Subthreshold Micropulse Laser Therapy (SML) in Retinitis Pigmentosa

NCT07088705 | Enrolling By Invitation DMC

• 1 other identifier: 2022/ABM/03/00014
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction Retinitis pigmentosa (RP) is the most common form of genetic retinal degenerative disease. The disease is progressive and leads to blindness and permanent disability within a few years of diagnosis. The etiology of RP is multifactorial. It combines genetic (multiple inheritance patterns) and environmental factors, which makes it difficult to develop effective causal therapy. Many potential methods of RP treatment have been described so far, but the lack of unequivocal evidence of the therapeutic effectiveness of these methods implies a lack of RP therapy standards. Few analyzes have shown that the use of a red subthreshold micropulse laser (SML) with a wavelength of 810 nm causes a neurostimulatory effect on the retina. The subsequent introduction of a yellow laser with a wavelength of 577 nm, dedicated to edema and ischemic retinal diseases, re-initiated a series of questions about the effectiveness of both therapies and the treatment protocols used. This fact emphasizes the need for further verification and optimization of SML treatment regimens in Poland, which has a chance to become a new, widely available, non-invasive standard of treatment independent of the genetic pattern. The aim of the project The main goal of the experiment is to verify the effectiveness of SML and determine the optimal treatment protocol for SML based on a detailed analysis of molecular changes of selected pro-inflammatory, neurotrophic and angiogenic factors (IL-1α, IL-1β, IL-2, IL-4, IL-5, IL- 6 IL-8, IL-10, IL-12 p70, IL-13, IL-17A, CXCL8 / IL-8, MCP-1 / CCL2, MIP-1α / CCL3, MIP-1β / CCL4, IL-8 / CXCL8, CCL5 / RANTES, IP-10 / CXCL10, GM-CSF, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, BMP-4, BMP-7, BMP - 9, TIMP-1, t-PA, PAI-1, NGF, EGF, TNF-α, TGF-β1, TGF-β2, FGF, EGF, G-CSF, GM-CSF, HGF, PDGF-AA, PDGF- AB / BB, VEGF, PAI-1, COL1A1, TSP-2, IFN-γ, N-cadherin, E-selection and P-selection) in tears and peripheral blood of patients with RP. Moreover, the project aims to personalize the assessed treatment regimens by determining the correlation between these changes and the genotype and dynamics of functional changes of the retina in the eyes from the RP subjected to single stimulation with yellow and red SML. Materials and methods The study group will consist of 60 adult patients with retinitis pigmentosa diagnosed on the basis of a characteristic clinical picture confirmed by genome analysis using the whole exome sequencing method and full-field electroretinoography (ERG). In randomized selection, one eye of each patient will be randomly assigned to be stimulated with red (30 eyes) or yellow (30 eyes) SML, and second eye will be assigned to the sham procedure. This will ensure a comprehensive comparative assessment of the effectiveness of both types of SML against each other and against a placebo. The tear film will be collected by wetting the Schirmer strips placed under the lower eyelid before SML (T0) and 28 days (T1), 3 months (T2) and 6 months (T3) after the laser stimulation. In addition, approximately 7.5 ml of peripheral venous blood will be collected at corresponding time points. The assessment of the dynamics of functional changes based on the measurements of the best corrected visual acuity for distance and near vision, contrast sensitivity, microperimetry, 10-2 and 30-2 static perimetry, electroretinogram stimulated with the pattern (PERG) and multifocal electroretinogram (mfERG) in both eyes will be carried out at the time points T0, T1-T3. In addition, during the T0-T3 visits, the morphology of the eyeball, i.e. examination of the anterior segment and fundus of the eye in a slit lamp, examination of optical coherence tomography of the macula and ultrasound of the eyeball will be assessed. The quality of life of the participants of the experiment will be assessed on the basis of the standardized NEI VFQ-25 questionnaire. The quality of life assessment will take place both before the implementation of the SML and during subsequent follow-up visits. Expected project benefits Conducting the proposed experiment will result in verification of the effectiveness of the retinal stimulation by the yellow SML in comparison to the red SML in the eyes with retinitis pigmentosa. In addition, conducting genome analysis and monitoring changes in the concentration of pro-inflammatory, neurotrophic and angiogenic factors in the tear film and peripheral blood in combination with a detailed assessment of the dynamics of functional changes in the eyes with RP after stimulation with an immunomodulatory stimulus SML will enable optimization and personalization of this treatment method in relation to the genetic profile of the patient with RP. The expected results may direct further research on the search for an effective therapy for patients with RP or constitute the basis for the introduction of the world's first standard of adjuvant treatment in this disease entity.

Conditions

Retinitis Pigmentosa (RP)

Keywords

Retinitis Pigmentosa; subtreshold micropulse laser; treatment

Outcome Measures

Primary Outcomes (1)

• BCDVA improvement

  BCDVA improvement is defined as an increase of at least 5 letters demonstrated at at least two consecutive time points after the intervention compared to baseline measurements. BCDVA is visual acuity measured using standardized ETDRS charts, measuring the number of letters read correctly by the patient at a distance of 4 meters.

  The planned follow-up time is 6 months with visits before the intervention, at 1, 3 and 6 months after the SML procedure.

Secondary Outcomes (3)

• Improvement in the bioelectrical function of the central retina assessed by mfERG.

  The planned follow-up time is 6 months with visits before the intervention, at 1, 3 and 6 months after the SML procedure.

• The improvement of mean deviation (MD) in 10-2 perimetry.

  The planned follow-up time is 6 months with visits before the intervention, at 1, 3 and 6 months after the SML procedure.

• Improvement of a macular integrity and retinal sensitivity in a microperimetry test

  The planned follow-up time is 6 months with visits before the intervention, at 1, 3 and 6 months after the SML procedure.

Study Arms (3)

SML 577 nm

EXPERIMENTAL

Patient preparation will include obtaining informed consent, local anesthesia of the conjunctival sac with 0.05% proxymetacaine drops to reduce discomfort, and the administration of 0.1% tropicamide to dilate the pupil and increase access to the retina during laser stimulation. Next, a Volk macular contact lens (Volk Optical, Mentor, OH, USA) will be placed on the cornea using a viscoelastic agent. A modern 577 nm yellow laser (Supra Scan 577, Quantel Medical, Cedex, France) will be used for stimulation. The panmacular stimulation is planned, with the laser covering the entire central retinal area between the vascular arches, including the foveal region. Approximately 600 160-μm diameter impacts will be delivered per session using a 250-μm power output with a duration of 0.2 seconds and a 5% duty cycle.

Device: SML 577 nm

SML 810 nm

ACTIVE COMPARATOR

Preparation for SML using an 810 nm red laser will involve informed consent, local anesthesia of the conjunctival sac with 0.05% proxymetacaine drops to reduce discomfort during the procedure, and the administration of 0.1% tropicamide to dilate the pupil and increase access to the retina during laser stimulation. A Volk macular contact lens (Volk Optical, Mentor, OH, USA) will then be placed on the cornea using a viscoelastic agent. Central retinal stimulation will be performed using an 810 nm SML. The panmacular stimulation protocol will be used, with the laser covering the entire central retinal area between the vascular arcs, including the foveal region. During one session, approximately 1500-2000 confluent local applications of 200 μm diameter will be performed using 1.4 W of power with a duration of 0.15 seconds and a 5% duty cycle.

Device: SML 810 nm

Sham SML

SHAM COMPARATOR

It is worth emphasizing that the experiment was designed as a factorial study design with the patient blinded. To this end, patient preparation, laser treatment duration, and auditory and visual sensations during the sham procedure will be the same as those experienced with a truly lasered eye. Consequently, fellow eye of an each RP eye that undergone the SML stimulation in either arm 1 or 2 will be included in the sham group (60 eyes).

Other: Sham SML

Interventions

SML 577 nm DEVICE

A 577 nm yellow and 810 nm red lasers will be used for stimulation. The panmacular stimulation is planned, with the laser covering the entire central retina between the vascular arches, including the foveal region according to the study protocol. Patient preparation will include obtaining informed consent, local anesthesia of the conjunctival sac with 0.05% proxymetacaine drops to reduce discomfort, and the administration of 0.1% tropicamide to dilate the pupil and increase access to the retina during laser stimulation. Next, a Volk macular contact lens (Volk Optical, Mentor, OH, USA) will be placed on the cornea using a viscoelastic agent. A modern 577 nm yellow laser (Supra Scan 577, Quantel Medical, Cedex, France) will be used for stimulation. The panmacular stimulation is planned, with the laser covering the entire central retinal area between the vascular arches, including the foveal region.

SML 577 nm

SML 810 nm DEVICE

Preparation for SML using an 810 nm red laser will involve informed consent, local anesthesia of the conjunctival sac with 0.05% proxymetacaine drops to reduce discomfort during the procedure, and the administration of 0.1% tropicamide to dilate the pupil and increase access to the retina during laser stimulation. A Volk macular contact lens (Volk Optical, Mentor, OH, USA) will then be placed on the cornea using a viscoelastic agent. Central retinal stimulation will be performed using an 810 nm SML. The panmacular stimulation protocol will be used, with the laser covering the entire central retinal area between the vascular arcs, including the foveal region. During one session, approximately 1500-2000 confluent local applications of 200 μm diameter will be performed using 1.4 W of power with a duration of 0.15 seconds and a 5% duty cycle.

SML 810 nm

Sham SML OTHER

It is worth emphasizing that the experiment was designed as a factorial study design with the patient blinded. To this end, patient preparation, laser treatment duration, and auditory and visual sensations during the sham procedure will be the same as those experienced with a truly lasered eye. Consequently, fellow eye of an each RP eye that undergone the SML stimulation in either arm 1 or 2 will be included in the sham group (60 eyes).

Sham SML

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinically diagnosed RP, including (i) characteristic fundus appearance with waxy pallor of the optic disc; (ii) reduced retinal vessel diameter and intraretinal pigment deposits in the central periphery of the fundus; (iii) history of progressive night vision and/or color vision impairment, peripheral vision loss, photophobia, reduced visual acuity, and prolonged dark adaptation; (iv) peripheral narrowing to "tunnel vision" on visual field testing; (v) significant amplitude reduction with prolonged waveform latency or unrecordable readings on flash electroretinography (ERG) and confirmed by NGS panel sequencing covering all known genes responsible for retinal dystrophic diseases or Whole Exome Sequencing (WES);
• Age 18-70 years; - BCDVA no lower than 0.08 (according to the Snellen chart);
• Ability to provide informed consent.

You may not qualify if:

• Age \<18 years - \>70 years;
• Systemic diseases (acute inflammatory or autoimmune process, recent trauma, renal or hepatic failure, cardiovascular or neurological disease, stroke, cancer, diabetes, autoimmune diseases);
• Other eye diseases (e.g., glaucoma, age-related macular degeneration, vitreous degeneration); - Post-ocular surgery except uncomplicated cataract surgery;
• Cataract surgery or posterior capsulotomy less than 3 months prior to study enrollment;
• Systemic or topical use of immunomodulatory medications;
• Use of any other RP treatment, including dietary supplements, during the study or in the 3 months prior to enrollment.

Sponsors & Collaborators

• Marta P. Wiącek: lead
• Medical Research Agency, Poland: collaborator

Study Sites (1)

First Department of Ophthalmology, Pomeranian Medical University

Szczecin, 70-111, Poland

Location

MeSH Terms

Conditions

Retinitis Pigmentosa

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Retinal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: July 20, 2025
• First Posted: July 28, 2025
• Study Start: September 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): February 28, 2027
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will be available as soon as they will be acquired (August 2026) for at least 10 consecutive years.
• Access Criteria: The data will be available on a request directed to the principal investigator of the study. Especially the publishing journal and researchers planning to perform further analysis involving the study data are authorized.

Locations

PL (1)