Randomized Controlled Trial of LUtein as a Novel Neuroprotective Adjunctive Therapy to Improve Visual Outcome of Rhegmatogenous Retinal Detachment (LUNAR Study)

Retinal detachment is a major cause of blindness, particularly among contemporary Asian populations due to the high prevalence of myopia. Without timely treatment, retinal detachment invariably results in blindness. As the only effective treatment is surgery, much effort has been invested to enhancing surgical outcome of retinal detachment repair. Advances in new instrumentations, viewing systems and refined surgical techniques have all contributed to improved rate of retinal re-attachment (anatomical outcome). Nevertheless, successful re-attachment of the retina after surgery does not always restore vision (visual outcome), especially when retinal detachment involves the macula ("macula-off" retinal detachment). The reason for poor visual outcome is believed to be due to apoptosis of photoreceptors, which may occur early and rapidly after the onset of retinal detachment. Neuroprotection has therefore been considered a valid strategy to improve visual outcome of retinal detachment surgery. Lutein is a promising potent neuroprotective agent for the retina, and has been shown in preliminary clinical and laboratory studies that it could salvage photorecepters in retinal detachment. We hypothesize that oral intake of lutein soon after onset of retinal detachment could prevent photoreceptor neurons from dying and thus limit the loss of vision. To test such hypothesis, we propose to conduct a double-masked, randomized controlled trial to evaluate the efficacy of lutein as an adjuvant therapy to improve visual outcome for surgical repair of primary rhematogenous retinal detachment involving the macula in Asian Singaporeans. The potential clinical and scientific significance of this trial is clear. It may provide first evidence that pharmacological neuroprotection can be used as an effective therapeutic modality in the clinical management of retinal detachment, and result in a paradigm shift in clinical practice, ultimately leading to better visual outcome and quality of life for patients undertaking surgical repair of retinal detachment.

Study Overview

• Status: Completed
• Conditions: Retinal Detachment
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Lutein

Detailed Description

Retinal detachment is a major cause of blindness, particularly among contemporary Asian populations due to the high prevalence of myopia. Without timely treatment, retinal detachment invariably results in blindness. As the only effective treatment is surgery, much effort has been invested to enhancing surgical outcome of retinal detachment repair. Advances in new instrumentations, viewing systems and refined surgical techniques have all contributed to improved rate of retinal re-attachment (anatomical outcome). Nevertheless, successful re-attachment of the retina after surgery does not always restore vision (visual outcome), especially when retinal detachment involves the macula ("macula-off" retinal detachment). The reason for poor visual outcome is believed to be due to apoptosis of photoreceptors, which may occur early and rapidly after the onset of retinal detachment. Neuroprotection has therefore been considered a valid strategy to improve visual outcome of retinal detachment surgery. Lutein is a promising potent neuroprotective agent for the retina, and has been shown in preliminary clinical and laboratory studies that it could salvage photorecepters in retinal detachment. We hypothesize that oral intake of lutein soon after onset of retinal detachment could prevent photoreceptor neurons from dying and thus limit the loss of vision. To test such hypothesis, we propose to conduct a double-masked, randomized controlled trial to evaluate the efficacy of lutein as an adjuvant therapy to improve visual outcome for surgical repair of primary rhematogenous retinal detachment involving the macula in Asian Singaporeans. The potential clinical and scientific significance of this trial is clear. It may provide first evidence that pharmacological neuroprotection can be used as an effective therapeutic modality in the clinical management of retinal detachment, and result in a paradigm shift in clinical practice, ultimately leading to better visual outcome and quality of life for patients undertaking surgical repair of retinal detachment.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Primary macula-off RRD (i.e. one that has not previously been treated with surgery)
• Able and willing to provide informed consent

Exclusion Criteria:

• Known pre-existing macular other ocular diseases (e.g., age-related macular degeneration, myopic maculopathy, diabetic macular edema, corneal diseases)
• Trauma-related RRD
• Recurrent RRD
• Macula-on RRD
• Chronic RRD (symptoms >60 days)
• History of amblyopia in the affected eye
• Known allergy to or current use of lutein supplements
• Pregnant or breastfeeding women, children (age <21 years), prisoners, cognitively impaired persons

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; Patients taking inactive placebo tablets	Dietary supplement: Placebo; Inactive placebo tablet
Experimental: Lutein; Patients taking lutein supplement	Dietary supplement: Lutein; Lutein is a common oral supplement that may have neuroprotective effect on the human retina

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual acuity	Changes in best-corrected visual acuity (BCVA) from baseline to 6-month follow-up visit	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual acuity	Changes in best-corrected visual acuity from baseline to 12-month follow-up visit	12 month
Retinal anatomical changes	Recovery of ultrastructural retinal cell layer disruptions on optical coherence tomography scans (e.g., disappearance of outer retinal disruptions at 6 and 12 month visits)	6 and 12 month
Visual function	Changes in visual function as measured using Pelli-Robson Contrast Sensitivity and microperimetry testing for macular function	6 and 12 month
Quality of life measures	Changes in "Impact of Vision Impairment Profile" based on vision impairment validated questionnaires (Lamoureux EL, Pallant JF, Pesudovs K, Rees G, Hassell JB, Keeffe JE. The impact of vision impairment questionnaire: an assessment of its domain structure using confirmatory factor analysis and rasch analysis. Invest Ophthalmol Vis Sci. 2007;48(3):1001-1006.)	6 and 12 months

Collaborators and Investigators

• Sponsor: Singapore National Eye Centre

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2016
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): November 30, 2020

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: April 28, 2019
• First Posted (Actual): April 30, 2019

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Eye Diseases; Retinal Diseases; Retinal Detachment; Dissociative Disorders
• Other Study ID Numbers: R1148/50/2014

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No