Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies

Sponsor

Fondazione G.B. Bietti, IRCCS (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05976139

Collaborator

(none)

Enrollment

Location

Arm

24.2

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate whether subthreshold treatment with micropulsed laser can be effective in resolving macular edema in patients with inherited retinal dystrophy.

Visits will be performed after 1, 3, 6, 9, 12, 18, and 24 months after treatment. Laser treatment will be performed on the day of the first visit, and its repetition at subsequent visits between months 3 and 12 will be evaluated.

Evaluations of treatment effects will include:

comprehensive ophthalmologic examination
multifocal electroretinogram
OCT examination
OCT-angiography examination
retinography

Primary endpoint.

central retinal thickness, measured by OCT

Condition or Disease	Intervention/Treatment	Phase
Macular Edema Inherited Retinal Dystrophy Laser Retinopathy	Device: subthreshold treatment with micropulsed laser	N/A

Detailed Description

BACKGROUND:

Degenerative diseases of the visual system classified as rare and, in particular, those affecting the retina (known as Inherited retinal dystrophies, IRDs) cause very severe functional deficits. Their onset is in many cases particularly early with a consequent visual impact of extreme severity. They constitute a heterogeneous group from a clinical point of view, but in all of them the loss of photoreceptors causes progressive vision loss that can result in complete blindness.

These pathologies can be complicated by the presence of cataracts, epiretinal membrane and macular oedema (10-50%), resulting in a worsening of visual acuity. While surgical treatment is applicable for the first two complications, the treatment of macular oedema can make use of several options. Oral or topical diuretics (Acetazolamide) are still the first therapeutic approach and, if oedema persists despite treatment, intravitreal corticosteroid injection has been used in various reports. The injection of anti-Vascular Endothelial Growth Factor (VEGF) drugs and vitrectomy have also been proposed but with conflicting results. The use of topical non-steroidal drugs has been studied and proven to be valuable, although inferior to diuretic treatment in terms of visual recovery. The use of intravitreal corticosteroids is also not without possible further complications such as ocular hypertension and early onset of cataracts.

Despite some improvement in retinal oedema by taking the above-mentioned diuretics, relapses can be observed at the end of therapy, reason for taking longer periods (>12 weeks) of therapy. However, the same chronic continuation of diuretic therapy is not always desirable considering its possible adverse events such as tingling sensation, malaise, altered taste sensation and gastrointestinal disorders.

RATIONALE:

The application of the micropulsed subthreshold retinal laser to reduce retinal oedema in various diseases (diabetic oedema, central serous chorioretinopathy, age-related macular degeneration and retinal vein occlusion) has recently gained wide acceptance.

Retinal threshold refers to the tendency of the laser to cause tissue bleaching resulting in retinal cell death, the term sub-threshold implies that the laser uses such a small amount of energy that it does not cause irreversible damage to retinal structures. The term 'micropulsed' derives from the fact that the laser does not use a continuous wave but has a sub-100% duty cycle and the use of 'off' times is what distinguishes this type of laser from conventional lasers and allows the tissue to cool down, preventing laser-induced retinal damage.

The main characteristics of this type of laser are therefore that it does not cause visible retinal damage and that it has therapeutic effects.

One theory of how this type of laser works is through the action of the molecular protective mechanisms of the Heat Shock Protein (Hsp) family in the retina, including protein chaperone activity, stabilisation of the cytoskeleton and prevention of apoptosis mainly through inhibition of cytochrome C release through the phenomenon of 'resetting'. Another theory hypothesized the activation of leucocyte recruitment or remodeling of the extracellular matrix in the choroid and retina. Possible mechanisms of increased trophic factors (CNTF and FGF-2)14 and up-regulation of other factors (MMP-2, MMP-3, TNFα and Nos2) are covered.

TRIAL DESIGN:

Prospective, interventional, single-centre, open-label study involving consecutive enrolment (see sample size in section "Statistics") of patients with macular oedema in retinal dystrophies.

Each patient referred to the Outpatient Clinical and Research Center of Neuro-ophthalmology and Genetic and Rare Diseases with IRD and macular oedema treated for 3 months with diuretics and draining food supplements and without improvement of macular oedema or increase of the same (reduction of post-therapy CRT ≤20% compared to pre-therapy CRT) will be duly informed about the therapeutic option of this study protocol. After verification of the criteria for inclusion in the study and after signing of the informed consent, the patient will be considered eligible for treatment with micropulsed laser by the physicians of the Clinical and Research Center of Neuro-ophthalmology and Genetic and Rare Diseases and Medical Retina. The patient enrolled in the study will be clinically analysed with the instrumentation indicated below at regular intervals (screening/baseline, follow-up 1 [FU1] (1 month), FU2 (3 months), FU3 (6 months), FU4 (9 months), FU5 (12 months), FU6 (18 months) and FU7 (24 months).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Masking Description:

no masking

Primary Purpose:

Treatment

Official Title:

Treatment of Macular Oedema in Patients With Hereditary Retinal Dystrophies by Applying the Micropulsed Subthreshold Laser

Anticipated Study Start Date :

Jul 25, 2023

Anticipated Primary Completion Date :

Jul 30, 2025

Anticipated Study Completion Date :

Jul 30, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: inherited retinal dystrophies with macular oedema Laser treatment will be performed in patients with macular edema in IRD (experimental arm) who: underwent treatment with diuretics or nutritional drainage products for 3 months and subsequent 'wash-out' of one month 17,18 and had no reduction in macular oedema, in terms of central retinal thickness, of at least 20% compared with the initial assessment they have had an intravitreal injection of anti-VEGF or steroids, and after 3 months there is no reduction in central retinal thickness (CRT) of at least 20% compared to the initial assessment have after 3 months a thickness reduction <10% compared to baseline assessment, following initial treatment with micropulsed laser, and may be candidates for repeating treatment; are not eligible for diuretic therapy due to the presence of comorbidities.	Device: subthreshold treatment with micropulsed laser The laser instrument used is the Q 577® Laser System, Iridex, wavelength 577 yellow. The standard pattern used is: Power: 5% Duty Cycle Power 250 mw Pulse duration 200 ms Spot size 100 micron Pattern spacing 0.0 confluente, griglie 7x7

Arm

Intervention/Treatment

Experimental: inherited retinal dystrophies with macular oedema

Laser treatment will be performed in patients with macular edema in IRD (experimental arm) who: underwent treatment with diuretics or nutritional drainage products for 3 months and subsequent 'wash-out' of one month 17,18 and had no reduction in macular oedema, in terms of central retinal thickness, of at least 20% compared with the initial assessment they have had an intravitreal injection of anti-VEGF or steroids, and after 3 months there is no reduction in central retinal thickness (CRT) of at least 20% compared to the initial assessment have after 3 months a thickness reduction <10% compared to baseline assessment, following initial treatment with micropulsed laser, and may be candidates for repeating treatment; are not eligible for diuretic therapy due to the presence of comorbidities.

Device: subthreshold treatment with micropulsed laser

The laser instrument used is the Q 577® Laser System, Iridex, wavelength 577 yellow. The standard pattern used is: Power: 5% Duty Cycle Power 250 mw Pulse duration 200 ms Spot size 100 micron Pattern spacing 0.0 confluente, griglie 7x7

Outcome Measures

Primary Outcome Measures

assessment of significative change in retinal oedema compared to baseline [up to 24 months]
assessment of central retinal thickness by macular SD-OCT

Secondary Outcome Measures

To study changes in visual acuity between before and after treatment [up to 24 months]
LogMAr visual acuity values
To study the retinal function in the macular area before and after treatment. [up to 24 months]
response amplitude density, measured in nV/dg2 and analysed using multifocal electroretinogram, assessing the amplitude in 5 concentric rings centred on the fovea.
To study the retinal perfusion of the macular area by OCT-angiography before and after treatment. [up to 24 months]
vascular density (expressed as Retinal Vessel Density) before and after treatment, using OCT-angiography

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with inherited retinal disease
Age between 18 and 80 years
Conclusive molecular genetic study for IRD
Male or female patient
Presence of macular oedema assessed by sd-OCT with reduction ≤ 20% after 3 months of diuretics or draining supplements or 4 months after last anti-VEGF or steroid injection
Phakic and pseudophakic patients
Central Retinal thickness > 320 microns in men and > 305 microns in women
Informed consent freely granted and acquired before the start of the study
Participant has the ability to understand and willingness to follow study instructions and is likely to complete all required visits and procedures.

Exclusion Criteria:

Patients with cataract extraction prior to 6 months
Patients with IOP ≥ 20 mmHg
Patients with a clinical diagnosis of retinal dystrophy of unproven genetic origin
Patients with diabetes
Patients with central serous chorioretinosis, retinal vein occlusion, age-related degeneration
Patients with current or previous vitreo-retinal pathology or with indication for vitreo-retinal surgical therapy (tractional oedema)
Patients with a lack of target fixation at 32 cm
Pregnant women