The Individually-Marked Panretinal Laser phoTocoagulation for Proliferative Diabetic Retinopathy Study (TREAT)

NCT03113006 | Completed DMC

• 1 other identifier: S-20160168
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

Background Diabetic eye disease is the most frequent complication among the 320,000 Danes with diabetes. The formation of new vessels (PDR) in the inner part of the eye (retina) is a feared complication and a leading cause of blindness, since these vessels are fragile and often cause bleeding within the eye. Peripheral retinal laser treatment (PRP) halves the risk of blindness, but often comes with a high prize. The peripheral part of the retina is responsible for the visual field and the night vision, and PRP limits these abilities (i.e. loss of driving license). The technique of PRP has principally been the same for the past 40 years with standard treatment given for all patients. With this one size fits all approach, a substantial number of patients will either be treated too much or too little. Too little treatment is inefficient, and disease progression may occur. Excessive treatment may cause side effects like loss of visual fields and decreased night vision. Therefore, it is important to test if treatment can be applied on an individual basis to give high efficacy treatment with minimal side effects. IMPETUS 2018 - TREAT is the second of two studies aimed at making an individual design for retinal laser treatment. In IMPETUS 2018 - DETECT the investigators demonstrated that non-invasive examinations of the oxygen level and measurements of the retinal vascular tree provide important information of individual treatment response. For instance, if standard PRP led to three per cent higher retinal oxygen saturation, there was a 4-fold risk of disease progression despite treatment. Hence, such a patient would benefit from more treatment to avoid blindness. With these observations at hand, the investigators want to compare a less invasive treatment (individualized laser treatment) against the standard PRP. Another essential aspect in the treatment of PDR is to be able to give the right diagnosis and to evaluate the efficacy of laser treatment. So far, this has been performed by fluorescein angiography. However, this examination are highly person-dependent and unpleasant to patients, and a more objective approach is needed. Optical coherent tomography angiography (OCT-A) is a quick, noninvasive scanning of the retina which is ideal to visualize moving objects like blood within the retinal vessels. The method has been successfully implemented in a number of retinal diseases, but it has never been validated in PDR. Standard PRP is often performed in 3-4 sessions. However, it may be painful, and patients sometimes choose not to complete all sessions after the initial treatment has been given. There is insufficient knowledge of the patient-barriers to treatment, and it is important to address these in an individualized treatment design. Aim In this 6-month 1:1 randomized, prospective study the investigators want to investigate 1) whether individualized retinal laser treatment compared with standard PRP has the same efficacy but less side effects, 2) whether OCT-A can be used as an objective marker for disease activity, and 3) to obtain a better understanding of patient-reported barriers to standard laser treatment PRP and whether these can be addressed with personalized retinal laser treatment. Setup Fifty eight consecutively recruited patients (1 May 2017 - 30 April 2018) with newly diagnosed PDR referred to the Department of Ophthalmology, OUH, and randomly assigned to standard PRP (n=29) or individualized laser treatment (n=29). Intervention Standard laser treatment is performed in all four quadrants of the retina. Individualized laser treatment is only performed in the part(s) of the retina with proliferation(s). Both treatments are carried out at baseline (BL), and additional treatment is given at month three (M3) and/or (M6), if necessary. Investigations Retinal digital images, fluorescein angiography, OCT-A (BL, M3, M6). Test of visual fields, dark adaptation and quality of life (BL, M6). Semi-structured interview will be performed with five patients who have received PRP in one eye and individualized laser treatment in the other eye. This will address treatment experience, potential barriers to treatment, etc. What to measure: Differences in need for retreatment, night blindness, visual fields, visual acuity, bleeding in the eye, surgery, and quality of life between the groups.

Conditions

Proliferative Diabetic Retinopathy; PDR; Diabetes

Outcome Measures

Primary Outcomes (4)

• Need for retreatment between the groups

  Change in the progression of PDR, hence the difference in the need for retreatment between the standard laser treatment group vs. the individualized laser treatment group.

  At month 3 and 6

• Loss of visual fields between the groups

  Loss of visual field between the standard laser treatment group vs. the individualized laser treatment group.

  From baseline to month 6

• Change in dark adaptation between the groups

  Change in dark adaptation between the standard laser treatment group vs. the individualized laser treatment group.

  From baseline to month 6

• Sensitivity and specificity of OCT angiography as an expression of disease activity in PDR

  The specificity and sensitivity of OCT-A in detecting progression in PDR

  At month 6

Secondary Outcomes (4)

• Change in visual acuity between the groups

  From baseline to month 6

• Difference in proportion with the development of vitreous haemorrhage between the groups

  From baseline to month 6

• Need for surgical removal of the vitreous between the groups

  From baseline to month 6

• Change in quality of life between the groups

  From baseline to month 6

Study Arms (2)

Standard Panretinal Photocoagulation

ACTIVE COMPARATOR

Localized to all four retinal quadrants.

Procedure: Panretinal Photocoagulation

Individ. Panretinal Photocoagulation

EXPERIMENTAL

Localized to only the affected quadrants.

Procedure: Panretinal Photocoagulation

Interventions

Panretinal Photocoagulation PROCEDURE

Panretinal laser treatment of the retina in patients with proliferative diabetic retinopathy.

Also known as: PRP

Individ. Panretinal Photocoagulation; Standard Panretinal Photocoagulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diabetes mellitus.

You may not qualify if:

• Diabetic macular edema in the affected eye.
• Age \<18 years.
• Pregnancy.
• Ambiguities in refracting media on topical eye.

Sponsors & Collaborators

• Odense University Hospital: lead
• University of Southern Denmark: collaborator
• Velux Fonden: collaborator

Study Sites (1)

The Department of Ophthalmology, Odense University Hospital

Odense, The Region of Southern Denmarj, 5000, Denmark

Location

Related Publications (21)

• Grauslund J, Green A, Sjolie AK. Prevalence and 25 year incidence of proliferative retinopathy among Danish type 1 diabetic patients. Diabetologia. 2009 Sep;52(9):1829-35. doi: 10.1007/s00125-009-1450-4. Epub 2009 Jul 12.

  PMID: 19593541 BACKGROUND

• Grauslund J, Green A, Sjolie AK. Blindness in a 25-year follow-up of a population-based cohort of Danish type 1 diabetic patients. Ophthalmology. 2009 Nov;116(11):2170-4. doi: 10.1016/j.ophtha.2009.04.043. Epub 2009 Sep 10.

  PMID: 19744716 BACKGROUND

• Stefansson E. Ocular oxygenation and the treatment of diabetic retinopathy. Surv Ophthalmol. 2006 Jul-Aug;51(4):364-80. doi: 10.1016/j.survophthal.2006.04.005.

  PMID: 16818083 BACKGROUND

• Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology. 1981 Jul;88(7):583-600.

  PMID: 7196564 BACKGROUND

• Preliminary report on effects of photocoagulation therapy. The Diabetic Retinopathy Study Research Group. Am J Ophthalmol. 1976 Apr;81(4):383-96. doi: 10.1016/0002-9394(76)90292-0.

  PMID: 944535 BACKGROUND

• Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):766-85.

  PMID: 2062512 BACKGROUND

• Bandello F, Brancato R, Menchini U, Virgili G, Lanzetta P, Ferrari E, Incorvaia C. Light panretinal photocoagulation (LPRP) versus classic panretinal photocoagulation (CPRP) in proliferative diabetic retinopathy. Semin Ophthalmol. 2001 Mar;16(1):12-8. doi: 10.1076/soph.16.1.12.4223.

  PMID: 15487693 BACKGROUND

• Fong DS, Girach A, Boney A. Visual side effects of successful scatter laser photocoagulation surgery for proliferative diabetic retinopathy: a literature review. Retina. 2007 Sep;27(7):816-24. doi: 10.1097/IAE.0b013e318042d32c.

  PMID: 17891003 BACKGROUND

• Pahor D. Visual field loss after argon laser panretinal photocoagulation in diabetic retinopathy: full- versus mild-scatter coagulation. Int Ophthalmol. 1998;22(5):313-9. doi: 10.1023/a:1006367029134.

  PMID: 10826550 BACKGROUND

• Pender PM, Benson WE, Compton H, Cox GB. The effects of panretinal photocoagulation on dark adaptation in diabetics with proliferative retinopathy. Ophthalmology. 1981 Jul;88(7):635-8. doi: 10.1016/s0161-6420(81)34977-x.

  PMID: 7196565 BACKGROUND

• Ferris FL 3rd, Podgor MJ, Davis MD. Macular edema in Diabetic Retinopathy Study patients. Diabetic Retinopathy Study Report Number 12. Ophthalmology. 1987 Jul;94(7):754-60. doi: 10.1016/s0161-6420(87)33526-2.

  PMID: 3658347 BACKGROUND

• Chhablani J, Mathai A, Rani P, Gupta V, Arevalo JF, Kozak I. Comparison of conventional pattern and novel navigated panretinal photocoagulation in proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 2014 May 1;55(6):3432-8. doi: 10.1167/iovs.14-13936.

  PMID: 24787564 BACKGROUND

• Chhablani J, Sambhana S, Mathai A, Gupta V, Arevalo JF, Kozak I. Clinical efficacy of navigated panretinal photocoagulation in proliferative diabetic retinopathy. Am J Ophthalmol. 2015 May;159(5):884-9. doi: 10.1016/j.ajo.2015.02.006. Epub 2015 Feb 19.

  PMID: 25703478 BACKGROUND

• Inan UU, Polat O, Inan S, Yigit S, Baysal Z. Comparison of pain scores between patients undergoing panretinal photocoagulation using navigated or pattern scan laser systems. Arq Bras Oftalmol. 2016 Feb;79(1):15-8. doi: 10.5935/0004-2749.20160006.

  PMID: 26840160 BACKGROUND

• Torp TL, Kawasaki R, Wong TY, Peto T, Grauslund J. Improvement in retinal venous oxygen saturation after panretinal photocoagulation is predictive of progression of proliferative diabetic retinopathy. ARVO, 2016;6356-C0143.

  BACKGROUND

• Jorgensen CM, Hardarson SH, Bek T. The oxygen saturation in retinal vessels from diabetic patients depends on the severity and type of vision-threatening retinopathy. Acta Ophthalmol. 2014 Feb;92(1):34-9. doi: 10.1111/aos.12283. Epub 2013 Dec 16.

  PMID: 24330421 BACKGROUND

• Torp TL, Frydkjær-Olsen U, Hansen RS, Peto T, Grauslund J. Intra- and intergrader reliability of semiautomatic measurements of fundus fluorescein angiography leakage in proliferative diabetic retinopathy. European Journal of Ophthalmology, 2015;25(3):e7-e30.

  BACKGROUND

• Lee CS, Lee AY, Sim DA, Keane PA, Mehta H, Zarranz-Ventura J, Fruttiger M, Egan CA, Tufail A. Reevaluating the definition of intraretinal microvascular abnormalities and neovascularization elsewhere in diabetic retinopathy using optical coherence tomography and fluorescein angiography. Am J Ophthalmol. 2015 Jan;159(1):101-10.e1. doi: 10.1016/j.ajo.2014.09.041. Epub 2014 Oct 25.

  PMID: 25284762 BACKGROUND

• de Carlo TE, Bonini Filho MA, Baumal CR, Reichel E, Rogers A, Witkin AJ, Duker JS, Waheed NK. Evaluation of Preretinal Neovascularization in Proliferative Diabetic Retinopathy Using Optical Coherence Tomography Angiography. Ophthalmic Surg Lasers Imaging Retina. 2016 Feb;47(2):115-9. doi: 10.3928/23258160-20160126-03.

  PMID: 26878443 BACKGROUND

• Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL 3rd, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015 Nov 24;314(20):2137-2146. doi: 10.1001/jama.2015.15217.

  PMID: 26565927 BACKGROUND

• Vergmann AS, Sorensen KT, Torp TL, Kawasaki R, Wong T, Peto T, Grauslund J. Optical coherence tomography angiography measured area of retinal neovascularization is predictive of treatment response and progression of disease in patients with proliferative diabetic retinopathy. Int J Retina Vitreous. 2020 Nov 4;6(1):49. doi: 10.1186/s40942-020-00249-6.

  PMID: 33292695 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Anna S Vergmann, M.D.

  Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph. D. student

Study Record Dates

• First Submitted: March 24, 2017
• First Posted: April 13, 2017
• Study Start: May 1, 2017
• Primary Completion: August 27, 2019
• Study Completion: August 27, 2019
• Last Updated: August 29, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)