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.

Study Overview

• Status: Completed
• Conditions: Age-related Macular Degeneration; Diabetic Macular Edema; Retinal Vein Occlusion; Wet Macular Degeneration
• Intervention / Treatment: Drug: Dorzolamide-timolol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Wills Eye Hospital / Mid Atlantic Retina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient of Wills Eye Hospital Retina Service and/or Mid Atlantic Retina.
2. Volunteer patients age 18 years and older.
3. Healthy enough to participate in the study.
4. Willing and able to consent to participation in the study.
5. Diagnosis of wet age-related macular degeneration
6. 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
7. Injection of the same anti-VEGF agent for at least two visits prior to study enrollment
8. Fixed interval between at least two visits prior to study enrollment

Exclusion Criteria:

1. History of uveitis
2. Any ophthalmic surgery within previous 6 months, including cataract extraction.
3. Any history of vitrectomy
4. History of any glaucoma drop usage or prior glaucoma surgery
5. Systemic diuretic or corticosteroid usage
6. Any contraindication (bradycardia, decompensated heart failure, or reactive
7. airway disease) for topical use of a beta-blocker

8. Any history of sulfonamide allergy

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Dorzolamide-timolol; 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

Drug: Dorzolamide-timolol; On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration; Other Names: Cosopt

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Central Subfield Thickness (CST)	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	3 visits (8-12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Acuity	LogMAR Visual acuity on enrollment and final visit	3 visits (8-12 weeks)
Maximum Subretinal Fluid Height	Measurement based on SD-OCT	3 visits (8-12 weeks)
Maximum Pigment Epithelial Detachment Height	Measurement based on SD-OCT	3 visits (8-12 weeks)

Collaborators and Investigators

• Sponsor: Wills Eye
• Collaborators: Mid Atlantic Retina; J. Arch McNamara Research Fund
• Investigators: Principal Investigator: Jason Hsu, MD, Wills Eye Hospital, Mid Atlantic Retina

Publications and helpful links

General Publications

• Byeon SH, Kwon OW, Song JH, Kim SE, Park YS. Prolongation of activity of single intravitreal bevacizumab by adjuvant topical aqueous depressant (Timolol-Dorzolamide). Graefes Arch Clin Exp Ophthalmol. 2009 Jan;247(1):35-42. doi: 10.1007/s00417-008-0917-1. Epub 2008 Aug 6.
• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 1, 2015
• Primary Completion (ACTUAL): September 30, 2015
• Study Completion (ACTUAL): December 20, 2015

Study Registration Dates

• First Submitted: October 6, 2015
• First Submitted That Met QC Criteria: October 6, 2015
• First Posted (ESTIMATE): October 8, 2015

Study Record Updates

• Last Update Posted (ACTUAL): December 3, 2019
• Last Update Submitted That Met QC Criteria: December 1, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: macular edema; intravitreal injection; neovascular age-related macular degeneration; anti-vascular endothelial growth factor; dorzolamide-timolol; topical aqueous suppression
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Retinal Degeneration; Retinal Diseases; Embolism and Thrombosis; Venous Thrombosis; Thrombosis; Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Edema; Wet Macular Degeneration; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Timolol; Dorzolamide
• Other Study ID Numbers: IRB#14-435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes