Intravitreal Adalimumab in Inherited and Degenerative Retinal Diseases (ADARET)

Intravitreal Adalimumab in Inherited and Degenerative Retinal Diseases: A Prospective Comparative Pilot Study

This prospective, comparative pilot study investigates the safety and functional outcomes of intravitreal adalimumab (ADA) in patients with Retinitis Pigmentosa (RP) and Extensive Macular Atrophy with Pseudodrusen-like Appearance (EMAP).

Participants will receive three intravitreal injections of adalimumab (2 mg/0.05 mL) at two-month intervals (M0, M2, M4).

The primary objective is to assess functional changes after 6 months, focusing on visual-field preservation (Field Preservation Deviation Index - FPDI, Mean Deviation - MD) and best-corrected visual acuity (LogMAR).

Secondary outcomes include alterations in 30-Hz flicker ERG amplitude, OCT parameters (central macular thickness and ellipsoid zone length), and ocular safety measures such as intraocular pressure and inflammatory response.

Study Overview

• Status: Active, not recruiting
• Conditions: Retinitis Pigmentosa (RP); Extensive Macular Atrophy With Pseudodrusen (EMAP)
• Intervention / Treatment: Drug: Intravitreal Adalimumab

Detailed Description

Retinitis pigmentosa (RP) represents a genetically and phenotypically heterogeneous group of inherited retinal dystrophies characterized by progressive photoreceptor degeneration, classically beginning with rod dysfunction and followed by cone loss. Patients typically present with nyctalopia, peripheral visual-field constriction, and, in advanced stages, central vision impairment. Despite significant advances in gene-specific, cell-based, and prosthetic approaches, most patients currently lack broadly applicable interventions capable of slowing or reversing disease progression across RP's wide genotypic spectrum.

Recent evidence reframes RP as not only a genetic degenerative process but also a state of chronic para-inflammation in the outer retina. Microglial activation, breakdown of the blood-retinal barrier, and overexpression of pro-inflammatory cytokines-particularly tumor necrosis factor-alpha (TNF-α)-have been implicated in accelerating photoreceptor apoptosis and secondary cone degeneration. Within this biological context, adalimumab (ADA), a fully human monoclonal antibody that selectively inhibits TNF-α, offers a mechanism-based therapeutic rationale for mitigating inflammatory injury in RP.

This prospective, single-arm pilot study was designed to evaluate the functional impact and ocular safety of intravitreal adalimumab in patients with RP. Participants received three intravitreal ADA injections (2 mg/0.05 mL) at two-month intervals (M0, M2, M4). The primary assessments included best-corrected visual acuity (BCVA, LogMAR), visual-field metrics (FPDI, MD, PSD; using 10-2 for advanced and 24-2 for less advanced disease), and 30-Hz flicker ERG when measurable. Structural endpoints comprised OCT-derived central macular thickness and ellipsoid zone (EZ) length. Outcomes were analyzed for pre-post change over six months (M0-M6) and feasibility in a real-world clinical research setting.

This exploratory study aims to generate foundational data to guide future controlled trials of anti-TNF therapy in inherited retinal degenerations with inflammatory components.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • São Paulo
    • São José do Rio Preto, São Paulo, Brazil, 15010-100
      • Rubens Siqueira Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age ≥ 18 years.

• Clinical diagnosis of retinitis pigmentosa (RP) or EMAP (Extensive Macular Atrophy with Pseudodrusen-like Appearance) confirmed by multimodal evaluation.
• Best-corrected visual acuity (BCVA) ≥ counting fingers at 1 meter (approximately ≤ 1.9 logMAR) in the study eye.
• Measurable visual field on iCare COMPASS (10-2 or 24-2) with acceptable reliability indices.
• Clear ocular media adequate for safe intravitreal injection and high-quality OCT imaging.
• Ability and willingness to provide written informed consent.
• Ability to comply with scheduled study visits (Baseline [M0], Day 7-14 after injections, Month 2 [M2], Day 7-14, Month 4 [M4], Day 7-14, and Month 6 [M6]).
• For ERG subset only: presence of a recordable baseline 30-Hz flicker ERG response (signal-to-noise ratio ≥ 3:1 and amplitude ≥ 3.0 µV).
• Note: Absence of a measurable flicker ERG response does not exclude participation in the main study.

Exclusion Criteria:

• Active ocular inflammation (anterior, intermediate, or posterior uveitis) or infectious ocular disease in the study eye.
• Active choroidal neovascularization or other macular diseases unrelated to RP or EMAP.
• Uncontrolled glaucoma (intraocular pressure > 21 mmHg despite therapy) or optic neuropathies not related to RP or EMAP.
• Significant media opacity that may impair imaging quality or safe intravitreal injection.
• Recent ocular interventions that may confound study outcomes, including:
• Intravitreal therapy within 3 months prior to enrollment.
• Periocular corticosteroid injection within 3 months prior to enrollment.
• Major intraocular surgery within 3 months prior to enrollment.
• Known hypersensitivity to adalimumab, povidone-iodine, local anesthetics, or any formulation components.
• Coagulopathy or contraindications to ocular injections (platelet count < 100,000/µL or INR > 1.5 unless corrected).
• Pregnancy or breastfeeding.
• Women of childbearing potential unwilling to use effective contraception during the study period.
• Uncontrolled systemic disease that increases risk or interferes with study participation or completion.
• Participation in another interventional clinical trial within 3 months prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: intravitreal injection of adalimumab; Participants receive intravitreal injections of adalimumab 2 mg/0.05 mL at baseline (M0), month 2 (M2), and month 4 (M4). This arm evaluates the effect of anti-TNF-α immunomodulation alone on visual function and retinal structure in patients with Retinitis Pigmentosa and EMAP.	Drug: Intravitreal Adalimumab; Participants receive intravitreal injections of adalimumab 2 mg/0.05 mL at baseline (M0), month 2 (M2), and month 4 (M4).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Field Preservation Deviation Index (FPDI)	Change (Δ) in Field Preservation Deviation Index (FPDI), expressed as a percentage (%), measured by automated perimetry using the iCare COMPASS system. The FPDI reflects the proportion of preserved visual field relative to age-matched normative data and provides a quantitative assessment of global visual field integrity. The outcome is defined as the difference between baseline (Month 0) and Month 6 values in the study eye.	Baseline to Month 6
Change in Mean Deviation (MD)	Change (Δ) in Mean Deviation (MD), expressed in decibels (dB), measured by automated perimetry using the iCare COMPASS system. Mean Deviation represents the average difference in retinal sensitivity compared with age-adjusted normative values, serving as a global index of visual field loss. The outcome corresponds to the difference between baseline (Month 0) and Month 6 measurements in the study eye.	Baseline to Month 6
Change in Best-Corrected Visual Acuity (BCVA)	Change (Δ) in Best-Corrected Visual Acuity (BCVA), expressed in logarithm of the minimum angle of resolution (LogMAR), measured using standardized Early Treatment Diabetic Retinopathy Study (ETDRS) charts under controlled testing conditions. BCVA assesses central visual function and foveal integrity. The outcome is defined as the difference between baseline (Month 0) and Month 6 BCVA values in the study eye.	Baseline to Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 30-Hz Flicker ERG Amplitude	Change (Δ) in 30-Hz flicker electroretinogram (ERG) amplitude, expressed in microvolts (µV), measured in accordance with International Society for Clinical Electrophysiology of Vision (ISCEV) standards. The 30-Hz flicker ERG primarily assesses cone-mediated retinal function and provides an objective measure of global photoreceptor and post-receptoral pathway integrity. The outcome corresponds to the difference between baseline (Month 0) and Month 6 values in the study eye.	Baseline to Month 6
Change in Central Macular Thickness (CMT)	Change (Δ) in central macular thickness (CMT), expressed in micrometers (µm), measured by spectral-domain optical coherence tomography (SD-OCT). CMT represents the average retinal thickness within the central macular subfield and serves as a structural biomarker of macular integrity, including retinal edema, atrophy, or remodeling. The outcome is defined as the difference between baseline (Month 0) and Month 6 measurements in the study eye.	Baseline to Month 6
Change in Ellipsoid Zone (EZ) Length	Change (Δ) in ellipsoid zone (EZ) length, expressed in micrometers (µm), measured by spectral-domain optical coherence tomography (SD-OCT). EZ length reflects the integrity and spatial extent of photoreceptor inner segment ellipsoid band and is a sensitive structural biomarker of photoreceptor preservation in degenerative retinal diseases. The outcome corresponds to the difference between baseline (Month 0) and Month 6 measurements in the study eye.	Baseline to Month 6
Change in Pattern Standard Deviation (PSD)	Change (Δ) in Pattern Standard Deviation (PSD), expressed in decibels (dB), measured by automated perimetry using the iCare COMPASS system. PSD reflects localized irregularities in visual field sensitivity and is particularly sensitive to focal or non-uniform patterns of visual field loss. The outcome is defined as the difference between baseline (Month 0) and Month 6 measurements in the study eye.	Baseline to Month 6

Collaborators and Investigators

• Sponsor: Centro de Pesquisa Rubens Siqueira

Publications and helpful links

General Publications

• Siqueira RC, Brandao CC. The Role of Cytokines in Degenerative Retinal Diseases: A Comprehensive Review. Biomedicines. 2025 Jul 15;13(7):1724. doi: 10.3390/biomedicines13071724.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2024
• Primary Completion (Actual): August 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: November 30, 2025
• First Submitted That Met QC Criteria: January 8, 2026
• First Posted (Actual): January 16, 2026

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: retinal degeneration; visual field; retinitis pigmentosa; Ellipsoid zone; ERG; intravitreal adalimumab
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinitis Pigmentosa; Retinal Degeneration
• Other Study ID Numbers: ADARET

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No