Ignite Creation Date:
2024-05-05 @ 5:23 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00442156
Status:
COMPLETED
Last Update Posted:
2016-08-26
First Post:
2007-02-27
Brief Title:
The Course of Response to Focal Photocoagulation for DME
Sponsor:
Jaeb Center for Health Research
Organization:
Jaeb Center for Health Research
Study Overview
Official Title:
The Course of Response to Focal Photocoagulation for Diabetic Macular Edema
Status:
COMPLETED
Status Verified Date:
2016-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Laser Resp
Brief Summary:
The study objective is to determine the course of changes in OCT measured macular thickness and visual acuity following a single session of focal photocoagulation for center-involved DME The response will be evaluated separately in eyes with and without prior focal photocoagulation for DME The purpose is to determine the proportion of eyes that continue to improve at least 5 letters in visual acuity or at least 10 in central retinal thickness after a session of focal photocoagulation In addition the study will explore whether any baseline factors can be identified that are predictive of the response
All subjects will have follow-up visits 8 weeks and 16 weeks post treatment At the 16-week visit study eyes are evaluated for change in retinal thickness and visual acuity from baseline
Treatment is to be deferred and follow up continued if visual acuity letter score has improved by 5 or OCT central subfield thickness has decreased by 10 compared with baseline
If visual acuity letter score has not improved by at least 5 and OCT central subfield thickness has not decreased by at least 10 then the eye is classified as not improved and the investigator may provide additional treatment Follow up ends for eyes that receive additional treatment at this visit However if the investigator and participant elect to defer additional treatment even if deferral criteria are not met then follow up will continue until the study eye receives additional treatment for DME
Eyes continuing in follow up have visits every 8 weeks 1week as long as there has been continued improvement in visual acuity letter score improved 5 or retinal thickness central subfield thickness decreased by 10 compared with the visit 16 weeks earlier The longest follow-up time will be 48 weeks
By providing information on the length of time during which clinically meaningful improvement occurs following focal photocoagulation clinicians will be better able to determine when further photocoagulation or other treatments should be considered for persistent DME Depending on the results of this study a future randomized clinical trial will be considered comparing the more aggressive retreatment photocoagulation regimen currently serving as the standard DRCR Network approach to focal photocoagulation for macular edema with the less aggressive regimen evaluated in this protocol
All subjects will have follow-up visits 8 weeks and 16 weeks post treatment At the 16-week visit study eyes are evaluated for change in retinal thickness and visual acuity from baseline
Treatment is to be deferred and follow up continued if visual acuity letter score has improved by 5 or OCT central subfield thickness has decreased by 10 compared with baseline
If visual acuity letter score has not improved by at least 5 and OCT central subfield thickness has not decreased by at least 10 then the eye is classified as not improved and the investigator may provide additional treatment Follow up ends for eyes that receive additional treatment at this visit However if the investigator and participant elect to defer additional treatment even if deferral criteria are not met then follow up will continue until the study eye receives additional treatment for DME
Eyes continuing in follow up have visits every 8 weeks 1week as long as there has been continued improvement in visual acuity letter score improved 5 or retinal thickness central subfield thickness decreased by 10 compared with the visit 16 weeks earlier The longest follow-up time will be 48 weeks
By providing information on the length of time during which clinically meaningful improvement occurs following focal photocoagulation clinicians will be better able to determine when further photocoagulation or other treatments should be considered for persistent DME Depending on the results of this study a future randomized clinical trial will be considered comparing the more aggressive retreatment photocoagulation regimen currently serving as the standard DRCR Network approach to focal photocoagulation for macular edema with the less aggressive regimen evaluated in this protocol
Detailed Description:
Focal photocoagulation is the only treatment that has been demonstrated to be beneficial for diabetic macular edema In the ETDRS focal photocoagulation of eyes with macular edema reduced the risk of moderate visual loss decrease of 15 or more letters by approximately 50 from 24 to 12 three years after initiation of treatment For eyes with center-involved DME and visual acuity worse than 2040 that were treated with focal photocoagulation the 15-letter improvement rate at 1 year was 11 and at 3 years was 16
In the ETDRS focal photocoagulation treatment for diabetic macular edema involved direct treatment to discrete lesions between 500 microns and 3000 microns from the center of the macula that were thought to be causing retinal thickening or hard exudates with or without grid treatment to other macular areas of retinal thickening or non-perfusion The lesions treated directly included microaneurysms identified on fluorescein angiography that either filled or leaked intraretinal microvascular abnormalities IRMA or pruned capillaries that leaked fluorescein Grid treatment was applied in the ETDRS to areas of thickened retina that showed diffuse fluorescein leakage or areas of non-perfusion identified as capillary dropout on fluorescein angiography Areas of non-perfusion in the macula could be treated with grid at the discretion of the treating ophthalmologist Areas that had both discrete lesions and diffuse leakage or capillary dropout would receive a combination of direct and grid treatment Re-treatment was applied at four month intervals if clinically significant macular edema persisted one or more treatable lesions were identified and the investigator believed these lesions were responsible for the edema The median number of focal laser treatments applied in the ETDRS was 38
The mechanism of action of focal photocoagulation is not fully understood however it is clear that the retinal pigment epithelium RPE absorbs the majority of the laser energy and thermal injury occurs at the level of the RPE Studies have shown that photocoagulation can eventually result in retinal and apparent RPE atrophy 200-300 larger than the original laser spot size These areas of expanded atrophy can lead to loss of central vision central scotomata and decreased color vision Consequently many retinal specialists today tend to treat with lighter less intense laser burns than originally specified in the ETDRS
In addition to the concern regarding the spread of intense laser burns there are a number of other reasons that retinal specialists today have modified the treatment procedures originally specified in the ETDRS protocol These reasons include the advent of new lasers and the clinical observation that different techniques such as focal photocoagulation with lighter burns or grid treatment alone may be similar in beneficial effect as the original ETDRS treatment protocol A modified ETDRS focal photocoagulation protocol adapted from the original ETDRS approach has been adopted as the standard laser technique for DME used in DRCRnet studies
There are limited data on the course of visual acuity and central retinal thickness after a single focal photocoagulation session for DME In prior DRCRnet DME treatment protocols that included a laser arm according to the re-treatment protocol eyes received a second focal photocoagulation session at 35- 4 months which was the first follow-up visit unless there was substantial improvement defined as at least a 50 decrease in retinal thickening of the central subfield measurement on OCT As a result it is unknown what proportion of eyes with lesser degrees of improvement would have continued to improve and the time course for further improvement following the initial photocoagulation session given additional time In one study conducted by DRCRnet of eyes that had not been previously treated for DME among 113 eyes in the modified ETDRS laser treatment group with baseline OCT central subfield 250 microns a 50 or more reduction in OCT central subfield thickening was present at 35 months in only 28 25 The table below categorizes the 85 eyes that did not meet this measure of improvement at 35 months with regard to improvement in visual acuity of at least 5 letters andor reduction in central subfield thickness of at least 10 The 5 letter reduction was selected based on the 95 confidence interval for change determined in a study that evaluated the validity and reliability of the electronic ETDRS visual acuity testing procedure that is used in DRCRnet protocols The 10 threshold was selected based on the DRCRnet OCT reproducibility study which found that a 10 change in central subfield thickness was likely to be real Forty-seven 42 eyes that met the protocol requirement for repeat photocoagulation at the first follow-up visit had an improvement in either visual acuity of at least 5 letters central subfield of at least a 10 reduction or both at this follow-up visit
Other DRCRnet protocols provide data on the course following a single photocoagulation session through 4 months of follow up In a pilot study designed to evaluate peribulbar corticosteroids for mild DME OCT central subfield thickness 250 microns and visual acuity 2040 or better at baseline modified ETDRS focal photocoagulation was the treatment given to the control group Follow-up visits occurred after 1 2 and 4 months before the eye was eligible to be retreated Twenty-one of the 37 eyes in the laser group had not been previously treated with focal photocoagulation for DME and 17 eyes had been previously treated with focal photocoagulation A 50 or more reduction in OCT central subfield thickening occurred in 11 30 of the 37 eyes at 17 weeks Fourteen 38 eyes that would have met the criteria for re-treatment had an improvement in either visual acuity of at least 5 letters central subfield of at least 10 or both at 17 weeks
In another pilot study evaluating intravitreal bevacizumab for DME OCT central subfield thickness 275 microns and visual acuity 2032 or worse at baseline modified ETDRS focal photocoagulation was the treatment given to the control group Follow-up visits occurred after 3 6 9 and 12 weeks before the eye was eligible to be retreated There were 7 eyes in the laser group that had not been previously treated with focal photocoagulation for DME and 12 eyes that had been previously treated with focal photocoagulation Among these 19 eyes a 50 or more reduction in OCT central subfield thickening occurred in 3 16 at 12 weeks Ten 53 eyes that would have met criteria for re-treatment had an improvement in either visual acuity of at least 5 letters central subfield of at least 10 or both at 12 weeks
The data from these three protocols indicate that a substantial number of eyes receiving focal photocoagulation either an initial course or repeat application will show improvement in central retinal thickness after 3-4 months that is at least 10 but is less than 50 of the baseline thickening It is for these eyes that further knowledge of the course of retinal thickening and visual acuity without additional interventions is needed to assess whether the present requirements for re-treatment are more aggressive than they need to be
In the ETDRS focal photocoagulation treatment for diabetic macular edema involved direct treatment to discrete lesions between 500 microns and 3000 microns from the center of the macula that were thought to be causing retinal thickening or hard exudates with or without grid treatment to other macular areas of retinal thickening or non-perfusion The lesions treated directly included microaneurysms identified on fluorescein angiography that either filled or leaked intraretinal microvascular abnormalities IRMA or pruned capillaries that leaked fluorescein Grid treatment was applied in the ETDRS to areas of thickened retina that showed diffuse fluorescein leakage or areas of non-perfusion identified as capillary dropout on fluorescein angiography Areas of non-perfusion in the macula could be treated with grid at the discretion of the treating ophthalmologist Areas that had both discrete lesions and diffuse leakage or capillary dropout would receive a combination of direct and grid treatment Re-treatment was applied at four month intervals if clinically significant macular edema persisted one or more treatable lesions were identified and the investigator believed these lesions were responsible for the edema The median number of focal laser treatments applied in the ETDRS was 38
The mechanism of action of focal photocoagulation is not fully understood however it is clear that the retinal pigment epithelium RPE absorbs the majority of the laser energy and thermal injury occurs at the level of the RPE Studies have shown that photocoagulation can eventually result in retinal and apparent RPE atrophy 200-300 larger than the original laser spot size These areas of expanded atrophy can lead to loss of central vision central scotomata and decreased color vision Consequently many retinal specialists today tend to treat with lighter less intense laser burns than originally specified in the ETDRS
In addition to the concern regarding the spread of intense laser burns there are a number of other reasons that retinal specialists today have modified the treatment procedures originally specified in the ETDRS protocol These reasons include the advent of new lasers and the clinical observation that different techniques such as focal photocoagulation with lighter burns or grid treatment alone may be similar in beneficial effect as the original ETDRS treatment protocol A modified ETDRS focal photocoagulation protocol adapted from the original ETDRS approach has been adopted as the standard laser technique for DME used in DRCRnet studies
There are limited data on the course of visual acuity and central retinal thickness after a single focal photocoagulation session for DME In prior DRCRnet DME treatment protocols that included a laser arm according to the re-treatment protocol eyes received a second focal photocoagulation session at 35- 4 months which was the first follow-up visit unless there was substantial improvement defined as at least a 50 decrease in retinal thickening of the central subfield measurement on OCT As a result it is unknown what proportion of eyes with lesser degrees of improvement would have continued to improve and the time course for further improvement following the initial photocoagulation session given additional time In one study conducted by DRCRnet of eyes that had not been previously treated for DME among 113 eyes in the modified ETDRS laser treatment group with baseline OCT central subfield 250 microns a 50 or more reduction in OCT central subfield thickening was present at 35 months in only 28 25 The table below categorizes the 85 eyes that did not meet this measure of improvement at 35 months with regard to improvement in visual acuity of at least 5 letters andor reduction in central subfield thickness of at least 10 The 5 letter reduction was selected based on the 95 confidence interval for change determined in a study that evaluated the validity and reliability of the electronic ETDRS visual acuity testing procedure that is used in DRCRnet protocols The 10 threshold was selected based on the DRCRnet OCT reproducibility study which found that a 10 change in central subfield thickness was likely to be real Forty-seven 42 eyes that met the protocol requirement for repeat photocoagulation at the first follow-up visit had an improvement in either visual acuity of at least 5 letters central subfield of at least a 10 reduction or both at this follow-up visit
Other DRCRnet protocols provide data on the course following a single photocoagulation session through 4 months of follow up In a pilot study designed to evaluate peribulbar corticosteroids for mild DME OCT central subfield thickness 250 microns and visual acuity 2040 or better at baseline modified ETDRS focal photocoagulation was the treatment given to the control group Follow-up visits occurred after 1 2 and 4 months before the eye was eligible to be retreated Twenty-one of the 37 eyes in the laser group had not been previously treated with focal photocoagulation for DME and 17 eyes had been previously treated with focal photocoagulation A 50 or more reduction in OCT central subfield thickening occurred in 11 30 of the 37 eyes at 17 weeks Fourteen 38 eyes that would have met the criteria for re-treatment had an improvement in either visual acuity of at least 5 letters central subfield of at least 10 or both at 17 weeks
In another pilot study evaluating intravitreal bevacizumab for DME OCT central subfield thickness 275 microns and visual acuity 2032 or worse at baseline modified ETDRS focal photocoagulation was the treatment given to the control group Follow-up visits occurred after 3 6 9 and 12 weeks before the eye was eligible to be retreated There were 7 eyes in the laser group that had not been previously treated with focal photocoagulation for DME and 12 eyes that had been previously treated with focal photocoagulation Among these 19 eyes a 50 or more reduction in OCT central subfield thickening occurred in 3 16 at 12 weeks Ten 53 eyes that would have met criteria for re-treatment had an improvement in either visual acuity of at least 5 letters central subfield of at least 10 or both at 12 weeks
The data from these three protocols indicate that a substantial number of eyes receiving focal photocoagulation either an initial course or repeat application will show improvement in central retinal thickness after 3-4 months that is at least 10 but is less than 50 of the baseline thickening It is for these eyes that further knowledge of the course of retinal thickening and visual acuity without additional interventions is needed to assess whether the present requirements for re-treatment are more aggressive than they need to be
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| U10EY018817-03 | NIH | None | None |
| U10EY014229-07 | NIH | None | None |
| U10EY014231-09 | NIH | None | httpsreporternihgovquickSearchU10EY014231-09 |