreal anti-VEGF drugs is not completely understood, some studies have suggested that outflow through the anterior chamber may contribute. We hypothesized that by decreasing aqueous production, outflow may also be reduced which could delay the clearance of intravitreal drugs. As a result, we chose topical dorzolamide-timolol since it is a potent aqueous suppressant and is readily available due to its common use in the treatment of glaucoma. The current study aimed to evaluate the efficacy of topical dorzolamide-timolol on anatomic and visual outcomes in anti-VEGF non-responders with neovascular AMD. Significance: The results of this study will help delineate whether topical aqueous suppression may be useful as adjuvant therapy in patients receiving chronic intravitreal anti-VEGF injections.

Wet Macular Degeneration, Age-related Macular Degeneration, Diabetic Macular Edema, Retinal Vein Occlusion

dorzolamide-timolol, topical aqueous suppression, neovascular age-related macular degeneration, macular edema, intravitreal injection, anti-vascular endothelial growth factor

On enrollment, eligible patients will have visual acuity testing, intraocular pressure, dilated fundoscopic examination, SD-OCT scan and will then receive the same intravitreal pharmacologic agent administered at prior visit. Subsequent follow-up visits will be at an identical interval to pre-enrollment visit intervals (4, 5, or 6 week intervals) for the study duration. Each subsequent visit will consist of visual acuity testing, intraocular pressure, dilated fundoscopic examination, SD-OCT scan, and intravitreal injection of same pharmacologic agent as prior visits At study conclusion, mean central macular thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height will be measured over the study period for all patients

On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration

Mean central subfield thickness (CST) on spectral domain optical coherence tomography (SD-OCT) on 1 visit prior to enrollment and all visits subsequent to study enrollment

Inclusion Criteria: Patient of Wills Eye Hospital Retina Service and/or Mid Atlantic Retina. Volunteer patients age 18 years and older. Healthy enough to participate in the study. Willing and able to consent to participation in the study. Diagnosis of wet age-related macular degeneration Prior treatment with at least 4 injections of anti-VEGF agents in the past 6 months and persistent intraretinal and/or subretinal fluid on SD-OCT at each visit during this period Injection of the same anti-VEGF agent for at least two visits prior to study enrollment Fixed interval between at least two visits prior to study enrollment Exclusion Criteria: History of uveitis Any ophthalmic surgery within previous 6 months, including cataract extraction. Any history of vitrectomy History of any glaucoma drop usage or prior glaucoma surgery Systemic diuretic or corticosteroid usage Any contraindication (bradycardia, decompensated heart failure, or reactive airway disease) for topical use of a beta-blocker Any history of sulfonamide allergy -

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Sridhar J, Hsu J, Shahlaee A, Garg SJ, Spirn MJ, Fineman MS, Vander J. Topical Dorzolamide-Timolol With Intravitreous Anti-Vascular Endothelial Growth Factor for Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol. 2016 Apr;134(4):437-43. doi: 10.1001/jamaophthalmol.2016.0045.

Obeid A, Hsu J, Ehmann D, Gao X, Sridhar J, Chiang A, Park CH, Ho AC. TOPICAL DORZOLAMIDE-TIMOLOL WITH INTRAVITREOUS ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINAL VEIN OCCLUSION: A PILOT STUDY. Retin Cases Brief Rep. 2021 Mar 1;15(2):120-126. doi: 10.1097/ICB.0000000000000752.