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

• Sponsor: Wills Eye (Other)
• Overall Status: Completed
• CT.gov ID: NCT02571972
• Collaborator: J. Arch McNamara Research Fund (Other), Mid Atlantic Retina (Other)
• Enrollment: 14
• Location: 1
• Arm: 1
• Actual Duration (Months): 10.6
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Wet Macular Degeneration; Age-related Macular Degeneration; Diabetic Macular Edema; Retinal Vein Occlusion	Drug: Dorzolamide-timolol	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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).
• Actual Study Start Date: Feb 1, 2015
• Actual Primary Completion Date: Sep 30, 2015
• Actual Study Completion Date: Dec 20, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Mean Central Subfield Thickness (CST) [3 visits (8-12 weeks)]

   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

Secondary Outcome Measures

1. Visual Acuity [3 visits (8-12 weeks)]

   LogMAR Visual acuity on enrollment and final visit

2. Maximum Subretinal Fluid Height [3 visits (8-12 weeks)]

   Measurement based on SD-OCT

3. Maximum Pigment Epithelial Detachment Height [3 visits (8-12 weeks)]

   Measurement based on SD-OCT

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Wills Eye Hospital / Mid Atlantic Retina	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Wills Eye
• J. Arch McNamara Research Fund
• Mid Atlantic Retina

Investigators

• Principal Investigator: Jason Hsu, MD, Wills Eye Hospital, Mid Atlantic Retina

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Jason Hsu, MD, PI, Wills Eye
• ClinicalTrials.gov Identifier: NCT02571972
• Other Study ID Numbers: IRB#14-435
• First Posted: Oct 8, 2015
• Last Update Posted: Dec 3, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Keywords provided by Jason Hsu, MD, PI, Wills Eye: dorzolamide-timolol; topical aqueous suppression; neovascular age-related macular degeneration; macular edema; intravitreal injection; anti-vascular endothelial growth factor
• Additional relevant MeSH terms: Macular Degeneration; Macular Edema; Retinal Vein Occlusion; Wet Macular Degeneration; Edema; Timolol; Dorzolamide

Study Results

Participant Flow

Arm/Group Title	Dorzolamide-timolol
Arm/Group Description	On enrollment, eligible patients will be started on topical dorzolamide 2%-timolol 0.5% 1 drop in the study eye twice daily for the study duration
Period Title: Overall Study
STARTED	14
COMPLETED	10
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Dorzolamide-timolol
Arm/Group Description	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 Dorzolamide-timolol: On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration
Overall Participants	10
Overall Eyes	10
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	78.2
Sex: Female, Male (Count of Participants)
Female	4 40%
Male	6 60%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (participants) [Number]
United States	10 100%
Intravitreous anti-vascular endothelial growth factor (VEGF) agent (Eyes) [Count of Units]
Aflibercept	8
Ranibizumab	2
Prior injections with same anti-VEGF drug (Injections) [Mean (Full Range) ]
Mean (Full Range) [Injections]	21.9
Pseudophakic (Eyes) [Count of Units]
Count of Units [Eyes]	8
Current treatment interval (Eyes) [Count of Units]
Every 4 weeks	8
Every 5 weeks	1
Every 6 weeks	1

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Only 8 of 10 eyes completed study visit 3. The protocol only required follow-up through study visit 2.

Arm/Group Title	Dorzolamide-timolol
Arm/Group Description	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 Dorzolamide-timolol: On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration
Measure Participants	10
Pre-enrollment visit	422.9 (100.9)
Enrollment visit	419.7 (95.9)
Study visit 1	364.5 (76.3)
Study visit 2	346.7 (99.9)
Study visit 3	326.9 (115.5)
Final visit	334.1 (103.0)

2. Secondary Outcome

Title	Visual Acuity
Description	LogMAR Visual acuity on enrollment and final visit
Time Frame	3 visits (8-12 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dorzolamide-timolol
Arm/Group Description	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 Dorzolamide-timolol: On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration
Measure Participants	10
Measure Eyes	10
Baseline	0.54 (0.53)
Final	0.48 (0.29)

3. Secondary Outcome

Title	Maximum Subretinal Fluid Height
Description	Measurement based on SD-OCT
Time Frame	3 visits (8-12 weeks)

Outcome Measure Data

Analysis Population Description

Only 8 of 10 eyes completed study visit 3. The protocol only required follow-up through study visit 2.

Arm/Group Title	Dorzolamide-timolol
Arm/Group Description	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 Dorzolamide-timolol: On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration
Measure Participants	10
Measure Eyes	10
Pre-enrollment visit	111.5 (101.3)
Enrollment visit	126.6 (78.2)
Study visit 1	77.9 (70.7)
Study visit 2	62.0 (59.7)
Study visit 3	56.5 (58.0)
Final visit	49.5 (54.1)

4. Secondary Outcome

Title	Maximum Pigment Epithelial Detachment Height
Description	Measurement based on SD-OCT
Time Frame	3 visits (8-12 weeks)

Outcome Measure Data

Analysis Population Description

Only 8 of 10 eyes completed study visit 3. The protocol only required follow-up through study visit 2.

Arm/Group Title	Dorzolamide-timolol
Arm/Group Description	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 Dorzolamide-timolol: On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration
Measure Participants	10
Measure Eyes	10
Pre-enrollment visit	275.4 (170.7)
Enrollment visit	277.4 (174.9)
Study visit 1	258.9 (173.7)
Study visit 2	227.8 (163.0)
Study visit 3	275.4 (160.8)
Final visit	239.9 (163.0)

Adverse Events

Time Frame	8 months
Arm/Group Title	Dorzolamide-timolol
Arm/Group Description	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 Dorzolamide-timolol: On enrollment, eligible patients will be started on topical dorzolamide-timolol in the study eye twice daily for the study duration
All Cause Mortality
	Dorzolamide-timolol
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Serious Adverse Events
	Dorzolamide-timolol
	Affected / at Risk (%)	# Events
Total	0/14 (0%)
Other (Not Including Serious) Adverse Events
	Dorzolamide-timolol
	Affected / at Risk (%)	# Events
Total	0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.