Effect of Repeated Low-Level Red-Light Therapy on Visual Field Damage in Primary Open-angle Glaucoma

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effect of repeated low-level red-light therapy on existing visual field damages in primary open-angle glaucoma patients.

Detailed Description
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Glaucoma is one of the main causes of visual impairment worldwide. Elevated intraocular pressure (IOP) is an important risk factor for glaucoma and the majority of anti-glaucoma therapies focus on the control of IOP. However, IOP-lowering treatments cannot directly attenuate optic neurodegeneration and rescue vulnerable retinal ganglion cells (RGCs). The glaucomatous symptoms could continue to deteriorate in some patients after optimal IOP control, which highlighted the need for alternative therapies targeting neuroprotection. Chronic ischemia is another potential factor in the pathogenesis of glaucoma. Clinical trials suggested that calcium channel blockers such as nilvadipine could increase ocular blood flow and postpone visual field deterioration in normal-tension glaucoma. Furthermore, it was found that Ginkgo biloba extract, another vasoactive drug, could reverse existing visual field damages, which indicated that improved ocular circulation would salvage dysfunctional RGCs and its efficacy could be observed in a relatively short time frame. The repeated low-level red-light (RLRL) therapy has regulatory effects on blood supply, which provides an innovative and non-invasive approach for the treatment of glaucoma. Considering the possible ischemic mechanism of POAG, it is expected that RLRL therapy could improve ocular circulation and reverse compromised visual functions. Using a randomized clinical trial with cross-over design, the purpose of this study is to investigate the effect of RLRL therapy on existing visual field damages in POAG patients. This study is a 24-week, prospective, randomized, cross-over clinical trial, enrolling POAG patients with well-controlled IOP as participants. Study participants will be randomly allocated to two groups, with one group receiving RLRL therapy from the 1st to the 12th week and the other receiving RLRL therapy from the 13th to the 24th week. Use of IOP-lowering medications is allowed throughout the 24 weeks. An interim analysis to ensure the safety of RLRL therapy is scheduled after the 12th week. Linear mixed models will be used to determine changes in visual field and assess other secondary outcomes.

Official Title
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Effect of Repeated Low-Level Red-Light Therapy on Visual Field Damage in Primary Open-angle Glaucoma: A Randomized Cross-over Clinical Trial

Conditions
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Open Angle Glaucoma, Eye Diseases

Intervention / Treatment
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* Device: RLRL therapy
* Drug: Routine IOP-lowering medications


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-69 years; Diagnosis of primary open-angle glaucoma with definite visual field defects in either eye (MD <-3dB); Well-controlled IOP in both eyes (IOP<21mmHg). Exclusion Criteria: Severe visual field defects in either eye (MD <-22dB); Visual field defects caused by other diseases in either eye; Unreliable results of visual field or IOP measurements in either eye; Diagnosis of other ocular diseases in active phase in either eye; History of refractive surgeries in either eye; History of other ophthalmic laser treatments or intraocular surgeries in the last 3 months in either eye; Refusing to inform consents or having difficulties to take part in follow-ups in next 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>RLRL therapy with routine IOP-lowering medications in the 1st-12th weeks then crossing to only routine IOP-lowering medications in the 13th-24th weeks | Device: RLRL therapy<br>* Each RLRL treatment lasts three minutes. RLRL treatments will be performed twice a day, with at least four hours between each RLRL treatment.<br>* Other names: Repeated Low-Level Red-Light Therapy;Drug: Routine IOP-lowering medications<br>* Medications prescribed for IOP control by glaucoma specialists in the outpatient.<br>* Other names: Anti-glaucoma medications;|
| Experimental: Group B<br>Only routine IOP-lowering medications in the 1st-12th weeks then crossing to RLRL therapy with routine IOP-lowering medications in the 13th-24th weeks | Device: RLRL therapy<br>* Each RLRL treatment lasts three minutes. RLRL treatments will be performed twice a day, with at least four hours between each RLRL treatment.<br>* Other names: Repeated Low-Level Red-Light Therapy;Drug: Routine IOP-lowering medications<br>* Medications prescribed for IOP control by glaucoma specialists in the outpatient.<br>* Other names: Anti-glaucoma medications;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of mean deviations (MD) in visual field tests | The twelve-week changes of MD are characterized as differences between the 12-week follow-up visit and the baseline visit or differences between the 24-week visit and the 12-week follow-up visit. The Humphrey Visual Field Analyzer will be used to measure MD (dB). | 12 weeks and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of mean deviations (MD) in visual field tests | The four-week changes of MD are characterized as differences between the 4-week follow-up visit and the baseline visit or differences between the 16-week visit and the 12-week follow-up visit. The Humphrey Visual Field Analyzer will be used to measure MD (dB). | 4 weeks and 16 weeks | 
| Incidence rates of significant reversal of visual field damages | The four-week and twelve-week incidence rates of significant reversal of visual field damages are rates of POAG patients with MD reversal ≥ 3dB between the 4-/12week follow-up visits and the baseline visit or between the 16-/24-week follow-up visits and the 12-week follow-up visit. The Humphrey Visual Field Analyzer will be used to measure MD (dB). | 4 weeks, 12 weeks, 16 weeks and 24 weeks | 
| Changes of pattern standard deviations (PSD) in visual field tests | The four-week and twelve-week changes of PSD are characterized as differences between the 4-/12week follow-up visit and the baseline visit or differences between the 16-/24-week visit and the 12-week follow-up visit. The Humphrey Visual Field Analyzer will be used to measure PSD (dB). | 4 weeks, 12 weeks, 16 weeks and 24 weeks | 
| Changes of the thickness of parapapillary retinal nerve fiber layer | The four-week and twelve-week changes of the thickness of parapapillary retinal nerve fiber layer (RNFL) are characterized as differences between the 4-/12week follow-up visits and the baseline visit or differences between the 16-/24-week follow-up visits and the 12-week follow-up visit. Spectralis HRA OCT and Optovue OCT will be used to measure the thickness of parapapillary RNFL (μm). | 4 weeks, 12 weeks, 16 weeks and 24 weeks | 
| Changes of the thickness of perifoveal ganglion cell-inner plexiform layer | The four-week and twelve-week changes of the thickness of perifoveal ganglion cell-inner plexiform (CG-IPL) are characterized as differences between the 4-/12week follow-up visits and the baseline visit or differences between the 16-/24-week follow-up visits and the 12-week follow-up visit. Spectralis HRA OCT and Optovue OCT will be used to measure the thickness of perifoveal CG-IPL (μm). | 4 weeks, 12 weeks, 16 weeks and 24 weeks | 
| Changes of the thickness of central macular choroid | The four-week and twelve-week changes of the thickness of central macular choroid are characterized as differences between the 4-/12week follow-up visits and the baseline visit or differences between the 16-/24-week follow-up visits and the 12-week follow-up visit. DRI OCT Triton and Optovue OCT will will be used to measure the thickness of central macular choroid (μm). | 4 weeks, 12 weeks, 16 weeks and 24 weeks | 
| Changes of the parapapillary capillary density | The four-week and twelve-week changes of parapapillary capillary density (CD) are characterized as differences between the 4-/12week follow-up visits and the baseline visit or differences between the 16-/24-week follow-up visits and the 12-week follow-up visit. DRI OCT Triton and Optovue OCT will will be used to measure parapapillary CD (%). | 4 weeks, 12 weeks, 16 weeks and 24 weeks | 
| Change of the perifoveal capillary density | The four-week and twelve-week changes of perifoveal capillary density (CD) are characterized as differences between the 4-/12week follow-up visits and the baseline visit or differences between the 16-/24-week follow-up visits and the 12-week follow-up visit. DRI OCT Triton and Optovue OCT will be used to measure perifoveal CD (%). | 4 weeks, 12 weeks, 16 weeks and 24 weeks | 
| Incidence rates of treatment-emergent adverse events | The four-week and twelve-week incidence rates of treatment-emergent adverse events are rates of treatment-emergent adverse events between the 4-/12week follow-up visits and the baseline visit or between the 16-/24-week follow-up visits and the 12-week follow-up visit. Subjects will be asked to report any treatment-emergent adverse event, including but not limited to glare, flash blindness, and afterimages. | 4 weeks, 12 weeks, 16 weeks and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open-angle glaucoma, Repeated low-level red-light therapy, Visual field