Retinitis PigmentosaSL-MPLNCT04234438
Management of Cystoid Macular Edema Secondary to Retinitis Pigmentosa Via Subliminal Micropulse Yellow Laser
A study testing SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France) in people with Retinitis Pigmentosa and Cystoid Macular Edema, run by Ankara Universitesi Teknokent at 2 sites in Turkey (Türkiye).
Trial summary
Purpose: To investigate the effects of subliminal micropulse yellow laser application on central macular thickness and best corrected visual acuity in cystoid macular edema secondary to retinitis pigmentosa patients. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Retinitis Pigmentosa, Cystoid Macular Edema
- What is being tested?
- SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesTurkey (Türkiye)
- Study dates
- 1 Jan 2018to 30 Dec 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of any phenotypic variation of RP
- Presence of separeted intraretinal cysts
- Central macular thickness ≥ 500 µm
- Unresponsive to systemic or topical carbonic anhydrase inhibitors
- No interventional treatment for macular edema in the last 3 months
Who cannot join
- Patients with signs of inflammation, such as cells in the vitreous, intraretinal white dots, septa-free edema
- Patients responding to systemic or topical carbonic anhydrase inhibitors
- Any interventional treatment has been applied for macular edema in the last 3 months
- The presence of other causes that may lead to CME such as epiretinal membrane, vitreous traction, diabetes or uveitis.
Trial locations and contacts
2 sites in 1 country.
Turkey (Türkiye)2 sites
Ankara University Biotechnology Institute
Ankara, Türkiye, 06312
Umut Arslan
Ankara, Türkiye, 06312
About this study
Purpose: To investigate the effects of subliminal micropulse yellow laser application on central macular thickness and best corrected visual acuity in cystoid macular edema secondary to retinitis pigmentosa patients.
Read the detailed description
Retinitis pigmentosa (RP) is a progressive photoreceptor and retinal pigment epithelial (RPE) degeneration that begins as a night vision loss, resulting in narrowing of the visual field and legal blindness. RP is a heterogeneous genetic disorder, affecting 1/3000- 8000 people worldwide. RP is the result of mutation in one of more than 260 genes. These genes are responsible for the synthesis of peptides involved in the visual cycle. These genes are also responsible for the synthesis of growth factors responsible for the conversion of glucose to adenosine triphosphate (ATP) or responsible for the removal of metabolic wastes.
The incidence of cystoid macular edema (CME) in RP has been reported as between 10% - 50%. There are several hypotheses about the pathogenesis of cystoid macular edema in RP. The first hypothesis is explained by Müller cell hypertrophy and its paracrine effects. Mutations in the retinal pigment epithelium disrupt the synthesis of some growth factors. Stress caused by apoptosis in rod cells in the periphery leads to ectopic synaptogenesis of Müller cells in the central. Müller cells undergo copensatory hypertrophy and synthesize excessive growth factors. This paracrine effect provides protection of central vision. Edema in a certain level is considered to be protective to photoreceptors and should not be treated. But if edema is excessive and prolonged leads to a break in synaptic connections in the neural retina and an increase in neurodegeneration. CME also deteriorates central visual quality in patients with impaired peripheral vision. Treatment should be considered only if the edema is excessive and disrupts central vision. According to our clinical experience, when central macular thickness exceeds 500 microns, central visual quality of the patient decreases and requires treatment.
Other pathophysiological causes of CME in RP are explained by low grade inflammation and retinal autoantibodies. In some genetic mutation types of RP, such as the X-linked RPGR gene mutation; vitritis, lipofuscin deposits and inflammation are predominant. Ciliopathy leads to inflammation and CME, which increases photoreceptor loss rate. Immediate treatment of inflammation-induced edema can slow disease progression. Inflammatory edema appears as cystoid macular edema, whereas compensatory edema due to Müller cell hypertrophy is seen as separeted intraretinal cysts. Inflammatory edema responds well to carbonic anhydrase inhibitors, while compensatory edema does not.
The results of the treatment of CME in RP are controversial, as the compensatory or inflammatory distinction is not made clearly. Treatments such as grid laser photocoagulation, oral acetazolamide, topical carbonic anhydrase inhibitors, intravitreal therapy with corticosteroids or anti-vascular endothelial growth factor agents and pars plana vitrectomy may be effective in some cases with CME secondary to RP. Most of these treatments have either insufficient response or excessive side effects.
To our knowledge, so far, we have not found a scientific publication about the use of micropulse yellow laser for treatment cystoid macular edema secondary to retinitis pigmentosa.
Subliminal micropulse laser (SL-MPL) is a method developed to reduce the laser-induced thermal damage caused by conventional laser therapy for treatment some macular diseases. In the micropulse mode, laser is applied in short pulses, thereby reducing the thermal energy generated in the target area. The coagulation scars do not form with SL-MPL treatment. Sublethally injured RPE cells induce an up- and down regulation of various growth factors (GFs) [pigment epithelium-derived factor (PEDF), vascular endothelial growth factor (VEGF) inhibitors, VEGF inducers, permeability factors, etc.] which restores the pathologic imbalance.
The aim of this study was to investigate the effect of yellow (577 nm) SL-MPL therapy on central macular thickness (CMT) and on best corrected visual acuity (BCVA) in patients with cystoid macular edema secondary to retinitis pigmentosa.
- Conditions
- Retinitis Pigmentosa, Cystoid Macular Edema
- Being tested
- SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France)
- Keywords
- Retinitis pigmentosa, Cystoid macular edema, Intraretinal cysts, Subliminal micropulse laser
- Medical subject headings
- Retinitis Pigmentosa, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France)Device
Macular laser treatment was applied after pupil dilation and topical anesthesia. Laser application was performed with a Mainster Standard contact laser lens (Volk Optical, Mentor, OH, USA). To determine the appropriate personalized calibration value, single-spot test shot was applied under the green filter to a non-edematous area of the macula outside the temporal vascular arcade. The laser power was gradually increased until it formed a barely visible laser spot. The power of the micropulse pattern laser was set at 50% of the power needed to form a barely visible laser spot. Laser parameters used were 200 ms duration, 160 µm spot diameter, low operating cycle (5%), and zero spacing with 5x5 pattern shape. SL-MPL was applied to the areas where edema was detected in OCT and examination.
| Study group | Role | What they receive |
|---|---|---|
| Before application | Active comparator | 32 eyes of 29 patients who had cystoid macular edema secondary to retinitis pigmentosa Before subliminal micropulse laser application Receives: Device: SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France) |
| After application | Active comparator | 32 eyes of 29 patients who had cystoid macular edema secondary to retinitis pigmentosa After 12 months subliminal micropulse laser application Receives: Device: SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central macular thickness
It is obtained by measuring the distance between the internal limiting membrane and the bruch membrane in the center of fovea by OCT.
Measured: Change from baseline central macular thickness at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2020
- Study start1 Jan 2018
- Primary completion30 Oct 2019
- Study completion30 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Retinitis PigmentosaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Prospective open-label clinical trial, included 32 eyes of 29 patients who had cystoid macular edema secondary to retinitis pigmentosa. Patients were treated by subliminal micropulse yellow laser for one session. Central macular thickness and best corrected visual acuity changes were investigated just before the treatment and 1 year later after the one session of the treatment.
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ankara Universitesi Teknokent
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Umut Arslan, Ankara Universitesi Teknokent
- Investigators
- Umut Arslan, MD, Principal investigator, Ankara Universitesi Teknokent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04234438
- Sponsor's protocol ID
- 20-1249-17
- Acronym
- SL-MPL
- Status last verified
- Jan 2020
- First submitted
- 16 Jan 2020
- Last updated
- 23 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bakthavatchalam M, Lai FHP, Rong SS, Ng DS, Brelen ME. Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review. Surv Ophthalmol. 2018 May-Jun;63(3):329-339. doi: 10.1016/j.survophthal.2017.09.009. Epub 2017 Oct 5.
PubMed 28987613Scholz P, Altay L, Fauser S. A Review of Subthreshold Micropulse Laser for Treatment of Macular Disorders. Adv Ther. 2017 Jul;34(7):1528-1555. doi: 10.1007/s12325-017-0559-y. Epub 2017 May 24.
PubMed 28540655Luttrull JK. Improved retinal and visual function following panmacular subthreshold diode micropulse laser for retinitis pigmentosa. Eye (Lond). 2018 Jun;32(6):1099-1110. doi: 10.1038/s41433-018-0017-3. Epub 2018 Feb 16.
PubMed 29449615Arslan U. Management of cystoid macular edema secondary to retinitis pigmentosa via subliminal micropulse yellow laser. Lasers Med Sci. 2021 Mar;36(2):317-323. doi: 10.1007/s10103-020-03031-0. Epub 2020 May 4.
PubMed 32363437
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Management of Cystoid Macular Edema Secondary to Retinitis Pigmentosa Via Subliminal Micropulse Yellow Laser
- ClinicalTrials.gov ID
- NCT04234438
- Acronym / sponsor ID
- SL-MPL / 20-1249-17
- Conditions
- Retinitis Pigmentosa, Cystoid Macular Edema
- Keywords
- Retinitis pigmentosa, Cystoid macular edema, Intraretinal cysts, Subliminal micropulse laser
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Ankara Universitesi TeknokentUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 30 Oct 2019 (actual)
- Study completion
- 30 Dec 2019 (actual)
- First posted
- 21 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Purpose: To investigate the effects of subliminal micropulse yellow laser application on central macular thickness and best corrected visual acuity in cystoid macular edema secondary to retinitis pigmentosa patients.
Detailed description
Retinitis pigmentosa (RP) is a progressive photoreceptor and retinal pigment epithelial (RPE) degeneration that begins as a night vision loss, resulting in narrowing of the visual field and legal blindness. RP is a heterogeneous genetic disorder, affecting 1/3000- 8000 people worldwide. RP is the result of mutation in one of more than 260 genes. These genes are responsible for the synthesis of peptides involved in the visual cycle. These genes are also responsible for the synthesis of growth factors responsible for the conversion of glucose to adenosine triphosphate (ATP) or responsible for the removal of metabolic wastes.
The incidence of cystoid macular edema (CME) in RP has been reported as between 10% - 50%. There are several hypotheses about the pathogenesis of cystoid macular edema in RP. The first hypothesis is explained by Müller cell hypertrophy and its paracrine effects. Mutations in the retinal pigment epithelium disrupt the synthesis of some growth factors. Stress caused by apoptosis in rod cells in the periphery leads to ectopic synaptogenesis of Müller cells in the central. Müller cells undergo copensatory hypertrophy and synthesize excessive growth factors. This paracrine effect provides protection of central vision. Edema in a certain level is considered to be protective to photoreceptors and should not be treated. But if edema is excessive and prolonged leads to a break in synaptic connections in the neural retina and an increase in neurodegeneration. CME also deteriorates central visual quality in patients with impaired peripheral vision. Treatment should be considered only if the edema is excessive and disrupts central vision. According to our clinical experience, when central macular thickness exceeds 500 microns, central visual quality of the patient decreases and requires treatment.
Other pathophysiological causes of CME in RP are explained by low grade inflammation and retinal autoantibodies. In some genetic mutation types of RP, such as the X-linked RPGR gene mutation; vitritis, lipofuscin deposits and inflammation are predominant. Ciliopathy leads to inflammation and CME, which increases photoreceptor loss rate. Immediate treatment of inflammation-induced edema can slow disease progression. Inflammatory edema appears as cystoid macular edema, whereas compensatory edema due to Müller cell hypertrophy is seen as separeted intraretinal cysts. Inflammatory edema responds well to carbonic anhydrase inhibitors, while compensatory edema does not.
The results of the treatment of CME in RP are controversial, as the compensatory or inflammatory distinction is not made clearly. Treatments such as grid laser photocoagulation, oral acetazolamide, topical carbonic anhydrase inhibitors, intravitreal therapy with corticosteroids or anti-vascular endothelial growth factor agents and pars plana vitrectomy may be effective in some cases with CME secondary to RP. Most of these treatments have either insufficient response or excessive side effects.
To our knowledge, so far, we have not found a scientific publication about the use of micropulse yellow laser for treatment cystoid macular edema secondary to retinitis pigmentosa.
Subliminal micropulse laser (SL-MPL) is a method developed to reduce the laser-induced thermal damage caused by conventional laser therapy for treatment some macular diseases. In the micropulse mode, laser is applied in short pulses, thereby reducing the thermal energy generated in the target area. The coagulation scars do not form with SL-MPL treatment. Sublethally injured RPE cells induce an up- and down regulation of various growth factors (GFs) [pigment epithelium-derived factor (PEDF), vascular endothelial growth factor (VEGF) inhibitors, VEGF inducers, permeability factors, etc.] which restores the pathologic imbalance.
The aim of this study was to investigate the effect of yellow (577 nm) SL-MPL therapy on central macular thickness (CMT) and on best corrected visual acuity (BCVA) in patients with cystoid macular edema secondary to retinitis pigmentosa.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective open-label clinical trial, included 32 eyes of 29 patients who had cystoid macular edema secondary to retinitis pigmentosa. Patients were treated by subliminal micropulse yellow laser for one session. Central macular thickness and best corrected visual acuity changes were investigated just before the treatment and 1 year later after the one session of the treatment.
| Arm | Type | Receives |
|---|---|---|
| Before application | Active comparator | Device: SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France)32 eyes of 29 patients who had cystoid macular edema secondary to retinitis pigmentosa Before subliminal micropulse laser application |
| After application | Active comparator | Device: SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France)32 eyes of 29 patients who had cystoid macular edema secondary to retinitis pigmentosa After 12 months subliminal micropulse laser application |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of any phenotypic variation of RP
- Presence of separeted intraretinal cysts
- Central macular thickness ≥ 500 µm
- Unresponsive to systemic or topical carbonic anhydrase inhibitors
- No interventional treatment for macular edema in the last 3 months
Key exclusion criteria (4 listed)
- Patients with signs of inflammation, such as cells in the vitreous, intraretinal white dots, septa-free edema
- Patients responding to systemic or topical carbonic anhydrase inhibitors
- Any interventional treatment has been applied for macular edema in the last 3 months
- The presence of other causes that may lead to CME such as epiretinal membrane, vitreous traction, diabetes or uveitis.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France)Macular laser treatment was applied after pupil dilation and topical anesthesia. Laser application was performed with a Mainster Standard contact laser lens (Volk Optical, Mentor, OH, USA). To determine the appropriate personalized calibration value, single-spot test shot was applied under the green filter to a non-edematous area of the macula outside the temporal vascular arcade. The laser power was gradually increased until it formed a barely visible laser spot. The power of the micropulse pattern laser was set at 50% of the power needed to form a barely visible laser spot. Laser parameters used were 200 ms duration, 160 µm spot diameter, low operating cycle (5%), and zero spacing with 5x5 pattern shape. SL-MPL was applied to the areas where edema was detected in OCT and examination. | Device | After application, Before application |
Primary outcome
Central macular thickness
Time frame: Change from baseline central macular thickness at 12 months
It is obtained by measuring the distance between the internal limiting membrane and the bruch membrane in the center of fovea by OCT.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2020.
- Results publication: PubMed 28987613Bakthavatchalam M, Lai FHP, Rong SS, Ng DS, Brelen ME. Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review. Surv Ophthalmol. 2018 May-Jun;63(3):329-339. doi: 10.1016/j.survophthal.2017.09.009. Epub 2017 Oct 5.
- Results publication: PubMed 28540655Scholz P, Altay L, Fauser S. A Review of Subthreshold Micropulse Laser for Treatment of Macular Disorders. Adv Ther. 2017 Jul;34(7):1528-1555. doi: 10.1007/s12325-017-0559-y. Epub 2017 May 24.
- Results publication: PubMed 29449615Luttrull JK. Improved retinal and visual function following panmacular subthreshold diode micropulse laser for retinitis pigmentosa. Eye (Lond). 2018 Jun;32(6):1099-1110. doi: 10.1038/s41433-018-0017-3. Epub 2018 Feb 16.
- Derived from this study: PubMed 32363437Arslan U. Management of cystoid macular edema secondary to retinitis pigmentosa via subliminal micropulse yellow laser. Lasers Med Sci. 2021 Mar;36(2):317-323. doi: 10.1007/s10103-020-03031-0. Epub 2020 May 4.
- Individual participant dataSharing planned: No
Related trials for Retinitis Pigmentosa
RecruitingObservational study
Rod and Cone Mediated Function in Retinal Disease
Retinal Degeneration, Retinitis Pigmentosa
RecruitingObservational study
Cell Collection to Study Eye Diseases
Retinal Disease, AMD
Recruiting
Brain Stimulation Effects on Orientation and Mobility Skills in Adults With Vision Impairment
Retinitis Pigmentosa (RP), Rod Cone Dystrophy
RecruitingObservational study
Universal Rare Gene Study: A Registry and Natural History Study of Retinal Dystrophies Associated With Rare Disease-Causing Genetic Variants
Inherited Retinal Degeneration, Retinitis Pigmentosa
Active, not recruitingObservational study
Rate of Progression in EYS Related Retinal Degeneration
Retinitis Pigmentosa, Eye Diseases
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Umut Arslan, MD principal investigator
Ankara Universitesi Teknokent
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SL-MPL treatment protocol was performed with a 577 nm yellow laser (EasyRet, Quantel Medical, Cedex, France) in people with Retinitis Pigmentosa and Cystoid Macular Edema, run by Ankara Universitesi Teknokent at 2 sites in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Central macular thickness (time frame: Change from baseline central macular thickness at 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04234438, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2020.