Non Proliferative Diabetic RetinopathyPhase 4NCT00563043
Changes in Electroretinogram and Contrast Sensitivity After PASCAL Treatment
A Phase 4 study testing PASCAL laser treatment in people with Non Proliferative Diabetic Retinopathy and Proliferative Diabetic Retinopathy, run by Asociación para Evitar la Ceguera en México at 1 site in Mexico.
Trial summary
Laser photocoagulation has become the treatment of choice in PDR. Laser photocoagulation has become the treatment of choice in PDR. The aim is to destroy a substantial portion of the peripheral retina in order to reduce the angiogenic stimulus (decrease the difference between oxygen demand and the administration). Read more about this study
- Who is it for?
- Ages 25 to 95 years
- Conditions the study is for
- Non Proliferative Diabetic Retinopathy, Proliferative Diabetic Retinopathy
- What is being tested?
- PASCAL laser treatment
- Type of treatment
- Surgery or procedure
- How many people
- 8 participants
- Where
- 1 siteMexico
- Study dates
- Oct 2007to Feb 2008
- Phase
- Phase 4
- 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 25 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients older than 25 years, with a diagnosis of severe NPDR or PRD.
- Good pupil mydriasis (minimum 5mm) With clear media
- Patients without previous laser treatment or treatment with antiangiogenic drug.
Who cannot join
- Patients who do not accept informed consent.
- Patients with clinical macular Edema before treatment.
- Significant corneal opacity.
- Patients with other eye diseases that interfere with the studies required for the monitoring of patients.
- History of refractive surgery, glaucoma or ocular hypertension, intraocular inflammation, choroiditis multifocal, retinal detachment, optic neuropathy (4).
- Patients with tractional retinal detachment due to abundant fibrovascular
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Asociaciòn para Evitar la Ceguera en Mèxico
Mèxico, Mexico City, 04030
About this study
Official title: Pattern Scan Laser System vs Regular Photocoagulation System: Changes in Electroretinograms and Contrast Sensitivity Post Treatment.
Laser photocoagulation has become the treatment of choice in PDR. Laser photocoagulation has become the treatment of choice in PDR. The aim is to destroy a substantial portion of the peripheral retina in order to reduce the angiogenic stimulus (decrease the difference between oxygen demand and the administration). Their effectiveness is determined by the extent of destruction of the retina (2.4).
Read the detailed description
Introduction:
The concept of retinal photocoagulation was introduced by Meyer-Schwickerath for treatment of diabetic retinopathy in the 50s (1, 6). The first successfully used laser was the arc xenon laser (polychromatic, inefficient, and hard to handle). Then the ruby and argon laser appeared (with mayor improvements in design and management). The modern era of photocoagulation as we know it began in the late 70s.
With these available technologies, the focal photocoagulation, the panretinal photocoagulation and the grid photocoagulation were developed. Witch proved effective for the treatment of severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy in different multicenter studies (ETDRS, DRS) (1.6).
Patients usually receive from 1200 to 1500 laser shots in 2 to 4 sessions lasting from 10 to 20 minutes, during 2 to 4 weeks. The procedure can be time consuming, tedious and painful.
Until now little has changed in the overall design of lasers of 30 years ago. The differences are the introduction of fibre optics and air-based cooling systems. These innovations do not have any impact on the way in which the treatment or the success.
Early efforts to improve photocoagulation included complex recognition systems and eye tracking to try to manage a fully automated process. That required a preview image of the retina. Attempts were also made to determine the appropriate dose of energy for getting the job done. The complexity of these systems prevented their clinical use (1).
The PASCAL is a system of semiautomatic pattern laser, which allows much faster processing, accuracy and control of treatment by a doctor at all times. The difference with the regular laser systems is that PASCAL manages a dual frequency Nd: YAG that works at a wavelength of 532nm, which is capable of firing a single shot from up to 56 shots in pre patterns (1x1, 2 x2, 3x3, 4x4, 5x5). By using time exposures of between 10 and 20 ms, you can make multiple shots at the same time that a shot with conventional laser is done (100 ms). These short pulses allow energy laser focus better in the tissues, produces less pain, Reduce the heat delivered to the choroid, and less diffusion of heat with the subsequent less damage to surrounding tissues (1).
The first study was published in the Retina 2006, by Blumenkanz, Palanker, Marcelino, et al. In which describe their use in rabbit's retinas. In which compared the effect of a number of pulses of different durations and powers. They applied exposition of 10, 20, 50 and 100 ms. The study found that at lower exposure time is required energy of 2 to 3 times more to produce the same effect, but the pulse had less energy. As they increased the exposure time, les power was needed, but the pulsed had also more energy. As the energy increased the shots was less homogeneous, less localized and changes in the final size (110-170micm) (1).
ERG: It reflects the activity of the retina in "mass". In studies of the effect of photocoagulation on the activity of the retina, it have typically been used the amplitude of them a and b wave as criteria of tissue destruction. But there is no consistency among the various studies that have already reported variations of 10 to 95% in the amplitude (especially in wave b) due to the variability in the length of effective ablation of the retina. Others suggest that a wave to be smaller than the b, showing an injury in the primary layer of photoreceptors. Others say that the decline was equal in both waves. But something we all conclude is that the response in the ERG is reduced more than expected based in the coagulated area. But when it is higher, the fall in the ERG is more than what was expected (60% of destruction = 80% decrease of ERG). An average photocoagulation destroys about 40% of the retina approximately (5).
The destruction of the peripheral retina decreases the ERG response, besides laser affect regions of adjacent tissue, causing deterioration in the transmission of signals from the photoreceptors in the proximal retina. What explains the previous reports of large decrease in amplitude on the basis of the area coagulated (2). The laser energy is absorbed by the RPE cells, and the adjacent layer of photoreceptors. What also produces external injury to the retina so you can also observe an increase in the implicit time (3).
A few years ago changing arc xenon to argon marked a difference in the amount of burned retina and decrease in the implicit time and amplitudes of the waves (5).
Macular Edema: Is recognized as a potential adverse effect of panretinal photocoagulation. Witch may transitory or permanent decrease the visual acuity of the patient. Approximately 60% of photocoagulated patients show an increase in the foveal thickness. Despite the fact that it has been said that a change of the self-distribution of blood flow is responsible for this increase in the thickness, today it is believed that these changes are due to post-laser inflammation. Despite that it is performed outside of the vascular arches; it is generally formed by those within.
The inflammation factors, in addition to the direct effect that is exercised on intracellular unions have shown themselves capable of producing a change in the barrier mediated leukocytes. These factors are produced in the peripheral region to the photocoagulated area. The laser stimulates the production of adhesion molecules in the area around the shot and in the non photocoagulated area, which produces bearings and recruitment of leukocytes, secondary accumulation in the posterior pole and subsequent alteration of the hemato-retinal barrier (7).
- Being tested
- PASCAL laser treatment
- Keywords
- Pattern Scan Laser., Photocoagulation., Diabetic retinopathy treatment., Laser treatment., Electroretinogram., a wave., b wave., Implicit time.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PASCAL laser treatmentProcedure or surgery
Patterns Scan Laser treatment in patients with PDR.
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in a wave amplitude
Measured: 12 weeks
changes in b wave amplitude
Measured: 12 weeks
changes in ERG implicit time
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2007 (estimated)
- Study startOct 2007
- Primary completionOct 2007
- Study completionFeb 2008
Why it stopped: Undefined
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Non Proliferative Diabetic RetinopathyStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Asociación para Evitar la Ceguera en México
- Sponsor type
- University, hospital or other
- Investigators
- Raul Velez-Montoya, MD, Principal investigator, Asociaciòn para Evitar la Ceguera en MèxicoHugo Quiroz-Mercado, MD, Principal investigator, Asociaciòn para Evitar la Ceguera en MèxicoVirgilio Morales-Canton, MD, Principal investigator, Asociaciòn para Evitar la Ceguera en MèxicoJuan Manuel Jimenez-Sierra, MD, Principal investigator, Asociaciòn para Evitar la Ceguera en Mèxico
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00563043
- Sponsor's protocol ID
- PASCAL002
- Status last verified
- May 2024
- First submitted
- 22 Nov 2007
- Last updated
- 30 May 2024
- Results posted
- No
- Data monitoring committee
- No
Publications
Blumenkranz MS, Yellachich D, Andersen DE, Wiltberger MW, Mordaunt D, Marcellino GR, Palanker D. Semiautomated patterned scanning laser for retinal photocoagulation. Retina. 2006 Mar;26(3):370-6. doi: 10.1097/00006982-200603000-00024. No abstract available.
PubMed 16508446Perlman I, Gdal-On M, Miller B, Zonis S. Retinal function of the diabetic retina after argon laser photocoagulation assessed electroretinographically. Br J Ophthalmol. 1985 Apr;69(4):240-6. doi: 10.1136/bjo.69.4.240.
PubMed 4039601Greenstein VC, Chen H, Hood DC, Holopigian K, Seiple W, Carr RE. Retinal function in diabetic macular edema after focal laser photocoagulation. Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3655-64.
PubMed 11006264Varano M, Parisi V, Tedeschi M, Sciamanna M, Gallinaro G, Capaldo N, Catalano S, Pascarella A. Macular function after PDT in myopic maculopathy: psychophysical and electrophysiological evaluation. Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1453-62. doi: 10.1167/iovs.04-0903.
PubMed 15790915Liang JC, Fishman GA, Huamonte FU, Anderson RJ. Comparative electroretinograms in argon laser and xenon arc panretinal photocoagulation. Br J Ophthalmol. 1983 Aug;67(8):520-5. doi: 10.1136/bjo.67.8.520.
PubMed 6683566Rema M, Sujatha P, Pradeepa R. Visual outcomes of pan-retinal photocoagulation in diabetic retinopathy at one-year follow-up and associated risk factors. Indian J Ophthalmol. 2005 Jun;53(2):93-9. doi: 10.4103/0301-4738.16171.
PubMed 15976463Nonaka A, Kiryu J, Tsujikawa A, Yamashiro K, Nishijima K, Kamizuru H, Ieki Y, Miyamoto K, Nishiwaki H, Honda Y, Ogura Y. Inflammatory response after scatter laser photocoagulation in nonphotocoagulated retina. Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1204-9.
PubMed 11923267
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pattern Scan Laser System vs Regular Photocoagulation System: Changes in Electroretinograms and Contrast Sensitivity Post Treatment.
- ClinicalTrials.gov ID
- NCT00563043
- Acronym / sponsor ID
- PASCAL002
- Keywords
- Pattern Scan Laser., Photocoagulation., Diabetic retinopathy treatment., Laser treatment., Electroretinogram., a wave., b wave., Implicit time.
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Undefined
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Asociación para Evitar la Ceguera en MéxicoUniversity, hospital or other
- Study start
- Oct 2007 (actual)
- Primary completion
- Oct 2007 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 26 Nov 2007 (estimated)
- 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.
Laser photocoagulation has become the treatment of choice in PDR. Laser photocoagulation has become the treatment of choice in PDR. The aim is to destroy a substantial portion of the peripheral retina in order to reduce the angiogenic stimulus (decrease the difference between oxygen demand and the administration). Their effectiveness is determined by the extent of destruction of the retina (2.4).
Detailed description
Introduction:
The concept of retinal photocoagulation was introduced by Meyer-Schwickerath for treatment of diabetic retinopathy in the 50s (1, 6). The first successfully used laser was the arc xenon laser (polychromatic, inefficient, and hard to handle). Then the ruby and argon laser appeared (with mayor improvements in design and management). The modern era of photocoagulation as we know it began in the late 70s.
With these available technologies, the focal photocoagulation, the panretinal photocoagulation and the grid photocoagulation were developed. Witch proved effective for the treatment of severe non-proliferative diabetic retinopathy, proliferative diabetic retinopathy in different multicenter studies (ETDRS, DRS) (1.6).
Patients usually receive from 1200 to 1500 laser shots in 2 to 4 sessions lasting from 10 to 20 minutes, during 2 to 4 weeks. The procedure can be time consuming, tedious and painful.
Until now little has changed in the overall design of lasers of 30 years ago. The differences are the introduction of fibre optics and air-based cooling systems. These innovations do not have any impact on the way in which the treatment or the success.
Early efforts to improve photocoagulation included complex recognition systems and eye tracking to try to manage a fully automated process. That required a preview image of the retina. Attempts were also made to determine the appropriate dose of energy for getting the job done. The complexity of these systems prevented their clinical use (1).
The PASCAL is a system of semiautomatic pattern laser, which allows much faster processing, accuracy and control of treatment by a doctor at all times. The difference with the regular laser systems is that PASCAL manages a dual frequency Nd: YAG that works at a wavelength of 532nm, which is capable of firing a single shot from up to 56 shots in pre patterns (1x1, 2 x2, 3x3, 4x4, 5x5). By using time exposures of between 10 and 20 ms, you can make multiple shots at the same time that a shot with conventional laser is done (100 ms). These short pulses allow energy laser focus better in the tissues, produces less pain, Reduce the heat delivered to the choroid, and less diffusion of heat with the subsequent less damage to surrounding tissues (1).
The first study was published in the Retina 2006, by Blumenkanz, Palanker, Marcelino, et al. In which describe their use in rabbit's retinas. In which compared the effect of a number of pulses of different durations and powers. They applied exposition of 10, 20, 50 and 100 ms. The study found that at lower exposure time is required energy of 2 to 3 times more to produce the same effect, but the pulse had less energy. As they increased the exposure time, les power was needed, but the pulsed had also more energy. As the energy increased the shots was less homogeneous, less localized and changes in the final size (110-170micm) (1).
ERG: It reflects the activity of the retina in "mass". In studies of the effect of photocoagulation on the activity of the retina, it have typically been used the amplitude of them a and b wave as criteria of tissue destruction. But there is no consistency among the various studies that have already reported variations of 10 to 95% in the amplitude (especially in wave b) due to the variability in the length of effective ablation of the retina. Others suggest that a wave to be smaller than the b, showing an injury in the primary layer of photoreceptors. Others say that the decline was equal in both waves. But something we all conclude is that the response in the ERG is reduced more than expected based in the coagulated area. But when it is higher, the fall in the ERG is more than what was expected (60% of destruction = 80% decrease of ERG). An average photocoagulation destroys about 40% of the retina approximately (5).
The destruction of the peripheral retina decreases the ERG response, besides laser affect regions of adjacent tissue, causing deterioration in the transmission of signals from the photoreceptors in the proximal retina. What explains the previous reports of large decrease in amplitude on the basis of the area coagulated (2). The laser energy is absorbed by the RPE cells, and the adjacent layer of photoreceptors. What also produces external injury to the retina so you can also observe an increase in the implicit time (3).
A few years ago changing arc xenon to argon marked a difference in the amount of burned retina and decrease in the implicit time and amplitudes of the waves (5).
Macular Edema: Is recognized as a potential adverse effect of panretinal photocoagulation. Witch may transitory or permanent decrease the visual acuity of the patient. Approximately 60% of photocoagulated patients show an increase in the foveal thickness. Despite the fact that it has been said that a change of the self-distribution of blood flow is responsible for this increase in the thickness, today it is believed that these changes are due to post-laser inflammation. Despite that it is performed outside of the vascular arches; it is generally formed by those within.
The inflammation factors, in addition to the direct effect that is exercised on intracellular unions have shown themselves capable of producing a change in the barrier mediated leukocytes. These factors are produced in the peripheral region to the photocoagulated area. The laser stimulates the production of adhesion molecules in the area around the shot and in the non photocoagulated area, which produces bearings and recruitment of leukocytes, secondary accumulation in the posterior pole and subsequent alteration of the hemato-retinal barrier (7).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 25 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Patients older than 25 years, with a diagnosis of severe NPDR or PRD.
- Good pupil mydriasis (minimum 5mm) With clear media
- Patients without previous laser treatment or treatment with antiangiogenic drug.
Key exclusion criteria (6 listed)
- Patients who do not accept informed consent.
- Patients with clinical macular Edema before treatment.
- Significant corneal opacity.
- Patients with other eye diseases that interfere with the studies required for the monitoring of patients.
- History of refractive surgery, glaucoma or ocular hypertension, intraocular inflammation, choroiditis multifocal, retinal detachment, optic neuropathy (4).
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 |
|---|---|---|
| PASCAL laser treatmentPatterns Scan Laser treatment in patients with PDR. | Procedure or surgery | – |
Primary outcome
Changes in a wave amplitude
Time frame: 12 weeks
changes in b wave amplitude
Time frame: 12 weeks
changes in ERG implicit time
Time frame: 12 weeks
Results and safety
The study was stopped early (reason given: Undefined). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2024.
- Background: PubMed 16508446Blumenkranz MS, Yellachich D, Andersen DE, Wiltberger MW, Mordaunt D, Marcellino GR, Palanker D. Semiautomated patterned scanning laser for retinal photocoagulation. Retina. 2006 Mar;26(3):370-6. doi: 10.1097/00006982-200603000-00024. No abstract available.
- Background: PubMed 4039601Perlman I, Gdal-On M, Miller B, Zonis S. Retinal function of the diabetic retina after argon laser photocoagulation assessed electroretinographically. Br J Ophthalmol. 1985 Apr;69(4):240-6. doi: 10.1136/bjo.69.4.240.
- Background: PubMed 11006264Greenstein VC, Chen H, Hood DC, Holopigian K, Seiple W, Carr RE. Retinal function in diabetic macular edema after focal laser photocoagulation. Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3655-64.
- Background: PubMed 15790915Varano M, Parisi V, Tedeschi M, Sciamanna M, Gallinaro G, Capaldo N, Catalano S, Pascarella A. Macular function after PDT in myopic maculopathy: psychophysical and electrophysiological evaluation. Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1453-62. doi: 10.1167/iovs.04-0903.
- Background: PubMed 6683566Liang JC, Fishman GA, Huamonte FU, Anderson RJ. Comparative electroretinograms in argon laser and xenon arc panretinal photocoagulation. Br J Ophthalmol. 1983 Aug;67(8):520-5. doi: 10.1136/bjo.67.8.520.
- Background: PubMed 15976463Rema M, Sujatha P, Pradeepa R. Visual outcomes of pan-retinal photocoagulation in diabetic retinopathy at one-year follow-up and associated risk factors. Indian J Ophthalmol. 2005 Jun;53(2):93-9. doi: 10.4103/0301-4738.16171.
- Background: PubMed 11923267Nonaka A, Kiryu J, Tsujikawa A, Yamashiro K, Nishijima K, Kamizuru H, Ieki Y, Miyamoto K, Nishiwaki H, Honda Y, Ogura Y. Inflammatory response after scatter laser photocoagulation in nonphotocoagulated retina. Invest Ophthalmol Vis Sci. 2002 Apr;43(4):1204-9.
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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.
Raul Velez-Montoya, MD principal investigator
Asociaciòn para Evitar la Ceguera en Mèxico
Hugo Quiroz-Mercado, MD principal investigator
Asociaciòn para Evitar la Ceguera en Mèxico
Virgilio Morales-Canton, MD principal investigator
Asociaciòn para Evitar la Ceguera en Mèxico
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PASCAL laser treatment in people with Non Proliferative Diabetic Retinopathy and Proliferative Diabetic Retinopathy, run by Asociación para Evitar la Ceguera en México at 1 site in Mexico.
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 3 inclusion and 6 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: stopped early, as of the sponsor's last update on 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Undefined). Results are not available in the source record.
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?
Changes in a wave amplitude (time frame: 12 weeks). The study lists 3 primary outcomes in all. 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 NCT00563043, which also lists 7 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 30 May 2024.