Clinical trial NCT02571972: Dorzolamide-timolol Drops With Injections to Treat AMD, RVO or DME.
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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Wet Macular Degeneration
Age-related Macular Degeneration
Diabetic Macular Edema
Retinal Vein Occlusion
Keywords: dorzolamide-timolol
topical aqueous suppression
neovascular age-related macular degeneration
macular edema
intravitreal injection
anti-vascular endothelial growth factor
Lead sponsor: Wills Eye
Sponsor class: OTHER
Collaborators: name: J. Arch McNamara Research Fund
name: Mid Atlantic Retina
First posted: 2015-10-08
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

   -

Primary outcomes:
measure: Mean Central Subfield Thickness (CST)
timeFrame: 3 visits (8-12 weeks)
Secondary outcomes:
measure: Visual Acuity
timeFrame: 3 visits (8-12 weeks)
measure: Maximum Subretinal Fluid Height
timeFrame: 3 visits (8-12 weeks)
measure: Maximum Pigment Epithelial Detachment Height
timeFrame: 3 visits (8-12 weeks)
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Wills Eye Hospital / Mid Atlantic Retina
state: Pennsylvania
Study officials:
affiliation: Wills Eye Hospital, Mid Atlantic Retina
name: Jason Hsu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.