A 12-month, Randomized, Efficacy and Safety Study of 0.5 mg Ranibizumab vs Laser in Chinese Diabetic Macular Edema (DME) Patients

A 12-month, Randomized, Double-masked, Multicenter, Laser-controlled Phase III Study Assessing the Efficacy and Safety of 0.5 mg Ranibizumab Dosed PRN in Subjects With Visual Impairment Due to Diabetic Macular Edema in Chinese Patients

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02259088

Acronym

REFINE

Enrollment

384

Registered

2014-10-08

Start date

2014-11-05

Completion date

2017-01-17

Last updated

2019-02-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetic Macular Edema, Visual Impairment

Keywords

DME, macular edema, vision impairment, Chinese, diabetes

Brief summary

Study of efficacy and safety of 0.5 mg ranibizumab in Chinese patients with diabetic macular edema (DME)

Detailed description

The purpose of this study was to provide efficacy and safety data on 0.5 mg ranibizumab intravitreal injections compared to laser photocoagulation in Chinese patients with visual impairment due to DME. Treatment was driven by achieving vision stabilization.

Interventions

DRUGRanibizumab (RFB002)

Ranibizumab 0.5 mg/0.05 mL for intravitreal injection

PROCEDURELaser

Laser photocoagulation according to Early Treatment Diabetic Retinopathy Study (ETDRS) guidelines

DRUGSham injection

Imitation of an intravitreal injection consisting of an empty vial and an injection syringe without a needle

PROCEDURESham laser

Imitation of an active laser

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: * Male or female Chinese patients ≥ 18 years of age with diabetes mellitus and with HbA1c ≤10.0% * Stable medication for diabetes within 3 months prior to Visit 1 * Visual impairment due to DME with BCVA score between 78 and 39 letters as measured by ETDRS-like charts at 4 meters Key

Exclusion criteria

* Stroke or myocardial infarction less than 3 months prior to screening visit * Uncontrolled hypertension * Active ocular infection or intraocular inflammation in any eye * Treatment with any anti-angiogenic drugs within 3 months prior to baseline visit in any eye * Active proliferative diabetic retinopathy in study eye * Use of other investigational drugs within 30 days and systemic anti-VEGF drugs within 6 months prior to baseline visit * Prior laser photocoagulation or intraocular procedure within 3 months prior to baseline in study eye * History of intravitreal corticosteroid treatment in phakic study eye, and in aphakic or pseudophakic within 3 months prior to screening

Design outcomes

Primary

Measure	Time frame	Description
Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12	Baseline, Monthly from Month 1 through Month 12	Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged \[(Month1+Month2+...+Month12)/12\], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Secondary

Measure	Time frame	Description
Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Baseline, Monthly from Month 1 through Month 12	CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT). A negative change value indicates an improvement in macular edema, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.
Percentage of Patients With BCVA Gain of ≥ 10 and ≥ 15 Letters From Baseline at Month 12	Baseline, Month 12	Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
Percentage of Patients With BCVA Loss of < 10 and < 15 Letters From Baseline to Month 12	Baseline, Month 12	Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
Percentage of Patients With BCVA ≥ 73 Letters at Month 12	Month 12	Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. BCVA ≥ 73 letters is approximately equivalent to 20/40 on a Snellen chart. One eye (study eye) contributed to the analysis.
Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3	Monthly from Month 3 through Month 12	Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Nine monthly BCVA values were averaged \[(Month4+Month5+...+Month12)/9\],and the Month 3 BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
Mean Change From Baseline in Patient-Reported Visual Functioning at Month 6 and Month 12, Composite Score	Baseline, Month 6, Month 12	Visual functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in visual functioning, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported General Health at Month 6 and Month 12	Baseline, Month 6, Month 12	General health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general health, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported General Vision at Month 6 and Month 12	Baseline, Month 6, Month 12	General vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in general vision, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12	Baseline, Month 6, Month 12	Color vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in color vision, while a negative change value indicates a worsening.
Mean Change From Baseline in BCVA (Letters) at Each Visit	Baseline, Monthly from Month 1 through Month 12	Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.
Mean Change From Baseline in Patient-Reported Ocular Pain at Month 6 and Month 12	Baseline, Month 6, Month 12	Ocular pain was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in ocular pain, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported Near Activities at Month 6 and Month 12	Baseline, Month 6, Month 12	Near activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in near activities, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported Distance Activities at Month 6 and Month 12	Baseline, Month 6, Month 12	Distance activities were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in distance activities, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported Social Functioning at Month 6 and Month 12	Baseline, Month 6, Month 12	Social functioning was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in social functioning, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported Mental Health at Month 6 and Month 12	Baseline, Month 6, Month 12	Mental health was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in mental health, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported Roles Difficulties at Month 6 and Month 12	Baseline, Month 6, Month 12	Roles difficulties were assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in roles difficulties, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported Dependency at Month 6 and Month 12	Baseline, Month 6, Month 12	Dependency was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in dependency, while a negative change value indicates a worsening.
Mean Change From Baseline in Patient-Reported Driving at Month 6 and Month 12	Baseline, Month 6, Month 12	Driving was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in driving, while a negative change value indicates a worsening. Note: Many patients did not answer the driving related question as they did not drive at all.
Mean Number of Ranibizumab Re-treatments Received in the Study Eye From Month 3 Onward	Monthly from Month 3 through Month 12	A ranibizumab re-treatment was defined as an administration of ranibizumab injection at a scheduled visit following at least one non-missed visit where ranibizumab was not administered in the study eye due to visual acuity stabilization. This outcome measure was pre-specified for the Ranibizumab 0.5 mg arm only.
Mean Change From Baseline in Patient-Reported Peripheral Vision at Month 6 and Month 12	Baseline, Month 6, Month 12	Peripheral vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in peripheral vision, while a negative change value indicates a worsening.

Countries

China

Participant flow

Pre-assignment details

After eligibility confirmation, patients were randomized in a 4:1 ratio to 2 treatment arms.

Participants by arm

Arm	Count
Ranibizumab (RFB002) 3 initial intravitreal injections to the study eye at Day 1, Month 1 and Month 2, followed by as-needed intravitreal injections of ranibizumab 0.5 mg guided by VA stabilization, plus sham laser	307
Laser Laser photocoagulation applied to the study eye at Day 1, followed by active laser photocoagulation at intervals no shorter than 3 months apart, plus sham injections	77
Total	384

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	6	4
Overall Study	Death	2	0
Overall Study	Lost to Follow-up	2	0
Overall Study	Physician Decision	5	2
Overall Study	Protocol deviation	5	0
Overall Study	Subject/guardian decision	8	8

Baseline characteristics

Characteristic	Ranibizumab (RFB002)	Laser	Total
Age, Continuous	58.6 years STANDARD_DEVIATION 8.7	59.0 years STANDARD_DEVIATION 9.19	58.7 years STANDARD_DEVIATION 8.79
Best Corrected Visual Acuity	59.6 letters STANDARD_DEVIATION 10.53	58.2 letters STANDARD_DEVIATION 9.43	59.3 letters STANDARD_DEVIATION 10.32
Sex: Female, Male Female	168 Participants	38 Participants	206 Participants
Sex: Female, Male Male	139 Participants	39 Participants	178 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	116 / 307	30 / 75
serious Total, serious adverse events	57 / 307	15 / 75

Outcome results

Primary

Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Twelve monthly BCVA values were averaged \[(Month1+Month2+...+Month12)/12\], and the baseline BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Time frame: Baseline, Monthly from Month 1 through Month 12

Population: Full Analysis Set (FAS). Missing values imputed by the mean value last observation carried forward (MV-LOCF).

Arm	Measure	Value (MEAN)	Dispersion
Ranibizumab (RFB002)	Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12	6.8 letters	Standard Deviation 6.58
Laser	Mean Average Change From Baseline in Best-Corrected Visual Acuity (BCVA) (Letters) to Month 1 Through 12	1.1 letters	Standard Deviation 7.73

p-value: <0.00195% CI: [4.1, 7.5]Cochran-Mantel-Haenszel

Secondary

Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. Nine monthly BCVA values were averaged \[(Month4+Month5+...+Month12)/9\],and the Month 3 BCVA value was subtracted from the average. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Time frame: Monthly from Month 3 through Month 12

Population: Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF).

Arm	Measure	Group	Value (MEAN)	Dispersion
Ranibizumab (RFB002)	Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3	Average Change from Baseline Month 4 to Month 12	0.3 letters	Standard Deviation 4.51
Ranibizumab (RFB002)	Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3	Month 3	66.4 letters	Standard Deviation 10.66
Laser	Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3	Month 3	59.2 letters	Standard Deviation 12.63
Laser	Mean Average Change in BCVA From Month 4 to Month 12 Compared to Month 3	Average Change from Baseline Month 4 to Month 12	0.2 letters	Standard Deviation 6.08

Secondary

Mean Change From Baseline in BCVA (Letters) at Each Visit

Visual acuity with eyeglasses was assessed in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts at an initial testing distance of 4 meters. A letter score was calculated based on the number of letters correctly identified at the specified distance. A positive change value indicates an improvement in visual acuity, while a negative change value indicates a worsening. One eye (study eye) contributed to the analysis.

Time frame: Baseline, Monthly from Month 1 through Month 12

Population: Full Analysis Set (FAS) with missing values imputed by the last observation carried forward (LOCF). The number analyzed is the number of patients with a value for both baseline and the specific post-baseline visit.

Arm	Measure	Group	Value (MEAN)	Dispersion
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 6	6.8 letters	Standard Deviation 8
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 2	5.8 letters	Standard Deviation 6.44
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 7	6.8 letters	Standard Deviation 7.95
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 4	6.6 letters	Standard Deviation 7.23
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 8	7.4 letters	Standard Deviation 8.12
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 1	4.0 letters	Standard Deviation 5.59
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 9	7.3 letters	Standard Deviation 8.18
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 10	7.2 letters	Standard Deviation 8.45
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 5	6.8 letters	Standard Deviation 7.41
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 11	7.8 letters	Standard Deviation 8.55
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 12	7.8 letters	Standard Deviation 8.72
Ranibizumab (RFB002)	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 3	6.9 letters	Standard Deviation 6.91
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 12	2.5 letters	Standard Deviation 8.78
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 11	1.7 letters	Standard Deviation 9.35
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 1	-0.9 letters	Standard Deviation 5.5
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 2	0.0 letters	Standard Deviation 8.08
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 3	1.1 letters	Standard Deviation 9.18
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 4	0.0 letters	Standard Deviation 11.64
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 5	0.6 letters	Standard Deviation 10.61
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 6	0.3 letters	Standard Deviation 11.01
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 7	1.3 letters	Standard Deviation 10.13
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 8	1.9 letters	Standard Deviation 9.69
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 10	1.6 letters	Standard Deviation 9.23
Laser	Mean Change From Baseline in BCVA (Letters) at Each Visit	Change from Baseline at Month 9	1.8 letters	Standard Deviation 9.33

Secondary

Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit

CSFT (the average retinal thickness of the circular area within 1 millimeter diameter around the foveal center) was assessed using Optical Coherence Tomography (OCT). A negative change value indicates an improvement in macular edema, while a positive change value indicates a worsening. One eye (study eye) contributed to the analysis.

Time frame: Baseline, Monthly from Month 1 through Month 12

Arm	Measure	Group	Value (MEAN)	Dispersion
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 2	-141.3 micrometers	Standard Deviation 146.15
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 3	-154.2 micrometers	Standard Deviation 147.94
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 4	-130.4 micrometers	Standard Deviation 152.6
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 9	-142.4 micrometers	Standard Deviation 156.03
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 1	-126.7 micrometers	Standard Deviation 140.59
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 5	-141.0 micrometers	Standard Deviation 153.28
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 6	-146.2 micrometers	Standard Deviation 154.87
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 7	-138.4 micrometers	Standard Deviation 161.04
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 8	-146.9 micrometers	Standard Deviation 154.68
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 10	-137.6 micrometers	Standard Deviation 152.73
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 11	-144.8 micrometers	Standard Deviation 159.87
Ranibizumab (RFB002)	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 12	-146.5 micrometers	Standard Deviation 157.61
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 11	-88.1 micrometers	Standard Deviation 170.11
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 2	-48.8 micrometers	Standard Deviation 133.22
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 6	-72.9 micrometers	Standard Deviation 152.47
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 3	-58.5 micrometers	Standard Deviation 157.3
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 10	-82.9 micrometers	Standard Deviation 166.16
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 4	-72.6 micrometers	Standard Deviation 149.13
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 8	-81.8 micrometers	Standard Deviation 151.89
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 7	-72.4 micrometers	Standard Deviation 150.86
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 12	-85.9 micrometers	Standard Deviation 166.6
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 1	-33.1 micrometers	Standard Deviation 113.34
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 9	-80.9 micrometers	Standard Deviation 157.69
Laser	Mean Change From Baseline in Central Sub-Field Thickness (CSFT) at Each Visit	Change from Baseline at Month 5	-72.3 micrometers	Standard Deviation 150.45

Secondary

Mean Change From Baseline in Patient-Reported Color Vision at Month 6 and Month 12

Color vision was assessed by the patient using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) on a scale from 0 to 100, where 0 = worst possible score and 100 = best. A positive change value indicates a perceived improvement in color vision, while a negative change value indicates a worsening.