Effects of 0.1% Nepafenac on Vitreous Inflammatory Biomarkers in Rhegmatogenous Retinal Detachment and Proliferative Vitreoretinopathy

NCT07162818 | Completed Phase 4

• 2 other identifiers: 21-01-0081PUTI Saintekes 2022 Grant
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

PVR remains the major cause of surgical failure in RRD repair.1 Prompt surgical management is the standard therapy in RRD repair. However, in many places, vitreoretinal (VR) surgery facilities is limited, such as in Indonesia, where mainly located within referral hospitals. Until recently, there has been no recommended pharmacological therapy before surgery to prevent the formation of PVR in RRD. . Previous studies involving the use of pharmacological agents, such as anti-inflammatory and anti-proliferative agents, have been reported to prevent the development of PVR. Nepafenac 0.1% eye drops is a potent NSAID that has been proven effective in preventing macular edema in cases of post-cataract surgery and diabetic retinopathy. This study aims to compare the levels of vitreous inflammatory biomarkers in RRD following the administration of preoperative nepafenac 0.1%. The inclusion criteria were patients of the age of 18 years old and above with macula-off RRD, grade A or B PVR, and RRD onset upon examination up to 1 month. The exclusion criteria included RRD patients with media opacification, a history of intraocular surgery in less than 3 months, other eye disease comorbidities (i.e., macular hole, epiretinal membrane), other systemic diseases, and a history of NSAID allergy.

Conditions

Proliferative Vitreoretinopathy; Rhegmatogenous Retinal Detachment

Keywords

Vitreous Inflammatory Biomarker; Nepafenac 0.1%; Proliferative Vitreoretinopathy; Rhegmatogenous Retinal Detachment

Outcome Measures

Primary Outcomes (4)

• Prostaglandin E2 (PGE2)

  Vitreous samples were thawed and prostaglandin E2 (PGE2) levels were analyzed using the Prostaglandin E2 Monoclonal ELISA Kit (Cayman Chemical Company, Ann Arbor, MI) using a competitive ELISA according to the manufacturer's instructions. Briefly, serial dilutions of standards (7.8-1000 pg/mL) were prepared. Standards, controls, and vitreous samples were added to microplate wells coated with a specific polyclonal antibody against mouse IgG, followed by the addition of the acetylcholinesterase-PGE2 conjugate tracer and the PGE2 monoclonal antibody. The plates were incubated overnight at 40°C. During incubation, competition occurred between PGE-2 in the samples/standards and the PGE2 monoclonal antibody. The PGE-2 antibody complex bound to the polyclonal antibody against mouse IgG on the well walls. The plate was washed, then Ellman's reagent was added to each well of the microplate. The plate was covered and incubated at room temperature on an orbital shaker for 60 minutes. The color f

  Through study completion, an average of 1 year

• Transforming Growth Factor β1 (TGF-β1)

  Vitreous samples were thawed and activated before the sandwich ELISA test using the Quantikine ELISA Human TGFβ-1 kit (R\&D Systems, MN, USA). Activation was performed by placing 40 μL of sample in a tube and adding 20 μL of 1N HCl, which was incubated for 10 minutes at room temperature. Next, the sample was neutralized by adding 20 μL of 1.2N NaOH and 0.5 M HEPES. Afterward, the sample was diluted 1:20 with RD5-53 calipers (a 1:4 dilution). Fifty μL of RD1-73 solution was added to each well of the microplate, followed by 50 μL of sample or standard, and incubated for 2 hours at room temperature. After the incubation period, the plate was washed three times with 400 μL of buffer. Afterward, anti-TGFb-1 conjugate was added to each well and incubated for another 2 hours at room temperature. After incubation, a wash was performed, then 100 μL of substrate solution was added, incubated for another 13 minutes at room temperature, protected from light, and the reaction was stopped by adding

  Through study completion, an average of 1 year

• Siklooksigenisase-2 (COX-2) Enzyme

  Vitreous samples were thawed and activated before the sandwich ELISA assay using the Human Cyclooxygenase 2 (COX-2) kit according to the protocol. The vitreous samples were added to the wells of a microtiter plate coated with a monoclonal antibody against COX-2. If COX-2 is present in the sample, it will bind to the antibody. To quantitatively determine the amount of COX-2 in the sample, standards with varying concentrations of COX-2 were added. After incubation, the COX-2 antibody on the well walls binds to the COX-2 in the sample or standard. After washing to remove any unbound components, a horseradish peroxidase (HRP)-conjugated polyclonal antibody was added. The microtiter plate was incubated and then washed. Next, substrate solution was added to each well of the microtiter plate. The HRP enzyme and substrate were allowed to react for a short incubation period. Only wells containing COX-2 showed a color change due to binding to the HRP-conjugated antibody. The enzyme-substrate re

  Through study completion, an average of 1 year

• Macrophage Cell Count

  The number of macrophages in vitreous samples was measured using flow cytometry, utilizing CD14 as a monocyte/macrophage marker. Pure vitreous samples were prepared according to a modification of the protocol adopted for cytology samples at the Faculty of Medicine, University of Indonesia (FKUI) Integrated Laboratory. After incubation for 10 minutes at room temperature in the dark, the samples were centrifuged for 5 minutes at 1500 rpm. The supernatant was discarded and washed with 2.5 mL of buffer solution. Antibody was added, and the samples were then incubated in the dark at room temperature for 20 minutes. After 20 minutes, excess antibody was washed away with buffer solution. Flow cytometry was performed using a FACSCanto II flow cytometer (Becton Dickinson, San Jose, CA). The results were analyzed using the FACSDiva program.

  Through study completion, an average of 1 year

Study Arms (2)

Nepafenac 0.1% eyedrops

EXPERIMENTAL

Nepafenac 0.1% is a topical NSAID pro-drug for the eye.

Drug: Nepafenac 0.1% eyedrops

Control

PLACEBO COMPARATOR

Cenfresh® sterile eye drops in 5 mL packaging containing 5mg Carmellose sodium

Drug: Control (placebo) group

Interventions

Nepafenac 0.1% eyedrops DRUG

The study eye drops were nepavenac 0.1% eye drops (NEVANAC 0.1%®, Alcon Laboratories, Inc., Fort Worth, Texas). Subjects were instructed to use eye drops on the side of the eye with the ARR, three times daily for five days before and on the day of surgery. Written instructions and a daily checklist to record the eye drop schedule were provided to each subject.

Nepafenac 0.1% eyedrops

Control (placebo) group DRUG

Cenfresh® eye drops (Cendo pharmaceutical, Indonesia) for the control group. Subjects were instructed to use eye drops on the side of the eye with the ARR, three times daily for five days before and on the day of surgery. Written instructions and a daily checklist to record the eye drop schedule were provided to each subject.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ARR with PVR grade A and B
• ARR onset more than 7 days and less than 1 month
• Macula off
• ARR patients with a minimum age of 18 years.
• Willing to follow the research stages and sign the informed consent.

You may not qualify if:

• ARR patients with media opacities that do not allow fundus examination
• History of undergoing intraocular surgery less than 3 months.
• ARR patients with comorbid eye diseases.
• ARR patients with systemic complications that make it impossible to undergo vitrectomy surgery.
• ARR sufferers who are known to have a history of allergies to the NSAID group.

Sponsors & Collaborators

• Indonesia University: lead

Study Sites (1)

Department of Ophthalmology, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo Hospital

Jakarta, Jakarta Pusat, Indonesia

Location

MeSH Terms

Conditions

Vitreoretinopathy, Proliferative

Interventions

nepafenac; Ophthalmic Solutions; Population Groups

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Solutions; Solutions; Pharmaceutical Preparations; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Demography; Population Characteristics

Study Officials

• Ari Djatikusumo, MD

  Department of Ophthalmology, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo Hospital, Indonesia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participants, the ophthalmologist conducting the eye examinations, and the outcome assessors will be blinded to group allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Ophthalmology Department, Faculty of Medicine Universitas Indonesia Cipto Mangunkusumo Hospital, Indonesia

Model Details: This study will compare the levels of vitreous inflammatory biomarkers in rhegmatogenous retinal detachment (RRD) with proliferative vitreoretinopathy (PVR), following the administration of pre-vitrectomy nepafenac 0.1%, as a method to prevent the progression of PVR.

Study Record Dates

• First Submitted: August 25, 2025
• First Posted: September 9, 2025
• Study Start: April 28, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: September 9, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)