Subthreshold Laser Treatment for Reticular Pseudodrusen Secondary to Age-related Macular Degeneration (PASCAL-RPD)

Prospective, randomized, controlled, longitudinal, interventional multicentric study involving patients with reticular pseudodrusen secondary to AMD.

The objective of this study is to establish the effectiveness of subthreshold laser treatment in increase/prevent the decrease of the retinal sensibility in patients with reticular pseudodrusen, and to reduce the progression of RPD to atrophy.

Approximately 50 naïve patients with reticular pseudodrusen who underwent subthreshold laser treatment in perifoveal area. These patients should be randomized in the 2 study arms of the study. Patients will be evaluated at Screening/Baseline and then revaluated and retreated at month 3, 6 and 9. At month 12, all patients will be evaluated with a full ocular examination, visual acuity measurement (VA), optical coherence tomography (OCT) with autofluorescence, OCT-angiography and microperimetry.

The rationale of the study is to prevent the evolution of reticular pseudodrusen to atrophic degeneration.

Study Overview

• Status: Recruiting
• Conditions: Macular Degeneration, Dry; Macular Degeneration, Senile; Laser Burn of Retina; Macular Degeneration Intermediate
• Intervention / Treatment: Device: Pascal Synthesis 577 sub-threshold laser (Topcon Corporation, Tokyo, Japan); Device: Pascal Synthesis 577 sham (Topcon Corporation, Tokyo, Japan)

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giuseppe Querques, MD, PhD; Phone Number: +390226434004; Email: querques.giuseppe@hsr.it

Study Locations

• Italy
  • Genova, Italy
    • Recruiting
    • Massimo Nicolò
    • Contact: Massimo Nicolò, MD; Phone Number: +390103538469; Email: massimonicolo@gmail.com
  • Milan, Italy, 20134
    • Recruiting
    • Giuseppe Querques
    • Contact: Giuseppe Querques, MD, PhD; Phone Number: +390226434004; Email: querques.giuseppe@hsr.it
    • Principal Investigator: Giuseppe Querques, MD, PhD
    • Principal Investigator: Riccardo Sacconi, MD, FEBO
    • Sub-Investigator: Enrico Borrelli, MD, FEBO
  • Rome, Italy
    • Recruiting
    • Mariacristina Parravano
    • Contact: Mariacristina Parravano; Phone Number: +390685356727; Email: mcparravano@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 50 years or older
• Presence of RPD secondary to AMD
• Best-corrected visual acuity (BCVA) between 20/20 and 20/400 inclusive
• Clear ocular media
• Ability to provide informed consent and attend all study visits

Exclusion Criteria:

• Presence of Geographic Atrophy (GA)
• Evidence of choroidal neovascularization in either eye
• Any prior treatment for AMD, aside from antioxidants
• Any corneal opacity, cataract formation and hemorrhage in the vitreous body, which may interfere with viewing by the laser surgeon of the target structures
• Aphakic eye with vitreous in the anterior chamber
• Neovascular Glaucoma
• Glaucoma caused by congenital angle anomalies
• Open angle of less than 90º or extensive peripheral anterior and low synechia, present circumferentially around the corner
• Significant corneal edema or reduced water clarity that obscures the view angle in detail
• Glaucoma secondary to active uveitis
• Any other ocular condition that would progress in the study period and confound visual acuity assessment
• Any ocular or systemic medication known to be toxic to the lens, retina or optic nerve Presence of idiopathic or autoimmune-associated uveitis
• Any intraocular surgery 3 months of entry
• Any prior thermal laser in the macula
• History of vitrectomy, filtering surgery, corneal transplant or retinal detachment surgery
• Previous therapeutic radiation in the ocular region in either eye
• Any treatment with an investigational agent in the previous 60 days before study entry
• Women of child-bearing potential, defined as all women less than 1 year postmenopausal or less than 6 weeks since sterilization (further definition can be found in Section 12.7) at Baseline, unless they are using highly effective methods of contraception during dosing of study treatment.
• Participation in an investigational drug, biologic, or device study within 6 Months prior to Baseline [Note: observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subthreshold laser group; To evaluate the efficacy of Subthreshold laser in the treatment of reticular pseudodrusen.	Device: Pascal Synthesis 577 sub-threshold laser (Topcon Corporation, Tokyo, Japan); The subthreshold laser treatment will be performed using subthreshold laser Pascal Synthesis 577 on a customized macular area.
Sham Comparator: Sham group; The light from the retinal illumination system on the laser device will be used instead of the laser beam in all follow-up evaluations.	Device: Pascal Synthesis 577 sham (Topcon Corporation, Tokyo, Japan); The laser treatment will be performed without any power (only the light beam) using subthreshold laser Pascal Synthesis 577 on a customized macular area.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the retinal sensitivity - 12 months	Functional changes in the retinal sensitivity on customized microperimetry from day 0 to month 12 (unit of measure: dB)	12 months
Anatomical changes using structural optical coherence tomography (OCT)	Anatomical changes will be evaluated with retinal thickness (unit of measure: microns)	12 months
Rate of Progression	Rate of progression to advance AMD (GA and/or neovascular AMD)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the retinal sensitivity - 6 months	Functional changes in the retinal sensitivity on customized microperimetry from day 0 to month 6 (unit of measure: dB)	6 months
Anatomical changes using fundus autofluorescence (FAF)	Anatomical changes will be evaluated analyzing the development of geographic atrophy using FAF	12 months
Genetic influence (% of AMD-associated single-nucleotide polymorphism (SNP) in treated patients)	The % of AMD-associated single-nucleotide polymorphism (SNP) will be evaluated analyzing the % of patients with an AMD-associated SNP in patients showing no progression vs progression to advance AMD (main outcome 3).	12 months
Anatomical changes using OCT-angiography (OCT-A)	Anatomical changes will be evaluated analyzing the perfusion density by means of OCT-A	12 months

Collaborators and Investigators

• Sponsor: Ospedale San Raffaele
• Collaborators: University of Rome Tor Vergata; University of Genova; Fondazione G.B. Bietti, IRCCS

Publications and helpful links

General Publications

• Querques G, Sacconi R, Gelormini F, Borrelli E, Prascina F, Zucchiatti I, Querques L, Bandello F. Subthreshold laser treatment for reticular pseudodrusen secondary to age-related macular degeneration. Sci Rep. 2021 Jan 26;11(1):2193. doi: 10.1038/s41598-021-81810-7.

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: April 7, 2021
• First Submitted That Met QC Criteria: April 12, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Retina; Age-related macular degeneration; Reticular pseudodrusen; Sub-threshold laser
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Geographic Atrophy
• Other Study ID Numbers: PASCAL-RPD

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
• product manufactured in and exported from the U.S.: No