Intravitreal Adalimumab in Inherited and Degenerative Retinal Diseases: A Prospective Comparative Pilot Study
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Centro de Pesquisa Rubens Siqueira
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Change in Field Preservation Deviation Index (FPDI)
Overview
Brief Summary
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.
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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).
Arms & Interventions
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.
Intervention: Intravitreal Adalimumab (Drug)
Outcomes
Primary Outcomes
Change in Field Preservation Deviation Index (FPDI)
Time Frame: Baseline to Month 6
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.
Change in Mean Deviation (MD)
Time Frame: Baseline to Month 6
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.
Change in Best-Corrected Visual Acuity (BCVA)
Time Frame: Baseline to Month 6
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.
Secondary Outcomes
- Change in Pattern Standard Deviation (PSD)(Baseline to Month 6)
- Change in 30-Hz Flicker ERG Amplitude(Baseline to Month 6)
- Change in Central Macular Thickness (CMT)(Baseline to Month 6)
- Change in Ellipsoid Zone (EZ) Length(Baseline to Month 6)
Investigators
Rubens Camargo Siqueira
MD,PhD
Centro de Pesquisa Rubens Siqueira